Objective Vascular dementia(VD)is a common cognitive dysfunction associated with cerebrovascular disease.This study is aimed at investigating the therapeutic effect of anisodine hydromide(AH)on VD and the potential antioxidative stress mechanisms involved.Methods A VD model was established in Sprague-Dawley(SD)rats through permanent bilateral common carotid artery occlusion.The rats were divided into a sham group,a VD model group,and AH treatment groups receiving AH at low,medium,or high doses(n=4).The neurological function of the rats in each group was evaluated using the Bederson scale,and limb coordination ability was assessed using the pole climbing test.Superoxide dismutase(SOD)and malondialdehyde(MDA)levels in the serum and brain were measured by enzyme-linked immunosorbent assay(ELISA)to assess the level of oxidative stress.In addition,apoptosis was assessed by TUNEL assay,and reactive oxygen species(ROS)levels in neuronal cells were determined using dichloro-dihydro-fluorescein diacetate(DCFH-DA)probe.The potential mechanism of action of AH on M receptors was investigated using M1-M5 inhibitors.Results Compared with the sham group,the nerve function and limb coordination of rats in the VD model group were significantly impaired(P＜0.01),and the SOD levels were significantly decreased in the serum([100.70±18.95]U/mL vs.[44.22±7.11]U/mL,P＜0.001)and the brain([131.77±8.34]U/mg vs.[84.39±4.10]U/mg,P＜0.01),MDA levels were significantly increased in the serum([12.03±1.01]nmol/mL vs.[17.74±1.00]nmol/mL,P＜0.001)and the brain([4.41±0.30]nmol/mg vs.[6.17±0.70]nmol/mg,P＜0.05).AH treatment significantly improved the neurological function and limb coordination ability of VD rats.In comparison with the VD group,the high-dose AH treatment group,in particular,exhibited the most significant increase in SOD levels in the serum([44.22±7.11]U/mL vs.[98.67±0.86]U/mL,P＜0.001)and the brain([84.39±4.10]U/mg vs.[162.83±17.36]U/mg,P＜0.001),and the most significant decrease in MDA levels in the serum([17.74±1.00]nmol/mL vs.[6.68±0.06]nmol/mL,P＜0.001)and the brain([6.17±0.70]nmol/mg vs.[3.96±0.77]nmol/mg,P＜0.01).AH also reduced the number of TUNEL positive cells(P＜0.01)in a dose-dependent manner.The percentage of apoptotic cells was(36.10±9.07)％,(9.60±5.63)％,and(3.43±0.92)％,respectively,for AH treatment at low,medium,and high concentrations,indicating that AH had an inhibitory effect on apoptosis.According to findings from the in vitro experiments,AH treatment reduced the MDA content(P＜0.01),increased the SOD activity(P＜0.01),and decreased the ROS levels of HT22 and NSC-34 cells in a dose-dependent manner.M2 receptor inhibitors could reduce the ROS level in oxidative stress injury,suggesting that AH,as an M receptor antagonist,might exert its effect by inhibiting the M2 receptor.Conclusion AH modulates SOD and MDA levels and reduces oxidative stress injury,thereby improving neurological function and limb coordination and showing potential therapeutic effects in VD.The neuroprotective effects of AH may be related to its antioxidative stress and antiapoptotic mechanisms,and the M2 receptor may be a potential target of its actions.These findings provide an important theoretical basis for the development of new therapeutic strategies for VD.

In addition to the typical respiratory symptoms, COVID-19 patients present with clinical manifestations of cardiovascular system damage, and they are at higher risk of intensive care or mortality. The mechanism of COVID-19's impact on the cardiovascular system is still unclear, therefore we need to pay close attention to it. Based on the existing research, this paper focused on the concurrent characteristics of the cardiovascular system diseases, summarized the possible mechanisms of cardiovascular system damage, including the coronavirus invaders directly into cardiomyocytes and its conduction system, with complications or accompanying conditions such as cytokine storm, imbalance of oxygen supply and demand, drug influence, stress and other damage to cardiovascular system. Meanwhile, current clinical manifestations and treatment methods of COVID-19 were summarized.

Objective:To explore the epidemiological characteristics of leptospirosis in Sichuan province from 2004 to 2018, and provide evidence for the prevention and control of leptospirosis.Methods:The descriptive epidemiology analysis was conducted based on the epidemic data of leptospirosis collected from the national notifiable infectious disease reporting information system (NNIDRIS) and sentinel surveillance system in 11 areas in Sichuan from 2004 to 2018. The ArcGIS 10.2 software was used for mapping. The SaTScan 9.1.1 software was used to analyze spatiotemporal scanning and characteristics of temporal-spatial clusters of leptospirosis.Results:A total of 2 834 cases of leptospirosis, including 41 deaths, were reported in Sichuan from 2004 to 2018, and the reported morbidity rate was 0.23/100 000 and the mortality rate was 0.003/100 000. It revealed that leptospirosis had an overall downward fluctuated trend. The incidence of leptospirosis had obvious seasonality, mainly from the last ten-day of August to the end of September, 1-2 weeks later after rice harvesting time. The reported cases were mainly males, the male to female ratio of the cases was 2.05∶1. The incidence was higher in age group 50-65 years. The majority of reported cases were farmers, accounting for 82.75% (2 345/2 834), followed by students, accounting for 12.74% (361/2 834). However, rare cases in students had been reported since 2011. In recent years, the high-incidence areas were alternating between Mabian, Muchuan counties along the Yangtze River and Yilong county located in the Jialing River basin. According to the spatial-temporal descriptive analyses by SaTScan, there were two clustering areas in the province where most cases occurred ( P<0.001). The average density of field rats in 11 sentinel surveillance areas was 5.44%(14 351/263 767), and the predominant field rats included Anourosorexsquamipes (69.07%), Apodemusagrarius (12.73%). Whatmore, the density of the Apodemusagrarius ranged from 4.60% to 0.19%, showing downward trend with the lowest level in 2018. The annual culture rate of Leptospira from rat kidney samples declined. During 2007-2018, the average positive rate of Leptospira antibodies in healthy people was 24.52%(3 271/13 339), and the predominant serogroup was Icterohaemorrhagiae. There was no replacement of Leptospira serogroup in recent years. Conclusions:The incidence of leptospirosis in Sichuan was extremely low during 2004-2018, and the incidence peak of leptospirosis occurred in rice harvesting period. The cases were mainly old farmers, and the high-risk areas were constantly alternating between the Yangtzi River and the Jialing River basin. Both the density and the carriage rate of Leptospira of Apodemusagrarius were low, and the predominant serogroup was Icterohaemorrhagiae. The average positive rate of leptospira antibodies in healthy people was very low.

The estrogen receptor (ER)-negative breast cancer subtype is aggressive with few treat-ment options available. To identify specific prognostic factors for ER-negative breast cancer, this study included 705,729 and 1034 breast invasive cancer patients from the Surveillance, Epidemiol-ogy, and End Results (SEER) and The Cancer Genome Atlas (TCGA) databases, respectively. To identify key differential kinase-substrate node and edge biomarkers between ER-negative and ER-positive breast cancer patients, we adopted a network-based method using correlation coefficients between molecular pairs in the kinase regulatory network. Integrated analysis of the clinical and molecular data revealed the significant prognostic power of kinase-substrate node and edge featuresfor both subtypes of breast cancer. Two promising kinase-substrate edge features, CSNK1A1-NFATC3 and SRC-OCLN, were identified for more accurate prognostic prediction in ER-negative breast cancer patients.

Objective To disuss the clinic characteristics,the etiologies and the misdiagnosis cause of hyperthyroidism featuring in vomit mainly.Methods The clinic data of 35 hyperthyroids featuring in vomit mainly were reviewed and analyzed.Results The hyperthyroids in this group were middle-aged female mainly whose symptoms showd that they vomit frequently with abdominal distention,thin,inappetence,chest congestion,palpitation;tachycardia;hypohepatia and electrolyte disturbance.Furthermore,their thyroid gland function assay is in concordance with the hyperthyroidism diagnosis.Treatment for antihyperthyroidism can get remarkable effects.Conclusion The patient showing vomit of unknown origin may be taken into account as hyperthyroid.The key points to prevent misdiagnosis are to detect thyroid gland function in time and to improve the understanding for un-typical hyperthyroidism.