BACKGROUND: There are few multi-city studies on the association between temperature and mortality in basin climates. This study was based on the Sichuan Basin in southwest China to assess the association of basin temperature with non-accidental mortality in the population and with the temperature-related mortality burden. METHODS: Daily mortality data, meteorological and air pollution data were collected for four cities in the Sichuan Basin of southwest China. We used a two-stage time-series analysis to quantify the association between temperature and non-accidental mortality in each city, and a multivariate meta-analysis was performed to obtain the overall cumulative risk. The attributable fractions (AFs) were calculated to access the mortality burden attributable to non-optimal temperature. Additionally, we performed a stratified analyses by gender, age group, education level, and marital status. RESULTS: A total of 751,930 non-accidental deaths were collected in our study. Overall, 10.16% of non-accidental deaths could be attributed to non-optimal temperatures. A majority of temperature-related non-accidental deaths were caused by low temperature, accounting for 9.10% (95% eCI: 5.50%, 12.19%), and heat effects accounted for only 1.06% (95% eCI: 0.76%, 1.33%). The mortality burden attributable to non-optimal temperatures was higher among those under 65 years old, females, those with a low education level, and those with an alternative marriage status. CONCLUSIONS Our study suggested that a significant association between non-optimal temperature and non-accidental mortality. Those under 65 years old, females, and those with a low educational level or alternative marriage status had the highest attributable burden.
Female ; Humans ; China/epidemiology* ; Cities ; Cold Temperature ; Hot Temperature ; Mortality ; Temperature ; Time Factors ; Middle Aged ; Male

Viral infection can induce endoplasmic reticulum stress(ERS)and unfolded protein re-sponse(UPR)in host cells,resulting in perturbation of endoplasmic reticulum homeostasis.To e-lucidate the action mechanism of isochlorogenic acid A(IAA)in regulating peste des petits rumi-nant virus(PPRV)-induced ERS and UPR,MTT assay,indirect immunofluorescence assay and Western blot were used to evaluate the anti-PPRV activity of IAA,and the effects of IAA on PPRV-induced ERS and PERK signaling pathway were studied by Western blot and quantitative real-time PCR.The results showed that the PPRV replication and virus-induced cytopathic in LDG-2 cells were significantly inhibited,and the survival rate of virus-infected cells was significantly in-creased due to IAA treatment.Compared with the virus control group,the expression levels of GRP78 and p-eIF2α,the ratios of p-PERK/PERK and p-eIF2α/eIF2α in IAA treated PPRV-infec-ted cells were significantly decreased.The expression level of GADD153 significantly decreased at 24,36 h,and significantly increased at 48,60 h.Furthermore,treatment with ERS inhibitor 4-PBA could significantly suppress the expression levels of GRP78,PPRV-N protein and GADD153 in PPRV-infected cells,and the ratios of p-eIF2α/eIF2α and p-PERK/PERK in PPRV-infected cells were also significantly decreased caused by treatment with IAA or 4-PBA and IAA combination.These findings implicated that the PPRV-induced ERS could be alleviated by inhibiting activation of the PERK-eIF2α-GADD1 53 signaling pathway,which led to restriction of PPRV replication in host cells.

Viral infection can induce endoplasmic reticulum stress(ERS)and unfolded protein reac-tion(UPR)in host cells.This study aims to further explore the effects of ERS induced by pest des petits ruminants virus(PPRV)infection on UPR signaling pathway,virus replication and apopto-sis of host cells.MTT assay,indirect immunofluorescence assay(IFA)and Western blot were used to observe the proliferation of PPRV in goat kidney cells(LDG-2).Western blot and real-time flu-orescence quantitative PCR(qRT-PCR)were used to observe the effects of PPRV infection on the expression levels of GRP78,PERK and its downstream signal molecules,apoptosis-related proteins Bcl-2 and Bax.The result indicated that the cell survival rate was significantly declined with evident cytopathic effect at 36 h post-infection,and the expression level of PPRV-N protein tended to be elevated,and was significantly higher than that of cell control at 30 h post-infection.Meanwhile,the expression levels of GRP78,p-eIF2α and GADD153,the ratio of p-PERK/PERK and p-eIF2α/eIF2α were significantly increased.Moreover,the expression levels of PPRV-N protein,GRP78,p-eIF2α and GADD1 53,the ratio of p-eIF2α/eIF2α and p-PERK/PERK were significantly decreased in PPRV-infected cells due to 4-PBA treatment.The expression level of apoptosis-related Bcl-2 was down-regulated,Bax was up-regulated,and the ratio of Bcl-2/Bax was significantly decreased.Therefore,the activation of PERK/eIF2α/GADD153 signaling pathway could be induced by PPRV infection resulting in alleviating of virus-induced ERS,which is beneficial to viral replication.Bloc-king PPRV-induced ERS could inhibit the activation of PERK signaling pathway and virus replica-tion.PPRV infection and prolonged ERS can induce apoptosis of LDG-2 cells.

MTT assay,indirect immunofluorescence assay(IFA)and real-time fluorescence quanti-tative PCR(qRT-PCR)were used to observe the proliferation of PPRV in goat kidney cells(LDG-2).Western blot and qRT-PCR were used to evaluate the effects of PPRV infection on the expres-sion levels of TLR2,MyD88,NF-κB signaling pathway-related factors and their downstream in-flammatory factors.The results indicated that the significantly decreased cell survival rate and ob-vious cytopathic effect were observed at 36 h post PPRV infection,and the mRNA expression level of PPRV-N gene was significantly up-regulated.At the same time,the expression levels of TLR2,MyD88,p-p65 and p-IκBα,the ratio of p-p65/p65 and p-IκBα/IκBα and the mRNA expression levels of downstream inflammatory factors TNFα,IL-1β,IL-4 and IL-10 were significantly increased.Mo-reover,the expression levels of PPRV-N mRNA,TLR2,MyD88,p-p65 and p-IκBα,the ratio of p-p65/p65 and p-IκBα/IκBα and the mRNA expression levels of downstream inflammatory factors IL-1β and IL-4 in PPRV-infected cells were significantly decreased in the presence of the inhibitor C29 of TLR2.These findings implied that the TLR2/MyD88/NF-κBα signaling pathway can be activated by PPRV infection,which is beneficial to the replication and spread of the virus.Blocking down the activation of TLR2 can inhibit MyD88/NF-κB signaling pathway and viral replication in PPRV-infected cells.

Objective:To explore whether renal artery involvement is an independent risk factor of acute renal injury (AKI) KDIGO stage 3 after moderate hypothermic circulatory arrest in patients with acute Stanford type A aortic dissection.Methods:From December 2015 to October 2017, 492 consecutive patients with acute Stanford A-type aortic dissection received surgical treatment, 486 of them were included in the study. All patients underwent aortic CTA to determine the extent of aortic dissection and renal artery involvement. According to the standard of Improving Global Outcomes (KDIGO), the renal function of patients after operation was graded. The risk factors of AKI KDIGO stage 3 were analyzed.Renal artery involvement and other risk factors were included in univariate analysis, and significant variables in univariate analysis were included in multivariate logistic regression analysis.Results:In 492 patients, 40 (8.13%) died in hospital, of which 6 died of severe bleeding during operation or failed to wean from cardiopulmonary bypass which lead to unable to leave the Weaning from cardiopulmonary bypass and these 6 patients were excluded in the research. Among 486 patients included in the study, 251 (51.64%) had AKI. Among them, 83 (17.08%) were in the KDIGO stage 1, 56 (11.52%) in stage 2 and 112 (23.05%) in stage 3.The results of univariate analysis showed that there were significant differences in renal artery involvement, age, time from onset to operation, D-dimer, leukocytes and platelets in peripheral blood, creatinine clearance rate, time of cardiopulmonary bypass during operation and aortic cross-clamping time( P>0.05). The above risk factors were included in multivariate logistic regression. The results showed that preoperative renal artery involvement ( OR=1.94, P=0.02), age ( OR=1.03, P=0.02), creatinine clearance rate<85 ml/min ( OR=2.28, P=0.001), and intraoperative cardiopulmonary bypass time ( OR=1.01, P=0.02) were independent risk factors. The incidence of AKI in patients with renal artery involvement was 54.65%, significantly higher than 41.98% in patients without renal artery involvement ( P>0.05). Conclusion:Renal artery involvement is an independent risk factor of AKI KDIGO stage 3 after moderate deep hypothermic circulatory arrest of acute Stanford type A aortic dissection.

Objective:To evaluate the diagnostic value of coronary angiography-based fractional flow reserve(caFFR)versus a wire-based fractional flow reserve(FFR)in elderly patients with stable ischemic heart disease.Methods:A total of 168 patients(186 vessels)who underwent a pressure wire(PW)-based FFR measurement from Jan.2015 to Dec.2019 in Beijing hospital were enrolled and analyzed retrospectively.Coronary angiography images and matched steady-state aortic pressure of patients were sent to the core laboratory for caFFR measurement under the blind method.All patients were divided into the non-elderly group(<65 years, n=93)and the elderly group(≥65 years, n=75). The diagnostic value of caFFR was evaluated by using the wire-based FFR cut-off value of ≤0.80 as the reference standard.The correlation and consistency of caFFR and wire-based FFR were analyzed, and compared between the non-elderly and elderly groups.Results:The caFFR had a good correlation and consistency with wire-based FFR in the elderly group( r=0.796, P<0.01). In non-aged versus elderly groups, diagnostic accuracy of caFFR was 91.9% versus 93.1%, diagnostic sensitivity of caFFR was 91.8% vs.93.2%, diagnostic specificity of caFFR was 92.3% vs.93.0%, all P>0.05.The area under the receiver-operating characteristic curve of caFFR had no significant difference between the non-elderly and elderly patients(0.964 vs.0.972, Z=0.00823, 95% CI: -0.037-0.052, P>0.05). Conclusions:The caFFR has a good diagnostic correlation and consistency with wire-based FFR in the elderly group, and caFFR's diagnostic performance in the elderly is similar to that in the non-elderly patients.

Objective:To study the risk factors of massive bleeding in patients with acute Stanford type A aortic dissection undergoing moderate hypothermic circulatory arrest repair.Methods:From January 2016 to October 2017, 486 consecutive patients with acute type A aortic dissection were included in the study. All operations were performed with moderate hypothermic circulatory arrest. The basic clinical data of patients were collected retrospectively. Massive bleeding was defined according to definition of Universal Definition of Perioperative Bleeding(UDPB) 4 class and the Blood Conservation Using Antifibrinolytics in a Randomized Trial(BART). Significant variables in univariate analysis were included in multivariate logistic regression analysis. Results:Thirty-four patients(7.00%) died in hospital. A total of one hundred and eighty-seven patients(38.48%) fulfilled criteria of the definition of BART massive bleeding. Forty-five patients(9.26%), 8 patients(1.65%), 114 patients(23.46%), 147 patients(30.25%) and 172 patients(35.39%) were in grade 0, grade 1, grade 2 and grade 4, respectively. With BART as the end point, the result of multivariate logistic regression showed that female gender( OR=3.32, P<0.001), anemia( OR=2.24, P=0.04), clearance creatine≤85 ml/min( OR=1.93, P=0.01), D-dimer level(every 500 ng/ml increase, OR=1.02, P=0.003), cardiopulmonary bypass(CPB) time( OR=1.01, P<0.001), total arch replacement(TAR, OR=2.40, P=0.02) were independent risk factors for massive bleeding, and the time from onset to operation( OR=0.86, P=0.01) was protective factor. With UDPB 4 class as the end point, multivariate logistic regression showed that creatinine clearance≤85 ml/min( OR=2.05, P=0.001), CPB time( OR=1.01, P=0.04) were independent risk factors for massive bleeding. The time from anset to operation( OR=0.85, P=0.002) and Bentall procedure( OR=0.65, P=0.04) were the protective factors. Conclusion:Massive bleeding was more common in acute Stanford type A aortic dissection. Female gender, poor preoperative renal function, high D-dimer level, early time accepting surgical operation and long CPB were independent risk factors. For high-risk patients, simple and effective surgical methods should be taken to reduce the risk of bleeding.

Objective:To investigate the role and mechanism of metformin in algesia of rats with type 2 diabetic neuropathic pain (DNP).Methods:Eighty sprague-dawley rats were randomly divided into normal control group ( n=15) and high-fat and high-glucose group ( n=65); normal diet and high-fat and high-sugar diet were given, respectively; before and 8 weeks after feeding, the body mass of rats and fasting blood glucose level were recorded, fasting insulin level was detected by ELISA, and insulin sensitivity index (ISI) was calculated. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) 8 weeks after feeding (baseline values) were measured in the high-fat and high-glucose group; after 12 h of fasting, intraperitoneal injection of streptozotocin (STZ, 35 mg/kg) was performed; 3 d after fasting, blood glucose was measured; 14 d after STZ injection, body mass was recorded and MWT and TWL were measured again: when MWT and TWL were ≤85% baseline values, it was defined that DNP model was successfully established ( n=45); and the left were into the diabetic painless group ( n=15). The rats with successful DNP were randomly divided into DNP group, DNP+vehicle group and DNP+metformin group ( n=15); 14 d after STZ injection, rats in the DNP+metformin group were given intraperitoneal injection of metformin (200 mg/kg) once daily for 14 consecutive d; DNP group did not accept any treatment, and rats in DNP+vehicle group were intraperitoneally injected with same amount of normal saline. MWT and TWL of all rats were measured 14 d after STZ injection, and 3, 7, 14 and 21 d after metformin injection. The expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α were detected by ELISA 7, 14 and 21 d after metformin injection. The fluorescence intensity of ionized calcium binding adaptor molecule-1 (Iba-1) in the spinal cord was detected by immunofluorescence staining, and the expression levels of Toll-like receptor 4 (TLR4), nuclear transcription factor (NF)-κB, phosphorylated (p)-NF-κB, adenylate activated protein kinase (AMPK), p-AMPK, and peroxisome proliferator activated receptor-γ coactivator (PGC)-1α in the spinal cord were detected by Western blotting 21 d after metformin injection. Results:(1) After 8 weeks of feeding, the body mass of rats in the high-fat and high-glucose group was significantly higher than that in the normal control group ( P<0.05); and the body mass of rats in the high-fat and high-glucose group was statistically lower than that in the normal control group 14 d after STZ injection ( P<0.05). Three d after STZ injection, the blood glucose level in high-fat and high-glucose group was significantly higher than that in normal control group ( P<0.05). After 8 weeks of feeding, the insulin level of high-fat and high-glucose group was statistically higher than that of normal control group, and the ISI in the high-fat and high-glucose group was significantly decreased as compared with that in the normal control group ( P<0.05). (2) As compared with those in the normal control group and diabetic painless group, MWT and TWL of DNP group and DNP+vehicle group were significantly decreased at each time point ( P<0.05). Three, 7, 14 and 21 d after metformin injection, MWT and TWL in DNP+metformin group were significantly increased as compared with those in DNP group and DNP+vehicle group ( P<0.05). (3) Seven, 14, and 21 d after metformin injection, the levels of IL-6, IL-1β and TNF-α in the spinal cord of rats in the DNP group and DNP+vehicle group were significantly increased as compared with those in the normal control group and diabetic painless group ( P<0.05); as compared with those in the DNP group and DNP+vehicle group, the levels of IL-6, IL-1β and TNF-α in the spinal cord of DNP+metformin group were significantly decreased ( P<0.05). (4) As compared with normal control group and diabetic painless group, the fluorescence intensity of Iba-1 and number of Iba-1 positive cells in the spinal cord tissues of DNP group and DNP+vehicle group were significantly increased ( P<0.05); while the fluorescence intensity of Iba-1 and number of Iba-1 positive cells in spinal cord tissues of DNP+metformin group were significantly decreased as compared with those in the DNP group and DNP+ vehicle group ( P<0.05). (5) As compared with those in the normal control group and diabetic painless group, the TLR4 and p-NF-κB protein expressions and p-NF-κB/NF-κB values in the spinal cord tissues of DNP group and DNP+vehicle group were significantly increased ( P<0.05); while those in the spinal cord tissues of DNP+metformin group were significantly decreased as compared with those in the DNP group and DNP+vehicle group ( P<0.05). As compared with those in the normal control group and diabetic painless group, the PGC-1α protein expression and p-AMPK/AMPK values in the spinal cord tissues of DNP group and DNP+vehicle group were significantly decreased ( P<0.05); while those in the spinal cord tissues of DNP+metformin group were significantly increased as compared with those in the DNP group and DNP+vehicle group ( P<0.05). Conclusion:Metformin, by activating AMPK/PGC-1α signaling pathway, may inhibit the TLR4/NF-κB expression, reduce the activation of microglia and the expressions of pro-inflammatory factors, and thus alleviate DNP.

Objective: To evaluate the impact of preoperative dual antiplatelet therapy on early outcome of acute type A aortic dissection(ATAAD) patients undergoing aortic surgery. Methods: From December 2015 to November 2017, 45 consecutive patients with ingestion of aspirin and clopidogrel underwent aortic repair surgery at our center. 37 out of 45 patients(83%) were propensity-matched with 74 control ATAAD patients without antiplatelet therapy undergoing aortic surgery in 1∶2 fashion. Thereby, bleeding-related outcome(death, reoperation for bleeding, postoperative blood loss within 12 h ≥2 000 ml and usage of rFⅦa) and blood transfusion requirement were compared. Results: Bleeding-related outcome occurred in 14(18.9%) and 9(24.3%) patients in control and antiplatelet group respectively(P=0.51). Postoperative blood loss within 12 hours was 490 ml in control group, compared to 500 ml in the antiplatelet group(P=0.85). There were no significant differences among the two groups in transfusion requirements of red blood cells, platelets and fresh frozen plasma. Multivariate regression analysis identified antiplatelet therapy as an nonsignifcant risk factor for bleeding-related outcome(OR=2.97, 95%CI: 0.87-10.21, P=0.08). Conclusion Preoperative dual antiplatelet therapy was not associated with increased risk of bleeding-related outcome and transfusion requirement, and was not a contraindication of emergent surgery for ATAAD patients.

Objective    To evaluate the involvement of renal artery in acute Stanford type A aortic dissection (TAAD) using CT angiography (CTA) and to analyze the difference of renal function among different types of renal artery involvement. Methods    From January 2016 to November 2017, 151 patients of acute TAAD with renal artery involvement were included in the study. There were 118 males and 33 females, with an average age of 47.93±10.53 years. All patients underwent aortic CTA to confirm the TAAD. According to CTA，involvement of one side of renal artery can be divided into four types: type A, large tear near renal artery orifice, difficult to distinguish true or false lumen; type B, the orifice of the renal artery originates entirely from the false lumen; type C, the orifice of the renal artery originates entirely from the true lumen; type D, renal artery dissection is observed, renal artery intima can be seen. The levels of serum creatinine (sCr) and creatinine clearance (CC) in all groups were analyzed and compared. Results    The results of one-way ANOVA analysis showed that there was no significant difference in sCr or CC among the groups (P>0.05). There was no significant difference in age, sex, proportion of hypertension history and onset time among the above groups (P>0.05). Conclusion    The three most common types of renal artery involvement were BC type, CC type, and AC type. The types of renal artery involvement do not affect renal function.