Objective·To establish a mouse model with dormant cancer and no obvious metastasis by combining the preimmune strategy with the mVenus-p27K-cell G0 phase indicator system,the DTR-HSV/TK suicide gene system,and the Luc2-tdTomato tracer system.Methods·The KPC1199 mouse pancreatic cancer cell line was transfected with the mVenus-p27K-cell G0 phase indicator system,the DTR-HSV/TK suicide gene system,and the Luc2-tdTomato tracer system to construct a stable expression cell line,KPC1199-PDL.After being cultured in the serum-free condition,KPC1199-PDL cells were sorted into mVenus(+)cells and mVenus(-)cells by flow cytometry,and the expression of G0 phase-related genes was verified by real-time fluorescence quantitative PCR(qPCR).Sensitivity of KPC1199-PDL cells to diphtheria toxin(DTX)and ganciclovir(GCV)was evaluated by CCK-8 assay.A transsplenic portal vein-hepatic metastasis model was constructed in wild-type C57BL/6 mice to validate the function of KPC1199-PDL cells in vivo by immunofluorescence technology.The KPC1199-PDL cells were injected subcutaneously into C57BL/6 mice,followed by in situ injection of DTX and GCV to ablate subcutaneous tumors 5 d later,to obtain preimmunized mice.The transsplenic portal vein-hepatic metastasis models were constructed in these mice.Bioluminescence imaging was used to evaluate subcutaneous tumor ablation and hepatic metastasis in the mice,and immunofluorescence assay was used to detect the distribution and dormant state of tumor cells in the livers of preimmunize mice.Results·The three tool systems were stably expressed in KPC1199-PDL cells,and their proliferative ability was not affected.In the serum starving condition,some KPC1199-PDL cells expressed the mVenus protein,indicating entry into the G0 phase;the mVenus(+)cells sorted out by flow cytometry exhibited significantly higher expression of G0 phase-related genes(all P<0.05)and significantly lower expression of the proliferation-related gene compared with mVenus(-)cells(P<0.05).The CCK-8 assay demonstrated high sensitivity of KPC1199-PDL cells to DTX and GCV.In vivo experiments confirmed that KPC1199-PDL cells could be effectively traced through tdTomato protein expression,and could indicate entry into the G0 phase through mVenus protein expression.Following subcutaneous tumor implantation and drug ablation,preimmunized mice were successfully obtained.In the subsequent transsplenic portal vein-hepatic metastasis model,no metastatic signals were observed in the liver by bioluminescence imaging,but single or small clusters of G0 phase tumor cells expressing both mVenus and tdTomato,not expressing the proliferation marker Ki67,were detected in liver tissue sections by immunofluorescence analysis.Conclusions·A recognizable and traceable dormant cancer model is constructed with the combination of the preimmune mouse model of pancreatic cancer,the mVeneus-p27K-indicator system,the DTR-HSV/TK suicide gene system,and the Luc2-tdTomato tracer system.

Objective:To investigate the level of self-management and daily physical activity in patients with type 2 diabetes mellitus (T2DM) of Zang and Han nationalities in Tibetan, China, and to compare the difference in daily management between T2DM patients of Zang and Han nationalities, to develop reasonable and effective chronic disease management strategies for long-term out-of-hospital management of T2DM patients of Zang nationalities.Methods:A total of 265 T2DM patients with glycosylated hemoglobin (HbA1c) ≥ 7% who were admitted to the Endocrinology Ward of the Hospital of Chengdu Office of People's Government of Tibet Autonomous Region from November 2020 to April 2021 and who were from different regions of Tibet were included in this study according to inclusion and exclusion criteria. The general data of all included patients were collected. Glucose and lipid metabolism-related indicators were determined. The Generalized Diabetes Self-Management Efficacy Scale and International Physical Activity Questionnaires (IPAQ) were used to evaluate patients' levels of self-management and daily physical activity.Results:The hemoglobin level in T2DM patients of Zang nationality was (154.09 ± 24.11) g/L, which was significantly higher than that in T2DM patients of Han nationality ( P < 0.05). The total cholesterol, fasting blood glucose, and low-density lipoprotein in T2DM patients of Zang nationality were (4.63 ± 1.41) mmol/L, (7.94 ± 2.19) mmol/L, and (2.75 ± 1.11) mmol/L, respectively, which significantly higher compared with T2DM patients of Han nationality (all P < 0.05). Compared with T2DM patients of Han nationality, T2DM patients of Zang nationality had lower self-management scores (81.40 ± 15.44) points, diet control scores (17.26 ± 4.97) points, physical exercise scores (11.67 ± 4.42) points, prevention and treatment of high and low blood sugar score (12.21 ± 5.72) points. The differences were statistically significant (all P < 0.05). Moderate-intensity physical activity was a significant difference between T2DM patients of Zang and Han nationalities ( P < 0.05). Conclusion:Compared with T2DM patients of Han nationality, T2DM patients of Zang nationality have lower overall self-management levels, including diet control, physical exercise, prevention and management of high and low blood glucose, and moderate-intensity physical activity. Targeted individualized education should be carried out according to the Tibetan cultural characteristics, to further develop an intervention method and an out-of-hospital management strategy for chronic disease, which are suitable for T2DM patients of Zang nationality.

Consecutively hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) in Wuhan, China were retrospectively enrolled from January 2020 to March 2020 to investigate the association between the use of renin-angiotensin system inhibitor (RAS-I) and the outcome of this disease. Associations between the use of RAS-I (angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)), ACEI, and ARB and in-hospital mortality were analyzed using multivariate Cox proportional hazards regression models in overall and subgroup of hypertension status. A total of 2771 patients with COVID-19 were included, with moderate and severe cases accounting for 45.0% and 36.5%, respectively. A total of 195 (7.0%) patients died. RAS-I (hazard ratio (HR)= 0.499, 95% confidence interval (CI) 0.325-0.767) and ARB (HR = 0.410, 95% CI 0.240-0.700) use was associated with a reduced risk of all-cause mortality among patients with COVID-19. For patients with hypertension, RAS-I and ARB applications were also associated with a reduced risk of mortality with HR of 0.352 (95% CI 0.162-0.764) and 0.279 (95% CI 0.115-0.677), respectively. RAS-I exhibited protective effects on the survival outcome of COVID-19. ARB use was associated with a reduced risk of all-cause mortality among patients with COVID-19.
Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; COVID-19 ; Humans ; Hypertension/drug therapy* ; Renin-Angiotensin System ; Retrospective Studies

Objective:To investigate the prevalence and risk factors of diabetic retinopathy (DR) in patients in Tibet.Methods:A total of 239 patients with DR who received treatment in Department of Endocrinology and Metabolism, Hospital of Chengdu Office of People's Government of Tibet Autonomous Region from December 2017 to December 2018 were included in this study. They were divided into Han nationality and Zang nationality groups according to ethnicity. The condition of DR was evaluated with nonmydriatic ocular fundus photography according to the staging criteria of the severity of retinopathy.Results:The prevalence of DR in Tibet was 18.0％. The prevalence of DR in Tibetan and Han patients with diabetes was 17.5% and 19.2%, respectively. There was no significant difference in the prevalence of DR between Tibetan and Han patients with diabetes ( χ2 = 0.10, P = 0.754). Logistic regression analysis revealed that the risk factors of developing DR in Tibet included diabetes duration ( OR = 1.14, 95% CI: 1.05-1.24, P < 0.05), insulin therapy ( OR = 2.74, 95% CI: 1.09-6.89, P < 0.05), fasting plasma glucose ( OR = 1.37, 95% CI: 1.07-1.75, P < 0.05) and hypertension ( OR = 1.98, 95% CI: 1.02-3.86, P < 0.05). Diabetes duration and fasting plasma glucose are independent risk factors of DR. However, although elevated glycated hemoglobin levels were high in Tibet, they could not be used to predict the risk for developing DR ( OR = 1.01, 95% CI: 0.82-1.25, P > 0.05). Conclusion:Hyperglycemia is an important risk factor of developing DR in Tibet. However, elevated glycated hemoglobin levels cannot be used to predict the risk of developing DR in Tibet. Findings from this study fill the gap in the research on DR prevalence and ethic difference of DR prevalence, providing scientific evidence for prevention and treatment of DR in high-altitude areas.

Objective:To screen risk factors of postoperative venous thromboembolism (VTE) in patients in department of spinal surgery and establish a risk prediction model and conduct external validation.Methods:This study was a case-control study. Using the convenient sampling method, a total of 93 patients with VTE who underwent spinal surgery from May 2019 to April 2021 in the Second Xiangya Hospital of Central South University were selected as as the thrombosis group, while 100 patients who underwent spinal surgery without VTE during the same period were selected as the control group. A self-designed questionnaire about the risk factors of VTE in patients undergoing spinal surgery was used to investigate the patients. Binomial Logistic regression was used to analyze the risk factors of postoperative VTE in patients with spinal surgery and R software was used to establish a nomogram prediction model. A total of 46 patients (23 patient with VTE and 23 patients without VTE) from Department of Spinal Surgery from May and June 2021 were selected to verify the prediction model.Results:Age ( OR=1.603, 95% CI: 1.036-2.483) , operation time ( OR=0.253, 95% CI: 0.123-0.518) , use of internal fixation ( OR=0.128, 95% CI: 0.043-0.384) , application of bone cement ( OR=0.176, 95% CI: 0.048-0.652) , D-dimer ( OR=0.360, 95% CI: 0.147-0.884) and plasma fibrinogen degradation product ( OR=0.024, 95% CI: 0.006-0.091) were risk factors for VTE in spinal surgery patients. The prediction model was established according to the risk factors. The prediction agreement rate of the model was 0.865 and the sensitivity was 0.742. The model was externally validated with a sensitivity of 0.761, a specificity of 0.565 and an area under the receiver operating characteristic curve of 0.810. Conclusions:Age, operation time, use of internal fixation, application of bone cement, D-dimer and plasma fibrinogen degradation products are risk factors for postoperative VTE in patients with spinal surgery. Predictive models based on risk factors can predict the risk of VTE in spinal surgery patients.

目的：通过检索挖掘多个肿瘤公共数据库中肝细胞癌（hepatocellular carcinoma，HCC）的相关数据，从转录本、蛋白质、基因突变、蛋白相互作用及相应的信号通路和功能富集等不同层面，揭示BRD（bromodomain）蛋白家族与HCC的相关性，探索BRD蛋白家族作为HCC的肿瘤进展及预后判断的潜在生物标志物价值。方法：从UALCAN数据库中获取BRD蛋白家族所有成员在HCC患者组织样本中的mRNA表达数据和患者临床信息并进行相关性分析。从TCGA数据库中获取BRD蛋白家族mRNA表达水平与HCC患者预后的数据并进行相关性分析。从The Human Protein Atlas数据库中获取BRD蛋白家族在HCC组织和正常肝组织中的免疫组化结果并进行对比分析。使用STRING数据库获取BRD蛋白家族的相互作用蛋白网络，并利用CYTOSCAPE软件对获取的相互作用蛋白进行KEGG和GO分析。结果：BRD家族7个成员均在HCC组织中高表达（P<0.01），并且与HCC患者肿瘤分级和临床分期正相关（P<0.01）,同时BRD8和BRD9的低表达提示HCC患者预后较好（P<0.05）。BRD相互作用蛋白主要参与组蛋白乙酰化修饰，并高度富集于HCC相关的信号通路。TP53基因突变HCC患者的BRD1、BRD3、BRD4、BRD7、BRD8和BRD9表达水平显著高于非突变患者（P<0.05）。结论：BRD蛋白家族分子能够作为HCC患者肿瘤分级、临床分期和预后判断的潜在靶标。

Uncontrolled chronic inflammation plays key roles in the carcinogenesis of hepatocellular carcinoma (HCC). Among the risk factors of HCC, such as chronic viral hepatitis, alcoholic hepatitis, non-alcoholic steatohepatitis and so on, the occurrence and development of uncontrolled chronic inflammation are the core factors of HCC. The damaged or dead hepatocytes generated during the process of chronic inflammation may lead to the activation of immune cells in the liver, resulting in hepatic inflammation. Chronic and prolonged liver inflammation promotes the occurrence of cancer. During this process, different injuries or death patterns of hepatocytes and progression of inflammation caused by activation of different immune cells play different roles in hepatic carcinogenesis, involving multiple pathological or pathophysiological processes such as liver injury, inflammation, and compensatory proliferation, as well as function alteration of various cells, signaling pathways, and regulatory molecules. Further studies on the regulatory mechanisms of hepatic inflammation-induced carcinogenesis are helpful to provide theoretical basis for the intervention of occurrence of HCC. This review focused on the research progress of regulatory mechanisms involved in the hepatic inflammation-induced carcinogenesis.

Objective To investigate the value of the reverse shock index multiplied by GlasgowComa scale score (rSIG) and serum translocator protein 18000 in the prognosis of patients with severe traumatic brain injury. Methods One hundred and fifteen patients with severe traumatic brain injury were divided into the survival group and death group. SPSS 20.0 software was used to compare the vital signs, rSIG and TSPO between the two groups, and the relationship between rSIG and TSPO was analyzed. Receiver operating characteristic (ROC) curve was used to predict the value of rSIG and TSPO and their combination in the prognosis of patients with severe traumatic brain injury. According to the best cut-off value of rSIG and TSPO of ROC curve, patients were divided into the rSIG ≤ 14.8 group and rSIG>14.8 group, and the TSPO ≤ 1.84 ng/mL group and TSPO>1.84 ng/mL group, and the mortality between the groups was compared. Results In 115 patients, rSIG of the survival group was significantly higher than that of the death group, and TSPO was significantly lower than that of the death group [(10.5±4.4) vs. (6.4±4.1), 1.0(0.3,1.9) ng/mL vs.3.4 (2.0, 4.6) ng/mL, P<0.01]. The ability of rSIG combined with TSPO to forecast the mortality of patients with severe traumatic brain injury is not superior to the predictive power of these two indicators alone. The serum TSPO value and 28-day mortality in the rSIG > 4.15 group were significantly higher than those in the rSIG ≤ 4.15 group. The rSIG value of the TSPO ≤ 1.84 ng/mL group was significantly higher than that of the TSPO>1.84 ng/mL group; the 28-day mortality was significantly lower than that in the TSPO>1.84 ng/mL group. The rSIG value was negatively correlated with serum TSPO value (r=-0.611, P<0.01). Conclusions rSIG value and serum TSPO value have good predictive value for the prognosis of patients with severe traumatic brain injury, and can provide certain guiding significance in clinical practice.

Objective We performed a diffusion tensor imaging (DTI) study to explore the value of mode of anisotropy (MO) and other DTI-derived indices in assessing white matter fiber damage with mild to moderate Alzheimer disease (AD) patients. Methods This study was a prospective study. From February 2015 to February 2018, 33 patients with mild to moderate AD according to criteria were prospectively recruited as AD group at the First Affiliated Hospital of Wenzhou Medical University. Twenty healthy age-, sex-matched volunteers were recruited as normoal conctrast (NC) group. All subjects were performed by conventional brain MRI and DTI scans. The MO, anisotropic fraction (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AxD) of white matter fibers were obtained from DTI images after TBSS post-processing. The statistical analyses of DTI indices between AD group and NC group were carried out in Functional MRI Software Library software. Results As compared with NC group, we found 1 cluster with significant decrease FA and increase RD in AD group, the affected fibers involving bilateral anterior thalamic radiation, corticospinal tract, cingulate gyrus, hippocampus, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, uncinated fasciculus, superior longitudinal fasciculus (P<0.05). The MD value increase(P<0.1) was found to coincide with the decrease of FA and the increase of RD, while no significant increase or decrease in P<0.05. Three clusters of MO increases (P<0.05) accompanying with increases of AxD were found in left anterior limb of internal capsule, bilateral posterior limb of internal capsule, posterior forceps, left centrum semiovale and parietal lobe. Two clusters of MO decreases (P<0.05) accompanying with decreases of FA and increases of RD were found in fornix, forceps, external capsule, centrum semiovale and left frontal lobe. Conclusions The combination of MO with DTI routine tensor indices (FA, RD, MD, AxD) can further reveal the microstructural damage of white matter fibers in AD, especially to crossing-fibers. The abnormalities of MO combined with FA, RD and MD reveal the degeneration of both bundles of crossing-fibers,and the abnormalities of MO combined with AxD reveal that the white matter damage was mainly caused by axon damage of one bundle of cross fibers.

Objective To evaluate the clinical value of enhanced 3D-SPACE-STIR sequence MR in brachial plexus injury post-ganglionic nerve.Methods Eighteen patients with suspected brachial plexus injury were examined by routine MRI,3D-SPACE-STIR sequence and enhanced scan.The position,morphology,signal intensity of the brachial plexus injury and its relation with the proximal and distal portions of the brachial plexus were evaluated by senior radiologists.The image quality of plain and enhanced 3D-SPACE-STIR was evaluated respectively.Results The CNR of plain scan and enhanced 3D-SPACE-STIR sequence images were 32.31+2.98 and 43.66+2.78 respectively and the difference was statistically significant.Plain and enhanced 3D-SPACE-STIR sequences of supraclavicular nerves display rate were 95.0% and 96.1% respectively without having statistically significant difference.However,the subclavicular segment of the brachial plexus showed the displaying rates of 66.7% and 94.4% and the difference was statistically significant.Moreover, the background suppression effect of enhanced scan was better than that of the plain scan.Conclusion Enhanced 3D-SPACE-STIR sequence can clearly show brachial plexus injury,and its image quality is better than that of the plain scan,which can provide important imaging basis for accurate diagnosis of brachial plexus injury.