Objective:To improve the teaching quality of Medical Microbiology by optimizing the teaching method,adjusting the teaching content and reforming the assessment model.Methods:The students of grade 2020 and 2021 of the same major were divided into the control group and the reform group.The control group received the traditional teaching method.The reform group received the"online + offline"blended teaching method,which integrates online learning resources and ideological and political education into the theoretical content of the curriculum.And the whole process assessment system was applied to the teaching method.The teaching quality was evaluated by the whole process examination results and questionnaire survey.Results:Compared with the control group,the score in the reform group was significantly improved(P＜0.01).Results of the questionnaire survey showed that students'satisfaction with the mixed teaching method reached 97.5% .The integration of hot issues of microbiology and curriculum ideological and political education significantly improved students'learning interest,and more students wanted to engage in the work of microbiology related fields in the future.Conclusion:The practice results show that optimizing the teaching method,adjusting the teaching content and reforming the assessment mode can stimulate the students'learning interest,improve the students'independent learning ability and improve the teaching quality.

Currently, there is still no effective curative treatment for the development of late-stage liver fibrosis. Here, we have illustrated that TB001, a dual glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) agonist with higher affinity towards GCGR, could retard the progression of liver fibrosis in various rodent models, with remarkable potency, selectivity, extended half-life and low toxicity. Four types of liver fibrosis animal models which were induced by CCl₄, α-naphthyl-isothiocyanate (ANIT), bile duct ligation (BDL) and Schistosoma japonicum were used in our study. We found that TB001 treatment dose-dependently significantly attenuated liver injury and collagen accumulation in these animal models. In addition to decreased levels of extracellular matrix (ECM) accumulation during hepatic injury, activation of hepatic stellate cells was also inhibited via suppression of TGF-β expression as well as downstream Smad signaling pathways particularly in CCl₄-and S. japonicum-induced liver fibrosis. Moreover, TB001 attenuated liver fibrosis through blocking downstream activation of pro-inflammatory nuclear factor kappa B/NF-kappa-B inhibitor alpha (NFκB/IKBα) pathways as well as c-Jun N-terminal kinase (JNK)-dependent induction of hepatocyte apoptosis. Furthermore, GLP-1R and/or GCGR knock-down results represented GCGR played an important role in ameliorating CCl₄-induced hepatic fibrosis. Therefore, TB001 can be used as a promising therapeutic candidate for the treatment of multiple causes of hepatic fibrosis demonstrated by our extensive pre-clinical evaluation of TB001.

Objective:To investigate the relationship between NOD-like receptor protein 3 (NLRP3) gene promoter region-30 single nucleotide polymorphism (SNP) (rs3738448) G/T and dilated cardiomyopathy (DCM) and its related risk factors.Methods:A case-control study method was used to collect 137 patients and 140 healthy controls; polymerase chain reaction-restriction endonuclease fragment length polymorphism technology combined with sequence alignment after DNA sequencing was used for data statistics; After Hardy-Weinberg balance test, the χ 2 test was used for correlation analysis; logistic regression was used to analyze the correlation between multiple risk factors and the SNP site and the incidence of DCM; SNPinfo database was used to predict and analyze the transcription factors affected by the SNP. Results:A total of GG and GT genotypes were detected at this SNP locus, and their genotype distributions were in line with Hardy-Weinberg equilibrium ( P>0.05). At the same time, the difference between the DCM group and the control group was significant ( P<0.05). Multivariate logistic regression analysis indicated that mean arterial pressure, C-reactive protein and B-type brain natriuretic peptide were independent risk factors for the onset of DCM (all P<0.05). The incidence of DCM in -30(RS3738448)G/T genotype GT group was 2.243 times higher than that in GG group (95% CI: 1.043-4.827, P<0.05). Logistic regression analysis under dominant, recessive and additive genetic models showed that there was a correlation between the dominant inheritance of SNP and the occurrence of DCM ( OR=0.44, AIC=370.4, BIC=381.3, P<0.05). Conclusions:The -30 (rs3738448) G/T SNP in the promoter region of the NLRP3 gene is associated with the pathogenesis of DCM, and provides population genetic data for the study of polymorphisms in the promoter region of NLRP3 gene.

Objective:To evaluate the operation effect of remote imaging network platform in a regional medical center.Methods:The workload data of remote imaging network in a regional medical center from 2017 to 2019 were analyzed.Results:137 medical institutions were connected to the remote imaging diagnosis network platform, and the number of imaging examinations in grass-roots medical institutions increased significantly. Part of the imaging examination in the superior medical center was gradually diverted to the subordinate medical institutions. However, limited by the ability of image diagnosis, grass-roots medical institutions relied on remote diagnosis of higher-level hospitals.Conclusions:Remote image diagnosis network is an important platform support for Internet plus medical health service, which can rapidly and effectively enhance the ability and level of imaging diagnosis in primary medical institutions.

With the rapid development of biotechnology, therapeutic peptide has been a hot area in the central nervous system drugs due to its features of easy to design and target specificity. However, therapeutic peptide is difficult to cross the blood brain barrier into the central nervous system and target cells, coupled with its in vivo instability, which seriously restricts its application in central nervous system diseases. This review focuses on the progress of therapeutic peptides across the blood brain barrier targeting the central nervous system, compares and analyses the methods of increasing therapeutic peptides penetration, specificity and stability in combination with other molecules, in order to provide help for the development of central nervous system drugs.

Objective To study the time-toxicity and dose-toxicity relationship of hepatotoxicity induced by Paracetamol Tablets (PT),Compound Paracetamol and Amantadine Hydrochloride Tablets (CPAH),Compound Dextromethorphan Hydrobromide Tablets (CDH),and Chaiqin Qingning Capsules (CQC) with single dose in mice.Methods In the Time-Toxicity relationship study,Kunming mice were randomly divided into control,PT,CPAH,CDH,and CQC group,and mice of.each drug administration group were randomly divided into nine subgroups according to the time (1,2,4,8,12,24,48,72 and 96 h after administration) of blood collection.The acetaminophen contents in PT,CPAH,and CDH groups were 425.98 mg/kg,and the dose of CQC group was 3 680.50 mg/kg.In the Dosage-Time relationship study,mice were randomly divided into control,PT,CPAH,CDH,and CQC high,medium and low dose group.The acetaminophen contents of high,medium,and low dose were 266.24,425.98,and 681.57 mg/kg in PT,CPAH,and CDH group,and the dose of CQC group was 1437.70,2300.31,and 3680.50 mg/kg,10 mice in each group,sex in half.Blood was collected 12 h after administration.Animal behavior was observed every day,blood and organs were collected at the corresponding time points,serum alanine aminotransferase (ALT),aspartate aminotransferase (AST),and alkaline phosphatase (ALP) level were detected,and the organs index of spleen and thymus,liver were calculated.Results There were no significant changes of ALT,AST,ALP,and organs index after once ig administration of CQC at dosage of 1437.70 mg/kg to 3680.50 mg/kg in mice.The study on time-toxicity relationship indicated that,after once administration of PT,CPAH,and CDH at 425.98 mg/kg,mice showed toxic symptom such as hypokinesia,dry hair and so on,12 h was the most obvious,24 ～ 72 h disappeared.The level of ALT,AST,and ALP in serum increased and reached to the peak at 12 h and then restored near normality after 72,24,and 24 h in PT,CPAH,and CDH group.Their organ index of liver,spleen and thymus all had no significant changes.The study on the dosage-toxicity relationship indicated that,there were no significant changes of animal behavior,ALT,AST,ALP,and organs index after once ig administration of PT,CPAH,and CDH at 266.24 mg/kg.Obvious liver injury can be induced by the three drugs with dosage of 425.98 to 681.57 mg/kg and the level of ALT,AST,and ALP increased significantly with the increase of dosage.Their liver index increased significantly with dosage of 681.57 mg/kg,but the organs index of spleen,thymus had no significant changes.Conclusion There was no hepatotoxicity after once ig administration of CQC with dosage of 3680.50 mg/kg in mice.Mice were once ig administration ofPT,CPAH,and CDH with a large dose,may induce acute liver injury and show obvious time-toxicity and dose-toxicity relationships.

Objective To study the dose-time-toxicity relationship of hepatotoxicity in mice with multiple administration of Paracetamol Tablets (PT),Compound Paracetamol and Amantadine Hydrochloride Tablets (CPAH),Compound Dextromethorphan Hydrobromide Tablets (CDH),and Chaiqin Qingning capsules (CQC).Methods Mice were randomly divided into control,PT,CPAH,CDH,and CQC high,medium,and low dose groups.The acetaminophen contents of high,medium,and low doses were 266.24,425.98,and 681.57 mg/kg in PT,CPAH,and CDH groups,and the doses of CQC group were 1437.70,2300.31,and 3 680.50 mg/kg,ig administration,once daily for 5 d.General state and toxicity of mice were observed.The changes of ALT,AST,AKP,TBIL,and ALB levels in serum and organ indexes of liver,spleen,thymus,and kidney were tested on day 1,3,7,11,and 14 after multiple administration.Results CQC with the dosage range of 1 437.70-3 680.50 mg/kg to mice within 14 d,has not yet induced the increase of AST,ALT,AKP,TBIL,and ALB levels and changes of organ indexes of liver,thymus spleen,and kidney compared with normal control (P ＞ 0.05).PT,CPAH,and CDH with repeated dose of 425.98-681.57 mg/kg could induce significant increase of the levels ofALT,AST,AKP,and TBIL which reached the peak on day 1 (P ＜ 0.05),and then gradually decreased on day 3-14.The level of ALB significant decreased on day 1-11 (P ＜ 0.05),and then gradually recovered on day 11-14.The liver index significant increased on day 1-3 (P ＜ 0.05),and recovered on day 7-14.Conclusion Multiple administration of CQC could not induce liver injury in mice within 14 d,while multiple administration ofPT,CPAH,and CDH could induce hepatotocixity in mice with a certain dose,and show an obvious dose-time-toxicity relationship.

Objective To optimize the fermentation conditions for Enterococcus faecalis (E.faecalis) and Saccharomyces cerevisiae (S.cerevisiae) mixed culture.Methods The optimum fermentation conditions for E.faecalis and S.cerevisiae mixed culture were identified by investigating the influence of initial pH,inoculum size,and ventilation rate of the culture broth on mixed microbial growth.Results The optimal initial pH of mixed microbial culture was 7.0 and the inoculation amounts of E.faecalis and S.cerevisiae were 4％ and 10％ respectively,when fermented in 600-mL pilot fermentor (liquid volume 40％) at 30 ℃,with ventilation rate of 0.2 L/min,for 20 h.At the end of the fermentation,the E.faecalis and S.cerevisiae counts were approximately 3.8 × 108 CFU/mL and 2.4 × 108 CFU/mL,respectively.Ventilation for the amount difference of E.faecalis was no significant (P ＞ 0.05),and for the amount difference of S.cerevisiae was statistically significant (P ＜ 0.05).Conclusion The E.faecalis and S.cerevisiae counts increased by 32.2％ and 31.5％ respectively,when the optimized conditions of fermentation culture were used.In this study,high mixed microbial counts were obtained,thus providing a reference for the preparation of large-scale production of mixed microbes.

Post-stroke aphasia is an acquired language disorder caused by stroke.It impaired the quality of life of patients and brought a heavy burden to family and the society.Unfortunately,the highly variable predictive factors make the prognosis of aphasia recovery difficult.Much of the researches indicated that the post-stroke aphasia recovery is associated with the patient-related and stroke-related factors.We searched the recent advances on the influence of patient-related factors and stroke-related factors on aphasia recovery.It showed that patient-related factors have no obvious effect on predicting aphasia recovery while the lesion (stroke)-related factors appeared close correlation with post-stroke aphasia recovery.The clinicians should pay more attention on lesion (stroke)-related factors when evaluate the outcome and give the intervention measures.

Objective To study the relationships between retinal microvascular disease and acute coronary event (ACE) among aged people. Methods A controlled study for senile people in communities was conducted. Xinglong Zhuang Coal Mine Community in Jining city, Shandong province was chosen to carry out the study, and the residents in that area aged≥60 years were asked to take questionnaire survey, physical and laboratory examinations. There were 139 cases met the diagnostic criteria of ACE being in the observation group, and 1 509 cases without ACE were assigned in the control group. The gender, age, smoking, alcohol intake, hypertension, diabetes mellitus, education, physical exercise, retinal microvascular disease, fasting blood-glucose, high density lipoprotein cholesterin (HDL-C), low density lipoprotein cholesterin (LDL-C), triacylglycerol (TG), systolic pressure, diastolic pressure, body mass index (BMI) were collected in the two groups to perform univariate analysis. Multivariate non-conditional logistic regression analysis was used for the factors with statistical significance to screen out the independent risk factors that could affect the occurrence of ACE. Results The univariate analysis showed:the risk factors that might cause the occurrence of ACE included age, gender, smoking, hypertension, diabetes mellitus, LDL-C, systolic pressure, diastolic pressure, BMI, and retinal microvascular disease (P<0.05 or P<0.01). In the ACE patients of observation group, the rates of presence of arteriovenous crossing sign [44.6%(62/139) vs. 27.8%(419/1 509)], hard exudates [9.4%(13/139) vs. 4.9%(74/1 509)] and cotton-wool patches [19.4%(27/139) vs. 7.3%(110/1 509)] in retinal microvascular disease were significantly higher than those in control group (P<0.05 or P<0.01). The logistic regression analysis showed:age [P=0.002, odds ratio (OR)=1.06, 95%confidence interval (95%CI)=1.04-1.09], smoking (P=0.032, OR=2.17, 95%CI=2.04-2.30), retinal microvascular disease (P = 0.010, OR = 2.33, 95%CI = 0.97 - 1.27), hypertension (P < 0.001, OR = 5.21, 95%CI=4.11-6.36), diabetes mellitus (P=0.021, OR=1.03, 95%CI=1.01-1.05) and LDL-C (P=0.020, OR=2.80, 95%CI = 2.65 - 2.99) were the independent risk factors for the occurrence of ACE. Conclusions Retinal microvascular disease is the independent risk factor for the occurrence of ACE. The retinal angiography can be a useful examination to forecast ACE.