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.

Bladder tumor is a common tumor in the urinary system, posing a serious threat to patients’ health and quality of life. The standard surgical method for non-muscle-invasive bladder cancer is the transurethral resection of bladder tumor. As a new type of minimally invasive treatment, transurethral holmium laser has shown unique advantages in the treatment of bladder tumors. This work introduces the epidemiological characteristics of bladder tumors and the limitations of traditional treatment methods and elaborates on the technical principles, development history of holmium laser and its application status in the treatment of bladder tumors. By analyzing clinical research data, it compares therapeutic effects between holmium laser and other treatment methods. It also presents the key points of surgical techniques, perioperative management strategies, and measures for the prevention and treatment of complications. This research discusses the current technical challenges and future development directions in holmium laser treatment, providing references for clinical practice and research.

Background: Malignant pleural effusion (MPE), a common complication of advanced cancers, is associated with poor prognosis and reduced quality of life. Although host–tumor interactions are known to drive MPE development, the associated immune dynamics during disease progression remain unclear. Using a Lewis lung carcinoma-induced MPE model in C57BL/6JNidfc mice, we systematically evaluated general parameters and immune cell changes at two-day intervals throughout disease progression. Results: The day of Lewis lung carcinoma cell injection into the pleural space was designated as day 0. By day 10 post-injection (p.i.), MPE-bearing mice exhibited ~ 10% body weight loss, marking the experimental endpoint. Pleural tumor mass and pleural effusion volume were minimal up to day 4 p.i. but increased sharply from day 6 onward.CD45⁺ immune cell counts rose over time, and days 6, 8, and 10 p.i. marked key stages of MPE progression. On day 6, B cells, T cells, and natural killer cells, but not macrophages and neutrophils, increased significantly compared to earlier timepoints. By day 8, all immune cell subsets except T cells exceeded day 6 levels, and at day 10, natural killer cell numbers declined while others continued to increase. Besides, the numbers of CD8⁺ T cells, Th1 cells, regulatory T cells, and M2 macrophages progressively increased from day 6 to 10. Based on these data, days 6 and 10 were defined as early and advanced MPE stages, respectively, with distinct immune phenotypes. In advanced MPE, CD8⁺ T cells displayed reduced IFN-γ, TNF-α, Granzyme B, Perforin, FasL, and Ki-67, but upregulated PD-1 and CTLA-4 relative to early stage. Similarly, Th1 cells showed decreased IFN-γ, TNF-α, and IL-2 production along with reduced Ki-67 expression. Advanced-stage M2 macrophages exhibited lower MHC-II levels and impaired phagocytosis, but higher PD-L1 and IL-10 production, while neutrophils showed reduced TNF-α release and phagocytic activity. Conclusions Our findings characterize the temporal immune dynamics associated with MPE progression in a mouse model, revealing a transition from an early immunostimulatory state to a late immunosuppressive state. This study enhances our understanding of MPE immunopathogenesis and provides a foundation for developing precise, stagespecific therapeutic strategies.

ObjectiveTo compare the differences between clinical and environmental sources of Acinetobacter baumannii （AB） at a tertiary hospital in Guangzhou in terms of molecular epidemiological characteristics， antimicrobial resistance， disinfectant tolerance， virulence and the distribution of related genes， as well as plasmid epidemiological characteristics； and to assess the association between environmental and clinical strains and the potential transmission risks associated with environmental contamination. MethodsA total of 118 clinical and 102 environmental AB isolates were collected from a tertiary hospital in Guangzhou between 2024 and 2025. Species identification was performed using mass spectrometry and 16S rRNA sequencing； minimum inhibitory concentrations （MICs） for eight antimicrobial agents were determined using the agar dilution method； biofilm formation capacity was assessed using the crystal violet staining method； A Galleria mellonella infection model was used to evaluate the virulence； whole-genome sequencing was employed for multilocus sequence typing （MLST）， phylogenetic analysis， and studies on the distribution of resistance， disinfectant resistance and virulence genes， and plasmid screening. ResultsA total of 38 known ST types were identified among the 220 AB strains， with ST2 and ST40 being the predominant lineages. Antimicrobial susceptibility testing revealed that the clinical infection group exhibited resistance to minocycline， imipenem and other antibiotics， as well as the tolerance levels to the disinfectants triclosan and benzalkonium bromide， were generally higher than those in the environmental group （P＜0.001）， and the detection rates of drug resistance genes such as bla_OXA-23 and adeB all exceeded 70.0%. Statistical analysis confirmed that the MIC values of TCS and BAB were significantly positively correlated with various antibiotic resistance phenotypes （P＜0.05）. In biofilm experiments， the proportion of strong biofilm-forming strains in the environmental group （64.7%） was significantly higher than that in the clinical infection group （11.9%；χ²=69.06， df=2， P＜0.000 1）， and the mortality rate of the strains increased with enhanced biofilm-forming ability. Furthermore， a total of 41 plasmid lineages and 219 insertion sequences were detected； ISs such as IS1006 and IS1007 were frequently co-occurring with resistance and virulence genes including bla_OXA-23 and katA. ConclusionsThe predominant lineages of AB in this tertiary hospital were ST2 and ST40. The clinical infection group generally exhibits higher levels of antibiotic resistance and tolerance to disinfectants compared to the environmental group， while biofilm-forming ability differs ： the environmental group dominates in strong biofilm formation， and the clinical group dominates in weak to moderate biofilm formation. Plasmids and ISs may be involved in the co-occurrence and dissemination control strategies and for the molecular epidemiological surveillance of multidrug-resistant bacteria.

Objective To analyze the association between relative fat mass index(RFM)and the risk of gallstones in adults.Methods Adult participants from the National Health and Nutrition Examination Survey(NHANES)were included.RFM was calculated based on the participants'height and waist circumference.The history of gallstone disease was obtained through self-reports.The relationship between RFM and the risk of gallstones was assessed using Logistic regression analy-sis,smooth curve fitting and subgroup analysis.Results A total of 4,874 participants were includ-ed in the study.The RFM level of gallstone subjects was significantly higher than that of non-gallstone subjects(P＜0.001).After adjusting for various confounders,RFM level was found to be independ-ently associated with the risk of gallstones(OR=1.095,95％CI:1.022 to 1.173,P=0.010).Smooth curve fitting analysis indicated that the risk of gallstone disease also increased as RFM levels increased.The results of subgroup analysis showed no significant differences in the relationship be-tween RFM and gallstones across different populations.Conclusion Higher RFM level is associated with an increased risk of gallstones in participants.RFM may serve as an economical,effective and convenient indicator for assessing the risk of gallstones,but further prospective studies are required to validate these findings.

OBJECTIVE: To explore the peripheral neural mechanism underlying representation along the distribution of stomach meridian induced by intestinal inflammatory reaction using diarrhea predominant-irritable bowel syndrome (IBS-D) mice. METHODS: Among 62 healthy male C57BL/6 mice of clean grade, 12 mice were randomly selected and divided into a control group and a model group, 6 mice in each group, additionally, 12 mice were randomly selected and divided into a Tianshu group, a Liangqiu group and a Zusanli group, 4 mice in each group. In the model group, citrobacter was administered orally to establish IBS-D model. In the control group and the model group, the visceral pain threshold was observed using fecal colorectal distension (fCRD) induced electromyography of external oblique muscle, the positive cell number of neutrophil in the colonic muscularis was detected by myeloperoxidase (MPO) staining, the number, location and distribution rule of Evans blue (EB) extravasation points were observed by injection of EB staining solution into the tail vein. In the Tianshu group, the Liangqiu group and the Zusanli group, fluorescent dye Dil was injected at bilateral "Tianshu" (ST25), "Liangqiu" (ST34) and "Zusanli" (ST36) respectively, to observe the dye-positive cell number in different dorsal root ganglion (DRG) segments. In the control group and the model group, the activation of satellite glial cells (SGCs) in different DRG segments was observed by immunofluorescence. RESULTS: Compared with the control group, in the model group, the area under curve of electromyography of external oblique muscle was increased at fCRD of 25, 50 and 75 μL distilled water (P<0.001, P<0.01); the MPO-positive cell number of neutrophil in the colonic muscularis was increased (P<0.01). Few EB extravasation points could be found in the control group, while there were much more EB extravasation points observed in the model group, which was specially distribution in the area of stomach meridian, from "Huaroumen" (ST24) to "Zusanli" (ST36), as well as the surface area dominated by L₂-L₅ segment of the spinal cord. The Dil-positive cells were mainly exhibited in the DRG of T₁₁, L₅ and L₄ segments in the Tianshu group, the Liangqiu group and the Zusanli group, respectively. Compared with the control group, the ratio of glial fibrillary acidic protein (GFAP)/glutamine synthetase (GS) co-expression was increased in the DRG of T₁₁, L₄ and L₅ segments in the model group (P<0.05, P<0.01). CONCLUSION The activation of SGCs within DRG of T₁₁, L₄ and L₅ segments may relate closely to the occurrence of the representation along the stomach meridian distribution in IBS-D mice.
Animals ; Male ; Mice ; Irritable Bowel Syndrome/therapy* ; Mice, Inbred C57BL ; Meridians ; Stomach/physiopathology* ; Humans ; Acupuncture Points ; Disease Models, Animal

OBJECTIVE: Poxviruses are zoonotic pathogens that infect humans, mammals, vertebrates, and arthropods. However, the specific role of ticks in transmission and evolution of these viruses remains unclear. METHODS: Transcriptomic and metatranscriptomic raw data from 329 sampling pools of seven tick species across five continents were mined to assess the diversity and abundance of poxviruses. Chordopoxviral sequences were assembled and subjected to phylogenetic analysis to trace the origins of the unblasted fragments within these sequences. RESULTS: Fifty-eight poxvirus species, representing two subfamilies and 20 genera, were identified, with 212 poxviral sequences assembled. A substantial proportion of AT-rich fragments were detected in the assembled poxviral genomes. These genomic sequences contained fragments originating from rodents, archaea, and arthropods. CONCLUSION Our findings indicate that ticks play a significant role in the transmission and evolution of poxviruses. These viruses demonstrate the capacity to modulate virulence and adaptability through horizontal gene transfer, gene recombination, and gene mutations, thereby promoting co-existence and co-evolution with their hosts. This study advances understanding of the ecological dynamics of poxvirus transmission and evolution and highlights the potential role of ticks as vectors and vessels in these processes.
Animals ; Poxviridae/physiology* ; Ticks/virology* ; Phylogeny ; Transcriptome ; Evolution, Molecular ; Poxviridae Infections/virology* ; Genome, Viral

Objective To investigate the effect of the structure of 3D-printed silk fibroin/hydroxypropyl methylcellulose(SF/HPMC)scaffolds on the growth of tracheal epithelial cells in vitro.Methods Six types of SF/HPMC scaffolds with different surface topography,pore size,and porosity were fabricated using a 3D printer by adjusting the concentration of SF/HPMC solutions and printing parameters,combined with freeze-drying.Normal human bronchial epithelial cell lines BEAS-2B were cultured on these scaffolds for 7 days.The cell proliferation was detected by CCK-8 assay and live/dead cell staining,and the cell morphology was observed by scanning electron microscopy(SEM).Results The porosity of 20%(weight percentage)SF/HPMC scaffolds with rough surface and smooth surface were 70.5%±2.0%and 65.5%±6.1%,respectively,and the porosity of 30%(weight percentage)SF/HPMC scaffolds with rough surface and smooth surface were 63.9%±2.1%and 59.6%±2.1%,respectively.The two pore sizes of the rough-surfaced 20%SF/HPMC scaffolds were(443.9±104.1)μm and(681.1±115.1)μm.BEAS-2B cells spread better on the rough-surfaced scaffolds,and their proliferation was higher on scaffolds with higher porosity and smaller pore sizes compared to those with lower porosity and larger pore sizes.Conclusion The 3D-printed SF/HPMC scaffolds are suitable for bronchial epithelial cell growth.Scaffolds with rough surfaces,higher porosity,and appropriate pore sizes might facilitate BEAS-2B cell growth.

Objective:By analyzing the genetic risk of triglyceride-glucose index(Tyg)and insulin resistance(IR)for cardiovascular disease(CVD), to elucidate the extent to which the contribution of Tyg to the risk of CVD development is influenced by IR genetic risk.Methods:In this study, we selected data from a cohort of elderly people in the Kunshan community, screened 7, 385 individuals with both clinical and genomic data, and calculated the polygenic risk score of insulin resistance(IRPRS)for each participant based on publicly available IR genome-wide association data, and assessed the effect of genetic risk and Tyg level on the risk of developing CVD using a multivariate Cox proportional risk model.Calculating interactions to assess the effects of genetic risk and Tyg levels on the risk of developing CVD, the effects of Tyg tertile grouping and IRPRS on the risk of developing CVD were assessed using a multivariate Cox proportional risk model, and subgroup analyses were performed for gender to assess the effects of Tyg tertile grouping and IRPRS on the risk of developing CVD by gender.Results:In the univariate Cox model, Q3 and IRPRS with the highest TYG levels were significantly associated with the risk of CVD, respectively( HR=1.59, 95% CI: 1.33-1.89; P<0.001; HR=1.61, 95% CI: 1.18-2.20; P=0.003).After adjusting for multiple confounders, the Q3 Group with the highest TYG level was still significantly associated with the risk of CVD( HR=1.28, 95% CI: 1.05-1.57; P=0.014), the Association of TYG with the risk of CVD did not change significantly( HR=1.29, 95% CI: 1.05-1.57; P=0.014).We conducted a subgroup analysis by sex and found that among older men, 13, the highest levels of TYG and IRPRS were significantly associated with CVD risk, respectively( HR=1.70, 95% CI: 1.31.2.20; P<0.001; HR=1.98, 95% CI: 1.24-3.15; P=0.004).After adding IRPRS to the model, the Association of TYG with the risk of CVD remained unchanged( HR=1.69, 95% CI: 1.31-2.19; P<0.001).After adjusting for various confounders, Tyg remained significantly associated with the risk of CVD( HR=1.39, 95% CI: 1.04-1.88; P=0.028), the results showed that TYG remained significantly associated with the risk of CVD( HR=1.41, 95% CI: 1.05-1.90; P=0.023), and the association did not decrease.No Association of IRPRS with CVD risk was found in older women. Conclusions:IRPRS and TYG are the risk factors of CVD, and diet, exercise, drugs and other external factors on TYG are the main risk factors of CVD.For individuals with high genetic factors, the risk of CVD can still be reduced by lifestyle adjustments such as diet, exercise and drug intervention.

Objective:To investigate the current status of maximum tongue pressure (MTP) in cardiac surgery inpatients and analyze its influencing factors, providing a basis for developing personalized nursing measures for high-risk groups.Methods:This cross-sectional study used a convenience sampling method to select cardiac surgery inpatients at Zhongshan Hospital, Fudan University, from January 2022 to April 2023. General and clinical data questionnaires, a swallowing tongue muscle evaluation training device, and a hand dynamometer were used for data collection. The random forest model and Lasso regression were employed to identify key influencing factors, and multiple linear regression was used to analyze the factors affecting MTP.Results:A total of 501 cardiac surgery inpatients meeting the inclusion and exclusion criteria were enrolled, including 308 males and 193 females, with a mean age of (56.94 ± 14.02) years. The mean MTP was (45.92 ± 9.57) kPa. When the lambda (λ) value was 0.181, the model achieved the best fit, identifying 10 key influencing factors in descending order of importance: age, handgrip strength, gender, BMI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), glomerular filtration rate, cardiac function grade, hemoglobin, history of stroke, and history of atrial fibrillation. Age, handgrip strength, low-level BMI, NT-proBNP, and history of stroke were determined as significant factors influencing MTP in cardiac surgery inpatients ( R2 = 0.324, F = 24.92, P<0.05). Conclusions:Nurses should pay close attention to the tongue muscle strength of cardiac surgery inpatients. Early assessment of MTP is essential for older patients, those with low handgrip strength, low BMI, elevated NT-proBNP, or a history of stroke. Targeted early identification and pre-rehabilitation measures should be implemented for patients with weakened tongue muscle strength.