To explore the role of the "Clinical Practice Guidelines" column and others in the Medical Joumnal of Peking Union Medical College Hospital (Med J PUMCH) in promoting diseiplinary development.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Aim To explore the effects of Lycium berry seed oil on Nrf2/ARE pathway and oxidative damage in testis of subacute aging rats. Methods Fifty out of 60 male SD rats, aged 8 weeks, were subcutaneously injected with 125 mg • kg"D-galactosidase in the neck for 8 weeks to establish a subacute senescent rat model. The presence of senescent cells was observed using P-galactosidase ((3-gal), while testicular morphology was examined using HE staining. Serum levels of testosterone (testosterone, T), follicle-stimulating hormone ( follicle stimulating hormone, FSH ) , luteinizing hormone ( luteinizing hormone, LH ) , superoxide dis-mutase ( superoxide dismutase, SOD ) , glutathione ( glutathione, GSH) and malondialdehyde ( malondial-dehyde, MDA) were measured through ELISA, and the expressions of factors related to aging, oxidative damage, and the Nrf2/ARE pathway were assessed via immunohistochemical analysis and Western blotting. Results After successfully identifying the model, the morphology of the testis was improved and the intervention of Lycium seed oil led to a down-regulation in the expression of [3-gal and -yH2AX. The serum levels of SOD, GSH, T, and FSH increased while MDA and LH decreased (P 0. 05) . Additionally, there was an up-regulated expression of Nrf2, GCLC, NQOl, and SOD2 proteins in testicular tissue ( P 0. 05 ) and nuclear expression of Nrf2 in sertoli cells. Conclusion Lycium barbarum seed oil may reduce oxidative damage in testes of subacute senescent rats by activating the Nrf2/ARE signaling pathway.

Objective:To discuss the effect of royal jelly acid(10-HDA)on the proliferation and migration of the human colon cancer SW620 cells based on the network pharmacology,and to clarify its related molecular mechanism.Methods:The active ingredients such as 10-HDA and their corresponding targets were retrieved by using the keyword"royal jelly"from the Traditiomal Chinese Medicine Systems Pharmacology(TMSCP)Database and the Traditiomal Chinese Medicine Integrated Database(TCMID);the small molecule targets were predicted by the Swiss Target Prediction Database.The GeneCards Database and the Online Mendelian Inheritance in Man(OMIM)Database were used to obtain the targets with the keyword"Colon Cancer";the protein-protein interaction(PPI)network was constructed by using the String Database and Cytoscape 3.8.0 Software to screen the core targets;the Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were analyzed by Metascape Database;the specific ingredient 10-HDA was screened for the in vitro activity experiments.The human colon cancer SW620 cells with good growth status were divided into control group and different doses(1,5,10,15,and 20 mmol·L-1)of 10-HDA groups.The viabilities of the cells in various groups were detected by MTT method and the survival rates of the cells were calculated.The SW620 cells were divided into control group,low dose(5 mmol·L-1)of 10-HDA group,middle dose(10 mmol·L-1)of 10-HDA group,and high dose(15 mmol·L-1)of 10-HDA group;Hoechst33342 staining method was used to observe the morphology of the cells in various groups;cell scratch test was used to detect the scratch healing rates of the cells in various groups;flow cytometry was used to detect the percentages of the cells at different cell cycles in various groups;biochemical method was used to detect the activities of total antioxidant capacity(T-AOC)and superoxide dismutase(SOD)in the cells in various groups;Western blotting method was used to detect the expression levels of B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),cysteine-containing aspartate proteolytic enzyme-3(Caspase-3),cysteine-containing aspartate proteolytic enzyme-9(Caspase-9),glycogen synthase kinase 3β(GSK3β),β-catenin,and cyclin D1 proteins in the cells in various groups.Results:Six active ingredients of royal jelly were screened out by the TCMSP Database,and 28 core targets of 10-HDA in the treatment of colon cancer were obtained.The GO function enrichment analysis mainly included the signaling pathways such as cell proliferation and apoptosis.The KEGG signaling pathway enrichment analysis included the cell cycle,prostate cancer,cell senescence,and p53 signaling pathways;the GSK3β/β-catenin signaling pathway was closely related to the cell cycle.Compared with control group,the viabilities of the cells in 5,10,15,and 20 mmol·L-110-HDA groups were decreased in a dose-dependent manner(P<0.05 or P<0.01),the numbers of apoptotic cells in different doses of 10-HDA groups were significantly increased,and the scratch healing rates of the cells were significantly decreased(P<0.05 or P<0.01);the percentages of the cells at S phase in middle and high doses of 10-HDA groups were significantly increased(P<0.05 or P<0.01),the activities of T-AOC and SOD in the cells in different doses of 10-HDA groups were significantly decreased(P<0.05 or P<0.01).Compared with control group,the expression level of Bcl-2 protein in the cells in low dose of 10-HDA group was significantly decreased(P<0.01),and the expression level of GSK3β protein was significantly increased(P<0.05);compared with control group,the expression levels of Bax,Caspase-3,Caspase-9,and GSK3β proteins in the cells in middle and high doses of 10-HDA groups were significantly increased(P<0.05 or P<0.01),and the expression levels of Bcl-2,β-catenin,and CyclinD1 proteins were significantly decreased(P<0.01).Conclusion:10-HDA can significantly inhibit the proliferation and migration of the colon cancer cells and promote the apoptosis and oxidation levels of the colon cancer cells,and its mechanism may be related to the activation of the GSK3β/β-catenin signaling pathway.

Purpose/Significance By integrating clinical and biological sample information,a big data research platform for biologi-cal sample information resources is built to provide one-stop data retrieval,integration and analysis services for researchers,and a data governance system is established,so as to improve the level of hospital clinical research infrastructure construction.Method/Process Common data model and data governance technology are adopted to integrate data sources from different vendors through extraction,trans-formation,loading and other steps to provide a unified data access portal.Result/Conclusion The big data research platform for biologi-cal sample information resources has the advantages of multi-dimensional data screening and rapid integrated analysis,which can pro-vide support for clinical research.

Objective To optimize the ethanol extraction technology parameters of Jinlei Compound through orthogonal experiment combined with beetle antennae search(BAS)-back propagation(BP)neural network.Methods On the basis of the optimal extraction concentration obtained by single factor investigation,the ratio of solid to liquid,extraction time and extraction times were set as the orthogonal test factors.The entropy weight method was used to calculate the comprehensive scores of the yield of luteolin,kaempferol,swertianin and dry paste.Then,the BAS-BP neural network model was established,and the optimum extraction process was predicted by the BAS.Results BAS-BP neural network optimized Jinlei Compound alcohol extraction process was as follows:solid-liquid ratio 1:10,extraction time of 0.5 h,extraction times of 3,the comprehensive score was 96.352 6.The optimal process parameters obtained by orthogonal design were:solid-liquid ratio 1:10,extraction for 0.5 h,extraction for 3 times,the comprehensive score 90.988 0.The comprehensive score of BAS-BP neural network model was slightly better than that of orthogonal experiment,but the difference between the two was small.The optimal extraction process of Jinlei Compound was determined by comprehensive production practice as the ratio of solid to liquid 1:10,extraction for 0.5 h,extraction for 3 times.Conclusion The optimized process based on BAS-BP neural network has higher extraction efficiency and good stability,which can provide reference for subsequent development and quality control.

The conversion of carbon dioxide into high value-added energy has become a research hotspot.In this study,by using Ti3AlC2 and CuCl2·2H2O as precursors,accordion-like two-dimensional Cu0/Cu2+-Ti3C2Tx catalysts modified with Cu0 nanoparticles and Cu2+ self-intercalation were successfully prepared for electrocatalytic reduction of CO2.The performance of the material was tested,and the results showed that in a CO2-saturated 0.5 mol/L KHCO3 electrolyte solution,compared with the original Ti3AlC2,the initial potential of the electrocatalytic conversion of CO2 to C2H4 over Cu0/Cu2+-Ti3C2Tx catalyst decreased from ?0.65 V(vs RHE)to?0.01 V(vs RHE).The maximum current density increased from 0.19 mA/cm2 to 2.5 mA/cm2,the double layer capacitance(Cdl)value increased from 2.61 mF/cm2 to 55.06 mF/cm2.The material showed higher catalytic activity and faster electron transfer rate(Charge transfer resistance(Rct)value was only 16.9 Ω).Moreover,the material showed high electrochemical active area and excellent stability.This research provided a promising method for designing and preparing elcetrocatalytic reduction(ECR)catalysts in the future.

Objective To comprehensively analyze the reported preparation methods for animal models of perimenopausal syndrome (PS), to compare the advantages and disadvantages of various preparation elements and detection indexes, so as to provide useful references for the optimization of the relevant animal models as well as the standardization of their application in the efficacy evaluation of new drugs.MethodsIn this paper, literature research methods were applied using "perimenopausal syndrome" as the subject term. The publication period of the literature was limited to January 2016 to February 2023. Relevant literature on the preparation of PS animal models was retrieved from databases such as China National Knowledge Infrastructure, Wanfang database, and PubMed. After screening the experimental literature that met the inclusion and exclusion criteria, detailed information on experimental animal strains, modeling methods, duration of drug administration, positive drugs, detection indexes and other relevant information were collected. After the above information was standardized, the PS animal model database was established using Excel 2010 software. The model preparation elements and evaluation indexes were summarized systematically, and the statistical results were processed and analyzed using Excel 2010 software.Results A total of 247 articles were screened. SD rats (164 times, 65.86%) and Wistar rats (35 times, 14.06%) were often used to prepare PS animal models. Bilateral ovariectomy (139 times, 53.87%) and natural aging (43 times, 16.80%) were chosen as modeling methods. The ages of rats used for modeling ranged from 7 weeks to 18 months, with 3-month-old rats (22 times, 21.78%) being the most common. The detection indexes were comprehensively evaluated from multiple perspectives, including serum biochemistry, vaginal exfoliated cell smear, histomorphology, general observation, behavioral observation, and organ tissue protein immunoblotting. Western medical evaluation indexes were commonly used to test the successful preparation of models, with vaginal exfoliated cell smears being the most frequently used method (125 times, 85.04%). A model was considered successfully prepared when estrous cycle disorder or irregularity was observed. Some literature also determined modeling success by detecting a significant decrease in serum estradiol levels (5 times, 3.04%). Traditional Chinese medicine (TCM) syndrome evaluation often used a combination of Chinese and Western medical evaluation indexes for comprehensive evaluation, with researchers determining the TCM syndrome through vaginal exfoliated cell smears supplemented by general observation (3 times, 2.04%).Conclusion There are many methods for preparing PS animal models, but there are still significant differences in the selection of animal species, age, criteria for successful modeling, and TCM syndrome evaluation in the related literature.

G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

Brasilicardin A, a diterpene glycoside isolated from pathogenic actinomycete Nocardia brasiliensis IFM 0406, has become a novel immunosuppressant candidate due to its significant immunosuppressive activity, low toxicity and unique mechanism of action. However, brasilicardin A and its analogues have become a research hotspot to the development of this promising immunosuppressant because of the low-yield production in the natural pathogenic producer and the synthetically challenging skeleton. According to the reported biosynthetic pathway of brasilicardin A, the function of involved diterpene synthase was analyzed by bioinformatics. Then the genes bra1-5 that synthesize the brasilicardin A skeleton were directionally amplified from the pathogenic strain N. brasiliensis IFM 0406, and heterologous expression was achieved successfully in Streptomyces albus R1. The compounds were isolated and purified by using various column chromatographies including silica gel column chromatography and semi-preparative HPLC. Six new brasilicardins were established and named brasilicardin H-M. The activity of brasilicardins was screened using lipopolysaccharide (LPS)-activated mouse primary macrophage inflammation model. Brasilicardin H-M exhibited good inhibitory activity on nitric oxide (NO) release with IC₅₀ values of 28.24 ± 3.70, 37.44 ± 2.00, 39.85 ± 4.02, 26.77 ± 4.40, 65.25 ± 1.48 and 15.24 ± 2.72 μmol·L^-1, respectively (indomethacin as the positive control with IC₅₀ value of 34.28 ± 4.10 μmol·L^-1). The results indicated that six compounds had potential anti-inflammatory activity. This study laid a foundation for the elucidation of the brasilicardin A biosynthetic pathway and evaluation of the structure-activity relationship as well as new drug developments.