OBJECTIVES: Intracranial aneurysm (IA) has an insidious onset, and once ruptured, it carries high rates of mortality and disability. Cardiometabolic factors may be associated with the formation and rupture of IA. This study aims to summarize the application of Mendelian randomization (MR) methods in research on cardiometabolic factors and IA, providing insights for further elucidation of IA etiology and pathogenesis. METHODS: Literature about MR-based IA studies published up to February 21, 2024, was retrieved from PubMed, Embase, Web of Science, CNKI, and Wanfang. Two researchers independently performed literature screening, data extraction, and quality assessment. A narrative synthesis approach was used to conduct a qualitative systematic review of the included studies. RESULTS: A total of 11 MR-based studies on IA published between 2017 to 2024 were included, of which 4 were rated as high quality. These studies investigated the associations between blood pressure, blood lipids, blood glucose, obesity-related indicators, and inflammatory cytokines with IA and its subtypes, though issues of duplication were noted. Four MR studies based on the same European population but using different instrumental variable selection criteria, as well as another MR study in a different European cohort, consistently identified blood pressure as a risk factor for IA and its subtypes. Findings for blood lipids, blood glucose, obesity-related indicators, and inflammatory cytokines were inconsistent across MR studies. CONCLUSIONS Blood pressure appears to increase the risk of IA and its subtypes. Associations between other cardiometabolic factors and IA/subtypes require further in-depth investigation. Given the inherent limitations of MR studies, causal inferences should be made cautiously in combination with other lines of evidence.
Humans ; Mendelian Randomization Analysis ; Intracranial Aneurysm/etiology* ; Risk Factors ; Blood Pressure ; Blood Glucose ; Obesity/complications* ; Cardiometabolic Risk Factors ; Lipids/blood*

Ring finger protein 213(RNF213)was first identified as a susceptible gene for Moyamoya disease,and also found to be associated with various vascular related diseases such as intracranial artery occlusion/stenosis,ischaemic stroke,intracranial aneurysm,cerebral arteriovenous malformation,etc.This article systematically reviewed the literature of RNF213,providing an overview of the association and possible mechanisms between RNF213 variation and related diseases,in order to provide reference for the prevention,diagnosis,and treatment of related diseases.

This study was designed to investigate the role of ring finger protein 20(RNF20)in host innate immunity against RNA viruses.Dual luciferase reporter assay was employed to examine the effects of RNF20 overexpression on Sendai virus(SeV)infection-induced activation of interferon a4(Ifna4)gene promoter in 293T human embryonic kidney epithelial cells.Rnf20 myeloid conditional knockout mouse model was constructed(Rnf2OF/F;Lyz2-Cre),and the frequency of myeloid subsets in the bone marrow,spleen,blood of Rnf20F/F;Lyz2-Cre mice and littermate Rnf20F/F mice were detected by flow cytometry.After bone marrow-derived macrophages(BMDMs)were cultured and subjected to the infection of SeV and vesicular stomatitis virus(VSV),Western blot was used to detect the phosphorylation of transcription factor interferon regulatory factor 3(IRF3)and nuclear factor-κB(NF-κB).ELISA was used to detect the production of IFN-β,TNF-α and IL-6,and Bulk RNA-sequencing was employed to explore transcriptional changes.Furthermore,M1 and M2 macrophage polarization was induced by LPS and IL-4,respectively,to confirm the changes revealed by transcriptome analysis.Data showed that RNF20 overexpression showed no significant effect on SeV infection-induced activation of Ifna4 gene promoter in 293T cells.There is almost no difference in the development of myeloid subsets between Rnf20F/F;Lyz2-Cre and Rnf2OF/F mice.After RNA viral infection of BMDMs from Rnf20F/F;Lyz2-Creand Rnf201 mice,the phosphorylation of IRF3 and NF-κB p65 and the expression of IFN-[3,TNF-α and IL-6 were comparable between the two groups,while the expression levels of several genes related to macrophage polarization were significantly different.The loss of RNF20 showed the tendency of hindering M1 macrophage polarization while promoting M2 macrophage polarization.In conclusion,RNF20 does not affect RNA viral infection-induced activation of IRF3 or NF-κB pathways,but it might get involved in the resolution of inflammation afterwards.

OBJECTIVES: Stroke has become the leading cause of death and disability among adults in China. This study aims to analyze the disease burden based on gender and age and the risk factors for stroke subtypes in China 2019, and to provide reference for targeted stroke prevention and control. METHODS: Based on 2019 data of the Global Burden of Disease (GBD), the gender and age in patients with different stroke subtypes (ischemic stroke, intracranial hemorrhage, subarachnoid hemorrhage) in China 2019 was described by using disability-adjusted life years (DALY), and attributable burden of related risk factors was analyzed. RESULTS: In 2019, the burden of intracranial hemorrhage was the heaviest one in China, resulting in 22.210 6 million person years of DALY, following by ischemic stroke and subarachnoid hemorrhage, resulting in 21.393 9 and 2.344 7 million person years of DALY, respectively. Among them, except the 0-14 age group, the disease burden of different subtypes of stroke in men was higher than that in women. The disease burden of ischemic stroke was increased with age in both men and women, with the heaviest disease burden in ≥70 years group. The disease burden of intracranial hemorrhage and subarachnoid hemorrhage was the heaviest in males aged 50-69 years old, and in females aged ≥70 years and 50-69 years, respectively. Metabolic factors were the main risk factors in all ages of different stroke subtypes, and the most important risk factor was high systolic blood pressure. Other risk factors were different between men and women. Smoking, high body mass index, high low-density lipoprotein, and outdoor particulate matter pollution were the main risk factors for stroke in men, while high body mass index, outdoor particulate matter pollution, and high fasting blood glucose were the main risk factors of stroke in women. The main risk were different among different age groups. CONCLUSIONS The burden and attributable risk factors for different stroke subtypes are discrepancy in different gender and age groups. Targeted interventions should be conducted in the future to reduce the burden of stroke.
Male ; Adult ; Humans ; Female ; Infant, Newborn ; Infant ; Child, Preschool ; Child ; Adolescent ; Middle Aged ; Aged ; Subarachnoid Hemorrhage/epidemiology* ; Quality-Adjusted Life Years ; Cost of Illness ; Stroke/etiology* ; Risk Factors ; China/epidemiology* ; Particulate Matter ; Ischemic Stroke ; Intracranial Hemorrhages/etiology*

Objective:To identify tooth number abnormalities on pediatric panoramic radiographs based on deep learning.Methods:Eight hundred panoramic radiographs of children aged 4 to 11 years meeting the inclusion and exclusion criteria were selected and randomly assigned by writing programs in Python (version 3.9) to the training set (480 images), verification set (160 images) and internal test set (160 images), taken in Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology between November 2012 to August 2020. And all panoramic radiographs of children aged 4 to 11 years taken in the First Outpatient Department of Peking University School and Hospital of Stomatology from June 2022 to December 2022 were collected as the external test set (907 images). All of the 1 707 images were obtained by operators to determine the outline and to label the tooth position of each deciduous tooth, permanent tooth, permanent tooth germ and additional tooth. The deep learning model with ResNet-50 as the backbone network was trained on the training set, validated on the verification set, tested on the internal test set and external test set. The images of test sets were divided into two categories according to whether there was abnormality of tooth number, to calculate sensitivity, specificity, positive predictive value and negative predictive value, and then divided into four types of extra teeth and missing permanent teeth both existed, extra teeth existed only, missing permanent teeth existed only, and normal teeth number, to calculate Kappa values. Results:The sensitivity, specificity, positive predictive value and negative predictive value were 98.0%, 98.3%, 99.0% and 96.7% in the internal test set, and 97.1%, 98.4%, 91.9% and 99.5% in the external test set respectively, according to whether there was abnormality of tooth number. While images were divided into four types, the Kappa value obtained in the internal test set was 0.886, and that in the external test set was 0.912. Conclusions:In this study, a deep learning-based model for identifying abnormal tooth number of children was developed, which could identify the position of additional teeth and output the position of missing permanent teeth on the basis of identifying normal deciduous and permanent teeth and permanent tooth germs on panoramic radiographs, so as to assist in diagnosing tooth number abnormalities.

Objective:To explore the clinical efficacy and adverse reactions of albumin-bound paclitaxel (Nab-P) and conventional paclitaxel combined with cisplatin and concurrent radiotherapy for the treatment of patients with locally advanced esophageal squamous cell carcinoma.Methods:Forty-nine patients with locally advanced esophageal squamous cell carcinoma admitted to the First People's Hospital of Suqian from November 2016 to May 2020 were included. Of the 49 patients, 23 cases were treated with Nab-P combined with cisplatin and concurrent radiotherapy (NP group), 26 cases were treated with conventional paclitaxel combined with cisplatin and concurrent radiotherapy (TP group). All patients received 2 cycles of chemotherapy. The curative efficacy was evaluated one month after the end of radiotherapy, and the curative effect and adverse reactions of the two treatment regimens were compared.Results:The objective remission rate in NP group was 78.3% (18/23), and the disease control rate was 100.0% (23/23). The objective response rate in TP group was 61.5% (16/26), and the disease control rate was 92.3% (24/26). The objective response rate and disease control rate in NP group were higher than those in TP group, but the differences were not statistically significant (both P > 0.05). The common adverse reactions were mainly hair loss, loss of appetite, bone marrow suppression, radiation esophagitis, radiation pneumonia, malaise and myalgia. The incidence rate of grade 3-4 acute bone marrow suppression in NP group (8.7%, 2/23) was lower than that in TP group (38.5%, 10/26), and the difference was statistically significant ( χ2 = 4.35, P = 0.037). The incidence rate of myalgia in NP group (26.1%, 6/23) was lower than that in TP group (61.5%, 16/26), and the difference was statistically significant ( χ2 = 4.85, P = 0.028). Conclusions:Nab-P combined with cisplatin and concurrent radiotherapy has good efficacy in the treatment of patients with locally advanced esophageal squamous cell carcinoma, and the incidence rate of adverse reactions is lower than that of conventional paclitaxel combined with cisplatin and concurrent radiotherapy, so that the regimen is safe.

The stem cell biology plays an important role in the application and research of the clinical medicine and biology. The breakthrough of the therapies for a variety of human diseases depends on the rapid growth of stem cell biology. It is of great significance to set up graduate curriculum of stem cell biology in the medical college. This article elaborates the design and implementation of the course of Stem Cell Biology including the selection of the teaching materials, design of course outline, teaching content, evaluation methods, teaching introspection and other aspects, thus providing references and communications in this field.

【Objective】 To analyze the cure time from diagnosis to cure of coronavirus disease 2019(COVID-19). 【Methods】 Based on the time of admission, diagnosis, and discharge of cured cases announced by the provincial and municipal health committees, the average period from diagnosis to discharge was calculated. And based on the aggregate data including the cumulative number of diagnoses, the number of curedcases and the number of deaths and their proportional relationship, we calculated the cure time. 【Results】 The cure time curve of 580 COVID-19 patients had skewed distribution, with a skewness of 1.09, a mean cure time of (14.6±6.7) days, a median of 13 days, and a 95% confidence interval (6.9, 21.0). The average cure time calculated based on the relationship between the cumulative number of diagnoses, the number of cured cases and the number of deaths was (13.3±3.5)d, with a median of 13.5 d. The average value of the cure time calculated based on the proportion of cured cases to the number of endpoints was (14.2±4.2)d, with the median number of 14.5 d. Based on the calculation of the relationship between the cumulative number of diagnosed cases, the number of cured cases and the number of deaths, the median cure time of cases with COVID-19 in Wuhan, Hubei Province, and the whole country was 15 days, 15.5 days and 15 days, respectively. The mediancure time for COVID-19cases in Wuhan, Hubei, and the whole country was 14 days. 【Conclusion】 The median cure time of COVID-19 is 13-15.5 days. There is some variation at different time of the outbreak, but there is not much difference between different regions.

【Objective】 To investigate the death time of patients with coronavirus disease 2019 (COVID-19). 【Methods】 The death time was calculated and analyzed using individual data and aggregated data through the daily notification of the epidemic situation and the death cases published on the website of the Heath Commission of China and provinces. 【Results】 In the 153 patients who died of COVID-19, the shortest time from onset to death was 4 days and the longest time was 50 days with the mean±standard deviation of (16.7±9.2) days. The median was 14 days and the 95% confidence interval was 4.6-42.9. The shortest time from admission to death was 1 day and the longest time was 50 days with the mean ± standard deviation of (12.1±7.8) days. The median was 11 days and the 95% confidence interval was 2-32.8. The time curve from diagnosis to death was skewed. The death time from diagnosis to death was 0 to 48 days with the mean ± standard deviation of (11.1±8.9) days. The median was 9 days, the interquartile interval was 10.5 days, and the 95% confidence interval was 0-35.4. It took 3 days from onset to admission and 1 day from admission to diagnosis. Aggregated data showed that the time from diagnosis to death of COVID-19 patients in China, China (except Hubei Province), Hubei Province and Wuhan City was 8, 9, 6 and 6 days, respectively. 【Conclusion】 The time from diagnosis to death of COVID-19 patients varied significantly, with the median time of 6-9 days in different regions.

Zinc levels are high in pancreatic β-cells, and zinc is involved in the synthesis, processing and secretion of insulin in these cells. However, precisely how cellular zinc homeostasis is regulated in pancreatic β-cells is poorly understood. By screening the expression of 14 Slc39a metal importer family member genes, we found that the zinc transporter Slc39a5 is significantly down-regulated in pancreatic β-cells in diabetic db/db mice, obese ob/ob mice and high-fat diet-fed mice. Moreover, β-cell-specific Slc39a5 knockout mice have impaired insulin secretion. In addition, Slc39a5-deficient pancreatic islets have reduced glucose tolerance accompanied by reduced expression of Pgc-1α and its downstream target gene Glut2. The down-regulation of Glut2 in Slc39a5-deficient islets was rescued using agonists of Sirt1, Pgc-1α and Ppar-γ. At the mechanistic level, we found that Slc39a5-mediated zinc influx induces Glut2 expression via Sirt1-mediated Pgc-1α activation. These findings suggest that Slc39a5 may serve as a possible therapeutic target for diabetes-related conditions.