Since its emergence in the 1980s, the human immunodeficiency virus (HIV) has caused a global pandemic, posing a severe threat to human life and health as well as social development. Although pre-exposure prophylaxis (PrEP) effectively curbs HIV transmission and antiretroviral therapy (ART) significantly extends the lifespan of patients, vaccines remain a pivotal tool for blocking transmission and ending the pandemic. The high genetic variability of HIV-1, the glycan shield of its envelope glycoproteins, and the long-term persistence of latent reservoirs have repeatedly led to bottlenecks in traditional vaccine strategies. In recent years, mRNA technology has offered a novel approach to addressing these challenges, leveraging advantages such as sequence programmability, short production cycles, native conformational expression of antigens, and self-adjuvant effects. In recent years, mRNA vaccine technology has emerged as a transformative solution to longstanding vaccinology challenges, characterized by its sequence programmability, rapid production cycles, native conformational antigen expression, and intrinsic self-adjuvanting properties. Unlike traditional platforms reliant on pathogen culture or recombinant proteins, mRNA vaccines can be expeditiously designed and updated based solely on viral genomic sequences. Lipid nanoparticle (LNP)-encapsulated mRNA facilitates endogenous antigen expression and presentation, simultaneously eliciting potent humoral and cellular immune responses. Within this landscape, self-amplifying mRNA (saRNA) further extends in vivo antigen expression to enhance the persistence of immune responses. Moreover, the LNP delivery system not only protects mRNA from degradation and mediates endosomal escape but also synergizes with mRNA to optimize immune activation via self-adjuvant effects. Importantly, mRNA platforms circumvent the pre-existing immunity associated with viral vectors and the genomic integration risks of DNA vaccines, positioning them as a cornerstone for global pandemic preparedness. This review systematically delineates recent advances in mRNA technology for HIV-1 vaccine development, focusing on four pivotal research frontiers. First, mRNA innovations building upon the RV144 trial optimize antigens through codon modification and multivalent designs to induce more durable and broad-spectrum immunity. Second, particulate mRNA vaccine strategies, utilizing virus-like particles (VLPs) and ferritin nanoparticles, achieve in situ antigen self-assembly, significantly enhancing B cell activation and reducing infection risks in non-human primate models. Third, germline-targeting mRNA vaccines address the low-affinity barrier of broadly neutralizing antibody (bNAp) precursors, efficiently activating rare precursor B cells and promoting affinity maturation. Fourth, therapeutic mRNA vaccines offer unique advantages for an HIV functional cure; combining immunogens with mRNA-encoded adjuvants potentiates cellular immunity, while LNP-mediated “shock-and-kill” strategies specifically activate latent reservoirs to guide immune clearance. Comparative analyses with traditional platforms reveal that mRNA technology redefines antigen production and presentation, simulating chronic infection through sustained expression and enabling dual-pathway presentation via endogenous synthesis. Furthermore, we explore the mechanistic innovations of mRNA vaccines in inducing bNAps: sustained in vivo production prolongs the activation window for precursor B cells and maintains germinal center (GC) reactions; endogenously expressed antigens adopt native conformations to expose conserved epitopes; and self-adjuvanting effects modulate the functions of antigen-presenting cells (APCs) and follicular helper T cells (Tfh), driving somatic hypermutation and affinity maturation. We also address critical clinical translation challenges, including immune durability, adaptability to special populations, and large-scale LNP manufacturing, while proposing targeted optimization strategies. In conclusion, this review establishes a theoretical framework for utilizing mRNA technology to overcome HIV-1 immune escape, transitioning from a descriptive paradigm to a problem-solving-based synthesis of evidence. By integrating preclinical and early clinical data, we bridge the gap between basic design and translational verification. mRNA technology is poised to become a central pillar inHIV-1 prevention and therapy, providing a robust toolset to achieve the global goal of ending the AIDS pandemic and offering a blueprint for vaccine development against other recalcitrant infectious diseases.

Temporal lobe epilepsy(TLE)is the most common form of focal epilepsy in adults,characterized by spontaneous recurrent seizures,with most patients experiencing drug resistance and cognitive dysfunction.MicroRNAs(miRNAs)play a critical role in the pathological process of TLE through their regulation of post-transcriptional gene expression.The pathogenesis of TLE has not been fully elucidated,lacking effective clinical therapeutic targets and prognostic markers.This review sum-marized the expression changes of miRNAs in TLE and their research progress as potential biomarkers,aiming to provide new insights into the early diagnosis,prognosis evaluation,and pathogenic mecha-nisms of TLE.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

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 evaluate the efficacy and safety of venetoclax in combination with multidrug chemotherapy in patients with newly diagnosed acute leukemia of ambiguous lineage (ALAL) .Methods:A retrospective analysis of clinical data was performed on patients with newly diagnosed ALAL who were hospitalized at Jiangsu Provincial People's Hospital from June 2021 to July 2024. Of the 13 patients who received initial induction therapy with venetoclax combined with multidrug chemotherapy, 8 received VAA+P regimen, and 5 received V+IA regimen. Patients with FLT3 mutation were treated with FLT3 inhibitor, and Ph + patients received an additional tyrosine kinase inhibitor. Overall survival (OS), disease-free survival (DFS), and adverse events were analyzed. Results:According to the World Health Organization 5th edition of the classification of hematolymphoid tumors, the immunophenotypes were T/myeloid mixed-phenotype acute leukemia (MPAL) ( n=4), B/myeloid MPAL ( n=7), and ALAL- not otherwise specified ( n=2). Of the seven patients with B/myeloid MPAL, four were Ph + and belonged to the group with specific gene abnormalities of ALAL. Three patients had FLT3 mutation (one with FLT3-TKD mutation and two with FLT3-ITD mutation). Prior to the second course of consolidation therapy, the efficacy of venetoclax induction therapy was evaluated, and a complete response rate of 100% was achieved in 13 patients. In the subsequent consolidation therapy phase, one patient discontinued treatment and was lost to follow-up; nine patients underwent allogeneic hematopoietic stem cell transplantation, four of whom died due to posttransplant complications and five achieved DFS. Of the three patients (≥70 years old) who received consolidation therapy as before, two achieved DFS and one died due to central nervous system leukemia. The median OS time was not reached in 13 patients; the 75th percentile survival time was 12.0 months, with a 12-month cumulative survival rate of 64.5%. The median DFS time was not reached in all patients; the 75th percentile DFS time was 8.2 months, with a 12-month cumulative DFS rate of 67.1%. All patients experienced grade 3 or 4 hematologic toxicity, including neutropenia and thrombocytopenia, during and after induction therapy. All patients recovered hematopoietic function after the initial induction therapy, with no fatal hemorrhage, tumor lysis syndrome, neurological adverse events, or grade 3 or higher organ toxicity, excluding preexisting conditions. Conclusion:Venetoclax in combination with multidrug chemotherapy was effective and associated with tolerable adverse reactions in patients with newly diagnosed ALAL.

Aim To investigate the antidepressant mechanism of hyperforin via the utilization of single-cell sequencing technology.Methods C57BL/6 mice were randomly divided into the control group,depres-sion model group,and hyperforin intervention group.The chronic unpredictable mild stress(CUMS)model was induced and drug interventions were administered for 28 d.Behavioral experiments were conducted to as-sess depressive symptoms,and hippocampal tissue was collected for single-cell RNA sequencing.Key cell populations and differentially expressed genes across groups were identified,followed by PPI network,GO,and KEGG enrichment analysis.Results Behavioral experiments indicated that CUMS successfully induced depressive symptoms in mice,while hyperforin im-proved depressive behavior.In the depression model group,the proportion of brain perivascular macrophages(PVM)increased,and this proportion decreased after hyperforin intervention,approaching the level seen in the control group.The top 20 common differentially ex-pressed genes in the PVM subpopulation were Saa3,Hbb-bs and Ccl24.PPI network analysis identified core targets,including Ccl2,Dhx9,C3,Msr1,Cxcl2 and Cx3cr1.KEGG enrichment analysis revealed pathways related to chemokines,phagosome formation,and inosi-tol phosphate metabolism.Conclusion The antide-pressant mechanism of hyperforin may be related to the regulation of Ccl24 and its related chemokine signaling pathway by PVM.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Objective To explore the effect of PCSK9 inhibitor combined with atorvastatin on carotid atherosclerosis and its anti-inflammatory effect in patients with hypertension complicated with type 2 diabetes mellitus.Methods A total of 100 patients with hypertension complicated with type 2 diabetes mellitus who were treated in Nanchang Third Hospital from October 2022 to August 2023 were selected as the research subjects.They were divided into the control group and the study group by the random number table method,with 50 cases in each group.Both groups of patients received conventional antihypertensive,hypoglycemic,and antiplatelet therapy.The control group took 20 mg of atorvastatin calcium tablets orally,once a night.On the basis of the control group,the study group was additionally given 150 mg of evolocumab injection(a PCSK9 inhibitor)by subcutaneous injection,once every two weeks.Both groups of patients were followed up for 24 weeks.The levels of blood lipids,blood glucose,inflammatory cytokines,carotid intima-media thickness(IMT),atherosclerotic plaque score and adverse reactions of the patients in the two groups before and after treatment were detected and compared.Results The levels of TC,TG and LDL-C in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P＜0.05).The levels of IL-1,IL-6,TNF-α,hs-CRP,as well as the ca-rotid IMT and atherosclerotic plaque score in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P＜O.05).During the treatment period,there was no significant difference in the occurrence of adverse reac-tions between the two groups(P＞0.05).Conclusion The combination of PCSK9 inhibitor and atorvastatin can effectively regulate the blood lipid levels of patients with hypertension complicated and type 2 diabetes mellitus,alleviate the inflammatory response,and improve the degree of carotid atherosclerosis in these pa-tients.

OBJECTIVES: To investigate the clinical characteristics and prognosis of chronic disseminated candidiasis (CDC) in children with acute leukemia (AL) following chemotherapy. METHODS: A retrospective analysis was conducted on children diagnosed with CDC (including confirmed, clinically diagnosed, and suspected cases) after AL chemotherapy from January 2015 to December 2023 at Fujian Medical University Union Hospital, Zhangzhou Municipal Hospital, and Quanzhou First Hospital Affiliated to Fujian Medical University. Clinical characteristics and prognosis were analyzed. RESULTS: The incidence of CDC in children with AL following chemotherapy was 1.92% (32/1 668). Among the children with acute lymphoblastic leukemia, the incidence of CDC in the high-risk group was significantly higher than in the low-risk group (P=0.002). All patients presented with fever unresponsive to antibiotics during the neutropenic period, with 81% (26/32) involving the liver. C-reactive protein (CRP) levels were significantly elevated (≥50 mg/L) in 97% (31/32) of the patients. The efficacy of combined therapy with liposomal amphotericin B and caspofungin or posaconazole for CDC was 66% (19/29), higher than with caspofungin (9%, 2/22) or liposomal amphotericin B (18%, 2/11) monotherapy. The overall cure rate was 72% (23/32). The proportion of patients with CRP ≥50 mg/L and/or a positive β-D-glucan test for more than 2 weeks and breakthrough infections during caspofungin treatment was significantly higher in the treatment failure group compared to the successful treatment group (P<0.05). CONCLUSIONS CDC in children with AL after chemotherapy may be associated with prolonged neutropenia due to intensive chemotherapy. Combination antifungal regimens based on liposomal amphotericin B have a higher cure rate, while persistently high CRP levels and positive β-D-glucan tests may indicate poor prognosis.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Antifungal Agents/therapeutic use* ; Candidiasis/diagnosis* ; Chronic Disease ; Leukemia/complications* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications* ; Prognosis ; Retrospective Studies

OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent