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: To investigate the barrier membrane fixation performance and enhanced guided bone regeneration (GBR) capability of a thermosensitive adhesive containing bioactive glass nanoparticles in order to provide a novel solution for membrane fixation during GBR procedures. Methods: M2NP@BGN (methoxyethyl acrylate-co-N-isopropylacrylamide-co-protocatechuic acid@Bioactive glass nanoparticle), a thermosensitive adhesive, was synthesized via free radical polymerization by compositing methoxyethyl acrylate, N-isopropylacrylamide, and protocatechuic acid into a basic adhesive that was modified with bioactive glass nanoparticle (BGN). The successful fabrication of basic adhesive M2NP was characterized by attenuated total reflection-Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The thermosensitive adhesive M2NP@BGN (BGN concentration of 1 mg/mL) was characterized by scanning electron microscopy and a rheometer. By adjusting the BGN concentration (0.1 mg/mL, 0.5 mg/mL, 1 mg/mL, and 2 mg/mL), the adhesive and mechanical strengths were investigated with a universal testing machine. Biocompatibility was evaluated with a cell counting kit-8 assay and hemolysis test to identify the optimal formulation. The optimal material’s extract was co-cultured with mouse bone marrow mesenchymal stem cells, and its osteogenic activity was examined in vitro by quantitative real-time PCR, alkaline phosphatase, and alizarin red S staining. The rat mandibular defect model was established, filled with bone graft, and divided into 3 groups based on membrane fixation method: M2NP@BGN (BGN concentration of 1 mg/mL) fixation group (M2NP@BGN), titanium nail fixation group (Nail), and unfixed control group (Negative). Bone regeneration was analyzed after 8 weeks by micro computed tomography and histological staining. Results: M2NP@BGN (BGN concentration of 1 mg/mL) was successfully synthesized and demonstrated rapid gelation under warm, humid conditions. The adhesive with a BGN concentration of 1 mg/mL exhibited the highest adhesive strength (P < 0.001) and significantly enhanced mechanical strength (P < 0.001) under 37℃ wet conditions. All formulations showed excellent biocompatibility, with cell viability > 80% and hemolysis ratio < 5%. M2NP@BGN (BGN concentration of 1 mg/mL) significantly upregulated the expression of Runx2 and Col I (P < 0.001) and enhanced the activity of osteogenic differentiation markers (P < 0.05). In the animal model, the M2NP@BGN group (BGN concentration of 1 mg/mL) achieved significantly higher bone volume fraction and better bone maturity compared to the negative and nail groups (P < 0.05). Conclusion M2NP@BGN (BGN concentration of 1 mg/mL) combines excellent wet adhesion with potent osteogenic activity, enhances the bone augmentation efficacy of membranes, and presents a novel fixation strategy with significant clinical translation potential for GBR therapy.

Objective To systematically review and quantitatively analyze the safety of biologic agents for the clinical treatment of psoriasis during pregnancy and lactation.Methods The literature from start of database to June 27,2023,was searched in MEDLINE(PubMed),Embase,Cochrane Library,and Web of Science by two researcher.Quality of included studies was assessed by the quality evaluation tool of case series from Australian JBI Evidence Based Healthcare Centre.According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA),a systematic review and was conducted to assess pregnancy or breastfeeding outcomes in psoriasis patients exposed to biologics within 3 months prior to pregnancy,during pregnancy or breastfeeding.Data on pregnancy and exposure characteristics were pooled,and the prevalence of adverse pregnancy outcome was summarized using a random effects model.Results A total of 54 studies involving 1206 pregnancies in 1177 female patients with psoriasis exposed to biologic agents were included in the analysis.Systematic review results demonstrated that the majority of the exposures were limited to early pregnancy,with pooled spontaneous abortion rates,elective abortion rates,overall mortality,preterm birth rates,incidence of low birth weights,and congenital anomalies similar to those of general population(P>0.05).Furthermore,no serious adverse reactions were reported during lactation.Conclusions The use of biologic agents in pregnant and breastfeeding women with psoriasis does not significantly increase the risk of adverse pregnancy outcomes and does not affect neonatal health or growth.However,the limited available safety data underscores the necessity of further studies to establish the relationship between psoriasis,biologic agents,and pregnancy/lactation outcomes,thereby providing comprehensive guidance for clinical practice.

Objective To develop a novel drainage catheter based on the anatomical structure of the mammary duct and establish a non-invasive treatment protocol for patients with acute high-tension breast milk cyst during lactation.Methods Ten primiparous patients with acute high-tension breast milk cyst during lactation,admitted to the postpartum clinics of three hospitals,were enrolled as study subjects.A novel drainage catheter was prepared using an epidural anesthesia catheter,and intubation was performed to unblock the obstructed mammary ducts.For cases with intubation failure,puncture as-piration was employed.Local cold compresses were applied to the breasts after treatment.Results Out of 10 patients,6 were successfully unblocked(successful group),and 4 failed(failure group).The duration of illness in the successful group was(6.00±0.82)days,which was shorter than that in the failure group[(9.50±1.80)days](P＜0.05).The insertion depth of the catheter in the successful group was(6.42±0.67)cm,which was greater than that in the failure group[(4.00±0.71)cm](P＜0.05).There was no statistically significant difference in cyst diameter between the two groups(P＞0.05).For patients in whom unblocking failed,puncture aspiration was performed,and 3 of them experienced recurrence after the initial puncture.Ultrasound-guided re-puncture aspiration and weaning were performed.One patient with evident inflammatory symptoms was administered systemic antibiotic therapy.After treatment,7 patients resumed lactation,and follow-up results indicated that all 10 patients were cured.Conclusion Acute high-tension breast milk cyst during lactation is rela-tively rare in clinical practice.The novel drainage catheter can achieve non-invasive unblocking of distally obstructed mammary ducts in the lactiferous sinus.The comprehensive treatment protocol can improve the overall cure rate and result in a high rate of resumed lactation post-treatment.

OBJECTIVE To investigate the application value of narrow-band CE-Chirp ASSR(NB CE-Chirp ASSR)and modulated acoustic ASSR in the assessment of hearing threshold in children with hearing impairment.METHODS Forty-eight children with sensorineural hearing loss were tested by pure tone audiometry(PTA),NB CE-Chirp ASSR and modulated acoustic ASSR.According to the results of pure tone audiometry,they were divided into mild to moderate group(48 ears)and severe to profound group(48 ears).The difference and correlation between pure tone hearing threshold and ASSR response threshold of different stimuli were compared between 500-4 000 Hz.RESULTS The absolute differences between the NB CE-Chirp ASSR response threshold and the PTA threshold in 48 children were all smaller than the differences between the modulated acoustic ASSR response threshold and the PTA threshold,and the differences were statistically significant(P<0.001).Under the same stimulus sound,the absolute difference between ASSR response threshold and pure tone hearing threshold in the mild to moderate group was higher than that in the severe to very severe group.The correlation coefficients between NB CE-Chirp ASSR threshold and pure tone hearing threshold are higher than those between modulated sound ASSR threshold and pure tone hearing threshold at 500-4 000 Hz.The test time of NB CE-Chirp ASSR[(20.92±9.33)min]was significantly shorter than that of modulated acoustic ASSR[(33.68±10.97)min](P=0.004).CONCLUSION NB CE-Chirp ASSR can more accurately assess the hearing threshold of children with different degrees of hearing loss than modulated acoustic ASSR.

Objective: To investigate the situation and influencing factors of school bullying experienced by primary and middle school students, so as to provide the basis for formulating school bullying intervention measures and promoting students' physical and mental health development. Methods: All the counties (cities, districts) in Zhejiang Province were stratified to urban and suburban areas, primary, junior high and senior high school students were selected using a stratified cluster sampling method. Basic information, lifestyle and school bullying were collected through questionnaire surveys. Factors affecting school bullying experienced by primary and middle school students were analyzed using a multivariable logistic regression model. Results: Totally 137 846 valid questionnaires were recovered, with an effective recovery rate of 97.17%. There were 72 526 males (52.61%) and 65 320 females (47.39%). There were 47 561 primary school students (34.50%), 47 701 junior high school students (34.61%) and 42 584 senior high school students (30.89%). A total of 3 987 students suffered from school bullying, accounting for 2.89%. The proportions of being maliciously teased, being intentionally excluded from group activities/isolated, being teased about physical defects or appearance, being hit/kicked/pushed/shoved/locked in a room, being threatened, and being extorted for money were 2.04%, 1.18%, 1.11%, 0.86%, 0.84% and 0.83%, respectively. Multivariable logistic regression analysis showed that the students who were males (OR=1.122, 95%CI: 1.048-1.202), lived in suburban areas (OR=1.322, 95%CI: 1.233-1.418), lived in areas with medium (OR=1.086, 95%CI: 1.006-1.173) or underdeveloped (OR=1.298, 95%CI: 1.191-1.415) economic level, had higher academic levels (junior high school, OR=1.380, 95%CI: 1.270-1.499; senior high school, OR=1.210, 95%CI: 1.083-1.351), lived on campus (OR=1.489, 95%CI: 1.372-1.616), engaged in fights (OR=6.029, 95%CI: 5.585-6.509), attempted to smoke (OR=1.320, 95%CI: 1.128-1.545), drank (OR=1.735, 95%CI: 1.575-1.912), were scolded and beaten by parents (OR=1.972, 95%CI: 1.822-2.135) and were obese (OR=1.240, 95%CI: 1.132-1.360) were more likely to experience school bullying. Conclusion The harm of school bullying to the physical and mental health of primary and middle school students should be taken seriously, and active policy measures should be adopted to strengthen intervention.

OBJECTIVE: To explore the results of four types of Urea cycle disorders (UCDs) in newborns from the Xuzhou region, assess the efficacy of newborn screening by tandem mass spectrometry (MS/MS), and analyze their genetic characteristics. METHODS: A retrospective analysis was performed using tandem mass spectrometry to screen for inherited metabolic disorders in 691 712 newborns at the Maternal and Child Health Care Hospital of Xuzhou from November 2015 to December 2023. Ten children (cases 1-10) were diagnosed with Ornithine transcarbamylase deficiency (OTCD), Carbamoylphosphate synthase 1 deficiency (CPS1D), Arginase deficiency (ARGD), and Argininosuccinate synthase deficiency (ASSD) based on MS/MS and genetic testing. This study was approved by the Medical Ethics Committee of Xuzhou Maternity and Child Health Care Hospital (Ethics No.XZFY2024-051K-01J). RESULTS: A total of 691 712 neonates were screened for UCDs using MS/MS, which identified 1 237, 1 237, 510, and 1 009 initial positive cases for OTCD, CPS1D, ASSD, and ARGD, respectively. After genetic testing, 1 case of OTCD, 1 case of CPS1D, 1 case of ASSD, and 7 cases of ARGD were confirmed. The overall positive predictive value for these four UCDs was 0.362%. Among the 10 diagnosed UCD cases, four novel variants were identified, which included OTC: c.1024C>A (p.L342M) and ASS1: c.826A>G (p.M276V), c.695C>T (p.P232L) and c.694C>T (p.P232S). Bioinformatic analysis has rated these as variants of uncertain clinical significance or likely pathogenic based on guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION The incidence of four UCDs in neonates from the Xuzhou area is relatively low, and there is a correlation between genetic variants and clinical phenotypes. For novel variants with uncertain clinical significance or suspected pathogenicity, their pathogenicity should be clarified in conjunction with clinical and biochemical indicators. The four novel pathogenic variants of UCDs identified in this study have enriched the mutational spectrum of UCDs-associated genes in the Xuzhou region.
Humans ; Infant, Newborn ; Tandem Mass Spectrometry/methods* ; Urea Cycle Disorders, Inborn/diagnosis* ; Neonatal Screening/methods* ; Genetic Testing/methods* ; Female ; Retrospective Studies ; Male ; Ornithine Carbamoyltransferase Deficiency Disease/diagnosis* ; Mutation ; Carbamoyl-Phosphate Synthase (Ammonia)/genetics* ; Ornithine Carbamoyltransferase/genetics*

Objective:To analyze the multimorbidity trends and influencing factors of internet addiction and depressive symptoms among middle school students in Zhejiang Province.Methods:From 2018 to 2023, a multistage stratified random cluster sampling method was used to select middle school students aged 12 to 18 in Zhejiang Province. Internet addiction and depression status were measured by the Internet Addiction Scale and the Center for Epidemiologic Studies Depression Scale. When both symptoms were present, it was defined as multimorbidity.The multivariate logistic regression model was used to analyze the influencing factors of multimorbidity among middle school students, and a trend Chi-square test was used to analyze the changing trends of internet addiction, depression and multimorbidity prevalence. Results:A total of 193 505 students were included in the study. From 2018 to 2023, the prevalence of multimorbidity of internet addiction and depressive symptoms among middle school students ranged from 2.7% to 3.5%. The prevalence of internet addiction ranged from 4.7% to 6.0%, while the prevalence of depressive symptoms ranged from 18.7% to 25.1%. Multivariate logistic regression showed that boarding students ( OR=1.34 , 95% CI: 1.26-1.42), low-frequency ( OR=1.59, 95% CI: 1.46-1.73), and high-frequency sugary drink consumption ( OR=3.91, 95% CI: 3.55-4.31) increased the risk of multimorbidity among middle school students. In contrast, higher frequencies of moderate-to-high-intensity exercise (medium: OR=0.54, 95% CI: 0.50-0.58; high: OR=0.49, 95% CI: 0.44-0.55) and sufficient sleep ( OR=0.52, 95% CI: 0.49-0.56) were protective factors. From 2018 to 2023, there was no significant change in the trend of multimorbidity prevalence among middle school students ( χ2trend=3.82, P=0.051). The prevalence of internet addiction showed an upward trend ( χ2trend=20.54, P<0.001), while depressive symptoms showed a downward trend ( χ2trend=181.41, P<0.001). Conclusion:The prevalence of internet addiction and depression symptoms among middle school students in Zhejiang Province remains stable from 2018 to 2023. The prevalence of internet addiction shows an upward trend, while the prevalence of depression symptoms shows a downward trend. The risk of multimorbidity is related to students′ boarding, consumption of sugary drinks, lack of exercise, and insufficient sleep.

Aim To explore the mechanisms of PM2.5 exposure exacerbating bleomycin(BLM)-induced idio-pathic pulmonary fibrosis(IFP)by regulating ferropto-sis via nuclear factor 2 related factor 2(Nrf2)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase(GPX)4 axis.Methods Forty C57BL/6J mice were randomized into the control,BLM,PM2.5,BLM+PM2.5 and sulforaphane(SFN,Nrf2 agonist)groups,with eight mice in each group.PM2.5 expo-sures were conducted to the BLM-induced IPF mice for two weeks.The lung function was measured,and the content of hydroxyproline(HYP)in lung tissue and the pathomorphology of lungs were observed.Reactive oxygen species(ROS),malondialdehyde(MDA),ferrous ion(Fe2+)and glutathione(GSH)of the lung tissue were measured by ELISA.The mRNA and pro-teins levels of Nrf2,SLC7A11,GPX4,collagen typeⅠ(COL-1),α-smooth muscle actin(α-SMA)were measured by quantitative polymerase chain reaction(qPCR)and Western blot.Results Compared with the control group,the lung function of mice was signif-icantly reduced(P＜0.01)in the BLM and PM2.5 groups,while lung tissue showed the characteristic pathological changes of pulmonary fibrosis such as a large number of inflammatory cell infiltration,alveolar wall fracture,thickening,collagen deposition,and sig-nificantly increased HYP,Fe2+,ROS,MDA(P＜0.05,P＜0.01),genes and proteins of COL-1,α-SMA(P＜0.01);and decreased GSH,Nrf2,SLC7A11,GPX4 genes and proteins(P＜0.05,P＜0.01).The above-mentioned lesions were markedly aggravated in the BLM+PM2.5 group compared with the BLM(P＜0.05)and PM2.5 groups(P＜0.01),and were also improved in the SFN group(P＜0.05,P＜0.01).Conclusions PM2.5 exposures can exac-erbate IPF-induced IPF in mice,and the regulating of Nrf2/SLC7 A1 1/GPX4 axis and ferroptosis might be in-volved in the related mechanisms.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.