[摘 要] 目的：基于生物信息学方法探究几丁质酶-3样蛋白2（CHI3L2）在脑胶质瘤中的表达和生物学过程及其对患者临床预后的影响。方法：以中国脑胶质瘤基因组图谱（CGGA）为训练集（n = 325）、癌症基因组图谱（TCGA）为验证集（n = 702），对CHI3L2与脑胶质瘤患者临床病理特征的关系、预后价值和生物学过程进行交叉验证分析。用Kaplan-Meier法进行生存分析，采用Cox回归模型分析CHI3L2表达及相关临床病理特征与脑胶质瘤患者预后的关系，利用受试者工作特征（ROC）曲线分析CHI3L2在脑胶质瘤诊断中的价值，用GO、KEGG及GSVA途径分析CHI3L2在脑胶质瘤中的潜在生物学过程，构建CHI3L2的列线图以校准曲线及C-Index值来评估预测的准确性。WB法和qPCR 法检测CHI3L2在正常星形胶质细胞HA1800、胶质瘤U215和U87细胞中蛋白质与mRNA水平表达的影响。选取长沙市中心医院病理科保存的7例正常脑组织、5例低级别胶质瘤（LGG, WHOⅠ~Ⅱ级）和6例胶质母细胞瘤（GBM，WHO Ⅳ级）标本进行免疫组化染色分析，验证CHI3L2在正常脑组织和不同级别脑胶质瘤组织中的表达情况。结果：CHI3L2在GBM（P < 0.000 1）、非1p/19q编码（P < 0.000 1）、IDH-野生型（P < 0.000 1）、非MGMT甲基化（P<0.01）患者中显著表达，对GBM具有一定的预测价值，并且是脑胶质瘤患者总生存期（OS）的独立预后因素（P < 0.001）。构建的列线图对脑胶质瘤患者的生存预后预测性良好。CHI3L2与LGG和GBM的免疫细胞浸润水平、肿瘤免疫微环境和免疫细胞均有显著关系。脑胶质瘤中CHI3L2蛋白（P < 0.05）和mRNA（P < 0.000 1）的表达水平与更高的恶性程度相关，免疫组化的结果进一步验证了这个发现。结论：CHI3L2的表达与脑胶质瘤的恶性程度、临床病理特征及预后关系密切，并且参与脑胶质瘤的肿瘤微环境和免疫浸润，有望成为脑胶质瘤治疗策略中的一个新靶点。

Objective: To describe the prevalence of alcohol consumption and the burden of hemorrhagic stroke and hypertensive heart disease attributed to alcohol consumption in adults aged ≥20 years in 31 provinces in China from 2005 to 2018. Methods: Data from several national representative surveys was used to estimate provincial alcohol exposure level of adults aged ≥20 years from 2005 to 2018 by using kriging interpolation and locally weighted regression methods. Global disease burden research method and data, and China's death cause surveillance data were used to calculate the population attributable fraction (PAF) of hemorrhagic stroke and hypertensive heart disease and the deaths due to alcohol consumption in men and women aged ≥20 years in 31 provinces in China. China census data of 2010 were used to calculate the attributable standardized mortality rate. Results: In 2005 and 2018, the prevalence of alcohol consumption was 58.7% (95%CI: 57.8%-59.5%) and 58.4% (95%CI: 57.6%-59.3%), respectively, in men and 17.0% (95%CI: 16.6%-17.4%) and 18.7% (95%CI:18.1%-19.3%), respectively, in women. The daily alcohol intake was 24.6 (95%CI: 23.8-25.3) g and 27.7 (95%CI: 26.8-28.7) g, respectively, in men and 6.3 (95%CI: 6.0-6.5) g and 5.3 (95%CI: 5.0-5.6) g, respectively, in women. Alcohol exposure level was higher in the provinces in central and eastern China than in western provinces. The lowest exposure level was found in northwestern provinces. From 2005 to 2018, the PAF of hemorrhagic stroke death due to alcohol consumption increased from 5.5% to 6.8%, the attributable deaths increased from 50 200 to 59 100, while the PAF of hypertensive heart disease death due to alcohol consumption increased from 7.0% to 7.7%, the attributable deaths increased from 15 200 to 29 300. The PAF of hypertensive heart disease and hemorrhagic stroke was higher in men than in women, and in central and eastern provinces than in western provinces. In 2018, the standardized mortality rates of hemorrhagic stroke and hypertensive heart disease attributed to alcohol consumption were 4.58/100 000 and 2.11/100 000, respectively. Conclusions: The prevalence of alcohol consumption in men and daily alcohol intake of drinkers were relatively high in China, especially in eastern provinces. Alcohol exposure level was lower in women than in men. Regional measures should be taken to reduce the alcohol intakes in men and current drinkers in order to reduce the health problems caused by alcohol consumption.
Adult ; Male ; Humans ; Female ; Hemorrhagic Stroke ; Hypertension/epidemiology* ; Alcohol Drinking/epidemiology* ; Heart Diseases/epidemiology* ; China/epidemiology*

Objective: To estimate the risk for type 2 diabetes mellitus (T2DM) death attributed to insufficient whole grain intake in seven regions of China from 2005 to 2018. Methods: Based on China National Nutrition and Health Surveys and China Adult Chronic Disease and Nutrition Surveillance, ordinary Kriging method and locally weighted regression were used to estimate the level of whole grain intake of Chinese residents from 2005 to 2018. Based on the results of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 and Chronic Diseases Risk Factors Surveillance in China, we calculated the population attributable fraction (PAF), attributable death number and attributable mortality rate of T2DM due to insufficient whole grain intake in people aged ≥20 years in different regions of China, and we used the 2010 Chinese census data to compare the changes in T2DM deaths attributed to insufficient intake of whole grains in seven regions of China. Results: The whole grain intake levels of Chinese people over 20 years old in 2002, 2010 and 2015 were 19.0 g/d, 14.3 g/d and 19.8 g/d, respectively. The estimated overall whole grain intake level was 20.1 g/d in Chinese residents in 2018, and the intake level was 19.4 g/d in men and 20.8 g/d in women. Among the seven regions, the intake level was highest in northern China (47.4 g/d) and lowest in southwestern China (6.0 g/d). In 2018, the PAF was lowest in northern China (12.8%) and highest in southwestern China (19.3%). From 2005 to 2018, the PAF varied in the seven regions, and the PAF in northeastern China fluctuated around 18.5%. Other regions showed downward trends, especially in northern China and northwestern China, decreased by 26.4% and 21.2%, respectively. Over the past 14 years, the number of attributable deaths in the seven regions showed upward trends, with the highest annual average growth rate of 6.7% in southern China and the lowest annual average growth rate of 2.4% in northern China. In 2018, the standardized T2DM mortality rate attributed to insufficient whole grain intake in China was 3.13/100 000, and the attributable mortality was 3.21/100 000 in men and 3.05/100 000 in women. The standardized attributable mortality rate was highest in southwestern China (3.97/100 000) and lowest in northern China (1.78/100 000). From 2005 to 2018, the standardized attributable mortality rate increased by 11.5% in men and decreased by 8.1% in women. The standardized attributable mortality rate in southwestern, southern and central China increased by 23.7%, 21.3% and 4.2%, respectively. The standardized attributable mortality rate in northern, northwestern, eastern and northeastern China decreased by 20.9%, 11.0%, 4.5% and 3.9%, respectively. Conclusion: The whole grain intake level of Chinese residents was low, and the whole grain intake of residents in all seven regions should be increased, especially in the southwest, and men should have more whole grain intake than women to reduce the death risk in patients with T2DM.
Adult ; Male ; Humans ; Female ; Young Adult ; Whole Grains ; Diabetes Mellitus, Type 2/epidemiology* ; Risk Factors ; Chronic Disease ; China/epidemiology*

Objective: To investigate the clinicopathological and molecular characteristics of hepatic fibrinogen storage disease (FSD) in children. Methods: The clinical, histopathologic, immunophenotypic, ultrastructural and gene sequencing data of 4 FSD cases were collected from September 2019 to January 2021 in the Children's Hospital of Fudan University, Shanghai, China. Retrospective analysis and literature review were conducted. Results: There were 4 cases of FSD, 3 males and 1 female, aged 3 years and 3 months to 6 years (median age, 3 years and 4 months). The clinical manifestations were abnormal liver function and abnormal blood coagulation function, for which 2 cases had family genetic history. Liver biopsies revealed that, besides liver steatosis, fibrosis and inflammation, there were single or multiple eosinophilic inclusion bodies of various sizes and surrounding transparent pale halo in hepatocytes. Immunohistochemistry showed that the inclusion bodies were positive for anti-fibrinogen. Under the electron microscope, they corresponded to the dilated cisternae of the rough endoplasmic reticulum, which were occupied by compactly packed tubular structures and arranged into a fingerprint-like pattern with curved bundles. Gene sequencing revealed that the 2 cases of FGG mutation were located in exon 8 c.1106A>G (p.His369Arg) and c.905T>C (p.Leu302Pro), and 1 case was located in exon 9 c.1201C>T (p.Arg401Trp). No pathogenic variant was detected in the other case. Conclusions: FSD is a rare genetic metabolic disease and clinically manifests as abnormal liver function with hypofibrinogenemia. In the background of liver steatosis, fibrosis and inflammation, there are eosinophilic inclusions with pale halo in the hepatocytic cytoplasm, which can be identified by anti-fibrinogen immunohistochemical staining. The fingerprint-like structures under electron microscope are helpful for the diagnosis, while FGG sequencing detects the pathogenic mutation of exon 8 or 9 that can clearly explain the phenotype. However, the diagnosis of FSD cannot be completely ruled out if the relevant mutations are not detected.
Child ; Child, Preschool ; China ; Female ; Fibrinogen/chemistry* ; Humans ; Liver/pathology* ; Liver Diseases/pathology* ; Male ; Metabolic Diseases/pathology* ; Retrospective Studies

This study was to investigate the protective effects of puerarin on myocardial ischemia/reperfusion (MI/R) injury and the underlying mechanism. The MI/R-model was established by ligating the left anterior descending artery (LAD) for 60 min followed by 24 h reperfusion, puerarin (10, 30, and 100 mg·kg^-1) was orally administered 20 min before reperfusion. Cardiac function, myocardial infarct index, cardiac damage markers, inflammatory cytokines, and apoptosis index were measured to evaluate the protective effects of puerarin on MI/R injury. The activation of Nod-like receptor protein 3 (NLRP3) inflammasome and Toll like receptor 4 (TLR4)/myeloid differentiation factor 88 (Myd88)/nuclear factor kappa B (NF-κB) pathway were determined by Western blot. All animal experimental procedures were approved by the ethics committee of the Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences. The results showed that puerarin could significantly improve cardiac function, reduce myocardial infarct size, decease the levels of lactic dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase-MB (CK-MB), and cardiac troponin T (cTnT) and suppress cardiomyocyte apoptosis. Meanwhile, puerarin could notably decrease the levels of inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Western blot analysis revealed that puerarin could downregulate the expression of TLR4, Myd88, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cleaved-caspase 1, cleaved-gasdermin-D (GSDMD), IL-1β, and IL-18, as well as the phosphorylation levels of inhibitor of NF-κB α (IκBα), IκB kinase β (IKKβ), and NF-κB. These findings demonstrated that puerarin could alleviate MI/R injury by suppressing NLRP3 inflammasome activation, possibly via TLR4/Myd88/NF-κB pathway.

Objective:To compare the characteristics of four commonly adopted animal models of hyperuricemia （HUA） for traditional Chinese medicine （TCM） screening， so as to choose the adequate model for screening Chinese herbs and herbal compounds capable of lowering the uric acid. Method:Fifty-four male SD rats were randomly divided into nine groups， namely the normal group， hypoxanthine （HX） + oxonic acid potassium salt （OAPS） model group， yeast extract （YE） + OAPS model group， low-dose adenine （AD） + ethambutol （EMB） model group， high-dose AD + EMB model group， and four positive drug allopurinol （Allo） groups. The modeling lasted for 14 d. The levels of serum uric acid （SUA）， urinary uric acid （UUA）， serum creatinine （SCr）， urea nitrogen （BUN）， kidney injury molecule 1 （KIM-1）， and neutrophil gelatinase-associated lipocalin （NGAL） were detected on the 3rd， 7th， and 14th days. Urine was collected on the 7th and 14th days to investigate changes in urine volume， and the crystals in the residual urine were observed under a polarizing microscope. After the modeling， the kidney was harvested and weighed， followed by pathological examination. Result:The urine volumes in the HX + OAPS model group and high-dose AD + EMB model group were significantly reduced （P<0.05）. The renal indexes of each model group， except for the YE + OAPS model group， were significantly elevated （P<0.05， P<0.01）. The increase in SUA of the HX + OAPS model group and YE + OAPS model group started later （P<0.05）. The KIM-1 and NGAL levels of the HX + OAPS model group rose significantly from the 7th day （P<0.05， P<0.01）， and the BUN increased significantly on the 14th day （P<0.05）. There was no significant difference in the above-mentioned indicators in the YE + OAPS model group. The SUA levels of the low- and high-dose AD + EMB model groups increased significantly on the 3rd day （P<0.05， P<0.01）， with a persistent increase found in the low-dose AD + EMB model group. Besides， the increase in BUN， KIM-1， and NGAL occurred later （P<0.05， P<0.01）. By contrast， the high-dose AD + EMB model group exhibited a transient increase in SUA. Moreover， the SCr， BUN， KIM-1， and NGAL elevation occurred earlier and were more obvious than those in the low-dose AD + EMB model group （P<0.01）. Remarkable histomorphological abnormalities were detected in the kidney of all model groups， except for the YE+OAPS model group， with the most severe injury present in the high-dose AD+EMB model group. Conclusion:The four models commonly used to screen TCM have their own characteristics. In the four models， the SUA elevation in the HX + OAPS model group and YE + OAPS model group started later， with the mild renal injury observed in the HX + OAPS model group instead of the YE + OAPS model group. The SUA of the low-dose AD + EMB model group increased rapidly and lasted for a long time， accompanied by mild renal injury. The SUA of the high-dose AD + EMB model group only showed a transient increase， accompanied by severe renal injury. The investigation on the characteristics and application of different models and the evaluation of these models based on sensitive and objective indicators are helpful for determining the suitable model for the screening of TCM targeting HUA in the future.

The demand for acquiring different languages has increased with increasing globalization. However, knowledge of the modification of the new language in the neural language network remains insufficient. Although many details of language function have been detected based on the awake intra-operative mapping results, the language neural network of the bilingual or multilingual remains unclear, which raises difficulties in clinical practice to preserve patients' full language ability in neurosurgery. In this review, we present a summary of the current findings regarding the structure of the language network and its evolution as the number of acquired languages increased in glioma patients. We then discuss a new insight into the awake intra-operative mapping protocol to reduce surgical risks during the preservation of language function in multilingual patients with glioma.
Brain Mapping ; Brain Neoplasms/surgery* ; Glioma/surgery* ; Humans ; Language ; Multilingualism

【Objective】To establish a cell model of radiation injury of human bone marrow mesenchymal stem cells（hBMMSC），and to provide experimental basis for further study on the pathogenesis of osteoradionecrosis of the jaws（ORNJ）.【Methods】After X-ray irradiation，the gene expression change of Beclin1，Sox2，Nanog，RUNX2 and OGN in hBMMSC were evaluated by Western blot and RT-qPCR. The apoptosis rate change was detected by Annexin- V/PI double staining method. The proliferation rate change was determined by clone formation experiment. The alkaline phosphatase activity change was detected by microplate method.【Results】The gene expressions of Beclin1 increased with the doses increased，while Sox2，Nanog，RUNX2 and OGN in hBMMSC were all down- regulated after irradiation. The apoptotic rate increased，the colony formation rate decreased and the alkaline phosphatase activity decreased also.【Conclusion】X-ray irradiation can cause ionizing radiation injury of hBMMSC. We successfully established a cell model of hBMMSC radiation injury，the model can be applied to the experimental study of the pathogenesis of ORNJ.

Background:Clinical outcomes of undifferentiated arthritis (UA) are diverse,and only 40 ％ of patients with UA develop rheumatoid arthritis (RA) after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17 (7.3％) patients failed to follow up during the study.Among the 217 patients who completed the study,83 (38.2％) patients went into remission.UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9％ vs.16.8％,x2=8.228,P=0.008),anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7％ vs.10.7％,x2 =43.897,P ＜ 0.001),and double-positivity rate of RF and anti-CCP antibody (38.1％ vs.4.1％,x2 =32.131,P ＜ 0.001) than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017,95％ confidence interval:5.803-55.938;P ＜ 0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.