Objective: To assess the status of sexual behaviors, HIV/AIDS knowledge awareness, and novel synthetic drug use among school attending young students in Guangdong Province, so as to provide evidence base for formulating targeted intervention strategies. Methods: From September to December 2024, a convenience sampling method was employed to conduct an anonymous online survey among 41 119 students from 20 higher education institutions and vocational colleges in Guangdong Province. Chi square test was utilized for rate comparisons and univariate analysis, and a multivariate Logistic regression model was applied to analyze factors associated with novel synthetic drug use. Results: The self reported rate of sexual behavior was 5.2%. Among sexually active students, the rates of unprotected sexual intercourse, having temporary sexual partners, and having commercial sexual partners were 32.4%, 34.5%, and 26.3%, respectively. The awareness rate of HIV related knowledge was 75.7%. The overall use rate of novel psychoactive substances(NPS) was 1.0%, and among sexually active students it was 6.5%. Multivariate Logistic regression analysis showed that students with sexual experience ( OR =4.15) and those with HIV testing history ( OR =9.38) had higher risks of NPS use; among sexually active students, those with unprotected sexual intercourse ( OR =6.83) and those with commercial sexual partners ( OR = 4.68 ) had higher risks of NPS use (all P <0.05). Conclusions The HIV/AIDS knowledge level among surveyed students needs further improvement, and high risk sexual behaviors are cross linked with novel synthetic drug use. It is recommended to carry out integrated health education for all students and implement comprehensive targeted interventions for sexually active students.

Objective To introduce the calculation of the DISO index in multi-dimensional data ranking for disease surveillance, and evaluate its applicability. Methods Using the data from the quality supervision and inspection of infectious disease reporting in Jingzhou City in a certain year as an example, the DISO index was used to rank 16 investigated medical institutions and compared with the TOPSIS method. The consistency between the two evaluation results was analyzed using Spearman correlation. Then, The DISO index from different medical institutions was used to evaluate the ranking of 8 counties (cities, districts). The evaluation indicators for the supervision and inspection included six items: report rate, timely report rate, completeness of report card filling, accuracy of report card filling, consistency rate with network information report, and completeness of valid ID number filling. Results Among the 16 medical institutions, 8 institutions had all six evaluation indicators at 100%. Using the two methods to rank the 16 medical institutions, the two methods showed that the 8 medical institutions with all six evaluation indicators at 100% were ranked first. There was a strong correlation between the rankings of the 16 medical institutions using the two methods (r_s=0.992, P=0.000). The three counties (cities, districts) with all six evaluation indicators at 100% were all ranked first, while country G was ranked seventh and country E was ranked eighth. Conclusion The results of the DISO index and the TOPSIS method were similar in one-dimensional ranking. DISO can be used for multi-dimensional ranking of disease surveillance data and deserves to be promoted and applied.

ObjectiveTo evaluate the therapeutic effect of Shenji Guben prescription （SJGB） on chronic obstructive pulmonary disease （COPD） in mice and to explore its potential therapeutic mechanism via transcriptomics. MethodsA mouse model of COPD was established by combined exposure to lipopolysaccharide （LPS） and cigarette smoke. C57BL/6J mice were randomly allocated into a control group， a model group， an acetylcysteine （78 mg·kg^-1·d^-1） group， and low- （7.5 g·kg^-1·d^-1）， medium- （15 g·kg^-1·d^-1）， and high-dose （30 g·kg^-1·d^-1） SJGB groups. After 13 weeks of modeling， oral administration was initiated and continued for 28 days. The therapeutic effects of SJGB were assessed based on body weight， lung function， lung tissue pathology， and inflammatory factors in bronchoalveolar lavage fluid （BALF）. Ultra-high performance liquid chromatography-tandem mass spectrometry （UHPLC-MS/MS） was employed to identify the active ingredients in SJGB. Transcriptomic profiling of lung tissue was performed by RNA-seq to identify differentially expressed genes （DEGs）， followed by gene ontology （GO） enrichment analysis， Kyotoencyclopedia of Genes and Genomes （KEGG） enrichment analysis， Gene Set Enrichment Analysis （GSEA）， and protein-protein interaction （PPI） network construction. Key genes were further validated by Western blot and Real‑time polymerase chain reaction （Real-time PCR）. ResultsAfter drug intervention， the final body weights of mice in medium- and high-dose SJGB groups were higher than those in the model group （P<0.05）. Compared with the model group， SJGB groups demonstrated a significant decrease in expiratory time （Te）， along with increases in peak expiratory flow （PEF）， 50% expiratory flow （EF50）， tidal volume （TV）， and expiratory volume （EV） （P<0.05）. High-dose SJGB ameliorated pathological changes in the lung tissue， reduced peribronchial inflammation scores， and decreased mean linear intercept （MLI） （P<0.01）. Compared with the model group， medium- and high-dose SJGB groups showed reductions in interleukin-6 （IL-6） and interleukin-1β （IL-1β） levels （P<0.01）. UHPLC-MS/MS revealed that the five most abundant components in SJGB were （S）-actinidine， ephedrine， pyroglutamic acid， methylephedrine， and coumarin. Transcriptomic analysis revealed 219 DEGs regulated by SJGB， suggesting that the anti-COPD effects of SJGB may be mediated through key genes such as cluster of differentiation 68 （CD68）， integrin subunit alpha X （ITGAX）， and cathepsin S （CTSS）， primarily involved in the lysosomal pathway. Western blot and Real-time PCR results confirmed that SJGB inhibited the expression of CD68， ITGAX， and CTSS compared with the model group （P<0.05）. ConclusionSJGB effectively improved the lung function and attenuated lung tissue inflammation in the mouse model of COPD by modulating the lysosomal pathway and related genes including CD68， ITGAX， and CTSS.

Imprinted genes play a key role in regulating mammalian placental and embryonic development. Here, we generated glutaminyl-peptide cyclotransferase-knockout (Qpct^-/-) mice utilizing the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) platform and identified Qpct as a novel anti-angiogenic factor in regulating mouse placentation. Compared with Qpct^+/+ mice, placentae and embryos (Qpct^-/+ and Qpct^-/-) showed significant overgrowth at embryonic Day 12.5 (E12.5), E15.5, and E18.5. Using single-cell transcriptome analysis of 32 309 cells from Qpct^+/+ and Qpct^-/- mouse placentae, we identified 13 cell clusters via single-nucleus RNA sequencing (snRNA-seq) (8880 Qpct^+/+ and 13 577 Qpct^-/- cells) and 20 cell clusters via single-cell RNA sequencing (scRNA-seq) (6567 Qpct^+/+ and 3285 Qpct^-/- cells). Furthermore, we observed a global up-regulation of pro-angiogenic genes in the Qpct^-/- background. Immunohistochemistry assays revealed a notable increase in the number of blood vessels in the decidual and labyrinthine layers of E15.5 Qpct^-/+ and Qpct^-/- mice. Moreover, the elevation of multiple pairs of ligand-receptor interactions was observed in decidual cells, endothelial cells, and macrophages, promoting angiogenesis and inflammatory response. Our findings indicate that loss of maternal Qpct leads to altered phenotypic characteristics of placentae and embryos and promotes angiogenesis in murine placentae.
Animals ; Female ; Pregnancy ; Mice ; Placentation/genetics* ; Single-Cell Analysis ; Gene Expression Profiling ; Mice, Knockout ; Transcriptome ; Placenta/blood supply* ; Neovascularization, Pathologic/genetics* ; Genomic Imprinting ; Single-Cell Gene Expression Analysis ; Angiogenesis

Allergen-specific immunotherapy（AIT） remains the only therapeutic approach with the potential to modify the natural course of allergic rhinitis（AR）. Nevertheless, considerable inter-individual variability exists in patients'responses to AIT. To facilitate more reliable assessment of treatment efficacy, the China Rhinopathy Research Cooperation Group（CRRCG） convened young and middle-aged nasal experts in China to formulate the present consensus. The recommended subjective outcome measures for AIT comprise symptom scores, medication scores, combined symptom and medication scores, quality-of-life assessments, evaluation of disease control, and assessment of comorbidities. Objective indicators may supplement these measures. Currently available objective approaches include skin prick testing, nasal provocation testing, and allergen exposure chambers. However, these methods remain constrained by practical limitations and are not yet appropriate for routine implementation in clinical efficacy evaluation. In addition, several biomarkers, including sIgE and the sIgE/tIgE ratio, sIgG4, serum IgE-blocking activity, IgA, cytokines and chemokines, as well as immune cell surface molecules and their functional activity, have been shown to have associations with AIT outcomes. While these biomarkers may complement subjective assessments, they are subject to significant limitations. Consequently, large-scale multicenter trials and real-world evidence are required to strengthen the evidence base. The present consensus underscores the necessity of integrating patients'subjective experiences with objective testing throughout the treatment process, thereby providing a more comprehensive and accurate framework for efficacy evaluation. Looking forward, future investigations should prioritize the incorporation of multi-omics data and artificial intelligence methodologies, which hold promise for overcoming current limitations in assessment strategies and for advancing both the standardization and personalization of AIT.
Humans ; Allergens/immunology* ; China ; Consensus ; Desensitization, Immunologic ; Immunoglobulin E ; Quality of Life ; Rhinitis, Allergic/therapy* ; Treatment Outcome ; East Asian People

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

Multiple system atrophy (MSA) is a rare neurodegenerative disease with complex clinical manifestations, presenting substantial challenges in clinical diagnosis and treatment. Its symptoms and the eight extraordinary meridians are potentially correlated; therefore, this article explores the association between MSA symptom clusters and the eight extraordinary meridians based on their circulation and physiological functions, as well as their treatment strategies. The progression from deficiency to damage in the eight extraordinary meridians aligns with the core pathogenesis of MSA, which is characterized by "the continuous accumulation of impacts from the vital qi deficiency leading to eventual damage". Liver and kidney deficiency and the emptiness of the eight extraordinary meridians are required for the onset of MSA; the stagnation of qi deficiency and the gradual damage to the eight extraordinary meridians are the key stages in the prolonged progression of MSA. The disease often begins with the involvement of the yin and yang qiao mai, governor vessel, thoroughfare vessel, and conception vessel before progressing to multiple meridian involvements, ultimately affecting all eight extraordinary meridians simultaneously. The treatment approach emphasizes that "the direct method may be used for joining battle, but indirect method will be needed in order to secure victory" and focuses on "eliminate pathogenic factors and reinforce healthy qi". Distinguishing the extraordinary meridians and focusing on the primary symptoms are pivotal to improving efficacy. Clinical treatment is aimed at the target, and tailored treatment based on careful clinical observation ensures precision in targeting the disease using the eight extraordinary meridians as the framework and core symptoms as the specific focus. Additionally, combining acupuncture, daoyin therapy, and other method may help prolong survival. This article classifies clinical manifestations based on the theory of the eight extraordinary meridians and explores treatment.

OBJECTIVE: The aim of this study is to analyze the clinical features and genetic etiology of a patient with multiple morphological abnormalities of the sperm flagella (MMAF) retrospectively. METHODS: A severely oligospermic patient from the Reproductive Center of the First Affiliated Hospital of Ningbo University was selected as the study subject. Clinical data and examination results were collected. High-throughput sequencing and bioinformatics were used to analyze the genetic etiology. And Sanger sequencing was employed to validate findings in the family. Transmission electron microscopy (TEM) was used to observe the sperm ultrastructure, and immunofluorescence analysis was performed to examine the localization of FSIP2 protein in the sperm. RESULTS: The patient presented with severe oligospermia, and sperm morphology displayed MMAF. TEM revealed fibrous sheath and 9+2 microtubule structural disruptions in the sperm. Sequencing identified compound heterozygous variants in the FSIP2 gene (c.17798C > T, c.5927T > G), inherited from the father and mother, respectively. According to the guidelines of the American College of Medical Genetics and Genomics, the variants were classified as pathogenic. The patient's spouse underwent intracytoplasmic single sperm injection, resulting in one embryo, but no clinical pregnancy occurred after embryo transfer. CONCLUSION This study reported the mutation of FSIP2 gene c.17798C > T, c.5927T > G in a patient with MMAF. These findings expand the mutational spectrum of the FSIP2 gene and provide insights for genetic and assisted reproductive counseling for patients with MMAF.
Humans ; Male ; Sperm Tail/pathology* ; Heterozygote ; Oligospermia/genetics* ; Spermatozoa ; Mutation ; Infertility, Male/genetics* ; Adult ; Pedigree ; Retrospective Studies ; Sperm Injections, Intracytoplasmic

BACKGROUND: Hypertension is associated with an increased risk of calcific aortic valve stenosis (CAVS). However, the directionality of causation between blood pressure traits and aortic stenosis is unclear, as is the benefit of antihypertensive drugs for CAVS. METHODS: Using genome-wide association studies (GWAS) summary statistics, we performed bidirectional two-sample univariable mendelian randomization (UVMR) to assess the causal associations of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) with CAVS. Multivariable mendelian randomization (MVMR) was conducted to evaluate the direct effect of hypertension on CAVS, adjusting for confounders. Drug target mendelian randomization (MR) and summary-level MR (SMR) were used to estimate the effects of 12 classes of antihypertensive drugs and their target genes on CAVS risk. Inverse variance weighting was the primary MR method, with sensitivity analyses to validate results. RESULTS: UVMR showed SBP, DBP, and PP have causal effects on CAVS, with no significant reverse causality. MVMR confirmed the causality between hypertension and CAVS after adjusting for confounders. Drug-target MR analyses indicated that calcium channel blockers (CCBs), loop diuretics, and thiazide diuretics via SBP lowering exerted protective effects on CAVS risk. SMR analysis showed that the CCBs target gene CACNA2D2 and ARBs target gene AGTR1 were positively associated with CAVS risk, while diuretics target genes SLC12A5 and SLC12A1 were negatively associated with aortic stenosis risk. CONCLUSIONS Hypertension has a causal relationship with CAVS. Managing SBP in hypertensive patients with CCBs may prevent CAVS. ARBs might exert protective effects on CAVS independent of blood pressure reduction. The relationship between diuretics and CAVS is complex, with opposite effects through different mechanisms.