This study aims to explore the role and mechanism of berberine in promoting the expression of aquaporin 4(AQP4) in astrocytes by regulating the expression of miR-383-5p in HepG2 cell-derived exosomes under insulin resistance(IR). The IR-HepG2 cell model was established with 1×10~(-6) mol·L~(-1) insulin. With metformin as the positive control, the safe concentrations of berberine and metformin were screened by cell counting kit-8(CCK-8) and lactate dehydrogenase(LDH) leakage assays, and the effect of berberine on the IR of HepG2 cells was evaluated by glucose consumption. NanoSight was used to measure the particle size and concentration of exosomes secreted by HepG2 cells in each group. HepG2 cell-derived exosomes in each group were incubated with astrocytes for 24 h, and the protein and mRNA levels of AQP4 in HA1800 cells were determined by Western blot and qRT-PCR, respectively. qRT-PCR was performed to determine the expression of miR-383-5p in HepG2 cell-derived exosomes and HA1800 cells after co-incubation. Western blotting was employed to determine the expression levels of miRNAs and proteins associated with exosome production and release in HepG2 cells. The results showed that 10 μmol·L~(-1) berberine and 1 mmol·L~(-1) metformin significantly alleviated the IR of HepG2 cells and reduced the concentration of exosomes in HepG2 cells. The exosomes of HepG2 cells treated with berberine and metformin significantly up-regulated the protein and mRNA levels of AQP4 in HA1800 cells. The mRNA level of miR-383-5p in HepG2 cell exosomes and HA1800 cells co-incubated with berberine and metformin decreased significantly. The intervention with berberine and metformin significantly down-regulated the expression of proteins associated with the production of miRNAs(Dicer, Drosha) as well as the production(Alix, Vps4A) and release(Rab35, VAMP3) of exosomes in IR-HepG2 cells. In conclusion, berberine can promote the expression of AQP4 in astrocytes by inhibiting the production and release of miR-383-5p in HepG2-derived exosomes under IR.
Humans ; MicroRNAs/metabolism* ; Berberine/pharmacology* ; Hep G2 Cells ; Exosomes/genetics* ; Aquaporin 4/metabolism* ; Insulin Resistance ; Astrocytes/drug effects*

The aging microenvironment, as a key driver of tumorigenesis and progression, plays a critical role in tumor immune regulation through one of its core features-the senescence-associated secretory phenotype (SASP). SASP consists of a variety of interleukins, chemokines, proteases, and growth factors. It initially induces surrounding cells to enter a state of senescence through paracrine mechanisms, thereby creating a sustained inflammatory stimulus and signal amplification effect within the tissue microenvironment. Furthermore, these secreted factors activate key signaling pathways such as NF-κB, cGAS-STING, and mTOR, which regulate the expression of immune-related molecules (such as PD-L1) and promote the recruitment of immunosuppressive cells, including regulatory T cells and myeloid-derived suppressor cells. This process ultimately contributes to the formation of an immunosuppressive tumor microenvironment. Furthermore, the article explores potential anti-tumor immunotherapy strategies targeting SASP and its associated molecular mechanisms, including approaches to inhibit SASP secretion or eliminate senescent cells. Although these strategies have shown promise in certain tumor models, the high heterogeneity among tumor types may result in varied responses to SASP-targeted therapies. This highlights the need for further research into adaptive stratification and personalized treatment approaches. Targeting immune regulatory mechanisms in the aging microenvironment-particularly SASP-holds great potential for advancing future anti-tumor therapies.

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 role and mechanism of tannic acid in renal ischemia-reperfusion injury(IRI)in mice.Methods Male C57BL/6J mice were randomly divided into sham operation group(Sham group),blank control group(Sham+TA group),experimental group(IRI group)and treatment group(IRI+TA group),with 20 mice in each group.The survival of mice after renal IRI was observed 48 h after surgery.Serum and renal tissue samples were collected from mice 24 h after IRI(5 mice per group),and the levels of blood urea nitrogen and serum creatinine were detected.The levels of inflammatory factors and ferroptosis-related indicators in renal tissue were detected.The pathological damage of renal tissue was assessed.The protein expression levels of glutathione peroxidase 4(GPX4)and acyl-CoA synthetase long-chain family 4(ACSL4)in renal tissue were detected.Molecular docking software was used to explore the binding activity of tannic acid with nuclear factor E2-related factor 2(Nrf2)and to verify the expression of Nrf2 and heme oxygenase-1(HO-1).Results Compared with the IRI group,the postoperative survival rate of mice in the IRI+TA group was higher(0 vs.60%),the levels of serum creatinine and blood urea nitrogen were decreased,the levels of interleukin(IL)-6,IL-1β,and tumor necrosis factor(TNF)-α in renal tissue were decreased,the renal tissue injury was improved,the levels of malondialdehyde and ferrous ions in renal tissue were reduced,the level of glutathione was increased,the expression of GPX4 was increased,and the expression of ACSL4 was decreased(all P<0.05).Tannic acid may form a suitable spatial complement with Nrf2,with a binding energy of-8.7 kcal/mol,indicating a strong binding ability of tannic acid with Nrf2.The protein levels of Nrf2 and HO-1 in the renal tissue of mice in the IRI+TA group were upregulated.Conclusions Tannic acid may bind to Nrf2 protein,activate the Nrf2/HO-1 pathway to inhibit ferroptosis,and alleviate renal IRI in mice.

Objective:To review the clinical status based on the best evidence of drug administration in patients with dysphagia, systematically analyze the obstacle factors and promoting factors in the process of evidence transformation, and formulate reform strategies.Methods:Based on the evidence-based nursing research method and the guidance of the Ottawa Model of Research Use (OMRU), the review indicators were developed based on the best evidence. The current status of clinical practice behaviors of 223 patients and 75 nurses in the Neurology, Neurosurgery and Geriatric departments of the Affiliated Hospital of Jiangsu University were reviewed from July to December 2021.Based on the results of the review, qualitative interviews were conducted with 32 potential adopters, and content analysis was used to assess the barriers and contributing factors to the clinical translation of evidence in three aspects: evidence-based change, potential adopters and practice environment, so as to develop effective strategies.Results:Based on the 22 best evidence selected, the evidence-based team developed 25 review indicators to carry out clinical review, showing that the compliance rate of 16 indicators were less than 60%. By analyzing and summarizing the interview results of potential adopters, the main obstacles leading to the low compliance rate of nurses were analyzed as follows: evidence-based reform changed the traditional work mode, and the application of evidence was not convenient; at the level of potential adopters, nurses had poor knowledge and practice, heavy work burden, and low awareness of patients and caregivers; at the level of practice environment, there was lack of nursing norms and procedures for clinical transformation of evidence, and the channels of multi-disciplinary collaboration and communication were not smooth. The main promoting factors were the perfect supervision mechanism of evidence-based nursing projects, the evidence-based group had rich experience in evidence transformation, the management was willing to change, and the practitioners were good at innovation.Conclusions:There is still a large gap between the clinical practice and the best evidence of drug administration in patients with dysphagia. The promoting factors should be fully utilized to overcome the obstacles and implement improvements to promote the effective transformation of evidence into clinical practice.

Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

Immunotherapy is an important breakthrough in canc-er treatment.Unfortunately,low drug concentration in tumor sites almost ineffectively initiates immune responses and thereby severely limits immune therapy applications in clinics.Nanoma-terials are well-recognized drug delivery system in cancer thera-py.Nanographene oxide(NGO)have shown immense perti-nence for anti-cancer drug delivery owing to their ultra-high sur-face area,chemical stability,good biocompatibility and excel-lent photosensitivity.In addition,functionalized modifications on the surface of NGO increase tumor targeting and minimize cy-totoxicity.This study focuses on reviewing the literature and up-dates on NGO in drug delivery and discussing the possibilities and challenges of NGO in cancer synergetic therapy.

Objective:To carry out an overview of systematic reviews on interventions to prevent the recurrence of diabetic foot ulcer (DFU) patients.Methods:Systematic reviews or Meta-analysis on interventions to prevent DFU recurrence were electronically retrieved from databases such as China National Knowledge Infrastructure, WanFang Data, VIP, China Biology Medicine disc, Joanna Briggs Institute (JBI) Evidence-Based Healthcare Center Database, Cochrane Library, PubMed, Embase, CINAHL and Web of Science. The search period was from database establishment to April 20, 2023. Two researchers independently searched and screened literature, and extracted data, and used AMSTAR 2 software and the quality evaluation criteria for systematic review of JBI Evidence-Based Healthcare Center to evaluate the methodological quality of the included literature. GRADE evaluation system was used for quality assessment of outcome indicators (DFU recurrence rate, effectiveness of measures to prevent DFU recurrence) .Results:A total of 24 systematic reviews were included. Studies showed that monitoring and intervention of foot skin temperature, therapeutic shoes or insoles, comprehensive intervention measures, and specific surgical methods could reduce the recurrence rate of DFU, while foot self-care, foot exercise, health education, and psychological intervention had no statistical effect on preventing DFU recurrence. The methodological quality of systematic reviews was generally low. The reports of four articles were relatively complete, 18 articles had certain defects, and two articles had serious defects. The evaluation of evidence quality showed that there were three pieces of moderate-quality evidence, seven pieces of low-quality evidence, and 30 pieces of extremely low-quality evidence.Conclusions:Existing evidence suggests that foot skin temperature monitoring and intervention, therapeutic shoes or insoles, comprehensive intervention measures, and specific surgical methods (such as Achilles tendon lengthening, metatarsophalangeal joint replacement, metatarsal head resection and so on) have a positive impact on preventing DFU recurrence. Rigorous and high standard research is still needed to verify the controversial issues, so as to provide reliable evidence for future clinical practice and studies.

Objective:To evaluate the efficacy of acute T-cell lymphoblastic leukemia(T-ALL)in children and explore the prognostic risk factors.Methods:The clinical data of 127 newly diagnosed children with T-ALL admitted to five hospitals in Fujian province from April 2011 to December 2020 were retrospectively analyzed,and compared with children with newly diagnosed acute precursor B-cell lymphoblastic leukemia(B-ALL)in the same period.Kaplan-Meier analysis was used to evaluate the overall survival(OS)and event-free survival(EFS),and COX proportional hazard regression model was used to evaluate the prognostic factors.Among 116 children with T-ALL who received standard treatment,78 cases received the Chinese Childhood Leukemia Collaborative Group(CCLG)-ALL 2008 protocol(CCLG-ALL 2008 group),and 38 cases received the China Childhood Cancer Collaborative Group(CCCG)-ALL 2015 protocol(CCCG-ALL 2015 group).The efficacy and serious adverse event(SAE)incidence of the two groups were compared.Results:Proportion of male,age ≥ 10 years old,white blood cell count(WBC)≥ 50 × 109/L,central nervous system leukemia,minimal residual disease(MRD)≥ 1％during induction therapy,and MRD ≥ 0.01％at the end of induction in T-ALL children were significantly higher than those in B-ALL children(P＜0.05).The expected 10-year EFS and OS of T-ALL were 59.7％and 66.0％,respectively,which were significantly lower than those of B-ALL(P＜0.001).COX analysis showed that WBC ≥ 100 x 109/L at initial diagnosis and failure to achieve complete remission(CR)after induction were independent risk factors for poor prognosis.Compared with CCLG-ALL 2008 group,CCCG-ALL 2015 group had lower incidence of infection-related SAE(15.8％vs 34.6％,P=0.042),but higher EFS and OS(73.9％vs 57.2％,PEFS=0.090;86.5％vs 62.3％,PoS=0.023).Conclusions:The prognosis of children with T-ALL is worse than children with B-ALL.WBC ≥ 100 × 109/L at initial diagnosis and non-CR after induction(especially mediastinal mass has not disappeared)are the risk factors for poor prognosis.CCCG-ALL 2015 regimen may reduce infection-related SAE and improve efficacy.

Objective:Abnormal programmed cell death in immune cells is associated with autoimmune diseases,but the patterns of programmed cell death in systemic lupus erythematosus(SLE)and especially lupus nephritis(LN)remain unclear.This study aims to explore the association between SLE,LN,and immune cell death patterns. Methods:Bulk RNA sequencing(bulk RNA-seq)and single-cell RNA sequencing(scRNA-seq)data were downloaded from the Gene Expression Omnibus(GEO)database.Bioinformatic analysis was conducted to explore the expression levels of genes related to 3 cell death patterns in peripheral blood mononuclear cells of SLE patients.Key cell subsets involved in the imbalance of cell death patterns were identified through scRNA-seq.Immunofluorescence was used to detect the expression levels of receptor interacting serine/threonine kinase 3(RIPK3),mixed-lineage kinase domain-like protein(MLKL),phosphorylated MLKL(pMLKL),caspase 1(CASP1),CD1c molecule(CD1C),C-type lectin domain containing 9A(CLEC9A),and X-C motif chemokine receptor 1(XCR1)in dendritic cells(DC).scRNA-seq was performed on kidney tissues collected from LN patients and healthy controls(HC)at the Third Xiangya Hospital of Central South University,followed by bioinformatic analysis to identify key cell subsets involved in the imbalance of cell death patterns.Pseudotime analysis and ligand-receptor analysis were used to explore the differentiation direction and cell communication of different DC subsets.Transient transfection was used to transfect RAW264.7 cells with empty plasmid,empty plasmid+dsDNA(HSV-DNA),empty plasmid+200 μmol/L tert-butyl hydroperoxide(TBHP),stimulator of interferon genes(STING)shRNA plasmid,STING shRNA plasmid+dsDNA(HSV-DNA),and STING shRNA plasmid+200 μmol/L TBHP.Annexin V-mCherry and SYTOX Green staining were used to detect cell death in each group.Western blotting was used to detect the activation of CASP1,gasdermin D(GSDMD),RIPK3,and MLKL in each group. Results:Bioinformatic analysis showed an imbalance in 3 cell death patterns in SLE and LN patients:Pro-inflammatory pyroptosis and necroptosis were activated,while anti-inflammatory apoptosis was inhibited.The key cell subsets involved were DC subsets,particularly focusing on CLEC9A+cDC1.Immunofluorescence results showed that the expression levels of RIPK3,MLKL,and CASP1 in DCs were higher in the SLE group compared to the HC group.pMLKL and CASP1 expression levels in renal cDC1 marked by CLEC9A and XCR1 were higher in the LN group than in the HC group.Pseudotime analysis and ligand-receptor analysis suggested that the CLEC9A+cDC1 subset in LN kidney tissues originated from peripheral circulation.Annexin V-mCherry and SYTOX Green staining results showed that the number of dead cells decreased in the STING shRNA transfection group compared to the empty plasmid group in RAW264.7 cells.Western blotting results showed that the activation of CASP1,GSDMD,RIPK3,and MLKL was decreased in the STING shRNA transfection group compared to the empty plasmid group. Conclusion:This study provides novel insights into the role of CLEC9A+cDC1 in the imbalance of cell death patterns in SLE and LN.