Genetically modified pigs for welfare assurance is crucial for conducting xenotransplantation. However, traditional experimental animal ethics principles cannot address the social benefits issues brought about by xenotransplantation, and there is a lack of ethical justification for the assurance of experimental animal welfare. Degrazia and Bechtel proposed six principles for the welfare of experimental animals: the principle of no alternative methods, the principle of expected net benefits, the principle of adequate defense of harm, the principle of no harm without necessity, the principle of basic needs and the principle of harm limit. This paper conducts an ethical-level argumentation on the six principles for the welfare of genetically modified pigs in xenotransplantation, and points out that these six principles are of great significance in closely integrating the social benefits of xenotransplantation with the welfare of genetically modified pigs, emphasizing the moral status of genetically modified pigs, and providing standards for the ethical review of the welfare of genetically modified pigs.

This paper summarizes Professor ZHAO Jiping's acupuncture diagnostic and therapeutic approach for tic disorders (TD). Focusing on the pathological characteristics of tic disorder (TD), this study analyzes TD's multilayered disease localization. Based on disease-based differentiation, it is proposed that the fundamental pathological location lie in the liver and brain, while the manifestation is in the sinew meridians. The core pathogenesis is characterized as "internal stirring of wind due to liver hyperactivity, upward disturbance of the mind in the brain, and external disharmony of the sinews", based on which the fundamental therapeutic principles are established as calming the liver and extinguishing wind, tranquilizing the mind and awakening the brain, and dredging and regulating the sinews. In clinical practice, attention is paid to meridian and acupoint examination, integrating the four diagnostic methods to assess the deficiency or excess of the liver, the state of the mind, and the condition of the sinews. Acupoint selection emphasizes three regulatory strategies: (1) liver regulation: Taichong (LR3), Hegu (LI4) are selected to soothe the liver and regulate qi; (2) brain regulation: Baihui (GV20), Shenting (GV24), Yintang (GV24⁺), Fengchi (GB20) are selected to calm the mind and stabilize the spirit; (3) sinew regulation: Yanglingquan (GB34), Zusanli (ST36), Quchi (LI11) are selected to regulate qi and blood and relax the sinews. Manipulation techniques, as well as various acupuncture and moxibustion methods, are also emphasized. A differential treatment framework of "layered disease localization-corresponding pathogenesis-precise acupoint selection and technique" has been established to provide a clinical guide for the diagnosis and treatment of TD.
Humans ; Acupuncture Therapy/history* ; Tic Disorders/diagnosis* ; Acupuncture Points ; Meridians ; Diagnosis, Differential ; China

Objective To explore the distribution of common TCM syndromes and symptoms of insomnia;To prepare for the construction of the theoretical framework and item pool of syndrome diagnosis and efficacy evaluation scale.Methods TCM guideline standards of insomnia,textbooks and journals over the years were retrieved,the information of TCM syndromes,syndrome elements and symptoms was extracted,the guideline textbook and journal database were established,and descriptive statistics,association rules,systematic clustering,factor analysis,potential categories and implicit structure analysis were carried out.Results Totally 116 guide standards and textbooks over the years were included,and 454 articles of journals were included.The high-frequency symptoms accounted for≥3%of the guide textbooks and journal databases were 87 and 79 categories,respectively,and the cumulative proportion was 87.48%and 87.75%,respectively.According to the analysis results,five common TCM syndromes and their characteristic symptom classification of insomnia were finally deduced.According to the frequency/person time distribution,they were heart and spleen deficiency syndrome,yin deficiency and fire hyperactivity syndrome,liver fire disturbing heart syndrome,phlegm heat disturbing heart syndrome,heart and gallbladder qi deficiency syndrome.Conclusion There are five common TCM syndromes of insomnia,and the characteristic symptoms of each TCM syndrome provide a reference source for the theoretical framework of syndrome diagnosis and efficacy evaluation scale and the establishment of item pool.

The MGF300-4L protein of African swine fever virus(ASFV),a virulence-associated fac-tor,degrades IKKβ through the chaperone-mediated autophagy and enhances the stability of IKBαto suppress the generation of IL-1β and TNF-α regulated by the NF-κB signaling pathway.To iden-tify the host proteins interacting with MGF300-4L,PK-15 cells were transfected with the eukary-otic plasmid expressing MGF300-4L and analyzed using immunoprecipitation-mass spectrometry(IP-MS)to identify the host proteins that interact with MGF300-4L.Additionally,gene ontology(GO)and KEGG pathway enrichment analyses were conducted.Furthermore,molecular docking a-nalysis,co-immunoprecipitation,and laser confocal microscopy assays were performed to validate the host proteins interacting with MGF300-4L.The IP-MS analysis identified 145 host proteins that potentially interact with MGF300-4L.Subsequent GO and KEGG pathway enrichment analy-ses revealed that these proteins are predominantly involved in metabolic,cellular,and innate immune responses.Through molecular docking prediction,co-immunoprecipitation assay,and laser confocal microscopy,we identified the interaction between MGF300-4L and STAT1.This study provides critical insights into the mechanisms underlying the interactions between MGF300-4L and the host proteins.

Objective To elucidate the role of gut microbiota in cognitive impairment induced by adolescent social isolation(ASI)and identify key pathogenic microbial communities.Methods Sixteen male C57BL/6 mice(postnatal days 21～23)were randomly assigned to a control group(group-housed,4/cage,n=8)or an ASI group(single-housed,1/cage,n=8).After 5 weeks of ASI(5-ASI),fecal samples underwent 16S rRNA sequencing for microbiota analysis.Cognitive behavior was assessed using open field,Y-maze,novel object recognition tests.Correlation analysis integrated microbial abundance with behavioral parameters to screen cognition-associated taxa.Results(1)Behavior:5-ASI mice showed unchanged locomotion(open field)but significantly reduced spontaneous alternation(Y-maze,P<0.01)and lower cognitive index(novel object recognition,P<0.001),confirming spatial and recognition memory deficits.(2)Microbiota:5-ASI mice exhibited decreased α-diversity(P<0.05)and altered β-diversity(P<0.001).LEfSe analysis revealed depleted taxa(e.g.,Prevotellaceae_NK3B31_group,Tyzzerella,Allobaculum,Ruminococcus)and enriched taxa(e.g.,Butyricicoccus,Lachnoclostridium).(3)Correlations:Positive associations with cognitive performance were observed for Prevotellaceae_NK3B31_group,Allobaculum,and Ruminococcus(P<0.05),while Butyricicoccus and Lachnoclostridium showed negative correlations(P<0.05).Conclusion Adolescent social isolation induces spatial/recognition memory impairment and gut microbiota dysbio-sis.Specific microbial alterations(Prevotellaceae_NK3B31_group,Butyricicoccus)correlate with cognitive deficits,providing novel insights into microbiota-mediated mechanisms and potential therapeutic targets.

AIM:To investigate the immunosuppressive effects of M2-like tumor-associated macrophages(M2-TAMs)on CD8+T cells within the tumor microenvironment of esophageal cancer.METHODS:Multiplex fluores-cence immunohistochemistry was used to analyze the distribution of immune cells in esophageal cancer tissues.An in vitro co-culture system was established,and flow cytometry along with Calcein-AM/PI staining was employed to assess the im-pact of M2-TAMs on CD8+T cell function.The GEPIA database was utilized to evaluate the prognostic significance of PDCD1 expression in esophageal cancer patients and to analyze the correlations between gene expressions.Immunohisto-chemistry(IHC)was performed to detect the expression of TGF-β1 in esophageal cancer tissues.Flow cytometry and en-zyme-linked immunosorbent assay(ELISA)were used to measure PD-1,IFN-γ and TNF-α expression in CD8+T cells fol-lowing treatment with a TGF-β1 inhibitor.RESULTS:Compared with early-stage(stage I)esophageal cancer patients,the patients with advanced disease(stages Ⅱ to Ⅳ)exhibited dynamic changes in the infiltration of CD4+T cells,CD8+T cells,Tregs,and M2-TAMs within tumor tissues,with significant correlations observed among these cell populations(P<0.05).The distribution of M2-TAMs and Tregs was positively correlated with poor prognosis(P<0.05),while that of CD8+T cells was negatively correlated(P<0.05).In contrast,CD4+T cell infiltration showed no significant association with clinical outcomes(P>0.05).Co-culture of CD8+T cells with M2-TAMs resulted in significant downregulation of CD107a,granzyme B,IFN-γ and TNF-α expression(P<0.01).Additionally,M2-TAM-treated CD8+T cells co-cultured with esophageal cancer cells led to reduced apoptosis of cancer cells.High expression of PDCD1 was significantly associated with poor prognosis(P<0.05),and significant correlations were observed between CD8A and PDCD1 expression,as well as between TGF-β1 and CD274 gene expression(P<0.01).TGF-β1 was also significantly associated with CD163+macro-phage infiltration and the progression of esophageal cancer(P<0.05).Treatment with a TGF-β1 inhibitor in the M2-TAM and CD8+T cell co-culture system significantly down-regulated PD-1 expression and increased the secretion of IFN-γ and TNF-α(P<0.01).CONCLUSION:The TGF-β1 derived from M2-TAMs inhibits the antitumor activity of CD8+T cells in the esophageal cancer microenvironment,suggesting potential therapeutic targets for overcoming immunosuppression in esophageal cancer.

Objective To explore the mechanism of modified Sijunzi Decoction in the intervention of premature ovarian failure(POF)rats through PTEN-mediated PI3K/AKT signaling pathway.Methods Totally 50 SPF-grade healthy female SD rats were divided into normal group(10 rats)and model group(40 rats).The model group was injected with cyclophosphamide to establish a POF model,and then randomly divided into model group and TCM low-,medium-and high-dosage group,with 10 rats in each group,TCM low-,medium-and high-dosage group were given modified Sijunzi Decoction 6.3,12.6,25.2 g/kg by gavage,the normal group and model group were given equal volume of normal saline,once a day for 28 days.The general condition and body mass of rats in each group were observed and recorded daily.After administration,the ovarian index was measured,HE staining was used to observe the morphology of ovarian tissue,ELISA was used to detect the contents of serum estradiol(E2)luteinizing hormone(LH),follicle-stimulating hormone(FSH),anti-Müllerian hormone(AMH),gonadotropin-releasing hormone(GnRH)and β-endorphin(β-EP),RT-PCR was used to detect the mRNA expression of PTEN,PI3K and AKT in ovarian tissue,Western blot was used to detect the protein expression of PTEN,PI3K,AKT,p-PI3K and p-AKT,immunohistochemistry was used to detect the positive expression of PTEN,PI3K and AKT.Results Compared with the normal group,the rats in the model group were depressed,the hair fell off,the diet and drinking water were reduced,the stools became thinner,the body mass was reduced(P<0.05),and the ovarian index was reduced(P<0.05),the ovarian tissue structure was disordered,the number of follicles decreased,and the contents of serum LH,FSH and GnRH increased(P<0.05),the contents of E2,AMH and β-EP decreased(P<0.05),the expression of PTEN mRNA and protein decreased(P<0.05),the expressions of PI3K and AKT mRNA and protein increased(P<0.05),and the expressions of p-PI3K and p-AKT protein increased(P<0.05).Compared with the model group,the general condition of rats in each dosage of TCM groups improved significantly,the body mass increased(P<0.05),ovarian index increased(P<0.05),the number of follicles in rat ovarian tissue increased,the contents of LH,FSH and GnRH decreased(P<0.05),the contents of E2,AMH and β-EP increased(P<0.05),the expression of PTEN mRNA and protein increased(P<0.05),the expression of PI3K and AKT mRNA and protein decreased(P<0.05),and the protein expression of p-PI3K and p-AKT decreased(P<0.05).Conclusion Modified Sijunzi Decoction may regulate the PI3K/AKT signaling pathway mediated by PTEN,repair the excessive consumption of follicles in ovarian tissue of POF rats,improve the ovarian function,so as to intervene the process of POF.

Objective To explore the effect of microRNA-381-3p(miR-381-3p)/MuRF1 axis on cardiopulmonary injury in hypoxia-induced pulmonary hypertension(HPH)mice and its potential mechanisms.Methods Sixty mice were randomly assigned to four groups:the normal control group(NC),the hypobaric hypoxia-induced pulmonary hypertension(HPH)group,the HPH+agomir control group and the HPH+miR-381-3p agomir analog group(HPH+miR-381-3p agomir),with 15 mice in each group.The HPH mouse model was established using a low-pressure and hypoxic artificial chamber.Three weeks prior to the establishment of the HPH model,miR-381-3p agomir and its corresponding control agomir were prepared by dissolving them in RNA-free phosphate-buffered saline(PBS)according to the experimental requirements.These solutions were administered via tail vein injection at a dose of 10 mg/kg,twice weekly for three consecutive weeks.Right heart function was assessed using echocardiography.Right ventricular systolic pressure(RVSP)was measured via cardiac catheterization.Pulmonary vascular remodeling was evaluated through hematoxylin and eosin(HE)staining.Levels of inflammatory cytokines in bronchoalveolar lavage fluid were quantified using enzyme-linked immunosorbent assay(ELISA).Real-time quantitative fluorescent PCR(RT-qPCR)was employed to analyze the mRNA expression levels of miR-381-3p and MuRF1.Potential targets of miR-381-3p were predicted,and pathway enrichment analysis was conducted.A dual-luciferase reporter gene assay was performed to confirm the direct regulatory effect of miR-381-3p on MuRF1.Results Compared with the NC group,the mRNA expression of miR-381-3p was significantly decreased in both the HPH group and the HPH+agomir control group,whereas the mRNA expression of MuRF1 was significantly increased(P＜0.05).In contrast,compared with the HPH group and the HPH+agomir control group,the mRNA expression of miR-381-3p was significantly increased in the HPH+miR-381-3p agomir group,while the mRNA expression of MuRF1 was significantly decreased(P＜0.05).Additionally,compared with the NC group,RVSP,right ventricular anterior wall thickness(RVAW),right ventricular hypertrophy index(RVHI),right ventricular collagen volume fraction(CVF),distal pulmonary artery wall thickness ratio(WT),pulmonary artery wall area ratio(WA),as well as IL-1β,IL-6 and TNF-α levels in alveolar lavage fluid were significantly increased in the HPH group and the HPH+agomir control group,whereas the right ventricular diameter(RVID)was significantly decreased(P＜0.05).Conversely,compared with the HPH group and the HPH+agomir control group,RVSP,RVAW,RVHI,right ventricular CVF,WT,Wa and RVID were decreased in the HPH+miR-381-3p agomir group,and IL-1β,IL-6,and TNF-α levels of alveolar lavage fluid were significantly decreased(P＜0.05).Furthermore,the downstream target genes of miR-381-3p were predicted in the database,and MuRF1 was a potential target,and the Cytoskeleton in muscle cells ranked first in the significant enrichment of target genes.Compared with WT-MuRF1+mimic control group,the luciferase activity was decreased in the WT-MuRF1+miR-381-3p mimic group(P＜0.05).There was no significant difference in the luciferase activity between the Mut-MuRF1+mimic control group and the Mut-MuRF1+miR-381-3p mimic group.Conclusion Overexpression of miR-381-3p can improve cardiopulmonary injury in HPH mice,and the mechanism may be related to the targeted inhibition of MuRF1 by miR-381-3p.

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Objective To explore the mechanism of modified Sijunzi Decoction in the intervention of premature ovarian failure(POF)rats through PTEN-mediated PI3K/AKT signaling pathway.Methods Totally 50 SPF-grade healthy female SD rats were divided into normal group(10 rats)and model group(40 rats).The model group was injected with cyclophosphamide to establish a POF model,and then randomly divided into model group and TCM low-,medium-and high-dosage group,with 10 rats in each group,TCM low-,medium-and high-dosage group were given modified Sijunzi Decoction 6.3,12.6,25.2 g/kg by gavage,the normal group and model group were given equal volume of normal saline,once a day for 28 days.The general condition and body mass of rats in each group were observed and recorded daily.After administration,the ovarian index was measured,HE staining was used to observe the morphology of ovarian tissue,ELISA was used to detect the contents of serum estradiol(E2)luteinizing hormone(LH),follicle-stimulating hormone(FSH),anti-Müllerian hormone(AMH),gonadotropin-releasing hormone(GnRH)and β-endorphin(β-EP),RT-PCR was used to detect the mRNA expression of PTEN,PI3K and AKT in ovarian tissue,Western blot was used to detect the protein expression of PTEN,PI3K,AKT,p-PI3K and p-AKT,immunohistochemistry was used to detect the positive expression of PTEN,PI3K and AKT.Results Compared with the normal group,the rats in the model group were depressed,the hair fell off,the diet and drinking water were reduced,the stools became thinner,the body mass was reduced(P<0.05),and the ovarian index was reduced(P<0.05),the ovarian tissue structure was disordered,the number of follicles decreased,and the contents of serum LH,FSH and GnRH increased(P<0.05),the contents of E2,AMH and β-EP decreased(P<0.05),the expression of PTEN mRNA and protein decreased(P<0.05),the expressions of PI3K and AKT mRNA and protein increased(P<0.05),and the expressions of p-PI3K and p-AKT protein increased(P<0.05).Compared with the model group,the general condition of rats in each dosage of TCM groups improved significantly,the body mass increased(P<0.05),ovarian index increased(P<0.05),the number of follicles in rat ovarian tissue increased,the contents of LH,FSH and GnRH decreased(P<0.05),the contents of E2,AMH and β-EP increased(P<0.05),the expression of PTEN mRNA and protein increased(P<0.05),the expression of PI3K and AKT mRNA and protein decreased(P<0.05),and the protein expression of p-PI3K and p-AKT decreased(P<0.05).Conclusion Modified Sijunzi Decoction may regulate the PI3K/AKT signaling pathway mediated by PTEN,repair the excessive consumption of follicles in ovarian tissue of POF rats,improve the ovarian function,so as to intervene the process of POF.