Multi-target combinatory strategy to overcome tumor immune escape / 医学前沿

Immune therapy has become the fourth approach after surgery, chemotherapy, and radiotherapy in cancer treatment. Many immune checkpoints were identified in the last decade since ipilimumab, which is the first immune checkpoint inhibitor to cytotoxic T-lymphocyte associated protein 4, had been approved by the US Food and Drug Administration (FDA) for the treatment of unresectable or metastatic melanoma in 2011. The use of several antibody drugs that target PD1/PD-L1 for various cancer treatments has been approved by the FDA. However, fewer people are benefitting from immune checkpoint inhibitor treatment in solid cancers. Approximately 80% of patients do not respond appropriately because of primary or acquired therapeutic resistance. Along with the characterization of more immune checkpoints, the combinatory treatment of multiimmune checkpoint inhibitors becomes a new option when monotherapy could not receive a good response. In this work, the author focuses on the combination therapy of multiple immune checkpoints (does not include targeted therapy of oncogenes or chemotherapy), introduces the current progression of multiple immune checkpoints and their related inhibitors, and discusses the advantages of combination therapy, as well as the risk of immune-related adverse events.

Role of artificial intelligence in the diagnosis and treatment of gastrointestinal diseases / 中华胃肠外科杂志

The rapid development of computer technologies brings us great changes in daily life and work. Artificial intelligence is a branch of computer science, which is to allow computers to exercise activities that are normally confined to intelligent life. The broad sense of artificial intelligence includes machine learning and robots. This article mainly focuses on machine learning and related medical fields, and deep learning is an artificial neural network in machine learning. Convolutional neural network (CNN) is a type of deep neural network, that is developed on the basis of deep neural network, further imitating the structure of the visual cortex of the brain and the principle of visual activity. The current machine learning method used in medical big data analysis is mainly CNN. In the next few years, it is the developing trend that artificial intelligence as a conventional tool will enter the relevant departments of medical image interpretation. In addition, this article also shares the progress of the integration of artificial intelligence and biomedicine combined with actual cases, and mainly introduces the current status of CNN application research in pathological diagnosis, imaging diagnosis and endoscopic diagnosis for gastrointestinal diseases.

Screening responsive or resistant biomarkers of immune checkpoint inhibitors based on online databases / 医学前沿

Immune checkpoint inhibitors are a promising strategy in the treatment of cancer, especially advanced types. However, not all patients are responsive to immune checkpoint inhibitors. The response rate depends on the immune microenvironment, tumor mutational burden (TMB), expression level of immune checkpoint proteins, and molecular subtypes of cancers. Along with the Cancer Genome Project, various open access databases, including The Cancer Genome Atlas and Gene Expression Omnibus, provide large volumes of data, which allow researchers to explore responsive or resistant biomarkers of immune checkpoint inhibitors. In this review, we introduced some methodologies on database selection, biomarker screening, current progress of immune checkpoint blockade in solid tumor treatment, possible mechanisms of drug resistance, strategies of overcoming resistance, and indications for immune checkpoint inhibitor therapy.

Molecular classification and precision therapy of cancer: immune checkpoint inhibitors / 医学前沿

On May 23, 2017, the US Food and Drug Administration (FDA) approved a treatment for cancer patients with positive microsatellite instability-high (MSI-H) markers or mismatch repair deficient (dMMR) markers. This approach is the first approved tumor treatment using a common biomarker rather than specified tumor locations in the body. FDA previously approved Keytruda for treatment of several types of malignancies, such as metastatic melanoma, metastatic non-small-cell lung cancer, recurrent or metastatic head and neck cancer, refractory Hodgkin lymphoma, and urothelial carcinoma, all of which carry positive programmed death-1/programmed death-ligand 1 biomarkers. Therefore, indications of Keytruda significantly expanded. Several types of malignancies are disclosed by MSI-H status due to dMMR and characterized by increased neoantigen load, which elicits intense host immune response in tumor microenvironment, including portions of colorectal and gastric carcinomas. Currently, biomarker-based patient selection remains a challenge. Pathologists play important roles in evaluating histology and biomarker results and establishing detection methods. Taking gastric cancer as an example, its molecular classification is built on genome abnormalities, but it lacks acceptable clinical characteristics. Pathologists are expected to act as "genetic interpreters" or "genetic translators" and build a link between molecular subtypes with tumor histological features. Subsequently, by using their findings, oncologists will carry out targeted therapy based on molecular classification.

Effect of community nutrition management in tertiary prevention of gestational diabetes mellitus / 中国医师杂志

Objective To establish the community sustainable nutrition management path of patients with gestational diabetes mellitus (GDM) and explore the effect in the tertiary prevention of GDM.Methods The number of pregnant women who delivered in the Jiangdong district of Ningbo city during January 2013 to December 2016 was 1 028.512 patients with GDM who delivered were enrolled in control group and 516 patients in study group.Prevalence rate of GDM,blood glucose,glycosylated hemoglobin (HbAlc),weight gain during pregnancy,pregnancy outcomes,satisfaction rate of blood glucose control were compared between two groups.Data was analyzed by SPSS 13.0 statistical software.Results Prevalence rate of GDM in study group was 7.69％,lower than control groupl 1.1％.Fasting blood glucose (FPG),1 hour blood glucose (1 h PG),macrosomia,low birth weight in study group were better than control group.Fetal distress,Intrauterine infection,Hydramnios,Amniotic fluid embolism,Placental abruption,pregnancy weight gain were similar in two groups.Conclusions The sustainable nutrition management path of the community has good effect in the tertiary prevention of gestational diabetes mellitus.

Clinical and pathologic features of gastric malignancies from Ruijin Hospital during 2005-2014 / 上海交通大学学报（医学版）

Objective·To analyze clinical and pathological characteristics of gastric malignancies from a single center of Ruijin Hospital,and provide references for making healthy policy on gastric tumors.Methods·The data sources were from hospital in-patients database including demographic information,family history,clinicopathological information,and census registering information during 2005 to 2014.The demographic data and clinicopathological data were analyzed.Results·The total number was 3 315 cases with gastric malignancies (2 184 male patients and 1 131 female patients).It was about 2 times as high in males as in females.The patient age was between 18 to 98 years old (mean 59.71 years old).Based on pathologic diagnosis,3 122 cases (94.2％) were gastric adenocarcinoma,others were gastrointestinal stromal tumors (5.5％),neuroendocrine tumor (0.2％) and malignant lymphoma (0.1％).Out of patients with gastric carcinoma,about 4.46％ of cases ran in families.Conclusion·Over 94％ cases of gastric malignancies are gastric carcinomas.Specific risk profiles of gastric carcinomas include age,gender and family factors.

Retrospect of 15-year construction and progress of biobank for gastrointestinal cancer in China / 中国肿瘤临床

Tumor biobank is a critical infrastructure for translational medicine research and precise medical research, which has been paid increasing attention in Western countries. Three different periods exist throughout the course of the 15-year construction and progress of the gastrointestinal cancer biobank in China. The periods include the following:construction of a project-driven biobank, which is closely related to the division's project;formation of a regional network of biobanks, which integrates multiple biobanks with different kinds of diseases;and enrollment of the project to national key basic research facilities by the government. The construction content of gastrointestinal cancer biobank has two stages:collection of peripheral blood and tumor tissues, patient body fluids (blood and urine), and tumor tissues;and information management of clinical and pathological details. The high-quality biospecimens safe-guard the strong support of many domestic projects and international research projects. This review summarizes the experiences and problems of gastrointestinal tumor biobanks in China. The author introduces quality control problems for long-term cryopreserved bio-specimens in deep freezer.

Quality control of nucleic acids and protein of freeze-preserving gastric cancer samples / 中国肿瘤临床

Objective:To explore the quality of inventory samples of a biobank stored in a deep freezer from 0 to over 10 years in Shanghai Ruijin Hospital. Methods:We extracted 24 pairs of stocked gastric cancer samples between 2003 and 2014. We used 1%aga-rose gel electrophoresis to analyze DNA and RNA purity and integrity while adding the RNA integrity number (RIN) for precise analysis. Bicinchonininc acid (BCA) assay was used for protein concentration evaluation. Coomassie brilliant blue method was used for protein integrity assay. Results: The samples were divided into four groups according to cryopreservation period (9 years). No significant difference in DNA integrity was found between the groups (P>0.05);however, DNA degradation in normal gastric mucosa was faster than that in gastric cancer tissue (P=0.023). The RIN significantly declined when the storage period was 6 years or longer (P=0.018). No significant difference in protein concentration was observed between different groups. Using Coo-massie brilliant blue method, we found significant differences in preserved proteins with different molecular weights. Proteins with varying molecular weights were detected in the groups with the following cryopreservation periods:>9 years, a small number of low-molecular-weight (average 36.5 KD) proteins;6-8 years, medium-molecular-weight (average 65.63KD) proteins;3-5 years, high-molecu-lar-weight (average 127.5 KD) proteins;<2 years, high-molecular-weight (average 160 KD) proteins. Conclusion:Cryopreservation does not exert an obvious effect on DNA. If the cryopreservation period is more than 5 years, serious degradation of RNA should occur;like-wise, degradation of proteins with higher molecular weight should occur.

Bioinformatics of tumor molecular targets from big data / 中华胃肠外科杂志

The big data from high throughput research disclosed 4V features: volume of data, variety of data, value for deep mining, and velocity of processing speed. Regarding the whole genome sequencing for human sample, at average 30x of coverage, a total of 100 GB of original data (compression FASTQ format) could be produced. Replying to the binary BAM format, a total of 150 GB data could be produced. In the analysis of high throughput data, we need to combine both clinical information and pathological features. In addition, the data sources of medical research involved in ethical and privacy of patients. At present, the costs are gradually cheaper. For example, a whole genome sequencing by Illumina X Ten with 30x coverage costs about 10,000 RMB, and RNA-seq costs 5000 RMB for a single sample. Therefore, cancer genome research provides opportunities for discovery of molecular targets, but also brings enormous challenges on the data integration and utilization. This article introduces methodologies for high throughput data analysis and processing, and explains possible application on molecular target discovery.

Evaluation of traditional pathological classification at molecular classification era for gastric cancer / 中华胃肠外科杂志

Histopathological classification is in a pivotal position in both basic research and clinical diagnosis and treatment of gastric cancer. Currently, there are different classification systems in basic science and clinical application. In medical literatures, different classifications are used including Lauren and WHO systems, which have confused many researchers. Lauren classification has been proposed for half a century, but is still used worldwide. It shows many advantages of simple, easy handling with prognostic significance. The WHO classification scheme is better than Lauren classification in that it is continuously being revised according to the progress of gastric cancer, and is always used in the clinical and pathological diagnosis of common scenarios. Along with the progression of genomics, transcriptomics, proteomics, metabolomics researches, molecular classification of gastric cancer becomes the current hot topics. The traditional therapeutic approach based on phenotypic characteristics of gastric cancer will most likely be replaced with a gene variation mode. The gene-targeted therapy against the same molecular variation seems more reasonable than traditional chemical treatment based on the same morphological change.

Application of genetically engineered mice model in the research of gastrointestinal tumor / 中华胃肠外科杂志

The gene knockout is based on the DNA homologous recombination and embryonic stem cell technology. It is an experimental method for modification of specific gene loci, which is one of the most direct means to clarifying gene functions. The similarity of genomes between mouse and human is as high as up to 95%. The life cycle of mice is relatively short, and easy to breed with stronger reproductive capacity. Therefore, the knockout mice are suitable for observing the whole process of disease pathogenesis. With genetic manipulation technology, researchers can produce the simulations of phenotypic effect by human genetic variation. This article focuses on genetically engineered mice models and their application in gastrointestinal cancer.

Change of liver function in recurrent hepatitis C after liver transplantation / 中华器官移植杂志

Objective To study the changes of serum liver functions in recurrent hepatitis C ~after liver transplantation.Methods The clinical data of 50 cases of recurrent hepatitis C (~simultaneously negative for serum HBV DNA) after liver transplantation were collected. The relationship between liver function parameters with the HCV RNA genotype, inflammation histological activity, fibrosis stage, steatosis grade and rejection was evaluated. Results ALT, AST and ?-GT were increased in recurrent hepatitis C. Among them, ?-GT was obviously elevated along with the ~aggravation of histological activity (P

Study of HCV genotype and histopathology on post-transplant recurrent hepatitis C / 中华器官移植杂志

Objective To explore the universal pathologic changes as well as the characteristic features of post-transplant hepatitis C caused by different HCV genotypes and study the relationship between pathologic change with HCV genotypes.Methods Fifty cases of HCV-related post-transplant hepatitis C with confirmative serum HCV RNA positivity and HBV DNA negativity between January 2001 to April 2002 were collected from Starzl transplant institute, Pittsburgh university. Liver biopsy from all cases was obtained at the same time. The parameters of histology activity index (HAI), hepatic fibrosis stage (HFS), liver steatosis (LS) and rejection were evaluated. The data were analyzed by SAS 6.12 statistical software using Wilcoxon method.Results Several HCV genotypes or subgenotypes such as 1a, 1b, 2, 3a and 4 were separated at this group. Although there was no statistical difference in HAI, HFS between individual genotype groups, there was significant difference in LS. More severe steatosis was found in HCV 3a and HCV 2 groups other than in HCV 1, HCV 4 groups ( P

Study on loss of heterozygosity of SMAD2 in primary gastric carcinoma / 中国普通外科杂志

Objective To investigate the role of loss of heterozygosity (LOH) of SMAD2 and its relationship with clinicopathological parameters of primary gastric carcinoma. Methods Fifty cases of primary gastric carcinoma were monitored by polymerase chain reaction -single strand conformation polymorphism (PCR- SSCP) and silver staining to detect SMAD2 LOH. Results The incidence of LOH was 40.0%(22/45) at D18S450 and 33.3%(16/48)at D18S460 . LOH occurred in SMAD2 was 55.1%(27/49).The rate of SMAD2 LOH was 72.0% (18/25) in primary gastric carcinoma with lymph node metastasis , which was significantly higher than that in without lymph node metastasis (P