Background Injury poses a serious threat to human health. As global warming continues to intensify, there is an urgent need to explore the impact of temperature changes on injury deaths. However limited research has focused on this issue. Objective To investigate the relationship between daily mean temperature change (Tm) and injury death, as well as to estimate the associated future death burden in Hunan Province. Methods We employed an individual-level, time-stratified case-crossing design to establish a conditional logistic regression model to analyze the exposure-response relationship between daily mean temperature change and injury death in Hunan Province from 2013 to 2018. Consequently, we conducted subgroup analysis of gender, age group, and injury type. Finally, we estimated the excess burden of injury death attributable to temperature changes under a sustainable development path [low emission scenario (SSP1-2.6)], regional competition path [high emission scenario (SSP3-7.0)], or fossil fuel development path [very high emission scenario (SSP5-8.5)]. Results The study collected 155577 injury deaths in Hunan Province. The results indicated that for each 1 ℃ increment in daily mean temperature, the cumulative excess risk (CER) of injury mortality among Hunan residents increased by 0.71% (95%CI: 0.53%, 0.90%). Notably, the CER for intentional injuries (1.06%, 95%CI: 0.51%, 1.61%) was higher than that for unintentional injuries (0.66%, 95%CI: 0.46%, 0.87%). Warmer temperatures were positively associated with CER of mortality due to drowning, falls, transport injuries, assaults, and suicides, while they were negatively associated with mortality due to poisoning. Compared with 2010–2019, for 2090–2099, the excess mortality rate (EMR) due to ambient temperature increase in Hunan Province under the SSP5-8.5 scenario (14.62/100000, 95%CI: 10.81/100000, 18.40/100000) would be higher than that of the SSP3-7.0 scenario (10.28/100000, 95%CI: 7.58/100000, 12.97/100000) and the SSP1-2.6 scenario (3.35/100000, 95%CI: 2.46/100000, 4.23/100000); the EMR would be around 2.5 times among men (20.64/100000, 95%CI: 14.44/100000, 26.8/100000) than that among women (8.33/100000, 95%CI: 3.98/100000, 12.6/100000). Among unintentional injuries, the leading contributors to EMR would be drowning (4.46/100000), falls (3.96/100000), and transport injuries (2.96/100000). And among intentional injuries, the EMR for suicide (2.08/100000) would be higher than that for assault (0.47/100000). Conclusion Climate warming will increase the total burden of injury-related deaths among residents in Hunan Province, especially in the absence of effective mitigation strategies and measures. It is necessary to strengthen the prevention and control of severe injuries closely related to temperature changes, such as drowning, falls, traffic, and suicides injuries, in order to reduce injury deaths associated with climate change.

Background Air pollution is a major public health concern. Air Quality Health Index (AQHI) is a very important air quality risk communication tool. However, AQHI is usually constructed by single-pollutant model, which has obvious disadvantages. Objective To construct an AQHI based on the joint effects of multiple air pollutants (J-AQHI), and to provide a scientific tool for health risk warning and risk communication of air pollution. Methods Data on non-accidental deaths in Yunnan, Guangdong, Hunan, Zhejiang, and Jilin provinces from January 1, 2013 to December 31, 2018 were obtained from the corresponding provincial disease surveillance points systems (DSPS), including date of death, age, gender, and cause of death. Daily meteorological (temperature and relative humidity) and air pollution data (SO₂, NO₂, CO, PM_2.5, PM₁₀, and maximum 8 h O₃ concentrations) at the same period were respectively derived from China Meteorological Data Sharing Service System and National Urban Air Quality Real-time Publishing Platform. Lasso regression was first applied to select air pollutants, then a time-stratified case-crossover design was applied. Each case was matched to 3 or 4 control days which were selected on the same days of the week in the same calendar month. Then a distributed lag nonlinear model (DLNM) was used to estimate the exposure-response relationship between selected air pollutants and mortality, which was used to construct the AQHI. Finally, AQHI was classified into four levels according to the air pollutant guidance limit values from World Health Organization Global Air Quality Guidelines (AQG 2021), and the excess risks (ERs) were calculated to compare the AQHI based on single-pollutant model and the J-AQHI based on multi-pollutant model. Results PM_2.5, NO₂, SO₂, and O₃ were selected by Lasso regression to establish DLNM model. The ERs for an interquartile range (IQR) increase and 95% confidence intervals (CI) for PM_2.5, NO₂, SO₂ and O₃ were 0.71% (0.34%–1.09%), 2.46% (1.78%–3.15%), 1.25% (0.9%–1.6%), and 0.27% (−0.11%–0.65%) respectively. The distribution of J-AQHI was right-skewed, and it was divided into four levels, with ranges of 0-1 for low risk, 2-3 for moderate risk, 4-5 for high health risk, and ≥6 for severe risk, and the corresponding proportions were 11.25%, 64.61%, 19.33%, and 4.81%, respectively. The ER (95%CI) of mortality risk increased by 3.61% (2.93–4.29) for each IQR increase of the multi-pollutant based J-AQHI , while it was 3.39% (2.68–4.11) for the single-pollutant based AQHI . Conclusion The J-AQHI generated by multi-pollutant model demonstrates the actual exposure health risk of air pollution in the population and provides new ideas for further improvement of AQHI calculation methods.

OBJECTIVE: Cassiae Semen (CS, Juemingzi in Chinese) has been used for thousands of years in ancient Chinese history for relieving constipation, improving liver function as well as preventing myopia. Here we aimed to elucidate the anti-steatosis effect and underlying mechanism of CS against non-alcoholic fatty liver disease (NAFLD). METHODS: High-performance liquid chromatography (HPLC) was used to identify the major components of CS water extract. Mice were fed with a high-fat and sugar-water (HFSW) diet to induce hepatic steatosis and then treated with CS. The anti-NAFLD effect was determined by measuring serum biomarkers and histopathology staining. Additionally, the effects of CS on cell viability and lipid metabolism in oleic acid and palmitic acid (OAPA)-treated HepG2 cells were measured. The expression of essential genes and proteins involved in lipid metabolism and autophagy signalings were measured to uncover the underlying mechanism. RESULTS: Five compounds, including aurantio-obtusin, rubrofusarin gentiobioside, cassiaside C, emodin and rhein were simultaneously identified in CS extract. CS not only improved the diet-induced hepatic steatosis in vivo, as indicated by decreased number and size of lipid droplets, hepatic and serum triglycerides (TG) levels, but also markedly attenuated the OAPA-induced lipid accumulation in hepatocytes. These lipid-lowering effects induced by CS were largely dependent on the inhibition of fatty acid synthase (FASN) and the activation of autophagy-related signaling, including AMP-activated protein kinase (AMPK), light chain 3-II (LC3-II)/ LC3-1 and autophagy-related gene5 (ATG5). CONCLUSION Our study suggested that CS effectively protected liver steatosis via decreasing FASN-related fatty acid synthesis and activating AMPK-mediated autophagy, which might become a promising therapeutic strategy for relieving NAFLD.

Malaria still threatens global health seriously today. While the current discoveries of antimalarials are almost totally focused on single mode-of-action inhibitors, multi-targeting inhibitors are highly desired to overcome the increasingly serious drug resistance. Here, we performed a structure-based drug design on mitochondrial respiratory chain of

Objective:To assess the efficacy of immunosuppressor on treatment of Henoch-Sch?nlein purpura nephritis(HSPN).Methods:Literatures were searched in PubMed, Cochrane library, Web of Science, Wanfang database, CNKI and CBM database from inception to January 2021.The studies that investigated the effect of immunosuppressor on HSPN outcomes were included.Article screening, data extraction and quality assessment were accomplished by two investigators independently, and statistical analyses were performed by STATA 14.Results:Ten studies were included with 443 cases, of which, 245 cases were in the experimental group while 198 cases were in the control group.The Meta-analysis showed that the experimental group had higher complete remission rate( OR=1.95, 95% CI 1.19-3.22, P=0.009), total remission rate ( OR=2.92, 95% CI 1.74-4.88, P<0.001), proteinuria decreasing level ( SMD=0.35, 95% CI 0.09-0.61, P=0.008), the increasing level of serum albumin ( SMD=1.27, 95% CI 0.43-2.11, P=0.003) and the increasing level of estimated glomerular filtration rate ( SMD=0.48, 95% CI 0.21-0.76, P=0.001), lower relapse rate ( OR=0.19, 95% CI 0.05-0.72, P=0.015) as well as death rate ( OR=0.19, 95% CI 0.04-0.78, P=0.021)than those of the control group. Conclusion:The immunosuppressor could enhance complete remission rate, total remission rate, proteinuria decreasing level, the increasing level of serum albumin and the increasing level of estimated glomerular filtration rate, reduce relapse rate and death rate of HSPN patients.

Objective: To investigate visual acuity of pupils of grade 4-6 in Liaoning Province in 2019 and to analyze its influencing factors, and to provide the scientific basis for myopia prevention and intervention. Methods: A total of 16 716 students of grade 4-6 in 14 cities of Liaoning Province were selected by multi-stage stratified random cluster sampling, and the long-range visual acuity and refraction was evaluated and a questionnaire survey was conducted. Logistic regression analysis was used to analyze the in-fluencing factors of myopia in primary school students. Results: The myopic rate of grade 4-6 pupils in Liaoning Province was 49.17%. Multiple Logistic regression analysis found that the main factors affecting vision included urban and rural division, sex, recess, restriction of electronic products usage from parents, and heredity(OR=0.93, 1.29, 0.90, 0.82, 3.12, 1.61, 1.64, P<0.05). Among them, rural areas, outdoor activity during recess and restriction of electronic product usage from parents was associated with lower risk of myopia, in contrast, being girl and parental myopia was associated with higher risk of myopia. Conclusion The incidence of myopia among primary school students in Liaoning Province is relatively high, exterting high pressure on prevention and control. In order to prevent myopia in primary school students, Composite interventions should be developed including change students’ lear-ning style, eliminate unhealthy living habits and targeted propaganda and education.

BACKGROUND: Primary lung cancer and metastatic lung cancer are common malignant tumors of the lung and are the main cause of cancer-related death. Advanced lung cancer and lung metastatic cancer are mainly treated by systemic therapy, and local treatment is also an effective treatment for the refractory or recurrent lesions in the lungs after systemic treatment. ¹²⁵I radioactive particle implantation, as an efficient conformal radiotherapy, has a certain control effect on localized lung cancer. The purpose of this study was to investigate the clinical efficacy and safety of computed tomography (CT) guided percutaneous puncture of lung tissue with ¹²⁵I radioactive particle implantation in the treatment of advanced lung cancer and lung metastatic cancer. METHODS: Continuouslycollectedthe clinical and pathological data of 105 patients with advanced lung cancer and metastatic lung cancer treated by ¹²⁵I radioactive seed implantation in the Department of Thoracic Surgery, First Affiliated Hospital of Zhejiang University School of Medicine from January 1, 2014 to November 30, 2018. The patients were followed until March, 2019. The clinical efficacy and complications of seedimplantation were analyzed. RESULTS: A total of 105 patients were included in the study, 78 patients with advanced lung cancer and 27 patients with lung metastases. The median survival time after seed therapy was 395 days. The 1-year survival rate was about 78.1%, and the 2-year survival rate was about 56.1%. Seed implantation for advanced lung cancer is equivalent to lung metastasis. Seed combined with radiofrequency ablation, microwave ablation, and chemotherapy did not improve seed treatment. However, particle combined with external radiation therapy has a significant survival disadvantage compared with simple seed therapy. CONCLUSIONS The CT-guided ¹²⁵I radioactive seed implantation has controllable complications and can be used as a safe and effective treatment for advanced lung cancer and lung metastases.

OBJECTIVE：To stu dy the mechanism of improvement effects of Gastrodin injection on methamphetamine induced neurotoxic damage in rats via nNOS pathway. METHODS ：SD rats were randomly divided into control group ，methamphetamine group，regular-dose of gastrodin group ，double-dose of gastrodin group ，negative control （NC）adenovirus group ，NC adenovirus+ methamphetamine group ，NC adenovirus+gastrodin group and nNOS adenovirus+gastrodin group ，with 10 rats in each group. Control group was given normal saline intraperitoneally ，twice a day. Methamphetamine group was given methamphetamine intraperitoneally（7.5 mg/kg），twice a day. Regular-dose and double-dose of gastrodin groups were respectively given different doses of Gastrodin injection （10，20 mg/kg）intraperitoneally 30 min earlier ，once a day ，and then given methamphetamine intraperitoneally by the same way as methamphetamine group. NC adenovirus group was given NC adenovirus （4.8×107 PFU）3 μL once in the striatum and normal saline intraperitoneally ，twice a day. NC adenovirus+methamphetamine group was given NC adenovirus by the same way and methamphetamine （7.5 mg/kg）intraperitoneally，twice a day. NC adenovirus+gastrodin group was given NC adenovirus+methamphetamine by the same way ，meanwhile given Gastrodin injection intraperitoneally （20 mg/kg）30 min before methamphetamine ，once a day. nNOS adenovirus+gastrodin group was given nNOS adenovirus and methamphetamine by the same way ，meanwhile given Gastrodin injection intraperitoneally （20 mg/kg）30 min before methamphetamine ，once a day. Each group was given relevant medicine intraperitoneally 1 mL/100 g，for consecutive 3 days. The stereotyped behavior of rats were observed and scored ；the apoptotic rate ，the protein expression of apoptotic factors （Bcl-2，Bax，Cleaved caspase- 3），the levels of oxidative stress factors （MDA，SOD，GPx） and NO ，the protein expression of nNOS were detected. RESULTS ： Compared with control group ，stereotyped behavior score ，cell apoptosis rate of striatum ，protein expression of Bax ，Cleaved caspase-3 and nNOS ，the levels of MDA and NO were increased significantly in methamphetamine group ；while the protein expression of Bcl- 2 and the levels of SOD and GPx were decreased significantly （P＜0.05 or P＜0.01）. Compared with methamphetamine group ，stereotyped behavior score ，cell apoptosis rate of striatum ，protein expression of Bax ，Cleaved caspase- 3 and nNOS ，the levels of MDA and NO were decreased significantly in regular-dose and double-dose of gastrodin groups ；while the protein expression of Bcl- 2，the levels of SOD and GPx were increased significantly ，and most above indexes in double-dose of gastradin group were better than regular-dose of gastrodin group （P＜0.05 or P＜0.01）. Compared with NC adenovirus group ，cell apoptosis rate of striatum ，protein expression of Bax ，Cleaved caspase- 3 and nNOS ，the levels of MDA and NO were increased significantly in NC adenovirus+methamphetamine group ；while the protein expression of Bcl- 2，the levels of SOD and GPx were decreased significantly （P＜0.01）. Compared with NC adenovirus+methamphetamine group ，cell apoptosis rate of striatum ，protein expression of Bax ，Cleaved caspase- 3 and nNOS ，the levels of MDA and NO were decreased significantly in NC adenovirus+ gastrodin group ；while the protein expression of Bcl- 2，the levels of SOD and GPx were increased significantly （P＜0.01）. Compared with NC adenovirus+gastrodin group ，cell apoptosis rate of striatum ，protein expression of Bax ，Cleaved caspase- 3 and nNOS，the levels of MDA and NO were increased significantly in nNOS adenovirus+gastrodin group ；while the protein expression of Bcl- 2，the levels of SOD and GPx were decreased significantly （P＜0.01）. CONCLUSIONS ：Gastrodin injection can protect rats against neurotoxic damage induced by methamphetamine ，and the effect is related to the inhibition of nNOS-mediated apoptosis and oxidative stress.

Objective: To discuss the characteristics of symptoms improvement based on the follow-up evaluation of Eustachian tube balloon dilation medium to long-term efficacy in patients with symptomatic Eustachian tube dysfunction (SETD). Methods: Patients from 2015 to 2017 were followed up after Eustachian tube balloon dilation (with the sense of aural fullness, or tinnitus and hearing ambiguity). All participants had been done ETDQ-7 before surgery and were re-evaluated with ETDQ-7 in follow-up. The improvement of overall and individual symptoms scores in ETDQ-7, the effects of gender and the difference of scores at different stages (12-18 months, 18-24 months and 24-30 months) after the operation were analyzed. Results: There were 29 patients, including 16 males and 13 females, whose age ranged from 20 to 62 years old. The medium to long-term score of ETDQ-7 significantly declined after surgery (27.0±7.9 vs. 14.1±7.5, P<0.05). Among all symptoms, symptoms like "blockage feeling in ear or being like under the water, constriction feeling" , "sound of blisters or explosions in the ear" decreased obviously (P<0.05). Comparing different stages after surgery, the scores of ETDQ-7 existed no difference (P>0.05). And the difference of gender showed no significant influence on surgery effects. Conclusion The subjective symptoms of patients with Eustachian tube dysfunction diagnosed with SETD can be significantly improved in the medium to long-term follow-up after Eustachian tube balloon dilation, and the degree of improvement is not linearly related to the postoperative time.

Huntington's disease (HD) is a deadly neurodegenerative disease with abnormal expansion of CAG repeats in the huntingtin gene. Mutant Huntingtin protein (mHTT) forms abnormal aggregates and intranuclear inclusions in specific neurons, resulting in cell death. Here, we tested the ability of a natural heat-shock protein 90 inhibitor, Gedunin, to degrade transfected mHTT in Neuro-2a cells and endogenous mHTT aggregates and intranuclear inclusions in both fibroblasts from HD patients and neurons derived from induced pluripotent stem cells from patients. Our data showed that Gedunin treatment degraded transfected mHTT in Neuro-2a cells, endogenous mHTT aggregates and intranuclear inclusions in fibroblasts from HD patients, and in neurons derived from induced pluripotent stem cells from patients in a dose- and time-dependent manner, and its activity depended on the proteasomal pathway rather than the autophagy route. These findings also showed that although Gedunin degraded abnormal mHTT aggregates and intranuclear inclusions in cells from HD patient, it did not affect normal cells, thus providing a new perspective for using Gedunin to treat HD.