Isosteviol is a tetracyclic diterpenoid compound obtained by hydrolysis of natural stevia glycoside under acidic conditions. It has many pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory and antibacterial. Due to its low water solubility, low activity and low bioavailability, isosteviol has poor performance. In order to overcome these shortcomings, scholars have obtained a large number of isosteviol derivatives with novel structures and excellent activity. In this paper, we review the recent progress in the research on the structure modification, biological activity, structure-activity relationship and microbial transformation of isosteviol, in order to provide a reference for the development of new drugs of isosteviol and its derivatives.

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 analysis the job preference and heterogeneity of medical students by distinguishing their birthplaces,and to provide reference for optimizing the management of primary health care resources.Methods:Using a cluster sampling method,an online survey of discrete choice experiment was conducted with 925 medical students from six teaching hospitals in Beijing,741 valid questionnaires were obtained,the effective recovery rate was 80.1%.The mixed logit model was used to perform regression analysis on six job attributes and estimate the willingness to pay.Results:There were significant differences in the choice of work location among medical students from different birthplaces.The subgroup results showed that compared to medical students from city,undergraduates from rural and county district preferred a work with sufficient career development opportunities.The results of undergraduate subgroup showed that undergraduates from rural district preferred a work with good environment than those from other birthplaces.Conclusion:There is heterogeneity in job preferences of medical students from different birthplaces.Policy makers should pay attention to the medical students'birthplace,also take the educational level into account to optimize the diversified job attributes,formulating targeted intervention to attract primary health care talents.

There is still a lack of experience in the perioperative strategy for esophageal cancer patients in China during the epidemic of COVID-19. In December 2022, a 59-year-old male patient with esophageal cancer was admitted to our department. He received 2 cycles of neoadjuvant therapy before surgery, and developed COVID-19 perioperatively. After treatment, the infection symptoms of the patient were improved, and the postoperative recovery was satisfactory.

OBJECTIVE To establish the quality standard of Triadica cochinchinensis and to perform the acute toxicity study. METHODS Appearance properties, powder microscopic identification, and thin-layer chromatography(TLC) identification were researched. The specific chromatogram was established by HPLC. The content of cadmium(Cd), lead(Pb), arsenic(As), copper(Cu), and mercury(Hg) was determined by inductively coupled plasma-mass spectrometry(ICP-MS). Acute toxicity was studied by maximum dose. RESULTS The outer skin of herbs was dark brown, and the inner surface was light yellow brown and fibrous. Besides, crystal sheath fiber was common, and calcium oxalate clusters arranges in rows. In the TLC diagram of the test product, the fluorescent spots of the same color were displayed at the corresponding position of the control product(scopoletin, isofraxidin). Five common peaks were calibrated in the characteristic map and the three characteristic peaks(scopoletin, isofraxidin, dimethylfraxetin) were recognized. The content of the measured heavy metal elements was lower than the national limit standard. The linear correlation coefficient was R2 > 0.999. The precision, stability, repetitive RSD were < 10%. The average recovery rate of the added sample was 80%−120%, and the RSD was < 10%. The maximum dose of the acute toxicity test was 184.09 g·kg−1. The 14 d internal body mass, food intake, organ-body ratios, the serum glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, blood urea nitrogen, and creatinine were not significantly different by comparing with the normal controls. Therefore, no significant toxicity was observed. CONCLUSION The established standard can provide a reference for evaluating the quality of Triadica cochinchinensis. The heavy metal content of ten batches of medicinal materials is within the safe range. Acute toxicity test show that there is no obvious significant adverse teactions after oral administration, and the safe dose range is large, which can provide a reference for the subsequent development and utilization.

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC₅₀) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L^-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

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.

Talents are the main force for the development of traditional Chinese medicine（TCM）， and the construction of TCM talents and the reformation of talent evaluation system are essential to promote the inheritance and innovation of TCM. At present， we are still exploring and developing in the fields of the formulation， implementation and evaluation indicators of TCM talent evaluation system. However， there are shortcomings and difficulties. For instance， insufficient stratification in the evaluation， excessive emphasis on the quantity of achievements， neglecting the quality of the achievements and the actual contribution， imperfect assessment indicators， and the weak characteristics of TCM. Therefore， national ministries and commissions have jointly issued a document requesting to break the four only and set a new standard， in order to promote the construction of a scientific and technological talent evaluation system oriented by innovation value， ability and contribution. For the evaluation of TCM clinical talents， China Association for Science and Technology commissioned China Association of Chinese Medicine to build the China Clinical Cases Library of TCM（CCCL-TCM）， which aims at collecting the most authoritative and representative TCM clinical cases and exploring the advantages of applying clinical cases as masterpiece of achievement in TCM clinical talents evaluation. CCCL-TCM can promote the construction of a talent evaluation system that is more in line with the development characteristics of TCM industry， and to carry out relevant pilot in TCM colleges and institutions across the country in order to promote the reformation of TCM talent evaluation system.

Objective:To evaluate the relationship between gluten-free diet and rheumatoid arthritis (RA).Methods:Data were obtained from large-scale genome-wide association studies (GWAS), and genetic loci that are independent of gluten-free diet and RA of people of Europe2 were selected as instrumental variables. The gluten-free diet GWAS data included 64 949 individuals and 9 851 867 controls. Data were obtained from GWAS of 58 284 RA patients and 13 108 512 controls. The inverse variance weighted (IVW), MR Egger, weighted median method and weighted model were used to conduct two sample Mendelian randomization (MR) analysis. Cochran Q test and mendelian randomness pleiotropy residual sum and outlier (MR-PRESSO) were used to assess SNP heterogeneity. Applying the MR Egger intercept to test the level pleiotropy of SNP. The sensitivity analysis of the "leave one method" that evaluates whether MR studies were influenced by a single SNP. Results:After matching GFD and RA data, three SNPs were included as instrumental variables in the study. IVW showed that GFD could significantly reduce the risk of RA ( β=-60.83, s x=3.82, P<0.001). The weighted median method and weighted pattern also showed that the gluten free diet could reduce the risk of RA ( β=-57.97, s x=4.41, P<0.001; β=-55.81, s x=5.10, P=0.008). Sensitivity analysis of the correlation between GFD and RA showed that there might be heterogeneity between SNPs (Cochran Q test, Q=12.80, P=0.002). The MR-PRESSO results showed that no abnormal SNP was detected ( P=0.174). The forest map showed that SNPs was closely related to GFD and RA stability. The method comparison chart showed that the results of multiple testing methods were basically consistent. The funnel plot showed that SNPs were basically symmetrical, indicating that there was no pleiotropy in MR analysis. The MR Egger intercept test showed no horizontal pleiotropy in MR analysis (intercept value was-0.24, P=0.174). The sensitivity analysis of the "leave one method" is suggested that no single SNP had a significant impact on the overall results. Conclusion:Gluten free diet is related to the risk reduction of RA.

Humans ; Cardiovascular Diseases ; Enhancer of Zeste Homolog 2 Protein/metabolism* ; Histones ; Methyltransferases