OBJECTIVE To compare anti-ischemic stroke （IS） effect of different extraction parts from Gastrodia elata， and to provide reference for screening the anti-IS effective parts of G. elata. METHODS G. elata was extracted and separated by ethanol reflux extraction and ethyl acetate extraction. The rat model of diffuse cerebral thrombosis was induced by internal carotid artery injection of arachidonic acid （AA）； the anti-IS effect of G. elata powder， ethanol extract of G. elata， residue of ethanol extract of G. elata， ethyl acetate extract of G. elata， residue of ethyl acetate extract of G. elata， gastrodin and aspirin （positive control drug） were investigated with the content of Evans blue （EB） in the ischemic brain tissue as index. RESULTS Compared with model group， aspirin， ethanol extract of G. elata and ethyl acetate extract of G. elata could significantly decrease the content of EB in the ischemic brain tissue of model rats （P＜0.05）. G. elata powder had the tendency to reduce the content of EB in the ischemic brain tissue of model rats， without statistical significance （P＞0.05）. The residue of ethanol extract of G. elata， residue of ethyl acetate extract of G. elata and gastrodin had little effect on the content of EB in the ischemic brain tissue of model rats. CONCLUSIONS Both ethanol extract of G. elata and ethyl acetate extract of G. elata have anti-IS effects， which are stronger than that of G. elata powder.

Objective:To explore the changes of coagulation index levels in patients with type 2 diabetic foot and their correlation with pathological changes, in order to provide reference for clinical diagnosis of diabetic foot.Methods:133 patients with type 2 diabetes admitted to the Xiaoshan Hospital of Traditional Chinese Medicine in Hangzhou from Jun. 2018 to Jun. 2020 were selected. The patients were divided into type 2 diabetes group ( n=65) and diabetes foot group ( n=68) according to whether they had diabetes feet. In addition, 60 patients who had health examinations in our hospital during the same period were selected as the control group. Fibrinogen (FIB), thrombin time (TT), activated partial thromboplastin time (APTT) and prothrombin time (PT) were compared in each group, and Spearman method was used to analyze the correlation between each index and the occurrence of diabetes foot. Area under curve (AUC) of working characteristics of subjects (ROC) was used to analyze the diagnostic value of each index in diabetes foot. Results:The average FIB of control group, type 2 diabetes group and diabetes foot group was (2.86±0.50) g/L, (3.30±0.81) g/L, (4.43±1.16) g/L; The FIB level in diabetes foot group was significantly higher than that in type 2 diabetes group and control group, and that in type 2 diabetes group was significantly higher than that in control group ( P<0.05) ; The mean TT of control group, type 2 diabetes group and diabetes foot group was (17.60±2.01) s, (15.39±2.39) s, (13.49±2.84) s; The average APTT of control group, type 2 diabetes group and diabetes foot group was (32.02±4.22) s, (29.97±3.97) s, (25.69±4.07) s; The mean PT values of control group, type 2 diabetes group and diabetes foot group were (12.64±1.49) s, (11.41±1.04) s and (10.50±1.08) s. The TT, APTT and PT values in the diabetes foot group were significantly lower than those in the type 2 diabetes group and the control group, and those in the type 2 diabetes group were significantly lower than those in the control group ( P<0.05) ; The level of FIB index was positively correlated with the occurrence of diabetes foot, while TT, APTT and PT indexes were negatively correlated with the occurrence of diabetes foot ( P<0.05). The AUC values of FIB, TT, APTT and PT indexes for the diagnosis of diabetes foot were 0.898, 0.879, 0.859 and 0.871, respectively. Conclusions:There are significant differences in FIB, TT, APTT and PT index levels between diabetic foot patients and type 2 diabetic patients and healthy people, and the occurrence of diabetic foot is significantly related to blood coagulation indicators. The detection of blood coagulation indicators has certain clinical significance for the diagnosis of diabetic foot.

Genomic epidemiology, based on whole-genome sequencing technology and bioinformatics analysis, can make up for the shortcomings of traditional molecular typing methods and provide a novel insight for the genetic evolution and transmission of pathogenic fungi. The combination of genetic information and epidemiological methods of pathogenic fungi can predict fungi transmission routes and risks, and provide a theoretical basis for the development of public health strategies for fungi infection prevention and control. This paper summarizes the development of molecular epidemiology and genomic epidemiology, as well as the application of genomic epidemiology methods in the analyses of genetic relationship, origin, evolution, drug resistance, virulence, and genome-wide association of pathogenic fungi, and discusses the development of pathogenic fungi genomic epidemiology.

Background::Cancer immunotherapy has emerged as a promising strategy against triple-negative breast cancer (TNBC). One of the immunosuppressive pathways involves programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), but many patients derived little benefit from PD-1/PD-L1 checkpoint blockades treatment. Prior research has shown that MYC, a master transcription amplifier highly expressed in TNBC cells, can regulate the tumor immune microenvironment and constrain the efficacy of immunotherapy. This study aims to investigate the regulatory relationship between MYC and PD-L1, and whether a cyclin-dependent kinase (CDK) inhibitor that inhibits MYC expression in combination with anti-PD-L1 antibodies can enhance the response to immunotherapy. Methods::Public databases and TNBC tissue microarrays were used to study the correlation between MYC and PD-L1. The expression of MYC and PD-L1 in TNBCs was examined by quantitative real-time polymerase chain reaction and Western blotting. A patient-derived tumor xenograft (PDTX) model was used to evaluate the influence of a CDK7 inhibitor THZ1 on PD-L1 expression. Cell proliferation and migration were detected by 5-ethynyl-2′-deoxyuridine (EdU) cell proliferation and cell migration assays. Tumor xenograft models were established for in vivo verification. Results::A high MYC expression level was associated with a poor prognosis and could alter the proportion of tumor-infiltrating immune cells (TIICs). The positive correlation between MYC and PD-L1 was confirmed by immunostaining samples from 165 TNBC patients. Suppression of MYC in TNBC caused a reduction in the levels of both PD-L1 messenger RNA and protein. In addition, antitumor immune response was enhanced in the TNBC cancer xenograft mouse model with suppression of MYC by CDK7 inhibitor THZ1. Conclusions::The combined therapy of CDK7 inhibitor THZ1 and anti-PD-L1 antibody appeared to have a synergistic effect, which might offer new insight for enhancing immunotherapy in TNBC.

OBJECTIVE：To obs erve the protective effect of protoca techuic aldehyde（PAL）on neurovascular unit （NVU） homeostasis damage in rats after cerebral ischemia-reperfusion injury （CIRI）. METHODS ：SD rats were randomly divided into sham operation group ，model group ，PAL high-dose and low-dose groups （10，20 mg/kg），with 11 rats in each group. Administration groups were given relevant medicine intragastrically. Sham operation group and model group were given the same volume of normal saline intragastrically ，10 mL/kg once a day ，for 5 days. After last administration ，CIRI model was induced by suture method ；the ultrastructural changes of NVU were observed by transmission electron microscope. Western blot assay was used to detect the expression of NUV related proteins （MAP-2，GFAP，AQP-4）in cerebral tissue. Immunofluorescence staining was used to observe the positive expression of above proteins in cerebral cortex. RESULTS ：Compared with sham operation group ， blood-brain barrier （BBB）structure of model group was destroyed severely ，the vascular lumen became narrower ，lateral edema of endothelial cells was severe ，and the thickness of basement membrane varied ；the nuclei of neurons were pyknosis and there was a large area of edema in the surrounding tissues ；the structure of glial cells was seriously damaged ，the cell body was shrunk and organelles were lost ；protein expression （or positive expression ）of MAP- 2 in brain tissue （or cerebral cortex ）were significantly decreased （P＜0.05 or P＜0.01），while protein expression （or positive expression ） of GFAP and AQP- 4 were increased significantly（P＜0.01）. After PAL intervention ，the rats had less BBB damage ，and the morphology of vascular lumen and basement membrane were not completely destroyed ；the damage of neurons was alleviated ，the pyknosis of neurons was decreased ， the chromatin was homogeneous and the heterochromatin was decreased；the damage of glial cell structure was alleviated protein expression of GFAP and AQP- 4（except for low-dose group） in cerebral tissue and positive expression of MAP- 2 and GFAP protein in cerebral cortex were reversed @qq.com significantly （P＜0.05 or P＜0.01）. CONCLUSIONS ：PAL can protect the stability of NVU from damage in CIRI model rats； the mechanism may be related to up-regulating the expression of MAP- 2 protein in cerebral cortex and down-regulating the expression of GFAP and AQP- 4 protein in brain tissue.

The imbalance of lipid metabolism is an important factor causing a series of metabolic diseases such as non-alcoholic fatty liver disease (NAFLD) and hyperlipidemia.Liver X receptors is a member of the nuclear receptor superfamily, which maintains cholesterol homeostasis by regulating cholesterol absorption, transport, reverse cholesterol transport, biosynthesis and other functions.It plays an important role in maintaining lipid homeostasis by regulating de novo fat synthesis to maintain the balance of fatty acids in the body.

Objective:To investigate the predictive value of abnormal heart rate circadian rhythm for all-cause mortality in stage 5 chronic kidney disease (CKD 5) patients.Methods:The retrospective study was performed in CKD 5 patients enrolled from the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital) and the Affiliated BenQ Hospital of Nanjing Medical University from February, 2011 to December, 2019. A total of 159 healthy volunteers were enrolled as the healthy control group during the same period. The circadian rhythm of heart rate was monitored by 24-hour Holter. Related indices (including 24-hour, daytime and nighttime mean heart rate, night/day heart rate ratio, 24-hour maximum heart rate, 24-hour minimum heart rate and difference between maximum and minimum of 24-hour heart rate) were calculated. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Cox regression model was used to analyze the risk factors of all-cause mortality in CKD 5 patients. Kaplan-Meier survival curve and Log-rank test were used to compare the differences of cumulative mortality between high ratio group (night/day heart rate ratio>0.91) and low ratio group (night/day heart rate ratio≤0.91). The nonlinear relationship between night/day heart rate ratio and all-cause mortality was analyzed by restricted cubic spline plot. Time-dependent receiver operating characteristic (ROC) curve was used to analyze the predictive value of night/day heart rate ratio for all-cause mortality in CKD 5 patients.Results:A total of 159 healthy volunteers and 221 CKD 5 patients were included in this study. There were 123 males (55.66%) and the age was (52.72±13.13) years old in CKD 5 patients. The total median follow-up time was 50.0 months. Compared with controls, 24-hour, nighttime mean heart rate, 24-hour minimum heart rate in CKD 5 patients were increased (all P<0.05), furthermore, the night/day heart rate ratio was higher [(0.91±0.09) vs (0.81±0.08), P<0.001], showing "non-dipping heart rate". However, the 24-hour maximum heart rate and the difference between maximum and minimum of 24-hour heart rate in CKD 5 patients were lower than controls (both P<0.05). Multivariate Cox regression analysis showed that the increased night/day heart rate ratio (per 0.1 increase, HR=1.557, 95% CI 1.073-2.258, P=0.020) was an independent influencing factor for all-cause mortality in CKD 5 patients. Kaplan-Meier survival curve analysis showed that the cumulative mortality of the high ratio group was significantly increased than that of the low ratio group (Log-rank test χ 2=7.232, P=0.007). From the restricted cubic spline plot, there was a linear effect between night/day heart rate ratio and all-cause mortality ( P=0.141), and when night/day heart rate ratio was above 0.91, the risk of all-cause mortality was significantly increased in CKD 5 patients. According to time-dependent ROC curve, the accuracy of night/day heart rate ratio in predicting all-cause mortality was 70.90% even when the survival time was up to 70.0 months. Conclusions:The circadian rhythm of heart rate in CKD 5 patients displays "non-dipping" state. High night/day heart rate ratio is an independent influencing factor for all-cause mortality in CKD 5 patients.

Objective:To observe heart rate circadian rhythm in patients with chronic kidney disease (CKD) stage 5 and to analyze the effects of parathyroidectomy (PTX) on heart rate circadian rhythm in severe secondary hyperparathyroidism (SHPT) patients.Methods:A cross-sectional observation was performed in 213 patients with CKD stage 5 and 96 controls, and the patients were divided into those with severe SHPT (PTX group, n=70) and without severe SHPT (non-PTX group, n=143). Forty-six PTX patients were followed up prospectively. The baseline data were compared among these groups. Holter electrocardiogram was performed for each participant. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Multiple linear regression analysis was used to analyze the related factors of heart rate circadian rhythm in patients with CKD stage 5. Results:The 24-hour, daytime and nighttime mean heart rate in patients with CKD stage 5 were all higher than those in controls, especially in PTX group (all P<0.05). The night/day heart rate ratios of controls and CKD stage 5 patients were (0.81±0.08) and (0.91±0.08) respectively ( P<0.01). Correlation analysis showed 24-hour and daytime or nighttime mean heart rate in patients with CKD stage 5 were positively correlated with serum levels of phosphorus and ln(alkaline phosphatase), while nighttime mean heart rate and night/day heart rate ratio were positively related with serum intact parathyroid hormone level. After adjusting with postoperative follow-up period (median time: 10.9 months), 24-hour and nighttime mean heart rate, and night/day heart rate ratio in PTX patients all decreased significantly (all P<0.01). Conclusions:Heart rate is increased and circadian rhythm is abnormal in patients with CKD stage 5, which are related with mineral and bone disorder. PTX significantly decreases 24-hour and nighttime mean heart rate in severe SHPT patients, and improves the heart rate circadian rhythm.

Objective To investigate the sleep quality of pacemaker implanted patients,to analyze the relationships among neuroticism,positive psychological capital and sleep quality,and to examine the potential mediating effect of positive psychological capital on the relationship between neuroticism and sleep quality. Methods Using convenience sampling, a total of 178 pacemaker implanted patients were interviewed and analyzed in two tertiary hospitals of Shandong province. They were assessed with Big Five Inventory,The Positive Psycap Questionnaireand Pittsburgh Sleep Quality Indexfor the evaluation of neuroticism,positive psychological capital and sleep quality.The Process macro was used to test the mediating effect. Results The mean score of PSQI in patients with pacemaker implantation was (8.48± 4.50), and 71.3％of them had sleep problems.The scores of neuroticism had positively correlated with the PSQI scores(r=0.31, P<0.01), the scores of positive psychological capital had negatively correlated with the PSQI scores(r=- 0.39, P<0.01).The confidence interval from Bootstrap output indicated positive psychological capital played a mediating role between neuroticism and sleep quality (95％CI:0.06-0.23), mediation effect was 0.14, the percentage of mediation effect in total effect was 43.75％. Conclusions The relation of positive psychological capital to neuroticism and sleep quality among pacemaker implanted patients are intimate.Positive psychological capital could mediate the relationship between neuroticism and sleep quality. It is suggested that nurses can improve the patient′s sleep by enhancing the intervention of positive psychological capital according to the personality characteristics of patients.

[ ABSTRACT] AIM:To investigate the preventive effects of Clostridium butyricum ( C.butyricum) on the type of pylorus ligated gastric ulcer ( GU) in mice and the underlying mechanisms.METHODS:ICR mice were randomly divided into 4 groups:sham operation group, model group, C.butyricum pretreatment group and omeprazole pretreatment group. Gastric pyloric ligation was adopted to establish GU model in mice.The gastric juice was collected to measure the content of gastric free mucus, the pH of gastric juice and the activity of pepsin.The gastric tissues were collected for routine HE stai-ning to observe the pathological changes.The content of glycogen was detected by PAS staining.The protein expression of Bax and Bcl-2 in the gastric mucosa was also assessed by immunohistochemical staining.RESULTS: The HE and PAS staining showed that the C.butyricum pretreatment obviously attenuated the mucosa lesion induced by ligation.Compared with model group, the pH of gastric juice was significantly raised.The activity of pepsin fell off in C.butyricum group, which was lower than that in omeprazole group.In comparison with model group, the content of gastric free mucus was dra-matically increased and PAS staining showed a significant rise in C.butyricum group, but not in omeprazole group.The protein expression of Bax was decreased and the protein expression of Bcl-2 was upgraded in C.butyricum group than those in model group.CONCLUSION:C.butyricum protects gastric mucosa against the challenge of pylorus ligation in mice and its mechanism may be related to inhibiting gastric acid secretion and the activation of pepsin, increasing the production of gastric free mucus, strengthening the expression of bcl-2 gene and inhibiting the expression of bax gene.