ObjectiveTo identify protein biomarkers and potential therapeutic targets associated with metabolic dysfunction-associated fatty liver disease （MAFLD） through an integrative multi-omics analysis. MethodsLarge-scale plasma protein quantitative trait locus data were integrated with MAFLD genome-wide association study data， and a proteome-wide Mendelian randomization analysis was performed. Summary data-based Mendelian Randomization （SMR）/heterogeneity in dependent instruments （HEIDI） test and colocalization analysis were used to assess significant proteins. The independent samples t-test was used for comparison of continuous data with homogeneity of variance between two groups， and the Welch-corrected t-test was used for comparison of continuous data with heterogeneity of variance. The transcriptomic validation results were compared with the Mendelian randomization results to evaluate the changing trends of gene expression， and boxplots were used to display the expression distribution of candidate genes between groups. ResultsAmong 7 130 proteins analyzed， 40 showed a causal relationship with MAFLD， among which 26 increased the risk of MAFLD and 14 exerted a protective effect against MAFLD （FDR<0.05）. Nine proteins were supported by SMR/HEIDI （P_SMR<0.05， P_HEIDI>0.05）， and 14 showed a strong colocalization signal （PPH₄>0.9）. The transcriptomic analysis identified 5 differentially expressed proteins （all P<0.05）， i.e.， adenosine diphosphate-ribosylation factor-like GTPase 2， insulin-like growth factor binding protein 2， casein kinase 1 delta （CSNK1D）， leucine-rich repeat neuronal 1， and moesin （MSN）. In vitro validation showed upregulated expression levels of MSN （1.612±0.346 vs 0.569±0.077， P<0.05）， 14-3-3 protein theta （YWHAQ） （1.267±0.126 vs 0.313±0.029， P<0.05）， and CSNK1D （0.871±0.025 vs 0.431±0.080， P<0.05） and a downregulated expression level of histone deacetylase 8 （0.637±0.059 vs 1.097±0.260， P<0.05） in the MAFLD cell model. Functional annotation showed that CSNK1D participated in circadian and metabolic regulation， YWHAQ modulated the Hippo pathway and lipid signal transduction， and MSN was associated with cytoskeletal remodeling and fibrogenic responses. ConclusionThe integrative proteogenomic analysis in this study shows that CSNK1D， YWHAQ， and MSN may be key mediators in the pathogenesis of MAFLD. These proteins have the potential to serve as novel biomarkers and therapeutic targets， providing new directions for research on disease mechanisms and the development of intervention strategies.

The prevalence of chronic constipation among the elderly is significant, exerting adverse effects on both their physical and mental health.Presently, pharmacological therapy remains the predominant treatment modality for elderly patients with chronic constipation; however, prolonged use can lead to drug dependence, tolerance, and adverse effects.This article systematically reviews non-pharmacological interventions for chronic constipation in elderly patients, both domestically and internationally, aiming to provide a comprehensive reference for clinical practice.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

The prevalence of chronic constipation among the elderly is significant, exerting adverse effects on both their physical and mental health.Presently, pharmacological therapy remains the predominant treatment modality for elderly patients with chronic constipation; however, prolonged use can lead to drug dependence, tolerance, and adverse effects.This article systematically reviews non-pharmacological interventions for chronic constipation in elderly patients, both domestically and internationally, aiming to provide a comprehensive reference for clinical practice.

OBJECTIVES: To construct a quantitative index system with the integrated medical and nursing care assessment for the elderly service needs, this system can assess the cost of medical and care services accurately and objectively, so as to provide scientific basis for the allocation of old-age service resources in China. METHODS: Based on the survival needs of the Existence, Relation and Growth theory, an index system is constructed through literature analysis, group discussion, and expert correspondence. Analytic hierarchy process was used to determine the weights of indicators at all levels. The 3-grades service items corresponding to each index were quantified through the measurement of working hours, and the medical and nursing care needs of 624 disabled/demented elderly people over 60 years old in Changsha were investigated to evaluate their reliability and validity. RESULTS: The authoritative coefficients of the 2 rounds of expert correspondence were 88.5% and 88.6%, respectively, and the opinion coordination coefficients were 0.159 and 0.167, respectively. The final quantitative evaluation index system included 4 first-level indicators, 17 second-level indicators, and 105 third-level indicators. The service time of doctor ranged from 6.01 to 22.64 min, the service time of nurses ranged from 0.77 to 24.79 min, and the service time of caregiver ranged from 0.12 to 51.88 min. The Cronbach's αcoefficient was 0.73, the split-half reliability was 0.74, the content validity was 0.93, and the calibration validity was 0.781. CONCLUSIONS The quantitative evaluation index system of medical and nursing service need for the elderly can be used to accurately evaluate the medical and nursing service need.
Humans ; Aged ; Middle Aged ; Reproducibility of Results ; Surveys and Questionnaires ; Delphi Technique ; Nursing Care ; China

Objective:To explore the influencing factors and the impact of artificial liver treatment on the prognosis and survival of patients with acute-on-chronic liver failure (ACLF).Methods:Clinical data from 201 cases with ACLF from January 2016 to December 2019 was retrospectively analyzed. The survival rate was calculated by the Kaplan-Meier method, the log-rank test of univariate analysis, and the multivariate analysis of the stepwise Cox regression forward method.Results:The median survival time of patients was 6 months, and the survival rates at 6, 9, and 12 months were 51.2%, 38.3%, and 29.9%, respectively. In univariate analysis, age, presence or absence of hypertension and upper gastrointestinal bleeding, treatment method, model for end-stage liver disease (MELD) score, and cholinesterase were associated with prognosis ( P < 0.05). Multivariate regression analysis results showed that MELD score was the main factor affecting the 1-year prognosis of ACLF patients ( P = 0.002). Artificial liver treatment was beneficial for the 1-year prognosis of ACLF patients aged < 50 years or with a MELD score of ≥20 ( P < 0.05 ). The relative risk ratio (RR) of mortality was 2.55 times higher in patients with advanced age (≥50 years old) than that of younger patients ( P < 0.001). Regression analysis was performed using age as a stratification factor, and upper gastrointestinal bleeding was related to the prognosis of younger patients, while choline esterase was related to the prognosis of advanced age. Regression analysis after stratified MELD score showed that age and hypertension were related to the prognosis of patients with MELD score < 20, and treatment method and age were related to the prognosis of patients with MELD score≥20. Conclusion:Artificial liver treatment is beneficial for the 1-year prognosis of ACLF patients. Age, MELD score, hypertension, and upper gastrointestinal bleeding are independent risk factors affecting the prognosis of ACLF patients.

Objective: To understand the epidemiologic features of the rabies in Xishuang banna prefecture of Yunnan province, China in 2008-2017 and the viral molecular-evolution characteristics. Methods: The data of rabies case questionnaire were collected. The brain tissue samples from mad dogs, suspicious sick dogs and human brain tissue, saliva and cerebrospinal fluid samples from rabies patients were collected in Xishuangbanna. Coding region of nucleoprotein and glycoprotein genes were amplified by RT-PCR and sequenced. Homology and phylogenetic analysis were performed using the relevant bioinformatics software. Results: A total of 62 cases of human rabies were occurred in 28 districts of the 3 counties, Xishuangbanna prefecture in 2008-2017. Of them, 37 cases in Jinghong county, 15 in Menghai county and 10 in Mengla county. In which 48 cases were bitten by domestic dogs (77.42%), 11 cases were bitten by wild dogs (17.74%). Rabies case was occurred every year in the past decade. The seasonal incidence was not obvious. The majority of patients were aged from 30 to 59 years-old, with the youngest 1 year-old and the eldest 91 year-old. The male to female ratio was 1.70∶1, most cases were farmers. The nucleotide sequences of nucleoprotein gene of 9 virus strains (7 from Jinghong, 1 from Menghai and 1 from Mengla) were obtained from the samples of dogs and patients. Homology and phylogenetic analyses indicated that the 5 strains belonged to clade China-Ⅰ, 3 clade China-Ⅱ and 1 clade China-Ⅵ. The nucleotide sequences of glycoprotein gene of 5 virus strains (3 from Jinghong, 1 from Menghai and 1 from Mengla) were obtained from these positive samples, and all were clade China-Ⅰ, it is same with nucleoprotein genes analysis result from these 5 virus strains. These China-Ⅰ and China-Ⅱ strains from Xishuangbanna have a closer genetic relationship with same clade strains isolated from Pu’er and other prefectures of Yunnan province as well as Sichuan, Guizhou and Guangxi. The China-Ⅵ strain from Xishuangbanna share high homology and genetic relationship with China-Ⅵ strains isolated from southwestern Yunnan and neighbouring countries such as Myanmar, Laos and Vietnam in recent years. Conclusions In Xishuangbanna, rabies mainly occurred in rural area and domestic dog was the main source of transmission. These RABV clades China-Ⅰ, China-Ⅱ and China-Ⅵ were found in this region and the China-Ⅰ was principal clade. The transmission source of China-Ⅰ and China-Ⅱ were from adjacent areas in the province and China-Ⅵ was from Myanmar and Laos.

Objective To investigate the regulatory role of HK2 in the metastasis of hepatocellular carcinoma ( HCC) . Methods The protein expressions of HK2 in 73 HCC tumor tissues and paired adjacent non?tumor tissues were evaluated by using immunohistochemical analysis. The scratch wound healing assay and Transwell assay had been used to analyze the migration and invasion of HCC cells with HK2 knockdown. Expressions of epithelial?to?mesenchymal transition ( EMT) markers, such as E?cadherin, ZO?1, N?cadherin and vimentin,in HCC cells with HK2 knockdown were determined by qRT?PCR and Western blot analysis. Results The expression levels of HK2 in tumor tissues and adjacent non?tumor tissues were 5.39±3.40 and 2.16±1.55, respectively. The protein expression of HK2 was significantly higher in tumor tissues compared with adjacent non?tumor tissues of HCC (P<0.05). Knockdown of HK2 in HCC cells decreased the cell motility from 1.00±0.54 to 0.56±0.09 (P<0.05), andknockdown of HK2 in HCC cells decreased the number of invaded cells form 345±42 to 215±34 (P<0.05). The expression of epithelial markers ZO?1 and E?cadherin were up?regulated, while mesenchymal markers vimentin and N?cadherin were down?regulated in HCC cells when HK2 was knockeddown. Conclusions HK2 is up?regulated in HCC and promotes cell motility by stimulating EMT.

Objective To investigate the regulatory role of HK2 in the metastasis of hepatocellular carcinoma ( HCC) . Methods The protein expressions of HK2 in 73 HCC tumor tissues and paired adjacent non?tumor tissues were evaluated by using immunohistochemical analysis. The scratch wound healing assay and Transwell assay had been used to analyze the migration and invasion of HCC cells with HK2 knockdown. Expressions of epithelial?to?mesenchymal transition ( EMT) markers, such as E?cadherin, ZO?1, N?cadherin and vimentin,in HCC cells with HK2 knockdown were determined by qRT?PCR and Western blot analysis. Results The expression levels of HK2 in tumor tissues and adjacent non?tumor tissues were 5.39±3.40 and 2.16±1.55, respectively. The protein expression of HK2 was significantly higher in tumor tissues compared with adjacent non?tumor tissues of HCC (P<0.05). Knockdown of HK2 in HCC cells decreased the cell motility from 1.00±0.54 to 0.56±0.09 (P<0.05), andknockdown of HK2 in HCC cells decreased the number of invaded cells form 345±42 to 215±34 (P<0.05). The expression of epithelial markers ZO?1 and E?cadherin were up?regulated, while mesenchymal markers vimentin and N?cadherin were down?regulated in HCC cells when HK2 was knockeddown. Conclusions HK2 is up?regulated in HCC and promotes cell motility by stimulating EMT.

Objective To evaluate combined effect on different population through 2 459 data of SAA,hs-CRP and PCT from 8 three-level hospitals in Guangdong region.Methods Subjects were divided into five groups by ages,and every group had bacterial and virus type.In order to confirm diagnostic effect on infection,methods were performed including in tendency of SAA and hs-CRP,Paired t test between bacterial and virus group,efficiency of 3 indexes in judging infection depending on ROC and parameters,multiple logistic regression,consistency between positive bacterial infection and bacterial culture.Re-sults There were statistically significant differences in SAA and hs-CRP between bacterial and virus in infants and children (P <0.001).SAA had the biggest AUC area 0.824 with sensibility 71.8% and specificity 82.6% in younger group.Corre-sponding,hs-CRP had the biggest area 0.806 with sensibility 84%.There was the accuracy of 78.8% for differential diagno-sis in younger group,while 65.1% in elder group.AUC of SAA was 0.883 for positive bacterial culture with sensibility 71.2% and specificity 90.7%,accuracy of 95.2% for differential diagnosis.Conclusion There was obvious trend of age in SAA and hs-CRP,3 indexes could be used for differential diagnosis alone or combined,especially in younger group.SAA is the best index as a separated index.There is less value at ratio of SAA and hs-CRP.