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 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 understand the clinical applicability and implementation of expert consensus on the implementation and removal of protective restraints in psychiatry,and to provide references for promoting the standardized practice of psychiatric protective restraints and updating the consensus.Methods By the convenience sampling method,a questionnaire survey was conducted among nurses from 480 hospitals in 30 provinces from June 15 to July 15,2024.The survey was conducted using the instrument for evaluating clinical applicability of guide-lines(version 2.0)and a self-compiled questionnaire on the clinical implementation of the restraint consensus.Results A total of 7,844 valid questionnaires were collected,with a valid questionnaire recovery rate of 93.78％.The results of clinical applicability scoring showed that the consensus had the lowest availability score(64.72％)and the highest acceptability score(76.74％).The results showed that nurses' receiving training and the level of their hospitals were the main influencing factors for scores in various dimensions(P＜0.05).4,774 participants(87.42％)believed that the application of consensus could enhance the standardization of nurses' restraint operations.The safety rate of the restraint consensus was 79.51％,and the economic ratio was 76.87％.Among the evaluators,1,739(22.17％)believed that there were implementation obstacles in the consensus.Conclusion The clinical applicability of the consensus is relatively good,and the application of the consensus helps to improve the standardization of clinical operations.In the future,efforts should be made to strengthen the promotion and training of the consensus,develop hierarchical promotion strategies according to the characteristics of medical institutions,and improve the quality of evidence for the consensus,so as to further enhance the clinical application effect of the consensus.

Objective:To compare the clinical outcomes of arthroscopic Y-shaped suture suspension fixation and those of open reduction and internal fixation in the treatment of tibial insertion avulsion fractures of the posterior cruciate ligament (PCL).Methods:A retrospective study was conducted to analyze the clinical data from the 23 patients with PCL tibial avulsion fracture who had been admitted to Department of Sports Medicine, The Affiliated Changsha Central Hospital, University of South China, from May 2018 to May 2024. There were 15 males and 8 females with an age of (39.0±15.6) years. By the Meyers-McKeever classification, there were 20 cases of type Ⅱ and 3 cases of type Ⅲ. All patients were divided into 2 groups based on their different surgical schemes: an arthroscopic group of 11 cases treated with Y-shaped suture suspension fixation under arthroscopy and an open group of 12 cases treated with open reduction and internal fixation. The surgical time, intraoperative blood loss, and visual analog scale (VAS) pain scores, Lysholm knee function scores, and International Knee Documentation Committee (IKDC) subjective scores at 1 month after surgery and the last follow-up were recorded and compared between the 2 groups.Results:There was no statistically significant difference in the preoperative general information between the 2 groups, indicating comparability ( P>0.05). The 23 patients were followed up for (13.7±3.8) months after surgery. None of the patients experienced complications like incision infection, neurovascular damage, nonunion or delayed union of fracture. In the arthroscopic group, the surgical time was (97.1±11.1) min, significantly shorter than that in the open group [(64.7±9.0) min], and the intraoperative blood loss (14.9±6.6) mL, significantly less than that in the open group [(29.4±13.2) mL] ( P<0.05). At 1 month after surgery, the VAS pain score, Lysholm knee function score, and IKDC subjective score in the arthroscopic group were, respectively, 3.0 (2.0, 3.0) points, (72.0±4.8) points, and (67.3±2.9) points, all significantly better than those in the open group [5.0 (4.0, 5.0) points, (66.9±4.0) points, and (63.1±2.4) points] ( P<0.05). There was no statistically significant difference in the VAS pain score, Lysholm knee function score, or IKDC subjective score at the last follow-up between the 2 groups ( P>0.05). Conclusions:Both arthroscopic Y-shaped suture suspension fixation and open reduction and internal fixation can achieve satisfactory treatment outcomes for PCL tibial avulsion fractures. The latter shows an advantage in shorter surgical time, but the former advantages in less bleeding volume and better early efficacy.

The liver is the largest visceral organ in the human body, responsible for multiple important functions such as metabolism, detoxification, nutrient storage, and immune regulation. Hepatocytes located along the portal-central vein axis have heterogeneity in gene expression and function, which led to the concept of liver zonation. Cells in different regions play different roles in metabolic processes, and the coordination and cooperation between these cells are crucial for maintaining normal liver function. In recent years, the advancements in single-cell genomics and spatial transcriptomics technologies have significantly improved our understanding of liver zonation. This article summarizes the important role of metabolic zonation in maintaining liver function and its relationship with disease and aging, providing a theoretical basis for further research and therapeutic strategies.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

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.

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 spinal cord morphological changes and risk factors in upper cervical spine surgery using C 2 medial "in-out-in" pedicle screws in patients with atlantoaxial dislocation (AAD) and high-riding vertebral artery (HRVA). Methods:A retrospective analysis was conducted on 41 patients with AAD who underwent C 2 medial "in-out-in" pedicle screw implantation at our hospital between January 2019 and December 2023. The cohort included 12 males and 29 females, with a mean age of 47.6±10.3 years (range: 18-68 years). Among them, 30 patients received unilateral C 2 medial "in-out-in" screws, while 11 patients received bilateral screws. All patients underwent posterior reduction and internal fixation. Measurements included C 2 pedicle height, C 2 pedicle width, C 2 horizontal spinal canal width, screw invasion distance into the spinal canal, and spinal canal invasion rate based on CT findings. MRI evaluations included spinal canal-dura mater distance, dura mater-spinal cord distance, spinal canal-spinal cord distance, and spinal cord cross-sectional area. The change rate of spinal cord cross-sectional area was calculated and categorized into >20% decrease group (decreasing group) and ≤20% decrease group (non-decreasing group). Postoperative outcomes were assessed using the Visual Analogue Scale (VAS) and Japanese Orthopedic Association (JOA) scores. Results:The mean operative time was 165.5±30.1 minutes (range: 120-220 minutes). No spinal cord vascular injuries or severe complications were observed. However, five patients experienced cerebrospinal fluid (CSF) leakage, requiring delayed removal of drainage tubes, but their wounds healed successfully. Follow-ups (range: 6-24 months) showed no loosening of internal fixation, fractures, or bone graft nonunion, with a 100% bone fusion rate at 6 months postoperatively. VAS scores improved significantly from a preoperative median of 5.0 (3.5, 6.0) (range: 1-7) to 2.0 (2.0, 3.0) at 3 months and 1.0 (1.0, 1.0) at 6 months ( Z=36.716, P< 0.001). JOA scores improved from 10.0 (9.0, 12.0) (range: 4-14) preoperatively to 13.0 (11.0, 13.5) at 3 months and 14.0 (12.0, 15.0) at 6 months ( Z=67.093, P<0.001). The height of C 2 pedicle was 5.50±1.78 mm, the width of C 2 pedicle was 2.27±1.23 mm, the width of C 2 horizontal spinal canal was 23.76±4.91 mm, the spinal canal-dura mater distance was 3.08±0.85 mm, dura mater-spinal cord distance was 3.23±0.85 mm, the spinal canal-spinal cord distance was 6.31±1.11 mm, the distance of screw invasion into the spinal canal was 2.80±1.54 mm, the rate of spinal canal invasion was 12.1%±6.8%, the preoperative spinal cord cross-sectional area was 69.81±13.27 mm 2, and the postoperative spinal cord cross-sectional area was 68.81±13.94 mm 2. Based on spinal cord cross-sectional area changes, 32 patients were classified into the non-decreasing group, and 9 patients into the decreasing group. The intraclass correlation coefficient (ICC) values ranged from 0.733 to 0.984, indicating high measurement reliability. There were significant differences in the proportion of C 2 bilateral medial "in-out-in" screws (χ 2=6.903, P=0.009), the incidence of CSF leakage (χ 2=15.391, P<0.001), the distance of screw invasion into the spinal canal ( t=4.990, P<0.001) and the rate of spinal canal invasion ( t=4.045, P<0.001) in the decreasing group versus the non-decreasing group. The JOA scores of the non-decreasing group were significantly higher at 3 and 6 months postoperatively compared to the decreasing group ( P<0.05). No other parameters showed significant differences between the groups. Binary logistic regression analysis identified spinal canal invasion rate [ OR=1.963, 95% CI (1.010, 3.817), P=0.047] as an independent risk factor for spinal cord cross-sectional area reduction. The Jordan index was 0.875, with a spinal canal invasion rate threshold of 14.18%, a sensitivity of 1.000, a specificity of 0.875, and an AUC of 0.983, indicating strong predictive value. Conclusion:The C 2 medial "in-out-in" screw technique provides effective posterior fixation and fusion for AAD patients with HRVA. However, to minimize spinal cord morphological changes and associated risks, the spinal canal invasion rate should be kept below 14.18% when using this technique.

Prolactin, a peptide hormone primarily synthesized and secreted by lactotrophs in the anterior pituitary gland, plays key roles in lactation, reproduction, and immune regulation. Recent research has highlighted its critical involvement in maintaining metabolic homeostasis, with both elevated and deficient levels disrupting metabolic functions such as glucose and lipid metabolism, as well as energy regulation. This study reviews recent advancements in prolactin and its receptors′ role in metabolic regulation, emphasizing its pivotal contribution to metabolic homeostasis.