Objective To investigate the effect of levosimendan on the cyclic guanosine monophosphate-adenosin monophosphate synthase-interferon gene stimulating factor(cGAS-STING)signaling pathway during suspension-reperfusion in isolated rat myocardium.Methods The rats were divided into four groups(n=12)using random number table:continuous perfusion group(CO group),suspension-reperfusion group(SR group),suspension-reper-fusion+levosimendan group(SR-L group),and suspension-reperfusion+levosimendan+STING activator:DMXAA group(SR-LD group).Heart rate(HR),left ventricular end-diastolic pressure(LVEDP),left ventricular develop-mental pressure(LVDP),maximum rate of increase in left ventricular pressure(+dp/dtmax)and maximum rate of decrease in left ventricular pressure(-dp/dtmax),and Reperfusion Arrhythmia scores were recorded at the end of equilibrium perfusion(T0),30 min of reperfusion(T1),and 60 min of reperfusion(T2)respectively.Western blot was used to detect cGAS-STING signaling pathway and autophagy-related protein expression.The size of myocardial infarction was measured by using triphenyl tetrazolium chloride(TTC).Results Compared with CO group,SR group had decreased HR,LVDP,+dp/dtmax,and-dp/dtmax at T1 and T2,increase of LVEDP,Reperfusion Arrhythmia score,percentage of myocardial infarcted area,expression of myocardial tissue cGAS and STING pro-teins and increased LC3 Ⅱ/Ⅰratio,while p62 decreased(P<0.05);compared with SR group,SR-L group car-diac function indexes improved,myocardial tissue cGAS,STING protein expression was down-regulated,LC3 Ⅱ/Ⅰ ratio was decreased,and p62 was elevated(P<0.05);SR-LD group reversed the improvement of myocardial injury by levosimendan compared with SR-L.Conclusions Levosimendan may protect myocardial tissue by inhibi-ting the cGAS-STING signaling pathway,down-regulating cardiomyocyte autophagy and reducing myocardial infarc-tion size,so to improve cardial function.

Objective:To investigate the association of serum uric acid (SUA) with the outcome in patients with acute ischemic stroke (AIS) at one year after onset.Methods:Patients with AIS admitted to the Department of Neurology, Dagang Hospital, Tianjin Binhai New Area were included retrospectively. According to the modified Rankin Scale (mRS) score at 1 year after onset, patients were divided into a good outcome group (0-2) and a poor outcome group (>2). They were also divided into a survival group and a death group based on their survival status at 1 year after onset. The clinical baseline data and laboratory tests were compared. Multivariate logistic regression analysis was used to determine the associations of SUA with poor outcome and death in patients with AIS. Results:A total of 651 patients were enrolled, including 430 males (66.1%) aged 67.5±11.7 years. Four hundred and fourteen patients (63.6%) were in the good outcome group, and 237 (36.4%) were in the poor outcome group. There were 568 patients (87.3%) in the survival group and 43 (16.7%) in the death group. Univariate analysis showed that there were differences in age, atrial fibrillation, history of stroke or transient ischemic attack, baseline National Institutes of Health Stroke Scale (NIHSS) score, and pre-admission mRS score between the poor outcome group and the good outcome group. The homocysteine, SUA, white blood cell count, and creatinine in the poor outcome group were higher than those in the good outcome group, while the red blood cell count and hemoglobin were lower than those in the good outcome group (all P<0.05). There were differences in age, history of ischemic heart disease, atrial fibrillation, history of stroke or transient ischemic attack, baseline NIHSS score, pre-admission mRS score, and stroke etiology classification between the survival group and the death group. Hemoglobin and triglycerides in the survival group were higher than those in the death group, while the white blood cell count and creatinine were lower than those in the death group (all P<0.05). Multivariate logistic regression analysis showed that SUA was an independent risk factor for poor outcome in patients with AIS (odds ratio 1.004, 95% confidence interval 1.001-1.006; P<0.01), but there was no independent correlation with death. Conclusion:Higher SUA is an independent risk factor for poor outcome at one year after onset in patients with AIS.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

OBJECTIVE To screen the prescription and preparation method of Bupleurum nanoemulsion, and evaluate its quality, study the antipyretic effect. METHODS The emulsifier and co-emulsifier of the nanoemulsion were preliminarily screened, and then the prescription was screened by pseudo-ternary phase diagram. The quality evaluation of the appearance, particle size distribution, structure type, stability and content of the prepared Bupleurum nanoemulsion was performed. Wistar rats were further randomly divided into blank control group, model control group, positive control group(aspirin group), Bupleurum nanoemulsion high-dose, medium-dose and low-dose groups(18.00, 9.00, 3.00 g·kg−1). Except for the blank control group, the pathological model of fever rats was prepared in the other groups. According to the scheduled experimental requirements, rats in each group were given the corresponding drugs. And the temperature changes of rats in each group were recorded at 0.5, 1, 1.5, 2, 3 h to observe the antipyretic effect of Bupleurum nanoemulsion. RESULTS The best prescription of Bupleurum nanoemulsion: Tween-80 6 g and n-butanol 3 g, Bupleurum extract dissolved in pure water as water phase 20 mL, Bupleurum oil as oil phase 2 g. At room temperature, the Bupleurum nanoemulsion was a yellow-brown clear and transparent liquid, O/W nanoemulsion, with an average particle size of (77.21±3.66)nm, polydispersity index of 0.28±0.04, Zeta potential of (–18.81±1.42)mV, and saikosaponin content of 3.071 mg·mL−1, with good stability. In animal experiments, compared with the model control group, the rectal temperature of aspirin group and Bupleurum nanoemulsion high-dose group was significantly lower after the first administration(P<0.01), the rectal temperature of Bupleurum nanoemulsion middle-dose group was significantly lower after the first administration 2, 3 h(P<0.01). CONCLUSION The Bupleurum nanoemulsion is transparent and stable, and it has good antipyretic effect on fever rat model.

Literature analysis,expert consultation,case analysis and other methods were used to establish a public hospital specialty operation evaluation system suitable for high-quality development,including 2 first-level indicators of medical ability and economic operation and 13 second-level indicators.Urology surgery in the pilot hospital was taken as an example to carry out surgical operation effect evaluation.To strengthen the evaluation of public hospital specialized operation,it should pay attention to the evaluation of medical capacity,strengthen the cooperation of functional departments,and improve the supporting policies of operation,for better promoting the development of high-quality operation of hospitals.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

OBJECTIVE To study the efficacy of sinapine thiocyanate dissoluble microneedle （ST-DMN） for acupoint administration against bronchial asthma （BA）. METHODS The network pharmacology and molecular docking techniques were used to screen the core targets of sinapine thiocyanate （ST） against BA， and the pharmacodynamics of the top 3 core targets was studied. Firstly， ST-DMN was prepared （drug loading of ST was 1 mg/tablet）； secondly， 30 rats were divided into blank control group， model control group， blank microneedle group， Sinapine powder plaster group （positive control group） and ST-DMN group. Except for the blank control group， rats of other groups were sensitized with 10% ovalbumin （containing aluminum hydroxide adjuvant） and nebulized with 1% ovalbumin to induce the BA model. After modeling， blank control group did not receive any intervention； normal saline was applied to the Feishu acupoint and Dazhui acupoint of the rats in the model control group， while the blank microneedle group， Sinapine powder plaster group and ST-DMN group were given blank microneedle， Sinapis alba powder （plaster， 1.5 g） and ST-DMN （3 tablets at 2 acupoints） at same acupoint， once a day， for 28 consecutive days. After administration， the general symptoms were observed and the body mass of the rats was measured.pathological changes of lung tissues in rats was observed； the levels of prostaglandin endoperoxide synthase 2 （PTGS2）， GNYL matrix metalloproteinase-9 （MMP-9） and interleukin-2 （IL-2）in serum， bronchoalveolar lavage fluid （BALF） and lung tissues were determined. RESULTS Results of network pharmacology and molecular docking showed that the key targets of ST against BA were identified as PTGS2， MMP-9， IL-2， epidermal growth factor receptor， heat shock protein90AA1， etc. Pharmacodynamic experiments showed that compared with model control group， relieved cough， restored hair color， sensitive behavior， stable respiration and increased body weight were all found in ST-DMN group； the histopathological changes as the structure of lung tissue， infiltration of alveolar epithelial cells and pulmonary interstitial inflammatory cells were improved to different extent； the levels of PTGS2， MMP-9 and IL-2 in serum， BALF and lung tissue were significantly reduced （P＜0.05 or P＜0.01）. CONCLUSIONS The anti-BA effect of ST-DMN acupoint administration is good， the mechanism of which may be associated with decreasing the levels of PTGS2， MMP-9 and IL-2 in serum， BALF and lung tissue.

Objective:To systematically understand the global research progress in the construction and validation of lung cancer risk prediction models.Methods:"lung neoplasms" , "lung cancer" , "lung carcinoma" , "lung tumor" , "risk" , "malignancy" , "carcinogenesis" , "prediction" , "assessment" , "model" , "tool" , "score" , "paradigm" , and "algorithm" were used as search keywords. Original articles were systematically searched from Chinese databases (CNKI, and Wanfang) and English databases (PubMed, Embase, Cochrane, and Web of Science) published prior to December 2018. The language of studies was restricted to Chinese and English. The inclusion criteria were human oriented studies with complete information for model development, validation and evaluation. The exclusion criteria were informal publications such as conference abstracts, Chinese dissertation papers, and research materials such as reviews, letters, and news reports. A total of 33 papers involving 27 models were included. The population characteristics of all included studies, study design, predicting factors and the performance of models were analyzed and compared.Results:Among 27 models, the number of American-based, European-based and Asian-based model studies was 12, 6 and 9, respectively. In addition, there were 6 Chinese-based model studies. According to the factors fitted into the models, these studies could be divided into traditional epidemiological models (11 studies), clinical index models (6 studies), and genetic index models (10 studies). 15 models were not validated after construction or were cross-validated only in the internal population, and the extrapolation effect of models was not effectively evaluated; 8 models were validated in single external population; only 4 models were verified in multiple external populations (3-7); the area under the curve (AUC) of models ranged from 0.57 to 0.90.Conclusion:Research on risk prediction models for lung cancer is in development stage. In addition to the lack of external validation of existing models, the exploration of potential clinical indicators was also limited.

Objective:To investigate the association between metabolic syndrome (MS) components and renal cell cancer in Chinese males.Methods:All male employees and retirees of the Kailuan Group were recruited in the Chinese Kailuan Male Cohort Study. They had been experienced routine physical examinations ever two years since May 2006. A total of 104 274 males were prospectively observed by 31 December 2015. Information on demographics, height, weight, blood glucose, blood lipid, blood pressure, as well as the information of incident renal cell cancer cases were collected at the baseline investigation by questionnaire, physical measurement and laboratory test. Cox proportional hazards regression models were used to evaluate the association between baseline MS and MS components (body mass index, blood glucose, blood lipid, blood pressure) and the risk of renal cell cancer in males.Results:A total of 104 274 males were recruited in our study with a age of (51.21±13.46) years, with 823 892.96 person-years follow-up and the median follow-up time was 8.88 years. A total of 131 new renal cell cancer cases were identified in the Kailuan male cohort study, and the crude incidence density was 15.90 per 100,000 person-years. Compared with no MS, the hazard ratios ( HR) (95% CI) of MS was 1.97 (1.32-2.94).When compared with normal level, the HR (95% CI) of obesity or overweight, hypertension, and dyslipidemia was 1.49 (1.04-2.14), 1.56 (1.06-2.29), and 1.77(1.23-2.54), after adjusting for potential confounding factors (i.e., age, education, income, smoke, and alcohol drink), respectively. In addition, a statistically significant trend ( P for trend<0.001) of increased renal cell cancer risk with an increasing number of abnormal MS components was observed. Conclusion:Obesity or overweight, hypertension, dyslipidemia and MS may increase the risk of renal cell cancer for Chinese males.

Objective:To investigate the association between total cholesterol (TC) and primary liver cancer in Chinese males.Methods:Since May 2006, all the male workers, including the employees and the retirees in Kailuan Group were recruited in the Kailuan male dynamic cohort study. Information about demographics, medical history and TC levels was collected at the baseline interview, as well as information on newly-diagnosed primary liver cancer cases during the follow-up period. A total of 110 612 males were recruited in the cohort by 31 December 2015. TC levels were divided into four categories by quartile (<4.27, 4.27-4.90, 4.90-5.56 and ≥5.56 mmol/L), with the first quartile group serving as the referent category. Cox proportional hazards regression model was used to evaluate the association between TC levels and primary liver cancer risk.Results:By December 31, 2015, a follow-up of 861 711.45 person-years was made with a median follow-up period of 8.83 years. During the follow-up, 355 primary liver cancer cases were identified. Compared with the first quartile, the HR of incident primary liver cancer among participants with the second, third and highest quartile TC levels were 0.76 (95% CI: 0.58-1.01), 0.59 (95% CI: 0.43-0.79), and 0.36 (95% CI: 0.25-0.52), respectively after adjusting for age, educational level, income level, smoking status, drinking status, body mass index, and HBsAg status ( P for trend<0.001). Subgroup analyses found that the association between TC levels and primary liver cancer was robust (all P for trend<0.05). The results didn’t change significantly after exclusion of newly-diagnosed cases within the first 2 years, males with history of cirrhosis or subjects who took antihyperlipidemic drugs, participants with higher TC levels had a lower risk of primary liver cancer (all P for trend<0.05) and HR(95% CI) of incident primary liver cancer among participants with the highest quartile TC levels were 0.41 (0.28-0.61), 0.36 (0.25-0.53) and 0.38 (0.26-0.54), respectively. Conslusion:In this large prospective study, we found that baseline TC levels were inversely associated with primary liver cancer risk, and low TC level might increase the risk of primary liver cancer.