Research Progress of Key Molecular Events Related to Progression of Colorectal Cancer / 肿瘤防治研究

The continuous development of high-throughput and single-cell sequencing technologies and the emergence of spatial transcriptome sequencing have allowed the continuous discovery of temporal and spatial molecular events in the progression of colorectal cancer (CRC) to better understand its mechanism of malignant progression. Genetic variations (mutation of APC and P53, etc.) and mismatch repair of DNA, posttranscriptional regulation, such as epigenetic alteration, and dynamic alteration of complex molecular networks have their own special molecules that play key roles. Drug resistance and metastasis in the late stage of CRC progression are closely related to these key molecular events. This article reviews the research progress and explores key molecular events in the malignant progression of CRC to provide scientific basis and ideas for elucidating the regulatory mechanism of CRC and evaluating its prognosis prediction and treatment.

Global incidence and mortality of renal cell carcinoma in 2020 / 中华流行病学杂志

Objective: To analyze the global epidemiology of renal cell carcinoma (RCC) in 2020. Methods: The incidence and mortality data of RCC in the cooperative database GLOBOCAN 2020 of International Agency for Research on Cancer of WHO and the human development index (HDI) published by the United Nations Development Programme in 2020 were collated. The crude incidence rate (CIR), age-standardized incidence rate (ASIR), crude mortality rate (CMR), age-standardized mortality rate (ASMR) and mortality/incidence ratio (M/I) of RCC were calculated. Kruskale-Wallis test was used to analyze the differences in ASIR or ASMR among HDI countries. Results: In 2020, the global ASIR of RCC was 4.6/100 000, of which 6.1/100 000 for males and 3.2/100 000 for females and ASIR was higher in very high and high HDI countries than that in medium and low HDI countries. With the rapid increase of age after the age of 20, the growth rate of ASIR in males was faster than that in females, and slowed down at the age of 70 to 75. The truncation incidence rate of 35-64 years old was 7.5/100 000 and the cumulative incidence risk of 0-74 years old was 0.52%. The global ASMR of RCC was 1.8/100 000, 2.5/100 000 for males and 1.2/100 000 for females. The ASMR of males in very high and high HDI countries (2.4/100 000-3.7/100 000) was about twice that of males (1.1/100 000-1.4/100 000) in medium and low HDI countries, while the ASMR of female (0.6/100 000-1.5/100 000) did not show significant difference. ASMR continued to increase rapidly with age after the age of 40, and the growth rate of males was faster than that of females. The truncation mortality rate of 35-64 years old was 2.1/100 000, and the cumulative mortality risk of 0-74 years old was 0.20%. M/I decreases with the increase of HDI, with M/I as 0.58 in China, which was higher than the global average of 0.39 and the United States' 0.17. Conclusion: The ASIR and ASMR of RCC presented significant regional and gender disparities globally, and the heaviest burden was in very high HDI countries.

Exploring the application of decision analysis in public health emergencies / 上海预防医学

When facing two or more choices， sound decision-making is critical. In the field of clinical medical practice and public health， more and more researchers use decision-making analysis as an important tool to assist in making the optimal choices. Public health emergencies have the characteristics of group cases， sudden and uncertain. In addition to causing serious damage to public health， they may also have varying degrees of impact on socio-economic， psychological and even social stability. At present， we have not seen the application of mature and sound decision analysis in public health emergency response. This paper reviewed the development of decision analysis in the medical field and the application of common decision-making models in clinical practice. Combined with the current situation of global infectious disease outbreaks and prevention and control， this paper puts forward the concepts and prospects of establishing an auxiliary decision-making system for public health emergencies， aiming to provide a scientific method for medical and health workers to respond to public health emergencies.

Establishment and evaluation of the polygenic disease risk prediction model / 上海预防医学

To establish a disease risk prediction model based on genetic susceptibility genes and environmental risk factors， which can target high-risk population as early as possible， and intervene in the environmental risk factors in this population. Moreover， accurate screening of genetically susceptible populations can enhance the efficiency of health system. In recent years， with the maturation and cost reduction of high-throughput gene testing， gene testing has been widely used in individual clinical decision-making and will play a more important role in medical and health decision-making. The correlation between genetic testing and disease risk prediction is increasing， making it a prominent research topic in this field. This review summarizes the approaches for establishing and evaluating risk prediction models and discusses potential future challenges and opportunities.

Drafting reports of clinical studies / 上海预防医学

Clinical research reports serve as the presentation of scientific research findings and directly reflect the quality of the research. This article describes the writing of different types of clinical research reports， such as observational studies and randomized controlled trial studies， with a particular focus on randomized controlled trials. Each scientific research design has its reporting focus， and the writing of scientific research papers has uniform requirements and a specific writing format. Mastering the proper format of drafting research reports is of practical value and significant importance for conduction high-quality clinical research.

Selection and application of statistical methods in medical research / 上海预防医学

Statistics plays an important role in medical research， and the selection of appropriate statistical methods is crucial for drawing reliable and valuable conclusions. This paper provides a brief introduction to commonly used statistical analysis methods for medical data， covering descriptive analysis， parametric test， nonparametric test， correlation analysis， regression analysis， and analysis of survival data. It focuses on discussing the assumptions of multiple linear regression， logistic regression and Cox proportional risk regression， as well as how to choose the appropriate statistical methods for analyzing and interpreting medical data based on different research objectives and data types.

Epidemiological feature, viral shedding, and antibody seroconversion among asymptomatic carriers and symptomatic/ presymptomatic COVID-19 patients

Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. However, data concerning the epidemiological features, viral shedding, and antibody dynamics between asymptomatic SARS-CoV-2 carriers and COVID-19 patients remain controversial. We enrolled 193 subjects infected with SARS-CoV-2 in Ningbo and Zhoushan, Zhejiang, China from January 21 to March 6, 2020. All subjects were followed up to monitor the dynamics of immunoglobulin M (IgM) and IgG against SARS-CoV-2. Of those, 31 were asymptomatic carriers, 149 were symptomatic patients, and 14 were presymptomatic patients. Compared to symptomatic patients, asymptomatic carriers were younger and had higher levels of white blood cell and lymphocyte, lower levels of C-reactive protein and viral load, and shorter viral shedding duration. Conversion of IgM from positive to negative was shorter in asymptomatic carriers than in COVID-19 patients (P=0.030). The proportion of those persistently seropositive for IgG was higher in COVID-19 patients than in asymptomatic carriers (P=0.037). Viral load was higher in symptomatic than presymptomatic patients. Viral shedding was longer in presymptomatic patients than in asymptomatic carriers. Conclusively, asymptomatic carriers have a higher antiviral immunity to clear SARS-CoV-2 than do symptomatic patients and this antiviral immunity is not contributable to humoral immunity.

Effects of robotic and laparoscopic-assisted surgery on lymph node dissection and short-term outcomes in patients with Siewert II adenocarcinoma of esophagogastric junction / 中华胃肠外科杂志

OBJECTIVE@#To compare the effects of robotic and laparoscopic-assisted radical total gastrectomy on lymph node dissection and short-term outcomes in patients with Siewert type II adenocarcinoma of esophagogastric junction (AEG).@*METHODS@#Inclusion criteria: the tumor center was located between 2 cm above and below the esophagogastric junction and was confirmed as adenocarcinoma by endoscopic biopsy.@*EXCLUSION CRITERIA@#tumor with local invasion of the liver,spleen, pancreas or other organs; intraoperative finding of tumor dissemination or distant metastasis; patients undergoing palliative surgical treatment or preoperative neoadjuvant chemotherapy; patients with serious heart diseases, lung diseases, liver diseases, kidney diseases and other comorbidities; patients with multiple primary cancers;patients receiving emergency surgery. According to the above criteria, 82 patients with Siewert type II AEG who underwent gastrointestinal surgery at the Affiliated Hospital of Qingdao University from October 2014 to October 2018 were enrolled in the study. They were randomly divided into robotic surgery groups (41 cases) and laparoscopic group (41 cases) according to a computer-generated randomized allocation table. Both groups underwent radical total gastrectomy plus D2 lymph node dissection through the transabdominal esophageal hiatus approach. The intraoperative conditions and postoperative short-term outcomes were compared between two groups, including surgery time, intraoperative blood loss, length of esophagectomy, postoperative complications, postoperative gastrointestinal recovery time, length of hospital stay, postoperative unplanned reoperation rate and rehospitalization rate. Mean±SD is used for the measurement data that conforms to the normal distribution, and two independent sample t-tests are used to compare the two groups; the comparison of the count data is performed by the χ² test.@*RESULTS@#There were 35 males (85.4%) with age of (62.3±10.0) years and body mass index of (24.4±3.2) kg/m² in the robotic surgery group. There were 37 males (90.2%) with age of (62.5±10.0) years and body mass index of (23.8±2.6) kg/m² in the laparoscopic group. No significant differences in the baseline data between two groups were found (all P>0.05). All the patients of both groups completed R0 resection successfully without conversion to laparotomy or perioperative death. Compared with the laparoscopic group, the robotic group had less intraoperative blood loss [(70.7±39.9) ml vs. (110.2±70.6) ml, t=3.118, P=0.003], longer resected esophagus [(3.0±0.7) cm vs. (1.9±0.5) cm, t=8.759, P0.05). The highest lymph node metastasis rate was approximately 20% and observed in No.1, No.2, No.3, and No.7, followed by No.8a, No.9, No.11p, and No.110 with around 5%. The lymph node metastasis rate in other stations (No.4sa, No.4sb, No.4d, No.5, No.6, No.11d, No.12a, No.19, No.20 and No.111) was less than 5%.There were no significant differences in postoperative complication rate, postoperative fever time, postoperative exhaust and defecation time, fluid diet time, and postoperative hospital stay (all P>0.05). There were 2 patients(4.9%) with unplanned reoperation and 1 patient (2.4%) with unplanned re-admission in the laparoscopic group,while 3 patients (7.3%)with unplanned reoperation and 2 patients (4.9%)with unplanned re-admission in the robotic surgery group, whose differences were also not statistically significant (χ²=0.240,P=0.675;χ²=0.346,P=1.000).@*CONCLUSION@#Robot-assisted radical total gastrectomy for Siewert II AEG is safe and feasible, which is characterized by more sophisticated operation, less blood loss and higher quality of lymph node dissection, especially for subphrenic and inferior mediastinal lymph nodes.

Research on reform of epidemiology teaching / 中华流行病学杂志

Epidemiology is a traditional subject mainly based on principles and concepts,and its teaching method needs further improving to meet the requirement of the new trend of education reform.Lecture-based teaching,problem-based teaching,case-based teaching,and intemet based teaching,such as flip class,massive open online course and micro-lecture,all have its own unique merits in the practice of epidemiology teaching.So the combination of traditional teaching and online teaching is the most promising mode."Rain class",a mixed mode,is an efficient tool to present the epidemiology case more actually in class.Thus,teaching design and application of "rain class" are worth research.

Research on reform of epidemiology teaching / 中华流行病学杂志

Epidemiology is a traditional subject mainly based on principles and concepts,and its teaching method needs further improving to meet the requirement of the new trend of education reform.Lecture-based teaching,problem-based teaching,case-based teaching,and intemet based teaching,such as flip class,massive open online course and micro-lecture,all have its own unique merits in the practice of epidemiology teaching.So the combination of traditional teaching and online teaching is the most promising mode."Rain class",a mixed mode,is an efficient tool to present the epidemiology case more actually in class.Thus,teaching design and application of "rain class" are worth research.

Follistatin-like protein 1 plays a tumor suppressor role in clear-cell renal cell carcinoma / 癌症

BACKGROUND@#We previously showed that the expression of follistatin-like protein 1 (FSTL1) was significantly down-regulated in metastatic clear-cell renal cell carcinoma (ccRCC). In this study, we aimed to characterize the role of FSTL1 in the development of ccRCC.@*METHODS@#The effects of FSTL1 on cell activity and cell cycle were investigated in ccRCC cell lines with altered FSTL1 expression. Gene expression microarray assays were performed to identify the major signaling pathways affected by FSTL1 knockdown. The expression of FSTL1 in ccRCC and its effect on postoperative prognosis were estimated in a cohort with 89 patients.@*RESULTS@#FSTL1 knockdown promoted anchorage-independent growth, migration, invasion, and cell cycle of ccRCC cell lines, whereas FSTL1 overexpression attenuated cell migration. FSTL1 knockdown up-regulated nuclear factor-κB (NF-κB) and hypoxia-inducible factor (HIF) signaling pathways, increased epithelial-to-mesenchymal transition, up-regulated interleukin-6 expression, and promoted tumor necrosis factor-α-induced degradation of NF-κB inhibitor (IκBα) in ccRCC cell lines. FSTL1 immunostaining was selectively positive in epithelial cytoplasm in the loop of Henle, and positive rate of FSTL1 was significantly lower in ccRCC tissues than in adjacent renal tissues (P < 0.001). The multivariate Cox regression analysis showed that the intratumoral FSTL1 expression conferred a favorable independent prognosis with a hazard ratio of 0.325 (95% confidence interval 0.118-0.894). HIF-2α expression was negatively correlated with FSTL1 expression in ccRCC specimens (r = - 0.229, P = 0.044). Intratumoral expression of HIF-2α, rather than HIF-1α, significantly predicted an unfavorable prognosis in ccRCC (log-rank, P = 0.038).@*CONCLUSIONS@#FSTL1 plays a tumor suppression role possibly via repressing the NF-κB and HIF-2α signaling pathways. To increase FSTL1 expression might be a candidate therapeutic strategy for metastatic ccRCC.

Prospect of Ultra Performance Convergence Chromatography Technology and Applications in TCM Research and Quality Control / 世界科学技术-中医药现代化

The research and quality control of traditional Chinese medicine has meaningful importance, because it has influence not only in the health and treatment of patients, but also in the solid growth and development of phar-maceuticals companies. In some cases, for the complex of TCM, the common QC method on single or multi-target compounds can't really and truly disclose the quality of the Chinese materia medica. Therefore, a lot of researchers do plenty of works to make clear the effectiveness basis, to improve the quality and realize the modernization of TCM. All of these works close together with modern analysis and separation technology. In this article, a novel analy-sis technology-UltraPerformance Convergence Chromatography (UPC2) based its characters and applications should be introduced. It should be a helpful technology for the TCM researchers to facilitate the study and QC works.

Effects of down-regulation of integrin-beta(1) expression on migration and hepatic metastasis of human colon carcinoma / 华中科技大学学报（医学）（英德文版）

Organ-specific tumor cell adhesion to extracellular matrix (ECM) components and cell migration into host organs often involve integrin-mediated cellular processes. Direct integrin-mediated cell adhesion to ECM components in the space of Disse appears to be required for the successful liver metastatic formation of colon cancer. In the present study, human colon cancer HT-29 cells were transfected by liposome with integrin-beta(1) antisense oligodeoxynucleotide (ASODN). The integrin-beta(1) gene expression in HT-29 cells was significantly down-regulated. The migration of HT-29 cells was assayed using transwell cell culture chambers in vitro. The number of migrating HT-29 cells in experimental group was far less than that in control group (P<0.05). The models of hepatic metastasis in nude mice were established by the intrasplenic injection of transfected HT-29 cells. Thirty days later, the nude mice were killed and the average number of hepatic metastases (4.00+/-0.93 per mouse), average volume (10.10+/-6.50 mm(3) per mouse), average weight (0.0440+/-0.0008 g per mouse) in experimental group were remarkably reduced as compared with those in control group (P<0.05). Integrin-beta(1) expression in the hepatic metastasis was studied by immunohistochemistry (SP). Positive cell percentage of hepatic metastases in experimental group was markedly decreased as compared with that in control group (P<0.05). It was concluded that integrin-beta(1) may take part in hepatic metastasis, and down-regulation of integrin-beta(1) expression may play a key role in decreasing migration and hepatic metastasis of human colon carcinoma cells (HT-29).

Simultaneous determination of six flavonoids in Flos Chrysanthemi Indici by RP-HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To develop an HPLC method for the determination of luteolin-7-O-glycoside, apigenin-7-O-glycoside, linarin, luteolin, apigenin and acacetin in Flos Chrysanthemi Indici simultaneously.</p><p><b>METHOD</b>The reversed phase HPLC system consisting of a C18 column (4.6 mm x 250 mm, 5 microm) and a mixture of acetonitrile and 0.05% phosphate acid with gradient elution as the mobile phase was adopted. The absorbance was monitored at 326 nm.</p><p><b>RESULT</b>The linear response range was 1.08-21.5 mg x L(-1) (r = 0.9990), 0.278-5.57 mg x L(-1) (r = 0.9994), 5.58-112 mg x L(-1) (r = 0.9999), 0.521-10.4 mg x L(-1) (r = 0.9995), 0.162-3.25 mg x L(-1) (r = 0.9999) and 0.288-5.76 mg x L(-1) (r = 0.9998), respectively (n = 6). The average recoveries (n = 9) of six flavonoids were 96.34%-104.0%. All of RSD of precision (n = 6) and repeatability (n = 6) were less than 1.2% and 2.6%.</p><p><b>CONCLUSION</b>The validation data demonstrated that the method was accurate and repeatable, and can be ase to measure the six flavonoids in Flos Chrysanthemi Indici.</p>

Establishment of orthotopic mouse model of human renal cell carcinoma and expression analysis of metastasis-associated genes / 第二军医大学学报

Objective:To establish orthotopic mouse models of human renal cell carcinoma and to separate metastatic or non-metastatic renal cell carcinoma(RCC) from the same source.Methods: Surgical specimens/cell suspensions were transplanted into the various tissues of BALB/c nude mice(subcutis,cellular orthotopic injection into renal capsule,perinephrium,surgical orthotopic implantation into renal capsule).Tumorigenicity and metastasis were subsequently evaluated.Immunohistochemical analysis was employed to determine the expression of VEGF,bFGF,P16,Bcl-2 and C-met in the metastatic and non-metastatic RCC xenograft.Results: The incidences of tumorigenicity and metastasis of orthotopic model were the highest,being at 73.3%(11/15)and 20%(3/15),respectively.Compared with the non-metastastic RCC, VEGF expression was upregulated in the metastatic RCC(P

Separation of invasive subpopulation from primary human renal cell carcinoma via in vitro invasion assay / 第二军医大学学报

Objective:To isolate the invasive and non-invasive cells from primary human renal cell carcinoma(RCC) in vitro.Methods: Fresh RCC surgical specimens from 32 primary RCC patients were primarily cultured following enzyme digestion or mechanical minimization in vitro.In vitro invasion assay using the Transwell cultures coating Matrigel was performed for separation and recovery of invasive and non-invasive cells from the primary culture of 3 RCC patients.The concentration of Matrigel,recovery time and trypsinization were subsequently optimized.Results: The successful rate of primary culture was(90.6%)(29/32).Recovery of invasive cells was performed ideally when matrigel(diluted into 1.0 mg/ml and 20 ?l) was coated onto the filter of the well;cell suspension was at a concentration of 5?10~(5)/ml and invasive cells were recovered on the 5th day of culture.The growth of non-invasive cells was scattered,while that of the invasive cells was focal.The doubling time of invasive cells was 36.1 h and that of non-invasive was 50.6 h.Conclusion: The in vitro invasion assay using the Transwell is able to separate and recover the highly invasive primary RCC cells.The primary cells represent intact subpopulation composition,but it can hardly get through the life span of human primary tumor cells.