Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Six compounds were isolated from the ethyl acetate fraction of Citri Sarcodactylis Fructus by using various column chromatographic methods, such as MCI Gel CHP-20, ODS, Sephadex LH-20, silica gel and semipreparative HPLC. Their structures were identified to be citrusin G (1), citrusin H (2), citrusin E (3), syringin (4), coniferin (5), methylconiferin (6) by NMR, HR-ESI-MS, UV, IR spectra. Compounds 1 and 2 were new secondary metabolism products and 3-6 were obtained from the titled material for the first time. Compound 1 showed anti-renal fibrosis activity in TGF-β1-induced kidney proximal tubular cells.

Dental treatments for children and adolescents have unique clinical characteristics that differ from dental care for adults in terms of children's physiology, psychology, and behavior. These differences impose specific requirements on the application of local anesthesia in pediatric dental procedures. This article presents expert consensus on the principles of local anesthesia techniques in pediatric dental therapies, including the use of common anesthetic drugs and dosage control, safety and efficacy evaluation, and prevention and management of complications. The aim is to improve the safety and quality of pediatric dental treatments and offer guidance for clinical application by dentists.
Humans ; Child ; Anesthesia, Local/methods* ; Consensus ; Anesthesia, Dental/methods* ; Adolescent ; Anesthetics, Local/administration & dosage* ; Dental Care for Children

Objective To investigate the expression of small nuclear ribonucleoprotein D1 (SNRPD1) in the gastric cancer tissue and evaluate the predictive value of SNRPD1 expression level for the long-term prognosis of gastric cancer patients and the possible functioning mechanism of SNRPD1. Methods The UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) were employed to analyze the expression level of SNRPD1 in pan-cancer and its relationship with the prognosis of gastric cancer.The clinical data of 109 patients who underwent radical surgery for gastric cancer from January 2014 to January 2017 in the First Affiliated Hospital of Bengbu Medical University were retrospectively analyzed.Gastric cancer and paracancerous tissue samples were collected,and the expression of SNRPD1 was detected by immunohistochemical staining.Lentiviral transfection was employed to construct the BGC-823 gastric cancer cell models with stable high and low expression of SNRPD1,respectively.The CCK-8 assay and colony formation assay were employed to measure the proliferation of gastric cancer cells,and flow cytometry was used to analyze the cell cycle.Western blotting was employed to determine the expression levels of proteins in the signaling pathway. Results The data from UALCAN and GEPIA showed that SNRPD1 was highly expressed in the tissue of malignant tumors including gastric cancer (P<0.001).The expression level of SNRPD1 in the gastric cancer tissue was higher than that in the paracancerous tissue (P<0.001).Moreover,the expression level of SNRPD1 was positively correlated with the levels of carcinoembryonic antigen (P<0.001),carbohydrate antigen 19-9 (P<0.001),G stage (P=0.042),T stage (P=0.002),and N stage (P=0.027) in the patients with gastric cancer.The high expression of SNRPD1 had a predictive value for the long-term prognosis of gastric cancer (P<0.001),and it was an independent risk factor for the death of gastric cancer patients (P=0.003).The results of gene ontology and kyoto encyclopedia of genes and Genomes enrichment analyses showed that SNRPD1 was involved in the regulation of the cell cycle.The results of CCK-8 and colony formation assays showed that up-regulation of SNRPD1 promoted the proliferation of gastric cancer cells (P<0.001,P<0.001).The up-regulation of SNRPD1 up-regulated the expression of cyclin-dependent kinase 6 and G₁/S-specific cyclin-D1 (P<0.001,P=0.002),whereas the interference in SNRPD1 led to opposite results (P=0.004,P<0.001).SNRPD1 accelerated the G₁/S phase transition of gastric cancer cells (P<0.001).The overexpression of SNRPD1 promoted the expression of phosphorylated phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (Akt) in gastric cancer cells (P=0.043,P<0.001),whereas disruption of SNRPD1 inhibited their expression (both P<0.001).Insulin-like growth factor 1,an agonist of the PI3K/Akt signaling pathway,promoted the proliferation of gastric cancer cells with SNRPD1 disturbed (P=0.002). Conclusion High expression of SNRPD1 in the gastric cancer tissues is associated with poor prognosis,and it may promote tumor cell proliferation and regulate the cell cycle by activating the PI3K/Akt signaling pathway.
Humans ; Stomach Neoplasms/pathology* ; Prognosis ; Cell Line, Tumor ; Cell Proliferation ; Retrospective Studies ; Cell Cycle ; Male ; Female

Objective To analyze the research status of in situ simulation in the medical field and explore its hotspots and trends. Methods Relevant literature was searched in China National Knowledge Infrastructure and Web of Science core collection from the inception to February 2024.CiteSpace 6.3.R1 was used to analyze the authors,institutions,and keywords and draw visual knowledge maps. Results A total of 25 Chinese articles and 438 English articles were included.Only 14 English articles were from China.In Chinese articles,the authors with the largest number of articles were Dai Hengmao and Liu Shangkun,and the institution with the largest number of articles was Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology.There was little cooperation between the authors and institutions.In English articles,the author and institution with the largest number of articles was Auerbach Marc and Yale University,respectively,and the cooperation between authors and institutions was close.Emergency medicine,emergency event handling,and on-the-job training were the keywords with high frequency in Chinese articles.Patient safety,medical education,and cardiac arrest were the keywords with high frequency in English articles.A total of 4 clusters were generated for Chinese keywords and 13 clusters for English keywords. Conclusions The application of in situ simulation in the medical field is still in the initial stage,and the development is not balanced at home and abroad.The number of articles published and the cooperation between authors and institutions in China obviously lags behind those abroad.Treatment and care of emergency critical patients,emergency event handling and skill training,identification of latent safety threats,improvement of readiness,and promotion of medical quality improvement are the future research hotspots and research trends in this field.
Bibliometrics ; Humans ; China ; Simulation Training ; Education, Medical ; Emergency Medicine/education*

Objective To investigate the role of trichostatin A(TSA)in regulating CD4+T cell subpopulations during Escherichia coli(E.coli)inflammatory infections.Methods Male mice(8 weeks old,weighing 22～25 g)were randomly divided into 3 groups(n=16):a dimethyl sulfoxide(DMSO)control group,an infection group(DMSO+E.coli),and an intervention group(E.coli+TSA).E.coli was administered via intraperitoneal injection at a concentration of 3×10? CFU/mL to establish an infection model.The E.coli+TSA group was further subdivided into 3 subgroups based on different TSA concentrations(2.5,5.0,10.0 mg/kg).Then the samples were collected at different time points(12,24,48,96 h)after TSA intervention.The efficacy of TSA in treating E.coli-induced inflammatory responses and its relationship with CD4+T cell subsets were evaluated by survival rate observation,body weight monitoring,histopathological staining for small intestine,ELISA detection,transcriptomics sequencing,flow cytometry and RT-qPCR analysis.Results Compared with the E.coli group,5 mg/kg TSA significantly increased survival rate,suppressed body weight loss,improved pathological damage in the small intestinal,reduced serum TNF-α level in 24 h after infection(P<0.000 1),and elevated IL-10 level(P<0.05).Transcriptomic analysis revealed that 5 mg/kg TSA intervention for 24 h modulated the T cell differentiation signaling pathways,including those regulating FoxO,Th17,and Th1/2.Flow cytometry and RT-qPCR results showed that compared to the E.coli group,5 mg/kg TSA down-regulated the expression of the Th17 cell marker RORγt in mice 96 h after infection while significantly up-regulated the expression of the Treg cell marker Foxp3(P<0.05).Conclusion TSA may alleviate bacterial infectious inflammatory diseases by regulating the differentiation of CD4+T cells toward the Treg subset while simultaneously inhibiting their differentiation toward the Th17 subset,thereby suppressing the release of proinflammatory cytokines.

Objective To investigate the critical role of macrophage M1 polarization in mediating the effect of periodontitis on the progression of chronic obstructive pulmonary disease(COPD).Methods Alveolar lavage fluid samples were collected from COPD patients with comorbid periodontitis,and gene expression analysis was performed to validate the changes in the expression of M1 polarization-related genes.A mouse model of COPD,with experimentally induced periodontitis,were established.Hematoxylin and eosin(HE)staining of pathological sections was performed to observe the effect of periodontitis on COPD progression.Flow cytometry,immunofluorescence staining,and reverse transcription quantitative polymerase chain reaction(RT-qPCR)were performed to analyze the effect of periodontitis on macrophage M1 polarization and the expression of relevant genes in the alveolar lavage fluid and lung tissues.Results In clinical samples of alveolar lavage fluid from COPD patients with periodontitis,the expression of macrophage M1 polarization-related genes,including CD86,inducible nitric oxide synthase(iNOS),interleukin(IL)-1β,tumor necrosis factor(TNF)-α,IL-23,and IL-6,was upregulated compared with that of COPD patients without periodontitis.Analysis of a mouse disease model revealed that periodontitis affected the growth of COPD mice,with the final body mass of mice in the periodontitis and COPD comorbid group([21.3±0.52]g,day 34)lower than that of the COPD group([23.93±0.45]g,day 34).Pathological sections of the lung tissue showed that periodontitis exacerbated COPD progression,with more pronounced alveolar expansion and alveolar wall destruction observed in the periodontitis and COPD comorbid group.Flow cytometry revealed a higher proportion of M1-polarized macrophages in alveolar lavage fluid from COPD and periodontitis comorbid mice([31.36±2.51]%)compared with the COPD mice([23.19±1.07]%).Immunofluorescence assays indicated that periodontitis also promoted macrophage M1 polarization in the lung tissue of COPD mice.Gene expression analysis demonstrated that M1 polarization-related gene expression was significantly upregulated in both the alveolar lavage fluid and lung tissue of mice in the COPD and periodontitis co-morbid group compared to the COPD group.Conclusion Periodontitis exacerbates COPD progression by promoting macrophage M1 polarization in the lungs.Enhancing oral hygiene management and targeting the inhibition of macrophage M1 polarization may represent new therapeutic strategies for the clinical prevention and control of COPD.

ObjectiveTo identify key factors influencing cognitive function in the elderly, including traditional Chinese medicine (TCM) constitutional classification, and to rank their relative importance.MethodsWe used cross-sectional data from seven geographical regions across mainland China. The Changsha version of the Montreal Cognitive Assessment was used to assess cognitive function. A “least absolute shrinkage and selection operator” (LASSO) model, multivariate linear regression analysis, and random forest (RF) model were used. Subgroup analyses were performed to examine the correlation between key TCM constitution types and cognitive function in different population subgroups.ResultsA total of 24 803 individuals aged 60 and above were included in the study. We selected 18 influential factors using the LASSO model. Higher education, being married, and having insurance were positively correlated with cognitive function in the elderly (all P .05). In contrast, poor sleep, vision impairment, hearing impairment, basic activities of daily living disability, instrumental activities of daily living disability, depression, hypertension, coronary heart disease, diabetes, stroke, yang-deficiency constitution (YADC), yin-deficiency constitution (YIDC), qi deficiency constitution (QDC), and blood stasis constitution (BSC) were negatively correlated with cognitive function (all P .05). YIDC and BSC affected all dimensions of cognitive function (all P .05). YADC mainly affected attention, language, abstraction (verbal analogies), memory, and orientation to time and place dimensions (P .001). QDC mainly affected language and abstraction (verbal analogies) dimensions (P .05). The negative correlations between BSC, YADC, YIDC, and QDC scores and cognitive function revealed statistically significant differences across most subgroups. The RF model identified education, BSC, and poor sleep quality as the three most influential factors in our study.ConclusionBSC, YADC, YIDC, and QDC were associated with cognitive decline in the elderly. Our findings provide new perspectives and significant references for interventions for early-stage cognitive disorders.