Disability Rates Research Articles

Magnetically driven hydrogel microrobots for enhancing the therapeutic effect of anlotinib on osteosarcoma

IntroductionOsteosarcoma, characterized by high mortality and disability rates, poses a significant challenge due to its complex genetic background and the absence of specific membrane receptors, which hinder effective targeted therapy. Active targeting has emerged as a promising approach to address this issue.MethodsIn this study, magnetically driven hydrogel robots (MMHR) were utilized to load and deliver drugs precisely to target sites. The drugs included SCR1481B16, a specific MET inhibitor proven to inhibit MET-driven tumor growth, and Anlotinib. The microrobots were designed to navigate under magnetic guidance, enhancing drug efficacy while minimizing damage to normal tissues.ResultsThe study explored the potential of MMHR loaded with SCR1481B16 and Anlotinib in the treatment of Anlotinib-resistant osteosarcoma. The microrobots were successfully designed and produced, demonstrating the ability to deliver drugs precisely to tumor sites. Evaluation of the microrobots showed an enhanced sensitivity of tumors to Anlotinib, providing new insights into the treatment of drug-resistant osteosarcoma.DiscussionTumors overexpressing MET often develop resistance to VEGFR-targeted drugs. The use of SCR1481B16 as a MET inhibitor in combination with Anlotinib, delivered by magnetically driven hydrogel microrobots, offers a novel strategy to overcome this resistance. However, further in-depth research and validation are required before the clinical application of this method can be considered.ConclusionIn conclusion, magnetically driven hydrogel microrobots loaded with SCR1481B16 provide a promising new strategy for enhancing the sensitivity of Anlotinib-resistant osteosarcoma, bringing hope for future clinical applications in the treatment of this challenging disease.

Current Status and Progress in Integrative Treatment of Acute Ischemic Cerebrovascular Disease

Acute ischemic cerebrovascular disease (AICD) poses a severe threat to human health, characterized by high incidence and disability rates. Western medicine currently offers multiple treatment methods, such as thrombolysis, anticoagulation, and cerebral circulation improvement, while traditional Chinese medicine demonstrates unique advantages in herbal prescriptions, proprietary Chinese medicines, acupuncture, and massage therapies. Integrative treatment approaches combining Chinese and Western medicine have become widespread in clinical practice, yet challenges remain in optimizing specific treatment plans and elucidating mechanisms of action. This paper aims to comprehensively analyze the current status of integrative treatment for AICD, outline its developmental trajectory, and provide insights for enhancing treatment efficacy.

Traumatic Brain Injury as a Public Health Issue: Epidemiology, Prognostic Factors and Useful Data from Forensic Practice

Traumatic brain injury (TBI) represents a major public health problem, being a leading cause of disability and mortality among young people in developed countries. Head trauma occurs across all age groups, each experiencing consistently high rates of mortality and disability. This review aims to present an overview of TBI epidemiology and its socioeconomic impact, alongside data valuable for prevention, clinical management, and research efforts. Methods: A narrative review of TBI was performed with a particular focus on forensic pathology and public health. In fact, this review highlighted the economic and epidemiological aspects of TBI, as well as autopsy, histology, immunohistochemistry, and miRNA. Results: These data, together with immunohistochemical markers, are crucial for histopathological diagnosis and to determine the timing of injury onset, a fundamental aspect in forensic pathology practice. There is compelling evidence that brain injury biomarkers may enhance predictive models for clinical and prognostic outcomes. By clarifying the cause of death and providing details on survival time after trauma, forensic tools offer valuable information to improve the clinical management of TBI and guide preventive interventions. Conclusions: TBI is one of the most common causes of death today, with high costs for health care spending. Knowing the different mechanisms of TBI, reduces health care costs and helps improve prognosis.

The burden and trends of heart failure caused by ischemic heart disease at the global, regional, and national levels from 1990 to 2021.

Ischemic heart disease (IHD) is a major cause of heart failure (HF), a condition expected to increasingly affect global health and economics. This study evaluates the global burden, trends, and disparities of HF linked to IHD, aiming to inform health policy development. Data from the Global Burden of Disease Study 2021 (GBD2021) is analyzed using Joinpoint regression, decomposition analysis, and Bayesian age-period-cohort analysis (BAPC). Health disparities are assessed through the Socio-demographic Index (SDI) via the Slope Index of Inequality (SII) and the Concentration Index (CI), with future trends projected from 2022 to 2045. In 2021, global HF cases due to IHD were over 19.16 million, with an age-standardized prevalence rate (ASPR) of 228.31 per 100 000 [95% UI, 188.18 to 279.55] and age-standardized years lived with disability (ASYLDs) rate of 20.43 per 100 000 [95% UI, 13.55 to 28.7].In 2021, there was a 2.87% increase in ASPR and ASYLDs compared to 1990, primarily driven by population growth and aging.Significant reductions in global ASPR and ASYLDs disparities are observed, though the disease burden has intensified in countries with lower SDI levels. Projections indicate that by 2045, while the prevalence and YLDs for HF caused by IHD will increase, while the ASPR and ASYLDs are expected to decrease. The global burden of HF from IHD remains a significant concern. Urgent improvements in the allocation of medical resources and the implementation of effective prevention and management strategies are necessary to address this issue.

Abstract 4117645: Ischemic Heart Disease Trends in Canada: A 30-Year Epidemiological Study

Introduction: Ischemic heart disease (IHD) results from coronary artery blockages that impede myocardial blood flow. We aim to examine the temporal trends of IHD in Canada from 1990 to 2019, assessing age-standardized mortality, disability-adjusted life years (DALYs), and other health indicators. Methods: We analyzed data from the 2019 Global Burden of Disease study on Canadian IHD cases over three decades. The study investigated age-standardized deaths, DALYs, years lived with disability (YLDs), years of life lost (YLLs), prevalence, and incidence across both sexes. We performed statistical analyses using Microsoft Excel 16.63.1. Results: Over the period from 1990 to 2019, Canadian men and women experienced notable decreases in IHD incident rates [-45.11%], overall mortality [-60.64%], YLLs [-62.824%], prevalence [-26.778%], YLDs [-48.729%], and DALYs [-50.467%]. Detailed analysis revealed a reduction in death rates by 61.311% in men and 61.119% in women, while YLLs decreased by 63.115% for men and 63.808% for women. Similarly, DALYs showed a decline of 62.67% for men and 63.25% for women. Prevalence rates fell by 25.417% in women and 29.594% in men, whereas YLDs decreased by 51.148% for women and 49.172% for men. The 2019 data confirmed a per 100,000 population count of 48.78 YLDs, 1020.28 YLLs, and 1069.06 DALYs across both sexes. Conclusions: This study illustrates a significant decrease in ischemic heart disease (IHD) metrics in Canada from 1990 to 2019, highlighting notable reductions in mortality, prevalence, and disability rates among both genders. The findings underscore the effectiveness of healthcare improvements and public health initiatives and IHD. Despite these advancements, IHD continues to pose a substantial health challenge, indicating the need for ongoing efforts in medical care, policy-making, and lifestyle modifications to further alleviate the disease's burden in Canada.

Investigation of GPM6B as a novel therapeutic target in Osteoarthritis.

Osteoarthritis (OA) is the most common motor system disease in older people, characterized by a high incidence and significant social and economic burden. Women have a higher risk of OA, more severe clinical symptoms, and a higher rate of disabilities than men. However, the pathogenesis of OA remains unclear. Therefore, we screened for differentially expressed genes (DEGs) in OA patients of different sex and searched for new targets that may be involved in regulating the development of OA. The study compared the expression of DEGs in synovial fluid exosomes between male and female patients with OA through RNA sequencing combined with bioinformatics analysis using public data. To evaluate the screened DEGs, synovial tissue and fluid samples were obtained from patients with OA who underwent joint replacement surgery. SiRNA-mediated knockdown in vitro experiments were performed to investigate the role of glycoprotein membrane 6B (GPM6B). Meanwhile, GPM6B gene knockout mice were used to assess the in vivo pathological roles of GPM6B in OA. The results revealed that GPM6B is a potential target associated with OA. Immunofluorescence staining demonstrated that GPM6B was expressed in fibroblast-like synoviocytes (FLS) and macrophage-like synoviocytes in patients with OA. In vitro experiments confirmed that GPM6B knockdown can reduce the expression of inflammatory factors in primary FLS from patients with OA. Under inflammatory conditions, GPM6B knockdown can reduce the expression of matrix metalloproteinases as well as proliferation of FLS. In addition, using a destabilization of the medial meniscus-induced OA model, we revealed that GPM6B is associated with OA progression in mice. Thus, we provided evidence that GPM6B act as a new target associated with OA.

SURG-34. NEURO ENDOSCOPIC VS CRANIOTOMY APPROACH IN SUPRATENTORIAL HYPERTENSIVE INTRACEREBRAL HEMORRHAGE: AN UPDATED META-ANALYSIS

Abstract INTRODUCTION Intracerebral hemorrhage (ICH) is a serious medical condition associated with high mortality and disability rates. Surgical interventions, including neuro-endoscopic surgery (NES) and craniotomy, are employed to manage ICH and improve patient outcomes. This meta-analysis compares the effectiveness of NES versus craniotomy in treating ICH. METHODS A systematic literature search was conducted to identify relevant studies comparing NES with craniotomy for ICH. Inclusion criteria encompassed primary or secondary results from randomized controlled trials (RCTs) or observational studies (OSs) with confirmed supratentorial ICH. Data were extracted, and methodological quality was assessed using appropriate tools. Statistical analysis was performed using Comprehensive Meta-Analysis. RESULTS Twenty-six studies (n=3237 patients) were included in the analysis. NES was associated with significantly lower mortality compared to craniotomy (OR: 0.45, 95% CI 0.33 to 0.60, p < 0.00001). Hematoma evacuation rates were higher with NES (SDM: 1.505, 95% CI 0.835 to 2.160, p < 0.00001). NES also showed better functional outcomes (OR: 3.31, 95% CI 1.78 to 6.17, p = 0.0002) and reduced blood loss (SDM: -3.06, 95% CI -3.979 to -2.141, p = 0.000). Additionally, NES was associated with shorter hospital and ICU stays, shorter operative times, and fewer complications such as infection and rebleeding. CONCLUSION NES emerges as a promising alternative to craniotomy for treating ICH, offering advantages in terms of mortality reduction, improved functional outcomes, and fewer complications. Future studies should explore advancements in neuro-endoscopic techniques to optimize patient outcomes further.

Effects of a Virtual Trauma Clinic on admissions and length of stay for minor to moderate trauma.

To investigate the feasibility of a Virtual Trauma Clinic (VTC) for patients with minor to moderate trauma, and evaluate patient satisfaction and outcomes. One hundred VTC patients were matched 1:1 with historical patients from the hospital trauma registry who received conventional care. Matching was based on age ± 5 years, sex, mechanism of injury, Injury Severity Score ± 2, trauma team activation and day of week of presentation. VTC patients were sent surveys on experience and outcome measures. VTC was associated with reduced average hospital length of stay for admitted patients by 1.81 days (95% CI = -2.82, -0.79; P = 0.001) and reduced hospital admissions (odds ratio 0.26; 95% CI = 0.14, 0.48; P < 0.001). There was an avoidance of 199 inpatient bed days in total, with no trauma-related readmissions within 30 days post-hospital discharge. 92% of respondents (n = 22) rated the care they received from VTC as excellent or good. Patient-reported outcome surveys showed overall improvement in functional domains but evidence of ongoing disability, with persistent issues of pain and psychological distress at 1 month post-injury. Patients with minor to moderate trauma have ongoing care needs with high rates of pain, psychological distress and disability remaining prevalent long after discharge. VTC provided an innovative strategy for hospital avoidance with high levels of patient satisfaction and no adverse effects on safety. The overall quality of care for these patients was enhanced through the provision of standardised, patient-centred and multidisciplinary follow-up.

Comparison of strategies based on DTI visualisation for stereotactic minimally invasive surgery in the treatment of moderate-volume thalamo-basal ganglia cerebral haemorrhage: a protocol for a multicenter prospective study

IntroductionHypertensive intracerebral hemorrhage (HICH) is a condition associated with significant morbidity, mortality, and disability, particularly among the elderly population. The management of moderate thalamic-basal ganglia cerebral hemorrhage primarily relies on conservative approaches. Nevertheless, the rate of long-term disability remains high. In recent years, there has been significant advancement in minimally invasive surgery and diffusion tensor imaging techniques. Consequently, the utilization of Diffusion Tensor Imaging (DTI) technology in patients with cerebral haemorrhage allows for the identification of the haematoma’s location in relation to the Corticospinal Tract (CST). This enables the development of precise puncture pathways that can be visualized, thereby avoiding any potential damage to the CST.Methods and analysisDiffusion Tensor Imaging (DTI) is a method used to assess the structural and physiological characteristics of biological tissue by examining the diffusion behavior of water molecules.In the central nervous system, limb paralysis will be inevitable if the corticospinal tract is damaged. By employing DTI imaging techniques on individuals, it becomes possible to visualize the spatial relationship between the hematoma and the CST. This approach allows avoidance of the CST during preoperative planning of the puncture path, thus reducing secondary injuries caused by the procedure. The primary objective of this study was to assess the ability of patients in the minimally invasive surgery group and the conservative group to perform activities of daily living after 6 months of treatment. In addition, secondary outcomes included assessment of hematoma resorption/clearance ratios, cytokine levels, complication rates, and therapeutic indexes at different treatment durations, as well as long-term safety and efficacy at 2–3 years of follow-up. Furthermore, subgroup analysis, and sensitivity analysis were conducted to further analyze the data. Logistic single-variate and multivariate regression analyses were applied to understand the adverse factors affecting prognosis.Ethics and disseminationThe clinical study was reviewed and approved by the Ethics Committee of the First People’s Hospital of Yibin. The ethical number is: 2023 Review (64).Registration numberThis protocol is registered in the Prospective Registry of Chinese Clinical Trial Registries (PROCCTR). The full date of first registration is 28/12/2023. The registration number for PROCCTR is ChiCTR2300079252.

Transoral penetrating craniocerebral injury: a case report and literature review

A penetrating brain injury is a rare type of neurosurgical trauma associated with extremely high mortality and disability rates. Penetrating skull base injuries caused by arrows seldom occur because injuries caused by such weapons are more likely to be accidental. However, the number of self-inflicted injuries is increasing, and these injuries have varying patterns and high mortality rates. We report a case of a transoral penetrating craniocerebral injury caused by an arrow in a suicidal patient. Preoperative imaging is crucial for detecting and planning the surgical approach. Surgery is an effective treatment for this type of injury. Additionally, we reviewed previous case reports on this type of injury to provide recommendations for its clinical detection and treatment.

Employment status of multiple sclerosis patients in Japan

Aims We conducted a questionnaire survey on Japanese MS patients to determine the relationship of fatigue, depression, and physical activity limitations with the employment status. Materials and Methods The study was conducted to assess the Patient Reported Outcome of MS patients treated with disease modifying drug ≥6 months by recruiting MS patients from a web-based patient panel. Multiple regression analysis was performed by using items described in the Work Productivity and Activity Impairment Questionnaire-General Health Version 2.0 (WPAI-GH) and Fatigue Severity Scale (FSS), Quick Inventory of Depressive Symptomatology (Self-Report) (QIDS-SR), and Patient Determined Disease Step (PDDS). Results Employment rates decreased after MS development and were more pronounced in the group with advanced physical disability with PDDS score ≥ 3. Health-related activity limitations were higher with advanced disability. In the analysis of the 5 subdomains of WPAI-GH by FSS score, the domains “due to health reasons”, “disability rates during work”, “overall work disability among the employed”, and” health-related limitations” all increased with higher FSS scores.” In WPAI-GH by QIDS-SR, the work disability rate was higher in the depressed group than in the normal group, and health-related activity limitations increased with the greater depression. Limitations This is a cross-sectional survey and data are based on PRO, hence are subjective and are collected based on patients' overall responses. Some bias could be attributed to memory and literacy rates as this is an online survey. Conclusions The results suggested that the onset of MS prevented patients from working and forced them to resign from their jobs or give up full-time work. The rate of employment tended to be lower in the group with advanced limitations; suggesting that controlling the progression of limitations may lead to lower turnover, and the rate of health-related activity limitations was correlated with the degree of physical activity limitations, depression, and fatigue, respectively.

Hypoxic postconditioning modulates neuroprotective glial reactivity in a 3D cortical ischemic-hypoxic injury model

Stroke remains one of the major health challenges due to its high rates of mortality and long-term disability, necessitating the development of effective therapeutic treatment. This study aims to explore the neuroprotective effects of hypoxic postconditioning (HPC) using a cell-based 3D cortical ischemic-hypoxic injury model. Our model employs murine cells to investigate HPC-induced modulation of glial cell reactivity and intercommunication post-oxygen-glucose deprivation-reoxygenation (OGD-R) injury. We found that a single HPC session (1HPC) provided the most significant neuroprotection post-OGD-R compared to multiple intermittent hypoxic treatments, evidenced by improved spheroidal structure, enhanced cell survival and reduced apoptosis, optimal modulation of neuronal phenotypes, dampened ischemic responses, and augmented neurite outgrowth of spheroids. Furthermore, 1HPC suppressed both pro-inflammatory A1 and anti-inflammatory A2 astrocyte phenotypes despite the induction of astrocyte activation while reducing microglial activation with inhibited M1 and M2 reactive states. This was accompanied by a decrease in gene expression of the pro-inflammatory cytokines essential to microglia-astrocyte signaling, collectively suggesting a shift of glial cells away from their traditional reactive states for neuroprotection. This study highlights the potential of 1HPC as a novel therapeutic intervention for ischemic injury via the modulation of neuroprotective glial reactivity. Moreover, the 3D cortical ischemic-hypoxic injury model employed here holds enormous potential serving as a disease model to further elucidate the underlying mechanism of HPC, which can also extend to the applications in brain regeneration, drug development, and the modeling of neural diseases.

Analysis of Stroke Burden in China from 1990 to 2021 and Projections for the Next Decade.

This study aims to describe the temporal trends of stroke burden in different age and sex groups in China from 1990 to 2021, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs), and to compare these data with global figures. Using data from the Global Burden of Disease (GBD) database from 1990 to 2021, we analyzed changes in stroke burden in China and globally. The average annual percentage change (AAPC) was calculated using Joinpoint software to reflect trends. Stroke burden differences across various age groups and sexes were compared, and the ARIMA model was utilized for future projections. Between 1990 and 2021, the age-standardized incidence rate (ASIR) of stroke in China decreased from 226.938 to 204.753 per 100,000, while the global ASIR decreased from 180.973 to 141.553 per 100,000. The age-standardized prevalence rate (ASPR) in China increased from 1167.425 to 1301.42 per 100,000, whereas the global ASPR decreased from 1201.111 to 1099.31 per 100,000. The age-standardized mortality rate (ASMR) in China fell from 242.18 to 138.029 per 100,000, while the global ASMR decreased from 144.313 to 87.454 per 100,000. China's age-standardized DALY rate (ASDR) declined from 4834.791 to 2648.025 per 100,000, whereas the global ASDR decreased from 3078.952 to 1886.196 per 100,000. The AAPCs for ASIR, ASPR, ASMR, and ASDR in China were -0.370%, 0.326%, -1.793%, and -1.933%, respectively, compared to -0.291%, -0.807%, -1.601%, and -1.570% globally from 1990 to 2021. Age and sex significantly influenced the stroke burden, with higher incidence and mortality rates in males than in females. Projections for the next decade indicate that stroke incidence in China will remain stable, with an expected rise in ASPR, and declines in ASMR and ASDR. Globally, ASIR is expected to decline, while ASPR will rise, and ASMR and ASDR will continue to decrease. From 1990 to 2021, the incidence, mortality, and DALYs of stroke in China have decreased, while the prevalence has increased. Stroke burden is age-related, with higher prevalence in older adults and higher mortality in the elderly. Males are more susceptible to stroke and have a higher risk of death. Over the next decade, stroke prevalence in China is expected to rise, posing challenges due to population aging, even as mortality and disability rates decline. Sustained public health efforts will be necessary.

Development and evaluation of the Trauma Screener-Intellectual Disability: a post-traumatic stress disorder screening tool for adults with mild intellectual disability or borderline intellectual functioning.

This study aimed to evaluate the validity and reliability of the adult self-report and proxy version of the Trauma Screener-Intellectual Disability (TS-ID) in adults with mild intellectual disability or borderline intellectual functioning (MID-BIF). An optimal cut-off value was determined for the ratio of specificity to sensitivity for predicting the diagnosis of post-traumatic stress disorder (PTSD). The TS-ID was adapted from a Dutch Child and Adolescent Trauma Screener, for use with adults with MID-BIF. Outcomes based on the TS-ID were compared with the presence of PTSD, as classified using the Diagnostic Interview Trauma and Stressors-Intellectual Disability (Mevissen et al. 2018). The TS-ID adult version was administered to 97 participants with MID-BIF who lived in supported housing, whereas the TS-ID proxy version was administered to 92 family members or professional caregivers. The TS-ID adult version showed high internal consistency (Cronbach's α=.94) and excellent validity (AUC=.94) for distinguishing PTSD in adults with MID-BIF. Optimal specificity and sensitivity was found at a cut-off score of 18. Although the TS-ID proxy version demonstrated excellent internal consistency (Cronbach's α=.93), it showed no validity in statistically distinguishing PTSD in adults with MID-BIF. The TS-ID showed favourable psychometric qualities as a screening instrument of PTSD in the case for people with MID-BIF.

VCP enhances autophagy-related osteosarcoma progression by recruiting USP2 to inhibit ubiquitination and degradation of FASN

Osteosarcoma (OS) is a highly aggressive malignant tumor with a high rate of disability and mortality rates, and dysregulated autophagy is a crucial factor in cancer. However, the molecular mechanisms that regulate autophagy in OS remain unclear. This study aimed to explore key molecules that affect autophagy in OS and their regulatory mechanisms. We found that fatty acid synthase (FASN) was significantly increased in activated autophagy models of OS and promoted OS proliferation in an autophagy-dependent manner, as detected by LC3 double-labeled fluorescence confocal microscopy, western blotting, transmission electron microscopy (TEM), and cell functional experiments. Furthermore, co-immunoprecipitation combined with mass spectrometry (Co-IP/MS), ubiquitination modification, molecular docking, and protein truncation methods were used to identify FASN-interacting proteins and analyze their effects on OS. Valosin-containing protein (VCP) enhanced the FASN stability by recruiting ubiquitin specific peptidase-2 (USP2) to remove the K48-linked ubiquitin chains from FASN; domain 2 of VCP and the amino acid sequence () of USP2 were critical for their interactions. Gain- and loss-of-function experiments showed that the inhibition of FASN or USP2 attenuated the stimulatory effect of VCP overexpression on autophagy and the malignant phenotypes of OS cells in vitro and in vivo. Notably, micro-CT indicated that VCP induced severe bone destruction in nude mice, which was abrogated by FASN or USP2 downregulation. In summary, VCP recruits USP2 to stabilize FASN by deubiquitylation, thereby activating autophagy and promoting OS progression. The identification of the VCP/USP2/FASN axis, which mediates autophagy regulation, provides important insights into the underlying mechanisms of OS and offers potential diagnostic and therapeutic strategies for patients with OS.

BAK ameliorated cerebral infarction/ischemia–reperfusion injury by activating AMPK/Nrf2 to inhibit TXNIP/NLRP3/caspase-1 axis

BackgroundCerebral ischemia/reperfusion (I/R) injury is a serious vascular disease with extremely high mortality and disability rate. Bakuchiol (BAK) was found in leaves and seeds of Psoralea corylifolia Linn and has been shown to decrease inflammation and reduce oxidative stress, while the mechanism of BAK in ameliorating cerebral I/R injury remains unclear. MethodsMiddle cerebral artery occlusion reperfusion (MACO/R) was used to establish mouse model. The protective effect of BAK in MCAO/R mices was detected by performing neurological deficit testing, TTC staining, and H&E staining. Oxygen/glucose deprivation and reperfusion (OGD/R) was used to stimulate SH-SY5Y cells in vitro. Protein expression was detected by western blotting, gene expression was detected by quantitative real-time polymerase chain reaction and apoptosis was detected by immunofluorescence. ResultsOur study indicated that BAK protected ischemia–reperfusion injury in MACO/R mice, and upregulated superoxide dismutase (SOD) and the catalase (CAT) enzyme activity. BAK also inhibited the expression of TNF-α, IL-1β, IL-6, and IL-18 and suppressed apoptosis and pyroptosis both in MACO/R mice and in OGD/R SH-SY5Y cells. Further results showed that BAK could suppress TXNIP, ASC, NLRP3, and caspase-1 mRNA levels to reverse assembly of inflammasome. And BAK could also upregulate the expression of phosphorylated AMP-activated protein kinase (AMPK) and nuclear factor erythroid 2-related factor (Nrf2). In addition, Nrf2 inhibitor ML385 reversed the BAK induced reduction of TXNIP, ASC, NLRP3, and the AMPK inhibitor also abolished BAK’ the effect on the regulation of Nrf2 TXNIP, ASC, NLRP3, caspase-1, and pro-inflammatory cytokines. In conclusion, BAK, found in leaves and seeds of Psoralea corylifolia Linn, could ameliorated cerebral I/R injury through activating AMPK/Nrf2 to inhibit NLRP3 inflammasome, which might present new therapeutic strategy for cerebral I/R injury.

Leveraging Social Networks to Integrate Depression Treatment into Primary Health and Tuberculosis Care in Brazil.

Tuberculosis (TB) and depression are highly comorbid and linked to higher rates of death and disability. Several evidence-based treatments for depression have been successfully implemented in low- and middle-income countries, but more knowledge is needed on how to bring these innovations to scale within complex 'real world' public health systems. To explore whether the principles of social network analysis could be used to enhance receptivity to integrating depression treatment into primary care for individuals with and without TB in Brazil. We used existing scales to identify settings and providers with high receptivity and connectivity within the primary care network. We trained and supervised existing staff in three primary care sites to deliver a brief evidence-based intervention over one year, coupled with active dissemination activities. Afterwards, we reassessed receptivity among individuals involved, and not involved, in the pilot. Highly significant changes were observed in mental health literacy, attitudes towards evidence-based practices, work self-efficacy, and implementation leadership supporting our hypothesis. Limited social connections between primary care clinics precluded the examination of the hypothesis that targeting settings with high connectivity could capitalize on the information flow between and transcend the decentralized structure of the network, but leveraging the centralized nature of the TB program to integrate mental health services emerged as a promising alternative. The findings of this study strongly suggest that social networks may be leveraged to change individual providers' attitudes, thereby contributing to the enhanced dissemination of evidence-based interventions.

Safety and efficacy of individual target transcranial magnetic stimulation to stimulate the most negative correlate of DLPFC-pgACC in the treatment of major depressive disorder: study protocol of a double-blind, randomised controlled trial

IntroductionMajor depressive disorder (MDD) is a common mental disorder that is characterised by high morbidity, high rates of relapse, high rates of disability and, in severe cases, suicide ideas or...

Role of the PGAM5-CypD mitochondrial pathway in methylglyoxal-induced bone loss in diabetic osteoporosis

Diabetic osteoporosis (DOP) is a skeletal complication with a high rate of disability. It results in a great burden to the patient's family and society. Methylglyoxal (MG) is a toxic by-product of the glycolytic process that occurs during diabetic conditions. It causes osteoblastic injury and con-tributes to the initiation and development of DOP. Disruption of mitochondrial homeostasis has been implicated as a cause of dysregulated osteo-blastogenesis, an essential step in bone formation. It is unclear whether mitochondrial dysfunction is involved in MG-induced osteoblast dysfunction. In this study, we showed that mitochondrial dysfunction contributes to MG-induced MC3T3-E1 cell apoptosis and impaired differentiation. A significant reduction of mitochondrial membrane potential (MMP) and ATP production occurred in MG-induced osteoblasts as well as increasing mitochondrial reactive oxygen species (mtROS) and intracellular Ca2+. Classical antioxidant N-Acetylcysteine (NAC) significantly attenuated mitochondrial dysfunction as well as osteoblast apoptosis and osteogenic differentiation damage induced by MG. More importantly, we found that activating phosphoglycerate mutase family member 5 (PGAM5) and cyclophilin D (CypD), which contributes to mitochondrial homeostasis, is involved in MG-induced osteoblast injury. Both PGAM5 and CypD knockdown effectively reversed osteoblast viability and function, whereas PGAM5 or CypD overexpression aggravated osteoblast injury caused by MG. Moreover, the result of co-transfection revealed that PGAM5 is an upstream signaling molecule of CypD. By constructing type I diabetes mouse models, we further found that the expression of PGAM5 and CypD were both increased in the femur along with a reduction of ATP and increased TUNEL-positive cells. These results, for the first time, suggest that MG-induced mitochondrial dysfunction induces osteoblast injury through the PGAM5-CypD pathway. This study provides insight into the prevention and treatment of DOP. Lay summaryThis study highlights the role of mitochondria in regulating osteoblast viability and function under conditions of diabetic osteoporosis (DOP). We found that the PGAM5-CypD mitochondrial pathway is activated following glycolytic by-product methylglyoxal (MG) treatment, which contributes to mitochondrial dysfunction and osteogenic dysfunction. This mechanism implicates mitochondria as a potential therapeutic target for osteoporosis.

Immune regulation: a new strategy for traditional Chinese medicine-based treatment of granulomatous lobular mastitis.

Granulomatous lobular mastitis (GLM) presents significant challenges, including high rates of morbidity, recurrence, and disability, ultimately impacting women's health and quality of life. Local autoimmune imbalance involving dysregulated cytokines and immune cells has been recognized to play a key role in the pathology of GLM. Traditional Chinese medicine (TCM), with its multi-component, multi-pathway and multi-target characteristics, offers unique advantages and broad prospects in the treatment of GLM. Here, we review the relationship between immune dysregulation and GLM, as well as the regulatory mechanisms of TCM-based interventions, with the aim of providing new insights and foundational knowledge for the clinical treatment of GLM, while promoting the further application and development of TCM-based strategies for the treatment of GLM.