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.

Objective:A preliminary trial is conducted to explore whether perioperative(preoperative,intraoperative,and postoperative)electroacupuncture is more effective than postoperative electroacupuncture in improving gastrointestinal function for colorectal cancer patients.Methods and analysis:The study proposes a randomized,parallel-controlled,single-center trial involving 30 colorectal cancer patients aged 18-79 requiring elective surgery.Participants are randomly assigned to two groups,with equal allocation,where one group receives perioperative electroacupuncture,and the other group receives postoperative electroacupuncture.The treatment duration spans from preoperative to postoperative 72 h,with a subsequent 28-day follow-up period.The primary outcome is the time of first postoperative defecation.The secondary outcomes include the recovery time of postoperative bowel sounds,time of the first flatus,dietary recovery,postoperative gastrointestinal dysfunction frequency,quality of life scale,postoperative pain degree,time of the first ambulation,length of hospital stay,gastrointestinal hormone indicators,and adverse events.The coagulation function test,liver and renal function,and stool and blood routine serve as security biomarkers.The statistical analysis includes the t-test,rank-sum test,Chi-square test,and analysis of variance.A two-sided significance level is set at 5%.Discussion:This study aims to evaluate the feasibility and preliminary effectiveness of perioperative electroacupuncture for gastrointestinal function recovery following colorectal cancer surgery.The study's strengths include its randomized design,well-defined intervention periods,and multi-dimensional outcome assessment.Nevertheless,limitations,such as the small sample size and single-center setting,may affect external validity.The findings will guide protocol refinement and sample size estimation for future large-scale multi-center randomized controlled trials.

OBJECTIVE To explore the association of Helicobacter pylori infection with the expression levels of Ki67,caudal type homeobox transcription factor 2(CDX-2)and p53 protein in the gastric cancer patients so as to provide bases for improvement of prognosis of the gastric cancer patients.METHODS Totally 113 patients who were diagnosed with gastric cancer by gastroscopic examination and were treated in Shijiazhuang People's Hospital from Jan.2020 to Jan.2024 were assigned as the gastric cancer group,84 of whom were complicated with H.py-lori infection(the Hp-positive group),and 29 were negative for Hp(the Hp-negative group).Meanwhile,125 patients who had chronic atrophic gastritis were assigned as the non-gastric cancer group.The gastric mucosa tis-sue specimens were collected through gastroscopy,and the expression levels of Ki67,CDX-2 and p53 protein were detected.RESULTS The positive rate of H.pylori infection of the gastric cancer group was 74.34％,higher than 54.40％of the non-gastric cancer group(P＜0.05).The positive rate of H.pylori was higher in the gastric canc-er patients with lymphatic metastasis,infiltration depth of T3 to T4 and TNM stage of Ⅲ to Ⅳ stage than in the gastric cancer patients without lymphatic metastasis,infiltration depth of T1 to T2 and TNM stage of Ⅰ to Ⅱ stage(P＜0.05).The positive expression rates of gastric mucosa tissue Ki67,CDX-2 and p53 protein of the gastric cancer group were respectively 69.91％,52.21％and 79.65％,higher than 47.20％,0 and 24.00％of the non-gastric cancer group,there were significant differences(P＜0.05).The positive expression rates of gastric mucosa tissue Ki67,CDX-2 and p53 protein of the Hp-positive group were higher than those of the Hp-negative group(P＜0.05).CONCLUSION The gastric cancer is associated with the H.pylori infection and the expressions of Ki67,CDX-2 and p53.The H.pylori infection may lead to the abnormal expressions of Ki67,CDX-2 and p53 in gastric mucosa tissues of the gastric cancer patients,which is also associated with the clinicopathologic features.

Objective:To investigate the relationship between lipid levels and cognitive impairment in the elderly Chinese population using prospective cohort data.Methods:Based on the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) cohort, this study included 24 380 individuals aged ≥60 years who participated in the cognitive function follow-up survey from 2018 to 2019. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with cognitive impairment defined according to different educational levels: MMSE ≤17 for illiterate individuals, MMSE ≤20 for those with primary education and MMSE ≤24 for those with secondary education or above. Multivariable linear regression and logistic regression models were employed to examine the associations between six baseline lipid indicators and cognitive scores, as well as cognitive impairment. Additionally, restricted cubic splines were used to explore the exposure-dose relationship between lipid levels and cognitive function.Results:The study population had a median follow-up time of 11.6 years, with a baseline age of (59.7±6.8) years. Among the participants, 9 510 (39.0%) were males, and the mean MMSE score was 24.7±6.8. A total of 3 887 individuals (15.9%) were identified as cognitively impaired. The results of multivariable linear regression and logistic regression indicated that total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) levels were not only significantly positively associated with cognitive scores but also significantly associated with a lower risk of cognitive impairment. Each 1 mmol/L increase in these lipid levels corresponded to β values (95% CI) of 0.267 (0.173-0.361), 0.385(0.271-0.499) and 0.331(0.231-0.431), respectively. Each 1 mmol/L increase in these lipid levels corresponded to odds ratio ( OR) (95% CI) values of 0.915 (0.876-0.956), 0.875 (0.830-0.923) and 0.886 (0.848-0.927), respectively. The dose-response curve demonstrated that the negative association was primarily observed within the guideline-recommended optimal lipid level range. Specifically, when LDL-C was less than 3.4 mmol/L and non-HDL-C was less than 4.1 mmol/L, the corresponding OR (95% CI) values were 0.859 (0.796-0.926) and 0.876 (0.818-0.939). Conclusion:Lipid levels exhibit a certain linear negative association with cognitive impairment in elderly Chinese adults, with LDL-C and non-HDL-C demonstrating a stronger effect, particularly within the guideline-recommended optimal range.

Objective:Based on a propensity score matchied analysis, the impact of neoadjuvant therapy, namely the transcatheter arterial chemoembolization (TACE) combined with the targeted and immunotherapy, on the prognosis of patients undergoing liver resection for hepatocellular carcinoma (HCC).Methods:Clinical data of 226 patients who underwent surgical resection for HCC of China Liver Cancer (CNLC) stage Ib, IIa, IIb, and IIIa at the Second Affiliated Hospital of Anhui Medical University from February 2020 to December 2024 were retrospectively analyzed, including 201 males and 25 females, aged 64.6±9.4 years. Patients were divided into the neoadjuvant therapy group ( n=25) and the direct surgery group ( n=201). Propensity score matching was used to analyze the liver fibrosis-4 score, platelet count, prothrombin time, activated partial thromboplastin time, and tumor number of the two groups. Postoperative pathological assessment of liver resection was performed. The Kaplan-Meier method was used to analyze the prognosis, and the log-rank test was used to compare the survival rates of the two groups. Results:After propensity score 1: 3 matching, there were no statistically significant differences (all P>0.05) regarding the baseline characteristics of the two groups. Pathological assessment after hepatectomy: the complete pathological response rate was 8% (2/25), and the major pathological response rate was 36% (9/25). The recurrence-free survival rates at 1, 2, and 3 years after surgery in the direct surgery group and the neoadjuvant therapy group were 52.0%, 48.0%, and 42.7% versus 76.0%, 72.0%, and 68.0%, respectively ( χ2=4.76, P=0.029). The overall survival rates at 1, 2, and 3 years after surgery in the direct surgery group and the neoadjuvant therapy group were 80.0%, 78.7%, and 77.3% versus 100.0%, 96.0%, and 96.0%, respectively ( χ2=4.31, P=0.038). Conclusion:Neoadjuvant therapy could reduce the risk of postoperative recurrence and prolong patients survival

Objective:To investigate the role of the Smad3 signaling pathway in the process of silica-induced epithelial-mesenchymal transition (EMT) .Methods:In September 2022, lung epithelial cells (BEAS-2B) were exposed to different concentrations of silica suspension (0, 50, 100, and 150 μg/ml) for 6 and 12 hours. Additionally, SIS3, a specific inhibitor of phosphorylated Smad3 (p-Smad3) , was utilized to establish the p-Smad3 inhibition model. The cells were divided into four groups: blank control gruop, silica group, SIS3 intervention group, and SIS3 +silica group. Cell morphology was observed using an inverted fluorescence microscope, while cell viability was assessed using a Cell Counting Kit-8 (CCK-8) . The mRNA and protein expression levels of E-cadherin (E-Cad) , N-cadherin (N-Cad) , Vimentin, Smad3, and p-Smad3 were analyzed by Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Differences between two groups were compared using Student's t-test, and multiple group comparisons were analyzed using a one-way analysis of variance with the Student-Newman-Keuls test.Results:Compared with the blank control group, the morphology of BEAS-2B cells shifted from epithelial to mesenchymal cell-like following silica exposure, and the cell viability of BEAS-2B cells declined after exposure to 150 μg/ml silica for 6 and 12 hours. Furthermore, silica exposure led to significant reductions in mRNA and protein expression levels of the epithelial cellular marker (E-Cad) in BEAS-2B cells, accompanied by increased expressions of interstitial cellular markers (N-Cad and Vimentin) . Importantly, the level of p-Smad3/Smad3 expression levels was also elevated in silica-treated cells ( P<0.05) . Compared to the blank control group, the level of p-Smad3/Smad3 expression levels was significantty reduced. Moreover, compared to the silica group, the protein expression levels of N-Cad and Vimentin in the cell of the SIS3+silica group were significantly reduced, while the E-Cad expression was increased ( P<0.05) . Conclusion:Silica exposure can prmote the epithelial mesenchymaol transformotion process by activating smod3 signa ling pathuay, and in hibiting smad3 signa ling pathuay can effctively alleviate the occurrence of epithelial mesenchymal transformation process.

Preeclampsia(PE)is a severe pregnancy complication that poses significant risks to maternal and fetal health,and its pathogenesis remains unclear.Recent studies have shown that lactate dehydrogenase(LDH),a key enzyme in glycolysis,plays a piv-otal role in the development and progression of PE.This article reviews the abnormal changes in the levels of LDH and its isozymes in serum and placental tissue and their impact on the pathogenesis of PE and analyzes the molecular mechanisms by which LDH subunits contribute to placental dysfunction through multiple pathways including hypoxia,inflammation,autophagy dysregulation,and cellular damage.In addition,this article discusses the role of lactate,a metabolic product of LDH activity,in the pathogenesis of PE.LDH can be used as a potential biomarker for PE,and the regulation of non-metabolic functions and metabolic reprogramming mediated by LDH provide new targets for the prevention and treatment of PE.

Objective To systematically evaluate the performance and methodological quality of the risk prediction models for urinary incontinence after radical prostatectomy,so as to provide a reference for selecting the appropriate risk prediction tool.Methods A systematic search was conducted in PubMed,Web of Science,Cochrane Library,CINAHL,EMBASE,CNKI,Wanfang,VIP,and Chinese biomedical literature database from inception to Jan.23,2024.Two researchers independently conducted literature screening and data extraction,and the prediction model risk of bias assessment tool(PROBAST)was applied to assess the risk of bias and applicability of the included studies.MedCalc software was used to perform a meta-analysis of the area under curve(AUC)of the validation groups using the random effect model,and the publication bias and sensitivity analysis were also performed.Results A total of 8 studies were included,with a combined sample size of 7 216 cases.Six models reported the AUC values,and 7 models reported calibration.The applicability of 2 studies was acceptable,while 6 were poor.The most commonly used type of prediction model was logistic regression.After excluding models with extreme AUC values,the random-effects meta-analysis result was 0.840(95%confidence interval 0.786 to 0.895),with no heterogeneity(I2=0%,P=0.737).The bias risk was high in all 8 studies,mainly due to retrospective cohort data,transformation of continuous variables into binary variables,unaddressed missing data,selection of predictors based on univariate analysis,incomplete report of the model discrimination and calibration,and lack of external validation.Egger test result indicated no significant publication bias.Conclusion The development and validation process of the existing risk prediction models for urinary incontinence after radical prostatectomy is still imperfect.Future research should construct prediction models based on multicenter and large-sample data,strengthen the clinical applicability assessment of the models,and strictly follow the reporting standards and procedures,so as to establish high-quality risk prediction models for clinical practice.

Objective:Based on a propensity score matchied analysis, the impact of neoadjuvant therapy, namely the transcatheter arterial chemoembolization (TACE) combined with the targeted and immunotherapy, on the prognosis of patients undergoing liver resection for hepatocellular carcinoma (HCC).Methods:Clinical data of 226 patients who underwent surgical resection for HCC of China Liver Cancer (CNLC) stage Ib, IIa, IIb, and IIIa at the Second Affiliated Hospital of Anhui Medical University from February 2020 to December 2024 were retrospectively analyzed, including 201 males and 25 females, aged 64.6±9.4 years. Patients were divided into the neoadjuvant therapy group ( n=25) and the direct surgery group ( n=201). Propensity score matching was used to analyze the liver fibrosis-4 score, platelet count, prothrombin time, activated partial thromboplastin time, and tumor number of the two groups. Postoperative pathological assessment of liver resection was performed. The Kaplan-Meier method was used to analyze the prognosis, and the log-rank test was used to compare the survival rates of the two groups. Results:After propensity score 1: 3 matching, there were no statistically significant differences (all P>0.05) regarding the baseline characteristics of the two groups. Pathological assessment after hepatectomy: the complete pathological response rate was 8% (2/25), and the major pathological response rate was 36% (9/25). The recurrence-free survival rates at 1, 2, and 3 years after surgery in the direct surgery group and the neoadjuvant therapy group were 52.0%, 48.0%, and 42.7% versus 76.0%, 72.0%, and 68.0%, respectively ( χ2=4.76, P=0.029). The overall survival rates at 1, 2, and 3 years after surgery in the direct surgery group and the neoadjuvant therapy group were 80.0%, 78.7%, and 77.3% versus 100.0%, 96.0%, and 96.0%, respectively ( χ2=4.31, P=0.038). Conclusion:Neoadjuvant therapy could reduce the risk of postoperative recurrence and prolong patients survival

OBJECTIVE: To detect and analyze the expression and clinical significance of long non-coding RNA tyrosine kinase non-catalytic region adaptor protein 1-antisense RNA1 (NCK1-AS1) in patients with acute myeloid leukemia (AML). METHODS: 89 AML patients and 23 healthy controls were included from the People's Hospital Affiliated to Jiangsu University. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of NCK1-AS1 and NCK1 in bone marrow samples. The relationship between the expression of NCK1-AS1 and the clinical characteristics of patients were analyzed, as well as the correlation between NCK1-AS1 and NCK1. RESULTS: The expression level of NCK1-AS1 in all AML, non-M3 AML and cytogenetically normal AML (CN-AML) patients was significantly higher than that in the control group (P < 0.01, P < 0.05, P < 0.01, respectively). In non-M3 AML, patients with high NCK1-AS1 expression had a significantly lower hemoglobin level than those with low NCK1-AS1 expression (P =0.036), furthermore, NCK1-AS1 ^high patients had shorter overall survival than NCK1-AS1^low patients (P =0.0378). Multivariate analysis showed that NCK1-AS1 expression was an independent adverse factor in patients with non-M3 AML ( HR =2.392, 95% CI :1.089-5.255, P =0.030). In addition, NCK1 expression was also significantly upregulated in all AML, non-M3 AML and CN-AML patients compared with controls (P < 0.01, P < 0.01, P < 0.001, respectively). There was a certain correlation between NCK1-AS1 and NCK1 expression (r =0.37, P =0.0058). CONCLUSION High expression of NCK1-AS1 in AML indicates poor prognosis of AML patients.
Humans ; Leukemia, Myeloid, Acute/genetics* ; RNA, Long Noncoding/genetics* ; Oncogene Proteins/genetics* ; Adaptor Proteins, Signal Transducing/genetics* ; Prognosis ; Male ; Female ; Middle Aged ; Adult ; Case-Control Studies ; Clinical Relevance