BACKGROUND:Human periodontal ligament stem cells are potential functional cells for periodontal tissue engineering.However,long-term in vitro culture may lead to reduced stemness and replicative senescence of periodontal ligament stem cells,which may impair the therapeutic effect of human periodontal ligament stem cells. OBJECTIVE:To investigate the effect of oxymatrine on the stemness maintenance and osteogenic differentiation of periodontal ligament stem cells in vitro,and to explore the potential mechanism. METHODS:Periodontal ligament stem cells were isolated from human periodontal ligament tissues by tissue explant enzyme digestion and cultured.The surface markers of mesenchymal cells were identified by flow cytometry.Periodontal ligament stem cells were incubated with 0,2.5,5,and 10 μg/mL oxymatrine.The effect of oxymatrine on the proliferation activity of periodontal ligament stem cells was detected by CCK8 assay.The appropriate drug concentration for subsequent experiments was screened.Western blot assay was used to detect the expression of stem cell non-specific proteins SOX2 and OCT4 in periodontal ligament stem cells.qRT-PCR and western blot assay were used to detect the expression levels of related osteogenic genes and proteins in periodontal ligament stem cells. RESULTS AND CONCLUSION:(1)The results of CCK8 assay showed that 2.5 μg/mL oxymatrine significantly enhanced the proliferative activity of periodontal stem cells,and the subsequent experiment selected 2.5 μg/mL oxymatrine to intervene.(2)Compared with the blank control group,the protein expression level of SOX2,a stem marker of periodontal ligament stem cells in the oxymatrine group did not change significantly(P>0.05),and the expression of OCT4 was significantly up-regulated(P<0.05).(3)Compared with the osteogenic induction group,the osteogenic genes ALP,RUNX2 mRNA expression and their osteogenic associated protein ALP protein expression of periodontal ligament stem cells were significantly down-regulated in the oxymatrine+osteogenic induction group(P<0.05).(4)The oxymatrine up-regulated the expression of stemness markers of periodontal ligament stem cells and inhibited the bone differentiation of periodontal ligament stem cells,and the results of high-throughput sequencing showed that it may be associated with WNT2,WNT16,COMP,and BMP6.

OBJECTIVE: To investigate the whole-genome differential methylation profile of patients with high-altitude polycythemia (HAPC). METHODS: In this study, a total of 20 adult male patients with HAPC were included, including 10 Tibetan and 10 Han patients. The control group consisted of 20 healthy adult males, including 10 Tibetan and 10 Han patients. Peripheral blood was collected from each group for DNA extraction and quality inspection, and DNA libraries were constructed. The differential methylation regions (DMRs) between groups were detected using reduced representation bisulfite sequencing, with enriched regions compared to those of the control group. The differential enrichment regions were selected, and the intersection of the enriched regions was associated with genes. The methylation enrichment regions that differed significantly between groups were filtered based on the number of enriched samples in the enriched regions between the groups. GO, KEGG functional, and pathway analysis were performed on the differentially associated gene sets to reveal significant differences between the patients and control groups at the functional and pathway levels. RESULTS: In comparison with the control group, 17 152 sites with more than 25% difference and 15 558 sites with less than -25% difference were identified in Tibetan patients. The top 5 genes with the largest methylation differences between the two groups were MCCC2, RP3-399L15.3, ZNF621, RP11-394A14.2 and SLC39A10. The top significantly different pathways annotated in the differentially expressed genes pathway was serotonergic synapse. In comparison with the control group, 2 687 CpG sites with a greater than 25% difference and 2 602 CpG sites with a less than -25% difference were identified in Han patients. The top 5 genes with the largest methylation differences between the two groups were NAA25, CORO2B, PDC, ZNF853, and MLLT10. The top significantly different pathways annotated in the differentially expressed genes pathway were glutamatergic synapse, retrograde endocannabinoid signaling, Rap1 signaling pathway and cholinergic synapse. In comparison with the control group, 3 895 CpG sites with a greater than 25% difference and 3 969 CpG sites with a less than -25% difference were identified in HAPC patients. The maximum methylation difference between the two groups could reach 78.1%, while the minimum was -42.6%. The top 5 genes with the largest methylation differences between the two groups were MCCC2, ARSJ, CTNNA3, SLC39A10, and SWAP70. The top significantly different pathways annotated in the differentially expressed genes pathway was signaling pathways regulating pluripotency of stem cells. CONCLUSION The occurrence of HAPC may be related to abnormal changes in DNA methylation, and methylation sites may be helpful for the early diagnosis of HAPC.
Humans ; DNA Methylation ; Altitude ; Polycythemia/genetics* ; Male ; Adult ; CpG Islands

OBJECTIVE: To assess health equity in the Yangtze River region to improve understanding of the correlation between hand, foot, and mouth disease (HFMD) and socioeconomic factors. METHODS: From 2014-2016, data on HFMD incidence, population statistics, economic indicators, and meteorology from 26 cities along the Yangtze River were analyzed. A multi-city random-effects meta-analysis was performed to study the relationship between temperature and HFMD transmission, and health equity was assessed with respect to socio-economic impact. RESULTS: Over the study period, 919,458 HFMD cases were reported, with Shanghai (162,303) having the highest incidence and Tongling (5,513) having the lowest. Males were more commonly affected (male-to-female ratio, 1.49:1). The exposure-response relationship had an M-shaped curve, with two HFMD peaks occurring at 4 °C and 26 °C. The relative risk had two peaks at 1.30 °C (1.834, 95% CI: 1.204-2.794) and 31.4 °C (1.143, 95% CI: 0.901-1.451), forming an M shape, with the first peak higher than the second. The most significant impact of temperature on HFMD was observed between -2 °C and 18.1 °C. The concentration index (0.2463) indicated moderate concentration differences, whereas the Theil index (0.0418) showed low inequality in distribution. CONCLUSION The incidence of HFMD varied across cities, particularly with changes in temperature. Economically prosperous areas showed higher risks, indicating disparities. Targeted interventions in these areas are crucial for mitigating the risk of HFMD.
Female ; Humans ; Male ; China/epidemiology* ; Cities/epidemiology* ; Hand, Foot and Mouth Disease/transmission* ; Incidence ; Risk Factors ; Temperature

OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective:To understand the serotype distribution, drug resistance and molecular characterization of invasive non-typhoid Salmonella (iNTS) in Guangdong Province from 2018 to 2022 and provide scientific evidence for the prevention and treatment of blood flow infection caused by Salmonella. Methods:Serological identification, antimicrobial susceptibility testing, multilocus sequence typing (MLST), and whole genome sequencing were performed on Salmonella isolated from blood and stool samples in Guangdong from 2018 to 2022. Simultaneously, annotated the sequencing results for drug resistance genes and virulence factors by a microbial gene annotation system. Results:The 136 iNTS strains were divided into 25 serotypes, and Salmonella enteritidis accounted for 38.24% (52/136). The OR of other iNTS serotypes were calculated with Salmonella typhimurium as the control. The OR values of Oreninburg, Rysson, and Pomona serotypes were the highest, which were 423.50, 352.92, and 211.75, respectively. The drug resistance rate of iNTS was 0.74%-66.91%, which was lower than that of non-iNTS (3.90%-77.21%). The main iNTS of drug resistance were ampicillin and tetracycline, with resistance rates of 66.91% (91/136) and 50.00% (68/136), respectively, while the resistance rates to ciprofloxacin (5.88%,8/136), ceftazidime (5.88%,8/136), gentamicin (5.13%,7/136) and cefoxitin (0.74%, 1/136) were relatively low. iNTS carried a variety of drug-resistance genes and virulence factors, but no standard virulence factor distribution has been found. MLST cluster analysis showed that iNTS was divided into 26 sequence types, and ST11 accounted for 38.24% (52/136). Conclusions:The iNTS strains in Guangdong were dominated by Salmonella enteritidis, of which three serotypes, Oreninburg, Rison, and Pomona, may be associated with a higher risk of invasive infection during 2018 to 2022 . iNTS was sensitive to clinical first-line therapeutic drugs (cephalosporins and fluoroquinolones), with highly diverse sequences and clear phylogenetic branches. ST11 was the local dominant clone group.

Objective:To explore and analyze the clinical features of patients with immunoglobulin (Ig)G4-related hepatobiliary-pancreatic disease and the independent factors affecting the prognosis of IgG4-related sclerosing cholangitis (IgG4-SC).Methods:The clinical data of 179 adult cases diagnosed with IgG4-related hepato-pancreato-biliary disease in the Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2011 to December 2022 were retrospectively analyzed. Patients were divided into three groups: isolated IgG4-SC, IgG4-SC/type 1 autoimmune pancreatitis(type 1 AIP), and isolated AIP according to the clinical manifestations. Demographic characteristics, baseline biochemical immunological indexes, and imaging manifestations were analyzed. The treatment response rate and survival rate were compared. The COX proportional hazards model was used to analyze the independent factors related to prognosis.Results:The mean age of diagnosis of patients with IgG4-related hepatobiliary-pancreatic disease was 60.3±12.0 years. Males accounted for 74.9%, and the median follow-up time was 38 months. The 1-year clinical response rate of patients with isolated IgG4-SC was lower than that of IgG4-SC/AIP (67.9% vs. 91.7%, P=0.019), and the primary endpoint-free 5-year survival rate was significantly reduced (64.9% vs. 95.9%, P<0.001). COX regression analysis showed that having cirrhosis before treatment ( HR=6.708, P=0.004) and poor response after half a year of treatment ( HR=11.488, P=0.002) were independent risk factors associated with the occurrence of adverse events in hepatobiliary diseases among patients with IgG4-SC. Conclusions:The clinical response rate and survival rate of patients with isolated IgG4-SC are lower than those of patients with IgG4-SC/AIP. Patients with IgG4-SC who do not respond well at six months of treatment and who have progressed to cirrhosis before treatment are at significantly increased risk of adverse events.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To analyze the correlation between body fat distribution measured by quantitative CT (QCT) and body mass index in adults receiving physical examination.Methods:It was a cross-sectional study. From January to December 2021, 3 205 adults undergoing physical examination who met the inclusion criteria and underwent chest CT and QCT examination in the health management discipline of Henan Provincial People′s Hospital were selected as the research objects. The general data were collected; and the subcutaneous fat area, visceral fat area, total abdominal fat area, liver fat content, abdominal obesity and fatty liver detection rate were measured by QCT. According to body mass index, the subjects were divided into normal group (18.5-<24.0 kg/m 2, 1 343 cases), overweight group (24.0-<28.0 kg/m 2, 1 427 cases) and obesity group (≥28.0 kg/m 2, 435 cases). One-way analysis of variance and χ2 test were used to compare the differences of QCT indexes among the three groups. Pearson and Spearman correlation analysis were used to evaluate the correlation between QCT indexes and body mass index. Receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic effect of QCT on obesity and fatty liver. Results:Subcutaneous fat area, visceral fat area, total abdominal fat area, liver fat content, abdominal obesity and fatty liver detection rate in obese group were all significantly higher than those in overweight group and normal group [males, (147.60±46.44) vs (104.33±27.68), (73.46±22.65) cm 2; (297.46±54.70) vs (229.40±53.12), (159.57±49.68) cm 2; (445.06±70.24) vs (333.73±62.91), (233.02±61.87) cm 2; 11.30% (7.90%, 15.55%) vs 8.75% (6.50%, 11.70%), 6.60% (4.80%, 8.70%); 100.0% vs 96.0%, 64.0%; 92.9% vs 86.7%, 73.3%; females, (213.96±48.61) vs (155.85±35.31), (107.24±31.01) cm 2; (185.41±43.88) vs (142.48±41.75), (96.56±36.50) cm 2; (399.37±68.07) vs (298.33±56.86), (203.80±57.53) cm 2; 9.80% (6.90%, 13.30%) vs 7.30% (5.05%, 9.80%), 5.40%(3.50%, 7.20%); 96.4% vs 74.8%, 28.9%; 87.3% vs 75.6%, 56.5%], and were all positively correlated with body mass index (males, r/ rs=0.709, 0.738, 0.831, 0.402, 0.464, 0.225; females, r/ rs=0.798, 0.695, 0.841, 0.416, 0.605, 0.276) (all P<0.001). In both male and female subjects, the detection rates of obesity based on QCT were significantly higher than those based on body mass index (male, 86.9% vs 16.6%; female, 49.3% vs 8.9%), and the detection rates of fatty liver based on QCT were significantly higher than those based on ultrasound (male, 83.6% vs 57.1%; female, 65.2% vs 27.6%) (all P<0.001). ROC curve showed that when the visceral fat area of 142 cm 2 was used as the cut-off value for the diagnosis of obesity in male subjects, the sensitivity and specificity was 100% and 15.8%, respectively; and when the cut-off value of liver fat content 5.0% was used to diagnose fatty liver, the sensitivity and specificity was 88.9% and 25.1%, respectively. When the visceral fat area of 115 cm 2 was set as the cut-off value for the diagnosis of obesity in female subjects, the sensitivity and specificity was 96.4% and 55.3%, respectively; when the liver fat content of 5.0% was set as the cut-off value for the diagnosis of fatty liver, the sensitivity and specificity was 83.7% and 43.2%, respectively. Conclusions:The indexes of abdominal fat and liver fat measured by QCT in adults receiving physical examination are all positively correlated with body mass index. The effect of QCT in the diagnosis of obesity and fatty liver are both better than body mass index and ultrasound.