Objective: To examine the impact of heat waves and cold spells on the incidence of hemorrhagic stroke, so as to provide insights into prevention of hemorrhagic stroke. Methods: Data pertaining to the incidence of hemorrhagic stroke in Zibo City from 2015 to 2019 were collected from Shandong Provincial Management Information System for Chronic Diseases and Cause of Death Surveillance, and the meteorological data during the period from 2015 to 2019 were captured from National Meteorological Information Center of China. The air quality index (AQI) was collected from the National Daily Report of Urban Air Quality in China. Heat wave was defined as the highest daily temperature that was no less than the 90th percentile (P90), P92.5, P95 and P97.5 of the highest daily temperature in the warm season for at least 2, 3 or 4 days, and cold spell was defined as the lowest daily temperature that was no more than the P10, P7.5, P5 and P2.5 of the lowest daily temperature in the cold season for at least 2, 3 or 4 days. The effect of heat waves and cold spells on the incidence of hemorrhagic stroke was evaluated using a generalized additive model and described with relative risk (RR) and its 95%CI. Results: A total of 8 844 case with first-onset hemorrhagic stroke were recorded in Zibo City from 2015 to 2019. The lowest daily temperature that was no more than P10, P7.5 or P5 of the lowest daily temperature in the cold season for at least two days, or that was no more than P10 or P7.5 of the lowest daily temperature for at least 3 days resulted a remarkably increased risk of hemorrhagic stroke (lowest RR=1.187, 95%CI: 1.031-1.366; highest RR=1.242, 95%CI: 1.042-1.480), and after adjusting the effect of daily mean temperature, the lowest daily temperature that was no more than P10 or P7.5 of the lowest daily temperature in the cold season for at least two days, or that was no more than P10 of the lowest daily temperature for at least 3 days resulted a remarkably increased risk of hemorrhagic stroke (lowest RR=1.236, 95%CI: 1.009-1.513; highest RR=1.274, 95%CI: 1.023-1.585). However, there was no significant association between heat waves and the risk of hemorrhagic stroke. Conclusion Cold spells may increase the risk of hemorrhagic stroke, while no significant association is examined between heat waves and the risk of hemorrhagic stroke.

OBJECTIVE: To investigate the effects of manganese(Mn) and high fat diet(HFD) co-exposure on the neurological behavior and gut microbiota in mice, and to observe the correlation between them. METHODS: Specific pathogen free adult male C57 BL/6 mice were randomly divided into 4 groups. Mice in control group and Mn exposure group were fed with normal diet, while the HFD group and co-exposure group were fed with HFD. Both the Mn exposure group and the co-exposure group were exposed to 10 mg/(kg·d) manganese chloride by intraperitoneal injection, while the control group and HFD group were treated with 0.9% sodium chloride solution of the same volume, once per day for 60 consecutive days. At the end of exposure, the mice were subjected to experiments of neurological behaviors. Then, the mice were sacrificed and intestinal feces were collected. The relative abundance of gut microbiota(relative abundance>1.000%) was detected by high-throughput sequencing. RESULTS: After exposure, the body weight of the HFD group and the co-exposure group increased significantly(P<0.05), while that of the Mn exposure group decreased(P<0.05), compared with the control group. The latency, time in central, crossing, total distance and open arm time(OT%) of mice in the Mn exposure group were lower than that of the control group(P<0.05), and close arm time(CT%) prolonged(P<0.05). Compared with the control group and the HFD group, the latency, rearing, time in central, crossing, total distance, OT% and open arm entry(OE%) of mice in the co-exposure group decreased(P<0.05), and CT% increased(P<0.05). The total distance of mice in the co-exposure group was lower than that of the Mn exposure group(P<0.05). The relative abundance of Firmicutes increased(P<0.05), those of Bacteroidetes and Actinobacteria decreased in mice in the HFD group at the phylum level(P<0.05) compared with mice in the control group. The relative abundance of Firmicutes, Proteobacteria and Cyanobacteria increased(P<0.05), and Bacteroidetes and Actinobacteria decreased(P<0.05) in mice in the Mn exposure group. The relative abundance of Oscillospira, Bacteroides and Prevotella of mice in the HFD group reduced at the genus level(P<0.05) compared with the control group. The relative abundance of Lactobacillus increased in Mn exposure group(P<0.05), and Oscillospira, Bacteroides and Prevotella decreased(P<0.05). The relative abundance of Firmicutes, Cyanobacteria and Lactobacillus of mice in the co-exposure group increased(P<0.05), and those of the remaining 6 bacteria were lower(P<0.05) compared with mice in the other 3 groups. Among the mice of co-exposure group, the latency was positively correlated with Bacteroidetes(P<0.05). The rearing was positively correlated with Firmicutes(P<0.05) and negatively correlated with Actinobacteria(P<0.01). The OE% was negatively correlated with Firmicutes(P<0.05) and positively correlated with Actinobacteria(P<0.05). The crossing was positively correlated with Prevotella(P<0.05). CONCLUSION: Manganese combined with HFD had a synergistic effect on the abnormality of neurological behavior of mice. There are some correlation between the abnormality of neurological behavior and the homeostatic imbalance of intestinal flora in mice.

Objective: To establish a method for the determination of aluminum in blood, and to detect the aluminum content in the blood of occupational aluminum workers. Methods: The morning blood of the aluminum workers was collected in an anticoagulation tube, and the supernatant was centrifuged. The supernatant was diluted with 4% nitric acid containing 1% Triton for 24 h at room temperature, and the supernatant was centrifuged. The supernatant was filtered and the blood aluminum concentration was measured by inductively coupled plasma mass spectrometry and quantified by external standard method. Results: The detection limit of ICP-MS method was 0.39 μg/L, the linear range was 0-160 μg/L, the recoveries were 98.24%-99.65%, and the precision was 0.19%-0.28%. The recoveries of graphite furnace atomic absorption spectrophotometry (GFAAS) were 97.17%-111.18%, and the precision was 0.35%-0.44%. The average blood aluminum concentration of aluminum workers in the normal control group was (19.87±10.65) μg/L. The average blood aluminum concentration of aluminum workers in the expose group was (31.12±11.43) μg/L. Conclusion The method of ICP-MS for the determination of aluminum concentration in blood has a simple pretreatment process, high recovery rate, low detection limit and high precision, which is suitable for popularization.

Objective To explore the correlation and diagnostic value of serum visfatin (visfatin),high sensitive C reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α) in patients with different types of angina pectoris.Methods Eighty-four patients with angina pectoris who were treated in the Eighth hospital of Wuhan from January 2013 to December 2016 were selected as the research subjects,the patients were divided into stable angina pectoris (SAP) group with 39 cases and unstable angina pectoris (UAP) group with 45 cases according to the classification criteria of angina pectoris,Thirty-seven healthy volunteers in the outpatient department of the same period were selected as the control group.To compare the levels of serum visfatin,hs-CRP and TNF-alpha in three groups,analyze the correlation between the levels of serum visfatin and hs-CRP and TNF-alpha levels in patients with angina pectoris,and analyze the diagnostic value of the levels of serum visfatin,hs-CRP,TNF-α and plasma oxidized low density lipoprotein (Ox-LDL) by ROC curve.Results There were no significant differences in fasting blood glucose,uric acid,creatinine,total cholesterol (TC),triglyceride (TG),high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C) among the three groups (all P＞0.05).The systolic pressure (SBP) was (134.27± 11.96) mmHg and diastolic pressure (DBP) was (84.23 ± 7.15) mmHg in SAP group,the SBP was (135.98±12.33) mmHg and DBP was (84.47±7.22) mmHg in UAP group,which were all higher than SBP ((121.49±9.97)mmHg)and DBP ((77.38±6.94)mmHg) in the control group (all P＜0.05),but there was no significant differences between the SAP group and the UAP group (all P＞0.05).The level of visfatin in UAP group was (6.57± 1.36) μg/L,which was higher than that in SAP group ((4.62 ± 1.08) μg/L) and in control group((4.27± 1.03)μg/L) (all P＜0.05),but there was no significant differences between the SAP group and the control group (P＞0.05).The level of serum hs-CRP,TNF-α and plasma Ox-LDL were (12.38±2.63) mg/L,(4.35±0.28) ng/L and (617.32±53.48) μg/L in UAP group,and the level of serum hs-CRP,TNF-α and plasma Ox-LDL were (8.29 ± 1.74) mg/L,(1.82 ± 0.34) ng/L and (418.57±43.85) μg/L in SAP group,which were higher than hs-CRP (4.06±1.52) mg/L,TNF-α (0.98 ±0.13) ng/L,Ox-LDL (213.64±32.83) μg/L in control group(all P＜0.05),and the UAP group was higher than that in the SAP group (all P＜0.05).The level of serum visfatin in group SAP and group UAP had no significant correlation with age,body mass index,SBP,DBP,fasting blood glucose,uric acid,creatinine,total cholesterol,triglyceride,HDL cholesterol,low density lipoprotein cholesterol (all P ＞ 0.05).The serum visfatin level was positively correlated with serum hs-CRP,TNF-alpha level and plasma Ox-LDL level in SAP group.(r=0.687,0.634,0.656,all P＜0.05).The serum visfatin level was positively correlated with the serum hs-CRP,TNF-a level and Ox-LDL level in UAP group (r =0.721,0.652,0.673,all P＜ 0.05).ROC curve analysis showed that the levels of serum visfatin,hs-CRP,TNF-α and plasma Ox-LDL were all near 0.7,and the sensitivity and specificity were all above 0.6 identification of different types of angina pectoris.Conclusion The level of serum visfatin in patients with UAP was significantly higher than that of SAP patients,its level is related to serum hs-CRP,TNF-alpha and plasma Ox-LDL levels,the four indexes have a certain predictive value for different types of angina pectoris,and can provide reference for different types of angina.

OBJECTIVE:To optimize the extraction technology of asiaticosides from Centella asiatica. METHODS:Using to-tal amounts of asiaticoside and hydroxy asiaticoside as investigation indexes,single factor and orthogonal test were used to investi-gate the enzyme amount,enzymolysis time,enzymolysis temperature,ethanol volume fraction,liquid material ratio and ultrasonic extraction time and optimize the extraction technology of asiaticosides from C. asiatica by ultrasonic-enzyme method,and verifica-tion test was conducted. RESULTS:Optimal extraction technology was as follow as cellulose dosage of 12 mg/g,10-fold liquid ma-terial ratio added into 60% ethanol,enzyme hydrolysis for 60 min at 60 ℃,ultrasonic assisted extraction for 50 min. Average ex-traction rate of total asiaticosides was 1.92%(RSD=1.83%,n=3)in verification test. CONCLUSIONS:Ultrasonic-enzyme meth-od is stable and feasible for the extraction technology of asiaticosides from C. asiatica.

Objective To evaluate the effect of endoplasmic reticulum stress in trophocytes,in patients with intrahepatic cholestasis of pregnancy (ICP).Methods Sixty-one pregnant women who were hospitalized in Women's Hospital,School of Medicine,Zhejiang University from January to December 2015 were recruited.Thirty-one women who were diagnosed as ICP were defined as the ICP group and 30 healthy pregnant women were defined as the control group.The localization and expression intensity of glucose regulated protein 78 (GRP-78) in placental tissues were detected by immunohistochemistry technique.Electronic microscope was used to observe ultra-microstructure change of the endoplasmic reticulum in trophocytes and cell line Swan71.Reverse transcription (RT)-PCR and western blot were used to investigate the expression of GRP-78 mRNA and protein in Swan 71 cell.Results (1) GRP-78 protein was mainly expressed in the cytoplasm of cytotrophoblasts and syncytiotrophoblasts.The protein expression of GRP-78 in placentas of the ICP group (13.2±2.4) was significantly higher than that in the control group (7.8±1.3,P＜0.01).(2) The volume of endoplasmie reticulum did not increase and the microvilli developed well,with no swelling and no expansion of endoplasmic reticulum in the control group.In the ICP group,microvilli injury,endoplasmic reticulum edema were found;the volume of endoplasmic reticulum increased,with dilation,vacuolation and significant degranulation.After treated with 100 μmol/L cholyglycine for 24 hours,universal dilatation of the endoplasmic reticulum were seen in the Swan71 cells.(3) In Swan71 cells,cholylglycine displayed a concentration-dependent up-regulation on the expression of GRP-78.The expressions of GRP-78 mRNA in 0,25,50,100 μmol/L cholylglycine experimental group were 1.01±0.17,2.17±0.16,5.47±0.36,5.65 ± 0.82,respectively.The expression of GRP-78 protein in 0,25,50,100 μmol/L cholylglycine experimental group were 1.01±0.04,1.17±0.15,1.33±0.13,1.73±0.13,respectively.The expression of GRP-78 mRNA and protein in 100 and 50 μ mol/L cholylglycine experimental group were significantly higher than 0 μmol/L (all P＜0.01).Conclusion The obvious expansion of endoplasmic reticulum and the increased expression of GRP-78 in trophocytes indicated that endoplasmic reticulum stress of trophocytes may be involved in the pathogenesis of ICP.

ObjectiveTo investigate the clinical effect of EaLeSu on cervical intraepithelial neoplasia(CIN Ⅱ~Ⅲ)patients with HPV infection treated with loop electrosurgical excision procedure(LEEP). Methods 165 cases of CIN Ⅱ~Ⅲpatients with HPV infection who underwent LEEP operation were randomly divided into observation group(n=83)and control group(n=82). In the observation group,patients were given a piece of EaLeSu in cervical wound at once in postoperative and two vaginal EaLeSu per day from the first postoperative day for eight consecutive days. The patients in the control group were treated with routine debridement and wound dressing with iodine. We observed the vaginal drainage times within 4 weeks after operative,bleeding rate,cervical wound repair,and cervical HPV DNA infection after 6 months. Results There were significant differences in the bleeding rate,vaginal drainage time,cervical wound repair and HPV DNA infection between the two groups(P < 0.05). Conclusion EaLeSu showed a definite effect on cervical intraepithelial neoplasia(CIN Ⅱ~Ⅲ)patients with HPV infection treated with LEEP.

A number of biosimilars will be soon marketing due to the expiration of patent protection of their originators.Unlike classical chemical drugs,biotherapeutics are proteins with large and complex molecules produced by biological high-tech with sophisticated manufactural procedures.This leads to the difficulties of the copy of biosimilars from their originators,and the almost inevitable distinctions between the two products.Thus biosimilars are only similar but not identical to their reference drugs in terms of stracture,action,and safety.It is important for physicians to understand these differences before using biosimilars.Optimal management by a national regulatory authority with rigorous standards is very important in all aspects of authorization of the development,production,marketing,and postmarketing surveillances for biosimilars.

Objective To investigate the method of repairing great wounds on foots and ankles with posterior tibial artery perforator-based dicyto-pattern flaps from interior and posterior compartment of leg. Methods Eighteen patients with great foot wound were repaired with posterior tibial artery perforator-based dicyto-pattern flaps from interoposterior compartment of calf from January 2006 to December 2008. The patients were at age of 16-52 years, with flap areas for 20 cm ×6 cm-25 cm × 10 cm. The donor sites of flaps were repaired with free skin graft. Results All the flaps primarily survived except for one patient with partial necrosis (4.0 cm × 1.0 cm) in the distal part of the flap. Twelve patients were followed up for from two months to two years, which showed good color, texture and appearance of the flaps. Conclusion This kind of flap is one of ideal flaps to repair great foot and ankle wounds, for it takes advantages of reliable blood supply, wide repair scope, safe operation and avoidance of damage to the major artery.

Objective To adopt accurate and prompt nursing measures to prevent incidence of pressure through evaluation of risk factors of pressure ulcer during perioperation of thoracotomy, in order to increase nursing quality and life quality of patients. Methods The incidence of pressure ulcer in 100 patients after thoracotomy and its related risk factors were investigated by application of pressure ulcer risk factors evaluation scale, and the influence of related factors on incidence of pressure ulcer was com -pared. Results Single factor analysis showed that preoperative smoking, albumin content and prolonged postoperative turning over time had significant influence on incidence of pressure ulcer. Conclusions Patients after thoracotomy are high risk population of pressure ulcer. The pivotal period for ulcer prevention is from the operation day to 3 days after operation.