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.

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 study the application of CE-Chirp in the evaluation of hearing impairment in forensic medicine by testing the auditory brainstem response(ABR)in adults using CE-Chirp to ana-lyze the relationship between the V-wave response threshold of CE-Chirp ABR test and the pure tone hearing threshold.Methods Subjects(aged 20-77 with a total of 100 ears)who underwent CE-Chirp ABR test in Changzhou De'an Hospital from January 2018 to June 2019 were selected to obtain the V-wave response threshold,and pure tone air conduction hearing threshold tests were conducted at 0.5,1.0,2.0 and 4.0 kHz,respectively,to obtain pure tone listening threshold.The differences and statistical differences between the average pure tone hearing threshold and V-wave response threshold were compared in different hearing levels and different age groups.The correlation,differences and statistical differences between the two tests at each frequency were analyzed for all subjects.The lin-ear regression equation for estimating pure tone hearing threshold for all subjects CE-Chirp ABR V-wave response threshold was established,and the feasibility of the equation was tested.Results There was no statistical significance in the CE-Chirp ABR response threshold and pure tone hearing threshold dif-ference between different hearing level groups and different age groups(P>0.05).There was a good correlation between adult CE-Chirp ABR V-wave response threshold and pure tone hearing threshold with statistical significance(P<0.05),and linear regression analysis showed a significant linear correla-tion between the two(P<0.05).Conclusion The use of CE-Chirp ABR V-wave response threshold can be used to evaluate subjects'pure tone hearing threshold under certain conditions,and can be used as an audiological test method for forensic hearing impairment assessment.

Objective To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS).Methods The pretreatment conditions of solid phase extraction(SPE)were op-timized by orthogonal experimental design and the surface water samples were concentrated and ex-tracted by Oasis? HLB and Oasis? MCX SPE columns in series.The extracts were separated by Kine-tex? EVO C18 column,with gradient elution of 0.1%formic acid aqueous solution and 0.1%formic acid methanol solution.Q-TOF-MS'fullscan'and'targeted MS/MS'modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion,prod-uct ion and retention times.Results The 34 emerging contaminants exhibited good linearity in the con-centration range respectively and the correlation coefficients(r)were higher than 0.97.The limit of de-tection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%.The intra-day precision was 0.78%-18.70%.The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected,with a concentration range of 1.93-157.71 ng/L.Conclusion The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.

Objective To observe the effects of Tianma Gouteng Decoction combined with magnesium sulfate and Labetalol on lowering blood pressure and improving hemorheology in patients with gestational hypertension.Methods Ninety patients with gestational hypertension of liver-yang hyperactivity type were randomly divided into the combination group and the control group,with 45 cases in each group.The control group was treated with magnesium sulfate combined with Labetalol,and the combination group was treated with Tianma Gouteng Decoction on the basis of treatment for the control group.The course of treatment lasted for 5 days.The changes of systolic blood pressure(SBP),diastolic blood pressure(DBP),urinary protein level,and hemorheological indicators of the two groups were observed before and after the treatment.Moreover,the adverse pregnancy outcomes,adverse reactions,and patients'satisfaction of the two groups were compared.Finally,the influencing factors of patients'adverse pregnancy outcomes were investigated by logistic regression analysis.Results(1)After treatment,the SBP,DBP and urinary protein level of patients in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the combination group was significantly superior to that in the control group(P＜0.01).(2)After treatment,the hemorheological indicators of plasma viscosity,whole blood viscosity and hematocrit of patients in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the combination group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)The total incidence of adverse pregnancy outcomes in the combination group was 11.11%(5/45),which was significantly lower and that in the control group(33.33%,15/45),the difference being statistically significant(P＜0.05).(4)The patients'satisfaction of the combination group was 97.78%(44/45),which was significantly higher than that of the control group(84.44%,38/45),and the difference was statistically significant(P＜0.05).(5)The total incidence of adverse reactions in the combination group was 13.33%(6/45)and that in the control group was 8.89%(4/45),but the intergroup comparison showed no significant difference between the two groups(P＞0.05).(6)Logistic regression analysis of influencing factors showed that no medication of Tianma Gouteng Decoction combined with Labetalol and magnesium sulfate,and poor antihypertensive effect were the independent risk factors for adverse pregnancy outcomes in patients with gestational hypertension(all OR＞1,P＜0.05).Conclusion Tianma Gouteng Decoction combined with magnesium sulfate and Labetalol in treating gestational hypertension exerts certain antihypertensive effect,and the therapy can effectively improve the hemorheological indicators and the adverse pregnancy outcomes,and enhance the patients'satisfaction.

As public hospitals continue to expand,buildings continue to age,sporadic renovation projects are increas-ing,and expenditures are increasing.In order to ensure the safe,stable and efficient operation of the hospital,the piecemeal re-pair project has become an important basic guarantee for the hospital.There are many kinds of sporadic repair projects,and the projects are trivial and scattered.The contradictions among the needs,cost control,management ability and service quality of sporadic repair projects are becoming increasingly prominent,which has become the difficulty and pain point of logistics service management.In the practice of hospital sporadic repair project management,the traditional project management mode is broken,the whole process of fine management system is established,the level of management personnel and the whole process of the pro-ject are effectively integrated,and the management ability and service quality of sporadic maintenance projects are comprehensive-ly improved.

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.

Objective To investigate the effects of astragaloside Ⅳ on cardiac hypertrophy in chronic heart failure(CHF)rats,and the regulation of phosphoinositol-3-kinase/protein kinase B/glycogen synthase kinase 3 β(PI3K/Akt/GSK3β)signaling pathway.Methods CHF rat model was established by anterior descending coronary artery ligation,and randomly divided into model group,control group and experimental-L,-M,-H groups,with 8 rats in each group.Another 8 rats were hooked up without ligature as blank group.The experimental-L,-M,-H groups were given 20,40 and 80 mg·mL-1 astragaloside solution according to the dose of 5 mL·kg-1.The control group was given 1.50 mg·kg-1 lisinopril solution at a dose of 5 mL·kg-1.Both blank group and model group were given equal volume of 0.9％NaCl.Six groups of rats were given the drug once a day for 8 weeks by intragastric administration.The cardiac function of rats was measured by echocardiography,the cross-sectional area of cardiomyocytes was observed by wheat embryo lectin staining,and the expression levels of PI3K,Akt and GSK3β were detected by Western blot.Results The left ventricular ejection fraction of experimental-H,control,model and blank groups were(66.27±5.18)％,(67.75±4.98)％,(46.67±3.68)％and(81.65±6.46)％;left ventricular end-diastolic diameter was(0.53±0.05),(0.55±0.05),(0.45±0.02)and(0.57±0.05)mm;the cross-sectional areas of cardiomyocytes were(1.97±0.13),(1.61±0.18),(3.56±0.59)and(1.00±0.04)mm;the relative expression levels of phosphorylated PI3K protein were 0.45±0.04,0.71±0.07,0.11±0.02 and 0.85±0.06;the relative expression levels of phosphorylated Akt protein were 0.43±0.05,0.75±0.06,0.10±0.03 and 0.82±0.06;the relative expression levels of phosphorylated GSK3 β protein were 0.47±0.04,0.85±0.05,0.12±0.04 and 0.89±0.08,respectively.The above indexes of experimental-H group and control group were significantly different from those of model group(all P＜0.05).Conclusion Astragaloside Ⅳ can improve cardiac dysfunction and inhibit myocardial hypertrophy in CHF rats,which may be related to the regulation of PI3 K/Akt/GSK3 β signaling pathway.

Objective To study the pharmacokinetic and pharmacodynamic characteristics of compound levodopa/carbidopa(250 mg/25 mg)and levodopa/benserazide(200 mg/50 mg)in patients with Parkinson's disease(PD).Methods This experiment used a levodopa challenge test with a randomized crossover design.In the first week,20 PD patients orally received either 275 mg of compound levodopa/carbidopa or 250 mg of levodopa/benserazide on an empty stomach,and in the second week,they received the other treatment.The levodopa blood concentration was measured using high-performance liquid chromatography-tandem mass spectrometry,and motor symptoms were evaluated using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Ⅲ.Results Data from 17 patients in the compound levodopa/carbidopa group and 18 patients in the levodopa/benserazide group was included in the analysis.After administration,the Cmax values of compound levodopa/carbidopa and levodopa/benserazide groups were(3 563.76±1 003.06)and(3 642.44±1 192.70)ng·mL-1;the tmax values were(1.10±0.44)and(1.03±0.55)h;the t1/2 values were(1.52±0.15)and(1.68±0.27)h;the AUC0-t values were(7 625.19±1 706.85)and(5 846.07±1 191.16)ng·mL-1·h;the mean residence time(MRT)values were(2.39±0.361)and(2.14±0.37)h,respectively.There were no statistically significant differences in the Cmax,tmax,and t1/2 values between the two groups(all P＞0.05).Compared with the levodopa/benserazide group,the compound levodopa/carbidopa group increased levodopa AUC and prolonged MRT(all P＜0.05).The improvement in motor symptoms and levodopa blood concentration showed consistent trends at various time points in both groups.The compound levodopa/carbidopa group showed significantly better improvement in motor function at 6 and 8 hours after medication compared to the levodopa/benserazide group[(-10.82±8.91)points vs(-5.17±6.78)points,(-7.88±10.05)points vs(-2.11±4.84)points;both P＜0.05].Conclusion The pharmacokinetic and pharmacodynamic characteristics of compound levodopa/carbidopa are similar to those of levodopa/benserazide.