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.

Insulin-like growth factor 2 (IGF2) is a critical endocrine mediator implicated in male reproductive physiology. To investigate the correlation between IGF2 protein levels and various aspects of male infertility, specifically focusing on sperm quality, inflammation, and DNA damage, a cohort of 320 male participants was recruited from the Women's Hospital, Zhejiang University School of Medicine (Hangzhou, China) between 1 st January 2024 and 1 st March 2024. The relationship between IGF2 protein concentrations and sperm parameters was assessed, and Spearman correlation and linear regression analysis were employed to evaluate the independent associations between IGF2 protein levels and risk factors for infertility. Enzyme-linked immunosorbent assay (ELISA) was used to measure IGF2 protein levels in seminal plasma, alongside markers of inflammation (tumor necrosis factor-alpha [TNF-α] and interleukin-1β [IL-1β]). The relationship between seminal plasma IGF2 protein levels and DNA damage marker phosphorylated histone H2AX (γ-H2AX) was also explored. Our findings reveal that IGF2 protein expression decreased notably in patients with asthenospermia and teratospermia. Correlation analysis revealed nuanced associations between IGF2 protein levels and specific sperm parameters, and low IGF2 protein concentrations correlated with increased inflammation and DNA damage in sperm. The observed correlations between IGF2 protein levels and specific sperm parameters, along with its connection to inflammation and DNA damage, underscore the importance of IGF2 in the broader context of male reproductive health. These findings lay the groundwork for future research and potential therapeutic interventions targeting IGF2-related pathways to enhance male fertility.
Humans ; Male ; Insulin-Like Growth Factor II/metabolism* ; Infertility, Male/genetics* ; DNA Damage ; Adult ; Inflammation/metabolism* ; Spermatozoa/metabolism* ; Semen Analysis ; Semen/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Histones/metabolism* ; Interleukin-1beta/metabolism*

BACKGROUND:Studies have found that inhibition of tumor necrosis factor receptor-associated factor 6 improves myocardial function and promotes myocardial autophagy in sepsis,but the specific mechanism is not clear.OBJECTIVE:To explore the effect of inhibiting tumor necrosis factor receptor-associated factor 6-regulated mTORC1/ULK1 autophagy signaling pathway on myocardial injury in sepsis mice.METHODS:Thirty male Kunming mice were randomly divided into sham operation group,cecal ligation and puncture group(model group),model+tumor necrosis factor receptor-associated factor 6 specific inhibitor C25-140(model+C)group,model+C25-140+autophagy inhibitor 3-methyladenine(model+C+3-MA)group,and model+C25-140+mTORC1-specific agonist MHY1485(model+C+M)group.The cecum of mice in the sham operation group was not ligated or punctured.The mice in the other groups underwent cecum ligation and puncture to establish the mouse sepsis model.C25-140,3-methyladenine,and MHY1485 were intraperitoneally injected 0.5 hours after surgery according to the grouping.Myocardial tissue was obtained 24 hours after surgery.Hematoxylin-eosin staining was used to evaluate myocardial inflammatory lesions.Transmission electron microscopy was used to observe the changes in the autophagic bodies and mitochondrial microstructures of myocardial cells.TUNEL assay was used to detect myocardial cell apoptosis.PCR was used to detect the relative expression of tumor necrosis factor receptor-associated factor 6 mRNA.Western blot assay was used to detect the expression of related proteins.RESULTS AND CONCLUSION:(1)Compared with sham operation group,myocardial inflammatory cell infiltration and fibrous edema were observed in the model group.The mitochondria of the cells were obviously swollen,and autophagosomes were occasionally seen;cardiomyocyte apoptosis increased significantly;the expression of tumor necrosis factor receptor-associated factor 6,phosphorylated nuclear factor κB P65/P65,p-mTOR/mTOR,p-ULK1/ULK1,P62 and Bax protein increased,and the expression of Bcl2 protein decreased(P＜0.05).(2)Compared with the model group,myocardial inflammation and fibrous edema were alleviated in the model+C group.Myocardial mitochondrial swelling was reduced and autophagosomes increased;cardiomyocyte apoptosis decreased;the expression of phosphorylated nuclear factor κB P65/nuclear factor-κB P65,p-mTOR/mTOR,p-ULK1/ULK1,P62,and Bax protein decreased,while the Beclin-1 and Bcl2 protein increased(P＜0.05).(3)Compared with the model+C group,myocardial autophagosomes decreased and myocardial mitochondrial swelling was more obvious in the model+C+3-MA group.Myocardial inflammation was aggravated;myocardial cell apoptosis increased;the expression of phosphorylated nuclear factor κB P65/nuclear factor κB P65,P62,and Bax protein increased,and the Beclin-1 and Bcl2 protein decreased(P＜0.05).(4)Compared with the model+C group,the expression of p-mTOR/mTOR and p-ULK1/ULK1 in the model+C+M group increased,and the Beclin-1 and microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ protein expression decreased(P＜0.05).It is concluded that inhibition of tumor necrosis factor receptor-associated factor 6 regulates mTORC1/ULK1 autophagy signal to promote myocardial autophagy and participate in the protection of myocardial injury in sepsis.

Objective:To analyze the distribution characteristics and influencing factors of prolonged length in the elderly patients at a tertiary hospital.Methods:Medical records of patients receiving inpatient care at Xiangya Hospital, Central South University in Hunan province during January 1, 2021 and December 31, 2023 were collected.The generalized estimating equation(GEE)model was used to analyze the factors influencing prolonged hospitalization in elderly patients.Results:A total of 144 921 elderly inpatients were included, aged 60 to 104 years, with 84 950 males and 59 971 females.The average length of hospitalization was 7.81 days, with 2 614 patients hospitalized for more than 30 days (1 663 males and 951 females), and the average length of stay for these patients was 44.93 days.Most of the patients with prolonged length were hospitalized for 30 to 40 days, and in the group of aged 60-74 years.Disease categories mainly were related to health conditions, healthcare facility contact, tumors, and circulatory system diseases.The GEE model analysis showed that nosocomial infection [ OR(95% CI): 5.836(4.716-7.221)], age≥90 [ OR(95% CI): 2.415(1.680-3.472)], surgery [ OR(95% CI): 3.543(2.925-4.291)], number of complications>4[ OR(95% CI): 2.378(2.091-2.704)], unplanned hospital readmissions within 31 days [ OR(95% CI): 1.748(1.525-2.004)]were risk factors of prolonged hospitalization; female [ OR(95% CI): 0.901(0.824-0.986)] and no transferred hospitalization [ OR(95% CI): 0.154(0.140-0.169)] were protective factors. Conclusions:Prolonged hospitalization is related to the clinical and social factors.Administration department of the hospital should strengthen the monitoring of these influencing factors, reduce or prevent the occurrence of prolonged length of stay by adopting targeted measures, and further realize rational allocation of medical resources.

OBJECTIVE To standardize the strategies for prevention and control of Chikungunya(CHIK)in healthcare in-stitutions so as to reduce the risk of transmission in the institutions.METHODS A working group comprising the ex-perts in hospital infection control,infectious diseases,and microbiology systematically reviewed domestic and international evidence and current guidelines,integrated China's vector ecology and healthcare realities,conducted two rounds of Delphi to achieve expert consensus,and graded the evidence and recommendation strength using the Oxford Centre for Evidence Based Medicine system.RESULTS The consensus issues 18 actionable recommendations on triage,patient mosquito-proof isolation,integrated vector control,protection of susceptible populations,environmental cleaning and disinfection,specimen management,medical textile handling,and outbreak emergency response,with each statement assigned an evi-dence level and recommendation strength.CONCLUSION This consensus is for the first time in China to provide evidence-graded strategies for control of CHIK in healthcare institutions,offering work flow-oriented,implementable guidance for clinicians,laboratorians,and infection-control personnel under different risk scenarios and enhancing the comprehensive coping capacity of the healthcare institutions.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Objective To evaluate the diagnostic value of transrectal contrast-enhanced ultrasound (CEUS) for rectal cancer with intestinal stenosis caused by tumors. Methods Forty-nine patients with rectal cancer underwent transrectal CEUS and magnetic resonance imaging (MRI) before surgery.Intraoperative tumor localization and postoperative pathological results were taken as the gold standard for diagnosis.The differences in T stage,localization,and tumor length of rectal cancer were compared between the two methods. Results The total accuracy rates of transrectal CEUS and MRI in diagnosing T stage were 75.5% (36/49) and 67.3% (33/49),which had no significant difference (χ²=0.8,P=0.371).The total accuracy rates of transrectal CEUS and MRI in judging tumor localization were 79.5% (39/49) and 77.5% (38/49),which had no significant difference (χ²=0.061,P=0.806).The measurement results of tumor length in pathological examination had no significant difference from the transrectal CEUS results (t=1.42,P=0.162) but a significant difference from the MRI results (t=3.38,P=0.001).Furthermore,transrectal CEUS detected 8 (16.3%) cases of colonic polyps among the 49 patients,while MRI did not detect colon lesions. Conclusions Transrectal CEUS has good consistency with MRI in T staging and localization judgement of rectal cancer with intestinal stenosis,and this method can more accurately evaluate the tumor length and simultaneously evaluate whether there is a lesion in the entire colon at the proximal end of stenosis.It can be used as a supplementary examination before rectal cancer treatment in clinical practice.
Humans ; Rectal Neoplasms/complications* ; Male ; Middle Aged ; Female ; Aged ; Contrast Media ; Ultrasonography ; Adult ; Magnetic Resonance Imaging ; Constriction, Pathologic/diagnostic imaging* ; Aged, 80 and over ; Intestinal Obstruction/etiology*

BACKGROUND:Studies have found that inhibition of tumor necrosis factor receptor-associated factor 6 improves myocardial function and promotes myocardial autophagy in sepsis,but the specific mechanism is not clear.OBJECTIVE:To explore the effect of inhibiting tumor necrosis factor receptor-associated factor 6-regulated mTORC1/ULK1 autophagy signaling pathway on myocardial injury in sepsis mice.METHODS:Thirty male Kunming mice were randomly divided into sham operation group,cecal ligation and puncture group(model group),model+tumor necrosis factor receptor-associated factor 6 specific inhibitor C25-140(model+C)group,model+C25-140+autophagy inhibitor 3-methyladenine(model+C+3-MA)group,and model+C25-140+mTORC1-specific agonist MHY1485(model+C+M)group.The cecum of mice in the sham operation group was not ligated or punctured.The mice in the other groups underwent cecum ligation and puncture to establish the mouse sepsis model.C25-140,3-methyladenine,and MHY1485 were intraperitoneally injected 0.5 hours after surgery according to the grouping.Myocardial tissue was obtained 24 hours after surgery.Hematoxylin-eosin staining was used to evaluate myocardial inflammatory lesions.Transmission electron microscopy was used to observe the changes in the autophagic bodies and mitochondrial microstructures of myocardial cells.TUNEL assay was used to detect myocardial cell apoptosis.PCR was used to detect the relative expression of tumor necrosis factor receptor-associated factor 6 mRNA.Western blot assay was used to detect the expression of related proteins.RESULTS AND CONCLUSION:(1)Compared with sham operation group,myocardial inflammatory cell infiltration and fibrous edema were observed in the model group.The mitochondria of the cells were obviously swollen,and autophagosomes were occasionally seen;cardiomyocyte apoptosis increased significantly;the expression of tumor necrosis factor receptor-associated factor 6,phosphorylated nuclear factor κB P65/P65,p-mTOR/mTOR,p-ULK1/ULK1,P62 and Bax protein increased,and the expression of Bcl2 protein decreased(P＜0.05).(2)Compared with the model group,myocardial inflammation and fibrous edema were alleviated in the model+C group.Myocardial mitochondrial swelling was reduced and autophagosomes increased;cardiomyocyte apoptosis decreased;the expression of phosphorylated nuclear factor κB P65/nuclear factor-κB P65,p-mTOR/mTOR,p-ULK1/ULK1,P62,and Bax protein decreased,while the Beclin-1 and Bcl2 protein increased(P＜0.05).(3)Compared with the model+C group,myocardial autophagosomes decreased and myocardial mitochondrial swelling was more obvious in the model+C+3-MA group.Myocardial inflammation was aggravated;myocardial cell apoptosis increased;the expression of phosphorylated nuclear factor κB P65/nuclear factor κB P65,P62,and Bax protein increased,and the Beclin-1 and Bcl2 protein decreased(P＜0.05).(4)Compared with the model+C group,the expression of p-mTOR/mTOR and p-ULK1/ULK1 in the model+C+M group increased,and the Beclin-1 and microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ protein expression decreased(P＜0.05).It is concluded that inhibition of tumor necrosis factor receptor-associated factor 6 regulates mTORC1/ULK1 autophagy signal to promote myocardial autophagy and participate in the protection of myocardial injury in sepsis.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.