Abstract

     Cancer screening is a source of much debate. At the interface between public health, specialist care, economics and public health policy, it creates tensions between professional groups, politicians, the media and the public. A screening test may be cheap but applying it to a population (with rigorous quality control and effective downstream processing of patients with abnormal results) creates a huge workload and cost. Screening can also have profound psychological effects. People with false-positive results require investigation yet are usually eventually found not to have cancer. Unless screening can be shown to reduce mortality from specific cancers, the resources used are better spent on improving care, and this has led to disparities in screening recommendations between countries. Advances in understanding the genetic basis of cancer are likely to provide new approaches to cancer risk assessment and new challenges for developing screening strategies, by risk-banding populations based on polymorphisms in low-penetrance cancer risk genes. The American Cancer Society guidelines for cancer screening, reviewed annually, represent a global gold standard that is difficult to emulate in most healthcare economies because of cost and under-capacity for downstream processing of abnormal findings. Tailoring cancer screening recommendations to a country’s health economy is an essential public health intervention.

Introduction

     Cancer screening seems so logical to all healthcare workers and patients alike. We all know that early cancer is curable in the majority of cases and later stage disease is not. So, picking up cancer before a patient has symptoms would seem ideal. The problem is that none of the tests available are perfect. And the resources spent on screening programmes may well be better spent on speeding up appropriate referral of symptomatic patients. Here, we will consider the advantages of screening along with the downside for the common cancers.

     The long-awaited publication of the independent review on national cancer screening programmes in England makes grim reading.1 Two disastrous information technology failures e one in breast cancer and the other in cervical cancer e were revealed in 2018. Thousands of patients were simply deleted from the computer database by accident. New technologies such as the faecal immunochemical test (FIT) and once-only colonoscopy programmes are still not fully rolled out even though plans were unveiled 8 years ago. And although much talked about, artificial intelligence currently plays little part in data interpretation except in research settings. Crucially, the consumer uptake of each of the three major programmes e breast, colon and cervix e is in decline, especially in deprived areas. The impact of coronavirus disease (COVID-19) has been severe and services are only just beginning to clear the huge backlog generated.2

The future

     New technology such as the microanalysis of circulating DNA e so-called liquid biopsy e could radically change the situation. Future changes in cancer screening will lead to profound ethical, educational, commercial and medical challenges. Completion of the Human Genome Project, the ability to handle large volumes of sequence data, and rapid and inexpensive assays for mutations using gene-chip technology will transform the assessment of cancer risk. Commercial pressures have caused the major pharmaceutical companies to invest heavily in genomics, and their interest will lead to the discovery of new drugs and more specific tailoring of therapies to individual patients. It is likely that groups of individuals with no family history of cancer will be identified as being at significantly increased risk of developing cancer. Devising optimal screening schedules for such groups will be a major challenge.

     The biggest problem of all is motivating the customers. The compliance rate varies enormously across the world, driven by education, socioeconomic factors and deprivation.5 The educated worried well are likely to go for every free test offered by the health system. The socially excluded residents of the neighbouring poorer districts on the wrong side of the tracks will not visit the doctor until they have advanced stage 4 cancer. And yet private clinics offer top of the range health screening for >£3000 of scans and tests to the gullible wealthy with no evidence of benefit. To save lives most effectively, we must target the poor.

Abstract

Background. Perioperative sleep disorders exert a severe adverse impact on postoperative recovery. Recently, some observational studies reported that acupuncture-point stimulation (APS) provided benefits for promoting perioperative sleep quality. However, the effects of APS on perioperative sleep disorders following general anesthesia have not been thoroughly assessed by any systematic study and meta-analysis. Therefore, we conducted this systematic review and meta-analysis to reveal the effects of APS on perioperative sleep disorders. Methods. Eight databases (Chinese: CNKI, VIP, CBM, and Wanfang; English: PubMed, Embase, Web of Science, and Cochrane Library) were thoroughly searched to find randomized controlled trials (RCTs) that indicated a link between APS and the occurrence of perioperative sleep disorders. We applied RevMan 5.4 (Cochrane Collaboration) and Stata 16.0 (Stata Corp) to conduct our meta-analysis. In addition, the trial sequential analysis (TSA) tool was utilized to estimate the validity and reliability of the data. Results. In this study, nine RCTs with 719 patients were conducted. Compared to the control group, APS significantly improved perioperative subjective sleep quality (SMD: −1.36; 95% CI: −1.71 to −1.01; ). Besides, it increased perioperative TST (preoperative period MD = 24.29, 95% CI: 6.4 to 42.18, ; postoperative period MD = 45.86, 95% CI: 30.00 to 61.71, ) and SE (preoperative MD = 3.62, 95% CI: 2.84 to 4.39, ; postoperative MD = 6.43, 95% CI: 0.95 to 11.73, ). The consequence of trial sequential analysis further confirmed the reliability of our meta-analysis results. Conclusion. According to the currently available evidence, APS could effectively improve perioperative sleep quality and play an essential role in decreasing the incidence of perioperative sleep disorders.

Introduction

Sleep is vital for overall health as it influences the quality of life and physical functioning [1]. Good sleep quality is a sign of wellbeing, whereas poor sleep quality raises comorbidity, mortality, and medical expenses [2]. Despite advances in operative and anesthetic procedures, sleep disorders continue to be a concern in the perioperative period. Perioperative sleep problems, as compared to household sleep disorders, have gained more attention recently, such as reduced nighttime sleep, fragmentation of sleep, and circadian rhythm disruptions at night after admission [3,C4]. The proportion of sleep disorders in hospitalized patients (64%–73.1%) is much higher than that in people at home (30.6%–41.2%) due to the surgical stress response, ward environment, and patients’ underlying diseases [5–7]. Perioperative sleep problems were noted in several observational studies to be important risk factors for poor recovery [8] and were associated with anxiety, altered pain perception, and postoperative cognitive dysfunction (such as delirium), further deteriorating the patient’s physical state [1, 6, 7, 9]. Moreover, it was suggested that perioperative sleep disorders might lead to postoperative fatigue, episodic hypoxemia, cardiovascular disorders, metabolic impairment, and immune disorders [10, 11]. Enhancing perioperative sleep quality is probably related to improved health, surgery effect, and patient safety [9]. Unfortunately, there are no specific therapeutic strategies for perioperative sleep disorders. Even though it was reported that pharmaceutical therapies, such as benzodiazepines and other sedating agents, might improve perioperative sleep quality, the potentially addictive nature and risk of tolerance restricted their clinical application [9].

In complementary and alternative medicine, acupuncture-point stimulation (APS) was employed to improve perioperative sleep quality [12]. According to the theory of traditional Chinese medicine (TCM), APS refers to stimulating the body’s acupoints with various methods, including acupressure (manual stimulation), acupuncture (sterile needle stimulation), laser acupuncture, electrical stimulation (transcutaneous electrical acupoint stimulation and electrical acupuncture), magnetic acupuncture (stimulation with special equipment), moxibustion therapy, and auricular point pressing, with the goal of achieving therapeutic effects such as sleep improvement and pain management [13–18]. APS has been an integral part of traditional Chinese medicine treatment. Based on the traditional Chinese medicine meridian theory, the body’s qi circulation is restored when target acupoints along meridians are stimulated [14]. It was reported that APS might lower the risk of poor sleep quality due to its considerable analgesic and sedative effects [19, 20]. Recently, a significant number of RCTs were carried out on the effects of APS on perioperative sleep disorders [8, 15]. Besides, a previous review concluded that EA might work to alter neurotransmitter concentrations and reduce the levels of norepinephrine and dopamine so as to enhance the quality of postoperative sleep quality after general anesthesia [12]. However, this study not only did not conduct a statistical assessment of the efficiency of EA on inpatients’ sleep quality during the postoperative period but also did not examine preoperative sleep quality thoroughly [12].

Conclusion

Taken together, our systematic review and meta-analysis suggested that APS could effectively improve perioperative sleep disorders, indicating that it was worthwhile to offer such therapies in perioperative healthcare institutions. Although our results had certain clinical implications of APS for the treatment of perioperative sleep disorders, more studies are needed to offer stronger evidence to further verify our conclusions in the future.

Abstract

Background. Rasagiline or pramipexole monotherapy has been suggested for the management of early Parkinson’s disease (PD). The aim of this research was to systematically review the clinical efficacy and safety of rasagiline or pramipexole in early PD (defined as disease duration ≤5 years and Hoehn and Yahr stage of ≤3). Methods. Randomized controlled trials (RCTs) of rasagiline or pramipexole for early PD published up to September 2021 were retrieved. Outcomes of interest included changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) Parts II and III and the incidence of adverse events. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated, and heterogeneity was measured with the I2 test. Results. Nine rasagiline and eleven pramipexole RCTs were included. One post hoc analysis of one rasagiline study was included. Five studies for each drug were included in meta-analyses of the UPDRS scores. The rasagiline meta-analysis focused on patients receiving 1 mg/day. Rasagiline and pramipexole significantly improved UPDRS Part II and III scores when compared to placebo. Significant heterogeneity among the studies was present (I2 > 70%). Neither rasagiline nor pramipexole increased the relative risk for any adverse events, serious adverse events, or adverse events leading to withdrawal when compared with placebo. Conclusion. Applying a Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach to summarize the evidence, we found moderate confidence in the body of evidence for the efficacy of rasagiline or pramipexole in early PD, suggesting further well-designed, multicenter comparative RCTs remain needed.

Introduction

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized clinically by bradykinesia, tremor, rigidity, and postural instability and histologically by neuronal inclusions composed of α-synuclein. Nonmotor symptoms including olfactory dysfunction, rapid eye movement, sleep behavior disorder, mood disorders, and autonomic dysfunction often precede the appearance of motor symptoms by several months or years [1, 2]. These motor and nonmotor symptoms can adversely affect a patient’s quality of life [3]. The incidence of PD is rising and increases with age [4, 5].

Early management of PD could prolong the ability of a patient to stay in working life and improve their overall quality of life [6, 7]. Levodopa is widely considered one of the most effective treatments for PD, but its use is often delayed because of drug-induced dyskinesias and wearing-off and on-off fluctuations [8, 9]. Alternatives to levodopa in early pharmacologic treatment of PD are dopamine agonists and monoamine oxidase B (MAO-B) inhibitors [10, 11]. A meta-analysis by Chang and coworkers (2017) [12] showed the irreversible inhibitor of MAO-B inhibitor rasagiline to have benefits both as a monotherapy and in combination with another intervention. The safety profile of rasagiline was similar to that of placebo in a systematic review of its use in PD patients [13]. Pramipexole, a nonergoline, D3-preferring dopamine agonist, is another treatment option for the management of motor symptoms associated with PD [14]. A recent systematic review showed that combined pramipexole and levodopa therapy was superior to levodopa monotherapy for the improvement of clinical symptoms in PD patients [15].

Prior systematic reviews evaluating the efficacy and safety of either rasagiline or pramipexole have evaluated patient populations at all stages of the disease. The goal of this study was to focus on the safety and efficacy of these drugs in early PD. Defining early PD in our review was based on the duration of PD in affected patients (five years or less) as well as the presence of mild to moderate symptoms based on the Hoehn and Yahr scale. The Hoehn and Yahr scale is commonly used in clinical studies to stage the level of functional disability and impairment seen in PD patients [16].

Results
4.1. Description of the Included Rasagiline Studies
The key characteristics of the nine rasagiline studies are reported in Table 1. One study [21] compared pramipexole and rasagiline as interventions and is included in this portion of the analysis. One post hoc analysis of a randomized controlled trial [22] met the inclusion criteria and was included in the systematic review. There were a total of 2121 patients in the studies, and 1059 patients were on rasagiline: 738 patients had a dose of 1 mg/day, 307 had a dose of 2 mg/day, and 14 had a dose of 4 mg/day. The mean age of study populations ranged from 59.3 to 70.2 years. The mean duration of PD ranged from 2.5 months to 4.8 years. The proportion of the study population who were males in the intervention groups ranged from 42.9 to 76.9%. There were four studies where other PD medications were either discontinued before the study or patients were PD-drug naïve [21, 23–25]. The rest of the studies allowed other PD medications with stable dosage for more than 4 weeks before the start of the study [26–29]. Rescue LD was accepted in one rasagiline study if PD symptoms worsened, and the current therapy did not relieve the symptoms [28]. Hoehn and Yahr stage was ≤3 in every study. The overall discontinuation rates were 7.3% and 10.7% in the rasagiline and placebo groups, respectively. One study reported seven discontinued patients without indicating which intervention the patients were using [27].

Abstract

Osteoporosis (OP) is a metabolic bone disease with a high incidence rate worldwide. Its main features are decreased bone mass, increased bone fragility and deterioration of bone microstructure. It is caused by an imbalance between bone formation and bone resorption. Ginsenoside is a safe and effective traditional Chinese medicine (TCM) usually extracted from ginseng plants, having various therapeutic effects, of which the effect against osteoporosis has been extensively studied. We searched a total of 44 relevant articles with using keywords including osteoporosis, ginsenosides, bone mesenchymal cells, osteoblasts, osteoclasts and bone remodeling, all of which investigated the cellular mechanisms of different types of ginsenosides affecting the activity of bone remodeling by mesenchymal stem cells, osteoblasts and osteoclasts to counteract osteoporosis. This review describes the different types of ginsenosides used to treat osteoporosis from different perspectives, providing a solid theoretical basis for future clinical applications.

Introduction

Osteoporosis (OP) is a metabolic bone disease characterized by decreased bone mass and destruction of bone tissue microstructure, leading to increased bone fragility and susceptibility to fractures ( Gopinath, 2023 ). A global epidemiological survey on osteoporotic vertebral fractures showed that one in three women and one in five men over the age of 50 will be directly affected by osteoporosis for the rest of their lives ( Laird et al., 2023 ). A study on the prediction of hip fractures in Asia estimated that by 2050, the direct cost of osteoporotic fractures in Asia alone may reach at least $15 billion per year ( Cheung et al., 2018 ). Therefore, early detection and treatment of osteoporosis is crucial for preventing fractures and reducing the burden on the global health care system.

Normal bone homeostasis in the human body is mainly maintained by osteoblasts differentiated from bone marrow mesenchymal stem cells (BMSCs) and osteoclasts produced by the fusion of monocytes and macrophages ( Guo et al., 2023 ; Kular et al., 2012 ), which participate in bone reconstruction and exert the sequential function of absorbing old bone and forming new bone ( Harris et al., 2023 ; Iantomasi et al., 2023 ) ( Fig. 1 ). The main cause of OP is aging, while secondary causes include genetic diseases, endocrine diseases, gastrointestinal diseases, blood diseases, neurological diseases, rheumatism and autoimmune diseases ( Patel and Wairkar, 2023 ). In addition, lifestyle changes, such as vitamin D and calcium deficiency, high salt intake, alcohol consumption, and smoking, also significantly increase the risk of osteoporosis. These factors can lead to an imbalance in bone cell activity and disrupt the dynamic cycle of bone formation and absorption, thereby affecting bone homeostasis and exacerbating OP ( Beekman et al., 2023 ).

Conclusion

In recent years, there has been increasing research on the treatment of osteoporosis with ginsenosides. Therefore, this review describes the possible mechanisms of different types of treatment for osteoporosis from three aspects, BMSCs, osteoblasts, and osteoclasts, and summarizes their specific signaling pathways or key factor mechanisms. However, this treatment method is still in the initial stage of clinical transformation, and there are still many obstacles between its experimental results and clinical application, such as in terms of combination therapy, drug delivery pathways, bioavailability, and combination with biochemical materials. With increasing attention given to the role of ginsenosides in bone reconstruction, ginsenosides may become a new drug for treating osteoporosis and promoting fracture healing and a powerful candidate for cytokines in tissue engineering bone.

Abstract

Background
Heart failure has an estimated global prevalence of 64.3 million cases, with an average age of a person living with heart failure at 75.2 years. Approximately 20% of residents living in nursing homes (a long-term residential care environment for some individuals) report living with heart failure. Residents living with heart failure in nursing home environments are often frail, have reduced quality of life, higher rates of rehospitalisation and mortality, and greater complications in heart failure management. Further, nursing home staff often lack the knowledge and skills required to provide the necessary care for those living with heart failure. Interventions for improving heart failure management in nursing homes have proven effective, yet there is a lack of understanding regarding interventions for optimising care provision. The aim of this review was to synthesise the current evidence on educational interventions to optimise care provided to people with heart failure in nursing homes.

Methods
A scoping review with four databases searched: Medline, CINAHL, Web of Science, and EMBASE. Relevant reference lists were searched manually for additional records. Studies of nursing home staff or resident outcomes associated with changes in care provision (i.e., resident quality of life, staff knowledge of heart failure) were included. Results from the charting data process were collated into themes: intervention outcomes, changes to practice, and implementation and process evaluation.

Results
Seven papers were deemed eligible for inclusion. Most studies (n=6) were comprised of nursing home staff only, with one comprised only of residents. Study aims were to improve heart failure knowledge, interprofessional communication, heart failure assessment and management. Positive changes in staff outcomes were observed, with improvements in knowledge, self-efficacy, and confidence in providing care reported. No difference was reported concerning nursing home resident outcomes. Interprofessional communication and staff ability to conduct heart failure assessments improved post-intervention. Changes to practice were mixed, with issues around sustainability reported. Nursing home staff highlighted their appreciation towards receiving education, recommending that videos, images, and humour could improve the intervention content.

Conclusions
There is a paucity of evidence around educational interventions to support residents living with heart failure in nursing homes. However, available evidence suggests that educational interventions in nursing homes may improve care through improving staff self-efficacy and confidence in providing care, heart failure knowledge and interprofessional communication. The complexity of implementing educational interventions in the nursing home setting must be considered during the development process to improve implementation, effectiveness, and sustainability.

Background

Heart failure, defined as a clinical syndrome characterised by structural and/or functional changes to the heart (Bozkurt et al., 2021), has an estimated prevalence of 64.3 million cases worldwide (Savarese et al., 2022). People living with heart failure often present with three or more comorbidities, such as hypertension, diabetes mellitus and chronic kidney disease, which increases the severity of heart failure symptoms and negatively impacts quality of life and prognosis (Groenewegen et al., 2020). The presence of multi-comorbidities increases the complexity to effectively manage patients with heart failure (Conrad et al., 2018). Consequently, difficulties in management have resulted in higher rates of rehospitalisation (Groenewegen et al., 2020, Komajda, 2015, Wachter and Rommel, 2022), placing a significant demand on hospital facilities and personnel, and incurring substantial healthcare costs (Cleland et al., 2019, Conrad et al., 2018, Lesyuk et al., 2018, Urbich et al., 2020).

Due to an ageing population, improvements in diagnostic testing, and greater survival rates following a cardiovascular event, the incidence of heart failure is expected to continue to rise (Lippi and Sanchis-Gomar, 2020, Savarese et al., 2022). The prevalence of heart failure increases with age, from 1% for those <55 years to 10% for those aged >70 years (McDonagh et al., 2021). In the USA between 2001 and 2014, of the 14.6 million individuals hospitalised due to heart failure, 75.3% were classified as older people (>65 years) (Akintoye et al., 2017). The mean age of this population is 75.2 years (Norhammar et al., 2023).

Conclusions

The findings from this review highlight the potential of interventions implemented in nursing homes for improving care provision to residents with heart failure. However, outcomes reported across the included studies were mostly focused on nursing home staff. Thus, future research is needed to determine whether such interventions are effective in improving outcomes associated with nursing home residents. Also, future research should aim to determine whether such interventions can produce long-term effects and sustainability. Education was a common intervention component employed across the studies, provided face-to-face to nursing home staff. Participant feedback, although limited, indicated that education was well-received and beneficial, improving heart failure knowledge of staff. However, this study reported poor participant attendance at the sessions, with the intervention facilitator indicating that this approach was burdensome. The delivery of a digital intervention may provide greater success, reducing the burden on staff and the need for an intervention facilitator. A digital approach also provides participants with the ability to access the intervention at a time that suits them, potentially improving intervention acceptability, user engagement, and likelihood of success.

Abstract

Cancer vaccines based on tumor cell components have shown promising results in animal and clinical studies. The vaccine system contains abundant tumor antigen components, which can activate the immune system by antigens. However, their efficacy has been limited by the inability of antigens delivery, which are the core components of vaccines, further fail to be presented and activation of effective cells. Nanotechnology offers a novel platform to enhance the immunogenicity of tumor-associated antigens and deliver them to antigen-presenting cells (APCs) more efficiently. In addition, nanotreatment of tumor cells derivate active ingredients could also help improve the effectiveness of cancer vaccines. In this review, we summarize recent advances in the development of cancer vaccines by the combination of nanotechnology and tumor-based ingredients, including liposomes, polymeric nanoparticles, metallic nanoparticles, virus-like particles and tumor cells membrane, tumor lysate, and specific tumor antigens. These nanovaccines have been designed to increase antigen uptake, prolong antigen presentation, and modulate immune responses through codelivery of immunostimulatory agents. We also further discuss challenges and opportunities in the clinical translation of these nanovaccines.

Introduction

Cancer immunotherapy has revolutionized cancer treatment by harnessing the immune system to recognize and attack cancer cells [1–3]. Among various immunotherapeutic approaches, cancer vaccines have attracted significant attention due to their potential to induce long-lasting and specific immune responses against tumor cells [4–7]. By comparison with surgery, it hardly produce large wounds, nor does it cause higher toxicity in normal tissues and drug tolerance like chemotherapy in the treatment of tumor. However, the clinical efficacy of cancer vaccines based on tumor cell components, such as peptides and proteins, is limited by their poor immunogenicity and inefficient delivery to antigen presentation cells (APCs). Although, many cancer vaccines were applied with the immune-stimulatory agents, such as the programmed cell death protein 1 (PD-1), CpG oligonucleotide, etc. The clinical response rates remain low, especially in the hypoimmunogenic tumors. As we all know, pancreatic cancer is a more difficult type for immunotherapy as a low immunogenic tumor. Therefore, there are few effective cancer vaccines that can actively promote the pancreatic cancer treatment. Meanwhile, limited by the specific tumor antigens, the development of cancer vaccines was extremely difficult.

The field of cancer vaccines has seen significant advancements in recent years, with numerous studies focusing on different aspects of vaccine development and application [8–12]. These advances have been facilitated by the exploration of various types of cancer vaccines, including those targeting viral antigens, neoantigens, and other tumor-specific antigens [13–16]. One approach in cancer vaccine research involves targeting shared antigens from viral infections linked to certain cancer types, such as Epstein–Barr virus and HPV. Studies have shown promising results with vaccines targeting viral antigens like Epstein–Barr nuclear antigen 1 and latent membrane proteins, as well as HPV-related antigens, demonstrating favorable antitumor efficacy and the potential to establish durable T cell memory in rapidly progressing HPV-positive tumors [17]. Another significant area of research is neoantigen cancer vaccines. Neoantigens, derived from nonsynonymous cell variants, are only expressed in tumor cells and can bypass thymus-negative selection, leading to robust neoantigen-specific T cell responses [14]. Advances in genomic and transcriptional profiling have made identifying putative neoantigens possible, although challenges remain in predicting which neoantigens can effectively induce neoantigen-specific T cell responses [18–20]. Cancer vaccines are being developed to stimulate antitumor immunity with tumor antigens delivered in various forms, such as cells, peptides, viruses, and nucleic acids [21–24]. These vaccines aim to overcome tumor heterogeneity and reverse the immunosuppressive microenvironment. Challenges in the field include single antigen targeting, weak immunogenicity, off-target effects, and impaired immune response [25–27]. Current research and reviews provide insights into the principle of action, components, classification, delivery methods, and progress of cancer vaccines, offering a broader perspective for future vaccine design.

Recent studies have shown that tumor antigens can be used for the design of cancer vaccines without the necessity to identify, parse, and reconstruct certain antigens [28–31]. A novel concept has been proposed that the whole antigen vaccine systems derived from tumor cells could be designed to conquer cancer treatments [32–34]. The tumor cells themselves are a huge antigen pool with countless tumor antigen epitopes, which can be used to activate antitumor immune response. Among them, more studies have focused on the application of tumor cell membrane as tumor antigens to stimulate APCs and further activate the antitumor immune response of T cells. In addition, the activation of T cells in immune response requires the involvement of costimulatory molecules. Some studies are based on this theoretical foundation, using genetic engineering to modify tumor cell membranes. By retaining antigen on the cell membrane and inducing the expression of costimulatory molecule CD80, T cells can be directly activated, thereby achieving antitumor immune response [35] (Figure 1). Of course, many studies combine tumor cell membranes that retain tumor antigens with other functional molecules to directly activate dendritic cells (DCs) for antigen presentation, leading to the activation of T cell immune response. These are two different approaches aimed at achieving the same goal [36–38]. A series of nanovaccines developed on this basis have been widely used in the treatment of different tumor cells and preclinical experiments.

Abstract

Liver fibrosis is an intrahepatic chronic damage repair response caused by various reasons such as alcoholic liver, fatty liver, viral hepatitis, autoimmune diseases, etc., and is closely related to the progression of liver disease. Currently, the mechanisms of liver fibrosis and its treatment are hot research topics in the field of liver disease remedy. Mesenchymal stem cells (MSCs) are a class of adult stem cells with self-renewal and multidirectional differentiation potential, which can ameliorate fibrosis through hepatic-directed differentiation, paracrine effects, and immunomodulation. However, the low inner-liver colonization rate, low survival rate, and short duration of intervention after stem cell transplantation have limited their wide clinical application. With the intensive research on liver fibrosis worldwide, it has been found that MSCs and MSCs-derived exosomes combined with drugs have shown better intervention efficiency than utilization of MSCs alone in many animal models of liver fibrosis. In this paper, we review the interventional effects and mechanisms of mesenchymal stem cells and their exosomes combined with drugs to alleviate hepatic fibrosis in vivo in animal models in recent years, which will provide new ideas to improve the efficacy of mesenchymal stem cells and their exosomes in treating hepatic fibrosis in the clinic.

Introduction

The liver is mainly composed of hepatocytes, hepatic stellate cells (HSCs), and liver sinusoidal endothelial cells (LSECs) that perform a comprehensive range of hepatic functions, such as detoxification, bile acid synthesis, and participation in various metabolic processes. However, a variety of stimuli, such as alcohol, drugs, inflammation, or cholestasis, often cause damage to hepatocytes resulting in abnormal liver function and a series of pathophysiologic changes [1] . Liver fibrosis is a common intermediate pathological process of various chronic liver diseases, which is mainly manifested by diffuse excessive deposition of extracellular matrix, leading to abnormal changes in liver tissue structure and affecting the normal physiological functions of liver severely [2] . Clinically, if liver fibrosis is not effectively reversed or curbed, it will progress to irreversible cirrhosis, hepatocellular carcinoma, and other end-stage liver diseases, eventually, leading to the death of patients [3] . Therefore, finding effective therapeutic strategies to ameliorate liver fibrosis in patients is of great importance in preventing the development of end-stage liver diseases.

In the clinical setting, liver transplantation is mostly used for the treatment of end-stage liver diseases, but liver transplantation cannot be widely used due to the defects of extremely rare donors, high cost, rejection, etc [4] . Currently, mesenchymal stem cells for the treatment of liver disease have become a hot spot in the field of biomedicine. As the intermediate pathological process of end-stage liver disease, mesenchymal stem cells can effectively ameliorate hepatic fibrosis through hepatogenic differentiation, immunomodulation, paracrine effects, and other mechanisms [5] . However, it has been reported that MSCs transplanted in the body may have some disadvantages such as low inner-liver colonization and short duration of intervention, which affect their therapeutic efficacy [6] . Nowadays, an increasing number of researchers have demonstrated in animal models of liver fibrosis that the combination of MSCs with drugs can boost the therapeutic effect of MSCs in the treatment of liver fibrosis by promoting the homing of MSCs, differentiating them into functional hepatocyte-like cells, improving the microenvironment, inhibiting the activation of HSCs, and modulating the signaling pathway, and so on. In addition, MSCs-derived extracellular vesicles with the advantages of higher penetrability and lower carcinogenicity also effectively ameliorate liver fibrosis with ultimate safety. What’s more, nanoscale intracellular vesicles can also be used as carriers of natural drugs for drug delivery. This provides new ideas to solve the poor efficiency of MSCs in the treatment of liver fibrosis in the clinic.

Discussion and outlook

Liver fibrosis, as an intermediate pathological process from chronic liver disease to cirrhosis and hepatocellular carcinoma, has become a research hotspot for the treatment of liver diseases due to its reversible properties. However, there is no very effective means to treat liver fibrosis in clinical practice. MSCs, as a kind of pluripotent stem cells, have no ethical issues and wide sources compared with liver transplantation and hepatocyte transplantation, which have attracted much attention in animal experiments and clinical studies of cell transplantation for the treatment of liver fibrosis. Unfortunately, MSCs confront with the challenges such as in vivo microenvironment inadaptation and attenuation of inflammatory response ability after isolation and culture in vitro [45] , which ultimately leads to a low colonization rate and short duration of intervention after transplantation of MSCs into the liver [6] . Therefore, it has not been widely used in clinical practice.

Abstract

Axillary surgery for patients with breast cancer (BC) in 2024 is becoming increasingly specific, moving away from the previous ‘one size fits all’ radical approach. The goal is to spare morbidity whilst maintaining oncologic safety. In the upfront surgery setting, a first landmark randomized controlled trial (RCT) on the omission of any surgical axillary staging in patients with unremarkable clinical examination and axillary ultrasound showed non-inferiority to sentinel lymph node (SLN) biopsy (SLNB). The study population consisted of 87.8% postmenopausal patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative BC. Patients with clinically node-negative breast cancer and up to two positive SLNs can safely be spared axillary dissection (ALND) even in the context of mastectomy or extranodal extension. In patients enrolled in the TAXIS trial, adjuvant systemic treatment was shown to be similar with or without ALND despite the loss of staging information. After neoadjuvant chemotherapy (NACT), targeted lymph node removal with or without SLNB showed a lower false-negative rate to determine nodal pathological complete response (pCR) compared to SLNB alone. However, oncologic outcomes do not appear to differ in patients with nodal pCR determined by either one of the two concepts, according to a recently published global, retrospective, real-world study. Real-world studies generally have a lower level of evidence than RCTs, but they are feasible quickly and with a large sample size. Another global real-world study provides evidence that even patients with residual isolated tumor cells can be safely spared from ALND. In general, few indications for ALND remain. Three randomized controlled trials are ongoing for patients with clinically node-positive BC in the upfront surgery setting and residual disease after NACT. Pending the results of these trials, ALND remains indicated in these patients.

Introduction

Axillary surgery for breast cancer (BC) has evolved significantly from a previous “one size fits all” approach that involved radical surgery, including lymph node dissection extending from the axilla to the neck, to an increasingly granular and individualized surgical treatment. Axillary lymph node dissection (ALND) was the standard of care for all patients with BC until the nineties, which was considered to be a therapeutic procedure. The rationale behind it was that a complete surgical removal of locoregional tumor residues would result in improved survival, a hypothesis that has never been proven and was already questioned by the NSABP-04 trial [1,2,3]. In this landmark study, patients with clinically node-negative and node-positive BC were shown to have similar 10-year overall survival outcomes, no matter whether ALND or axillary radiotherapy (ART) were performed [3]. These results could be confirmed in clinically node-negative patients, who underwent breast-conserving surgery (BCS) and adjuvant radiotherapy of the breast [4]. Therefore, radical surgery and its associated morbidity was increasingly questioned. Axillary staging information was still deemed necessary, leading to the development of the sentinel lymph node (SLN) biopsy (SLNB). Whilst showing a false-negative rate of around 10%, excellent oncologic outcomes were achieved [5,6,7,8]. Notably, SLNB dramatically reduced surgical morbidity and improved quality of life [5,9,10,11,12,13,14,15,16,17]. Nevertheless, approximately 5% of patients still experience surgery-related morbidity [9]. Therefore, studies to identify patients in whom surgical axillary staging can be altogether abandoned have been initiated.

Conclusions

Efforts to de-escalate axillary surgery in BC have led to major changes in treatment paradigms, sparing thousands of women the associated morbidity of ALND whilst remaining oncologically safe, as shown in randomized controlled trials with a high level of evidence. Few indications for ALND remain, with real-world studies being indicative of safe omission possibilities even if ITCs are found after NACT. Such studies generally have a lower level of evidence. However, they can address clinically relevant questions in a global manner, quickly, with the largest number of participants, and therefore the strongest statistical power available. For patients with clinically node-positive BC, the results of three randomized controlled trials—namely, the Alliance A011202 trial, the ADARNAT trial, and the OPBC-03/TAXIS trial—are eagerly awaited.

Abstract

One in eight women will develop breast cancer in the US. For women with moderate (15–20%) to average (12.5%) risk of breast cancer, there are few options available for risk reduction. For high-risk (>20%) women, such as BRCA mutation carriers, primary prevention strategies are limited to evidence-based surgical removal of breasts and/or ovaries and anti-estrogen treatment. Despite their effectiveness in risk reduction, not many high-risk individuals opt for surgical or hormonal interventions due to severe side effects and potentially life-changing outcomes as key deterrents. Thus, better communication about the benefits of existing strategies and the development of new strategies with minimal side effects are needed to offer women adequate risk-reducing interventions. We extensively review and discuss innovative investigational strategies for primary prevention. Most of these investigational strategies are at the pre-clinical stage, but some are already being evaluated in clinical trials and others are expected to lead to first-in-human clinical trials within 5 years. Likely, these strategies would be initially tested in high-risk individuals but may be applicable to lower-risk women, if shown to decrease risk at a similar rate to existing strategies, but with minimal side effects.

Introduction

For women in the US, breast cancer (BC) is the most prevalent cancer and the second-leading cause of cancer-related deaths. Projections for 2023 estimate that 55,720 women will be diagnosed with carcinoma in situ, 297,790 with invasive carcinoma, and 43,170 women will die from BC [1]. With the number of new diagnoses still on the rise, one in eight women will develop BC within their lifetime, but all women are at risk. Therefore, there is a need to develop new strategies for primary prevention with a focus on high-risk (>20%) individuals, but that can also be applied to moderate- (15–20%) and average (12.5%)-risk individuals.

There are well-established risk factors that contribute to the absolute risk of developing BC [2,3]. There are modifiable risk factors such as having a healthy diet, regular exercise, and limiting alcohol consumption [2,4]. Cumulative exposure of breast tissue to estrogen is an important risk factor for BC. This risk can be minimized by various actions such as having their first-born before age 30, limiting the use of hormonal birth control medications, and avoiding hormone replacement therapy. Non-modifiable risk factors that increase cumulative exposure to estrogen include younger age at menarche and older age at natural menopause [2]. There are non-modifiable genetic risk factors that include known mutations in a high-penetrant BC gene such as BRCA1 and BRCA2, cumulative interaction of risk-associated alleles of BC susceptible SNPs, and/or family history with multiple incidences of BC [5]. There are also non-modifiable risk factors related to the personal history of radiation therapy to the chest, and the number of breast biopsies [4].

Conclusions and Future Directions

BC is the leading cause of new cancer cases and is the second leading cause of cancer-related deaths in women. The limited, approved prevention interventions available for high-risk individuals can have severe and long-term side effects that deter many women from making proactive choices. Regrettably, BC prevention is an area of translational research that is currently underfunded by federal agencies [182]. Therefore, emerging and novel approaches for the primary prevention of BC that provide the same or superior protection while minimizing the side effects of current interventions should be pursued and prioritized. These approaches seek to eradicate BC and align well with NIH’s All of US Research Program—a nationwide initiative for precision health interventions that proactively prevent rather than treat disease in high-risk individuals. We provide a comprehensive review of emerging approaches for BC prevention based on non-modifiable risk factors that put women at a higher risk of developing BC. Virtually all of these studies were performed in rodent models of BC, which have some limitations and challenges for direct translation to at-risk individuals. Additional scalability and validation studies in larger animal models will be an important step in bridging the gap between discovery and clinical evaluation. Although currently underutilized, rabbit studies should be considered as an appropriate intermediate model. Evolutionarily, anatomically, and physiologically, rabbit mammary glands are more similar to humans than those of rodent models or other large animals such as cows and sheep [183,184]. Female rabbits have four pairs of mammary glands each containing four ductal trees [177], which can be cannulated for ID injection [177,185,186,187,188,189] using a procedure very similar to ID administration of contrast agents in clinical ductography [190,191] and chemotherapeutic agents in first-in-human clinical research [92,145]. Alternatively, or complementary to validation studies in larger animals, judicious determination based on the scientific rigor and clinical feasibility of these emerging approaches should be applied to prioritize those interventions more likely to have an impact on primary prevention of BC.

Abstract

Background
General practitioners play a pivotal role in the diagnosis attention-deficit/hyperactivity disorder (ADHD) in adults. This systematic review aims to determine the effectivity and feasibility of screening tools for ADHD in adults in primary care.

Method
A literature search was performed in PubMed, Cochrane Library, Ovid, ERIC, PsycInfo, PSYNDEX and Embase in November 2022. Sensitivity and specificity were considered as primary outcomes. Further psychometric properties, feasibility in general practice as well as digital practicability were evaluated as secondary outcomes. Risk of bias was assessed via QUADAS-2/C. A narrative data synthesis and meta-analysis was performed (PROSPERO: CRD42022374597).

Results
A total of fifty-eight studies were included in data analysis. These studies referred to eighty-four various screening tools. ASRS-6 (DSM-V), WURS-25, CAARS-s:sV and TRAQ10 are suitable instruments for screening of ADHD in adults in primary care. The highest test accuracy was shown by ASRS 6 (DSM-V) (Sensitivity=0.83 [0.67–0.92], Specificity=0.87 [0.93–0.8], AUC=0.92, I2=8.6–12.3 %).

Limitations
Included studies used rating scales as reference standard. Some studies compared study groups to control groups with an unknown ADHD status and there is a large degree of heterogeneity between the populations. Some studies referred to the best-balanced results of sensitivity and specificity under a certain cut-off, that has not been determined before.

Conclusion
Feasibility studies are needed to provide more evidence for WURS-25 and CAARS-s:sV. The determination of sufficient cut-offs is important, to improve the identification of ADHD in adults by general physicians.

Introduction

Attention-deficit/hyperactive disorder (ADHD) according to the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) and hyperkinetic disorder (F90) or attention deficit without hyperactivity (F98.8) according to the International Classification of Diseases, editions 10 and 11 (ICD-10/11)) is commonly known as a childhood disorder which is characterized by altered hyperactivity, inattention and impulsivity (Drechsler et al., 2020). These symptoms persist until adulthood in about 50 % of all diagnosed patients (Sibley et al., 2017, 2022). Moreover, patients show characteristic features, which include executive dysfunction, disorganization and emotional distress, leading to an impairment of their daily lives (Barkley, 1997; Wender, 1998). Common comorbidities are depression, borderline personality disorder, social phobia, anxiety, or substance abuse (Fayyad et al., 2017; Kessler et al., 2006). Although a prevalence of approximately 2–3 % of ADHD in adults is estimated, only 0.2–0.4 % are actually diagnosed in Germany (Fayyad et al., 2017; Bachmann et al., 2017; de Zwaan et al., 2012). A possible reason seems to be a gap in medical care for young adults in a time of transition after leaving the pediatric setting (Eklund et al., 2016; Robb and Findling, 2013). Moreover, ADHD might be masked by other psychiatric symptoms and comorbidities (Retz et al., 2013). A missing or failed diagnosis prevents access to optimal medical care in the form of an evidence-based treatment of affected adults. General practitioners are considered to act as so-called „gatekeepers“, a role that is characterized by the initial identification of patients (Kwon et al., 2023; French et al., 2020). Consequently, there is a distinct need for appropriate diagnostic tools in primary care, as has already been identified in relevant guidelines (Eom and Kim, 2023; National Institute for Health and Care Excellence: Guidelines, 2018). There are many different screening tools, which differ in relevant aspects of the disorder. Some screening tools evaluate childhood symptoms, whereas others focus on current adult symptoms. Some screening tools are based on DSM-5 criteria, others on Utah criteria or no specified criteria. They differ in time or way of application, number of items, and scoring methods. For example, the choice of cutoff scores in ADHD screening tools directly influences clinical decision-making, including the initiation of treatment interventions. A higher cutoff score may exclude individuals who, despite exhibiting significant symptoms, do not meet the stringent criteria, potentially denying them access to necessary interventions. Conversely, a lower cutoff score could lead to the inclusion of individuals with mild symptoms, leading to over-treatment. The variability in cutoff points complicates the determination of treatment eligibility, potentially affecting the efficacy and efficiency of ADHD management strategies. Until, there is no comprehensive overview of validated studies including a quantitative meta-analysis (Taylor et al., 2011). Therefore, the aim of the study was to evaluate screening tools for ADHD in adults, considering sensitivity, specificity and feasibility for primary care.

Conclusion

Our findings show that screening tools as the ASRS-6 (DSM-V), the WURS-25, the CAARS-s:sV and the TRAQ10 are suitable instruments for screening of ADHD in adults in primary care due to their high validity and perceived feasibility in this setting. The best evidence exists for the ASRS-6, which was included in our meta-analysis. For more evidence concerning feasibility of the WURS-25 as well as the CAARS-s:sV, which also were part of the meta-analysis, feasibility studies are required. Regarding other tests like the TRAQ10 with equivalent promising results but insufficient options of comparison there is a need of further validation studies to create more evidence in that part. The determination of cut-offs is of great importance since it affects the ability of a screening tool distinguishing between real and false positives respectively negatives. Further research is required to identify the optimal cut-off of the different tests for a general population sample as we find it in primary care. Hence, the identification of ADHD in adults by general physicians would be improved without leading to increased misdiagnoses.

Abstract

Background. Psychological distress is a progressive health problem that has been linked to decreased quality of life among university students. This meta-analysis reviews existing randomized controlled trials (RCTs) that have examined the effects of mindfulness-based stress reduction (MBSR) on the relief of psychosomatic stress-related outcomes and quality of life among university students. Methods. The PubMed, EMBASE, Web of Science, PsycINFO (formerly PsychLit), Ovid MEDLINE, ERIC, Scopus, Google Scholar, ProQuest, and Cochrane Library databases were searched in November 2023 to identify the RCTs for analysis. Data on pathology (anxiety, depression, and perceived stress), physical capacity (sleep quality and physical health), and well-being (mindfulness, self-kindness, social function, and subjective well-being) were analyzed. Results. Of the 276 articles retrieved, 29 met the inclusion criteria. Compared with control therapies, the pooled results suggested that MBSR had significant effects, reducing anxiety (SMD = −0.29; 95% CI: −0.49 to −0.09), depression (SMD = −0.32; 95% CI: −0.62 to −0.02), and perceived stress (SMD = −0.41; 95% CI: −0.60 to −0.29) and improving mindfulness (SMD = 0.34; 95% CI: 0.08 to 0.59), self-kindness (SMD = 0.57; 95% CI: 0.30 to 1.12), and physical health (SMD = −0.59; 95% CI: −1.14 to −0.04). No significant differences were observed in sleep quality (SMD = −0.20; 95% CI: −0.06 to 0.20), social function (SMD = −0.71; 95% CI: −2.40 to 0.97), or subjective well-being (SMD = 0.07; 95% CI: −0.18 to 0.32). The quality of the evidence regarding sleep quality and physical health outcomes was low. Conclusions. MBSR therapy appears to be potentially useful in relieving functional emotional disorders. However, additional evidence-based large-sample trials are required to definitively determine the forms of mindfulness-based therapy that may be effective in this context and ensure that the benefits obtained are ongoing. Future studies should investigate more personalized approaches involving interventions that are tailored to various barriers and students’ clinical characteristics. To optimize the effects of such interventions, they should be developed and evaluated using various designs such as the multiphase optimization strategy, which allows for the identification and tailoring of the most valuable intervention components.

Introduction

Mindfulness therapy is a standardized psychological intervention that aims to reduce stress, encourage mindful thinking habits, and allow recipients to manage difficult emotional processing. It focuses on the concentration of one’s attention in the moment, nonsubjective judgment, and openness to accepting personal experience and involves corresponding behavioral training, such as attention training, body scanning, and sitting meditation [1]. Previous research on psychological interventions has found that mindfulness therapy can help reduce stress among university students and affects their overall quality of life and the psychological functions to which they adapt [2].

The theoretical support and the understanding of the operating mode are reasonable but still have differences. Thus, the mental health benefits, potential effects, and limitations of mindfulness therapy for university students warrant further examination. Although education and social support can be effective in preventing and treating the underlying psychological problems among university students with poor mental health, such interventions do not always affect or improve psychological well-being [3, 4].

The most prevalent psychological symptoms among university students are anxiety, mental stress, and emotional distress, which can result in decreased functioning in the context of academic and interpersonal stress. Global mental health surveys conducted by the World Health Organization (WHO) indicate that mental disorders are highly prevalent among university students, with 12-month prevalence rates ranging from 20.3% to 45% of university students over the age of 18 [5–7]. The prevalence rates of insomnia, depressive symptoms, and anxiety symptoms were 37.80%, 48.20%, and 36.70%, respectively, among Chinese university students during the COVID-19 pandemic [8]. In a randomized controlled trial with 11,169 university students conducted by the WHO, students had increasing intentions to use mental health services: The results indicated lifetime use rates of 12.6% and 7.3% for psychotherapy and medication for emotional problems, respectively. Suicidal thoughts and behaviors and nonsuicidal self-injury within the preceding 12 months were also common, with 21.1% of students in the sample reporting suicidal ideation, 10.6% reporting suicide plans, 0.4% reporting suicide attempts, and 6.8% reporting nonsuicidal self-injury [5]. Furthermore, one previous study found that high-compliance mental health services had a significant effect on students’ intention to seek mental health services in the next semester [9–11].

Results

3.1. Description of Studies
A total of 276 studies items were initially obtained through the database search. Using NoteExpress, 193 deduplicated studies were obtained, and the remaining 220 items were obtained. After reviewing their titles and abstracts, 135 studies that were of incompatible research types were excluded. A total of 13 articles were further excluded after reading the full text, and the remaining 29 studies [24–53] were retained for data extraction. The baselines of the trials were comparable. The literature search process and results are shown in Figure 1.

Abstract

Background
Progress has been achieved in many fields in understanding the biological mechanisms of depression, including genome-wide association analysis, neurotransmitter system function, brain regions and neural networks, inflammatory response, neuroplasticity, neuroimaging, and neuro electrophysiology. These progresses provide a reliable basis for developing the medical and physical therapies for depression. However, the current treatments developed from biological mechanisms can only address less than 60% of depressive symptoms and have limited efficacy in improving social functioning and reducing recurrence. Studies have explored the non-biological mechanisms of depression in mental fields. These progresses are helpful to develop more interventions that could alleviate depressive symptoms, improve functional impairments, and reduce recurrence, thereby promoting a more comprehensive recovery in depressed patients. However, there is not a systematic and deep review to highlight the non-biological mechanisms of depression.

Methods
This study summarizes the recent progress in the non-biological fields of depression by searching publications on human studies in PubMed, PMC, and Google Schooler with exclusion of animal studies.

Results
This study reviews the intergenerational transmission characteristics, the relationship between depression and emotional trauma, cognitive deficit, relationship impairment, self-function, sense of the meaning of life, motivation deficit, and psycho-rationality of depression.

Conclusions
This study was clarified the non-biological mechanisms and characteristics of depression and provided a theoretical basis for the development of non-drug interventions.

Introduction

To date, studies on the pathogenesis of depression are mainly focus on its biological mechanisms (Miao & Chang, 2021), including studies on epigenetic alterations, genome-wide association, neurotransmitter system, brain regions and neural networks, inflammatory responses, neuroplasticity, neuroimaging, and neuro electrophysiological changes (Li et al., 2021). The outstanding contributions of these studies provide a theoretical basis for pharmacotherapy and physical therapy of depression (Li et al., 2019). However, the current treatments developed from biological mechanisms can only relieve 58% of depressive symptoms (Ormel et al., 2019). Moreover, these current pharmacotherapy and physical therapy have limited efficacy in improving prognosis and social function, as well as reducing relapse rates (Cieślik et al., 2020). The cognitive behavioral therapy has been shown to be highly effective in treating depression but has limited impact on generational deficits and trauma-related emotional responses in the symptomatic components of depressive symptoms (Johnsen, T. J., & Friborg, O. 2015). The eye movement desensitization and reprocessing therapy has shown some positive outcomes in helping individuals to reprocess traumatic memories of some emotional traumas, but it is not appropriate for traumatized populations of all backgrounds and can exacerbate symptoms in some populations. Therefore, its limitations and side effects need to be considered (Shapiro, F. 2014). Thus, exploration of new mechanisms and subsequent development of new treatments is an urgent need for patients with depression.

Results

3.1. Non-biological transgenerational transmission of depression
Intergenerational transmission of pathological psychology refers to the phenomenon that psychological disorders or problems presented in the previous generation can reappear in the next generation, or that the behavior or psychological trauma of the previous generation causes mental and psychological problems in the next generation. These problems may span generations and manifest in different ways and degrees (Cooke et al., 2019). In recent years, evidence on the intergenerational transmission of depression has been accumulated. In the biomedical field, family and twin studies have repeatedly validated that the intergenerational transmission of depression is often a result of gene-mediated genetic disorders or epigenetic inheritance (Goodman, 2020, Park et al., 2019). However, the non-biological transgenerational mechanisms of depression have also attracted attention recently (Gotlib et al., 2020).

More and more non-biological transmissions have been observed, while the intergenerational phenomenon of depression and its transmission ways have different explanations (Hentges et al., 2021). For example, parental depression may be transmitted to the next generation through multiple pathways: intergenerational transmission of trauma (Hankerson et al., 2022); intergenerational damage to emotions, self-esteem, and cognition; family culture; parenting style; and behavioral consequences etc. (Kang et al., 2021, Risi et al., 2021, Kujawa et al., 2020, Johnco et al., 2021). These transgenerational mechanisms may indirectly influence the biological changes that evolve into the symptoms of depression (Allison et al., 2023). In the intergenerational transmission of depression, offspring may not inherit the symptoms of depression, but instead display a variety of psychological dysfunctions a variety of psychological dysfunctions, including a tendency to react negatively to emotions (Israel & Gibb, 2024), a state of self-esteem hypersensitivity, cognitive biases, and excessive self-focus (Woody et al., 2022). In addition, offspring may also display relationships with alienation, control, and unclear boundaries (Wei et al., 2023), and even the characteristics of illness that appear in early adulthood or suicidal tendencies (Gijzen et al., 2021).

Abstract

Language impairments often appear in patients with schizophrenia and are potential targets for rehabilitation. Clinical practice and research should be intimately connected. The aim was to perform a narrative review of the assessment and intervention tools that have been used for the rehabilitation of schizophrenia patients with language and communication impairments. Two types of tools, general and specific, were developed for both purposes. General tools include the Positive and Negative Syndrome Scale for assessment, and the Integrated Psychological Therapy for intervention. The specific tools used to evaluate language and communication impairments include the Scale for the Assessment of Thought, Language and Communication, the Formal Thought Disorder scales (for caregivers and patients), and the Thought and Language Disorder scale. The most recent language-specific intervention tools include the Cognitive Pragmatic Treatment, Conecta-2, Let’s talk! Multimodal Speech-Gesture training, Speech Therapy Intervention Group, and PragmaCom. These tools primarily involve psychopathology/psychiatry, psychology, linguistics, speech and language therapy, and nursing. In conclusion, a wide range of assessment and intervention tools are available for the rehabilitation of language and communication impairments associated with schizophrenia. An integrative and interdisciplinary approach should always be considered for rehabilitation of language and communication in patients with schizophrenia throughout their lifetime.

Introduction

Language is a basic skill in humans that facilitates communication with their environment, mainly with other humans. Communication has also been recognized by the International Communication Project as a human right which is embedded within Article 19 of the Universal Declaration of Human Rights [1]. This project highlights the importance of human communication and the significant impact of communication disabilities on every aspect of life, including positive social relationships, literacy, and employment, and the need to enable those with communication disability to fully access and participate in society [2].

1.1. Heterogeneity of language and communication impairments in schizophreniaAccording to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders [3], a key feature of the schizophrenia spectrum as well as of other psychotic disorders is disorganized speech. However, the term ‘disorganized speech’ remains ambiguous and is often used as a replacement of the formerly used term ‘formal thought disorder’ (FTD), clinically considered as ‘impairments in the production of language and subjective alterations in the thought process’ [4]. In fact, the term FTD was replaced by ‘disorganized speech’ as the latter can be object to direct observation and assessment, whereas the former can only be deduced from other deviations in overt behaviour.

Conclusions

We conclude that: i) there is currently a wide range of assessment and intervention tools that cover various language and communication impairments in schizophrenia; ii) the rehabilitation of language and communication requires an integrative and interdisciplinary approach, and should always be considered in patients with schizophrenia throughout their lifetime; and iii) further research on the assessment and intervention tools for the rehabilitation of language and communication in patients with schizophrenia is needed.