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 establish management index system for rational drug use of key monitoring drugs， and provide reference for the management of key monitoring drugs in the hospitals. METHODS First， the management index system for rational drug use of key monitoring drugs was drafted by collecting the evidence from related medical literature. Next， using a modified Delphi method， twenty experienced experts from the fields of pharmacy， medical practice， healthcare insurance， and finance were selected to participate in two rounds of questionnaire consultations. Based on the expert enthusiasm coefficient， authority coefficient， degree of opinion concentration， and degree of coordination， the final indicators were determined to establish a management index system for rational drug use of key monitored drugs in medical institutions. RESULTS The expert enthusiasm coefficients reached 100% in both rounds of consultation. In first-level， second-level and third-level indicators， the authority coefficients of experts were 0.89， 0.86 and 0.87， and coordination coefficients of the experts in importance score were 0.300 （P＜ 0.05）， 0.125 （P＜0.05） and 0.139 （P＜0.05）， respectively. The average score for the importance of all indicators reached over 3.5， in which the full score ratio ranged from 35% to 100%. Except that the variation coefficient of a third-level indicator “number of specifications purchased for key monitored drugs” was 0.26， the variation coefficients of rest indicators were less than or equal to 0.25. Based on the results of expert consultation， final version of the management index system established in this study， including two first-level indicators （drug procurement and use， and rational drug use）， five second-level indicators （such as the accessibility， cost-effectiveness） and twenty third-level indicators （such as the number of specifications purchased for key monitored drugs， the increase in the cost of key monitored drugs）. CONCLUSIONS The management index system established in this study possesses high reliability and strong operability， and may provide a reference for the management of key monitoring drugs in the hospitals.

Objective To analyze the characteristics of adverse drug reactions （ADR） reported in Sixth People’s Hospital South Campus, Shanghai Jiaotong University from 2021 to 2023, to provide reference for promoting rational clinical drug use. Methods ADR data reported in our hospital were collected retrospectively, including patients’ basic information, drugs causing adverse reactions, types of adverse reactions and outcomes. Descriptive analysis methods were used to summarize and analyze the data. Results A total of 979 cases of ADR were reported in our hospital from 2021 to 2023. The highest proportion of patients with ADR occurred in the age range of 31 to 50, and more male patients （63.5%）. The top five drugs involved with adverse reactions were antibiotics （48.8%）, Chinese medicine injections（19.2%）, vitamins（7.5%）, Chinese traditional medicine（7.2%）, equine tetanus immunoglobulin（6.3%）. Among antibiotics, cefuroxime, ceftazidime and cefotiam were the majority. The organs/systems involved in all ADR were mainly skin and accessories damage （55.4%）. The clinical manifestations were rash, itching, and maculopapular rash. Conclusion From 2021 to 2023, the most common drugs causing adverse drug reactions in our hospital were mainly antibacterial drugs, and the rational clinical use of antibacterial drugs still needs to be concerned.

OBJECTIVE To study the effects of enteral immune microecological nutrition combined with ω-3 fish oil fat emulsion on postoperative recovery， immune function， liver function and inflammation level in patients with hepatocellular carcinoma resection， as well as the safety of the medication. METHODS A total of 106 patients with hepatocellular carcinoma admitted to our Hospital from June 2020 to December 2023 were selected and divided into control group and study group according to the random number table method， with 53 cases in each group. After undergoing hepatocellular carcinoma resection， control group was given Intacted protein enteral nutrition solution+Enhanced enteral immune microecological nutrition， and the study group was given ω-3 fish oil fat emulsion injection based on the control group. The clinical indicators （postoperative exhaust time， defecation time， postoperative ambulation， and hospital stay）， liver function indicators [alanine transaminase （ALT）， lactate dehydrogenase （LDH）， aspartate transaminase （AST）]， immune function indexes （CD3+ ， CD4+ ， CD8+ ， CD4+/CD8+）， inflammatory factor indexes [tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， IL-6， IL-8]， and indicators of intestinal mucosal barrier [D-lactic acid， intestinal fatty acid binding protein （I-FABP）] were compared between 2 groups， and the occurrence of ADR was recorded. RESULTS Compared with the control group， the postoperative exhaust time， postoperative defecation time， and hospital stay of the study group were shortened significantly， and postoperative ambulation increased significantly （P＜0.05）. After treatment， ALT， LDH， AST， CD8+， inflammatory factors， D-lactic acid and I-FABP of 2 groups were significantly lower than before treatment， and the study group was significantly lower than the control group （P＜0.05）； CD4+， CD3+， and CD4+/CD8+ of two groups were significantly higher than before treatment， and the study group was significantly higher than the control group （P＜0.05）. There was no significant difference in the incidence of ADR between 2 groups （P＞0.05）. CONCLUSIONS Enteral immune microecological nutrition combined with ω-3 fish oil fat emulsion injection can shorten the recovery time of patients after hepatocellular carcinoma resection， improve immune function， reduce inflammatory response， and improve liver function with good safety.

As a serious cardiovascular disease, atherosclerosis (AS) causes chronic inflammation and oxidative stress in the body and poses a threat to human health. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a member of the phospholipase A2 (PLA2) family, and its elevated levels have been shown to contribute to AS. Lp-PLA2 is closely related to a variety of lipoproteins, and its role in promoting inflammatory responses and oxidative stress in AS is mainly achieved by hydrolyzing oxidized phosphatidylcholine (oxPC) to produce lysophosphatidylcholine (lysoPC). Moreover, macrophage apoptosis within plaque is promoted by localized Lp-PLA2 which also promotes plaque instability. This paper reviews those researches of Chinese medicine in treating AS via reducing Lp-PLA2 levels to guide future experimental studies and clinical applications related to AS.
Humans ; 1-Alkyl-2-acetylglycerophosphocholine Esterase ; Medicine, Chinese Traditional ; Atherosclerosis/drug therapy* ; Lipoproteins ; Plaque, Atherosclerotic ; Biomarkers

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*

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Objective To analyze the acupoint selection rules of acupuncture for the treatment of tic disorders in children based on data mining techniques.Methods A computerized search was conducted for the clinical research literature on acupuncture treatment of tic disorders in children included in the CNKI,Wanfang,VIP,SinoMed,and PubMed databases from January 1992 to December 2022.A database was established by Excel 2019 to count the commonly used treatment methods and analyze the high-frequency application methods acupuncture(high-frequency acupoints,channel entry of acupoints,acupoint association rules,and acupoint clustering),auricular point seed-pressing(high-frequency auricular points,and acupoint association rules),and the high frequency division of cluster needling of scalp point.Results A total of 190 valid literature articles were included,involving 270 acupuncture prescriptions;among them,184 acupoints were counted in the acupuncture method,with a total application frequency of 1 906 times,and the high-frequency application of the acupoints in descending order were Baihui(DU20),Taichong(LR3),Fengchi(GB20),Hegu(LI4),Sanyinjiao(SP6),Neiguan(PC6),Shenmen(HT7),Zusanli(ST36),Yintang(EX-HN3),Sishencong(EX-HN1);and the high-frequency meridians were governor vessol,foot taiyang stomach meridian,foot taiyang stomach meridian,foot shaoyang gallbladder meridian,hand taiyang large intestine meridian,foot taiyang bladder meridian,foot jueyin gallbladder meridian;three sets of strong association rules and five clusters of acupoints were analyzed by SPSS modeler 18.0 and IBM SPSS Statistics 26.0 software.There were 29 acupoints of auricular point seed-pressing,application total frequency was 206 times,high-frequency application of auricular points in descending order of Shenmen(HT7),liver,heart,subcortex,kidney;four groups of acupoint strong association rules were obtained through the analysis of SPSS modeler 18.0 software.A total of 14 zones were involved in the application of cephalic acupoint plexus zoning,of which the high-frequency zones were parietal anterior temporal diagonal,parietal parietal 1,and chorea tremor control zone.Conclusion Acupuncture treatment of tic disorders in children,according to its pathogenesis(liver hyperactivity,kidney depletion,spleen deficiency,phlegm disturbance,etc.)and tic site,select acupoints compatibility,and mostly choose yang meridian acupoints,which is related to the nature and treatment characteristics of wind pathogen.Children's tic disorders are closely related to emotional disorders,therefore acupuncture and auricular acupoints all emphasize the method of soothing the liver and clearing the heart,and regulating the emotional state.Cluster needling of scalp point mostly used parietal temporal anterior oblique line,parietal 1 line,and dance tremor control area for the treatment of tic disorders.For children,auricular point seed-pressing and cluster needling of scalp point has the minimun of pain,the effect of treatment is long,and it is not easy to have dangerous situations such as bent needle,broken needle and so on.

Corona virus disease 2019(COVID-19)epidemic has been effectively controlled,but its related complications still cannot be ignored,especially the cardiovascular circulatory system is the active site of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Angiotensin-converting enzyme 2(ACE2)is a type Ⅰ transmembrane glycoprotein that is highly expressed in heart,kidney and testis.Spike protein of SARS-CoV-2 invades host cells by binding to the cell surface receptor ACE2.However,there are still many deficiencies in the clinical application of vaccines and drugs developed based on this target.As a molecular chaperone,cyclophilin A(CypA)promotes protein folding and T cell activation.CD147 is one of the most widely studied CypA receptors,and the interaction of CypA/CD147 plays an important role in the entry of SARS-CoV-2 into host cells.However,there are few reports on the invasion of SARS-CoV-2 into the cardiovascular system through the CypA/CD147 signaling pathway.Based on this,this article summarizes the previous research evidence and the research basis of the research group,and reviews the structure and function of CypA/CD147,the role of CypA/CD147 in cardiovascular disease,and the cardiovascular disease caused by SARS-CoV-2 targeting CypA/CD147 signal pathway,in order to provide reference for the diagnosis and treatment of the COVID-19 complicated with cardiovascular system diseases.

Objective To investigate the effects of neuroligin-1,-2(NLGN-1,-2)on oligodendrocyte(OLs)differentiation and myelination in the central nervous system.Methods OLs were cultured in vitro in the presence of different concentrations of NLGN-1 and NLGN-2.Morphological differentiation of OLs was observed by immunofluorescent staining and mRNA expression levels of myelin-associated genes were detected by Real-time PCR.Western blotting was used to detect the expression of myelin-related proteins.Results NLGN-1,-2 accelerated the differentiation of oligodendrocyte precursor cells(OPCs)into mature OLs,and promoted the ability of myelin sheath formation.In vitro culture conditions,the dosage of 500 μg/L had the best promotion effect on OLs differentiation and maturation,and NLGN-2 had better promoting effect than that of NLGN-1.Furthermore,the mRNA expression levels of myelin-associated genes myelin protein P0(MPZ),myelin basic protein(MBP)increased after the neuroligins treatments detected by Real-time PCR.Western blotting result showed that the expressions of MBP and MPZ increased significantly after 500 μg/L treatment with NLGN-1 and NLGN-2 for 12 hours.Conclusion NLGN-1,-2 promote OLs differentiation and myelination.The positive effect of NLGN-2 is greater than that of NLGN-1 significantly,suggesting that the treatment with inhibitory synaptic-associated cytokines may improve the ability of myelin sheath formation in the central nervous system.