Xanthine oxidase (XO) is an important therapeutic target for the treatment of hyperuricemia and gout. Based on the previously identified potent XO inhibitor 1, seventeen oxadiazoles and their ring-opening analogues were designed and synthesized via the bioisostere replacement strategy. Among them, compounds 2l, 2n, and 3b showed obvious XO inhibitory activity at the concentration of 10 μmol·L^-1, and compound 3b exhibited an IC₅₀ value of 1.45 μmol·L^-1.

Background Swimming is becoming increasingly popular for its combined leisure and fitness benefits. However, polluted swimming pool water may pose various health risks. Previous studies have indicated that health indicators of swimming venues have lower qualification rates compared to other public places, highlighting the urgent need to optimize hygiene management measures. Objective To assess the overall hygiene status and identify the key factors influencing water quality in Shanghai’s swimming venues from 2010 to 2024, and to provide a scientific basis for optimizing water quality management. Methods Water quality was assessed in three stages (2010—2019, 2020—2022, and 2023—2024) based on the monitoring data of Shanghai’s swimming venues (2010—2024). The influences of monitoring stage, region, season, scale, day of week, and per capita attendance on water quality were analyzed using chi-square tests and logistic regression. Results From 2010 to 2024, water quality was monitored in 1478 swimming venues. The compliance rates of turbidity, pH, urea, oxidation-reduction potential, free residual chlorine, combined residual chlorine, total bacteria, coliforms, and heat-resistant coliforms in swimming pool water, and free residual chlorine in the foot disinfection basin water samples were 99.56%, 94.73%, 73.00%, 47.50%, 56.55%, 54.12%, 97.74%, 99.49%, 99.90%, and 69.19%, respectively. The overall water quality compliance rate was 85.28%. The main non-compliant indicators for swimming pool water were urea, ORP, free residual chlorine, and combined residual chlorine, along with free chlorine residual in the foot disinfection basin water samples. Using the period before the implementation of the new national standard as reference, the results of logistic regression revealed that the qualification rates of urea, ORP, and free residual chlorine in the swimming pool water samples, as well as free residual chlorine in foot disinfection basin water samples, were significantly higher during the two phases after launching the new standard (2020–2022 and 2023–2024), and the associated odds ratios (95%CI) were 1.28 (1.00, 1.64) and 1.48 (1.12, 1.95), 13.35 (7.63, 23.37) and 10.78 (7.00, 16.60), 2.54 (1.81, 3.58) and 3.18 (2.41, 4.20), and 3.14 (2.14, 4.60) and 2.83 (1.89, 4.23), respectively. Compared with the reference group, those sampled in urban pools and in non-summer seasons showed higher qualification rates of urea and ORP; in contrast, the pools with high visitor flow showed lower qualification rates of free residual chlorine in both water samples of swimming pools and foot disinfection basins (P<0.05). Conclusion The implementation of the new national standard has effectively enhanced the management standards and significantly improved overall water quality of swimming venues in Shanghai. However, the compliance rates of free residual chlorine and urea in swimming pool water still need further improvement. The compliance of some indicators is influenced by region, season, scale, and average passenger flow, particularly in small suburban swimming venues. Future efforts should focus on refining water quality management strategies and enhancing public health management.

This study aimed to investigate the effect and underlying mechanisms of Zexie Decoction against liver injury in rats with hyperlipidemic acute pancreatitis(HLAP). The network pharmacology-related databases were used to screen the active components and potential targets of Zexie Decoction, as well as the disease targets of HLAP. A protein-protein interaction(PPI) network of the overlapping targets was constructed. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis and Gene Ontology(GO) functional enrichment analysis were performed on the overlapping targets. Sprague-Dawley(SD) rats were randomly divided into sham group, model group, low-dose Zexie Decoction group, and high-dose Zexie Decoction group. Enzyme-linked immunosorbent assay(ELISA) kits were used to detect serum biochemical indicators. Hematoxylin-eosin(HE) staining was used to observe the pathological morphology of the pancreas and liver tissues, while oil red O staining was employed to assess hepatic steatosis. Immunofluorescence staining was used to detect the expression of IL-1β and NLRP3 in pancreatic tissues. Western blot analysis was conducted to evaluate the expression levels of proteins related to oxidative stress, endoplasmic reticulum stress, the PI3K/AKT signaling pathway, and autophagy. Network pharmacology predictions identified 721 targets of Zexie Decoction and 2 486 targets associated with HLAP, with 279 overlapping targets. GO enrichment analysis yielded 1 112 entries, and KEGG enrichment analysis identified 179 signaling pathways. Experimental results showed that Zexie Decoction could reduce the levels of lipid metabolites, serum enzymes, and inflammatory cytokines in HLAP rats, alleviate pathological damage to the pancreas and liver, decrease hepatic lipid accumulation, and decrease the expression of IL-1β and NLRP3 in pancreatic tissues. In addition, Zexie Decoction significantly upregulated the expression of antioxidant stress-related proteins NRF2 and HO-1, downregulated the expression of endoplasmic reticulum stress-related proteins BiP, xBP1s, p-eIF2α, eIF2α, and ATF4, inhibited the expression of PI3K and phosphorylation of AKT, increased the expression of autophagy-related proteins Beclin1, ATG3, ATG5, and ATG12, and reduced the expression of p62. In conclusion, Zexie Decoction can improve HLAP, and its mechanism may be associated with alleviating oxidative stress and endoplasmic reticulum stress, inhibiting the PI3K/AKT pathway, and inducing autophagy in hepatocytes.
Animals ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Rats ; Pancreatitis/genetics* ; Hyperlipidemias/genetics* ; Male ; Liver/injuries* ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Interleukin-1beta/genetics* ; Humans

Urinary incontinence is a common complication following robot-assisted radical prostatectomy (RARP). Urethral length has been identified as a factor affecting postoperative continence recovery. In this meta-analysis, we examined the association between use of the maximal urethral length preservation (MULP) technique and postoperative urinary continence in patients undergoing RARP. We conducted a comprehensive search of PubMed, Web of Science, Embase, and the Cochrane Library up to December 31, 2023. The quality of the literature was assessed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed to synthesize data and calculate the odds ratio (OR) from eligible studies on continence and MULP. Six studies involving 1869 patients met the eligibility criteria. MULP was positively associated with both early continence (1 month after RARP; Z = 3.62, P = 0.003, OR = 3.10, 95% confidence interval [CI]: 1.68-5.73) and late continence (12 months after RARP; Z = 2.34, P = 0.019, OR = 2.10, 95% CI: 1.13-3.90). Oncological outcomes indicated that MULP did not increase the overall positive surgical margin rate or the positive surgical margin status at the prostate apex (both P > 0.05). In conclusion, the use of the MULP technique in RARP significantly improved both early and late postoperative continence outcomes without compromising oncological outcomes.
Humans ; Prostatectomy/adverse effects* ; Robotic Surgical Procedures/methods* ; Male ; Urethra/surgery* ; Urinary Incontinence/prevention & control* ; Postoperative Complications/etiology* ; Prostatic Neoplasms/surgery* ; Organ Sparing Treatments/methods*

Stroke, a major cerebrovascular disease, has high morbidity and mortality. Effective methods to reduce the risk and improve the prognosis are lacking. Currently, uric acid (UA) is associated with the pathological mechanism, prognosis, and therapy of stroke. UA plays pro/anti-oxidative and pro-inflammatory roles in vivo. The specific role of UA in stroke, which may have both neuroprotective and damaging effects, remains unclear. There is a U-shaped association between serum uric acid (SUA) levels and ischemic stroke (IS). UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke (AIS). Urate-lowering therapy (ULT) plays a protective role in IS with hyperuricemia or gout. SUA levels are associated with the cerebrovascular injury mechanism, risk, and outcomes of hemorrhagic stroke. In this review, we summarize the current research on the role of UA in stroke, providing potential targets for its prediction and treatment.
Humans ; Uric Acid/metabolism* ; Stroke/drug therapy* ; Animals ; Hyperuricemia/drug therapy* ; Ischemic Stroke/blood* ; Biomarkers/blood*

‍ ObjectiveTo investigate the serum level of HBV RNA in untreated or treatment-experienced patients with chronic hepatitis B （CHB） and the correlation between serum HBV RNA level and the duration of antiviral therapy with nucleos（t）ide analogues （NAs）. MethodsA total of 300 patients with CHB who attended Department of Infectious Diseases in The First Affiliated Hospital of Shihezi University School of Medicine from February to July， 2022， were enrolled as subjects. Related clinical data were collected， and according to the duration of antiviral therapy， they were divided into untreated group with 73 patients， treatment duration ≤1 year group with 91 patients， and treatment duration >1 year group with 136 patients. Serum HBV RNA load， HBV DNA load， and HBsAg concentration were measured for all patients. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups， further pairwise comparison using Bonferroni method； the chi-square test was used for comparison of categorical data； a Spearman correlation analysis was used to investigate the degree of correlation between various indicators. ResultsThe positive rate of HBeAg was 18.3%， and among the patients with negative HBV DNA， the patients with positive HBV RNA accounted for 44.1% （86/195）. There was a significant difference in the distribution of the serum levels of HBV RNA， HBV DNA， and HBsAg between the positive HBeAg group and the negative HBeAg group （Z=10.740， 6.300， and 7.280， all P<0.05）. There was a significant difference in the distribution of DNA level between the untreated group and the treatment duration ≤1 year group （P<0.05）； there was a significant difference in the distribution of HBV RNA and HBV DNA levels between the untreated group and the treatment duration >1 year group （P<0.05）； there was a significant difference in the distribution of HBV RNA， HBV DNA， and HBsAg levels between the treatment duration ≤1 year group and the treatment duration >1 year group （P<0.05）. The correlation analysis between the duration of antiviral therapy and the levels of HBV RNA， HBV DNA， and HBsAg showed that the duration of antiviral therapy had an extremely weak negative correlation with the levels of HBV RNA and HBsAg （r=-0.247 and -0.138， both P<0.05） and a strong negative correlation with the level of HBV DNA （r=-0.771， P<0.001）. There was a low degree of correlation between the serum level of HBV RNA and the serum levels of HBV DNA and HBsAg （r=0.360 and 0.442， both P<0.001）. Further stratified analysis showed that in the untreated group， there was a strong positive correlation between HBV RNA and HBV DNA （r=0.752， P<0.001） and a moderate positive correlation between HBV RNA and HBsAg （r=0.559， P<0.001）； in the treatment duration ≤1 year group， there was a low degree of positive correlation between HBV RNA and HBV DNA/HBsAg （r=0.396 and r=0.388， both P<0.001）； in the treatment duration >1 year group， there was a low degree of positive correlation between HBV RNA and HBsAg （r=0.352， P<0.001）. ConclusionSerum HBV RNA is negatively correlated with the duration of treatment with NAs， and the correlation of HBV RNA with HBV DNA and HBsAg gradually decreases with the increase in the duration of treatment. Therefore， it can be used as a supplementary indicator for monitoring the level of virologic response in CHB patients to a certain extent， with a relatively high accuracy in reflecting the level of viral replication in untreated patients.

Objective:To evaluate the safety and efficacy of domestically produced magnetic sphincter augmentation (MSA) for gastroesophageal reflux disease.Method:This study is a prospective cohort study. Patients with typical heartburn and reflux symptoms (at least partial response to proton pump inhibitors), abnormal esophageal acid exposure and normal esophageal peristalsis were included, prospectively in the Department of Gastroesophageal Surgery, Rocket Force Characteristic Medical Center from June 2019 to September 2022. Patients with hiatal hernia >2 cm and severe esophagitis were excluded. The MSA was wrapped around the distal esophagus after esophageal hiatus repair by laparoscopy. A postoperative questionnaire survey was conducted to assess the relief of symptom, complications, the discontinuation rate of proton pump inhibitor, and surgical satisfaction. Gastroscopy, high-resolution esophageal pressure measurement, and pH value impedance monitoring were also reviewed. The pre- and postoperative rates were compared using the McNeinar χ2 test. Result:Currently, 23 patients with gastroesophageal reflux disease were enrolled and underwent MSA surgery. There were 20 males and 3 females, aged ( M (IQR)) 48 (14) years (range: 25 to 64 years). All cases were successfully implanted with MSA. Subjective indicators were followed for 17 (18) months (range: 14 to 53 months), while objective indicators were followed for 17 (1) months (range: 12 to 23 months). The postoperative gastrointestinal and extraesophageal symptom scores showed a significant decrease compared to preoperative levels as follows: the degree of subjective relief of overall digestive symptoms was 90 (20)% (range:0~100%), the degree of subjective relief of overall respiratory symptoms was 100(10)% (range: 10%~100%), the overall satisfaction rate was 83% (19/23), the proton pump inhibitor discontinuation rate was 70% (16/23). The proportion of esophagitis has decreased from 44% (10/23) to 9% (2/23) ( κ=0.169, P=0.039), The Hill grade of gastroesophageal valve morphology improved from 1 case of grade Ⅰ, 5 cases of grade Ⅱ, 10 cases of grade Ⅲ, and 7 cases of grade Ⅲ preoperative to 22, 1, 0, and 0 cases postoperative. The proportion of lower esophageal sphincter pressure below normal has decreased from 70% (16/23) to 35% (8/23) ( κ=0.170, P=0.012). There were 21 patients who restored normal esophageal acid exposure. Eleven patients had mild long-term dysphagia, but it didn′t affect their daily life. No postoperative device migration, erosion, or secondary surgical removal occurred. Conclusions:Laparoscopic implantation of the MSA device was safe and well tolerated. It can effectively control the symptoms of gastroesophageal reflux disease, reduce medication, restore normal cardia morphology and function, and esophageal acid exposure. The main postoperative complication was dysphagia, but it was relatively mild.

Oxidative stress is the result of imbalance between the formation of reactive oxygen species(ROS)and antioxidant level.Mitochondria are important organelles regulating oxidative stress.Telomerase reverse transcriptase(TERT)not only in the nucleus to maintain telomerase activity and telomere length,but also reversibly transits to mitochondria.Improving the activity of oxidative respiratory chain of mitochondria to reduce the production of mito-chondrial reactive oxygen species(mtROS)and to activate GSH system as well as autophagy pathway to promote the clearance of mtROS are all important to down-regulate the level of mtROS,which will alleviate oxidative stress and damage and keep the REDOX balance of cells and the normal function of the body.