OBJECTIVE To analyze the chemical constituents of the active parts of Piper wallichii. METHODS The petroleum ether-extract fraction was prepared from the methanol extract of P. wallichii. Separation and purification were performed using semi-preparative high-performance liquid chromatography. The structures of the compounds were identified by nuclear magnetic resonance spectroscopy. RESULTS Nineteen compounds were isolated from the petroleum ether-extract fraction from the methanol extract of P. wallichii， identified as 3-acetoxybenzyl benzoate （1）， 2-acetoxybenzyl benzoate （2）， 2-methoxybenzyl benzoate （3）， 3-methoxybenzyl benzoate （4）， 4-hydroxy-3-methoxybenzyl benzoate （5）， 3-hydroxybenzyl benzoate（6）， benzyl benzoate （7）， ganschisandrine （8）， lancifolin A （9）， （7R，8R，3′R）-7-acetoxy-3′，4′-dimethoxy-3，4-methylenedioxy-6′-oxo- Δ1′，4′，8′-8.3′-lignan （10）， （7S，8R，3′S）-Δ8′-3′，6′-dihydro-3′-methoxy-3，4-methylenedioxy-6′-oxo-8.3′，7.O.4′-lignan （11）， （7R， 8R，3′S）-Δ8′-3′，6′-dihydro-3′-methoxy-3，4-methylenedioxy-6′-oxo-8.3′，7.O.4′-lignan （12）， isodihydrofutoquinol A （13）， licarin A （14）， licarin B （15）， 2-（2′，5′-dimethoxyphenyl）-3，4- dimethyl-5-（3″，4″-dimethoxyphenyl）- tetrahydrofuran （16）， galgravin （17）， velutin （18）， and piyunin A （19）. CONCLUSIONS Compound 1 is a new benzyl benzoate compound. Compounds 3-5， 8 and 9 are isolated from the Piper genus for the first time， while compounds 2， 6， 10-13 and 15-19 are isolated from P. wallichii for the first time.

Background::In vitro fertilization (IVF) has emerged as a transformative solution for infertility. However, achieving favorable live-birth outcomes remains challenging. Current clinical IVF practices in IVF involve the collection of heterogeneous embryo data through diverse methods, including static images and temporal videos. However, traditional embryo selection methods, primarily reliant on visual inspection of morphology, exhibit variability and are contingent on the experience of practitioners. Therefore, an automated system that can evaluate heterogeneous embryo data to predict the final outcomes of live births is highly desirable. Methods::We employed artificial intelligence (AI) for embryo morphological grading, blastocyst embryo selection, aneuploidy prediction, and final live-birth outcome prediction. We developed and validated the AI models using multitask learning for embryo morphological assessment, including pronucleus type on day 1 and the number of blastomeres, asymmetry, and fragmentation of blastomeres on day 3, using 19,201 embryo photographs from 8271 patients. A neural network was trained on embryo and clinical metadata to identify good-quality embryos for implantation on day 3 or day 5, and predict live-birth outcomes. Additionally, a 3D convolutional neural network was trained on 418 time-lapse videos of preimplantation genetic testing (PGT)-based ploidy outcomes for the prediction of aneuploidy and consequent live-birth outcomes.Results::These two approaches enabled us to automatically assess the implantation potential. By combining embryo and maternal metrics in an ensemble AI model, we evaluated live-birth outcomes in a prospective cohort that achieved higher accuracy than experienced embryologists (46.1% vs. 30.7% on day 3, 55.0% vs. 40.7% on day 5). Our results demonstrate the potential for AI-based selection of embryos based on characteristics beyond the observational abilities of human clinicians (area under the curve: 0.769, 95% confidence interval: 0.709–0.820). These findings could potentially provide a noninvasive, high-throughput, and low-cost screening tool to facilitate embryo selection and achieve better outcomes. Conclusions::Our study underscores the AI model’s ability to provide interpretable evidence for clinicians in assisted reproduction, highlighting its potential as a noninvasive, efficient, and cost-effective tool for improved embryo selection and enhanced IVF outcomes. The convergence of cutting-edge technology and reproductive medicine has opened new avenues for addressing infertility challenges and optimizing IVF success rates.

Aim To analyze serum exosome sequencing data from patients with coronary heart disease(CHD)and normal subjects by using bioinformatics-related methods to construct a competitive endogenous ln-cRNA-miRNA-mRNA(ceRNA)regulatory network,to mine the predicted potential Chinese medicines,and to perform preliminary validation of the biological processes and core Chinese medicines involved in the ceRNA network.Methods We used exoRbase data-base to obtain the expression matrix of differential genes,combined with the raw letter method to con-struct the ceRNA network,and performed GO analysis and KEGG analysis on the differential mRNAs in the network,and used COREMINE database to predict the biological processes and core target genes involved in the ceRNA network,and to screen the herbal medi-cines with potential therapeutic effects;AVECs oxida-tive damage cell model was constructed in vitro,and the cytoskeleton,tube-forming function,cell prolifera-tion,LDH leakage rate,ROS level and p-AKT,AKT,p-PI3K and AKT protein expression were examined to verify the action pathways and targets of the core Chi-nese medicine Salvia miltiorrhiza for the treatment of coronary heart disease.Results Compared with nor-mal subjects,395 mRNAs,80 miRNAs,60 lncRNA differential genes,and 80 miRNAs were predicted in serum exosomes of coronary heart disease,and the constructed ceRNA sub-network,mainly consisted of 21 lncRNAs,80 miRNAs,and 82 mRNAs;AKT1,VEGFA,IL1B and other genes in the network.The abnormally expressed mRNAs were involved in biologi-cal processes such as oxidative stress and signaling pathways such as PI3 K/Akt,and Dan Shen,Chuanx-iong and Panax notoginseng were most closely related to exosome-mediated biological processes and core genes in coronary heart disease.The active ingredients of tanshinone ⅡA,the core Chinese medicine,could pro-mote vascular endothelial cell proliferation,tube for-mation,skeleton formation and repair,reduce LDH leakage rate and ROS level,and promote the expres-sion of p-AKT and p-PI3K protein.Conclusion There is a complex ceRNA regulatory network trans-duction in coronary artery disease serum exosomes,and traditional Chinese medicine can be used to treat CHD through multi-target intervention,and Dan Shen,Chuanxiong and Panax notoginseng are expected to be candidate sources of traditional Chinese medicine,a-mong which the active ingredient of Dan Shen,tanshi-none ⅡA,activates PI3 K/Akt signaling pathway to play a protective role against oxidative stress-injured cells,and treats CHD.

Aim To disclose the subcellular localiza-tion,expression pattern,cellular physiological function and possible molecular mechanism of C12ORF56,a novel gene located at q14.2 of chromosome 12,in the pathogenesis of lung cancer.Methods ONCOMINE database was applied to investigate the mRNA level dif-fering of C12ORF56 between normal and lung cancer tissues.Analysis based on LinkedOmics,Metascape,String and GSEA database or tools provided indication of potential cellular physiological functions of C12ORF56 in the developing of lung cancer.C12ORF56 was knocked down via siRNA and the pro-liferation of NCI-H1073 cells were observed by EdU and CCK-8 assay.RT-qPCR was used to detect the ex-pression level of C12ORF56 of lung cancer cells on dif-ferent cycle phases.The core sequence regions of pro-moter affecting the transcription of C12ORF56 gene were analyzed by Jaspar online-tools and verified by dual-luciferase assay.Results C12ORF56 was highly expressed in lung cancer cells,especially in squamous cell lung cancer.C12ORF56 correlated with cell cy-cle,cancer immune,DNA replication.Knockdown of C12ORF56 reduced NCI-H1703 cell proliferation.Conclusion The up-regulation of C12ORF56 is in-volved in the development of lung cancer by enhancing lung cancer cell proliferation.

Aim To investigate the mechanism of Banxia Baizhu Tianma Decoction(BBTD)in interfer-ing methamphetamine(MA)addiction using network pharmacology.Methods The mechanism of BBTD intervention in MA addiction was analyzed using net-work pharmacology,and MA-dependent SH-SY5Y cell model was further constructed to observe the effects of BBTD on cell model and PI3K-Akt pathway.Results A total of 88 active ingredients and 583 potential tar-gets of BBTD were screened.KEGG analysis showed that BBTD might intervene in MA addiction through PI3K-Akt,cAMP and other pathways.The molecular docking results showed that key active ingredients ex-hibited strong binding ability with core targets of PI3K-Akt pathway.In vitro experiments showed that MA-de-pendent model cells had shorter synapses,tended to be elliptical in morphology,had blurred cell boundaries,showed typical cell damage morphology,and had high intracellular expression of cAMP(P＜0.01)and low expression of 5-HT(P＜0.05).BBTD intervention could counteract the above morphology,cAMP,and 5-HT changes,suggesting that it had therapeutic effects on MA-dependent model cells.Western blot showed that MA modeling elevated the p-PI3K/PI3K(P＜0.05)and p-Akt/Akt(P＜0.01);BBTD inter-vention decreased their relative expression.Conclu-sions Gastrodin and other active ingredients in BBTD have therapeutic effects on MA addiction,and the mechanism may be related to regulation of PI3K-Akt pathway relevant targets.

Flavonoids are a class of compounds with a variety of biological activities widely found in nature,mainly including an-tioxidant,anti-inflammatory,antibacterial,anti-tumor,anti-al-lergic,hypoglycemic,cardiovascular protection and other phar-macological effects.In recent years,the anti-neuroinflammatory effects of flavonoids have received widespread attention,and studies have found that they can improve neuroinflammation and exert neuroprotective effects through multiple pathways and chan-nels.Neuroinflammation,as one of the important etiological and predisposing factors of neurodegenerative diseases,suppression of neuroinflammation is considered an important tool for the pre-vention and treatment of neurodegenerative diseases.This paper reviews the relationship between neuroinflammation and neurode-generative diseases,and summarizes the possible mechanisms of action of flavonoids intervening in neuroinflammation to treat neurodegenerative diseases,with a view to providing references for further basic research on flavonoid components and new re-search ideas and methods for the development of drugs for the treatment of neurodegenerative diseases.

Objective:To explore the mechanism of hepatitis B virus(HBV)inhibiting M1 macrophages to promote immune escape,and to provide targets and strategies for antiviral therapy.Methods:The human monocyte cell line THP-1 was induced into M1 macrophages with PMA+LPS+IFN-γ.Cell morphological changes and the expressions of CD68,CD86,HLA-DR and functional molecules IL-1β,IL-6,TNF-α in M1 macrophages were detected by flow cytometry and RT-qPCR to identify M1 macrophages.HBV stable replication cell line HepG2.2.15 were co-cultured with M1 macrophages,and the expression of HBV-DNA was detected by qP-CR.The expression of CD68,CD86 and HLA-DR were detected by flow cytometry.The expressions of functional molecules TLR4,NLRP3,Caspase-1,pro-caspase-1,caspase-1 p20,IL-1β and IL-18 in M1 macrophages were determined by RT-qPCR and Western blot.Apoptosis rate was detected by flow cytometry,and the expression of apoptosis related protein cleaved-caspase-3 was determined by Western blot.Results:THP-1 was successfully induced to differentiate into M1 macrophages.M1 macrophages inhibited HBV repli-cation(P<0.05).HBV inhibited the expressions of CD68,CD86 and HLA-DR in M1 macrophages(P<0.01).HBV inhibited the ex-pressions of TLR4,NLRP3,Caspase-1,caspase-1 p20,IL-1β and IL-18 in M1 macrophages(P<0.01).HBV induced M1 macro-phage apoptosis(P<0.05).Conclusion:HBV inhibits M1 macrophages and their functional molecules TLR4,NLRP3 and down-stream factors,reduces the synthesis and secretion of inflammatory factors,induces apoptosis,and then promotes immune escape,re-sulting in the persistence and replication of HBV in the body.

Objective:To explore the journey map of patients with chronic constipation during fecal microbiota transplantation.Methods:This study adopted phenomenological methods. From October to December 2023, purposive sampling was used to select chronic constipation follow-up patients who underwent fecal microbiota transplantation at the Intestinal Microecology Center of Shanghai Tenth People's Hospital as respondents for semi-structured interviews. Colaizzi 7-step analysis method and NVivo 11.0 software were used for data analysis.Results:A total of 15 interviewees were interviewed. During fecal microbiota transplantation, the journey map of constipation patients included stages, mood changes, touchpoints, themes, emotional experiences and opportunities. The patient's experience and needs were summarized into three themes and ten sub-themes, including pre-transplant adaptation disorders to new environments (unfamiliarity and confusion-admission coordination disorders, anxiety and expectations-diverse complex emotions, puzzle and helplessness-asymmetric doctor and patient information), effectiveness-related psychological and social experiences in transplantation (attention and expectations-longing for positive efficacy, perception of benefits and risk avoidance, shame and inferiority-treatment stigmatization experience, questioning and despair-unrealized expectations, treatment resistance-sensitive economic burden), post-transplant transition dilemmas (inaccessible medical services-lack of continuous treatment and nursing, disease recurrence troubles) .Conclusions:This study visualizes the experiences and needs of constipation patients during microbiota transplantation through a patient journey map and identifies multidimensional issues and needs of patients. Clinical medical and nursing staff should pay attention to the needs of patients at different stages of the treatment process when formulating intervention programs to improve the quality of fecal microbiota transplantation nursing.

Cases of human infection with H7 subtype avian influenza virus(AIV)combined with five NA subtypes(N2,N3,N4,N7,and N9)have been reported.This study was aimed at establishing a method for simultaneous detection and dif-ferential diagnosis of H7 and five NA subtypes of AIV.Seven pairs of specific primers were designed according to the conserved sequences of the HA gene of H7 subtype AIV,the NA gene of five NA AIV subtypes,and the M gene of all AIV subtypes.A high-throughput GeXP typing method was established for simultaneous detection of the H7 subtype and the five NA subtypes of AIV by using GeXP multiple gene expression and capillary electrophoresis analysis technology.The specificity and sensitivity of the method were determined,and clinical samples were tested.The specificity results indicated that this method was able to simultaneously detect seven target genes in a single tube;each pair of specific primers was able to detect the corresponding AIV subtype,and the universal detection primers were able to detect all subtypes of AIV,with no cross-reaction with other common avian disease pathogens.Sensitivity results demonstrated that this method was able to simultaneously detect seven target genes with a threshold detection limit was 100 copies/μL.The detection results for 150 clinical samples were consistent with those of viral isolation and identification.The high-throughput GeXP method for simultaneous differential diagnosis of the H7 subtype and five subtypes of AIV established in this study has advantages of high specificity,high sensitivity,rapidity,and simplicity,thus providing a new detection method for the effective prevention and control of AIV.

Objective To explore the metabolic markers of social anxiety disorder in schizophrenia patients with social anxiety disorder through metabolomic sequencing analysis.Methods From December 2022 to December 2023,a case-control study was carried out in the Neuropsychiatric Prevention and Control Hospital of Fuzhou Second General Hospital.One hundred sixty patients with schizophrenia were included in the study.The Diagnostic and Statistical Manual of Mental Disorders,fourth edition(DSM-Ⅳ)and Liebowitz social anxiety scale(LSAS)scores were used to classify subjects as patients with social anxiety disorder(n=64)and controls without social anxiety disorder(n=96).Peripheral blood samples were collected for non-targeted metabolomic sequencing,and the metabolites with statistical differences were analyzed by receiver operating characteristic(ROC)curve to find metabolic markers that may affect social anxiety disorder in schizophrenia patients.Results There were significant differences in 12 metabolites between the two groups(P<0.05).In ROC curve analysis,the top 3 metabolites with area under curve(AUC)values were 3-O-trans-coumaryl-alphetolic acid(AUC=0.637),3-mercaptopropionic acid(AUC=0.602)and nona-2-acylcarnitine(AUC=0.600).Conclusion In this study,the potential diagnostic metabolic markers of 3-O-trans-coumaryl-alphitoic acid,3-mercaptopropionic acid,nonyl-2-acylcarnitine as diagnostic metabolic markers can effectively distinguish patients with schizophrenia social anxiety disorder from patients with schizophrenia without social anxiety disorder.