Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.

Objective:To investigate the differences between high-frequency ultrasound-guided manual detorsion combined with surgery(MD+S)and surgery alone in the treatment of testicular torsion,and to provide some new evidence for the timely diagno-sis and treatment of the disease.Methods:We retrospectively analyzed the clinical data on 134 cases of unilateral testicular torsion within 48 hours treated in our hospital by MD+S or by surgery alone from January 2015 to May 2022.We statistically analyzed the age distribution,and duration and degrees of testicular torsion,followed by comparison between the two groups.Results:In the 134 ca-ses,the median age of onset was 15(13-19)years old,the median onset-to-visit time was 15(8-25)hours,and the median de-gree of torsion was 360°(180°-1080°).Of the total number of patients,21 underwent testicular excision and the other 113 were treated with the testis preserved,with no statistically significant difference in age distribution between the two groups(P＞0.05),and a higher rate of testis resection in those with longer duration and greater angle of torsion(P＜0.05).Totally,33 of the patients were assigned to the MD+S group and 101 to the surgery alone group.According to the actual clinical conditions and excluding those with torsion time longer than 24 hours and torsion angle greater than 720 °,28 of the patients underwent ultrasound-guided MD+S(with 1 case of testis resection,3.6％),and 68 received surgery alone(with 7 cases of testis resection,10.3％).The rate of testis resection was higher in the surgery alone than that in the MD+S group,but with no statistically significant difference between the two groups(P＞0.05),which was considered to be related to the small sample size in this study.Conclusion:The popularization of testicular torsion knowledge can shorten the onset-to-visit time,and reasonable manual detorsion before emergency surgery can reduce the rate of testis resection.

Objective:To explore the effects of medication interval on the quality of split-dose bowel preparation and analyze the independent risk factors affecting the quality of bowel preparation.Methods:This pilot study involved two centers. Adult outpatients who underwent screening, surveillance, and diagnostic colonoscopy in the First Affiliated Hospital of Naval Medical University ( n=46) and the Fifth Hospital of Zhangjiakou ( n=20) between April and June 2023 were enrolled. Bowel preparation was conducted based on the guideline. Patients were divided into the short-interval group (4-<10 hours, n=45) and the long-interval group (10-16 hours, n=21) based on the time between the two administrations of polyethylene glycol during bowel preparation. Differences in terms of patient-reported outcome measurements (patient-reported willingness to repeat the bowel preparation regimen, satisfaction with bowel preparation, satisfaction with sleep), defecation frequency, Boston bowel preparation scale scores, bowel preparation bubble scores, bowel preparation qualified rates, polyp detection rates and incidence of adverse events were compared. Relevant factors influencing bowel preparation quality were analyzed by univariate logistic regression. Results:There were no significant differences in patient-reported willingness to repeat the bowel preparation regimen [88.9% (40/45) VS 85.7% (18/21), χ2<0.001, P>0.999], the satisfaction with bowel preparation [65.9% (29/45) VS 57.1% (12/21), χ2=0.469, P=0.493], or the satisfaction with sleep quality [35.6% (16/45) VS 28.6% (6/21), χ2=0.314, P=0.575] between the short-interval and long-interval groups. Similarly, no significant differences were observed between the groups in defecation frequency (11.3±4.8 VS 10.2±4.4, t=0.861, P=0.395), Boston bowel preparation scale scores (8.2±1.4 scores VS 7.9±1.2 scores, t=1.024, P=0.311), bowel preparation bubble scores (8.6±1.0 scores VS 8.4±1.5 scores, t=0.672, P=0.506), bowel preparation qualified rates [88.9% (40/45) VS 90.5% (19/21), χ2<0.001, P>0.999], polyp detection rates [33.3% (15/45) VS 47.6% (10/21), χ2=1.242, P=0.265], or incidence of adverse events [24.4% (11/45) VS 14.3% (3/21), χ2=0.381, P=0.537]. Univariate logistic analysis suggested that a low-fiber diet ( OR=8.100, 95% CI:1.400-46.849, P=0.019) was an influencing factor for qualified bowel preparation. Conclusion:Medication interval of the two doses of polyethylene glycol in a split-dose bowel preparation regimen for colonoscopy has no significant impact on bowel preparation quality. Notably, preoperative low-fiber diet emerges as an independent protective factor for qualified bowel preparation.

Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17％.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49％.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3％at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100％.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.

Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.

Based on network pharmacology,through molecular docking and experimental validation,the study explored the mechanism of the Hypericum japonicum-Rehmannia glutinosa-Salvia ple-beian compound(HRS)in the treatment of liver injury.Mice were randomly divided into a control group(CON group),a model group(CCL4 group),a high-dose drug group(HRS-H group),and a low-dose group(HRS-L group).A mouse liver injury model was established using CCL4 induction,liver tissue pathological morphology was observed,and the relative expression levels of liver in-flammatory cytokine genes was measured.Active ingredients of traditional Chinese medicine and targets related to Chinese medicine and diseases were obtained from databases such as Herb,TCM-SP,PubChem,Swiss Target Prediction,Gene Cards and DisGeNET.The intersection of targets was used to obtain potential drug targets.The potential targets were analyzed for protein-protein inter-action(PPI)using the string database and a network diagram of"drug-active component-intersec-tion target"was constructed using Cytoscape.DAVID database was used for GO and KEGG path-way analysis,and Auto Dock Tools software was used for molecular docking.Finally,the results of molecular docking by examining the expression of key target genes and downstream genes such as those related to the PI3K-AKT pathway and the autophagy pathway were experimentally valida-ted.Results:Animal experiment results showed that compared to the CON group,the CCL4 group of mice exhibited disrupted liver architecture,hepatocyte steatosis,vacuolization,and extensive in-flammatory cell infiltration.These characteristics were ameliorated by drug treatment groups with the HRS-H group demonstrating superior effects compared to the HRS-L group.RT-qPCR results from mouse livers showed significantly increased relative expression of TNF-α and INOS mRNA compared to the CON group in the CCL4 group(P＜0.01),and significantly increased IL-1β mR-NA relative expression(P＜0.05).Compared to the CCL4 group,the HRS-H group showed signifi-cantly decreased TNF-α,INOS,and IL-1β mRNA relative expressions(P＜0.01).155 potential tar-gets for HRS in alleviating liver damage were identified through network pharmacology,with top-ranked key target points including STAT3,SRC,PIK3R1,PIK3CA,AKT1,HSP90A11,EGFR,and ESR.Key active ingredients included Tetramethoxyluteolin,Hispidulin,Eupafolin,Kaempferol,and Eupaformonin.GO enrichment analysis yielded 940 entries,and KEGG enrichment analysis yielded 177 biological pathways.Molecular docking results showed a strong binding ability between the main components of HRS and key target points.RT-qPCR results showed increasing trends for EGFR,PI3KCA,HSP90A11,and NF-κB mRNA compared to the CON group in the CCL4 group,significantly increased AKT1 mRNA relative expression(P＜0.05),significant decreases in ULK1,ATG5,LC3B,and ATG7 mRNA relative expressions(P＜0.05),and extremely significant decreases in PTEN,ATG13,BECLIN-1,ATG16L1,ATG12,ATG4B,and ATG3 mRNA relative expressions(P＜0.01).Compared to the CCL4 group,the HRS-H group showed significantly de-creased PI3KCA,HSP90A11,and NF-κB mRNA relative expressions(P＜0.05),extremely signif-icantly decreased EGFR,AKT1,and mTOR mRNA relative expressions(P＜0.01),increased ULK1 relative expression trends,significantly increased PTEN,ATG16L1,ATG5,LC3B,and ATG7 mRNA relative expressions(P＜0.05),extremely significantly increased ATG13,BECLIN-1,ATG12,ATG4B,and ATG3 mRNA relative expressions(P＜0.01).Conclusion:The HRS ex-erts hepatoprotective effects through multi-component,multi-pathway approaches,with alleviating inflammation and promoting hepatocyte autophagy through PI3K-AKT pathway likely being im-portant mechanisms for its protective effects.

Based on network pharmacology,through molecular docking and experimental validation,the study explored the mechanism of the Hypericum japonicum-Rehmannia glutinosa-Salvia ple-beian compound(HRS)in the treatment of liver injury.Mice were randomly divided into a control group(CON group),a model group(CCL4 group),a high-dose drug group(HRS-H group),and a low-dose group(HRS-L group).A mouse liver injury model was established using CCL4 induction,liver tissue pathological morphology was observed,and the relative expression levels of liver in-flammatory cytokine genes was measured.Active ingredients of traditional Chinese medicine and targets related to Chinese medicine and diseases were obtained from databases such as Herb,TCM-SP,PubChem,Swiss Target Prediction,Gene Cards and DisGeNET.The intersection of targets was used to obtain potential drug targets.The potential targets were analyzed for protein-protein inter-action(PPI)using the string database and a network diagram of"drug-active component-intersec-tion target"was constructed using Cytoscape.DAVID database was used for GO and KEGG path-way analysis,and Auto Dock Tools software was used for molecular docking.Finally,the results of molecular docking by examining the expression of key target genes and downstream genes such as those related to the PI3K-AKT pathway and the autophagy pathway were experimentally valida-ted.Results:Animal experiment results showed that compared to the CON group,the CCL4 group of mice exhibited disrupted liver architecture,hepatocyte steatosis,vacuolization,and extensive in-flammatory cell infiltration.These characteristics were ameliorated by drug treatment groups with the HRS-H group demonstrating superior effects compared to the HRS-L group.RT-qPCR results from mouse livers showed significantly increased relative expression of TNF-α and INOS mRNA compared to the CON group in the CCL4 group(P＜0.01),and significantly increased IL-1β mR-NA relative expression(P＜0.05).Compared to the CCL4 group,the HRS-H group showed signifi-cantly decreased TNF-α,INOS,and IL-1β mRNA relative expressions(P＜0.01).155 potential tar-gets for HRS in alleviating liver damage were identified through network pharmacology,with top-ranked key target points including STAT3,SRC,PIK3R1,PIK3CA,AKT1,HSP90A11,EGFR,and ESR.Key active ingredients included Tetramethoxyluteolin,Hispidulin,Eupafolin,Kaempferol,and Eupaformonin.GO enrichment analysis yielded 940 entries,and KEGG enrichment analysis yielded 177 biological pathways.Molecular docking results showed a strong binding ability between the main components of HRS and key target points.RT-qPCR results showed increasing trends for EGFR,PI3KCA,HSP90A11,and NF-κB mRNA compared to the CON group in the CCL4 group,significantly increased AKT1 mRNA relative expression(P＜0.05),significant decreases in ULK1,ATG5,LC3B,and ATG7 mRNA relative expressions(P＜0.05),and extremely significant decreases in PTEN,ATG13,BECLIN-1,ATG16L1,ATG12,ATG4B,and ATG3 mRNA relative expressions(P＜0.01).Compared to the CCL4 group,the HRS-H group showed significantly de-creased PI3KCA,HSP90A11,and NF-κB mRNA relative expressions(P＜0.05),extremely signif-icantly decreased EGFR,AKT1,and mTOR mRNA relative expressions(P＜0.01),increased ULK1 relative expression trends,significantly increased PTEN,ATG16L1,ATG5,LC3B,and ATG7 mRNA relative expressions(P＜0.05),extremely significantly increased ATG13,BECLIN-1,ATG12,ATG4B,and ATG3 mRNA relative expressions(P＜0.01).Conclusion:The HRS ex-erts hepatoprotective effects through multi-component,multi-pathway approaches,with alleviating inflammation and promoting hepatocyte autophagy through PI3K-AKT pathway likely being im-portant mechanisms for its protective effects.

BACKGROUND:How to effectively promote bone regeneration and bone reconstruction after bone injury has always been a key issue in clinical bone repair research.The use of biological and degradable materials loaded with bioactive factors to treat bone defects has excellent application prospects in bone repair. OBJECTIVE:To investigate the effect of polylactic acid-glycolic acid copolymer(PLGA)composite scaffold modified by lysine-grafted graphene oxide nanoparticles(LGA-g-GO)on osteogenic differentiation and new bone formation. METHODS:PLGA was dissolved in dichloromethane and PLGA scaffold was prepared by solvent evaporation method.PLGA/GO composite scaffolds were prepared by dispersing graphene oxide uniformly in PLGA solution.LGA-g-GO nanoparticles were prepared by chemical grafting method,and the PLGA/LGA-g-GO composite scaffolds were constructed by blending LGA-g-GO nanoparticles at different mass ratios(1%,2%,and 3%)with PLGA.The micromorphology,hydrophilicity,and protein adsorption capacity of scaffolds of five groups were characterized.MC3T3 cells were inoculated on the surface of scaffolds of five groups to detect cell proliferation and osteogenic differentiation. RESULTS AND CONCLUSION:(1)The surface of PLGA scaffolds was smooth and flat under scanning electron microscope,while the surface of the other four scaffolds was rough.The surface roughness of the composite scaffolds increased with the increase of the addition of LGA-g-GO nanoparticles.The water contact angle of PLGA/LGA-g-GO(3%)composite scaffolds was lower than that of the other four groups(P<0.05).The protein adsorption capacity of PLGA/LGA-g-GO(1%,2%,and 3%)composite scaffolds was stronger than PLGA and PLGA/GO scaffolds(P<0.05).(2)CCK-8 assay showed that PLGA/LGA-g-GO(2%,3%)composite scaffold could promote the proliferation of MC3T3 cells.Alkaline phosphatase staining and alizarin red staining showed that the cell alkaline phosphatase activity in PLGA/LGA-g-GO(2%,3%)group was higher than that in the other three groups(P<0.05).The calcium deposition in the PLGA/GO and PLGA/LGA-g-GO(1%,2%,and 3%)groups was higher than that in the PLGA group(P<0.05).(3)In summary,PLGA/LGA-g-GO composite scaffold can promote the proliferation and osteogenic differentiation of osteoblasts,and is conducive to bone regeneration and bone reconstruction after bone injury.

Objective To analyze the medication rules of traditional Chinese medicine compound patents for the prevention and treatment of urinary tract infection(UTI)through data mining technology.Methods The patents of traditional Chinese medicine compounds for the prevention and treatment of UTI in patent announcement module of China National Intellectual Property Administration website as data sources.The statistical analysis platforms of Excel 2021,IBM SPSS Modeler 18.0 and IBM SPSS Statistics 27.0 were used for frequency of use,medicinal properties,association rule analysis,and systematic clustering analysis and finally visualized by Cytoscape 3.7.2,RStudio.Results Through screening,a total of 179 compound patents met the inclusion criteria,involving 466 kinds of Chinese materia medica,and the top 5 high-frequency drugs were Pugongying,Huangbai,Gancao,Jinyinhua,Bianxu.The medicinal properties are mainly cold and mild;The medicinal taste is characterized by sweetness,bitterness,and bitterness;The main meridians of drugs are liver,lung and kidney meridians.Common couplet medicines included Qumai-Bianxu,Gancao-Bianxu and the three herb drug combinations included Cheqianzi-Qumai-Bianxu,Gancao-Qumai-Bianxu.A total of 5 high-frequency combinations of traditional Chinese medicine were obtained by cluster analysis.Conclusion This study preliminarily reveals the compatibility and medication rules of traditional Chinese medicine in the treatment of UTI,which provides data support for the optimization of clinical syndrome differentiation and treatment system and the development of new prescriptions.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.