AIM: To investigate the effect of interleukin-8(IL-8)on the regulation of monocyte chemotactic protein-1(MCP-1)secreted by lens epithelial cells(LEC)during cell migration in the development of posterior capsule opacification(PCO).METHODS: A rat lens capsule model was established and cultured in medium supplemented with 10% fetal bovine serum. Upon migration of LEC to 30%-50% of the posterior capsule, serum was removed. The capsule was subsequently divided into two groups: a control group and an IL-8(15 ng/mL)treatment group. LEC migration was captured at multiple time points. The secretion and mRNA expression of MCP-1 were quantified using ELISA and RT-qPCR, respectively. Immunofluorescence was used to assess MCP-1 expression in the different experimental groups. SRA01/04 cells were divided into three groups: control, IL-8(15 ng/mL), and IL-8(15 ng/mL)+200 μmol/L Bindarit(BND)groups, with migration measured by the Transwell assay. Additionally, SRA01/04 cells were divided into negative control(NC), NC+15 ng/mL IL-8, and 15 ng/mL IL-8+p65 siRNA groups, and MCP-1 secretion and mRNA expression were further analyzed by ELISA and RT-qPCR.RESULTS:LEC migration in the rat lens capsule cultured in vitro showed that the cells migration of the 15 ng/mL IL-8 group significantly increased at 48, 72 and 96 h(all P<0.05). ELISA results revealed that MCP-1 levels in SRA01/04 cells from the 15 ng/mL IL-8-treated group were markedly higher than those in the control group at both 12 and 24 h(all P<0.05). RT-qPCR analysis also demonstrated a significant increase in MCP-1 mRNA expression in the 15 ng/mL IL-8 group at both time points(all P<0.05). Immunofluorescence staining indicated greater MCP-1 expression in capsular epithelial cells of the 15 ng/mL IL-8 group at 24 h(P=0.007). Transwell assays further confirmed increased cell migration in the 15 ng/mL IL-8 group compared to the control group(P=0.001), while the migration reduced in the 15 ng/mL IL-8+200 μmol/L BND group compared to the 15 ng/mL IL-8 group(P=0.003). Moreover, ELISA and RT-qPCR results demonstrated a significant increase in MCP-1 secretion and mRNA expression in the NC+15 ng/mL IL-8 group at both 12 and 24 h compared to the NC group(all P<0.01). In contrast, MCP-1 secretion and mRNA expression were reduced in the 15 ng/mL IL-8+p65 siRNA group compared to the NC+15 ng/mL IL-8 group at both time points(all P<0.01).CONCLUSION: IL-8 promotes the migration of residual epithelial cells and regulates the secretion and expression of MCP-1 in LEC. The mechanism underlying IL-8's effects appears to be mediated through the activation of the NF-κB/p65 signaling pathway.

BACKGROUND: Approximately 40% of individuals with diabetes worldwide are at risk of developing diabetic kidney disease (DKD), which is not only the leading cause of kidney failure, but also significantly increases the risk of cardiovascular disease, causing significant societal health and financial burdens. This study aimed to describe the burden of DKD and explore its cross-country epidemiological status, predict development trends, and assess its risk factors and sociodemographic transitions. METHODS: Based on the Global Burden of Diseases (GBD) Study 2021, data on DKD due to type 1 diabetes (DKD-T1DM) and type 2 diabetes (DKD-T2DM) were analyzed by sex, age, year, and location. Numbers and age-standardized rates were used to compare the disease burden between DKD-T1DM and DKD-T2DM among locations. Decomposition analysis was used to assess the potential drivers. Locally weighted scatter plot smoothing and Frontier analysis were used to estimate sociodemographic transitions of DKD disability-adjusted life years (DALYs). RESULTS: The DALYs due to DKD increased markedly from 1990 to 2021, with a 74.0% (from 2,227,518 to 3,875,628) and 173.6% (from 4,122,919 to 11,278,935) increase for DKD-T1DM and DKD-T2DM, respectively. In 2030, the estimated DALYs for DKD-T1DM surpassed 4.4 million, with that of DKD-T2DM exceeding 14.6 million. Notably, middle-sociodemographic index (SDI) quintile was responsible for the most significant DALYs. Decomposition analysis revealed that population growth and aging were major drivers for the increased DKD DALYs in most regions. Interestingly, the most pronounced effect of positive DALYs change from 1990 to 2021 was presented in high-SDI quintile, while in low-SDI quintile, DALYs for DKD-T1DM and DKD-T2DM presented a decreasing trend over the past years. Frontiers analysis revealed that there was a negative association between SDI quintiles and age-standardized DALY rates (ASDRs) in DKD-T1DM and DKD-T2DM. Countries with middle-SDI shouldered disproportionately high DKD burden. Kidney dysfunction (nearly 100.0% for DKD-T1DM and DKD-T2DM), high fasting plasma glucose (70.8% for DKD-T1DM and 87.4% for DKD-T2DM), and non-optimal temperatures (low and high, 5.0% for DKD-T1DM and 5.1% for DKD-T2DM) were common risk factors for age-standardized DALYs in T1DM-DKD and T2DM-DKD. There were other specific risk factors for DKD-T2DM such as high body mass index (38.2%), high systolic blood pressure (10.2%), dietary risks (17.8%), low physical activity (6.2%), lead exposure (1.2%), and other environmental risks. CONCLUSIONS DKD markedly increased and varied significantly across regions, contributing to a substantial disease burden, especially in middle-SDI countries. The rise in DKD is primarily driven by population growth, aging, and key risk factors such as high fasting plasma glucose and kidney dysfunction, with projections suggesting continued escalation of the burden by 2030.
Humans ; Global Burden of Disease ; Risk Factors ; Male ; Female ; Disability-Adjusted Life Years ; Diabetic Nephropathies/epidemiology* ; Middle Aged ; Diabetes Mellitus, Type 2/epidemiology* ; Adult ; Diabetes Mellitus, Type 1/complications* ; Aged ; Adolescent ; Young Adult ; Quality-Adjusted Life Years

The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

Humans ; Diabetes Mellitus, Type 1 ; Hypoglycemia/chemically induced* ; Hypoglycemic Agents/adverse effects* ; China ; Blood Glucose ; Insulin

Objective:To examine the validity and reliability of the Chinese version of the Body Acceptance by Others Scale-2(BAOS-2)in adults.Methods:Totally 616 adults(aged 18-56 years)were selected to test the structural validity,and internal consistency reliability of the scale.The Body Appreciation Scale-2(BAS-2),Func-tionality Appreciation Scale(FAS),Self-Compassion Scale(SCS),Self-Esteem Scale(SES)and Satisfaction with Life Scale(SWLS)were used as criteria to test criterion validity.A sample of 55 adults was retested 2 weeks later for the test-retest reliability.Results:The exploratory factor analysis extracted one factor,and the factor loading range of each item was 0.59-0.76.The confirmatory factor analysis showed that the factor model fit indices were acceptable(x2/df=2.99,CFI=0.91,GFI=0.90,TLI=0.89,RMR=0.04,RMSEA=0.08).The scores of the Chinese version of BAOS-2 were positively correlated with the scores of BAS-2,FAS,SCS,SES and SWLS(r=0.43-0.66,Ps＜0.001).The Cronbach a of the Chinese version of BAOS-2 was 0.90,and the test-retest reliabili-ty(ICC)was 0.65.Conclusion:The Chinese version of the Body Acceptance by Others Scale-2(BAOS-2)has i-deal validity and reliability.

Objective:To explore the journey map of patients with chronic constipation during fecal microbiota transplantation.Methods:This study adopted phenomenological methods. From October to December 2023, purposive sampling was used to select chronic constipation follow-up patients who underwent fecal microbiota transplantation at the Intestinal Microecology Center of Shanghai Tenth People's Hospital as respondents for semi-structured interviews. Colaizzi 7-step analysis method and NVivo 11.0 software were used for data analysis.Results:A total of 15 interviewees were interviewed. During fecal microbiota transplantation, the journey map of constipation patients included stages, mood changes, touchpoints, themes, emotional experiences and opportunities. The patient's experience and needs were summarized into three themes and ten sub-themes, including pre-transplant adaptation disorders to new environments (unfamiliarity and confusion-admission coordination disorders, anxiety and expectations-diverse complex emotions, puzzle and helplessness-asymmetric doctor and patient information), effectiveness-related psychological and social experiences in transplantation (attention and expectations-longing for positive efficacy, perception of benefits and risk avoidance, shame and inferiority-treatment stigmatization experience, questioning and despair-unrealized expectations, treatment resistance-sensitive economic burden), post-transplant transition dilemmas (inaccessible medical services-lack of continuous treatment and nursing, disease recurrence troubles) .Conclusions:This study visualizes the experiences and needs of constipation patients during microbiota transplantation through a patient journey map and identifies multidimensional issues and needs of patients. Clinical medical and nursing staff should pay attention to the needs of patients at different stages of the treatment process when formulating intervention programs to improve the quality of fecal microbiota transplantation nursing.

Objective To systematically evaluate the predictive value of controlling nutritional status(CONUT)score for short-term neurological function and clinical outcome of stroke.Methods Cochrane library,PubMed,Web of Science,Embase,CNKI,Wan-fang,VIP,and CBM were searched by computer to find studies on the use of CONUT score to evaluate the nutritional status and follow-up of stroke patients from the establishment of the database to April 11,2023.Literature was searched and screened independently by two researchers.The Newcastle-Ottawa scale(NOS)was used to evaluate the quality of the included studies.Stata 15.Osoftware was used for Meta-analysis.Results A total of 12 literatures were included,all of which were high quality.Meta-analysis results showed that high CONUT score(≥2)was strongly associated with poorer functional outcomes(OR=1.41,95％CI:1.25-1.60,P＜0.001,I2=49.4％),and associated with increased mortality(OR=2.85,95％CI:2.03-4.00,P＜0.001,I2=0)increase.Conclusion High CONUT score may be a predictor of neurological recovery status and survival outcome in patients after stroke,and the prognostic mechanism of CONUT score in stroke patients is unclear and needs to be confirmed by further studies.

Objective To explore the dilemmas faced by surrogate decision-makers of severe stroke patients in treatment decision-making,and to provide a basis for developing decision support strategies.Methods From April to December 2023,through phenomenological qualitative research with 16 surrogate decision-makers with severe stroke patients from ICU of the department of neurology in a tertiary hospital in Jing'an District,Shanghai.semi-structured in-depth interviews were used to examine the perceptions of decision-making on surrogate.Data were analyzed via Braun's style of thematic analysis.Results 4 themes and 10 sub-themes were identified.Theme 1:negative emotional dilemmas(urgent decision-making leads to anxiety,fear,and unknown stroke trajectory increases the sense of uncertainty).Theme 2:supportive environment dilemmas(lack of information support delays decision-making;lack of family support increases decision-making stress;insufficient economic support increases the burden of decision-making).Theme 3:the dilemma of weighing the pros and cons(difficult trade-offs between risk and reward,tough decisions between reality and ethics,conflicting choices of life and dignity).Theme 4:preference management dilemmas(practical difficulties in adhering to patient preferences,impediments to decision-making due to unknown patient preferences).Conclusion Surrogate decision-makers of severe stroke patients face multiple decision-making dilemmas.Healthcare professionals should provide emotional support in multiple ways and comprehensive support to reduce the decision-making dilemmas experienced by surrogate decision-makers,as well as implement death education for surrogate decision-makers and promote advance care planning to reduce their decision-making stress.

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Objective To compare the diagnostic performance of PI-RADS v2.1 and PI-RADS v2 in the detection of clinically significant prostate cancer(csPCa) by Meta-analysis. Methods The major biomedical databases were searched (CNKI, CBM, Medline, and Embase) with the keywords "PIRADS v2.1" or "PI-RADS v2.1". The Quality Assessment of Diagnostic Accuracy Studies Tool v2 (QUADAS-2) was used to evaluate literature quality. Meta-analysis was performed using STATA17.0 and ReMan5.4 software. Forest plots were used to represent the sensitivity and specificity of PI-RADS v2.1 and PI-RADS v2 for each study. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were combined, and diagnostic performance was evaluated using asummary receiver operating characteristic curve (SROC). Subgroup analysis was performed on three covariables: tumor location, threshold, and the nationality of authors. Results A total of 12 studies were included, involving 3 158 patients and 3 243 lesions. Forall zones and the whole gland, PI-RADS v2.1 had a larger area under the SROC curve (AUC) for csPCa performance, compared with PI-RADS v2. Subgroup analysis: PI-RADS v2.1 also had a larger area under the SROC (AUC) to detect transitional zone csPCa. Different diagnostic thresholds: when a score of 4 was used for the threshold, PI-RADS v2.1 had the maximum area under SROC (AUC) for csPCa performance detection. Author nationality: Researches of PI-RADS v2.1 in Chinese authors had the largest area under the SROC (AUC) in detecting csPCa performance. Conclusion Compared with PI-RADS v2, the diagnostic performance of PI-RADS v2.1 in detecting csPCa is not obviously improved and overall specificity is still low.