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.

To explore the role of the "Clinical Practice Guidelines" column and others in the Medical Joumnal of Peking Union Medical College Hospital (Med J PUMCH) in promoting diseiplinary development.

Objective To explore the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) accompanied with KMT2D gene mutation and the impact of its co-mutated genes on prognosis. Methods Clinical data of 155 newly diagnosed DLBCL patients were obtained. The second-generation sequencing method was used to detect 475 hotspot genes, including KMT2D mutation. Patients were divided into the KMT2D mutation group and KMT2D wild-type group based on the presence or absence of KMT2D gene mutation. Clinical characteristics, differences in co-mutated genes, and survival differences between the two groups were compared. Results The frequency of KMT2D mutation was 31%, which is predominantly observed in elderly patients (P=0.07) and less in the double-expressor phenotype (P=0.07). Compared with the KMT2D wild-type group, KMT2D gene mutation was associated with higher co-mutation rates of CDKN2A (OR=2.82, P=0.01) and BCL2 (OR=3.84, P=0.016), while being mutually exclusive with MYC gene mutation (OR=0.11, P=0.013). In univariate survival analysis, no statistically significant difference in overall survival (OS) was found between the KMT2D mutation group and the wild-type group (P=0.54). Further analysis of the prognostic significance of KMT2D with other gene mutations indicated that patients with KMT2D^mutBTG2^mut had poorer OS than those with KMT2D^wt BTG2^mut (P=0.07) and KMT2D^wt BTG2^wt (P=0.05). On the contrary, patients with KMT2D^mut CD79B^mut had better OS than those with KMT2D^mut CD79B^wt (P=0.09), with no prognostic impact observed for other co-mutated genes. Multivariate Cox regression analysis revealed that Ann Arbor stages Ⅲ and Ⅳ (HR=2.751, 95%CI: 1.169-6.472, P=0.02), elevated LDH levels (HR=2.461, 95%CI: 1.396-4.337, P=0.002), Ki-67 index>80% (HR=1.875, 95%CI: 1.066-3.299, P=0.029), and KMT2D^mutBTG2^mut(HR=4.566, 95%CI: 1.348-15.471, P=0.015) were independent risk factors for OS in patients with DLBCL (P<0.05). Conclusion DLBCL patients with KMT2D mutation often have multiple gene mutations, among which patients with a co-mutated BTG2 gene have poor prognosis.

Objective To understand the individual dose monitoring of occupational external exposure for radiation workers in Wuhan City and analyze the dose change trend, and to provide a scientific basis for radiation protection management of radiation workers. Methods The data on the monitoring results of occupational external exposure of radiation workers in Wuhan City from 2017 to 2021 were collected through the National Personal Dose Registration System, and the individual dose levels of different years, different occupational categories, and different levels of hospitals were analyzed. Results A total of 9 134 radiation workers were investigated, with an average annual effective dose per capita of 0.20 mSv/a. The overall personal annual effective dose from 2017 to 2021 showed a decreasing trend (P<0.001). The per capita annual effective dose in medical applications was higher than that in industrial applications (0.22 mSv vs 0.14 mSv; P<0.001). Among medical applications, diagnostic radiologists had the highest average annual effective dose (0.27 mSv), and among industrial applications, industrial irradiators had the highest average annual effective dose (0.29 mSv). The proportion of personnel with personal annual effective doses exceeding 1 mSv was higher in interventional radiology and industrial nondestructive testing (4.90% and 1.90%). The annual effective dose per capita in Class I and unrated hospitals was higher (0.35 mSv). Conclusion The average annual effective dose of radiation workers in Wuhan City has decreased year by year and has not exceeded the national standard limit (20 mSv). Radiation protection management still needs to focus on personnel with personal annual effective doses exceeding 1mSv in interventional radiology and industrial nondestructive testing, and supervision over primary healthcare institutions and industrial radiation should be strengthened.

Objective To quantitatively evaluate the association of short-term exposure to ambient submicron particulate matter (PM₁) with hospital admissions for angina in older adults. Methods A case-crossover study was conducted among 46 687 older adults hospitalized for angina from 2016 to 2019 in Guangzhou medical institutions. Grid data on ambient PM₁ concentrations in Guangzhou were obtained from the ChinaHighAirPollutants (CHAP) dataset. Exposure to PM₁ was assessed according to each subject's residential addresses. Conditional logistic regression model was used to analyze the the exposure-response association between PM₁ and hospital admissions for angina. Results From 2016 to 2019, the average exposure level of PM₁ on the same day of hospital admissions (lag 0) for angina was 21.0 ± 11.5 μg/m³. The results of main model analysis showed that lag 0 day exposure to ambient PM₁ was significantly associated with a higher odds of hospital admissions for angina in older adults. Each 10 μg/m³ increase of PM₁ exposure level was significantly associated with a 1.31% (95% CI: 0.05%, 2.59%) increased odds of angina admissions. Results from a two-pollutant model adjusting for O₃ showed that the association between short-term exposure to PM₁ and odds of hospitalization for angina remained stable. According to the results of the above model, it was estimated that the excess hospitalization attributable to ambient PM₁ exposure accounted for 2.46% (95% CI: 0.09%, 4.76%) of the total admissions in Guangzhou during 2016-2019, corresponding to 1539 (95% CI: 54, 2976) admissions. No significant effect modification on the associations was observed by sex, age, or season. Conclusion Short-term exposure to ambient PM₁ was significantly associated with an increased odds of hospital admissions for angina in older adults.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Cellular dysfunction caused by vesicle transport is associated with a variety of diseases.The trans-Golgi network(TGN)to endosome transport is an important pathway of vesicle transport,and its defects leading to protein balance disorders has been linked to many diseases such as cancer,neurodegenerative diseases and diabetes mellitus.Gol-gi-associated gamma-adaptin ear-containing ADP-ribosylation factor-binding protein 2(GGA2)is a crucial protein in-volved in TGN-endosomal transport.It plays a significant role in the regulation of several diseases,including cancer,Al-zheimer disease,type 2 diabetes mellitus and cerebral ischemia,by mediating protein transport with important biological significance.This article provides an overview of the molecular structure of GGA2,its role in regulating clathrin-mediated protein transport between TGN and endosomes,and its potential implications for a variety of diseases.