Objective:To investigate the role of the CD38/p53/ME1 axis in regulating T cell mitochondrial function and senescence during HIV infection.Methods:The expression of CD38 on T cells was examined in HIV-infected individuals receiving antiretroviral therapy(ART), untreated HIV-infected individuals, and HIV-negative healthy controls. Flow cytometry was used to compare senescence markers and mitochondrial function between CD38 + and CD38 - T cells. Malic enzyme 1(ME1) mRNA levels were measured by qRT-PCR in T cells treated with the CD38 inhibitor 78c. Mitochondrial function and senescence were assessed in T cells treated with an ME1 inhibitor. The regulatory mechanism of CD38-mediated ME1 downregulation was further explored. Results:Compared to healthy controls, T cells from HIV-infected individuals exhibited significantly elevated CD38 expression, which persisted despite ART. CD38 + T cells showed increased senescence (CD28 -CD57 + subset) and mitochondrial dysfunction[depolarization and reactive oxygen species(ROS) accumulation]. CD38 inhibition upregulated ME1 mRNA level ( P<0.05). ME1 suppression led to mitochondrial impairment (reduced membrane potential and elevated ROS) and senescence in T cells. Mechanistically, CD38 depletion increased NAD + levels and SIRT1 activity, while SIRT1/p53 inhibition rescued ME1 expression, suggesting CD38 regulates ME1 via the NAD + /SIRT1/p53 axis. Conclusions:The CD38/p53/ME1 axis drives T cell senescence in HIV infection by disrupting mitochondrial function. Targeting this pathway may ameliorate CD38-associated T cell dysfunction and immune aging.

Objective To analyze the current status and research frontiers of Huanglian Jiedu decoction based on bibliometrics.Methods By retrieving Chinese and English literature related to Huanglian Jiedu decoction in multiple databases from January 12000 to December 31 2024.A total of 1237 and 102 Chinese and English literature were included respectively,and the literature were analyzed by bibliometrics analysis.Results The keyword analysis showed that metabolomics,network pharmacology,mechanism pathway and autophagy regulation were the research hotspots of Huanglian Jiedu decoction.Conclusion The research field of Huanglian Jiedu decoction should integrate clinical and basic advantages,expand experimental protocols,strengthen long-term efficacy and safety evaluation,and explore multi-target and multi-disease synergistic effects and drug interactions.

Hungary, as the first European country to legislate TCM, its legislation experience has significant implications for the international development of TCM. This article reviewed the historical process of TCM legislation in Hungary, summarized its legislative achievements, and analyzed the problems encountered during the implementation process. It was found that the current challenges faced by TCM legislation in Hungary mainly include constraints from the dominance of modern medicine, restrictions from strict qualification requirements, insufficient public awareness, difficulties in TCM registration, and challenges in policy coordination and cooperation. Based on these findings, the article proposed countermeasures such as improving the legal framework, strengthening educational cooperation, enhancing public awareness, promoting the mutual recognition of standards between China and Europe, and deepening China-Hungary collaboration. These measures aim to further improve the legislation and implementation of TCM in Hungary, thereby promoting the healthy development of TCM in Hungary and the global service trade of TCM.

To review the clinical characteristics, short-term outcomes, and risk factors of patients with infective endocarditis(IE) who underwent surgical treatment at a single center, and to summarize treatment experience.

BACKGROUND:The energy metabolism and polarization state of macrophages play a crucial role in the progression of atherosclerosis.Traditional Chinese Medicine(TCM)has shown significant therapeutic potential for prevention and treatment of atherosclerosis by regulating macrophage metabolic pathways.OBJECTIVE:To review the research progress in AMP-activated protein kinase regulation of macrophage energy metabolism and polarization and explore the mechanism of TCM in the prevention and treatment of atherosclerosis.METHODS:A computerized search was conducted on the databases including Web of Science,PubMed,and CNKI,covering relevant literature up to June 2024.The search terms were"AMPK,fatty acid oxidation,macrophage polarization,Traditional Chinese Medicine,atherosclerosis,coronary heart disease"in Chinese and English.A total of 62 articles were finally included for review.RESULTS AND CONCLUSION:The shiftin macrophage energy metabolism from oxidative phosphorylation to glycolysis plays a key role in the progression of atherosclerosis.The activation of AMP-activated protein kinase in macrophages promotes fatty acid oxidation and M2 polarization,exerting anti-inflammatory effects and stabilizing arterial plaques.TCM monomers(such as ginseng,astragalus,and polygonatum)and compounds(such as Huanglian Jiedu Decoction,Yangxin Shumai Granules,and Tiaogan Daozhuo Formula)influence macrophage metabolism and cellular function by regulating the AMP-activated protein kinase pathway and intervening in multiple signaling pathways,such as nuclear factor-κB,peroxisome proliferator-activated receptor γ,and mammalian target of rapamycin,thereby achieving therapeutic effects.Future research should focus on the interactions between AMP-activated protein kinase,metabolism,and polarization pathways,as well as how TCM exerts its therapeutic effects through these pathways,providing new strategies for the treatment of atherosclerosis.

BACKGROUND:Mn can participate in oxidation-reduction reactions in various organisms.For example,as a metal-assisted group in superoxide dismutase 2,Mn plays a role in helping to remove reactive oxygen species.Therefore,the development of novel anti-oxidative stress materials containing Mn has become a research focus in recent years.OBJECTIVE:To investigate the protective effect of Mn bioceramic powder material on oxidative stress damage to chondrocytes by reducing the reactive oxygen species pathway.METHODS:Bioceramic powders containing Mn were prepared by molten salt method.Primary mouse chondrocytes were isolated and cultured.Bioceramic powder containing 0,0.15,and 0.30 mg/mL of Mn was added into H2O2 solution.The H2O2 clearance rate was detected after incubation without light.The passage 2 to passage 4 chondrocytes were co-cultured with complete media containing Mn-containing bioceramic powder with different mass concentrations(0,0.15,and 0.30 mg/mL).Cell viability was detected by cell live/dead staining.The passage 2-4 chondrocytes(or cartilage tissue)were divided into four groups for intervention:Complete culture medium was added to the blank control group.The H2O2 group was added and cultured with complete medium containing H2O2.H2O2+low mass concentration Mn powder group was cultured by adding H2O2+0.15 mg/mL Mn-containing bioceramic powder.The complete medium containing H2O2+0.30 mg/mL Mn-containing bioceramic powder was added to the H2O2+high mass concentration Mn powder group.Viability of chondrocytes was detected by CCK-8 assay.Generation of reactive oxygen species of chondrocytes was detected by 2,7-dichlorofluorescein diacetate probe.Expression of chondrocyte-related factors was detected by qRT-PCR.The tissue structure and function of cartilage were detected by toluidine blue staining.RESULTS AND CONCLUSION:(1)Both doses of Mn-containing bioceramic powders could significantly remove H2O2 in vitro,and they were concentration dependent.The results of cell live/death staining showed that 0.15 mg/mL bioceramic powder containing Mn had chondrocyte safety,and 0.30 mg/mL bioceramic powder containing Mn had chondrocytotoxicity.(2)The results of CCK-8 assay showed that the two mass concentrations of Mn-containing bioceramic powders could significantly reduce the inhibitory effect of H2O2 on chondrocyte viability,and inhibit the generation of reactive oxygen species induced by H2O2 in chondrocytes in a mass concentration dependent manner.Both kinds of Mn-containing bioceramic powders could reverse the H2O2-induced increase of mRNA expression of a disintegrin and metalloproteinase with thrombospondin motifs-5 and decrease of proteoglycan mRNA expression in chondrocytes.(3)Toluidine blue staining results showed that both concentrations of Mn-containing bioceramic powder could protect the integrity of cartilage tissue structure under oxidative stress,and 0.30 mg/mL of Mn-containing bioceramic powder could also reduce the functional damage of cartilage tissue.(4)The results indicate that the Mn-containing bioceramic powder can protect chondrocytes under oxidative stress by clearing reactive oxygen species,maintaining the extracellular matrix homeostasis.However,0.30 mg/mL Mn-containing bioceramic powder has certain chondrocytotoxicity,so 0.15 mg/mL Mn-containing bioceramic powder is preferred for follow-up studies.

Objectives:To explore the predictive value of angiography-derived index of microcirculatory resistance(Angio-IMR)for early prognosis in patients with acute ST-segment elevation myocardial infarction(STEMI)after percutaneous coronary intervention(PCI).Methods:This multicenter study enrolled 1 629 consecutive STEMI patients who underwent successful PCI at three grade A tertiary hospitals(The Second Affiliated Hospital,Zhejiang University School of Medicine;Shengjing Hospital of China Medical University;Renji Hospital,Shanghai Jiao Tong University School of Medicine)from June 1,2017,to May 31,2020.According to postoperative Angio-IMR,patients was stratified into two groups:the Angio-IMR>40 group(n=508)and the Angio-IMR≤40 group(n=1 121).The incidence of major adverse cardiovascular events(MACE;defined as a composite endpoint including cardiac death,heart failure rehospitalization,cardiogenic shock,malignant arrhythmia,cardiopulmonary resuscitation and stent thrombosis)within 1-month post-PCI was compared between the two groups.Results:The median Angio-IMR after PCI was 32.4(22.3,42.6).The cumulative incidence of early-term MACE was significantly higher in patients with Angio-IMR>40,compared to those with Angio-IMR≤40(5.5%vs.2.3%,log-rank P<0.001).Multivariate Cox regression analysis showed that Angio-IMR>40 was an independent predictor of early-term MACE(HR=2.07,95%CI:1.20-3.58,P=0.009).The addition of Angio-IMR enhanced the predicting performance of the clinical risk model to predict early adverse outcomes(AUC:0.820 vs.0.794,P=0.043).Conclusions:In patients with STEMI after PCI,Angio-IMR can predict the occurrence of early-term MACE.The incorporation of Angio-IMR to clinical models significantly improves the model ability to predict early adverse outcomes in these patients.

Objective:To elucidate the mechanism by which Clostridium butyricum alleviates atopic dermatitis (AD) from three aspects: immune cells, gut microbiota, and the metabolites of gut microbiota, short-chain fatty acids (SCFAs), and provide a theoretical reference for clinical probiotic-assisted treatment of AD. Methods:A model of 2, 4-dinitrochlorobenzene (DNCB)-induced AD was established using BALB/c mice. Three groups including control group, AD group, and Clostridium butyricum intervention group were set up with 20 mice in each group. The dermatitis score, scratching score, pathological conditions and mast cell infiltration at the lesion site, and the levels of cytokines related to Th1/Th2 and Th17/Treg as well as IgE levels in serum samples were analyzed. Gut microbiota was detected by 16S rRNA gene sequencing. The contents of SCFAs in mouse fecal samples were detected by gas chromatography-mass spectrometry. Spearman correlation analysis was performed to investigate the correlation between the cytokines related to Th1/Th2 and Th17/Treg, gut microbiota, and SCFAs. Comparisons between groups were performed using one-way analysis of variance with Turkey post hoc test correction. Results:Clostridium butyricum intervention down-regulated various inflammatory indexes and alleviated pathological changes in AD mice, elevated the levels of IFN-γ ( P<0.05) and IL-10 ( P<0.01), reduced the levels of IL-4, IL-17 and IgE ( P<0.01), and maintained the balance of Th1/Th2 ( P<0.01) and Th17/Treg ( P<0.001). Besides, the intervention improved intestinal dysbiosis by decreasing the abundance of conditionally pathogenic bacteria such as Prevotellaceae_ UCG-001 ( P<0.01) and increasing the abundance of beneficial bacteria such as Lachnospiraceae_ NK4A136_ group and norank_ f_ Oscillospiraceae ( P<0.05), and enhanced the production of SCFAs ( P<0.05). Correlation analysis showed that allergy-associated immune cytokines were strongly correlated with the composition of gut microbiota and the content of SCFAs. Conclusions:Clostridium butyricum may regulate the microbiota-SCFAs signaling response by inhibiting the colonization of harmful bacteria and increasing the abundance of beneficial bacteria. This, in turn, increases the level of SCFAs, decreases the number of pro-inflammatory cytokines, and maintains the balance of Th1/Th2 and Th17/Treg in the body. Therefore, Clostridium butyricum may alleviate allergic diseases.

Objective To analyze the current status and research frontiers of Huanglian Jiedu decoction based on bibliometrics.Methods By retrieving Chinese and English literature related to Huanglian Jiedu decoction in multiple databases from January 12000 to December 31 2024.A total of 1237 and 102 Chinese and English literature were included respectively,and the literature were analyzed by bibliometrics analysis.Results The keyword analysis showed that metabolomics,network pharmacology,mechanism pathway and autophagy regulation were the research hotspots of Huanglian Jiedu decoction.Conclusion The research field of Huanglian Jiedu decoction should integrate clinical and basic advantages,expand experimental protocols,strengthen long-term efficacy and safety evaluation,and explore multi-target and multi-disease synergistic effects and drug interactions.

Objective:To elucidate the mechanism by which Clostridium butyricum alleviates atopic dermatitis (AD) from three aspects: immune cells, gut microbiota, and the metabolites of gut microbiota, short-chain fatty acids (SCFAs), and provide a theoretical reference for clinical probiotic-assisted treatment of AD. Methods:A model of 2, 4-dinitrochlorobenzene (DNCB)-induced AD was established using BALB/c mice. Three groups including control group, AD group, and Clostridium butyricum intervention group were set up with 20 mice in each group. The dermatitis score, scratching score, pathological conditions and mast cell infiltration at the lesion site, and the levels of cytokines related to Th1/Th2 and Th17/Treg as well as IgE levels in serum samples were analyzed. Gut microbiota was detected by 16S rRNA gene sequencing. The contents of SCFAs in mouse fecal samples were detected by gas chromatography-mass spectrometry. Spearman correlation analysis was performed to investigate the correlation between the cytokines related to Th1/Th2 and Th17/Treg, gut microbiota, and SCFAs. Comparisons between groups were performed using one-way analysis of variance with Turkey post hoc test correction. Results:Clostridium butyricum intervention down-regulated various inflammatory indexes and alleviated pathological changes in AD mice, elevated the levels of IFN-γ ( P<0.05) and IL-10 ( P<0.01), reduced the levels of IL-4, IL-17 and IgE ( P<0.01), and maintained the balance of Th1/Th2 ( P<0.01) and Th17/Treg ( P<0.001). Besides, the intervention improved intestinal dysbiosis by decreasing the abundance of conditionally pathogenic bacteria such as Prevotellaceae_ UCG-001 ( P<0.01) and increasing the abundance of beneficial bacteria such as Lachnospiraceae_ NK4A136_ group and norank_ f_ Oscillospiraceae ( P<0.05), and enhanced the production of SCFAs ( P<0.05). Correlation analysis showed that allergy-associated immune cytokines were strongly correlated with the composition of gut microbiota and the content of SCFAs. Conclusions:Clostridium butyricum may regulate the microbiota-SCFAs signaling response by inhibiting the colonization of harmful bacteria and increasing the abundance of beneficial bacteria. This, in turn, increases the level of SCFAs, decreases the number of pro-inflammatory cytokines, and maintains the balance of Th1/Th2 and Th17/Treg in the body. Therefore, Clostridium butyricum may alleviate allergic diseases.