Objective:To explore the safety and efficacy of immune checkpoint inhibitors(ICI)for patients with tumor recurrence after liver transplantation(LT).Methods:A single-center retrospective study was conducted for 6 recipients of tumor recurrence after LT on a therapy of ICI admitted into Shulan(Hang Zhou)Hospital from September 2015 to June 2018.The authors examined the occurrences of graft rejection and clinical outcomes of overall response rate, progression-free survival and overall survival after dosing of PD-1/PD-L1 inhibitors.Results:Six patients enrolled with tumor recurrence on a therapy of ICI undergoing LT due to hepatocellular carcinoma (HCC). Nivolumab (n=4) and duvalizumab (n=2) were administrated.The median session of treatment was 8.3(2-31) cycles.The disease outcomes were stable (3/6, 50%) and progressive (3/6, 50%), The progression-free survival time of 3 disease-controlled patients was 1.5, 16.2 and 18 months and the median survival time after recurrence was 19.75(10.8-37.8) months.Rejection occurred in 1 patients (1/6, 16.7%) and the occurring time of rejection was 28 days after PD-1 inhibitor dosing.After acute rejection, high-dose corticosteroids and immunoglobulin were ineffective and the patient died from acute rejection related liver failure.Conclusions:ICI may be employed as a salvage treatment for tumor recurrence after LT for HCC.Due to a possibility of severe acute rejection, usage should be cautious under close monitoring of liver function.

Background It is projected that the frequency, density, and duration of compound hot extreme may increase in the 21st century in the context of global warming. Objective To explore the association between compound hot extreme and blood pressure, and identify sensitive populations. Methods This was a cross-sectional study. The study subjects were from six Guangdong Province Chronic Disease and Nutrition Surveys during 2002 through 2015. A questionnaire was administered to the participants with questions about demographic information, drinking and smoking status, and measurements on their height, weight, and blood pressure were also collected. We chose the data of May, September, and October to explore the association between compound hot extreme and blood pressure. Compound hot extreme means a hot day with a proceeding hot night. Daily meteorological data were obtained from China Meteorological Data Service Centre. We employed inverse distance weighting to interpolate the temperature and relative humidity values for each participant. A distributed lag non-linear model was used to estimate the association between compound hot extreme and blood pressure. Stratified analyses by sex, age, area, body mass index (BMI), smoking status, and drinking status were also performed to identify sensitive populations. A sensitivity analysis was conducted by adjusting the degrees of freedom for lag spline and removing relative humidity. Result A total of 10967 participants without history of hypertension were included in this study. The average systolic blood pressure (SBP) was 120.8 mmHg and the average diastolic blood pressure (DBP) was 74.5 mmHg. The proportion of participants who experienced hot day, hot night, or compound hot extreme were 9.34%, 17.95% and 2.90%, respectively. Compared to hot day, hot night and compound hot extreme were related with decreased blood pressure, and the effect of compound hot extreme was stronger: the changes and 95%CI for SBP was −6.2 (−10.3-−2.1) mmHg, and for DBP was −2.7 (−5.2-−0.2) mmHg. Compound hot extreme induced decreased SBP among male, population ≥ 65 years, and those whose BMI < 24 kg·m^-2, and their ORs (95%CIs) were −6.2 (−10.7-−1.6). −19.1 (−33.0-−5.1), and −6.7 (−11.8~−1.6) mmHg, respectively, and also decreased DBP among population ≥ 65 years, and its OR (95%CI) was −8.4 (−15.6-−1.1) mmHg. During compound hot extremes, participants living in rural areas showed decreased SBP and DBP, and the ORs (95%CIs) were −10.5 (−16.6-−4.5) and −4.4 (−7.7-−1.1) mmHg respectively, while those living in urban areas showed increased SBP, and the OR (95%CI) was 9.7 (2.9-16.5) mmHg. A significant decrease in blood pressure [OR (95%CI)] was also found in non-smokers [DBP, −3.7 (−6.6-−0.8) mmHg] and non-drinkers [SBP, −4.8 (−9.4-−0.2) mmHg; DBP, −3.4 (−6.0-−0.9) mmHg]. Conclusion Compound hot extreme is negatively associated with SBP, and being male, aged 65 years and over, and having BMI < 24 kg·m⁻² may be more sensitive to compound hot extreme.

Background In recent years, the incidence of metabolic syndrome (MS) is increasing significantly in China. Some studies have found that temperature is related to single metabolic index, but there is a lack of research on associated mechanism and identifying path of the influence of temperature on MS. Objective Based on the data of Guangdong Province, to investigate the effect of temperature on MS and its pathway. Methods A total of 8524 residents were enrolled by multi-stage random sampling from October 2015 to January 2016 in Guangdong. Basic characteristics, behavioral characteristics, health status, and physical activity level were obtained through questionnaires and physical examinations, and meteorological data were obtained from meteorological monitoring sites. We matched individual data both with the temperature data of the physical examination day and of a lag of 14 d. A generalized additive model was used to explore the exposure-effect relationship between temperature and MS and its indexes, calculate effect values, and explore the effects of single-day lag temperature. Based on the literature and the results of generalized additive model analysis, a path analysis was conducted to explore the pathways of temperature influencing MS. Results The association between daily average temperature on the current day or lag 14 day and MS risk was not statistically significant. When daily average temperature increased by 1 ℃, the change values of fasting blood-glucose (FBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), and high density lipoprotein cholesterol (HDL-C) were −0.033 (95%CI: −0.040-−0.026) mmol·L⁻¹, −0.662 (95%CI: −0.741-−0.583) mmHg, −0.277 (95%CI: −0.323-−0.230) mmHg, and −0.005 (95%CI: −0.007-−0.004) mmol·L⁻¹ respectively. The effects of average daily temperature on FBG, blood pressure, HDL-C, and waist circumference lasted until lag 14 day. The effects of daily average temperature on SBP and DBP were the largest on the current day. Daily average temperature of current day had direct and indirect effects on FBG and SBP. Temperature had an indirect effect on TG, and the intermediate variables were waist circumference and FBG, with an indirect effect value of −0.011 (95%CI: −0.020-−0.002). The indirect effects of daily average temperature on SBP, FBG, and TG were weak. Conclusion There is no significant correlation between temperature and risk of MS, and daily average temperature of current day could significantly affected blood pressure and FBG with a lag effect. Daily average temperature of current day has indirect effects on FBG and TG.

Background Stroke has become a main cause of death in China. With global warming, the studies on temperature and stroke have attracted much attention. Objective To analyze he relationships between heatwave and the years of life lost (YLL) by different subtypes of stroke by controlling temporal and spatial effects with Bayesian spatio-temporal model, and to study the modifiers of the health effect of heatwave. Methods The daily information of stroke deaths, meteorological data, and air pollutant data in 40 districts and counties of Guangdong Province were collected during the warm seasons (from May to October) in the years from 2014 to 2017. The individual YLL was first calculated by matching age and gender according to the life table, and then the daily YLL rate (person-years/100 000 people) was obtained by summarizing the daily YLL and correcting it with the population of each district or county. Bayesian spatio-temporal model was used to fit a proposed exposure-response relationship between heatwave and the YLL rates of different subtypes of stroke. Finally, stratified analyses were conducted by age (<65 years, ≥65 years), gender (male, female), and region (Pearl River Delta and non-Pearl River Delta regions) to identify the major modifiers for the association between heatwave and stroke mortality. Results During the warm seasons from 2014 to 2017, a total of 23 heatwave events occurred in the 40 districts or counties of Guangdong Province, cumulatively lasting for 145 d. A total of 30 852 stroke deaths were recorded in the same time periods. The average daily YLL rate of total stroke was (2.39±3.63) person-years/100 000 people, and those for hemorrhagic stroke and ischemic stroke were (1.54±2.99) person-years/100 000 people and (0.84±1.85) person-years/100 000 people, respectively. Heatwave was associated with increased YLL rate of stroke in residents, and it had a greater impact on ischemic stroke with a lag effect. The largest cumulative effect of heatwave was at lag 0-1 day, which was associated with an increased YLL rate of total stroke and ischemic stroke by 0.17 (95%CI: 0.03-0.29) person-years/100 000 people and 0.13 (95%CI: 0.06-0.20) person-years/100 000 people, respectively. The results of stratified analyses showed that heatwave had a larger effect on ischemic stroke in residents of aged 65 years or older, male, and non-Pearl River Delta regions, and the rates of YLL increased by 1.11 (95%CI: 0.58-1.55), 0.13 (95%CI: 0.03-0.23), and 0.20 (95%CI: 0.07-0.32) person-years/100 000 people, respectively; Heatwave only had an effect on hemorrhagic stroke in residents aged 65 years or older with an increased YLL rate of 0.79 (95%CI: 0.26-1.31) person-years/100 000 people. Conclusion Heatwave could elevate the level of years of life lost associated with stroke in Guangdong residents, with greater impacts on ischemic stroke of the aged, men, and residents in non-Pearl River Delta regions, and on hemorrhagic stroke in the elderly.

Background Global warming may increase the frequency of compound hot extreme (CHE).However, there is still a lack of studies assessing the associations between CHE and preterm birth (PTB), and the underlying biological mechanisms remain unclear. Objective To estimate the association of exposure to CHE during pregnancy with PTB, and to explore the roles of inflammatory, endothelial dysfunction, and oxidative stress in the association between CHE and PTB. Methods All participants were selected from the Prenatal Environments and Offspring Health (PEOH), a prospective birth cohort conducted in Guangzhou. In this study, a total of 2449 participants who gave birth from May to October in 2014 to 2017 were enrolled, and among them blood samples were collected from 311 preterm (n=43) and full-term (n=268) pregnant women at the time of delivery. A hot day/night was identified as a day when the daily maximum temperature/minimum temperature was higher than its 90th percentile in the study period, and a CHE was defined as having both a hot night and a following hot day. The meteorological data were obtained from the China Meteorological Data Sharing Service System. Anusplin was used to assess the daily maximum temperature, daily minimum temperature, and relative humidity of the participant residence. Enzyme-linked immunosorbent assay (ELISA) was used to measure C reactive protein (CRP), endothelin-1 (ET-1), and malondialdehyde (MDA) levels in maternal serum, and their results were transformed by natural logarithm. A distributed lag nonlinear model was used to investigate the associations of exposures to hot day, hot night, and CHE during pregnancy with PTB at different lag days, and a logistic regression model was used to investigate the associations of CRP, ET-1, and MDA with PTB. Results The incidence rate of PTB was 6.2% in all selected participants. Compared with the non-hot day, the RRs (95%CIs) of CHE in lag 3, 7, and 14 days on PTB were 1.43 (1.12-1.84), 1.24 (1.08-1.43), and 1.17 (1.05-1.30), respectively, and the cumulative effects (% difference) (95%CI) of CHE in lag 14 days on maternal serum CRP, ET-1, and MDA were 0.33% (−0.45%-1.12%), 0.59% (0.11%-1.07%), and 0.57% (0.09%-1.05%), respectively. Compared with the Q1 (lowest quartile) for CRP, ET-1 and MDA, the RRs (95%CIs) of Q4 (highest quartile) for PTB were 1.27 (0.50-3.22), 1.51 (0.61-3.72), and 2.07(0.81-5.27), respectively. Conclusion Maternal exposure to CHE during pregnancy might be associated with an increased risk of PTB. Prenatal exposure to CHE is positively associated with maternal serum CRP, ET-1, and MDA, and the three biochemical indicators are also positively associated with PTB. However, the above conclusions still need further confirmation.

Background Dengue fever is a mosquito-borne disease transmitted by Aedes aegypti and Aedes albopictus. Under the background of climate change, there are great challenges in the prevention and control of dengue fever, posing a serious health risk to the population. Objective To analyze the mechanism of temperature on dengue fever transmission and estimate the risk of dengue fever under different climate change scenarios by establishing a coupled human-mosquito dynamics model using Guangzhou as a research site, and to provide reference for adaptation to climate change. Methods Reported dengue fever cases and meteorological data from January 1, 2015 to December 31, 2019 in Guangzhou were collected from Guangdong Provincial Center for Disease Control and Prevention and China Meteorological Data Service Centre, respectively. The temperature data under three Representative Concentration Pahtyway (RCP2.6, RCP4.5, and RCP8.5) scenarios in 2030s (2031–2040), 2060s (2061–2070), and 2090s (2091–2099) were calculated by five general circulation models (GCMs) provided by the fifth phase of the Coupled Model Intercomparison Project. A dengue fever transmission dynamics (ELPSEI-SEIR) model was constructed to analyze the mechanism of temperature affecting dengue fever transmission by fitting the dengue fever epidemic trend from 2015–2019, and then the daily mean temperature under selected RCP scenarios for 2030s, 2060s, and 2090s was incorporated into the established dynamics model to predict the risk of dengue fever under different climate change scenarios in the future. Results From January 1, 2015 to December 31, 2019, a total of 4 234 cases of dengue fever were reported in Guangzhou, including 3741 local cases and 493 imported cases. The regression results showed that the model well fitted the dengue fever cases in Guangzhou from 2015 to 2019, and the coefficient of determination R2 to evaluate goodness of fit and the root mean squared error were 0.82 and 1.96, respectively. A U-shaped or inverted U-shaped relationship between temperature and mosquito habits could directly affect the number of mosquitoes and the transmission of dengue fever. We also found that temperature increase in most future scenarios could promote the transmission of dengue fever, and the epidemic period was significantly wider than the baseline stage. The epidemic of dengue fever would peak in the 2060s under the scenarios of RCP2.6 and RCP4.5. The estimated incidence of dengue fever was predicated to be highest in the 2030s and then decrease in the following years under RCP8.5, and in the 2090s, the incidence would decrease significantly, but the incidence peak would be earlier in each year, mainly from May to July. Conclusion Temperature can directly affect mosquito population and dengue fever transmission by affecting mosquito habits. The cases of dengue fever will increase under most climate scenarios in the future. However, the epidemic risk of dengue fever may be suppressed, and the epidemic season may be advanced under RCP8.5.

Objective:To identify the threshold of a health warning system based on the association of apparent temperature and years of life lost (YLL).Methods:Daily mortality records and meteorological data were collected from 364 Chinese counties for 2006-2017. Distributed lag nonlinear model and multivariate Meta-analyses were applied to estimate the association between the apparent temperature and YLL rate. A regression tree model was employed to estimate the warning thresholds of the apparent temperature. Stratified analyses were further conducted by age and cause of death.Results:The daily YLL rate was 23.6/10 5. The mean daily apparent temperature was 15.7 ℃. U-shaped nonlinear associations were observed between apparent temperature and YLL rate. The actual temperature-caused YLL rate for the elderly was higher than the young population. The daily excess deaths rate increased with the higher effect levels. Conclusions:Regression tree model was employed to define the warning threshold for meteorological health risk. The present study provides theoretical support for the weather-related health warning system.

Objective:To study the association between apparent temperature (AT) and the incidence of hand,foot, and mouth disease (HFMD) and its spatial heterogeneity in 46 cities in Guangdong, Anhui and Jilin provinces, and provide scientific evidence for the early warning of HFMD.Methods:The data of HFMD incidence and meteorological factors from 2009 to 2018 in Guangdong province, 2009 to 2015 in Anhui province, and 2013 to 2018 in Jilin province were collected. Distributed lag non-linear models were constructed to investigate the association between AT and the incidence of HFMD in 46 cities from three provinces in China. Meta-analysis was used to pool the city-specific estimates, and Meta-regression was applied to analyze the factors that may cause spatial heterogeneity.Results:The relationship between daily AT and the incidence of HFMD in 46 cities appeared nonlinear. The association in Guangdong was similar to that in Jilin, and the risk of HFMD increased with the increase of AT. While the risk of HFMD in Anhui first increased with the increase of AT, and peaked at 18.1 ℃ and then went down. AT on different levels showed different lag impacts and the higher AT showed greater and longer lag impact. The spatial heterogeneity of associations may have been caused by latitude, longitude, average temperature, and average sunshine hours.Conclusions:AT is a comprehensive index to evaluate the association between temperature, relative humidity and wind speed and the incidence of HFMD. Higher AT may increase the risk of HFMD. The AT and HFMD relationship across spatial heterogeneity varies depending on geographic location and meteorological conditions.

Objective: To evaluate the exported risk of novel coronavirus pneumonia (NCP) from Hubei Province and the imported risk in various provinces across China. Methods: Data of reported NCP cases and Baidu Migration Indexin all provinces of the country as of February 14, 2020 were collected. The correlation analysis between cumulative number of reported cases and the migration index from Hubei was performed, and the imported risks from Hubei to different provinces across China were further evaluated. Results: A total of 49 970 confirmed cases were reported nationwide, of which 37 884 were in Hubei Province. The average daily migration index from Hubei to other provinces was 312.09, Wuhan and other cities in Hubei were 117.95 and 194.16, respectively. The cumulative NCP cases of provinces was positively correlated with the migration index derived from Hubei province, also in Wuhan and other cities in Hubei, with correlation coefficients of 0.84, 0.84, and 0.81. In linear model, population migration from Hubei Province, Wuhan and other cities in Hubei account for 71.2%, 70.1%, and 66.3% of the variation, respectively. The period of high exported risk from Hubei occurred before January 27, of which the risks before January 23 mainly came from Wuhan, and then mainly from other cities in Hubei. Hunan Province, Henan Province and Guangdong Province ranked the top three in terms of cumulative imported risk (the cumulative risk indices were 58.61, 54.75 and 49.62 respectively). Conclusion The epidemic in each province was mainly caused by the importation of Hubei Province. Taking measures such as restricting the migration of population in Hubei Province and strengthening quarantine measures for immigrants from Hubei Province may greatly reduce the risk of continued spread of the epidemic.

Objective To compare the epidemiological characteristics of COVID-19 in Guangzhou and Wenzhou, and evaluate the effectiveness of their prevention and control measures. Methods Data of COVID-19 cases reported in Guangzhou and Wenzhou as of 29 February, 2020 were collected. The incidence curves of COVID-19 in two cities were constructed. The real time reproduction number ( R t ) of COVID-19 in two cities was calculated respectively. Results A total of 346 and 465 confirmed COVID-19 cases were analysed in Guangzhou and Wenzhou, respectively. In two cities, most cases were aged 30-59 years (Guangzhou: 54.9%; Wenzhou: 70.3%). The incidence curve peaked on 27 January, 2020 in Guangzhou and on 26 January, 2020 in Wenzhou, then began to decline in both cities. The peaks of imported COVID-19 cases from Hubei occurred earlier than the peak of COVID-19 incidences in two cities, and the peak of imported cases from Hubei occurred earlier in Wenzhou than in Guangzhou. In early epidemic phase, imported cases were predominant in both cities, then the number of local cases increased and gradually took the dominance in Wenzhou. In Guangzhou, the imported cases was still predominant. Despite the different epidemic pattern, the R t and the number of COVID-19 cases declined after strict prevention and control measures were taken in Guangzhou and in Wenzhou. Conclusion The time and scale specific differences of imported COVID-19 resulted in different epidemic patterns in two cities, but the spread of the disease were effectively controlled after taking strict prevention and control measures.