Age-related driving mechanisms of retinal diseases and neuroprotection by transcription factor EB-targeted therapy

Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.

Analysis of the influencing factors and clinical related characteristics of pulmonary tuberculosis in patients with type 2 diabetes mellitus

BACKGROUND In China,the prevalence of type 2 diabetes mellitus(T2DM)among diabetic patients is estimated to be between 90%-95%.Additionally,China is among the 22 countries burdened by a high number of tuberculosis cases,with approximately 4.5 million individuals affected by active tuberculosis.Notably,T2DM poses a significant risk factor for the development of tuberculosis,as evidenced by the increased incidence of T2DM coexisting with pulmonary tuberculosis(T2DMPTB),which has risen from 19.3%to 24.1%.It is evident that these two diseases are intricately interconnected and mutually reinforcing in nature.AIM To elucidate the clinical features of individuals diagnosed with both T2DM and tuberculosis(T2DM-PTB),as well as to investigate the potential risk factors associated with active tuberculosis in patients with T2DM.METHODS T2DM-PTB patients who visited our hospital between January 2020 and January 2023 were selected as the observation group,Simple DM patients presenting to our hospital in the same period were the control group,Controls and case groups were matched 1:2 according to the principle of the same sex,age difference(±3)years and disease duration difference(±5)years,patients were investigated for general demographic characteristics,diabetes-related characteristics,body immune status,lifestyle and behavioral habits,univariate and multivariate analysis of the data using conditional logistic regression,calculate the odds ratio(OR)values and 95%CI of OR values.RESULTS A total of 315 study subjects were included in this study,including 105 subjects in the observation group and 210 subjects in the control group.Comparison of the results of both anthropometric and biochemical measures showed that the constitution index,systolic blood pressure,diastolic blood pressure and lymphocyte count were significantly lower in the case group,while fasting blood glucose and high-density lipoprotein cholesterol levels were significantly higher than those in the control group.The results of univariate analysis showed that poor glucose control,hypoproteinemia,lymphopenia,TB contact history,high infection,smoking and alcohol consumption were positively associated with PTB in T2DM patients;married,history of hypertension,treatment of oral hypoglycemic drugs plus insulin,overweight,obesity and regular exercise were negatively associated with PTB in T2DM patients.Results of multivariate stepwise regression analysis found lymphopenia(OR=17.75,95%CI:3.40-92.74),smoking(OR=12.25,95%CI:2.53-59.37),history of TB contact(OR=6.56,95%CI:1.23-35.03)and poor glycemic control(OR=3.37,95%CI:1.11-10.25)was associated with an increased risk of developing PTB in patients with T2DM,While being overweight(OR=0.23,95%CI:0.08-0.72)and obesity(OR=0.11,95%CI:0.02-0.72)was associated with a reduced risk of developing PTB in patients with T2DM.CONCLUSION T2DM-PTB patients are prone to worse glycemic control,higher infection frequency,and a higher proportion of people smoking,drinking alcohol,and lack of exercise.Lymphopenia,smoking,history of TB exposure,poor glycemic control were independent risk factors for T2DM-PTB,and overweight and obesity were associated with reduced risk of concurrent PTB in patients with T2DM.

Risk factors for running-related injuries:An umbrella systematic review

Purpose:This umbrella systematic review(SR) of SRs and meta-analysis seeks to comprehensively synthesize existing literature to identify and consolidate the diverse range of risk factors contributing to running-related injuries(RRIs).Methods:Systematic searches were conducted on June 28,2023,across Web of Science,SPORTDiscus,Scopus,PubMed,and Cochrane Library.We included SRs,whether accompanied by meta-analyses or not,that focused on investigating risk factors for RRIs within observational studies.The methodological quality of the SRs was evaluated using the Assessing the Methodological Quality of Systematic Reviews Ⅱ.To assess the extent of overlap across reviews,the corrected covered area metric was calculated.Results:From 1509 records retrieved,13 SRs were included.The degree of overlap between SRs was low(4%),and quality varied from critically low(n=8) to low(n=5).Two hundred seven outcomes assessed in 148 primary studies were identified as being associated with the occurrence of RRIs.The effect sizes of the associations for which risk measures were reported(n=131) were classified as large(n=30,23%),medium(n=38,29%),small(n=48,37%) or no effect(n=15,11%).Running/training characteristics,health and lifestyle factors,along with morphological and biomechanical aspects,exhibit large effect sizes in increasing the risk for RRIs.Conclusion:Drawing from the outcomes of the low-quality SRs and associations with large effect sizes,our findings indicate that running/training characteristics and health and lifestyle factors,as well as morphological and biomechanical aspects,are all implicated in elevating the risk of RRIs,emphasizing the multifactorial basis of injury incidence in running.Given the low quality and heterogeneity of SR,individual findings warrant cautious interpretation.

Arterial Hypertension-Related Factors within Custodial Settings of Southern Benin in 2023

Introduction: Hypertension, a non-communicable disease, is a major public health threat worldwide, accounting for a high level of morbidity and mortality. Although it has been extensively published among the general population, further research is needed to understand the reality of hypertension within the custodial setting. This study aimed to investigate the factors associated with arterial hypertension in custodial settings in southern Benin in 2023. Methods: This was a cross-sectional, descriptive, analytical study held in prisons in southern Benin from March to April 2023, involving inmates selected by two-stage random sampling. In the first stage, four prisons out of the six in the southern region of Benin were selected by simple random sampling. In the second stage, the prisoners were selected by systematic random sampling, with the sampling frame being the numbered list of eligible prisoners in each prison selected. Data collected by observation and questionnaire survey were analyzed using Stata 11 software. Hypertension was defined as systolic blood pressure ≥ 140 mmHg and diastolic blood pressure ≥ 90 mmHg. Overweight was defined by a body mass index (weight/height2 (kg/m2) ≥ 25. Factors associated with hypertension were identified by multiple logistic regression, at a 5% threshold of significance. Results: Altogether 336 inmates aged 37.55 ± 1.72 years were surveyed. The prevalence of hypertension in custodial settings in southern Benin in 2023 was 31.32% (95% CI [17.06;52.57]). Associated factors were inmate age (ORa = 3.36 95% CI: [1.94;5.85]) and abnormal waist circumference (ORa = 2.61 95% CI [1.27;5.40]). Conclusion: The prevalence of arterial hypertension in prisons of southern Benin (31.32%) is high when compared with the national average (25.9% (22.5-29.3)). The ministries of the Interior and Health need to collaborate to involve inmates in preventive strategies for non-communicable diseases, including hypertension.

A Cross-Sectional Study on The Prevalence of Anemia in Maintenance Hemodialysis and Peritoneal Dialysis Patients and Its Related Factors

Objective:To study the prevalence of anemia,the proportion of hemoglobin(Hb)levels,the treatment methods,and the influencing factors of Hb levels in maintenance hemodialysis(MHD)and peritoneal dialysis patients.Methods:In this study,602 patients with maintenance hemodialysis and continuous ambulatory peritoneal dialysis were enrolled from December 2020 to December 2022 in our hospital,and their medical records were collected and summarized.The main contents included the patient’s gender,age,primary disease,dialysis duration,dialysis method,the use of erythropoietic stimulating agents(ESA),intravenous iron,and laboratory tests.A Hb index exceeding 110 g/L was set as the standard for the prevalence of anemia.Results:The rate of anemia in patients undergoing blood purification was 83%.The proportion of ESA use was 84.1%,and the proportion of iron use was 76.7%,of which the proportion of intravenous iron used was 17.0%,and the proportion of folic acid used was 28.3%.Conclusion:The incidence of anemia in MHD patients was relatively high,with a low proportion of patients reaching the standard Hb levels.Risk factors include albumin(ALB)levels,iron storage,white blood cells,C-reactive protein,cholesterol,etc.Nutritional support,iron supplementation,and prevention of micro-inflammatory reactions can effectively promote the improvement of Hb indicators in dialysis patients to prevent anemia.

Analysis of Factors Related to Vasovagal Response in Apheresis Blood Donors and the Establishment of Prediction Model Based on BP Neural Network Algorithm

Objective:To analyze the factors related to vessel vasovagal reaction(VVR)in apheresis donors,establish a mathematical model for predicting the correlation factors and occurrence risk,and use the prediction model to intervene in high-risk VVR blood donors,improve the blood donation experience,and retain blood donors.Methods:A total of 316 blood donors from the Xi'an Central Blood Bank from June to September 2022 were selected to statistically analyze VVR-related factors.A BP neural network prediction model is established with relevant factors as input and DRVR risk as output.Results:First-time blood donors had a high risk of VVR,female risk was high,and sex difference was significant(P value<0.05).The blood pressure before donation and intergroup differences were also significant(P value<0.05).After training,the established BP neural network model has a minimum RMS error of o.116,a correlation coefficient R=0.75,and a test model accuracy of 66.7%.Conclusion:First-time blood donors,women,and relatively low blood pressure are all high-risk groups for VVR.The BP neural network prediction model established in this paper has certain prediction accuracy and can be used as a means to evaluate the risk degree of clinical blood donors.

Contractor-Related Factors and Performance of Bridge Construction Projects Implemented by Kenya National Highways Authority (KeNHA) Kenya

The performance of bridge projects in Kenya is poor in terms of completion by schedule, cost, and quality (scope). Yet, there is less evidence of empirical research on what factors contribute to this outcome. This study aimed to bridge this gap by examining the effects of contractor-related factors on the performance of bridge construction projects in Kenya through a case study of the Bridge projects Implemented by the Kenya National Highway Agency (KeNHA). The theory of constraints (TOC) was adopted as its theoretical framework. Descriptive research was used, and the target population was 18 bridge construction projects, which were the units of analysis from 2012 to 2022. In each of these projects, 18 respondents, namely clients, consultants, contractors, engineers, environment and social guards, project managers, stakeholders, subcontractors, technical advisors, and inspectors, were included in a target population of 144 respondents. A census was conducted and a structured questionnaire was administered from which a response rate of 68% was achieved. The information was analyzed using descriptive, correlation, and multiple linear regression analysis. The contractor-related factors considered in the study were staff and management factors. The findings indicated that staff and management factors had a positive and significant outcome on performance of bridge construction projects. The study recommends continuous training and a safe learning environment for staff to improve their skills and performance in future projects. The study also recommends that a special category for bridge contractors be created in Kenya’s National Construction Authority rankings to ensure that only qualified contractors implement the Bridge projects.

A Prognostic Model Based on Colony Stimulating Factors-related Genes in Triple-negative Breast Cancer

Objective Triple-negative breast cancer(TNBC)is the breast cancer subtype with the worst prognosis,and lacks effective therapeutic targets.Colony stimulating factors(CSFs)are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells,playing an important role in the malignant progression of TNBC.This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes(CRGs),and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy.Methods We downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database.Through LASSO Cox regression analysis,we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score(CRRS).We further analyzed the correlation between CRRS and patient prognosis,clinical features,tumor microenvironment(TME)in both high-risk and low-risk groups,and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy.Results We identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model.Kaplan-Meier survival curves,time-dependent receiver operating characteristic curves,and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival,and the predictive ability of CRRS prognostic model was further validated using the GEO dataset.Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients.Moreover,patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil,ipatasertib,and paclitaxel.Conclusion We have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs,which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment.Moreover,the key genes within this model may represent potential molecular targets for future therapies of TNBC.

Status,outcome,and related factors of postpartum hypertension in the Shanghai community

BACKGROUND Postpartum hypertension poses a considerable health risk.Despite research on gestational hypertension,comprehensive studies focusing on postpartum hypertension in communities are limited.Understanding its prevalence and associated risk factors is crucial for effective prevention and management.AIM To provide insights for postpartum hypertension’s prevention and management.METHODS In total,3297 women who gave birth between June 2021 and December 2022 in Xuhui District,Shanghai were selected.Blood pressure was measured thrice within one month post-delivery during home visits.Eighty-six women with hypertension were followed up for four months to analyze hypertension persistence and its related risk factors.A predictive model for persistent postpartum hypertension was established and verified using the Nomo diagram model.RESULTS Hypertension prevalence 1 month post-delivery was 2.61%(86/3297).Among the 86 pregnant women,32(37.21%)had persistent hypertension at four months post-delivery.Multivariate logistic regression analysis revealed that older age[odds ratio(OR)=1.212;95%confidence interval(CI):1.065–1.380]and higher pre-pregnancy body mass index(BMI)(OR=1.188;95%CI:1.006–1.404)were associated with hypertension(OR=10.781;95%CI:1.006–1.404)during pregnancy.A 95%CI of 1.243–93.480 is a risk factor for persistent postpartum hypertension.The Nomograph model accurately predicted the risk of persistent postpartum hypertension,demonstrating high precision.CONCLUSION In Xuhui,older age,higher pre-pregnancy BMI,and gestational hypertension are risk factors for persistent postpartum hypertension.Our prediction model can identify high-risk individuals,thereby improving patient quality of life.

Analysis on Fuji Apple Tree Structures and Related Factors under Different Pruning Modes

To determine the correlations between the tree structuresof Fuji apple with different pruning modes and each factor, the data about 3 tree structures which were free spindle short shoot, free spindle long shoot and slenderspindle short shoot in Xingtang County of Hebai Province were investigated, then by SPSS anal- ysis, the correlations between the taperingness and each growth factor of inserted small branch were compared. The results showed that the taperingness of central trunk of free spindle dwarf-shoot Fuji apple treeshad negative correlations with each factor of inserted small branch, while the taperingness of central trunk of free spin- dle long-shoot Fuji apple treeshad positive correlations with each factor of inserted small branch, the taperingness of central trunk of slenderspindle short-shootFuji ap- ple treeshad negative correlation with total thickness of inserted small branch, but had positive correlations with other factors. This study can provide a scientifictheo- retical basis for the pruning technology of high-density planting trees grafting by dwarfing self-rooted rootstock.

Clinical Features of Renal Insufficiency due to Multiple Myeloma and Related Risk Factors

Objective: To study clinical features of the patients with multiple myeloma(MM) accompanied by renal insufficiency and investigate the related risk factors of renalimpairment. Methods: A control study of clinical characteristics was performed between 91 patientswith renal insufficiency due to MM and 165 patients with normal renal function in MM during the sameperiod. The data were statistically analyzed by chi-square test and logistic regression analysis.Results: Renal insufficiency was the initial presentation in 48 (52.7%) of the 91 patients, and 30(62.5%) of the 48 patients were misdiagnosed. The prognosis of group with renal insufficiency wassignificantly poorer than that of group with normal renal function: mortality in 3 months, 3months-1 year was 26/91 vs 14/165 (P 【 0.0001), 14/91 vs 12/165 (P 【 0.05) respectively, andpatients survived 】 1 year was 18/91 vs 95/165 (P 【 0.0001). The incidence of hypercalcemia,hyperuricemic, severe anemia, high serum M-protein concentration and lytic bone lesions weresignificantly higher in renal insufficiency group than those in control group (P 【 0.05). Logisticregression analysis identified 5 risk factors of renal impairment, including, severe anemia(Exp(β)=13.819, P 【 0.0001), use of nephrotoxic drugs (Exp(β)=6.217, P = 0.001), high serumM-protein concentration (Exp(β) = 5.026, P = 0.001), male (Exp(β)=3.745, P=0.006), andhypercalcemia (Exp(β)=3A72, P=0.006), but age, serum density of uric acid, type of serum M-protein,and Bence Jones proteinuria were not significantly associated with renal insufficiency. Conclusion:Renal insufficiency was a common early complication of MM, which often resulted in misdiagnosis.The status of these patients tended to be very bad, with many other complications, when MM wasdiagnosed, so their prognosis was poor. The occurrence of renal insufficiency in patients with MMand hypercalcemia, severe anemia, high serum M-protein concentration, especially use of nephrotoxicdrugs should be alert.

Risk factors for congenital nasolacrimal duct obstruction in children under two years of age

·AIM:To identify various risk factors that may play a significant role in the development of congenital nasolacrimal duct obstruction(CNLDO).·METHODS:This observational case-control study included a case group of 122 children less than two years of age with CNLDO who underwent probing and irrigation treatment at the ophthalmology department of Imam Khomeini Hospital in Ahvaz,Iran,from June 2022 to June2024.A control group of 122 age-matched children without CNLDO was also included for comparison.Data was collected from the children's medical records.·RESULTS:The study found a significant correlation between the occurrence of CNLDO and several maternal factors,such as preeclampsia,the use of levothyroxine,hypothyroidism,having more than three pregnancies(gravidity>3),natural pregnancy,and gestational diabetes mellitus.Additionally,in children,factors,such as oxygen therapy,anemia,reflux,jaundice,and a family history of CNLDO in first-degree relatives were associated with CNLDO,and maternal preeclampsia and hypothyroidism were found to significantly increase the risk of developing CNLDO in children.·CONCLUSION:Given that CNLDO affects both premature and full-term children,the present findings may potentially facilitate the early identification of children and infants at risk of nasolacrimal duct obstruction,thereby preventing the onset of chronic dacryocystitis.

Association between autoimmune gastritis and gastric polyps:Clinical characteristics and risk factors

BACKGROUND The relationship between autoimmune gastritis(AIG)and gastric polyps(GPs)is not well understood.AIM To explore the clinical characteristics and risk factors of AIG with GPs in patients.METHODS This double center retrospective study included 530 patients diagnosed with AIG from July 2019 to July 2023.We collected clinical,biochemical,serological,and demographic data were of each patient.Logistic regression analyses,both multivariate and univariate,were conducted to pinpoint independent risk factors for GPs in patients with AIG patients.Receiver operating characteristic curves were utilized to establish the optimal cutoff values,sensitivity,and specificity of these risk factors for predicting GPs in patients with AIG.RESULTS Patients with GPs had a higher median age than those without GPs[61(52.25-69)years vs 58(47-66)years,P=0.006].The gastrin-17 levels were significantly elevated in patients with GPs compared with those without GPs[91.9(34.2-138.9)pmol/mL vs 60.9(12.6-98.4)pmol/mL,P<0.001].Additionally,the positive rate of parietal cell antibody(PCA)antibody was higher in these patients than in those without GPs(88.6%vs 73.6%,P<0.001).Multivariate and univariate analyses revealed that PCA positivity[odds ratio(OR)=2.003,P=0.017],pepsinogen II(OR=1.053,P=0.015),and enterochromaffin like cells hyperplasia(OR=3.116,P<0.001)were significant risk factors for GPs,while pepsinogen I was identified as a protective factor.CONCLUSION PCA positivity and enterochromaffin like cells hyperplasia are significant risk factor for the development of GPs in patients with AIG.Elevated gastrin-17 levels may also play a role in this process.These findings suggest potential targets for further research and therapeutic intervention in managing GPs in patients with AIG.

Social function scores and influencing factors in patients with residual depressive symptoms

BACKGROUND At present,the influencing factors of social function in patients with residual depressive symptoms are still unclear.Residual depressive symptoms are highly harmful,leading to low mood in patients,affecting work and interpersonal communication,increasing the risk of recurrence,and adding to the burden on families.Studying the influencing factors of their social function is of great significance.AIM To explore the social function score and its influencing factors in patients with residual depressive symptoms.METHODS This observational study surveyed patients with residual depressive symptoms(case group)and healthy patients undergoing physical examinations(control group).Participants were admitted between January 2022 and December 2023.Social functioning was assessed using the Sheehan Disability Scale(SDS),and scores were compared between groups.Factors influencing SDS scores in patients with residual depressive symptoms were analyzed by applying multiple linear regression while using the receiver operating characteristic curve,and these RESULTS The SDS scores of the 158 patients with depressive symptoms were 11.48±3.26.Compared with the control group,the SDS scores and all items in the case group were higher.SDS scores were higher in patients with relapse,discon-tinuous medication,drug therapy alone,severe somatic symptoms,obvious residual symptoms,and anxiety scores≥8.Disease history,medication compliance,therapy method,and residual symptoms correlated positively with SDS scores(r=0.354,0.414,0.602,and 0.456,respectively).Independent influencing factors included disease history,medication compliance,therapy method,somatic symptoms,residual symptoms,and anxiety scores(P<0.05).The areas under the curve for predicting social functional impairment using these factors were 0.713,0.559,0.684,0.729,0.668,and 0.628,respectively,with sensitivities of 79.2%,61.8%,76.8%,81.7%,63.6%,and 65.5%and specificities of 83.3%,87.5%,82.6%,83.3%,86.7%,and 92.1%,respectively.CONCLUSION The social function scores of patients with residual symptoms of depression are high.They are affected by disease history,medication compliance,therapy method,degree of somatic symptoms,residual symptoms,and anxiety.

Burden of mental disorders and risk factors in the Western Pacific region from 1990 to 2021

BACKGROUND The burden of mental disorders(MD)in the Western Pacific Region(WPR)re-mains a critical public health concern,with substantial variations across demogra-phics and countries.AIM To analyze the burden of MD in the WPR from 1990 to 2021,along with associated risk factors,to reveal changing trends and emerging challenges.METHODS We used data from the Global Burden of Disease 2021,analyzing prevalence,incidence,and disability-adjusted life years(DALYs)of MD from 1990 to 2021.Statistical methods included age-standardisation and uncertainty analysis to address variations in population structure and data completeness.RESULTS Between 1990 and 2021,the prevalence of MD rose from 174.40 million cases[95%uncertainty interval(UI):160.17-189.84]to 234.90 million cases(95%UI:219.04-252.50),with corresponding DALYs increasing from 22.8 million(95%UI:17.22-28.79)to 32.07 million(95%UI:24.50-40.68).During this period,the burden of MD shifted towards older age groups.Depressive and anxiety disorders were predominant,with females showing higher DALYs for depressive and anxiety disorders,and males more affected by conduct disorders,attention-deficit hyperactivity disorder,and autism spectrum disorders.Australia,New Zealand,and Malaysia reported the highest burdens,whereas Vietnam,China,and Brunei Darussalam reported the lowest.Additionally,childhood sexual abuse and bullying,and intimate partner violence emerged as significant risk factors.CONCLUSION This study highlights the significant burden of MD in the WPR,with variations by age,gender,and nation.The coronavirus disease 2019 pandemic has exacerbated the situation,emphasizing the need for a coordinated response.

Assessment of Dependent Performance Shaping Factors in SPAR-H Based on Pearson Correlation Coefficient

With the improvement of equipment reliability,human factors have become the most uncertain part in the system.The standardized Plant Analysis of Risk-Human Reliability Analysis(SPAR-H)method is a reliable method in the field of human reliability analysis(HRA)to evaluate human reliability and assess risk in large complex systems.However,the classical SPAR-H method does not consider the dependencies among performance shaping factors(PSFs),whichmay cause overestimation or underestimation of the risk of the actual situation.To address this issue,this paper proposes a new method to deal with the dependencies among PSFs in SPAR-H based on the Pearson correlation coefficient.First,the dependence between every two PSFs is measured by the Pearson correlation coefficient.Second,the weights of the PSFs are obtained by considering the total dependence degree.Finally,PSFs’multipliers are modified based on the weights of corresponding PSFs,and then used in the calculating of human error probability(HEP).A case study is used to illustrate the procedure and effectiveness of the proposed method.

Subretinal fibrosis secondary to neovascular age-related macular degeneration:mechanisms and potential therapeutic targets

Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.

Language Training Centers: Factors Related to Their Success

A survey of language training centers(LTCs)in Dalian,China was conducted,to ascertain the strengths and weaknesses,or the differentiating factors,of such centers.The survey was undertaken to understand the current landscape of after-school institutes in the region,particularly those that offer training in English as a second/foreign language.The information uncovered by the research is considered beneficial not only to entrepreneurs who may wish to be involved in this industry,but also to college English majors who may wish to teach at an LTC.

Microvesicles derived from mesenchymal stem cells inhibit acute respiratory distress syndrome-related pulmonary fibrosis in mouse partly through hepatocyte growth factor

BACKGROUND Pulmonary fibrosis is one of the main reasons for the high mortality rate among acute respiratory distress syndrome(ARDS)patients.Mesenchymal stromal cell-derived microvesicles(MSC-MVs)have been shown to exert antifibrotic effects in lung diseases.AIM To investigate the effects and mechanisms of MSC-MVs on pulmonary fibrosis in ARDS mouse models.METHODS MSC-MVs with low hepatocyte growth factor(HGF)expression(siHGF-MSC-MVs)were obtained via lentivirus transfection and used to establish the ARDS pulmonary fibrosis mouse model.Following intubation,respiratory mechanics-related indicators were measured via an experimental small animal lung function tester.Homing of MSC-MVs in lung tissues was investigated by near-infrared live imaging.Immunohistochemical,western blotting,ELISA and other methods were used to detect expression of pulmonary fibrosis-related proteins and to compare effects on pulmonary fibrosis and fibrosis-related indicators.RESULTS The MSC-MVs gradually migrated and homed to damaged lung tissues in the ARDS model mice.Treatment with MSC-MVs significantly reduced lung injury and pulmonary fibrosis scores.However,low expression of HGF(siHGF-MSC-MVs)significantly inhibited the effects of MSC-MVs(P<0.05).Compared with the ARDS pulmonary fibrosis group,the MSC-MVs group exhibited suppressed expression of type I collagen antigen,type III collagen antigen,and the proteins transforming growth factor-βandα-smooth muscle actin,whereas the siHGF-MVs group exhibited significantly increased expression of these proteins.In addition,pulmonary compliance and the pressure of oxygen/oxygen inhalation ratio were significantly lower in the MSC-MVs group,and the effects of the MSC-MVs were significantly inhibited by low HGF expression(all P<0.05).CONCLUSION MSC-MVs improved lung ventilation functions and inhibited pulmonary fibrosis in ARDS mice partly via HGF mRNA transfer.

Targeting nuclear factor erythroid 2-related factor 2-regulated ferroptosis to treat nervous system diseases

By critically examining the work,we conducted a comprehensive bibliometric analysis on the role of nuclear factor erythroid 2-related factor 2(NRF2)in nervous system diseases.We also proposed suggestions for future bibliometric studies,including the integration of multiple websites,analytical tools,and analytical approaches,The findings presented provide compelling evidence that ferroptosis is closely associated with the therapeutic challenges of nervous system diseases.Targeted modulation of NRF2 to regulate ferroptosis holds substantial potential for effectively treating these diseases.Future NRF2-related research should not only focus on discovering new drugs but also on designing rational drug delivery systems.In particular,nanocarriers offer substantial potential for facilitating the clinical translation of NRF2 research and addressing existing issues related to NRF2-related drugs.