Bioinformatics analysis of survival-related genes in pancreatic cancer based on GEO and TCGA database / 西安交通大学学报(医学版)

【Objective】 Based on Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database, survival analysis was used to screen the key prognostic genes involved of pancreatic cancer patients. 【Methods】 Two pancreatic cancer gene chips (Microarray) from the GEO database and transcriptome sequencing (RNA-seq) from the TCGA database were used to filter the survival-related genes using Kaplan-Meier (KM) analysis and Cox risk model, and the target genes were intersected. Prognosis-associated genes were screened first and then pathway enrichment analysis or immune-enrichment analysis was performed based on these genes to find out their potential molecular mechanisms in regulating pancreatic cancer. 【Results】 In this study, five survival-related genes (i.e., CDO1, DCBLD2, FAM83A, ITGA3 and SLC16A3) were screened out. Multifactorial Cox regression analysis and clinical correlation analysis showed that high CDO1 expression was a protective factor for pancreatic cancer prognosis, and its antitumor effect was associated with its role in inhibiting the malignant biological behavior of pancreatic cancer cells and promoting the infiltration of immune killer cells in pancreatic cancer. 【Conclusion】 This study suggests that CDO1 is a potential tumor suppress gene of pancreatic cancer, and the tumor inhibition effect of CDO1 may be related to its role in remodeling the immune microenvironment of pancreatic cancer.

Effect of shRNA silencing of Sp1 on radiosensitivity of glioma cells / 中华放射肿瘤学杂志

Objective:To evaluate the effect of down-regulation of Sp1 expression on the radiosensitivity of glioma cells.Methods:The oligonucleotide sequence encoding shRNA was designed and synthesized, and cloned into LV3 (H1/GFP & Puro) vector to construct the recombinant. U251 and U87 cells were infected with recombinant lentivirus, then the stably-transfected cell lines were obtained by puromycin screening. The expression levels of Sp1 mRNA and protein were detected by RT-PCR and Western blot. Cell survival was detected by clonal survival assay, cell cycle was determined by flow cytometry, and DNA damage was measured by immunofluorescence assay, respectively.Results:At 72 h after infection, high expression of Sp1 lentiviral vector was observed in two cell lines under fluorescence microscope. RT-PCR and Western blot confirmed that the expression levels of Sp1 mRNA and protein were significantly down-regulated in both transfected cells (both P<0.01) and the silencing rates of Sp1 were above 90%. The sensitization enhancement ratio (SER) of shRNA-U251 and shRNA-U87 cells at 10% cell survival level were 1.39 and 1.18, respectively. After irradiation, the G 2/M phase ratio and the number of γ-H2AX foci in two Sp1 knockout groups were significantly increased. Conclusion:shRNA silencing of Sp1 increases the G 2/M phase arrest induced by X-ray, aggravates the degree of DNA double-strand breaks, and improves the radiosensitivity of glioma cells.

Characteristics and Clinical Implication of UGT1A1 Heterozygous Mutation in Tumor / 中国肺癌杂志

BACKGROUND@#The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear.@*METHODS@#A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization.@*RESULTS@#There were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not.@*CONCLUSIONS@#In clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.

Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods

SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used anti-viral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further and studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.

An overview of multiple linear regression model and its application / 中华预防医学杂志

Multiple Linear Regression (MLR) is a generalization of simple linear regression and is one of the commonly used models in multivariate statistical analysis. This article introduces the MLR model from the perspective of practical application. Four parts, including basic principle, application examples, the application condition and diagnosis, and the extension of the model, are sequentially illustrated in this article. Particularly, in the last part, alternative methods of the model are introduced when the application condition of the model is not met. We sincerely hope that this article could make our audiences have a better understanding of the MLR model in order to improve the efficiency of data utilization and statistical analysis by correctly performing this model in their research.

Overview of logistic regression model analysis and application / 中华预防医学杂志

Logistic regression is a kind of multiple regression method to analyze the relationship between a binary outcome or categorical outcome and multiple influencing factors, including multiple logistic regression, conditional logistic regression, polytomous logistic regression, ordinal logistic regression and adjacent categorical logistic regression. This paper illustrates the basic principle, independent variable selection and assignment, applied condition, model evaluation and diagnosis for multiple logistic regression model. Moreover, the principle and application for polytomous logistic regression and ordinal logistic regression models were also introduced. By providing SAS codes and detailed explanations of the result for an example of obesity, readers could be able to better understand logistic regression model, and apply this method correctly to their research and daily work, so as to improve their capacity of the data analysis.

Design and analysis of two groups interrupt time series / 中华流行病学杂志

Interrupted time-series (ITS) is a quasi-experimental design which evaluates the effectiveness of an intervention based on time-series outcome variables. Compared with the single group of ITS, the two groups of ITS can better control the influence of pre-interventional confounding factors and evaluate the effectiveness of the intervention. This paper summarizes the principles and statistical methods of two groups of ITS by an example of evaluating vaccine effect on the incidence of a disease in two cities. The regression model is fitted by Prais-Winsten method and Newey-West method and the results are explained and compared in detail. When the intervention is performed with other confounding interventions at the same time, the two groups of ITS can be more effective to balance the existing trends before the intervention, and evaluate the effectiveness of intervention. The method of two groups of ITS has important practical significance, providing new insights in program evaluation.

The design of interrupted time series and its analytic methods / 中华预防医学杂志

Interrupted time series (ITS) is a statistical method for the quasi-experimental design specific to the outcome of time series, in which the effectiveness of an intervening measure is evaluated by examining change in slope and immediate change in level. The key feature of ITS is that the secular trend of time series prior to the intervention can be effectively controlled so as to accurately estimate the intervention effect. The design principle and statistical method for ITS were illustrated by an example of evaluating halving policy for the expert registration fee in the general hospital of a city. The segmented linear regression was used to fit the above time series data and the results were explained in detail. Meanwhile, the study design and model fitting along with explanations of the results with respect to the effects of two types of successive interventions and on different time-points of an intervention were illustrated as well in this paper. The existed upward or downward trend should be taken into account in order to accurately estimate the intervention effect as it exists in most of the public health surveillance data. Two parameters, known as change in slope and immediate change in level, were employed to evaluate the effect of the intervention. The ITS analysis can be widely applied to the program evaluation as it could enrich methods of the evaluation compared to the traditional model of the program evaluation.

Overview of multivariate regression model analysis and application / 中华预防医学杂志

Analyses of the multivariate regression model are ued very widely in the medical research. Analytical methods of the mutivariate regression model including multiple linear regression, logistic regression, Poisson regression and Cox proportional hazard model were introduced in this article. The contents of the article covered the application conditions of regression models, analytical procedures, strategies of selecting independent variables, extended discussions of regression models and application notes. It is expected that authors could understand the principle of the mutivariate regression model, accurately use these analytical methods in their research, improve the efficiency of data utilization, and enhance the level of statistical analyses.

The caregiver burden and related factors on quality of life among caregivers for patients with lung cancer / 中华肿瘤杂志

Objective@#To explore the influence of caregiver burden on quality of life among caregivers for patients with lung cancer in Beijing.@*Methods@#From August to October in 2017, 336 caregivers for patients with primary lung cancer from a large tertiary hospital were recruited to this survey by convenient sampling method. The Caregiver Reaction Assessment (CRA) and the WHO Quality of Life-BREF (WHOQOL-BREF) Instruments were used to evaluate the caregiver burden and quality of life. The demographic characteristics were evaluated using Pearson chi-square or Fisher′s exact tests. In addition, using the 4 dimensions of quality of life scale as the dependent variables while the 5 dimensions of caregiver burden and demographic variables as the explanatory variables, we conducted the multiple linear stepwise regression analysis (the defaults were 0.15 for FORWARD and BACKWARD).@*Results@#The scores of family caregivers′ esteem, impact on schedule, impact on finances, impact on health and lack of family support were 4.30±0.47、3.55±0.74、3.10±0.91、2.60±0.78、2.32±0.73, respectively. Regression results showed that demographic factors, including marriage, occupation and relationship with patients and impact on health, caregivers′ esteem and impact on finances dimensions of caregiver burden were the factors which influenced the quality of life of caregivers.@*Conclusions@#The caregiver burden in patients with lung cancer is mainly focused on impact on schedule and finances. Impact on health, finances and caregivers′ esteem (seven items were reverse-scored) are significantly negatively correlated with quality of life of caregivers.

Health economic evaluation reporting guideline and application status / 中华预防医学杂志

Using the guidelines of health economic evaluation reporting is conducive to regulating the contents of this reporting, improving the quality of studies into health economics evaluation. This article summarized the history of the guidelines and specified the instrument used to study " Quality of Health Economic Studies (QHES)" and the checklist about Consolidated Health Economics Evaluation Reporting Standards (CHEERS)-the two specific evaluation contents in this guideline, the article also introduced its present application status of the guideline and its pros and cons. The checklist of CHEERS emphasized the evaluation of this report, while QHES instrument focused on quantitative evaluation on the quality of economic studies. Despite different emphasis, the two guides are actually mutually complemented.

The practice and experience of clinical scenarios discussion teaching for medical students be-fore clinical probation / 中华医学教育探索杂志

Objective To investigate the learning outcome of clinical scenarios discussion im-plemented in teaching medical students before clinical probation. Methods Using standardized pa-tients (SP) to simulate the clinical common difficult situation, all eight year program clinical medicine students (84) of Grade 2008 who were about to enter the clinical probation were given clinical commu-nication education guidance. Through five classification variables questionnaire and return visit, the teaching effect was evaluate. Epidata 3.0 was used to input data, and the SPSS 15.0 was used to make descriptive analysis of the questionnaire and proportion comparison. Results We found 35.4%(29) and 63.4%(52) of subjects liked and approval this training, respectively;90.2%(74) of the subjects thought the diffi-culty of this train was moderate; 77.3% (65) of subjects believed that it was necessary to set the clinical scenarios discussion before clinical probation. Conclusions The implementation of clinical scenarios discussion before clinical probation was effective on inducing the medical students to pay attention to the doctor-patient communication, and deep thinking about the communication notice mat-ters and cop-ing styles in clinical environment.

Prognostic study in ST-elevated myocardial infarction patients with or without left ventricular aneurysms / 中华急诊医学杂志

Objective To determine the renal function compromised in patients after ST-segment elevation myocardial infarction (STEMI) with left ventricular aneurysms (LVA) by measurement of serum cystatin C (Cy-C) concentrations and Cy-C-based eGFR.Methods A total of 355 patients admitted from January 2011 to December 2012 could be categorized into group A (STEMI without LVA,n =183) and group B (STEMI with LVA,n =172) confirmed by echocardiography in 24 hour after admission.Of them,273 patients were treated with primary percutaneous coronary intervention (PCI) after admission and included in the analysis.Cy-C-based estimated glomerular filtration rate (eGFR) and creatinine (Cr)-based eGFR were calculated for evaluating cardiac function in tern to assess the magnitude of compromised renal function.The correlation between magnitude of compromised renal function and in-hospital mortality was analyzed.Distributions of categorical variables were compared using the chi-square test.Continuous variables were compared by one-way ANOVA with the Bonferroni test.Results The in-hospital mortality rate of whole patient cohort was 14.0％.Mortality in the group B was 18.6％ and in the group A was 9.8％ (P ＜ 0.01).With multivariable regression analysis,the compromised renal function was found when the Cr-based eGFR was ＜60 mL/ (min · 1.73 m2) or Cy-C-based eGFR was ＜ 60 mL/min/1.73m2 which were independently associated with in-hospital mortality (OR 0.13,95％ CI 0.02-0.7,P =0.02 ; OR 0.01,95％CI 0.003-0.05,P ＜ 0.01).Compared with the acute myocardium infarction (AMI) patients with chronic kidney disease (CKD) stage 2,the Cy-C based eGFR was greater in the AMI patients with LVA group (P ＜ 0.05),and compared with AMI with CKD stages 3 or CKD 3-5,this difference was also significant (P ＜ 0.01).Conclusions Renal dysfunction was an independent predictor of in-hospital mortality in patients with STEMI,especially in patients with LVA.Cy-C and Cy-C based eGFR were more sensitive to judge renal dysfunction in STEMI patients with LVA.

Analysis of the incidence of short-term illness in four counties of Hunan Province / 中南大学学报(医学版)

OBJECTIVE@#To determine the prevalence and incidence of illness of two-week duration, and the factors influencing these, among residents 15 years and older in four counties of Hunan Province.@*METHODS@#Data were sampled from four counties of Hunan Province for the Fourth National Health Service Survey. Incidence and two-week prevalence of disease were used to assess the health service needs of residents. A non-conditional, stepwise logistic regression was employed to explore the influencing factors.@*RESULTS@#The two-week prevalence and incidence were 11.5% and 3.9%, respectively, in four counties of Hunan. The three leading diseases of two-week prevalence were: respiratory diseases, digestive diseases, and musculoskeletal diseases. Non-conditional stepwise logistic regression showed that urban residents had 0.64 times the risk of two-week illness compared with the rural residents (P< 0.05); residents in the 45-59 year age group and the 60+ year age group had 1.69 and 2.62 times the risk of two-week illness compared with residents in the 15-44 year age group, respectively (P<0.05). The widowed had 1.91 times the risk of prevalence of two-week illness contrasted to singles (P<0.05); the students had 0.29 times the risk of two-week illness contrasted to the workers (P<0.05); urban residents had 0.63 times the risk of two-week illness compared with the rural (P<0.05); the widowed had 2.37 times the risk of incidence of two-week illness compared with singles (P<0.05).@*CONCLUSION@#The majority of health service needs of residents of four counties is generated by three diseases: respiratory diseases, digestive diseases, and musculoskeletal diseases. Relatively, rural residents, the elderly, employed persons and the widowed have higher health service needs than others and deserve specific attention.

Fractional anisotropy and somatosensory evoked potentials in the postcentral gyrus subcortex after acute infarction of the posterior limb of the internal capsule / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the relationship between fractional anisotropy (FA) and somatosensory evoked potentials (SEP) in the postcentral gyrus subcortex in patients with acute infarction of the posterior limb of the internal capsule.</p><p><b>METHODS</b>Thirty-one patients with acute infarction of the posterior limb of the internal capsule underwent diffusion tensor imaging to obtain the FA values of the subcortical region of the postcentral gyrus with manual placement of the regions of interest (ROI). SEP and the sensory functions of the patients were examined and graded.</p><p><b>RESULTS</b>In each SEP grade group, the FA values of the subcortical region of the postcentral gyrus were significantly decreased on the diseased side compared to those of the normal side (P<0.05). The FA values of the diseased side differed significantly between patients with different SEP grades (P<0.05), and increased SEP abnormalities were associated with lowered FA values. The sensory function of the patients was positively correlated to the grade of SEP (r=0.520, P<0.05).</p><p><b>CONCLUSION</b>For patients with acute infarction of the posterior limb of the internal capsule, the changes of FA in the postcentral gyrus subcortex on the diseased side are correlated and complementary to SEP in evaluating the prognosis.</p>

Investigation of traffic law violations among middle school students in Hunan province and the influencing factors / 中南大学学报(医学版)

OBJECTIVE@#To determine the incidence of traffic law violations among middle school students of Hunan province and to identify the influencing factors.@*METHODS@#Stratified sampling and cluster sampling were used to randomly select students from 96 classes of 16 middle schools. Road traffic law violations were measured through recalling the occurrence of 5 common violations in the prior year. Most of influencing factors were collected by self-designed questionnaire except for family support function and parenting that were measured by the family assessment device (FAD) and the parenting locus of control scale (PLOC), respectively. Kruskal Wallis H test and multinomial logistic regression were used to analyze the data.@*RESULTS@#The overall incidence rate of five common traffic law violations among middle school students in Hunan province fell between 16.6%-43.3%. Except for running against traffic light or not using pedestrian crossings (8.2%), students with the other 4 traffic law violations merely accounted for less 4%. The rates of students with 1, 2, 3, 4 and 5 kinds of traffic law violations were 25.3%, 17.8%, 10.2%, 6.2% and 3.4%, respectively. Logistic regression showed that there were 3 factors (area, junior or senior high school, and single child or not), 5 factors (area, junior or senior high school, sex, single child or not, and class leader or not) and 6 factors (type of school, junior or senior high school, sex, class leader or not, family support function, and type of family education) significantly associating with the occurrence of 1, 2, and 3 or more traffic law violations, respectively.@*CONCLUSION@#Only a small proportion of students often or almost always break traffic law or break several traffic laws at the same time. Students with serious traffic law violations should be targeted by school safety education and intervention.