Purpose: Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function. Materials and Methods: Male Sprague–Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection. Results: The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways. Conclusions Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.

BACKGROUND:Various proteins,signaling pathways,and inflammatory mediators are involved in the pathophysiological process of osteoarthritis.The development of small molecule drugs targeting these proteins,signaling pathways,and inflammatory mediators can effectively delay the progression of osteoarthritis and ameliorate its clinical manifestations. OBJECTIVE:To review the research progress of small molecule drugs in the treatment of osteoarthritis based on the pathogenesis of osteoarthritis. METHODS:PubMed,CNKI,and WanFang databases were searched with English search terms"osteoarthritis,arthritis,osteoarthrosis,degenerative,arthritides,deformans,small molecule drugs,small molecule inhibitors,small molecule agents"and Chinese search terms"osteoarthritis,small molecule drugs,small molecule inhibitors."A total of 68 articles were included for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Currently,studies concerning the pathogenesis of osteoarthritis remain unclear.The occurrence and development of osteoarthritis are strongly associated with proteins,cytokines,and signal transduction pathways,so its therapeutic mechanism is relatively complex.Currently,targeting proteins,cytokines,and signal transduction pathways related to osteoarthritis with small molecule drugs has become a major research focus.(2)Small molecule drugs frequently possess visible intracellular or extracellular targets and efficacy,containing enhancing cartilage repair,resisting joint degradation,attenuating inflammation,and relieving pain.Other anti-osteoarthritis small molecule drugs have shown promise in promoting stem cell chondrogenic differentiation and cartilage matrix reconstruction.(3)At present,small molecule drugs targeting the pathophysiological process of osteoarthritis to delay the progression of osteoarthritis are still in the experimental stage,but most of these small molecule drugs have shown the expected results in the experimental process,and there are no relevant studies to illustrate the efficacy of small molecule drugs in the treatment of osteoarthritis.(4)Small molecule drugs for the treatment of osteoarthritis have reached the expected experimental results in the basic experimental stage.Numerous studies have exhibited that small molecule drugs can target the suppression of specific proteins,cytokines,and signal transduction pathways that cause osteoarthritis,so as to treat osteoarthritis.Nevertheless,its safety and effectiveness still need to be identified by further basic and clinical studies.This process needs to be investigated and studied by more scholars.(5)At present,many scholars in and outside China have made contributions to the treatment of osteoarthritis.Compared with traditional treatment methods,small molecule drugs reveal better efficacy and safety in the basic experimental stage,and it is expected to become an emerging method for the treatment of osteoarthritis in the future to rid patients of pain.

Objective To investigate whether successful percutaneous coronary intervention(PCI)could improve symptoms and quality of life(QOL)in left main disease and/or 3-vessel disease patients with diabetes.Methods Patients with left main disease and/or 3-vessel disease who underwent PCI in the First Affiliated Hospital of Air Force Medical University from April 2018 to May 2021 were consecutively enrolled and subdivided into 2 groups:diabetes and no diabetes.Detailed baseline characteristics,symptoms,including dyspnea and angina,assessed with the Rose dyspnea scale(RDS),Seattle angina questionnaire(SAQ),the European quality of life-5 dimensions(EQ-5D)and 12-item short-form health survey(SF-12)questionnaire respectively,procedural details,and 1 month and 1 year follow-up data were collected.Results Among 440 left main disease and/or 3-vessel disease patients,disease was present in 176(40.00％),who had more hypertension,peripheral artery disease,and LCX lesion(all P＜0.05).The incidence of major adverse cardiovascular events(MACE)and all-cause mortality were similar between the two groups(both P＞0.05)at 1 month follow-up,while all-cause mortality in diabetes patients was significantly higher than those without diabetes at 1 year follow-up(P=0.013).Low left ventricular ejection fraction was an independent risk factor for MACE and all-cause mortality at 1 month and 1 year follow-up after successful revascularization(all P＜0.05).Most importantly,symptoms,including dyspnea and angina,and QOL were markedly improved regardless of diabetes both at 1 month and 1 year follow-up(all P＜0.05).Diabetes patients showed improved dyspnea and QOL at similar degree to the non-diabetes patients(all P＞0.05)and a more significantly relieved angina(P=0.013).Additionally,the number of chronic total occlusion(CTO)per patient was identified as an independent risk factor of dyspnea(OR 0.723,95％CI 0.525～0.997,P=0.048)and angina relief(OR 0.686,95％CI 0.473～0.995,P=0.047),and the contrast volume(OR 0.995,95％CI 0.992～0.999,P=0.008)as an independent risk factor of QOL improvement in diabetic patients.Conclusions Successful PCI is beneficial for relieving symptoms and improving quality of life in patients with diabetes who have left main disease and/or 3-vessel disease.

This study aims to screen the diagnostic biomarkers for fecal antigen of Echinococcus granulosus(E.granulosus)in dogs with high specificity and sensitivity.The sheep-derived EgPSC artificially infected dogs were collected,and the negative and positive fecal samples of dogs with E.granulosus were prepared by arecoline hydrobromide leakage method.Polyclonal antibody,negative fecal antigen-polyclonal antibody conjugates and positive fecal antigen-polyclonal antibody conju-gates were purified by ammonium sulfate precipitation and affinity chromatography,three groups of samples were detected by ELISA and Western blot,LC-MS/MS and bioinformatics analysis were performed on the three groups of samples.The positive fecal antigen-polyclonal antibody con-jugate was used as the treatment group,the polyclonal antibody and the negative fecal antigen-polyclonal antibody conjugates were used as the control groups to screen the unique peptides of the treatment group.ELISA and Western blot showed that only the positive fecal antigen-polyclonal antibody conjugates were positive.According to LC-MS/MS and bioinformatics analysis,11 unique peptides were screened out only in the treatment group.Among them,3 proteins were related to E.granulosus,namely dysferlin,integrator complex 9 and diagnostic antigen gp50,which were mem-brane-associated proteins,INT complex components and diagnostic antigens.This study has pre-liminarily screened out three candidate canine E.granulosus fecal antigen diagnostic markers,pro-viding a reference for further exploration of diagnostic standards for E.granulosus,screening of echinococcosis target genes,and vaccine development.

Objective:To observe the expression level of long noncoding RNA RP11-97C16.1 in bladder cancer tissues and its relationship with the survival time of bladder cancer patients, and to explore the role and potential molecular mechanism of RP11-97C16.1 in the proliferation of bladder cancer cells.Methods:The expression difference of RP11-97C16.1 in bladder cancer tissue and adjacent tissue was analyzed by TCGA database, and the relationship between the expression level of RP11-97C16.1 and the survival time of bladder cancer patients was analyzed by GEPIA database. The expression of RP11-97C16.1 in four bladder cancer cell lines (T24, MGH-U3, J82, UM-UC-3) was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The UM-UC-3 cells were divided into RP11-97C16.1 group and control group, and the transfectants were pcDNA-RP11-97C16.1 plasmid and negative control plasmid, respectively. The expression levels of RP11-97C16.1 and miR-3687 were detected by RT-qPCR. The viability and proliferation ability of UM-UC-3 cells were detected by cell counting kit-8 (CCK8) and colony formation assay. The complementary relationship between RP11-97C16.1 and miR-3687 was verified by dual-luciferase reporter gene assay. The expression levels of Cyclin E2, CDK2, CDK4, CDK6 and Cyclin D2 were detected by Western blotting. Measurement data were expressed as mean ± standard deviation ( ± s), independent sample t-test was used for comparison between two groups, and one-way analysis of variance was used for comparison between multiple groups. Results:Compared with adjacent tissues, the expression of RP11-97C16.1 in bladder cancer tissues was significantly decreased ( P<0.01). Compared with patients with lower expression of RP11-97C16.1, patients with higher expression of RP11-97C16.1 had longer overall survival time ( P<0.01). Compared with the SV-HUC-1 cell line, the expression of RP11-97C16.1 was significantly decreased in the four bladder cancer cell lines ( P<0.01). In UM-UC-3 cells in which RP11-97C16.1 was upregulated, the expression of miR-3687 was decreased ( P<0.01). Compared with the control group, up-regulation of RP11-97C16.1 could significantly reduce the proliferation ability of UM-UC-3 cells ( P<0.05), and decrease the number of bladder cancer cell colonies ( P<0.01). RP11-97C16.1 could target and bind miR-3687 ( P<0.01). Compared with the control group, overexpression of RP11-97C16.1 could significantly decreased the expression of Cyclin E2, CDK2, CDK4, CDK6, and Cyclin D2 proteins. Conclusions:The expression of RP11-97C16.1 is low in bladder cancer tissue, and patients with higher expression of RP11-97C16.1 have a longer survival time. Up-regulation of RP11-97C16.1 can down-regulate the expression of miR-3687, thereby inhibiting the proliferation of bladder cancer cells UM-UC-3.

Health think tanks serve as a crucial intellectual support for the Healthy China strategy. The authors systematically analyzed the definitions, classifications, and operational status of health think tanks, categorizing them into five types: government-affiliated think tanks, university and research institute think tanks, social think tanks, hospital think tanks, and corporate think tanks. It was indicated that current health think tanks had significant room for improvement in both quantity and influence, particularly concerning deeper integration with policy decision-making and interdisciplinary collaboration. Although these think tanks played a unique role in supporting government decision-making, issues such as lagging institutional development, insufficient collaborative effectiveness, and difficulties in translating research findings into practice remained prominent. To enhance the ability of think tanks to serve the Healthy China strategy, this study proposed strategies including strengthening top-level design, improving participation mechanisms, optimizing management and evaluation systems, establishing data-sharing platforms, and deepening collaborative governance, with the aim of fostering the healthy development of China′s health think tanks.

Objective:To summarize the characteristics of hemodynamically significant patent ductus arteriosus (hsPDA) in very low birth weight (VLBW) preterm infants and evaluate the efficacy and safety of transcatheter PDA closure (TCPC).Methods:This was a retrospective study including five VLBW preterm infants who were diagnosed with hsPDA by echocardiography at Women and Children's Hospital, Qingdao University from January to December 2024 and underwent transcatheter closure after pharmacological therapy failure. Follow-up assessments were conducted at 6 months after operation to evaluate PDA closure status, survival outcomes, and the occurrence of complications. Descriptive statistical analysis was used to summarize the demographic characteristics and clinical data.Results:The cohort comprised three males and two females. The median gestational age was 28 (24-29) weeks, and the median birth weight was 1 000 (670-1 220) g. The median age and birth weight at surgery were 25 (13-36) d and 1 200 (810-1 400) g, respectively. The PDA diameter was 3.8 (2.3-4.1) mm. PDA closure was successfully achieved in all five infants using the Amplatzer Piccolo? occlude, with no major procedure-related complications. All patients were weaned from mechanical ventilation and discharged. At 6-month follow-up, all five infants survived with no residual shunt, left pulmonary artery stenosis, or aortic coarctation on echocardiography.Conclusions:TCPC is feasible and safe for VLBW preterm infants when pharmacological therapy is ineffective or contraindicated. Larger cohorts and extended follow-up are needed to assess long-term outcomes and potential complications.

Objective:To investigate the clinical data, drug resistance and treatment prognosis of Cryptococcus neoformans isolated from patients with acquired immunodeficiency syndrome(AIDS) in a hospital in Shanghai. Methods:The clinical data of AIDS patients with Cryptococcus neoformans infection in Shanghai Public Health Clinical Center from January 2014 to December 2023, and the drug sensitivity to 5 antifungal drugs in vitro, treatment and prognosis were retrospectively analyzed. Results:From January 2014 to December 2023, there were 295 AIDS patients with Cryptococcus neoformans infection in our hospital, with 255 males and 40 females. CD4 + T lymphocyte counts ≤100 cells/μl were detected in 251 patients. A total of 384 strains of Cryptococcus neoformans were isolated from the 295 patients, with the highest detection rate in cerebrospinal fluid samples (65.9%, 253/384), followed by blood samples (29.4%, 113/384). The sensitivity of 384 strains of Cryptococcus neoformans to 5-fluorocytosine was the highest (98.5%, 379/384), followed by fluconazole (95.6%, 367/384) and amphotericin B (95.3%, 366/384). After treatment against cryptococcal infection, 252 patients (86.0%, 252/293) were discharged and 20 patients (6.8%, 20/293) died. The other 2 cases were not treated for cryptococcal infection. Conclusions:As Cryptococcus neoformans is an important pathogen of AIDS patients, clinicians should actively carry out laboratory examination of Cryptococcus and rational drug use according to the results of drug sensitivity test, while alert to the occurrence of drug resistance.

Purpose: Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function. Materials and Methods: Male Sprague–Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection. Results: The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways. Conclusions Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.

Objective:To evaluate the short-term outcomes of robotic double-flap technique following proximal gastrectomy in patients with carcinoma of esophagogastric junction(AEG).Methods:Clinical data of 5 AEG cases undergoing robotic double-flap technique following proximal gastrectomy were analyzed at the Department of Gastrointestinal Surgery, Peking University First Hospital from Dec 2023 to Aug 2024 .Results:All the 5 patients were of Siewert Ⅱ type AEG. Robot-assisted radical proximal gastrectomy and esophagogastric double-flap anastomosis were successfully completed. The operation time was (361±63) min, the installation time was (21±11) min, the anastomosis time was (90±21) min, and the median intraoperative blood loss was 100 (50,200) ml. The median number of intraoperative lymph nodes resected was 23 (14,32), the first postoperative exhaust time was (4.8±1.1) d, and postoperative hospital stay was (14.6±8.8) d. Postoperative abdominal distension occurred in 1 patient, and no significant anastomotic stenosis or anastomotic leakage was observed by upper gastroenterography. After conservative treatment, the patient recovered. None of them had Clavien-Dindo grade ≥Ⅲ complications. There were no anastomotic complications such as anastomotic leakage, anastomotic hemorrhage and anastomotic stenosis.Conclusion:Robotic double-flap technique following proximal gastrectomy is a safe and effective treatment for AEG.