Tong Su

Epidemiological and etiological characteristics of hand, foot, and mouth disease in Ningbo, China, 2008–2011

BACKGROUND Outbreaks of hand, foot, and mouth disease (HFMD) in central China have caused public health concerns since 2007. It is of particular public health significance to update epidemiology of HFMD in port cities. OBJECTIVE To investigate epidemical, etiological and clinical characteristics of HFMD in Ningbo, China, from 2008 to 2011. STUDY DESIGN From May 2008 to December 2011, a total of 37,404 HFMD cases including 196 severe and 12 fatal cases were investigated. Human enteroviruses from 2360 cases were determined by real-time RT-PCR. The VP1 gene of EV71 from 78 cases and CA16 from 21 cases, the VP4 gene from 28 cases, and full-length genomes of 10 isolates were analyzed. Neutralizing antibodies were evaluated in 258 healthy subjects. Parameters associated with severe HFMD were evaluated. RESULTS Annual incidence of HFMD was 3066.8/100,000 in the population of ≤5 years. EV71 C4a, CA16 B1, and other enteroviruses accounted for 63.7%, 24.0% and 12.3%, respectively. The genomes of EV71 from fatal and non-fatal cases were nearly identical. The positive rates of neutralizing antibody to EV71 increased from 13.5% to 67.6% in 1- to 5-year healthy groups. The neutralizing antibody to CA16 B1 isolate was negative. EV71, exposure history and certain early manifestations including fever, vomiting, limb exanthema and peripheral neutrophil ratio were significantly associated with HFMD severity. CONCLUSIONS HFMD mainly caused by EV71 C4a and CA16 B1 is seriously epidemic in Ningbo. Future emphasis should be paid on EV71 immuno-prophylaxis and early identification of severe cases upon the etiological and clinical characteristics.

Development of Autoantibody Signatures as Novel Diagnostic Biomarkers of Non–Small Cell Lung Cancer

Purpose: To select autoantibody signatures as noninvasive biomarkers of non–small cell lung cancer (NSCLC). Experimental Design: A phage cDNA expression library was constructed with fresh samples from 30 lung cancer patients and biopanned using serum pools of 10 NSCLC patients and 10 healthy controls. A six–phage peptide detector was discovered by two-step immunoscreenings and was validated in an independent set of 90 NSCLC patients and 90 matched healthy controls, 30 NSCLC patients with chemotherapy, and 12 chronic obstructive pulmonary disease (COPD) patients. The expression of a peptide target was validated by using immunohistochemistry. Factors affecting NSCLC-related death were evaluated by Cox regression analysis. Results: Six phage peptide clones showing higher seroreactivity than others in 30 NSCLC patients were selected for diagnostic validation. The six–phage peptide detector was able to discriminate between NSCLC patients and healthy controls with a sensitivity and specificity of >92%, and had similar validity for indicating NSCLC at early stage. The seroreactivity of the six phage peptides was significantly higher in the NSCLC patients than in those with chemotherapy and the COPD patients, respectively. Of the six phage peptides, one encoded a peptide showing 100% homology to olfactomedin 1. Expression of olfactomedin 1 protein was significantly higher in lung adenocarcinoma than in lung cancer of other histologic types and normal lung tissues. The autoantibody signature was not associated with the prognosis of the NSCLC patients. Conclusions: The six–phage peptide detector stands out as promising diagnostic biomarkers for NSCLC, unlikely for NSCLC relapse after chemotherapy. Olfactomedin 1 may be a novel target of lung adenocarcinoma. Clin Cancer Res; 16(14); 3760–8. ©2010 AACR.

Risk factor for clear cell renal cell carcinoma in Chinese population: a case-control study.

BACKGROUND Risk factors for clear cell renal cell carcinoma (ccRCC) differ among populations and remain controversial. We carried out a hospital-based case-control study to examine the effects of health status, lifestyle, and some genetic polymorphisms on ccRCC risk in Chinese subjects. METHODS Between 2007 and 2009, 250 newly diagnosed, histologically confirmed ccRCC cases and 299 sex-, age-matched healthy controls provided complete information including consumption of tea and alcohol, smoking, occupational exposure, body mass index (BMI), hypertension, diabetes, and urolithiasis by face-to-face interview in Shanghai. Genetic polymorphisms of cytochrome P450 mono-oxygenase (CYP1A1: 6235T>C, 4889A>G, and 4887C>A), glutathione S-transferase (GSTP1: 342A>G), and N-acetyltransferase (NAT2: 481C>T, 590G>A, and 857G>A) were identified by PCR-RFLP and DNA sequencing. Adjusted odds ratio (AOR) and 95% confidence interval (CI) were derived through multivariate logistic regression. RESULTS Green tea intake (≥500 ml/d) was inversely associated with ccRCC risk, with an AOR of 0.34 (95% CI 0.21-0.55). BMI (≥25 kg/m(2)), hypertension, and urolithiasis were independently associated with an increased risk of ccRCC, with AOR (95% CI) of 2.10 (1.32-3.34), 2.49 (1.57-3.93), and 3.33 (1.12-9.89), respectively. No association was observed between smoking, alcohol consumption, or occupational exposure with ccRCC risk. The polymorphisms and their interactions with the environmental exposures were mostly not associated with ccRCC risk. CONCLUSION BMI (≥25 kg/m(2)), hypertension, and urolithiasis are independently associated with an increased risk, whereas green tea intake (≥500 ml/d) is independently associated with a decreased risk of ccRCC. The polymorphisms of the xenobiotic-metabolizing enzymes are weakly associated with ccRCC risk in Chinese subjects.

Non-coding RNAs in hepatitis B or C-associated hepatocellular carcinoma: Potential diagnostic and prognostic markers and therapeutic targets

Non-coding RNA (ncRNA), a class of RNAs that do not code protein but have regulatory functions, can regulate gene expression and replication of hepatitis B virus or hepatitis C virus and play an important role in the virus-host interaction and the development of hepatocellular carcinoma (HCC). Deregulated ncRNAs in surgically removed hepatic tissues and circulation can be prognostic and diagnostic markers, respectively. ncRNAs functioning as either tumor suppressors or oncogenes can be therapeutic options. Here, we summarize the deregulated ncRNAs associated with the infections and HCC and focus on their roles on early diagnosis, prognosis prediction and therapeutic option of HCC.

Associations of Polymorphisms in DNA Repair Genes and MDR1 Gene with Chemotherapy Response and Survival of Non-Small Cell Lung Cancer

Objectives We aimed to determine the associations of genetic polymorphisms of excision repair cross-complementation group 1 (ERCC1) rs11615, xeroderma pigmentosum group D (XPD/ERCC2) rs13181, X-ray repair cross complementing group 1 (XRCC1) rs25487, XRCC3 rs1799794, and breast cancer susceptibility gene 1 (BRCA1) rs1799966 from the DNA repair pathway and multiple drug resistance 1 (MDR1/ABCB1) rs1045642 with response to chemotherapy and survival of non-small cell lung cancer (NSCLC) in a Chinese population. Materials and Methods A total of 352 NSCLC patients were enrolled to evaluate the associations of the six SNPs with response to chemotherapy and overall survival. Logistic regressions were applied to test the associations of genetic polymorphisms with response to chemotherapy in 161 advanced NSCLC patients. Overall survival was analyzed in 161 advanced and 156 early stage NSCLC patients using the Kaplan-Meier method with log-rank test, respectively. Multivariate Cox proportional hazards model was performed to determine the factors independently associated with NSCLC prognosis. Results BRCA1 rs1799966 minor allele C (TC+CC vs. TT, OR = 0.402, 95%CI = 0.204−0.794, p = 0.008) and MDR1/ABCB1 rs1045642 minor allele A (GA +AA vs. GG, OR = 0.478, 95%CI = 0.244−0.934, p = 0.030) were associated with a better response to chemotherapy in advanced NSCLC patients. Survival analyses indicated that BRCA1 rs1799966 TC+CC genotypes were associated with a decreased risk of death (HR = 0.617, 95% CI = 0.402−0.948, p = 0.028) in advanced NSCLC patients, and the association was still significant after the adjustment for covariates. Multivariate Cox regression analysis showed that ERCC1 rs11615 AA genotype (P = 0.020) and smoking (p = 0.037) were associated with increased risks of death in early stage NSCLC patients after surgery. Conclusions Polymorphisms of genes in DNA repair pathway and MDR1 could contribute to chemotherapy response and survival of patients with NSCLC.

Antiviral treatment to prevent chronic hepatitis B or C-related hepatocellular carcinoma

Antiviral treatment is the only option to prevent or defer the occurrence of hepatocellular carcinoma (HCC) in patients chronically infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). The approved medication for the treatment of chronic HBV infection is interferon-α (IFNα) and nucleos(t)ide analogues (NAs), including lamivudine, adefovir dipivoxil, telbivudine, entecavir and tenofovir disoproxil fumarate. IFNα is the most suitable for young patients with less advanced liver diseases and those infected with HBV genotype A. IFNα treatment significantly decreases the overall incidence of HBV-related HCC in sustained responders. However, side effects may limit its long-term clinical application. Orally administered NAs are typically implemented for patients with more advanced liver diseases. NA treatment significantly reduces disease progression of cirrhosis and therefore HCC incidence, especially in HBV e antigen-positive patients. NA-resistance due to the mutations in HBV polymerase is a major limiting factor. Of the NA resistance-associated mutants, A181T mutant significantly increases the risk of HCC development during the subsequent course of NA therapy. It is important to initiate treatment with NAs that have a high genetic barrier to resistance, to counsel patients on medication adherence and to monitor virological breakthroughs. The recommended treatment for patients with chronic HCV infection is peg-IFN plus ribavirin that can decrease the occurrence of HCC in those who achieve a sustained virological response and have not yet progressed to cirrhosis. IFN-based treatment is reserved for patients with decompensated cirrhosis who are under evaluation of liver transplantation to reduce post-transplant recurrence of HCV. More effective therapeutic options such as direct acting antiviral agents will hopefully increase the response rate in difficult-to-treat patients with HCV genotype 1. However, the risk of HCC remains in cirrhotic patients (both chronic HBV and HCV infection) if treatment is initiated after cirrhosis is established. Future research should focus on investigating new agents, especially for those patients with hepatic decompensation or post-transplantation.

Knowledge Levels and Training Needs of Disaster Medicine among Health Professionals, Medical Students, and Local Residents in Shanghai, China

Background Disaster is a serious public health issue. Health professionals and community residents are main players in disaster responses but their knowledge levels of disaster medicine are not readily available. This study aimed to evaluate knowledge levels and training needs of disaster medicine among potential disaster responders and presented a necessity to popularize disaster medicine education. Methods A self-reporting questionnaire survey on knowledge level and training needs of disaster medicine was conducted in Shanghai, China, in 2012. A total of randomly selected 547 health professionals, 456 medical students, and 1,526 local residents provided intact information. The total response rate was 93.7%. Results Overall, 1.3% of these participants have received systematic disaster medicine training. News media (87.1%) was the most common channel to acquire disaster medicine knowledge. Although health professionals were more knowledgeable than community residents, their knowledge structure of disaster medicine was not intact. Medical teachers were more knowledgeable than medical practitioners and health administrators (p = 0.002). Clinicians performed better than public health physicians (p<0.001), whereas public health students performed better than clinical medical students (p<0.001). In community residents, education background significantly affected the knowledge level on disaster medicine (p<0.001). Training needs of disaster medicine were generally high among the surveyed. ‘Lecture’ and ‘practical training’ were preferred teaching methods. The selected key and interested contents on disaster medicine training were similar between health professionals and medical students, while the priorities chosen by local residents were quite different from health professionals and medical students (p<0.001). Conclusions Traditional clinical-oriented medical education might lead to a huge gap between the knowledge level on disaster medicine and the current needs of disaster preparedness. Continuing medical education and public education plans on disaster medicine via media should be practice-oriented, and selectively applied to different populations and take the knowledge levels and training needs into consideration.

EFFECTS OF ANTIVIRAL THERAPY ON THE RECURRENCE OF HEPATOCELLULAR CARCINOMA AFTER CURATIVE RESECTION OR LIVER TRANSPLANTATION

Context Hepatocellular carcinoma (HCC) is a fatal disease. Chronic hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection is the major cause of HCC. High viral replication rate and related hepatic/systematic inflammation are the major risk factors in HCC recurrence after hepatectomy or liver transplantation. Evidence Acquisition Some of the carcinogenesis-related HBV mutations are also associated with poor prognosis for HCC patients. Antiviral therapy is an option for improving HCC prognosis after surgery. In case of HBV-associated HCC, treatment with interferon and nucleos(t)ide analogues (NAs), especially interferon, is effective in improving the prognosis. However, long-term use of NAs increases the possibility of developing drug-resistant viral mutations such as the HBV rtA181T/sW172 mutation, which increases the risk of HCC recurrence. Results In cases of HCV-associated HCC, standard interferon with or without ribavirin therapy is effective in improving the prognosis of HCV-associated HCC; however, some HCV mutations, such as the amino acid substitution M91L, are associated with treatment failure and a poor prognosis. Therapeutic efficacy needs to be confirmed using largescale, randomized, placebo-controlled clinical trials. Conclusions Surveillance of viral mutations during antiviral treatment and a better understanding of the associations of HCC recurrence with viral load, inflammation-associated signaling, and environmental factors can aid the development of more effective strategies for the prevention of HCC recurrence after surgery.

Establishment and characterization of clear cell renal cell carcinoma cell lines with different metastatic potential from Chinese patients

AbstractsBackgroundClear cell renal cell carcinoma (ccRCC) cell lines with distinct metastatic potential are essential to study the mechanism of ccRCC metastasis. However, none of them originated from Chinese.MethodsPrimary cell cultures were performed using a primary tumor of a 49-year-old male ccRCC patient and a metastatic tumor of a 62-year-old male patient who had received nephrectomy to excise primary ccRCC 10 years ago. Cell growth, microstructure, cytogenetics, cytometry, expression of metastasis-associated molecules, tumorigenesis and metastasis were subsequently characterized.ResultsTwo successive cell lines named NRCC from the primary ccRCC and MRCC from the metastatic ccRCC were established, respectively. Compared to NRCC, MRCC exhibited stronger anchorage-independent growth and invasion potentials and contained more glycogen granules in the cytoplasm. Gains of chromosomes and some translocations were the major chromosomal aberrations in both cell strains. CD24 expression was more frequent in MRCC than in NRCC and the same was true for CD56. The transcriptional levels of TNF α, IL-6, VEGF, HIF2 α, MMP2, and RhoC were significantly higher in MRCC than in NRCC. Cytosolic IκBα protein was more degraded in MRCC than in NRCC following TNFα treatment. Both cell lines had strong tumorigenicity in athymic nude mice. However, MRCC had strong potential in generating metastasis to lung and hemorrhagic ascites than NRCC following orthotopic transplantations.ConclusionsCancer cells isolated from metastatic ccRCC have more malignant and metastatic potential than those from the primary tumor from the patients who shared the similar race background. Establishment of MRCC and NRCC may provide suitable models with which to investigate molecular mechanisms of ccRCC metastasis.

Genetic variation in the GSTM3 promoter confer risk and prognosis of renal cell carcinoma by reducing gene expression.

Background:Glutathione S-transferase mu 3 (GSTM3) has been proven to be downregulated in renal cell carcinoma (RCC). We aimed to characterise the role of GSTM3 and its genetic predisposition on the occurrence and postoperative prognosis of RCC.Methods:The effect of GSTM3 on RCC aggressiveness was examined using transfection and silencing methods. Glutathione S-transferase mu 3 expression in renal tissues was examined by immunohistochemistry. The associations of rs1332018 (A-63C) and rs7483 (V224I) polymorphisms with RCC risk were examined using 400 RCC patients and 802 healthy controls. The factors contributing to postoperative disease-specific survival of RCC patients were evaluated using the Cox proportional hazard model.Results:Glutathione S-transferase mu 3 silencing increased the invasion and anchorage-independent growth of RCC cell lines. rs1332018 (AC+CC vs AA), which correlated with low expression of GSTM3 in kidney, was associated with RCC risk (odds ratio, 1.446; 95% confidence interval (CI), 1.111–1.882). rs1332018 variants and low GSTM3 expression significantly predicted unfavourable postoperative survivals of RCC patients (P<0.05). rs1332018 variants independently predicted a poor prognosis (hazard ratio, 2.119; 95% CI, 1.043–4.307).Conclusion:Glutathione S-transferase mu 3 may function as a tumour suppressor in RCC. rs1332018 genetic variants predispose the host to downregulating GSTM3 expression in kidney, facilitate carcinogenesis, and predict an unfavourable postoperative prognosis of RCC.