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.

Objective: To investigate the regional differences in the incidence of urothelial carcinoma among kidney transplant recipients between northern and southern China，so as to provide reference for early diagnosis of this disease. Methods: A comprehensive search was conducted across multiple databases，including CNKI，Wanfang，CBM，and PubMed，using the keywords “kidney transplantation” and “tumor” to collect clinical data from qualified kidney transplant centers.The latest and most complete literature data published by 17 transplant centers in northern China and 14 in southern China were included.Statistical analyses were performed to compare the incidence of post-transplant urothelial carcinoma and non-urothelial malignancies. Results: A total of 37 475 kidney transplant recipients were included，among whom 837 (2.23%) developed post-transplant malignancies，including urothelial carcinoma (366/837，43.73%)，non-urothelial carcinoma (444/837，53.05%)，and malignancies with unspecified pathology (27/837，3.23%).The incidence of malignancies was significantly higher in northern China than in southern China [(2.82±1.39)% vs. (1.67±0.83)%，P=0.011]，with a particularly pronounced difference in the incidence of urothelial carcinoma [(1.68±1.12)% vs. (0.32±0.32)%，P<0.001].No significant difference was observed in the incidence of non-urothelial carcinoma between the two regions [(1.11±0.56)% vs. (1.35±0.65)%，P=0.279].Additionally，female transplant recipients exhibited a higher incidence of malignancies than males in both regions (southern China：2.38% vs. 1.80%; northern China：8.93% vs. 2.52%). Conclusion: The incidence of urothelial carcinoma following kidney transplantation is significantly higher in northern China than in southern China，underscoring the importance of implementing regular tumor screening for kidney transplant recipients，particularly for female patients in northern China，to facilitate early diagnosis and timely intervention.

Humans ; Nasal Polyps/epidemiology* ; Cross-Sectional Studies ; Rhinosinusitis ; Asthma/epidemiology* ; Sinusitis/epidemiology* ; Chronic Disease

Objective To observe the effect of intra-arterial nimodipine perfusion after interventional embolization in the treatment of symptomatic cerebral vasospasm(SCVS)after aneurysmal subarachnoid hemorrhage(aSAH)and explore its influence on vascular endothelial function.Methods Patients with SCVS after aSAH were divided into treatment group and control group according to cohort methods.Both groups received interventional embolization based on symptomatic supportive treatment,and were given conventional 3H treatments such as blood dilution,dilatation and pressure enhancement after surgery,and the treatment group was additionally given intra-arterial perfusion of nimodipine(20％nimodipine was injected by electronic pump through the femoral artery sheath at a rate of 0.2 mg·min-1 for 2 mg once a day,vascular sheath was removed and nimodipine tablet after 7 days of medication was taken orally for 60-120 mg twice a day after meals),and both groups were treated for 14 days.The cerebrovascular blood flow velocity,laboratory indicators,postoperative complications and prognosis were compared between the two groups.Results There were 41 cases in treatment group,and 38 cases in control group.After 2 weeks of treatment,the average blood flow velocities of anterior cerebral artery(ACA)in treatment group and control group were(84.32±5.27)and(93.46±5.61)cm·s-1,the average blood flow velocities of middle cerebral artery(MCA)were(86.05±5.94)and(95.23±6.37)cm·s-1,the average blood flow velocities of posterior cerebral artery(PCA)were(59.41±4.82)and(71.56±5.39)cm·s-1 respectively(all P＜0.05).The levels of serum endothelin-1(ET-1)in treatment group and control group after 2 weeks of treatment were(76.32±10.58)and(94.16±10.98)pg·mL-1;the levels of vascular endothelial growth factor(VEGF)were(127.45±14.83)and(164.85±15.62)ng·mL-1;the levels of soluble fms-like tyrosine kinase-1(sFlt-1)were(103.67±15.34)and(114.98±16.43)ng·L-1;the levels of plasma soluble intercellular adhesion molecule-1(sCAM-1)were(234.81±62.79)and(285.36±90.24)ng·mL-1;the levels of hypoxia-inducible factor-2α(HIF-2α)were(98.74±7.56)and(102.49±8.35)pg·mL-1;the levels of serum nitric oxide(NO)were(43.16±4.91)and(39.72±5.37)mmol·L-1,all with significant difference(all P＜0.05).The incidence rates of delayed cerebral vasospasm(DCVS)and hydrocephalus were 4.88％and 9.76％in treatment group after surgery,lower than 21.05％and 28.95％in control group(all P＜0.05).The proportion of Glasgow outcome scale(GOS)score of 5 points in treatment group at 3 months after surgery was higher than that in control group(78.05％vs 55.26％,P＜0.05).Conclusion After interventional embolization,intra-arterial perfusion of nimodipine for SCVS after aSAH can help to relieve the inflammatory response,improve the vascular endothelial function and reduce the cerebral blood flow velocity,and it plays a positive role on reducing the cerebral tissue injury and improving the prognosis of patients.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective To observe the clinical efficacy and safety of tofacitinib tablets combined with hydroxychloroquine tablets in the treatment of patients with refractory rheumatoid arthritis.Methods Patients with refractory rheumatoid arthritis were randomly divided into control and treatment groups.The control group was given enteric-coated sulfasalazine tablets 1.0 g per time,three times a day,orally+methotrexate tablets 10 mg per time,once a week,orally+hydroxychloroquine sulfate tablets 0.2 g per time,twice a day,orally.The treatment group received citrate tofacitinib tablets 5 mg per time,twice a day,orally,on the basis of control group.Two groups were treated for 6 months.The clinical efficacy,disease activity,joint pain level,rheumatoid factor(RF),and adverse drug reactions were compared between the two groups.Results Treatment group was enrolled 80 cases,4 cases dropped out,and 76 cases were included in the statistical analysis.Control group was enrolled 80 cases,8 cases dropped out,and 72 cases were included in the statistical analysis.After treatment,the total effective rates of treatment and control groups were 54.05％(40 cases/76 cases)and 16.22％(12 cases/72 cases)with significant difference(P＜0.05).After treatment,the disease activity score in 28 joints scores of treatment and control groups were(2.69±0.73)and(3.32±0.84)points;the visual analog scale scores were(2.72±0.71)and(3.31±0.68)points;the RF levels were(184.61±32.14)and(201.32±30.73)U·mL-1;the differences were statistically significant(all P＜0.05).The adverse drug reactions in the treatment group were gastrointestinal reactions,mild liver damage and elevated blood pressure,while those in the control group were gastrointestinal reactions and mild liver damage.The incidences of total adverse drug reactions in the treatment and control groups were 19.74％and 29.17％without significant difference(P＞0.05).Conclusion Tofacitinib tablets combined with hydroxychloroquine tablets have a definitive clinical efficacy in the treatment of refractory rheumatoid arthritis patients,which can significantly reduce the disease activity and relieve joint pain,without increasing the incidence of adverse drug reactions.

Objective: To evaluate the incidence, treatment, and survival outcomes of Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumor (MGCT-NDG). Methods: A retrospective study was performed on Swyer syndrome patients with MGCT-NDG between January 2011 and December 2022 in Peking Union Medical College Hospital to investigate their characteristics and outcomes. Results: A total of 15 patients (4.9%, 15/307) with Swyer syndrome were identified in 307 MGCT-NDG patients. The average age at diagnosis of MGCT-NDG and Swyer syndrome were (16.8±6.7) and (16.7±6.6) years, respectively. Six cases were preoperatively diagnosed as Swyer syndrome, of which 4 cases received bilateral gonadectomy with or without hysterectomy, while the other 2 cases underwent removal of gonadal tumor and unilateral gonadectomy with hysterectomy, respectively. Of the 9 patients postoperatively diagnosed as Swyer syndrome, unilateral gonadectomy, removal of gonadal tumor, and unilateral gonadectomy with hysterectomy were performed in 6 patients, 2 patients, and 1 patient, respectively. Mixed malignant germ cell tumor (MGCT;10 cases), yolk sac tumor (4 cases), and immature teratoma (1 case) were the pathological subtypes, in the descending order. There were International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ in 6 cases, stage Ⅱ in 3 cases, stage Ⅲ in 5 cases, and stage Ⅳ in 1 case, respectively. Eleven patients received reoperation for residual gonadectomy after a average delay of (7.9±6.2) months, including 8 MGCT-NDG patients and 1 gonadoblastoma patient, no tumor involved was seen in the remaining gonads in the other 2 cases. Ten patients experienced at least one recurrence, with a median event free survival of 9 months (5, 30 months), of which 2 patients received surgery only at the time of initial treatment. All patients with recurrence received surgery and combined with postoperative chemotherapy. After a median follow-up of 25 months (15, 42 months), 10 patients were disease-free, 3 patients died of the tumor, 1 died of side effects of leukemia chemotherapy, and 1 survived with disease. Conclusion: The incidence rate of Swyer syndrome in patients with MGCT-NDG is about 4.9%; timely diagnosis and bilateral gonadectomy should be emphasized to reduce the risk of reoperation and second carcinogenesis in this population.
Female ; Humans ; Retrospective Studies ; Gonadal Dysgenesis, 46,XY/surgery* ; Gonadoblastoma/surgery* ; Neoplasms, Germ Cell and Embryonal/surgery* ; Ovarian Neoplasms/pathology*

Objective To investigate the clinical efficacy of mitral valve repair technique in the treatment of rheumatic mitral valve lesions. Methods The clinical data of patients diagnosed with rheumatic mitral valve lesions and undergoing mitral valve repair under extracorporeal circulation in our department from 2021 to 2022 were retrospectively analyzed. Results A total of 100 patients were collected, including 78 females and 22 males with an average age of 52 years. There were no secondary open heart or death in the whole group. Extracorporeal circulation time was 136.3±33.1 min, aortic cross-clamping time was 107.6±27.5 min, ventilator use time was 12.9±5.9 h, ICU stay was 2.6±1.4 d, and vasoactive medication use was 823.4±584.4 mg. Before and after the surgery, there were statistical differences in the left ventricular end diastolic diameter, left atrial end systolic diameter, effective mitral valve orifice area, shortening rate of left ventricular short axis, mitral E-peak blood flow velocity, mean mitral transvalvular pressure difference, mitral pressure half-time, and cardiac function graded by New York Heart Association (P＜0.05). While there was no statistical difference in left ventricular ejection fraction or left ventricular end-diastolic volume (P>0.05). Conclusion Overall repair of rheumatic mitral valve lesions can significantly improve the cardiac function and hemodynamics of the patients, and is a good choice for patients with rheumatic mitral valve lesions.

Objective To explore the predictive value of cardiopulmonary exercise test (CPET) combined with clinical indexes in the postoperative complications. Methods The clinical data and CPET data (including lung function) of patients undergoing radical esophagectomy in Xuzhou Central Hospital from January 2018 to March 2022 were collected. Univariate analysis and multivariate logistic regression analysis were used to analyze the meaningful evaluation index for the occurrence of postoperative complications. Results A total of 77 patients with esophageal cancer were included, including 59 (76.6%) males and 18 (23.4%) females aged 47-80 years. There were 42 (54.5%) patients in the non-complication group and 35 (45.5%) patients in the complication group. Univariate analysis results showed that the occurrence of postoperative complications was significantly correlated with age, body mass index (BMI), smoking index, tumor stage, the length of postoperative hospital stay, peak work rate (WRpeak), peak kilogram oxygen uptake (VO2peak/kg), the ventilatory equivalent for carbon dioxide slope (VE/VCO2 slope), forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) and maximum expiratory flow rate (MMEF) (P<0.05). The results of multivariate logistic regression analysis showed that BMI [OR=1.35, 95%CI (1.03, 1.77), P=0.031], peakVO2/kg [OR=0.64, 95%CI (0.45, 0.93), P=0.018], oxygen uptake-anaerobic threshold (ATVO2) [OR=0.66, 95%CI (0.44, 0.98), P=0.044] and VE/VCO2 slope [OR=1.49, 95%CI (1.10, 2.02), P=0.011] were the related indexes of complications after radical resection of esophageal cancer. The sensitivity of BMI, VO2peak/kg, ATVO2/kg and VE/VCO2 slope in predicting postoperative complications was 82.10%, and the specificity was 87.44%, 95%CI (0.744, 0.955). Conclusion BMI, VO2peak/kg, ATVO2/kg and VE/VCO2 slope can be used as predictors for postoperative complications of esophageal cancer.

DNA origami is a powerful technique for generating nanostructures with dynamic properties and intelligent controllability. The precise geometric shapes, high programmability, and excellent biocompatibility make DNA origami nanostructures an emerging drug delivery vehicle. The shape, size of the carrier material, as well as the loading and release of drugs are important factors affecting the bioavailability of drugs. This paper focuses on the controllable design of DNA origami nanostructures, efficient drug loading, and intelligent drug release. It summarizes the cutting-edge applications of DNA origami technology in biomedicine, and discusses areas where researchers can contribute to further advancing the clinical application of DNA origami carriers.