Objective:To evaluate the association between heatwaves and fall-related mortality.Methods:A total of 61 421 fall-related mortality from 2013 to 2022 in 7 provinces of China were included in a time-stratified case-crossover design, with daily meteorological data derived from the fifth generation European Reanalysis dataset produced by the European Centre for Medium-Range Weather Forecasts. Conditional logistic regression chimeric distributed lag nonlinear model was used to analyze the association between heatwaves and fall-related mortality and stratified analysis was conducted according to gender and age.Results:Heatwaves were associated with an increased risk of fall-related morality. The risk of fall-related mortality during heatwaves was higher than during non-heatwave periods ( OR=1.11, 95% CI: 1.05-1.18). The attributable fraction of fall-related motality due to heatwaves was 10.25% (95% CI: 4.49%-15.36%). For each 1 ℃ increase above the heatwave threshold, the risk of fall-related mortality increased by 34% ( OR=1.34, 95% CI: 1.02-1.76). The effect of heatwave duration on fall-related mortality was not statistically significant. Stratified analyses indicated that women experienced a higher risk of fall-related mortality during heatwaves ( OR=1.13, 95% CI: 1.04-1.22) compared to man ( OR=1.10, 95% CI: 1.04-1.17). Conclusions:Heatwave increases the risk of fall-related mortality, and the intensity of heatwaves modify this risk. Women are vulnerable populations.

Objective:To evaluate the impact of short-term exposure to daytime heatwaves, nighttime heatwaves, and compound heatwaves on the risk of road traffic mortality and calculate the attributable mortality burden.Methods:This study collected road traffic mortality data from the Disease Surveillance System in Guangdong, Hunan, Zhejiang, Yunnan, and Jilin Provinces from 2013 to 2018. A time-stratified case-crossover design was used in this study, with the death date for each case serving as the case day. Control days were selected from the same year, month, and day of the week as the case day. A conditional logistic regression model was employed to estimate the cumulative associations of short-term exposure to daytime heatwaves, nighttime heatwaves, and compound heatwaves on the risk of road traffic mortality (lag 0-1 day) and to calculate the attributable fractions (AF).Results:Compared to non-heatwave days, the excess risk ( ER) of road traffic mortality on daytime heatwave days, nighttime heatwave days, and compound heatwave days was 5.3% (95% CI: 0.5%-10.2%), 4.9% (95% CI: 0.5%-9.4%) and 7.5% (95% CI: 2.3%- 12.9%), with corresponding AF of 5.0% (95% CI: 0.5%-9.3%), 4.7% (95% CI: 0.5%-8.6%), and 6.9% (95% CI: 2.3%-11.4%), respectively. Stratified analysis showed that the risk of traffic mortalities caused by daytime heatwaves was higher in females ( ER=15.7%, 95% CI: 5.8%-26.5%) than in males ( ER=1.8%, 95% CI: -3.6%-7.4%). Elderly individuals over 64 years old ( ER=10.9%, 95% CI: 0.3%- 22.6%) had a higher risk of road traffic mortalities from compound heatwaves than those under 45 years old ( ER=2.6%, 95% CI: -5.4%-11.2%). The risk of road traffic injury mortality from motor vehicle accidents caused by compound heatwaves ( ER=16.6%, 95% CI:2.4%-32.7%) was higher than that from non-motor vehicle accidents ( ER=5.7%, 95% CI:0.1%-11.5%). Conclusions:Short-term exposure to daytime heatwaves, nighttime heatwaves, and compound heatwaves was associated with an increased risk of road traffic mortality, with the strongest association observed for compound heatwaves. The mortality burden attributable to compound heatwaves was higher than that for daytime and nighttime heatwaves. Heatwaves were more significantly associated with road traffic mortality risk among females, elderly individuals over 64 years old, and motor vehicle accidents.

Objective:To study the etiological relationship between Yunnan sudden unexplained death (hereinafter referred to as YNSUD) and the desmosomal protein gene mutation of arrhythmogenic right ventricular cardiomyopathy (ARVC).Methods:From September 2019 to August 2020, a cross-sectional survey method was used to select 9 key counties (cities) of YNSUD in Yunnan Province as survey sites. Autopsy cardiac blood samples of YNSUD cases ( n = 11) were collected, and peripheral venous blood samples of co-occurring case ( n = 1), case relatives ( n = 128), and control population ( n = 60) were collected. Genomic DNA from blood was extracted. After PCR amplification, 97 exons of 5 ARVC desmosomal protein genes, including plakophilin-2 (PKP2), desmoglein-2 (DSG2), desmocollin-2 (DSC2), desmoplakin (DSP), and junction plakoglobin (JUP) were sequenced by Sanger method, and the gene mutation was analyzed. Results:Compared with the control population, YNSUD cases, co-occurring case and case relatives carried 52 gene mutation sites in 36 exons of the ARVC desmosomal protein gene, with a total mutation rate of 37.11% (36/97). Among them, there were 21 in DSP gene, 10 in DSG2 gene, 8 in PKP2 gene, 8 in DSC2 gene, and 5 in JUP gene. YNSUD cases, co-occurring case and case relatives carried two same gene mutation sites: DSG2 gene exon 15 c.3321 T>C synonymous mutation and JUP gene exon 3 c.213 T>C synonymous mutation.Conclusions:The mutation rate of ARVC desmosomal protein gene is relatively high in the population of YNSUD. The two same gene mutation sites (DSG2 gene c.3321 T>C and JUP gene c.213 T>C) carried by YNSUD cases, co-occurring case and case relatives may be associated with the pathogenesis of YNSUD.

Insulin is an important protein hormone that participates in multiple metabolic pathways.Biosynthetic insulin has been widely used in the treatment of type 1 and type 2 diabetes.Currently,the number of reported cases of insulin overdose both at home and abroad is gradually increasing,and insulin homicide is no longer a means of"committing murder without leaving a trace".At present,there are no systematic protocols for the identification of insulin overdose in the field of forensic medi-cine in China.This article introduces the causes,toxicological characteristics,forensic examination,labo-ratory testing methods and indicator reference of insulin overdose.Based on the identification practice and research results and referring to relevant studies on insulin overdose at home and abroad,this pa-per aims to provide recommendations and references for the formulation of forensic identification guide-lines for insulin overdose cases.

Objective To investigate the predictive value of changes in various indicators of routine blood tests for the severity of brain damage in patients with acute cerebral hemorrhage(ACH)in high-altitude regions.Methods A retrospective analysis was conducted using data from 249 inpatients diagnosed with ACH at a hospital in Xizang.Patient data,including demographic information and results of routine blood tests,were collected.Based on their Glasgow Coma Scale(GCS)scores,the patients were divided into 2 groups,a mild brain damage group(GCS≥13 points)and a moderate-to-severe brain damage group(GCS≤12 points).Demographic information and laboratory test results were compared between the two groups.Binary logistic regression analysis was performed to examine the relationship between indicators of routine blood tests and the severity of brain damage,and key indicators were identified.The receiver operating characteristic(ROC)curve analysis was used to evaluate the predictive performance of key indicators in various combinations for the severity of brain injury in ACH patients.Results The moderate-to-severe group had a higher proportion of high-altitude residents,as well as elevated levels of white blood cells(WBC),neutrophils(N),neutrophil-to-lymphocyte ratio(NLR),systemic inflammatory index(SII),neutrophil-to-platelet ratio(NPR),and C-reactive protein(CRP)-to-lymphocyte ratio(CLR),compared to the mild group.On the other hand,the levels of lymphocytes(L),platelets(PLT),and platelet-to-albumin ratio(PAR)in the moderate-to-severe group were lower than those in the mild group.Binary logistic regression analysis showed that WBC(OR=1.221,95%CI:1.127-1.322),CRP(OR=1.019,95%CI:1.004-1.033),CRP-to-albumin ratio(CAR)(OR=1.845,95%CI:1.137-2.996),and CLR(OR=1.018,95%CI:1.005-1.030)were positively associated with moderate-to-severe brain damage,and that their elevated levels were associated with an increase in risk by the corresponding folds.PAR(OR=0.845,95%CI:0.721-0.990)was negatively correlated with moderate-to-severe brain damage,with an increase resulting in a reduction of risk by 0.845 times.ROC curve analysis showed that,in the mild group,the combined AUC for WBC+CRP was 0.689(optimal cutoff value 0.19,specificity 0.776,95%CI:0.624-0.755);the PAR+CAR+CLR combination(CAR was not significant,P>0.05)had an AUC of 0.675(optimal cutoff value 0.19,specificity 0.760,95%CI:0.609-0.741);the key indicator combination of WBC+PAR+CLR(CRP was not significant,P>0.05)demonstrating the strong predictive performance moderate-to-severe brain damage,yielding an AUC of 0.737(optimal cutoff value 0.08,specificity 0.624,95%CI:0.676-0.798).Conclusion The indicator combinations of WBC+CRP,PAR+CLR,and WBC+PAR+CLR exhibit significant value for predicting the severity of brain injury in ACH patients and may serve as potential predictive tools for the severity of brain damage in patients with acute cerebral hemorrhage in high-altitude regions.

Objective:To observe the clinical effect of computed tomography(CT)-guided hematoma puncture drainage surgery combined with high-dose(≥50 000 U)urokinase in treating hypertensive intracerebral hemorrhage.Methods:The case data of a total of 90 patients with hypertensive intracerebral hemorrhage who underwent treatment in Zhangjiakou First Hospital from January 2022 to January 2023 were retrospectively selected as the study subjects.They were divided into a control group and an observation group using the average method,with 45 cases in each group.The conventional group received CT-guided hematoma puncture drainage surgery combined with conventional dose urokinase(20 000 U),while the observation group received CT-guided hematoma puncture drainage surgery combined with high-dose urokinase(50 000 U),with a 6-month follow-up for all patients.The changes of hematoma volume,length of hospital stay,levels of inflammatory indicators,the levels of hemodynamics,clinical efficacy,and incidence of postoperative complications after treatment between two groups were analyzed and compared.Results:After treatment,the hematoma volume at the 1st day[(34.64±5.53)mm3]and the 7th day[(34.64±5.53)mm3]post surgery of observation group were significantly lower than those[(44.57±6.85)mm3 and(16.64±3.24)mm3]of conventional group,and the differences of them between the two groups were statistically significant(t=7.567,10.570,P<0.05),respectively.The length of hospital stay of observation group[(16.86±6.63)d]was significantly lower than that of the control group[(23.47±10.34)d](t=3.610,P<0.05).The levels of matrix metalloproteinase-9(MMP-9),interleukin-6(IL-6),C-reactive protein(CRP),tumor necrosis factor-α(TNF-α)at 7th days post surgery of observation group were significantly lower than those of conventional group,and the differences of them between the two groups were statistically significant(t=5.826,10.202,7.661,2.724,P<0.05),respectively.The blood flow levels of middle cerebral artery(MCA),anterior cerebral artery(ACA),and posterior cerebral artery(PCA)after surgery in observation group were significantly higher than those in conventional group(t=2.833,3.329,3.973,P<0.05),respectively.The effective rate of treatment in observation group(95.56%)was significantly higher than that in conventional group(80.00%),and the difference was significant(x2=5.075,P<0.05).There was no significant difference in the incidence of postoperative complications between the two groups(P>0.05).Conclusion:CT-guided hematoma puncture drainage surgery combined with high-dose urokinase can significantly increase the dissolution rate of hematoma,and reduce the body's inflammatory response,and improve cerebral hemodynamic indicators,and effectively enhance clinical efficacy in treating hypertensive intracerebral hemorrhage,which have better treatment safety.

Coronary artery calcification often appears a variety of complex lesions,increasing coronary intervention of the difficulty of treatment,especially the severe calcification lesions,usually cannot be fully dilated,resulting in a reduced success rate of surgery,an increased rate of acute stent thrombosis and restenosis,and even a serious impact on the prognosis of patients.Intravascular lithotripsy(IVL)is increasingly used in calcified lesions.There is more and more evidence of using in stable angina pectoris and unstable angina pectoris,but its use in acute ST-segment elevation myocardial infarction is limited,and only a few cases have been reported abroad.Moreover,the consensus of Chinese experts in the diagnosis and treatment of coronary artery calcification in 2021 edition lists thrombotic lesions as contraindications of shock wave balloon.This case is the first time in China to report the use of shock wave balloon in patients with acute ST elevation myocardial infarction complicated with thrombus.In this case,the patient with acute ST elevation myocardial infarction complicated with thrombus was severely under expanded stent after stent implantation,and obtain good curative effect using shockwave balloon at selected time in hospital after intensive anticoagulant therapy.

This study investigated the expression of the soluble nontoxic mutant CRM197 of diphtheria toxin,to prepare a safe and effective recombinant CRM197 protein.Codon-optimized CRM197 gene sequences were cloned into the pCold Ⅱ and pET-28a(+)prokaryotic expression vectors.The successfully cloned recombinant plasmids were screened and transformed into Escherichia coli BL21(DE3)competent cells.After induction of expression,the protein expression type was determined through SDS-PAGE analysis.The conditions for expression of the solublerecombinant protein were then optimized.The recombinant CRM197 protein was purified through two rounds of Ni-NTA affinity chromatography.The purified protein was used to immunize mice,and antibody levels in the se-rum were measured with ELISA.The codon adaptation index(CAI)of the optimized sequence increased from 0.72 to 0.93.The recom-binant plasmids pET-28a(+)-CRM197 and pCold Ⅱ-CRM197 were successfully constructed,as confirmed through colony PCR and double digestion.Expression analysis revealed that pET-28a(+)-CRM197 was expressed primarily as inclusion bodies,whereas pColdⅡ-CRM197 was expressed predominantly in soluble form.The conditions for soluble protein expression via pCold Ⅱ-CRM197 were optimized.When the inoculum was 3%and the IPTG concentration was 0.4 mmol/L,induction at 20 ℃ for 24 h significantly increased the expression of the soluble target protein.The pCold Ⅱ-CRM197 recombinant protein was purified from the supernatant with Ni-NTA affinity chromatography,thus resulting in a target protein with a purity greater than 98%.ELISA after three rounds of immuniza-tion indicated that the levels of IgG,IgM,IgG1,and IgG2a antibodies in the serum in immunized mice were significantly higher than those in the control group.In summary,the CRM197 recombinant protein was successfully prepared with the pCold Ⅱvector and exhib-ited high soluble expression,high purity,and favorable immunogenicity.

Objective To analyze the MRI imaging characteristics of brain metastases in non-small cell lung cancer(NSCLC)with different epidermal growth factor receptor(EGFR)mutation types and programmed cell death-ligand 1(PD-L1)expression,and to provide imaging diagnostic support for patients who can't undergo genetic and immunohistochemical testing.Methods A retrospec-tive selection was performed in 88 patients diagnosed with brain metastases of NSCLC,all patients were divided into EGFR mutation group and wild group according to the results of genetic testing,and patients with EGFR mutation group were divided into EGFR mutation with PD-L1 expression positive group and EGFR mutation with PD-L1 expression negative group according to whether the expression of PD-L1 was≥1％.The clinical data and MR image characteristics of brain metastases were compared in EGFR mutation group and wild group,as well as in EGFR mutation with PD-L1 expression positive group and EGFR mutation with PD-L1 expres-sion negative group.Results There were statistically significant differences in smoking history and intracranial symptoms between EGFR mutation group and wild group(P＜0.05).The edema diameter,edema index and enhancement ratio of EGFR mutation group and wild group were(0.67±1.10)cm,0.39±0.54,0.32±0.17 and(1.57±2.04)cm,1.05±1.21,0.53±0.27,respectively,and the differences were statistically significant(P＜0.05).There were 43 cases and 23 cases in EGFR mutation group and wild group with ≥2 metastases,respectively,and the difference was statistically significant(P＜0.05).Compared with＞60 years old,there were 15 patients(75％)of EGFR mutation with PD-L1 expres-sion positive in≤60 years old(P＜0.05).Conclusion Compared with EGFR wild patients,patients with EGFR mutation have more brain metastases(≥2),milder enhancement,less peritumoral edema,and fewer intracranial symptoms at initial diagnosis,and patients with EGFR mutation aged≤60 years are more likely to have PD-L1 expression positive.

Objective To investigate the prevalence of hyperhomocysteincmia(HHcy)in a Tibetan population in Nagqu City and analyze the related influencing factors.Methods From May to June 2020 we recruited 758 hereditary Tibetan residents from Xinji Township,Jiaqiong Township and Seshong Township of Nagqu City as study subjects who met the inclusion criteria using the multi-stage whole cluster random sampling method.Structured questionnaires as well as clinical examinations were conducted.The prevalence of HHcy was analyzed by descriptive statistics,and the effects of different variables on the prevalence of HHcy were assessed using univariate analysis.Multifactorial Logistic regression analysis was made to explore the factors associated with the prevalence of HHcy.The expected value of each influencing factor in predicting the prevalence of HHcy was analyzed using the subject's receiver operating characteristic(ROC)curve.Results The number of HHcy among the 758 Tibetan population included amounted to 515 cases with a prevalence of 67.9％(95％CI:64.6％-71.2％).Gender,hypertension,hyperuricemia,hemoglobin abnormality,LDL-C abnormality,BMI,type of residence and duration of exercise were found to be significantly different between the two groups by univariate analysis(P＜0.05).In the multifactorial Logistic regression analysis,age,hemoglobin abnormality,diastolic blood pressure,hemoglobin volume,heart rate,HDL-C and BMI showed a positive correlation with the prevalence of HHcy,whereas gender,blood glucose abnormality,FBG,ALT,type of residence(rural)and length of exercise showed a negative correlation with the prevalence of HHcy,relative to the non-HHcy patients(P＜0.05).The area under the curve(AUC)of the ROC predictive model for HHcy prevalence was constructed as 0.785(sensitivity 0.701,specificity 0.737),and the risk of HHcy prevalence was predicted by age,sex,DBP,Hb,heart rate,FBG,HDL-C,BMI,type of residence and duration of exercise,with the critical values of age,DBP,Hb,heart rate,FBG,HDL-C being 46.5 years,77.5 mmHg,169.5 g/L,72.5 beats/min,3.65 mmol/L,and 1.66 mmol/L,respectively.For comparison with the ROC curve of the included traditional risk factor HHcy prediction model(AUC of 0.790,sensitivity 0.732,specificity 0.712),the results showed that the predictive ability of the two models was similar(P=0.075).Conclusion The Tibetan population in the three areas of Nagqu City has a high prevalence of HHcy,and a series of targeted measures should be taken to reduce the risk of related diseases.