Dezhong Xu’s research while affiliated with Air Force Medical University and other places

Severe cold exposure and pressure overload are both known to prompt oxidative stress and pathological alterations in the heart although the interplay between the two remains elusive. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel activated in response to a variety of exogenous and endogenous physical and chemical stimuli including heat and capsaicin. The aim of this study was to examine the impact of cold exposure on pressure overload-induced cardiac pathological changes and the mechanism involved. Adult male C57 mice were subjected to abdominal aortic constriction (AAC) prior to exposure to cold temperature (4°C) for 4 weeks. Cardiac geometry and function, levels of TRPV1, mitochondrial and autophagy-associated proteins including AMPK, mTOR, LC3B and P62 were evaluated. Sustained cold stress triggered cardiac hypertrophy, compromised depressed myocardial contractile capacity including lessened fractional shortening, peak shortening and maximal velocity of shortening/relengthening, enhanced ROS production and mitochondrial injury, the effects of which were negated by the TRPV1 antagonist SB366791. Western blot analysis revealed upregulated TRPV1 level and AMPK phosphorylation, enhanced ratio of LC3II/LC3I, and downregulated P62 following cold exposure. Cold exposure significantly augmented AAC-induced changes in TRPV1, phosphorylation of AMPK, LC3 isoform switch and p62, the effects of which were negated by SB366791. In summary, these data suggest that cold exposure accentuates pressure overload-induced cardiac hypertrophy and contractile defect possibly through a TRPV1 and autophagy-dependent mechanism.

Three-dimensional (3D) finite element models of a posterior mandibular segment and a distraction implant (DI) were created and assembled in this study. The diameter of distraction screw (DS) was set as input variable, ranging from 1.0 to 3.0mm, to analyze the stress and displacement, in order to obtain an optimal outcome of the DI. The results indicate that when the diameter of DS was 2.0mm, the stresses in jaw bone and DS and the displacement of DS reached a relatively low range. The diameter of DS significantly affects the stress distribution in DI and surrounding bone. The present study demonstrates that from clinical and biomechanical points of view, the optimal diameter of DS is 2.0mm.

To investigate the prevalence of occult HBV infection (OBI) among children and to characterize virology of occult HBV, we conducted an epidemiological survey. 186 HB-vaccinated infants born to HBsAg-positive mothers were included in the study. Serological tests for HBV markers were performed using commercial ELISA kits. Real-time quantitative PCR and nested PCR were used to detect HBV DNA. PCR products of the C and pre-S/S regions were sequenced and analyzed. 1.61% (3/186) infants were HBsAg positive, and 4.92% (9/183) infants were considered as occult infection. The viral load of mothers was associated with occult infection (P = 0.020). Incomplete three-dose injections of HB vaccine was associated with HBV infection (P = 0.022). Six OBI infants were positive for anti-HBs, but their titers were not greater than 100 mIU/mL. Seven isolated HBV pre-S/S sequences were obtained from nine OBI infants. Three of the sequences were genotype C, and four of the sequences were genotype C/D. Escape mutation S143L was found in the four sequences of genotype C/D. All seven sequences lacked G145R and other escape mutation in S region. Occult HBV infection was detected in anti-HBs positive infants born to HBsAg-positive mothers in China. Occult infection was associated with absent anti-HBs or with low anti-HBs level, high maternal viral loads and escape mutations in the S gene.

Hainan Province is the main area threatened by malaria in China. However, the epidemiologic patterns of malaria in this region are not yet defined. In this study, we determined the spatio-temporal distribution and variation of Plasmodium falciparum and Plasmodium vivax malaria in Hainan during 1995-2008 by using wavelet and cluster quantitative approaches. The results indicated a decreasing secular trend and obvious seasonal fluctuation of malaria in Hainan. In addition, the characteristic annual peak of malaria could not be detected after 2005. The southcentral region of Hainan has remained an area of relatively high malaria risk, but the incidence of P. falciparum malaria increased significantly in the southeast and southwest regions during 2002-2008. These findings identify epidemic patterns of malaria in Hainan, and are applicable for designing an effective and dynamic public health campaign to combat malaria in this region.

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. 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. 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. 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.

Hainan is one of the provinces most severely affected by malaria epidemics in China. The distribution pattern and major determinant climate factors of malaria in this region have remained obscure, making it difficult to target countermeasures for malaria surveillance and control. This study detected the spatiotemporal distribution of malaria and explored the association between malaria epidemics and climate factors in Hainan. The cumulative and annual malaria incidences of each county were calculated and mapped from 1995 to 2008 to show the spatial distribution of malaria in Hainan. The annual and monthly cumulative malaria incidences of the province between 1995 and 2008 were calculated and plotted to observe the annual and seasonal fluctuation. The Cochran-Armitage trend test was employed to explore the temporal trends in the annual malaria incidences. Cross correlation and autocorrelation analyses were performed to detect the lagged effect of climate factors on malaria transmission and the auto correlation of malaria incidence. A multivariate time series analysis was conducted to construct a model of climate factors to explore the association between malaria epidemics and climate factors. The highest malaria incidences were mainly distributed in the central-south counties of the province. A fluctuating but distinctly declining temporal trend of annual malaria incidences was identified (Cochran-Armitage trend test Z = -25.14, P < 0.05). The peak incidence period was May to October when nearly 70% of annual malaria cases were reported. The mean temperature of the previous month, of the previous two months and the number of cases during the previous month were included in the model. The model effectively explained the association between malaria epidemics and climate factors (F = 85.06, P < 0.05, adjusted R(2) = 0.81). The autocorrelations of the fitting residuals were not significant (P > 0.05), indicating that the model extracted information sufficiently. There was no significant difference between the monthly predicted value and the actual value (t = -1.91, P = 0.08). The R(2) for predicting was 0.70, and the autocorrelations of the predictive residuals were not significant (P > 0.05), indicating that the model had a good predictive ability. Public health resource allocations should focus on the areas and months with the highest malaria risk in Hainan. Malaria epidemics can be accurately predicted by monitoring the fluctuations of the mean temperature of the previous month and of the previous two months in the area. Therefore, targeted countermeasures can be taken ahead of time, which will make malaria surveillance and control in Hainan more effective and simpler. This model was constructed using relatively long-term data and had a good fit and predictive validity, making the results more reliable than the previous report. The spatiotemporal distribution of malaria in Hainan varied in different areas and during different years. The monthly trends in the malaria epidemics in Hainan could be predicted effectively by using the multivariate time series model. This model will make malaria surveillance simpler and the control of malaria more targeted in Hainan.

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.

To identify the clinical factors which predicted the outcome of ischemic stroke patients in northwest China. We retrospectively reviewed 489 consecutive patients with ischemic stroke admitted to the Neurology Department of Xijing Hospital. Demographic, clinical and laboratory data were recorded. Follow-up assessments were performed by telephone interviews or letters. The clinical outcome was assessed by using the modified Rankin Scale (mRS) and categorized as good (score 0-2) or poor (score 3-6) outcomes. Univariate and multivariate logistic regression analyses were performed to explore predictors of ischemic stroke. The follow-up period was up to 47 months (mean, 28.3 months). Fifty-five patients (11.2%) were lost. Among these 434 patients, 244 (56.2%) patients had good outcome and 190 (43.8%) had poor outcome. The poor outcome was associated with old age (OR: 3.505; CI 95%: 2.100-5.849), lower educational level (OR: 0.686; CI 95%: 0.570-0.825), having stroke history (OR: 2.481; CI 95%: 1.442-4.268), and higher NIHSS total score (OR: 2.619; CI 95%: 1.584-4.330). The results suggest that age, the educational level, stroke history, and NIHSS score are useful in the prediction of functional outcome of ischemic stroke in Chinese northwest area.