Objective: To investigate the survival status and influencing factors of people living with HIV/AIDS receiving anti-retroviral therapy (ART) ≥5 years in Weinan City, Shaanxi Province from 2004 to 2023, so as to provide the evidence for improving ART effects and quality of life of HIV/AIDS cases. Methods: Baseline data including age, CD4+ T lymphocyte (CD4 cell) count, and viral load, as well as follow-up data including death time and cause of death of HIV/AIDS cases aged ≥18 years receiving ART ≥5 years in Weinan City from 2004 to 2023 were collected through the China AIDS Comprehensive Response Information System. The time when HIV/AIDS cases received ART ≥5 years was taken as the starting point, and death from AIDS-related diseases was taken as the outcome. The follow-up end time was December 31, 2023. Multivariable Cox proportional hazards regression model was used to analyze the influencing factors for survival time of ART HIV/AIDS cases. Results: A total of 1 015 HIV/AIDS cases were included. The median age was 30.00 (interquartile range, 6.00) years. There were 874 males (86.11%) and 141 females (13.89%). As of December 31, 2023, 175 cases died, including 104 deaths due to AIDS-related diseases, with a case fatality rate of 10.25%. The median survival time was 110.48 (interquartile range, 7.89) months. Multivariable Cox proportional hazards regression analysis showed that the risk of death was lower in ART HIV/AIDS cases with homosexual contact infection (HR=0.486, 95%CI: 0.343-0.687), second-line treatment regimens (HR=0.263, 95%CI: 0.152-0.455), and CD4 cell count ≥200 cells/μL (200-<500 cells/μL, HR=0.209, 95%CI: 0.147-0.298; ≥500 cells/μL, HR=0.076, 95%CI: 0.044-0.132). The risk of death was higher in ART HIV/AIDS cases with viral load ≥1 000 copies/mL (HR=2.508, 95%CI: 1.774-3.546). Conclusions The survival time of HIV/AIDS cases receiving ART ≥5 years in Weinan City was mainly affected by route of infection, treatment regimen, CD4 cell count, and viral load. It is recommended to strengthen the monitoring and management of cases with high viral load, and carry out interventions for populations with different routes of infection, so as to reduce the case fatality rate and prolong survival time.

Ameloblastoma is a benign tumor characterized by locally invasive phenotypes,leading to facial bone destruction and a high recurrence rate.However,the mechanisms governing tumor initiation and recurrence are poorly understood.Here,we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution.Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response(IR),bone remodeling(BR),tooth development(TD),epithelial development(ED),and cell cycle(CC)signatures.Of note,we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence,which was dominated by the EZH2-mediated program.Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids.These data described the tumor subpopulation and clarified the identity,function,and regulatory mechanism of CC ameloblastoma cells,providing a potential therapeutic target for ameloblastoma.

Hereditary gingival fibromatosis (HGF) is a rare inherited condition with fibromatoid hyperplasia of the gingival tissue that exhibits great genetic heterogeneity. Five distinct loci related to non-syndromic HGF have been identified; however, only two disease-causing genes, SOS1 and REST, inducing HGF have been identified at two loci, GINGF1 and GINGF5, respectively. Here, based on a family pedigree with 26 members, including nine patients with HGF, we identified double heterozygous pathogenic mutations in the ZNF513 (c.C748T, p.R250W) and KIF3C (c.G1229A, p.R410H) genes within the GINGF3 locus related to HGF. Functional studies demonstrated that the ZNF513 p.R250W and KIF3C p.R410H variants significantly increased the expression of ZNF513 and KIF3C in vitro and in vivo. ZNF513, a transcription factor, binds to KIF3C exon 1 and participates in the positive regulation of KIF3C expression in gingival fibroblasts. Furthermore, a knock-in mouse model confirmed that heterozygous or homozygous mutations within Zfp513 (p.R250W) or Kif3c (p.R412H) alone do not led to clear phenotypes with gingival fibromatosis, whereas the double mutations led to gingival hyperplasia phenotypes. In addition, we found that ZNF513 binds to the SOS1 promoter and plays an important positive role in regulating the expression of SOS1. Moreover, the KIF3C p.R410H mutation could activate the PI3K and KCNQ1 potassium channels. ZNF513 combined with KIF3C regulates gingival fibroblast proliferation, migration, and fibrosis response via the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways. In summary, these results demonstrate ZNF513 + KIF3C as an important genetic combination in HGF manifestation and suggest that ZNF513 mutation may be a major risk factor for HGF.
Animals ; Humans ; Mice ; Fibromatosis, Gingival/pathology* ; Gingiva ; Kinesins/genetics* ; Mutation/genetics* ; Phosphatidylinositol 3-Kinases/genetics*

Tooth development is a complex process that involves precise and time-dependent orchestration of multiple genetic, molecular, and cellular interactions. Ameloblastin (AMBN, also named "amelin" or "sheathlin") is the second most abundant enamel matrix protein known to have a key role in amelogenesis. Amelogenesis imperfecta (AI [MIM: 104500]) refers to a genetically and phenotypically heterogeneous group of conditions characterized by inherited developmental enamel defects. The hereditary dentin disorders comprise a variety of autosomal-dominant genetic symptoms characterized by abnormal dentin structure affecting either the primary or both the primary and secondary teeth. The vital role of Ambn in amelogenesis has been confirmed experimentally using mouse models. Only two cases have been reported of mutations of AMBN associated with non-syndromic human AI. However, no AMBN missense mutations have been reported to be associated with both human AI and dentin disorders. We recruited one kindred with autosomal-dominant amelogenesis imperfecta (ADAI) and dentinogenesis imperfecta/dysplasia characterized by generalized severe enamel and dentin defects. Whole exome sequencing of the proband identified a novel heterozygous C-T point mutation at nucleotide position 1069 of the AMBN gene, causing a Pro to Ser mutation at the conserved amino acid position 357 of the protein. Exfoliated third molar teeth from the affected family members were found to have enamel and dentin of lower mineral density than control teeth, with thinner and easily fractured enamel, short and thick roots, and pulp obliteration. This study demonstrates, for the first time, that an AMBN missense mutation causes non-syndromic human AI and dentin disorders.
Adult ; Amelogenesis Imperfecta ; genetics ; Cells, Cultured ; China ; Codon ; Dentin ; abnormalities ; ultrastructure ; Female ; Humans ; Male ; Microsatellite Repeats ; Microscopy, Electron, Scanning ; Middle Aged ; Mutation, Missense ; Pedigree ; RNA ; analysis ; Transfection ; Whole Exome Sequencing

OBJECTIVE: Lymphoepithelial carcinoma (LEC) of salivary glands is a rare malignant neoplasm. The purpose of this research was to investigate the clinicalpathologic features and treatment methods of this rare disease. METHOD: The clinical data and treatment outcomes of 17 patients from 2006 to 2012 were reviewed retrospectively. RESULT: Ten males and seven females with a ratio of 1. 43:1 were involved. The II, III, IV stage cases were 7 (41.2%), 4 (23.5%), 6 (35.3%), respectively. The average follow-up duration was 2.56 years, and 12 patients had no evidence of recurrence. Five patients had local recurrence and (or) distant metastases within three years after surgery, including 4 deaths. CONCLUSION LEC in salivary gland is a high grade malignant tumor in oral and maxillofacial region, occurring predominately in parotid gland and submandibular gland. To prevent distant metastasis, radical surgery combined with chemoradiotherapy should be adopted.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasms, Squamous Cell ; pathology ; secondary ; Parotid Neoplasms ; pathology ; Rare Diseases ; pathology ; Retrospective Studies ; Salivary Gland Neoplasms ; pathology ; Salivary Glands ; pathology ; Submandibular Gland Neoplasms ; pathology ; Treatment Outcome