[摘 要] 目的：采用生物信息学方法探索结肠癌组织中与焦亡相关的基因，并探讨其与预后的关系，为结肠癌患者提供新的治疗靶点。方法：分别从TCGA数据库、GEO数据库中下载结肠癌患者的基因表达、转录数据及临床数据。利用R软件提取出TCGA转录数据中细胞焦亡基因的表达量，并找到差异表达基因，构建差异表达基因的蛋白互作网络。采用单因素分析、聚类分析将基因进行分型，比较两种亚型之间生存差异，得到预后相关基因。然后通过Lasso回归分析、交叉验证及优化，得到基因系数（Coef系数），构建一种结肠癌预后的预测模型。根据该预测模型计算出TCGA样本的中位风险得分，将样本分为高、低风险组。以GEO样本作为验证组，分别对TCGA、GEO样本进行生存分析（Kaplan-Meier分析）、绘制ROC曲线、绘制风险曲线、PCA和t-SNE分析。结合模型中的风险评分，分别采用单因素及多因素分析来寻找结肠癌患者的独立预后因素。对高、低风险组进行GO和KEGG分析。最后行ssGSEA分析，对每个样本进行免疫细胞及免疫相关功能打分，得到高、低风险组之间免疫细胞及免疫细胞相关功能的差异。结果：共鉴定了52个焦亡基因在结肠癌及正常结肠组织中的表达，筛选出40个差异基因。通过Cox回归和Lasso回归分析，构建了一个基于15个基因的结肠癌预后风险预测模型，并将结肠癌患者分为高、低风险两组，两组之间生存有明显差异（P<0.001）。根据预测模型计算出TCGA样本的风险评分，并得到的中位风险评分，利用GEO数据库结肠癌患者进行验证，结果显示高低风险组之间生存率存在明显差异（P=0.013）。发现预测模型计算出的风险评分是预测结肠癌患者生存的独立预后因素。对差异基因进行GO富集分析、KEGG富集分析、ssGSEA分析结果显示，高风险组患者免疫细胞浸润明显减少。结论：通过生物学信息方法构建了一个基于15个基因的结肠癌患者预后风险预测模型，这些基因在结肠癌免疫中也发挥重要作用。

Objective:To investigate Mycoplasma pneumoniae pneumonia (MPP) infected by Mycoplasma pneumoniae (MP) in children of different age and gender admitted to the Pediatric and Respiratory Departments of 31 public hospitals in different regions of Shandong province in autumn and winter, and to further analyze the epidemiological characteristics of MPP in children.Methods:A cross-sectional study was conducted to collect and summarize basic information, epidemiological characteristics of children with MPP, laboratory and etiological test results of hospitalized from 31 public hospitals in Shandong Province from September 1, 2021 to December 15, 2021 through questionnaire issuance.The differences between groups were compared by the χ2 test. Results:Among 39 970 children hospitalized in 31 hospitals from September 1, 2021 to December 15, 2021, 17 613 were diagnosed with MPP, with a prevalence rate of 44.07%.There were more children diagnosed with MPP in Eastern Shandong than those in other regions.Serological tests were the main method of confirming the disease (16 730 cases, 76.06%). The combined infections in MPP patients were primarily caused by the influenza B virus and Streptococcus pneumoniae.A total of 33.03% (5 817/17 613 cases)of children with MPP underwent bronchoscopy.The main indication was atelectasis, and mucosal erosion/ulcers were found in most of the children.The main complication of MPP was pleural atelectasis (23.47%, 4 133/17 613 cases). Severe intrapulmonary and extrapulmonary complications also occurred in some patients, including necrotizing pneumonia (0.53%, 94/17 613 cases), pulmonary embolism (0.16%, 29/17 613 cases) etc. Conclusions:The prevalence of MPP in children in Shandong province is high in autumn and winter.It is necessary to pay attention to the clinical examination indicators of hospitalized children with MPP, actively give treatment to children with MPP, prevent the occurrence of complications, and promote the physical recovery of children.

OBJECTIVE: To explore the genetic basis of three children with unexplained mental retardation/developmental delay. METHODS: Peripheral venous blood samples were collected for routine G-banding karyotyping analysis and chromosomal microarray analysis (CMA). Whole exome sequencing (WES) was also carried out for patient 3. RESULTS: The karyotypes of the 3 children were normal. The result of CMA analysis of patient 1 was arr[GRCh37]: 2q22/3(145 128 071-145 159 029)×1, with a 31 kb deletion, which was predicted to be a pathogenic copy number variation. The deletion has involved exons 8 to 10 of the ZEB2 gene. Patient 2 was arr[hg19]:2q22.3 (145 071 457-146 881 759)×1, with a 1.81 Mb deletion involving the ZEB2 and GTDC1 genes. Patient 3 was arr[GRCh37]: 9p23p23(11 698 261-12 106 261)×1, with a 408 kb deletion containing no disease-associated gene. WES has identified a c.2102C>A (p.Ser701*) variant in exon 8 of the ZEB2 gene, which was included in ClinVar database and rated as pathogenic, and verified by Sanger sequencing as a de novo variant. CONCLUSION For the substantial clinical and genetic heterogeneity of Mowat-Wilson-syndrome, CMA and WES are helpful to identify the etiology of children with developmental delay/mental retardation of unknown causes, particularly those with peculiar facial features and multiple congenital malformations.
Child ; DNA Copy Number Variations ; Facies ; Glycosyltransferases/genetics* ; Hirschsprung Disease ; Humans ; Intellectual Disability/genetics* ; Microcephaly/genetics*

Objective:To explore and optimize the teaching content of clinical case discussion course based on clinical pathophysiology and therapy (CPPT), and to improve the teaching quality of this course.Methods:Self-compiled evaluation form was sent to all the students who participated in this course in 2016-2017 school year, and the teaching satisfaction and teaching characteristics were evaluated. The differences of evaluation results from students with different educational programs or teachers with different seniority were compared, and the correlation between evaluation results and teachers' seniority was analyzed.Results:The students had a high evaluation on the course, but students from different programs had significant different comments on thinking inspiring, speech encouraging, questions guiding, process holding and effective feedback, as well as the self-evaluation of mastery degree. For teachers with different seniority, there were significant differences in scores in all aspects except speech encouraging, but no differences in mastery degree. Spearman analysis showed that there was a certain correlation between scores and teachers' seniority.Conclusion:The overall situation of the CPPT case discussion course in our school is worthy of recognition, but it needs to be improved in many aspects.

Objective:To investigate the clinical characteristics of patients with lymphoplasmacytic lymphoma/Waldenstr?m macroglobulinemia (LPL/WM), and the diagnosis and optimal treatment of LPL/WM.Methods:The clinical data of 13 LPL/WM patients treated in Zhongnan Hospital of Wuhan University from January 2013 to June 2018 were retrospectively analyzed, and the literature was reviewed.Results:The median age of 13 patients was 60 years old (35-79 years old). There were 12 males and 1 female. Initial symptom was fatigue or edema of both lower limbs for majority of patients. All patients had immunoglobulin M (IgM) monoclonal, 3 of them had elevated immunoglobulin G (IgG) level, including 1 patient with monoclonal IgG. LDH was increased in 2 patients. Coombs test was positive in 5 patients. MyD88 gene mutation status was detected in 8 patients, of which gene mutation in 5 patients was positive. Among 13 patients, 1 patient lost follow-up, 3 patients died, 9 patients were alive with the median survival of 36 months (19-81 months).Conclusions:Incidence of LPL/WM is relatively low with a generally indolent evolution, but heterogeneity is not negligible. Few patients have poor treatment response with a quick disease progress. The high-risk patients undergoing hematopoietic stem cell transplantation after remission-induction chemotherapy may improve the prognosis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) , which suppressed SARS-CoV-2 replication . In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers ( < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.

Objective To understand the effect of teacher training to provide reference for teachers' teaching methods in the standardization of clinical resident training.Method The teachers carried out five days of teacher training.Teacher training adopted the method of theory teaching and group discussion.The main content of the training had a "daily rounds with teaching","the proper use of ORIME evaluation","feedback of sandwich type","a minute tutor teaching method","SOAP method to report cases".Before the training,100 residents were randomly selected to evaluate the teaching in teaching teachers through self-designed questionnaire.After the training,the questionnaire survey was conducted among 100 residents again.All data were statistically analyzed by SPSS 22.0.The measurement data were represented by (mean or + standard deviation),and the date were compared by t test.Results Residents believed that after the teacher training,teachers' teaching level improved (P＜0.05).The three aspects of "general and phased learning goals","training students' clinical thinking ability through questions","requiring students to report cases and give guidance and feedback" were the most obvious.The pre training score was (3.28 ± 0.92) (3.31 ± 1.12) (3.55 ± 0.85),and the corresponding score was after training (3.98 ±0.85) (4.19 ± 0.85) (4.11 ± 0.74).Conclusion From the comparison of the survey results before and after the residents,the teachers' teaching modes,skills and methods have been improved after receiving teachers' training.

ABSTRACT:Objective To detect the expressions of thioredoxin (TRX1)and c-jun-activation-domain binding protein-1 (JAB1)in patients with acute myelogenous leukemia (AML)and healthy controls,and measure the TRX1 level in AML patients at different stages for evaluating its clinical significance.Methods The expressions of TRX1 and JAB1 in leukemia samples were analyzed by RT-PCR and Western blot at mRNA and protein levels, respectively.The correlation between TRX1 and JAB1,and the relationship between the gene expression and peripheral blood leukocytes count were also analyzed.Furthermore,serum TRX1 was measured by ELISA.Results TRX1 and JAB1 expressions at both mRNA and protein levels were obviously upregulated in leukemia patients (P<0.05). TRX1 was positively related to JAB1 in both newly diagnosed and recurrent AML patients.And high levels of TRX1 and JAB1 expressions were associated with white blood cell (WBC)counts in AML patients (P<0.05).Moreover, abundance of TRX1 in serum was significantly greater in AML patients,especially in the patients with recurrent AML,than in healthy donors (P<0.05).Conclusion There is a positive correlation between the expressions of TRX1 and JAB1 ,which is closely related to the occurrence and progression of AML.

OBJECTIVETo evaluate the efficacies of different treatments for recurrent cervical lymph nodes and the factors contributing to prognosis in patients with nasopharyngeal carcinoma after radiotherapy.

METHODSClinical data of 79 patients with nasopharyngeal carcinoma after radiotherapy were retrospectively analyzed, and all cases were diagnosed as having recurrent cervical lymph nodes by pathological examination. The factors including sex, age, the interval between completion of radiotherapy and recurrence, rN stage, treatment methods, and the location relationship between recurrent lesion and primary tumor in the neck were analyzed for prognosis. Kaplan-Meier curves, Log-rank test and Cox's proportional hazards regression mode were used in the statistical analysis.

RESULTSThe median recurrence time was 26 months, and the 1- , 3- and 5-year overall survival rates were 77.9%, 53.4% and 39.7%. Cox's proportional hazards regression mode analysis indicated that age, rN stage, treatment methods, and the location relationship between recurrent lesion and primary tumor were significantly prognostic factors.

CONCLUSIONSNeck dissection is superior to re-radiotherapy in treatment of recurrent cervical lymph nodes in nasopharyngeal carcinoma after radiotherapy. The patients younger than 45 years old, in early rN stage and for recurrence in the center region of primary tumor have a better prognosis.

Carcinoma ; Humans ; Kaplan-Meier Estimate ; Lymph Nodes ; pathology ; Nasopharyngeal Neoplasms ; radiotherapy ; Neck ; Neck Dissection ; Neoplasm Recurrence, Local ; surgery ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate ; Treatment Outcome

Objective To make the chromosome karyotype analysis of 130 patients with leukemia by using the improved chromosome short-term culture method.Methods We optimized the main factors with a single factor gradient experiment in short-term culture of bone marrow chromosome, including colchicines concentration, duration of action of colchicines,and hypotonic time.On this basis,we conducted the three-factors and three-level orthogonal experiment to achieve improved bone marrow chromosome preparation system,which was later applied in 130 patients with leukemia in our hospital.Results The orthogonal experiment results showed that the optimum conditions were colchicines concentration of 0.07 μg/mL,colchicines action time of 80 min,and hypotonic time of 35 min during the preparation of the bone marrow chromosome.Using this method,the chromosome preparation success rate reached 97.69% and the detection rate of abnormal karyotype reached 82.3% in the chromosome karyotype analysis.Conclusion Bone marrow chromosome preparation system with colchicines concentration of 0.07 μg/mL and colchicines action time of 80 min,and hypotonic time of 35 min is worthy of clinical promotion.