Jihong Xu

A phase I trial of intratumoral administration of recombinant oncolytic adenovirus overexpressing HSP70 in advanced solid tumor patients.

Our pre-clinical studies demonstrated that intratumoral vaccination with a recombinant oncolytic type 2 adenovirus overexpressing the heat shock protein (HSP)70 protein, designated as H103, can inhibit primary and metastatic tumors through enhanced oncolytic activity and HSP-mediated immune responses against shared and mutated tumor antigens. In the pre-clinical studies of local H103 administration, no significant toxicity was observed in the animal trials with mice, cavy or rhesus monkeys. A phase I clinical trial of intratumoral injection of H103 was conducted in the patients with advanced solid tumors. A total of 27 patients were injected intratumorally with H103 in a dose-escalation study from a dose of 2.5 × 107 to 3.0 × 1012 viral particles (VPs). The maximum tolerated dose of H103 was not defined. Two patients developed dose-limiting toxicities of grade III fever at the dose of 1.5 × 1012 VP and transient grade IV thrombocytopenia at the dose of 3.0 × 1012 VP. The common adverse events were mainly mild to moderate (grade I/II) in nature, including fever, mild injection-site reaction, leucopenia, lymphopenia, thrombocytopenia and hypochromia. The objective response (complete response+partial response) to H103-injected tumors was 11.1% (3/27), and the clinical benefit rate (complete response+partial response+minor response+stable disease) was 48.1%. Interestingly, transient and partial regression of distant, uninjected tumors was observed in three patients. The numbers of immune cells (CD4+ and CD8+ T cells, and natural killer cells) were elevated after H103 administration, but without statistical significance. This phase I trial demonstrates that intratumoral administration of H103 can be safely applied to cancer patients and shows promising clinical antitumor activity, warranting a further clinical investigation.

Prevalence of overweight and obesity in 15.8 million men aged 15–49 years in rural China from 2010 to 2014

Obesity has been increasing worldwide. Data on obesity status among men of reproductive age are scarce. This study aimed to assess the national prevalence and trend of overweight and obesity among reproductive-age men in rural China. In the nationwide population-based study, data were obtained from the National Free Preconception Health Examination Project in rural China from 2010 to 2014. Weight and height were measured in 16 161 982 men aged 15–49 years and their female partners (15 997 739 participants aged 15–49 years) before conception, and body mass index (BMI) was calculated. We found that the prevalence of combined overweight and obesity among men was 33.8% (33.7–33.9%) according to Chinese criteria (BMI ≥ 24.0 kg/m2), the corresponding rates of obesity were 6.3% (6.2–6.4%; BMI ≥ 28.0 kg/m2), respectively. The prevalence varied in different ethnic groups, geographic regions, age, education and GDP levels, and increasing trend was observed over the 5-year study period. In addition, 45.8% of couples had at least one of them as overweight or obesity. About one third of men aged 15–49 years before conception in rural China are overweight or obese. Overweight/obesity clusters in families, which highlights the importance of family involvement of early prevention of obesity in China.

Prevalence of Underweight, Overweight, and Obesity Among Reproductive-Age Women and Adolescent Girls in Rural China

OBJECTIVES To provide prevalence and trends of underweight, overweight, and obesity among reproductive-age women and adolescent girls in rural China. METHODS We measured weight and height in 16 742 344 women aged 20 to 49 years and 178 556 girls aged 15 to 19 years from the National Free Preconception Health Examination Project between 2010 and 2014. RESULTS Among women, the prevalence of underweight was 7.8% (95% confidence interval [CI] = 7.7%, 7.9%), and overweight or obesity was 16.5% (95% CI = 16.4%, 16.6%; World Health Organization criteria). Among adolescents, prevalence of underweight was 6.0% (95% CI = 5.7%, 6.2%; Centers for Disease Control and Prevention criteria) and overweight or obesity was 8.3% (95% CI = 7.9% to 8.8%; International Obesity Task Force criteria). According to Chinese criteria, overweight and obesity prevalence was 24.8% (95% CI = 24.7%, 24.9%) for women and 17.2% (95% CI = 16.6%, 17.8%) for adolescents, and underweight prevalence was 2.9% (95% CI = 2.8%, 3.1%) for adolescents. Considerable disparities existed in prevalence and trends within subpopulations (age groups, parity, region, education levels, and socioeconomic status). CONCLUSIONS Our results reveal coexisting underweight and overweight or obesity among rural women and adolescents of reproductive age, which requires public health attention.

Effect of folic acid supplementation on preterm delivery and small for gestational age births: A systematic review and meta-analysis

OBJECTIVE To investigate the effect of folic acid (FA) supplementation on the risks of preterm delivery (PTD) and small for gestational age births (SGA). DATA SOURCES Cohort studies were identified from MEDLINE, EMBASE, the Cochrane Library, CINAHL, and CBM from inception to January 2015. PARTICIPANTS AND INCLUDED STUDIES Healthy women who want to get pregnancy or being pregnant. MAIN OUTCOME MEASURES PTD and SGA. RESULTS The association of FA and PTD was significant when supplement initiated after pregnancy (RR=0.68, 95%CI, 0.52-0.90), whereas no effect was founded if the initiation time was before conception (RR=0.89, 95%CI, 0.80-1.01). The results for the association between FA supplementation and SGA showed significant protective effect: initiated before conception (RR=0.70, 95%CI, 0.57-0.85) and initiated after conception (RR=0.84, 95%CI, 0.81-0.89). CONCLUSION Folic acid supplementation is associated with a significant reduction on the risk of PTD when initiated after conception. It can also protect fetus from SGA.

Association of Long-term Exposure to Airborne Particulate Matter of 1 μm or Less With Preterm Birth in China

Importance Airborne particulate matter pollution has been associated with preterm birth (PTB) in some studies. However, most of these studies assessed only populations living near monitoring stations, and the association of airborne particulate matter having a median diameter of 1 &mgr;m or less (PM1) with PTB has not been studied. Objective To evaluate whether PM1 concentrations are associated with the risk of PTB. Design, Setting, and Participants This national cohort study used National Free Preconception Health Examination Project data collected in 324 of 344 prefecture-level cities from 30 provinces of mainland China. In total, 1 300 342 healthy singleton pregnancies were included from women who were in labor from December 1, 2013, through November 30, 2014. Data analysis was conducted between December 1, 2016, and April 1, 2017. Exposures Predicted weekly PM1 concentration data collected using satellite remote sensing, meteorologic, and land use information matched with the home addresses of pregnant women. Main Outcomes and Measures Preterm birth (<37 gestational weeks). Gestational age was assessed using the time since the first day of the last menstrual period. Cox proportional hazards regression analysis was used to examine the associations between trimester-specific PM1 concentrations and PTB after controlling for temperature, seasonality, spatial variation, and individual covariates. Results Of the 1 300 342 singleton live births at the gestational age of 20 to 45 weeks included in this study, 104 585 (8.0%) were preterm. In fully adjusted models, a PM1 concentration increase of 10 &mgr;g/m3 over the entire pregnancy was significantly associated with increased risk of PTB (hazard ratio [HR], 1.09; 95% CI, 1.09-1.10), very PTB as defined as gestational age from 28 through 31 weeks (HR, 1.20; 95% CI, 1.18-1.23), and extremely PTB as defined as 20 through 27 weeks’ gestation (HR, 1.29; 95% CI, 1.25-1.34). Pregnant women who were older (30-50 years) at conception (HR, 1.13; 95% CI, 1.11-1.14), were overweight before pregnancy (HR, 1.13; 95% CI, 1.11-1.15), had a rural household registration (HR, 1.09; 95% CI, 1.09-1.10), worked as farmers (HR, 1.10; 95% CI, 1.09-1.11), and conceived in autumn (HR, 1.48; 95% CI, 1.46-1.50) appeared to be more sensitive to PM1 exposure than their counterparts. Conclusions and Relevance Results from this national cohort study examining more than 1.3 million births indicated that exposure to PM1 air pollution was associated with an increased risk of PTB in China. These findings will provide evidence to inform future research studies, public health interventions, and environmental policies.

The association between ambient temperature and the risk of preterm birth in China

BACKGROUND With the gradual increase of global warming, the impact of extreme temperatures on health has become a focus of attention, however, its relationship with preterm birth remains unclear. OBJECTIVES To investigate the association between exposure to extreme temperatures and preterm birth. METHODS Temperature exposures and birth outcomes of 1,020,471 pregnant women from 132 cities in China were investigated. The pregnancy process was divided into different pregnancy periods. Study areas were divided into three categories (cold, medium, and hot areas) according to the local average temperature by cluster analysis. Average temperature data for each province used in the cluster analysis came from the China Statistical Yearbook 2013. Logistic regression was used to compare the effects of exposure to hot and cold conditions on the outcomes of pregnancy in different periods and regions. RESULTS A total of 1,020,471 singleton births were included, of which 73,240(7.2%) were preterm births. Compared with moderate temperatures (5th to 95th percentile), heat exposure (>95th percentile) in different periods of pregnancy increased the risk of preterm birth in hot areas. The most obvious increase was during the 3 months before pregnancy (odds ratio (OR)=1.229, 95% confidence interval (CI): 1.166-1.295). In contrast to heat exposure, cold exposure (<5th percentile) in hot areas reduced the risk of preterm birth; the protective effect was most pronounced in the 3 months before pregnancy (OR=0.784, 95% CI: 0.734-0.832). In medium and cold areas cold exposure also reduced the risk of preterm birth. The effect of exposure to extreme ambient temperatures throughout the entire pregnancy on preterm birth was similar to those of the periods above. CONCLUSIONS Acute and chronic exposure to extreme temperatures may affect the risk of preterm birth. Extreme heat is a risk factor for preterm birth and extreme cold is a protective factor.

Long‐Term Effects of Ambient Particulate Matter (With an Aerodynamic Diameter ≤2.5 μm) on Hypertension and Blood Pressure and Attributable Risk Among Reproductive‐Age Adults in China

Background Epidemiological evidence on the association between long‐term exposure to ambient fine particulate matter (with an aerodynamic diameter ≤2.5 μm; PM 2.5) and hypertension is mixed. We investigated the long‐term association between ambient fine particles and hypertension in reproductive‐age adults. Methods and Results This analysis included 39 348 119 reproductive‐age (20–49 years) participants from the National Free Preconception Health Examination Project from April 22, 2010 to December 31, 2015 across China. The estimation of annual average ambient PM 2.5 concentrations for each community was realized through using satellite‐based spatial statistical models. Linear mixed models and 2‐level logistic regressions adjusted for potential confounders with natural cubic splines were used to investigate the shape of PM 2.5–blood pressure and PM 2.5‐hypertension, respectively. The effect modification by sex, obesity, smoking status, age, diabetes mellitus, urbanity, race, and region was also taken into account. The concentration‐response relationship between PM 2.5 and hypertension was nonlinear, with a threshold concentration of 47.9 μg/m3. The odds ratio of hypertension related to a 10‐μg/m3 increase in PM 2.5 above threshold was 1.010 (95% confidence interval, 1.007–1.012). A 10‐μg/m3 increase in PM 2.5 above threshold corresponded to a 0.569 (95% confidence interval, 0.564–0.573) mm Hg elevation in systolic blood pressure and a 0.384 (95% confidence interval, 0.381–0.388) mm Hg elevation in diastolic blood pressure. There were 2.3% (95% confidence interval, 2.2%–2.4%) of the hypertension cases that could be attributed to PM 2.5 exposures in reproductive‐age adult populations. Conclusions Long‐term exposures to PM 2.5 above certain levels might increase population risk for hypertension and might be responsible for Chinas avoidable hypertension burden in reproductive‐age adults.

Prevalence of chronic hepatitis B and status of HBV care among rural women who planned to conceive in China

Globally, one third of prevalent chronic hepatitis B (CHB) virus infection (HBV) occurred in China. Assessing the prevalence of CHB infesction and status of HBV-related services among pre-conception women will provide insight into risks of mother to child transmission (MTCT). A cross-sectional analysis of data from the National Free Pre-pregnancy Checkups (NFPC) program in 2010–2014 was conducted. A standardized questionnaire which collected demographic information and enzyme-linked immunosorbent assays (ELISA) which tested serological HBV markers were applied. A total of 16,051,850 rural women aged 15–49 years were included. 5.2% of women were infected with CHB, among whom, 28.6% were also hepatitis B e antigen (HBeAg) positive. The most CHB concentrated places were distributed in southeastern coastal provinces. Women born after 1992 did not experience a higher level of vaccine-induced immunity compared to those born before 1992. Nine in ten rural women with CHB were not aware of their HBV status and a very small proportion of women (0.22%) had received antiviral treatment. Our data demonstrated an overall high-intermediate burden of CHB. Heterogeneity of geographic distribution, high proportion of HBeAg, insufficient awareness of HBV status, and low access to HBV treatment are challenges for preventing the MTCT.

The association between ambient PM2.5 exposure and the risk of preterm birth in China: A retrospective cohort study

BACKGROUND The relationship between PM2.5 exposure and preterm birth remains unclear. OBJECTIVES To explore the effect of exposure to PM2.5 on preterm birth in China. METHODS The birth outcomes of 426,246 pregnant women enrolled between January 2014 and December 2014 in NFPCP (National Free Pre-pregnancy Checkups Project) were collected, and their individual PM2.5 exposure values were estimated from the China National Environmental Monitoring Centre. The time of gestational exposure to PM2.5 was divided into four periods (the first trimester, the second trimester, the third trimester and the entire pregnancy). The average concentration and the corresponding quartiles of PM2.5 were calculated in these periods by the daily average PM2.5 data. Cox proportional hazards regression was used and he effects of maternal age, education level, occupation, second-hand smoking, alcohol use, pre-pregnancy BMI, babys sex, number of previous pregnancies, coastal areas and season of conception were adjusted for. RESULTS A total of 426,246 singleton births were included, among which 35,261 (8.3%) were preterm birth. Effect of each 10μg/m3 increase of PM2.5 on preterm birth was most significant during the third trimester (HR, 1.06; 95%CI, 1.06-1.07), and also significant during the first trimester (HR, 1.04; 95%CI, 1.03-1.04), the second trimester (HR, 1.02; 95%CI, 1.02-1.02) and the entire pregnancy (HR, 1.06; 95%CI, 1.05-1.06). Compared with the lowest quartile of PM2.5, other quartiles increased the risk of preterm birth, and were most significant during the third trimester (HR, 1.87; 95%CI, 1.69-2.06). Subgroup analysis showed that compared with other subgroups, women who were older than 30years, had low education level, worked as farmers, had male baby, had previous pregnancies, not live in coastal areas and pregnant in winter were more sensitive to PM2.5 exposure. CONCLUSIONS Ambient PM2.5 exposure during pregnancy played an important role in the pregnancy process and increased the risk of preterm birth.

Long-term exposure to fine particulate matter and tachycardia and heart rate: Results from 10 million reproductive-age adults in China

BACKGROUND Epidemiological evidence of the association of long-term ambient fine particulate matter (aerodynamic diameter ≤2.5 μm; PM2.5) exposure with resting heart rate is limited. We explored the association of long-term (3-year average) ambient PM2.5 exposure with tachycardia and resting heart rate. METHODS This cross-sectional study surveyed 10,427,948 reproductive-age (20-49 years) adults across China in 2015. Tachycardia was classified as a resting heart rate of >80 beats per minute (bpm). The annual average ambient PM2.5 concentrations were obtained from a hybrid satellite-based geophysical statistical model. Linear mixed models and mixed effects logistic regressions adjusted for potential confounding were performed to explore the associations of PM2.5 with resting heart rate and PM2.5 with tachycardia, respectively. The effect modifiers by sex, age, body mass index, urbanity, race, region, smoking status, and drinking status were also assessed. Attributable cases and population fraction were estimated according to the PM2.5- tachycardia relationship. RESULTS The mean age was 28 years, and 16.3% of the participants had tachycardia. The odds ratio for tachycardia was 1.018 (95% confidence intervals [CI]: 1.017, 1.020) per 10 μg/m3 increase in the 3-year average PM2.5 exposure. A 10 μg/m3 increase in the 3-year average ambient PM2.5 level was associated with a 0.076 (95% CI: 0.073, 0.079) bpm elevation in the resting heart rate. Of the tachycardia burden, 4.0% (95% CI: 3.8%, 4.3%) could be attributed to ambient PM2.5 exposure in Chinese reproductive-age adults. CONCLUSIONS Exposures to ambient PM2.5 were associated with elevated resting heart rate. It might be possible to decrease Chinas avoidable tachycardia burden in reproductive-age adults through decreasing PM2.5 levels.