The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response. However, single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways. The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications. To circumvent this issue, we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle (PNM) for cancer therapy. PNM was engineered by integrating the PI3K/mTOR inhibitor PF-04691502 (PF) and the broad spectrum CDK inhibitor flavopiridol (Flav) into a single nanoplatform, which showed tumor-specific accumulation, activation and deep penetration in response to the high glutathione (GSH) tumoral microenvironment. The codelivery of PF and Flav could trigger gasdermin E (GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response. Furthermore, the combination of PNM-induced immunogenic pyroptosis with anti-programmed cell death-1 (αPD-1) immunotherapy further boosted the antitumor effect and prolonged the survival time of mice. Collectively, these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/mTOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.

Objective To analyze the epidemiological characteristic of stroke incidence and mortality in Chongqing, and to provide suggestions for targeted prevention and control of stroke. Methods Data of reported cases of ischemic stroke (I63), hemorrhagic stroke (I61-I62), subarachnoid hemorrhage (I60), and unclassified stroke (I64) in Chongqing in 2018 was collected. SPSS 25.0 was used to calculate the incidence, age-standardized incidence rate (ASIR), mortality, age-standardized mortality rate (ASMR) and proportion of stroke. The incidence and mortality of stroke were compared by Chi-square test between males and females, and between central urban areas and suburban counties. Results In 2018, the incidence and ASIR of stroke were 294.61/105 and 222.43/105 in Chongqing, respectively. The mortality and ASMR of stroke were 116.34/105 and 85.81/105. The incidence, ASIR and proportion of ischemic stroke were 186.63/105, 139.17/105 and 63.35%, respectively. The incidence of ischemic stroke in male was higher than that in female (χ²=18.52, P<0.001). The incidence of ischemic stroke in central urban areas was higher than that in suburban counties (χ²=29.50, P<0.001). The mortality of ischemic stroke in male was higher than that in female (χ²=6.67, P=0.010). The mortality of ischemic stroke in suburban counties was higher than that in central urban areas (χ²=17.55, P<0.001). The incidence, ASIR and proportion of hemorrhagic stroke were 78.15/105, 60.44/105 and 26.53%, respectively. The incidence of hemorrhagic stroke in male was higher than that in female (χ²=27.64, P<0.001). The incidence of hemorrhagic stroke in suburban counties was higher than that in central urban areas (χ²=18.60, P<0.001). The mortality of hemorrhagic stroke was the highest among all subtypes of strokes. The mortality, ASMR and proportion of hemorrhagic stroke was 64.44/105, 48.28/105 and 55.39%, respectively. The mortality of hemorrhage stroke in male was higher than that in female (χ²=23.46, P<0.001). The mortality of hemorrhage stroke in suburban counties was higher than that in central urban areas (χ²= 43.57, P<0.001). Conclusion The incidence and mortality of stroke in Chongqing were lower than the national average levels. The incidence of ischemic stroke was higher than that of hemorrhage stroke. The mortality of hemorrhage stroke was higher than that of ischemic stroke. Men and suburban counties were the focus of stroke prevention and control in Chongqing.

Objective To investigate the prevalence of hypertension and its risk factors among residents with age between 35 and 75 years old in Chongqing and provide evidence for the prevention and control of hypertension. Methods During 2016-2018, 101036 eligible subjects aged 35-75 years from 8 sites of China Patient-centered Evaluative Assessment of Cardiac Events in Chongqing were interviewed and examined. The data were analyzed by SPSS 20.0. The difference of the prevalence of hypertension of different population were compared chi-square test. Risk factors of hypertension was identified by step backward multivariate Logistic regression model. Results The crude prevalence and age standardization prevalence of hypertension was 40.80% and 33.91% respectively. The results of multivariate logistic regression indicated that the risk factors of hypertension were residence, ethnicity, age, medical insurance ,drinking, present smoking , indoor passive smoking , overweight , obesity , central obesity , diabetes and dyslipidemia ,while the protective factors of hypertension of those were education level and income. Conclusion The prevalence of hypertension was high among residents with age between 35 and 75 years old in Chongqing ; Residence, ethnicity, age, medical insurance, education level, income, drinking, present smoking , indoor passive smoking , overweight , obesity , central obesity , diabetes and dyslipidemia are the related factors of hypertension.

Objective To evaluate the clinical efficacy and safety of different stitching methods,over-the-scope-clip (OTSC) and metal clips combined with nylon rope (King closure),for full-layer gastric wall defect.Methods Data of 75 cases,who underwent endoscopic full-thickness resection (EFTR) of gastric SMTs from May 2015 to May 2018 in our endoscopy center were retrospectively analyzed.According to the closure method,the patients were divided into the OTSC group (20 cases) and the King closure group (55 cases).Comparison was made in gender,age,the largest diameter of tumor,the location of tumor,defect surface diameter,total operating time,defect closure time,closure success rate,the length of hospital stays,cost and postoperative complications between the two groups,Results The baseline data were comparable,and there were no significant differences in age,gender,tumor location,tumor diameter,and defect surface diameter between the two groups(all P＞0.05).The success rate of closure was 100％ in both groups.In terms of length of hospital stay,there was no significant difference between the two groups (t =1.13,P=0.268).The total operating time was 63.24±43.22 min in the King closure group versus 47.60± 18.13 min in the OTSC group (t =2.20,P =0.030).The closure time of the defect surface was 20.85 ± 16.35 min in the King closure group versus 10.95±5.20 min in the OTSC group (t =2.65,P=O.010).Hospitalization costs were 24 200±800 yuan in the King closure group versus 36 200±2 350 yuan in the OTSC group (t=6.21,P＜0.001).Postoperative abdominal elevation radiographs in both groups indicated a small amount of subphrenic free gas,and no intervention was given due to the small amount of gas and no obvious symptoms.No late bleeding,recurrent perforation,infection or other complications occurred after operation,and all patients were discharged successfully.Six months after surgery,15 patients (27％) in the King closure group developed metal clips or nylon rope residue,which were successfully removed by endoscopy.The anastomosis clamp of nighteen patients (95％) in the OTSC group were in the original position.None of the patient received open surgery.Conclusion OTSC and King closure are both safe and effective in the treatment of full-thickness defect of gastric wall.OTSC has the advantages of short total operation time and short closure time,but with high cost.

Objective To explore the distribution and antimicrobial resistance of pathogens causing healthcare-associated infection(HAI) in a hospital,and provide theoretical basis for rational use of antimicrobial agents and control of HAL Methods HAI occurred in patients in this hospital between 2011 and 2015 were chosen,distribution of major pathogens causing HAI and antimicrobial resistance were analyzed.Results A total of 852 pathogenic strains were isolated,including 458 (53.75 ％) strains of gram-negative bacteria,259 (30.40 ％) fungi,and 135 (15.85 ％) gram-positive bacteria,the top 4 pathogens were Klebsiella pneumoniae (n =159,18.66 ％),Candida albicans (n =119,13.97％),Acinetobacter baumannii (n =81,9.51％),and Escherichia coli (n =74,8.69 ％).Isolation rate of gram-negative bacteria increased from 47.41 ％ in 2012 to 61.57％ in 2015,fungi increased from 24.78％ in 2011 to 34.45％ in 2014 (2015 was 27.95％),gram-positive bacteria decreased from 26.55％ in 2011 to 10.48％ in 2015.Resistance rates of Escherichia coli and Klebsiella pneumoniae to imipenem and meropenem were 8.11％-12.58％;Acinetobacter baumannii had the lowest resistance rate to cefoperazone/sulbactam(23.46％),resistance rate of Candida albicans to fluconazole was up to 59.66％,vancomycin-resistant gram-positive bacteria was not found.Conclusion The major pathogens causing HAI are opportunistic pathogens,antimicrobial resistance is serious,the species and distribution varies with different years,it is necessary to enhance specimen detection rate,strengthen the monitoring on pathogen resistance,and use antimicrobial agents rationally.

Objective To explore the correlation of epicardial adipose tissue (EAT) volume with atrial fibrillation (AF) and its recurrence after radiofrequency ablation (RA).Methods Eighty-five AF patients (AF group) and 90 non-AF patients (control group) were chosen between January 2014 and May 2016.Their EAT volumes were measured by CT scanning.Patients in AF group after RA were followed up 6-18 months,and the recurrence of AF was recorded.The recurrence of AF within 3 months of RA was defined as blanking recurrence group (n =27) and non-blanking recurrence group (n =58),and that after 3 months of RA was defined as the 1 ong-term recurrence.Results The total EAT volume and left atrial EAT volume were significantly larger in blanking recurrence group than in non-blanking recurrence group [(118.71 ±28.94) cn3 vs (97.73 ±24.86)cm3,(29.98 ±8.09)cm3 vs (23.11 ±8.30)cm3,t =6.219,4.451,P ＜ 0.01].Multivariate logistic resgression analysis showed that total EAT volume and left atrial EAT volume were the independent risk factors for AF.All showed that total EAT volume and left atrial EAT volume were the independent risk factors for blanking recurrence.The incidence of long-term recurrence was significantly higher in blanking recurrence group [40.7％ (11/27)] than in non-blanking recurrence group [15.5 ％ (9/58)] (x2 =7.142,P ＜ 0.05).Conclusions The incidence of AF is higher in patients with a Iarger total EAT volume and a larger left atrial EAT volume and AF is easier to recur even though after RA.

Objective To study the relation of epicardial adipose tissue (EAT) thickness with 1eftventricular remodeling and dysfunction in dilated cardiomyopathy (DCM) patients.Methods One hundred and twenty DCM patients who received treatment from Febuary 2012 to February 2016 were served as DCM group,and 76 healthy subjects undergoing physical examination were served as control group.Their left ventricular end-diastolic diameter (LVEDD),left ventricular end systolic diameter (LVESD),left ventricular end diastolic volume (LVESV),left ventricular end systolic volume (LVEDV),left ventricular end diastolic volume index (LVEDVI),left ventricular end systolic volume index (LVESVI),sphericity index (SI),leftventricular ejection fraction (LVEF),and EAT thickness were measured by routine cardiac ultrasonography and compared between two groups.Results The levels of LVESD,LVEDD,LVESV,LVEDV,LVESVI,LVEDVI and EAT thickness in DCM group were significantly higher,and the levels of LVEF,SIS and SID in DCM group were significantly lower (P＜0.05).The EAT thickness in DCM group with NYHA class Ⅱ,Ⅲ,Ⅳ was (8.1 ± 1.8),(7.8 ± 2.0),(7.9 ± 1.7) mm,and there was significant difference (F=1.973,P＞ 0.05) Linear correlation analysis showed that the EAT thickness was positively related with the LVESD,LVEDD,LVESV,LVEDV,LVEDVI,LVESVI,SISand SID (r =0.247,0.231,0.256,0.267,0.293,0.281,0.261,0.237,P＜0.05).There was no relationship between EAT thickness and LVEF (r =0.132,P＞ 0.05).Logistic multifactor regression analysis showed that EAT thickness was an independent risk factor for left ventricular remodeling in DCM patients (OR =0.793,95％CI:0.431-1.734,P =0.039).Conclusions The EAT thickness is significantly related with the left ventricular remodeling and can be used as an independent risk factor for predicting left ventricular remodeling in DCM patients.

OBJECTIVETo evaluate the influence of extreme ambient temperature on mortality and years of life lost (YLL) in Chongqing.

METHODSThe daily mortality, meteorology and air pollution index data in Chongqing from the 1(st) January 2010 to the 31(st) December 2013 were collected. Distributed lag non-linear model (DLNM) was used to assess the influence of daily ambient temperature on daily number of deaths and daily YLL respectively. The delayed and cumulative effects of extreme temperature on sex, age, and cause-specific mortality were also assessed.

RESULTSThe relationships between ambient temperature and non-accidental, cardiovascular disease and respiratory disease mortalities and YLL were U-shaped or W-shaped. The effect of heat was obvious on that day, peaked on day 7, and lasted for two weeks, whereas the effect of cold was obvious a week later and lasted for a month. As 1 ℃ increase of ambient temperature, the cumulative relative risks (CRR) of high temperature across lag 0-7 days on non-accidental, respiratory disease and cardiovascular disease mortalities were 1.05 (95%CI: 1.03-1.07), 1.08 (95%CI: 1.05-1.11) and 1.05 (95%CI: 1.01-1.09) respectively. The effects of heat on YLL for each cause were 23.81 (95%CI: 12.31-35.31), 14.34 (95%CI: 8.98-19.70) and 4.43 (95%CI: 1.64-7.21), respectively. On cold days, 1 ℃ decrease of ambient temperature was correlated with an increase in CRR of 1.06 (95%CI: 1.04-1.08), 1.09 (95%CI:1.06-1.12) and 1.06 (95%CI: 1.02-1.11) from lag 0 to 14 for non-accidental, respiratory disease and cardiovascular disease mortalities, respectively. The estimated YLL were 23.34 (95%CI: 10.04-36.64), 16.39 (95%CI: 10.19-22.59) and 2.61 (95%CI: -0.61-5.82). People aged ≥65 years tend to have higher CRR and YLL than those aged <65 years. On high temperature days, the CRR in women was higher than that in men, while the YLL in women was lower than that in men. On low temperature days, both the CRR and YLL in women were higher than those in men.

CONCLUSIONSBoth high and low ambient temperature have adverse health effects. People aged ≥65 years are more sensitive to both high and low ambient temperature. Younger men are more sensitive to high ambient temperature and women and elder men are sensitive to low ambient temperature. It is necessary to take targeted measures to protect the population in Chongqing from the adverse influence of extreme ambient temperature.

Adult ; Aged ; Cardiovascular Diseases ; mortality ; China ; epidemiology ; Cold Temperature ; adverse effects ; Female ; Hot Temperature ; adverse effects ; Humans ; Life Expectancy ; trends ; Male ; Mortality ; trends ; Nonlinear Dynamics ; Respiratory Tract Diseases ; mortality ; Temperature

Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; China ; epidemiology ; Humans ; Middle Aged ; Plague ; epidemiology ; Yersinia pestis