Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

OBJECTIVES: To reprogram human placental fibroblasts (HPFs) into chemically induced epithelioid-like cells (ciEP-Ls) using a combination of small-molecule compounds. METHODS: HPFs cultured under normoxic conditions were identified using immunofluorescence assay, PCR and chromosomal karyotyping. Under hypoxic conditions (37 ℃, 5% O₂), HPFs were cultured in a medium containing small-molecule compounds C6TSEDRVAJZ (CHIR99021, 616452, TTNPB, SAG, EPZ5676, DZNep, Ruxolitinib, VTP50469, Afuresertib, JNK-IN-8, and EZM0414), and the cell morphology was observed daily. The expression levels of epithelial cell markers in the induced cells were detected by immunofluorescence, Western blotting and PCR. Chromosomal karyotyping of the induced cells was performed and the induction efficiency was calculated. RESULTS: Before induction, HPFs showed positive expressions of fibroblast surface markers CD34 and vimentin and were negative for epithelial surface markers. PCR results showed high expressions of fibroblast-specific genes S100A4 and COL1A1 in HPFs with a normal human diploid karyotype. After one day of induction, the HPFs underwent morphological changes from a multinodular spindle shape to a round or polygonal shape, which was morphologically characteristic of ciEP-Ls. On day 4 of induction, the cells exhibited high expressions of the epithelial cell markers E-cadherin and Lin28A. RT-qPCR results also showed that the cells expressed the epithelial markers Smad3, GLi3, PAX8, WT1, KRT19, and KRT18 with significantly down-regulated expressions of all the fibroblast surface markers and a normal human diploid karyotype. The reprogramming efficiency of HPFs into ciEP-Ls ranged from (64.53±2.8)% to (68.10±3.6)%. CONCLUSIONS The small-molecule compound combination C6TSEDRVAJZ is capable of inducing HPFs into ciEP-Ls under hypoxic conditions with a high induction efficiency.
Humans ; Fibroblasts/drug effects* ; Pregnancy ; Female ; Cell Differentiation/drug effects* ; Pyrimidines/pharmacology* ; Placenta/cytology* ; Cells, Cultured ; Pyridines/pharmacology* ; Pyrazoles/pharmacology* ; Epithelial Cells/cytology*

Objective This study aims to systematically evaluate the evidence-based medicine of traditional Chinese medicine(TCM)in the treatment of dry eye,analyze its efficacy and differences compared with modern Western medicine treatments,and provide a scientific basis for clinical application.Methods By searching Chinese and English databases(including CNKI,Wanfang Data,PubMed,Cochrane Library,etc.),we included meta-analyses and systematic reviews of TCM treatments for dry eye.Literature was screened according to strict inclusion and exclusion criteria,and relevant data were extracted and integrated for analysis.The Mantel-Haenszel fixed-effects model was used to calculate the relative risk(RR)and mean difference(WMD),with the effect size expressed as a 95％confidence interval,to analyze the efficacy in-dicators of TCM treatment for dry eye.Results A total of 21 articles were finally included,involving various TCM inter-ventions for dry eye(such as Chinese herbal medicine,acupuncture,and TCM external therapies).The results showed that TCM treatment was superior to Western medicine alone in improving the overall clinical efficacy[RR=1.63,95％CI(1.46,1.81),P＜0.05],prolonging tear film break-up time[MD=2.23,95％CI(1.85,2.60),P＜0.05],and increasing tear secretion[MD=1.49,95％CI(1.04,1.94),P＜0.05].In addition,acupuncture,the combination of Chinese herbal medicine and Western medicine,and TCM external therapies all demonstrated unique advantages in improving dry eye symptoms and tear function.Conclusion TCM treatment for dry eye shows significant efficacy in key indicators such as overall clinical efficacy,tear film break-up time,and tear secretion,with a high level of safety.

Objective This study aims to systematically evaluate the evidence-based medicine of traditional Chinese medicine(TCM)in the treatment of dry eye,analyze its efficacy and differences compared with modern Western medicine treatments,and provide a scientific basis for clinical application.Methods By searching Chinese and English databases(including CNKI,Wanfang Data,PubMed,Cochrane Library,etc.),we included meta-analyses and systematic reviews of TCM treatments for dry eye.Literature was screened according to strict inclusion and exclusion criteria,and relevant data were extracted and integrated for analysis.The Mantel-Haenszel fixed-effects model was used to calculate the relative risk(RR)and mean difference(WMD),with the effect size expressed as a 95％confidence interval,to analyze the efficacy in-dicators of TCM treatment for dry eye.Results A total of 21 articles were finally included,involving various TCM inter-ventions for dry eye(such as Chinese herbal medicine,acupuncture,and TCM external therapies).The results showed that TCM treatment was superior to Western medicine alone in improving the overall clinical efficacy[RR=1.63,95％CI(1.46,1.81),P＜0.05],prolonging tear film break-up time[MD=2.23,95％CI(1.85,2.60),P＜0.05],and increasing tear secretion[MD=1.49,95％CI(1.04,1.94),P＜0.05].In addition,acupuncture,the combination of Chinese herbal medicine and Western medicine,and TCM external therapies all demonstrated unique advantages in improving dry eye symptoms and tear function.Conclusion TCM treatment for dry eye shows significant efficacy in key indicators such as overall clinical efficacy,tear film break-up time,and tear secretion,with a high level of safety.

ObjectiveTo explore the possible mechanism of the Yiqi Jiedu formula （YQ） in treating ischemic stroke （IS） from the perspective of the microbial-gut-brain axis （MGBA）. MethodRats were randomly divided into five groups， with six in each group， including sham surgery group， model group， and low， medium， and high dose YQ groups （1， 5， and 25 mg·kg^-1）. Except for the sham surgery group， all other groups were established with a middle cerebral artery occlusion （MCAO） model using the thread occlusion method. The success of modeling was determined through neurobehavioral scoring， and the protective effect of YQ on IS was evaluated. Then， the changes in gut microbiota before and after MCAO modeling and YQ administration were compared using 16S rDNA sequencing technology， and the possible biological pathways related to the effect of this formula were analyzed. The expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-17A （IL-17A）， and interleukin-10 （IL-10） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression of tight junction proteins ZO-1 and Occludin in brain and intestinal tissue， and hematoxylin-eosin staining （HE） was used to observe pathological changes in the cerebral cortex and colon， so as to validate the possible mechanism of action. ResultYQ significantly improved the neurobehavioral score of MCAO rats （P<0.01） and played a good regulatory role in intestinal microbial disorders caused by enriched pathogens and opportunistic pathogens during the acute phase. Among them， significantly changed microorganisms include Morgentia， Escherichia Shigella， Adlercreutzia， and Androbacter. Bioinformatics analysis found that these bacteria may be related to the regulation of inflammation in the brain. Compared with the blank group， the detection of inflammatory factors in the serum of IS model rats showed an increase in inflammatory factors IL-6 and IL-17A （P<0.01） and a decrease in the content of anti-inflammatory factor IL-10 （P<0.01）. Compared with the model group， the content of inflammatory factors IL-6 and IL-17A in the serum of the treatment group decreased （P<0.05）， and that of anti-inflammatory factor IL-10 increased （P<0.01）. The expression results of barrier proteins ZO-1 and Occludin in brain and intestinal tissue showed that the expression levels of both decreased in IS model rats （P<0.05）， while the expression levels of both increased in the treatment group （P<0.05）. ConclusionAcute cerebral ischemia can lead to an imbalance of intestinal microbiota and damage to the intestinal barrier， and it can increase intestinal permeability. YQ can regulate intestinal microbiota imbalance caused by ischemia， inhibit systemic inflammatory response， and improve the disruption of the gut-blood brain barrier， preventing secondary cascade damage to brain tissue caused by inflammation. The MGBA may be an important mechanism against the IS.

The conventional acupoint therapy for rheumatoid arthritis often uses traditional Chinese medicine preparations in the dosage forms of powder, ointment, and paste. However, these dosage forms have obvious drawbacks, such as low transdermal absorption, strong skin irritation, and easy detachment. Creating a traditional Chinese medicine acupoint therapy characterized by high penetration, low toxicity, low irritation, and convenient administration is of great significance. With the development of new technology for modern traditional Chinese medicine preparations, modern dosage forms such as microemulsion, microparticle, hydrogel, and liposome are combined with acupoint administration, and the derived therapeutic methods include acupoint application, acupoint injection, microneedle, and nanoporous acupuncture needle. The combination of new dosage forms of traditional Chinese medicine preparations and acupoint administration has the advantages of high drug permeability, high retention, and the formation of drug acupoint storage. The accumulation of drugs in acupoints continuously amplifies the acupoint effect, achieving a synergistic effect of drug treatment and acupoint treatment(1+1>2). This article reviews the relevant research and improvement of new dosage forms of traditional Chinese medicine preparations combined with acupoint administration for the treatment of RA, providing new development ideas for the combination of traditional Chinese medicine acupoint therapy and modern new formulation technologies.
Humans ; Arthritis, Rheumatoid/drug therapy* ; Drugs, Chinese Herbal/administration & dosage* ; Acupuncture Points ; Dosage Forms ; Medicine, Chinese Traditional/methods* ; Animals

Objective:Operational efficiency and influencing factors of China's basic medical insurance system from 2020 to 2021 is conducted to provide reference for improving the operational efficiency and optimizing the input-output relationship.Methods:The super-efficiency SBM model based on unexpected output and the Malmquist index are used to measure the static and dynamic efficiency of resident medical insurance in 31 provinces in China,and Tobit regression analysis is employed to analyze the influencing factors.Results:The overall operational efficiency of resident medical insurance still needs improvement.The operational efficiency of resident medical insurance in the central and western regions is lower than that in the eastern region,and the gap is significant.Different levels and regions have differentiated main constraints on the operational efficiency of resident medical insurance.In terms of dynamic efficiency,the total factor productivity of resident medical insurance operation shows an increasing trend,mainly due to technological progress.In terms of influencing factors,the degree of aging,the level of medical expenses and the level of medical insurance supervision have a significant impact on the operational efficiency.Suggestions:Efforts should be made to bridge regional disparities,promote the equitable development of medical insurance,reasonably control the level of medical expenses,strengthen the supervision of medical insurance funds,and implement active aging policies.