Ke Men

Mother-to-infant transmission of hepatitis B virus: a Chinese experience.

Over 90% of infants infected with hepatitis B virus (HBV) caused by mother‐to‐infant transmission will evolve to carrier status, and this cannot be prevented until widespread administration of the HB vaccine and hepatitis B immune globulin (HBIG) is implemented. This prospective study of 214 infants born to HBsAg‐positive mothers was carried out to determine if either perinatal or intrauterine HBV transmission could be effectively prevented with HBIG and the HB vaccine. Peripheral blood was collected from mothers and from newborns before they received HBIG and the HB vaccine, as well as at 0, 1, 7, 24, and 36 months after birth. Infants born with an ratio of signal to noise(S/N) value of >5 for HBsAg (ABBOTT Diagnostic Kit) were defined as mother‐to‐infant transmission cases, those with an S/N between 5 and 50 were classified as perinatal transmission cases, and those with an S/N >50 were considered intrauterine transmission cases. Mother‐to‐infant transmission occurred in approximately 4.7% (10/214) of the infants; the perinatal transmission and intrauterine transmission rates were 3.7% (8/214) and 0.9% (2/214), respectively. The risk of mother‐to‐infant transmission increased along with maternal HBeAg or HBVDNA levels. After 36 months of follow‐up, all perinatal cases became HBsAg‐negative, whereas all intrauterine transmission cases evolved into carrier status. These results indicate that infants infected via intrauterine transmission cannot be effectively protected by HBIG and HB vaccine. J. Med. Virol. 83:791–795, 2011.

Factors associated with low cure rate of tuberculosis in remote poor areas of Shaanxi Province, China: a case control study

BackgroundThe directly observed therapy-short course (DOTS) strategy was introduced in Shaanxi province, China to improve tuberculosis (TB) control by means of improved case detection (target: > = 70%) and treatment success rates (target: > = 85%) in new smear positive (SS+) TB patients. At a provincial level the targets were both reached in 2005. However in 30 (28%) out of 107 counties of Shaanxi province the cure rate was below 85%. This study aimed to investigate patient and treatment characteristics associated with non-cure after tuberculosis (TB) treatment in these counties.MethodsIn this case-control study, new smear positive TB cases in 30 counties with a cure rate <85% were included. Cured patients were compared to non-cured patients using logistic regression analysis to assess determinants for non-cure.ResultsOf the 659 patients included, 153 (23.2%) did not have cure as treatment outcome. Interruption of treatment was most strongly associated with non-cure (OR = 8.7, 95% CI 3.9-18.4). Other independent risk factors were co-morbidity, low education level, lack of appetite as an initial symptom of TB disease, diagnosis of TB outside of the government TB control institutes, missing sputum re-examinations during treatment, and not having a treatment observer. Twenty-six percent of patients did not have a treatment observer. The non-cure rate was better for those with a doctor (odds ratio (OR) 0.38, 95% confidence interval (CI) 0.17-0.88) as treatment observer than for those with a family member (OR 0.62, 95%CI 0.37-1.03). The main reason for interrupted treatment mentioned by patients was presence of adverse effects during treatment (46.5%).ConclusionsInterruption of treatment was most strongly associated with non-cure. Although treatment observation by medical staff is preferred, in order to diminish the proportion of patients who do not have a treatment observer and thereby reduce the proportion of patients who interrupt treatment, we suggest making it possible for family members, after sufficient training, to be treatment observers in remote areas where it is logistically difficult to have village doctors observe treatment for all patients.

All-cause mortality and risk factors in a cohort of retired military male veterans, Xi'an, China: an 18-year follow up study.

BackgroundRisk factors of all-cause mortality have not been reported in Chinese retired military veterans. The objective of the study was to examine the risk factors and proportional mortality in a Chinese retired military male cohort.MethodsA total of 1268 retired military men aged 55 or older were examined physically and interviewed using a standard questionnaire in 1987. The cohort was followed up every two years and the study censored date was June30, 2005 with a follow-up of up to 18 years. Death certificates were obtained from hospitals and verified by two senior doctors. Data were entered (double entry) by Foxbase, and analysis was carried out by SAS for Windows 8.2. Multivariate Cox proportional hazard regression model was used to compute hazard ratio (HR) and 95% confidence interval (CI).ResultsThe total person-years of follow-up was 18766.28. Of the initial cohort of 1268 men, 491 had died, 748 were alive and 29 were lost to follow up. Adjusted mortality (adjusted for age, blood pressure, body mass index, cholesterol, triglycerides, alcohol, exercise, and existing disease) was 2,616 per 100,000 person years. The proportional mortality of cancer, vascular disease and Chronic Obstructive Pulmonary Disease (COPD) were 39.71%, 28.10% and 16.90% respectively. Multivariate analysis showed that age, cigarettes per day, systolic blood pressure, triglyceride, family history of diseases (hypertension, stroke and cancer), existing diseases (stroke, diabetes and cancer), body mass index, and age of starting smoking were associated with all-cause mortality, HR (95%CI) was1.083(1.062–1.104), 1.026(1.013–1.039), 1.009(1.003–1.015), 1.002(1.001–1.003), 1.330(1.005–1.759), 1.330(1.005–1.759), 1.444(1.103–1.890), 2.237(1.244–4.022), 1.462(1.042–2.051), 2.079(1.051–4.115), 0.963(0.931–0.996)and 0.988(0.978–0.999)respectively. Compared with never-smokers, current smokers had increased risks of total mortality [HR 1.369(1.083–1.731)], CHD [HR 1.805 (1.022–3.188)], and lung cancer [HR 2.939 (1.311–6.585)].ConclusionThe three leading causes of diseases were cancer, CHD and stroke, and COPD. Aging, cigarette smoking, high systolic blood pressure, high triglyceride, family history of cancer, hypertension and stroke, existing cases recovering from stroke, diabetes and cancer, underweight, younger age of smoking were risk factors for all-cause mortality. Quitting cigarette smoking, maintaining normal blood pressure, triglyceride and weight are effect control strategies to prevent premature mortality in this military cohort.

Association between genomic heterogeneity of hepatitis B virus and intrauterine infection.

Hepatitis B virus (HBV) intrauterine infection remains to be an important cause for a large number of persistent hepatitis B surface antigen (HBsAg) positive carriers in areas with a high HBV prevalence, particularly in China and Southeast Asia. In this study, the possible association between the HBV genomic heterogeneity and intrauterine infection was investigated by comparing the quasi species isolated from eight pairs of HBsAg-positive mothers and their neonates, who were infected intrauterinely with HBV, with clones from eight HBsAg-positive mothers whose neonates were not infected with HBV. The proportion of clones with specific mutations was compared among different subject groups, and phylogenetic analysis was performed to evaluate the significance of specific mutations. It was observed that the core promoter with conserved major functional regions and conserved hepatitis B e antigen (HBeAg) might be beneficial to HBV maternal-fetal transmission. Particularly, A1762T/G1764A mutations seemed to be disadvantageous for fetal infection. It was also shown that amino acid substitutions located in the immune epitopes of HBsAg were strongly associated with intrauterine HBV transmission. The clones with mutations such as amino acid P110S in preS1 region, P36L in preS2 region and C107R in S region might infect fetuses more readily. In addition, positively selected site analysis confirmed the above results.

Maternal hepatitis B virus (HBV) DNA positivity and sexual intercourse are associated with HBV intrauterine transmission in China: A prospective case–control study

Background and Aim:  Hepatitis B virus (HBV) intrauterine transmission from infected mothers contributes significantly to the persistence of the high number of HBV carriers. The aim of this study was to identify potential risk factors for HBV intrauterine transmission.

Establishment and characterization of a spontaneously immortalized trophoblast cell line (HPT-8) and its hepatitis B virus-expressing clone

BACKGROUND Most trophoblast cell lines currently available to study vertical transmission of hepatitis B virus (HBV) are immortalized by viral transformation. Our goal was to establish and characterize a spontaneously immortalized human first-trimester trophoblast cell line and its HBV-expressing clone. METHODS Chorionic villi of Asian human first-trimester placentae were digested with trypsin and collagenase I to obtain the primary trophoblast cell culture. A spontaneously immortalized trophoblast cell line (HPT-8) was analyzed by scanning and transmission electron microscopy, cell cycle analysis, immunohistochemistry and immunofluorescence. HPT-8 cells were stably transfected with the adr subtype of HBV (HPT-8-HBV) and characterized by PCR and enzyme-linked immunosorbent assay. RESULTS We obtained a clonal derivative of a spontaneously immortalized primary cell clone (HPT-8). HPT-8 cells were epithelioid and polygonal, and formed multinucleate, giant cells. They exhibited microvilli, distinct desmosomes between adjacent cells, abundant endoplasm, lipid inclusions and glycogen granules, which are all characteristic of cytotrophoblasts. HPT-8 cells expressed cytokeratin 7, cytokeratin 18, vimentin, cluster of differentiation antigen 9, epidermal growth factor receptor, stromal cell-derived factor 1 and placental alkaline phosphatase. They secreted prolactin, estradiol, progesterone and hCG, and were positive for HLA-G, a marker of extravillous trophoblasts. HPT-8-HBV cells were positive for HBV relaxed-circular, covalently closed circular DNA and pre-S sequence. HPT-8-HBV cells also produced and secreted HBV surface antigen and HBV e antigen. CONCLUSIONS We established a trophoblast cell line, HPT-8 and its HBV-expressing clone which could be valuable in exploring the mechanism of HBV viral integration in human trophoblasts during intrauterine infection.

High conservation of hepatitis B virus surface genes during maternal vertical transmission despite active and passive vaccination.

Objective: Our purpose was to explore the relationship between hepatitis B virus (HBV) gene heterogeneity and maternal vertical transmission. Methods: HBsAg-positive mothers and their neonates were selected and classified into a vertical infection neonate group (group N), a vertical infection mother group (group M) and a control group (group C). Serum HBsAg and HBeAg were examined. HBV gene fragments, including the pre-S1, and pre-S2 and S coding regions, were amplified and sequenced, and the genotype and serotype of the sequences were identified. Mutation sites and frequency of mutations were then compared between group N and group C. Results: A total of 104 HBV clone sequences were obtained. All obtained sequences belonged to genotype C and serotype adr. Upon comparing sequences between group N and group C, 4 nonsynonymous mutations were found with significant difference in mutation frequency (p < 0.05). When the mothers were both HBsAg and HBeAg positive, 10 nonsynonymous mutations were found. The frequencies of these mutations were significantly lower in group N than in group C (p < 0.05). Conclusion: The 10 HBV mutations were negatively associated with vertical transmission when maternal HBeAg was positive. Furthermore, the species that were vertically transmitted to the fetus were mainly wild-type.

A preliminary study on the molecular evolution of the two routes of intrauterine transmission of HBV

Intrauterine transmission of hepatitis B virus (HBV) is one of the main reasons for the failure of vaccination and plays an important role in areas with high HBV prevalence. In the present study, the quasispecies isolated from eight pairs of HBsAg-positive mothers and their neonates, who were infected with HBV by intrauterine transmission, were selected as study subjects. Phylogenetic trees of the HBV strains of each pair of mother and neonate were constructed, the topological structures were compared, and the distance between and within the quasispecies was calculated. The eight phylogenetic trees included four types. In the first type, the maternal and neonatal sequences clustered into one clade. In the second type, the sequences of the mothers and neonates formed separate monophyletic clusters, and the two clades were sister groups. In the third type, the strains of mother were the ancestors of the neonatal strains. In the fourth type, the strains of the mothers clustered with only some of the sequences of the neonate, and the other strains of the neonate formed another monophyletic group. Combined with the genetic distance, possible transmission routes of the eight cases are proposed.

Screening Cellular Proteins Binding to the Core Region of Hepatitis C Virus RNA Genome with Digoxin-Labeled Nucleic Acids

Objective: To screen and identify cellular proteins binding to the core region of hepatitis C virus (HCV) RNA genome. Methods: The plasmid pHCV core was constructed to generate in vitro transcripts of the core region of HCV RNA genome. Ultraviolet (UV) cross-linking experiment and competition analysis were performed to screen HepG2 cellular proteins, which interact with digoxin-labeled transcripts of the core region of HCV RNA genome. RNA-binding proteins were separated by immunoprecipitation, analyzed by electrophoresis on SDS-PAGE and detected by immunoblotting with anti-digoxingenin-AP. After being excised from SDS-PAGE, the proteins bands were analyzed by MALDI-TOF-MS. Results: Several cellular proteins of hepG2 cell specifically bound to the core region of HCV RNA genome. The binding of cellular proteins to digoxin-labeled HCV core RNA was competed out in proportion to the increasing amount of unlabeled RNA. One of the HCV RNA-binding proteins was the B (brain) isozyme of human phosphoglycerate mutase (PGAM-B) identified by MALDI-TOF-MS. Conclusion: PGAM-B could specifically bind to the core region of HCV RNA genome in vitro.

Prevalence of Disease Spectrum and Sick Leave Time Associated with Illness in Helicopter Pilots

INTRODUCTION The special working environment of helicopter pilots, such as high altitudes and high temperatures, may give them a special health status. There has been little research on helicopter pilot health issues in China. The aim of this study was to gain a clear understanding of the disease spectrum in helicopter pilots and to provide a scientific basis for disease control and prevention in this population. METHODS The annual aeromedical examination records and inpatient records of 516 helicopter pilots were collected by random sampling. The prevalence and sick leave time associated with each disease were computed. Spearman rank correlation analysis was employed to explore the relationship between prevalence and sick leave duration. RESULTS The organ systems with the highest prevalence of disease were the digestive system (32.36%), cardiovascular system (18.60%), and musculoskeletal system (12.40%), while those with the longest associated sick leave periods were the digestive system (574 d), musculoskeletal system (532 d), and nervous system (323 d). There were no significant correlations between prevalence and sick leave times of diseases in any system (r = 0.64). The diseases with the highest prevalence were fatty liver (9.88%), hyperlipidemia (6.98%), and polypoid lesion of the gallbladder (3.49%), while those with the longest sick leave times were ground syncope (157 d), chronic gastritis (145 d), and lumbar disc herniation (91 d). CONCLUSION Pilot health and performance were most affected by diseases of the digestive and musculoskeletal systems. Although not highly common, aero-related diseases (i.e., ground syncope) were also noteworthy for their long sick-leave times.