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Military Medical Research 2017年第4期4卷 229-235页

作者： Sanjeewa Jayachandra Rajakaruna wen-Bin Liu Yi-Bo Ding guang-wen cao Department of Epidemiology Second Military Medical UniversityShanghai2oo433China

Hospital-acquired infections(HAIs) are serious problems for healthcare systems, especially in developing countries where public health infrastructure and technology for infection preventions remain undeveloped. Here, we characterized how strategy and technology could be mobilized to improve the effectiveness of infection prevention and control in hospitals during the outbreaks of Ebola, Middle East respiratory syndrome(MERS), and severe acute respiratory syndrome(SARS) in Asia and West Africa. Published literature on the hospital-borne outbreaks of SARS, Ebola, and MERS in Asia and West Africa was comprehensively reviewed. The results showed that healthcare systems and hospital management in affected healthcare facilities had poor strategies and inadequate technologies and human resources for the prevention and control of HAIs, which led to increased morbidity, mortality, and unnecessary costs. We recommend that governments worldwide enforce disaster risk management, even when no outbreaks are imminent. Quarantine and ventilation functions should be taken into consideration in architectural design of hospitals and healthcare facilities. We also recommend that health authorities invest in training healthcare workers for disease outbreak response, as their preparedness is essential to reducing disaster risk.

关键词： SARS Ebola MERS Infection control Hospital-acquired infections Strategy Technology

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World Journal of Gastroenterology 2014年第16期20卷 4586-4596页

作者： wen-Jun Chang Yan Du Xin Zhao Li-Ye Ma guang-wen cao Department of Epidemiology Second Military Medical University Department of General Surgery Changhai HospitalSecond Military Medical University

Gastric cancer(GC),which is mainly induced by Helicobacter pylori(***)infection,is one of the leading causes of cancer-related death in the developing *** inflammation initiated by *** infection and maintained by inherent immune disorders promotes carcinogenesis and postoperative ***,the presence with *** in tumors has been linked to a better prognosis,possibly due to the induction of antitumor *** infiltrations of tumorassociated macrophages,myeloid-derived suppressor cells,neutrophils,Foxp3+regulatory T cells are correlated with poor *** infiltrating CD8+cytotoxic T lymphocytes,dendritic cells,and CD45RO T cells are generally associated with good prognosis of GC,although some subsets of these immune cells have inverse prognosis prediction *** ratios of Foxp3+/CD4+and Foxp3+/CD8+in tumors are associated with a poor prognosis;whereas high Th1/Th2ratio in tumors predicts a good *** levels of interleukin(IL)-6,IL-10,IL-32,and chemokine C-C motif ligands(CCL)7 and CCL21 in circulation,high expression of CXC chemokine receptor 4,chemokine C-C motif receptor(CCR)3,CCR4,CCR5,CCR7,hypoxiainducible factor-1α,signal transducer activator of transcription-3,cyclooxygenase-2,and orphan nuclear receptor 4A2 in tumors are associated with an unfavorable *** serum levels of matrix metalloproteinases(MMP)-3,MMP-7,and MMP-11 and increased levels of MMP-9,MMP-12,and MMP-21 in tumors are consistently associated with poor survival of *** emphasis should be put on the integration of these biomarkers and validation in large cohorts for personalized prediction of GC postoperative prognosis.

关键词： Gastric cancer Inflammation Biomarker Prognosis

Clinical relevance and public health significance of hepatitis B virus genomic variations

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World Journal of Gastroenterology 2009年第46期15卷 5761-5769页

作者： guang-wen cao Department of Epidemiology SecondMilitary Medical University Shanghai 200433 China

Ten hepatitis B virus （HBV） genotypes （A-J） and 34 HBV subgenotypes have been identified so far. HBV genotypes and subgenotypes have distinct geographical distributions, and have been shown to differ with regard to clinical outcome, prognosis, and response to interferon treatment. Infection with subgenotype A2 is frequently associated with high viral load, resulting in acute infection via horizontal transmission. Genotypes A and B are more sensitive to interferon treatment than genotypes D and C, respectively. Genotype B is more frequent in acute hepatitis than genotype C, whereas genotype C （C2） is more frequently associated with an increased risk of hepatocellular carcinoma （HCC）, mostly cirrhotic, as compared with genotype B （B2）. Genotype mixture is associated with high viral load and worse outcome of HBV infection. HBV mutations in the S genes, especially amino acids substitution at position 145 （G145R）, are associated with immune escape, whereas mutations in the PreS or S genes which impair HBsAg secretion could present a risk to blood safety. HBV variants harboring mutations in the viral polymerase gene that confer resistance to nucleoside analogs may be selected during antiviral therapy. Different genotypes have distinct mutation patterns in the PreS and EnhH/BCP/Precore regions. PreS deletions, C1653T, T1753V, and A1762T/G1764A are associated with an increased risk of HCC. HCC- associated HBV mutants may not transmit via motherto-child transmission, and are likely generated during HBV-induced pathogenesis. Examination of HBV mutations alone or in combination and host genetic suscep-tibility will be helpful in classifying the HBV-infected subjects who will develop HCC and need active antiviral treatments.

关键词： Hepatitis B virus Genotype Subgenotype Mutation Clinical Public health Evolution

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World Journal of Gastroenterology 2014年第21期20卷 6457-6469页

作者： Ji Lin Jian-Feng Wu Qi Zhang Hong-Wei Zhang guang-wen cao Department of Epidemiology Second Military Medical University

Chronic infections with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are the major causes of cirrhosis globally. It takes 10-20 years to progress from viral hepatitis to cirrhosis. Intermediately active hepatic inflammation caused by the infections contributes to the inflammation-necrosis-regeneration process, ultimately cirrhosis. CD8+ T cells and NK cells cause liver damage via targeting the infected hepatocytes directly and releasing pro-inflammatory cytokine/chemokines. Hepatic stellate cells play an active role in fibrogenesis via secreting fibrosis-related factors. Under the inflammatory microenvironment, the viruses experience mutation-selection-adaptation to evade immune clearance. However, immune selection of some HBV mutations in the evolution towards cirrhosis seems different from that towards hepatocellular carcinoma. As viral replication is an important driving force of cirrhosis pathogenesis, antiviral treatment with nucleos(t)ide analogs is generally effective in halting the progression of cirrhosis, improving liver function and reducing the morbidity of decompensated cirrhosis caused by chronic HBV infection. Interferon-α plus ribavirin and/or the direct acting antivirals such as Vaniprevir are effective for compensated cirrhosis caused by chronic HCV infection. The standard of care for the treatment of HCV-related cirrhosis with interferon-α plus ribavirin should consider the genotypes of IL-28B. Understanding the mechanism of fibrogenesis and hepatocyte regeneration will facilitate the development of novel therapies for decompensated cirrhosis.

关键词： Liver cirrhosis Hepatitis B virus Hepatitis C virus Evolution Immune cells Signaling pathway Hepatic stellate cells Antiviral therapy

Prediction and prophylaxis of hepatocellular carcinoma occurrence and postoperative recurrence in chronic hepatitis B virus-infected subjects

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World Journal of Gastroenterology 2016年第29期22卷 6565-6572页

作者： Yan Du Xue Han Yi-Bo Ding Jian-Hua Yin guang-wen cao Office of Clinical Epidemiology Obstetrics and Gynecology Hospital of Fudan University Division of Chronic Disease Control Center for Diseases Control and Prevention of Yangpu District Department of Epidemiology Second Military Medical University

Hepatocellular carcinoma(HCC) is one of the most common and highly fatal malignancies worldwide. Chronic infection with hepatitis B virus(HBV) is a major cause of HCC. High HBV replication rate and related non-resolving inflammation are the major risk factors of HCC occurrence and postoperative recurrence. Early prophylactic options are effective in reducing HCC occurrence and improving survival. Therefore, it is important to identify HBV-infected patients who are at a higher risk of developing HCC and HBV-HCC patients who are more likely to relapse after surgery, thus providing them with more precise prophylactic strategies. Several prediction models of HCC occurrence have been constructed, with satisfactory predictive accuracy and discriminatory ability. However, there is a lack of consensus for their clinical implementation. Several staging systems have been proposed for HCC prognosis. However, the accuracy of these staging systems based on demographic characteristics and clinical measurements needs to be further improved, possibly by systematically incorporating viral and inflammatory factors. Since antiviral treatments are effective in promoting liver function reserve, reducing HCC occurrence and prolonging postoperative survival in some HBV-infected subjects, it is very important to identify subgroups of HBV-infected patients who would most benefit from antiviral treatment.

关键词： Hepatocellular carcinoma Chronic hepatitis B Incidence Prognosis Prediction

Challenges of incorporating gene expression data to predict HCC prognosis in the age of systems biology

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World Journal of Gastroenterology 2012年第30期18卷 3941-3944页

作者： Yan Du guang-wen cao Department of Epidemiology Second Military Medical UniversityShanghai 200433China

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death *** recurrence of HCC after curative treatments is currently a major *** of subsets of patients with distinct prognosis provides an opportunity to tailor therapeutic approaches as well as to select the patients with specific sub-phenotypes for targeted ***,the development of gene expression profiles to improve the prediction of HCC prognosis is important for HCC *** several gene signatures have been evaluated for the prediction of HCC prognosis,there is no consensus on the predictive power of these *** systematic approaches to evaluate these signatures and combine them with clinicopathologic information may provide more accurate prediction of HCC ***,Villanueva et al developed a composite prognostic model incorporating gene expression patterns in both tumor and adjacent tissues to predict HCC *** this commentary,we summarize the current progress in using gene signatures to predict HCC prognosis,and discuss the importance,existing issues and future research directions in this field.

关键词： Gene expression signatures Hepatocellular carcinoma Prognosis

Role of nuclear receptor NR4A2 in gastrointestinal inflammation and cancers

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World Journal of Gastroenterology 2012年第47期18卷 6865-6873页

作者： Yi-Fang Han guang-wen cao Department of Epidemiology Second Military Medical University

NR4A2 is a transcription factor belonging to the steroid orphan nuclear receptor *** was originally considered to be essential in the generation and maintenance of dopaminergic neurons,and associated with neurological disorders such as Parkinson's ***,NR4A2 has been found to play a critical role in some inflammatory diseases and ***4A2 can be efficiently trans-activated by some proinflammatory cytokines,such as tumor necrosis factor-α,interleukin-1β,and vascular endothelial growth factor(VEGF).The nuclear factor-κB signaling pathway serves as a principal regulator of inducible NR4A expression in immune ***4A2 can trans-activate Foxp3,a hallmark specifically expressed in regulatory T(Treg) cells,and plays a critical role in the differentiation,maintenance,and function of Treg ***4A2 in T lymphocytes is pivotal for Treg cell induction and suppression of aberrant induction of Th1 under physiological and pathological *** density of Foxp3 + Treg cells is significantly associated with gastrointestinal inflammation,tumor immune escape,and disease ***4A2 is produced at high levels in CD133 + colorectal carcinoma(CRC) cells and significantly upregulated by cyclooxygenase-2-derived prostaglandin E 2 in a cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)-dependent manner in CRC *** cAMP/PKA signaling pathway is the common pathway of NR4A2-related inflammation and ***4A2 trans-activates osteopontin,a direct target of the Wnt/β-catenin pathway associated with CRC invasion,metastasis,and poor *** of endogenous NR4A2 expression attenuates VEGF-induced endothelial cell proliferation,migration and in vivo *** together,NR4A2 emerges as an important nuclear factor linking gastrointestinal inflammation and cancer,especially CRC,and should serve as a candidate therapeutic target for inflammation-related gastrointestinal cancer.

关键词： NR4A2 Inflammation Immune cells Signaling pathway Gastrointestinal carcinoma

Cancer Evo-Dev,a novel hypothesis derived from studies on hepatitis B virus-induced carcinogenesis

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Hepatoma Research 2017年第10期3卷 241-259页

作者： guang-wen cao Department of Epidemiology Second Military Medical UniversityShanghai 200433China

Non-resolving inflammation, which may be maintained by infection, pollution, and metabolic stimulants and their interactions with immunogenetic predisposition, provides a fertile field for cancer development. This is strongly evident in hepatocellular carcinoma. Here, the framework of a hypothesis called Cancer Evo-Dev is presented,based on the advances in hepatitis B virus-induced hepatocarcinogenesis. Several aspects central to this theory are as follows: (1) immune imbalance caused by the interaction of immunogenetic predispositions and hepatitis B virus infection maintains non-resolving inflammation;(2) active inflammation executants promote mutations in viral and host genomes via disbalancing mutagenic forces including cytidine deaminases and mutation-repairing forces including uracil-DNA glycosylases, thus promoting cancer-related somatic mutations and viral mutations;(3) a small percentage of the cells whose somatic mutations alter the survival signalling adapt to the inflammatory microenvironment, de-differentiate via demethylating role of cytidine deaminases, and reversely develop into tumor-initiating cells (TICs);(4) under the cultivation of some factors like POSTN from tumor-infiltrating fibroblasts and M2 macrophages, TICs acquire the stemness, cancer-stem cells obtain distinct metastatic and drug-resistant potentials under the selection pressure from distinct microenvironments;(5) glycolysis persistence in the presence of oxygen provides essential energy for cell survival and the raw material for DNA synthesis. Thus, cancer development is characterized by an evolutionary process of 'mutation-selection-adaptation'. The framework of Cancer Evo-Dev can be verified in other *** Evo-Dev lays theoretical foundation for understanding the mechanisms by which inflammation promotes cancer development, and it also plays a role in specific prophylaxis, prediction, and targeted treatment of cancers.

关键词： Inflammation hepatitis B virus mutations hepatoma Cancer Evo-Dev

Development and characterization of a guinea pig model for Marburg virus

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Zoological Research 2018年第1期39卷 32-41页

作者： Gary Wong wen-guang cao Shi-Hua He Zi-Rui Zhang wen-Jun Zhu Estella Moffat Hideki Ebihara Carissa Embury-Hyatt Xiang-Guo Qiu Special Pathogens Program National Microbiology LaboratoryPublic Health Agency of CanadaWinnipegManitoba R3E 3R2Canada Shenzhen Key Laboratory of Pathogen and Immunity State Key Discipline of Infectious DiseaseShenzhen Third People's HospitalShenzhen Guangzhou 518020China Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Department of Medical Microbiology and Infectious Diseases University of ManitobaWinnipegManitoba R3E 0J9Canada National Center for Foreign Animal Disease Canadian Food Inspection AgencyWinnipeg R3E 3M4Canada Department of Molecular Medicine Mayo ClinicRochesterMinnesota 55905USA

The Angolan strain of Marburg virus （MARV/Ang） can cause lethal disease in humans with a case fatality rate of up to 90%, but infection of immunocompetent rodents do not result in any observable symptoms. Our previous work includes the development and characterization of a MARV/Ang variant that can cause lethal disease in mice （MARV/Ang-MA）, with the aim of using this tool to screen for promising prophylactic and therapeutic candidates. An intermediate animal model is needed to confirm any findings from mice studies before testing in the gold-standard non-human primate （NHP） model. In this study, we serially passaged the clinical isolate of MARV/Ang in the livers and spleens of guinea pigs until a variant emerged that causes 100% lethality in guinea pigs （MARV/Ang- GA）. Animals infected with MARV/Ang-GA showed signs of filovirus infection including lymphocytopenia, thrombocytopenia, and high viremia leading to spread to major organs, including the liver, spleen, lungs, and kidneys. The MARV/Ang-GA guinea pigs died between 7-9 days after infection, and the LD50 was calculated to be 1.1x10-1 TCID50 （median tissue culture infective dose）. Mutations in MARV/Ang-GA were identified and compared to sequences of known rodent-adapted MARV/Ang variants, which may benefit future studies characterizing important host adaptation sites in the MARV/Ang viral genome.

关键词： Marburg virus Guinea pig Animal model Pathogenesis Host adaptation

The prevalence rates of major chronic diseases in retired and in-service Chinese military officers(2000-2016): a meta-analysis

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Military Medical Research 2018年第3期5卷 231-241页

作者： Thermite Mara Long-Teng Ma Shuo Wang Ling Wang Fan Yang Jia-Hui Song Yi-Chun cao Jian-Hua Yin guang-wen cao Department of Epidemiology Second Military Medical University

Background:Chronic diseases cause a tremendous burden to the military medical ***,the prevalence rates of major chronic diseases among military officers remain unclear in ***:China National Knowledge Infrastructure(CNKI),Wanfang Database,VIP Database for Chinese Technical Periodicals(VIP),Pub Med and Web of Science were searched for studies(from 2000 to 2016)concerning 6 major chronic diseases:hypertension,hyperlipidemia,diabetes mellitus,heart diseases,cerebrovascular diseases,and chronic obstructive pulmonary diseases(COPD)in Chinese military officers following strict inclusion and exclusion *** researchers independently extracted data from the included studies,and a fourth researcher reviewed and solved every *** analysis was performed with STATA 14.0 and R *** was evaluated by the I^2 value.A random effect model was performed to combine the heterogeneous *** Egger test was performed to test the publication ***:A total of 90,758 military officers derived from 75 articles were pooled *** bias was only observed in 37 studies reporting heart disease(P_(Egger test)=0.01).The overall prevalence rates of hypertension,hyperlipidemia,diabetes mellitus,heart diseases,cerebrovascular diseases,and COPD were 46.6%(95%CI 41.8%–51.5%),30.9%(26.4%–35.7%),20.7%(16.5%–25.7%),48.2%(41.7%–54.9%),20.2%(14.8%–26.9%)and 16.6%(12.9%–21.0%),*** prevalence rates of hypertension,diabetes,heart disease,cerebrovascular disease,and COPD,rather than hyperlipidemia,increased with age in Chinese military *** diseases(P_(Q-test)<0.001)and hypertension(P_(Q-test)<0.001)increased sharply in retired officers compared with officers in *** disease was more frequent in Northern Theater Command than in any other theater command(P_(Q-test)<0.001).Conclusion:Major chronic diseases heavily affect Chinese military officers,especially *** intervention s

关键词： Chronic diseases Meta-analysis Hypertension,Hyperlipidemia Diabetes Cerebrovascular disease Chronic obstructive pulmonary disease