OBJECTIVE To investigate the effect of betulin (BE) on the replication of rotavirus (RV) in vitro.METHODS ①MA104 cells were intervened with BE between 0.03125 and 64μmol·L-1 for 72 h,and MTT assay was used to detect the cell survival.② MA104 cells were infected with RV including Wa strains and SA-11 strains to establish a viral model.MA104 cells were divided into the cell control group,RV group and RV+BE groups.The cytopathic effect (CPE) method combined with MTT assay was used to detect the effect of BE on anti-RV adsorption,anti-RV biosynthesis and direct inhibition of RV.③The grouping was the same as in②,and RT-qPCR,Western blot and IF methods were used to detect the expression of RV structural protein VP6 after 24 h of BE incubation.④The grouping was the same as in②,and the ELISA kit was used to detect the concentrations of pro-inflammatory factors IL-6,IL-1β and TNF-α,anti-inflammatory factor IL-10 and type Ⅱ interferon IFN-γ in the cell supernatant after 24 h of BE incubation.⑤The grouping was the same as in②,and qPCR assay was used to detect the mRNA expression levels of Toll-like receptor 4 (TLR4),myeloid differentiation factor 88 (MYD88) and TNF receptor-associated factor 6 (TRAF6) after 24 h of BE incubation,Western blot assay was used to detect the expression levels of MYD88,IκBα,NF-κB p65,and p-NF-κB p65 after 24 h of BE incubation.RESULTS ① The maximum non-toxic concentration of BE towards MA104 cells was 1 μmol·L-1,and TC50 was 5.795 μmol·L-1.The concentrations of BE in the anti-RV experiments ranged from 0.03125μmol·L-1 to 1μmol·L-1.② In the anti-RV biosynthesis experiment,the inhibition rates of BE for RV-Wa between 0.0625 and 1 μmol·L-1 exceeded 50％,EC50 was 0.0485 μmol·L-1,and the value of TI was 119.48.The inhibition rates of BE for RV-SA-11 between 0.25 and 1 μmol·L-1 were above 50％,EC50 was 0.1226 μmol·L-1,and the value of TI was 47.27.In contrast,the effects of BE on anti-RV adsorption and direct inhibition of RV were not obvious.③ Compared with the RV group,BE inhibited the expression of VP6 (P＜0.01).④ Compared with the RV group,BE reduced the concentrations of IL-6,IL-1β and TNF-α(P＜0.01),but increased the concentrations of IL-10 and IFN-γ(P＜0.01).⑤Compared with the RV group,BE reduced the mRNA levels of TLR4,MYD88 and TRAF6 (P＜0.01),decreased the protein expression levels of MYD88 and p-NF-κB p65,and increased those of IκBα and NF-κB p65 (P＜0.01).CONCLUSION BE has anti-RV biosynthesis effect,and it may reduce inflammatory response caused by RV infection via TLR4/MYD88/NF-κB signaling pathway.

Intestinal stenosis is a common complication of inflammatory bowel disease (IBD) . Over 50% of Crohn′s disease (CD) patients develop to stricturing or penetrating phenotypes within 20 years of diagnosis. In ulcerative colitis (UC) patients, the incidence of stenosis varies from 2% to 11%. The occurrence of stenosis serves as an independent risk factor for surgery in CD and increases the risk of cancer in UC. Despite the increasing administration of biologic therapies, the progression from inflammatory phenotype to complicated phenotype has not decreased. This review summarizes the recent advances in the management of intestinal stricture in IBD, aiming to provide new insights.

Intestinal stenosis is a common complication of inflammatory bowel disease (IBD) . Over 50% of Crohn′s disease (CD) patients develop to stricturing or penetrating phenotypes within 20 years of diagnosis. In ulcerative colitis (UC) patients, the incidence of stenosis varies from 2% to 11%. The occurrence of stenosis serves as an independent risk factor for surgery in CD and increases the risk of cancer in UC. Despite the increasing administration of biologic therapies, the progression from inflammatory phenotype to complicated phenotype has not decreased. This review summarizes the recent advances in the management of intestinal stricture in IBD, aiming to provide new insights.

OBJECTIVE To investigate the effect of betulin (BE) on the replication of rotavirus (RV) in vitro.METHODS ①MA104 cells were intervened with BE between 0.03125 and 64μmol·L-1 for 72 h,and MTT assay was used to detect the cell survival.② MA104 cells were infected with RV including Wa strains and SA-11 strains to establish a viral model.MA104 cells were divided into the cell control group,RV group and RV+BE groups.The cytopathic effect (CPE) method combined with MTT assay was used to detect the effect of BE on anti-RV adsorption,anti-RV biosynthesis and direct inhibition of RV.③The grouping was the same as in②,and RT-qPCR,Western blot and IF methods were used to detect the expression of RV structural protein VP6 after 24 h of BE incubation.④The grouping was the same as in②,and the ELISA kit was used to detect the concentrations of pro-inflammatory factors IL-6,IL-1β and TNF-α,anti-inflammatory factor IL-10 and type Ⅱ interferon IFN-γ in the cell supernatant after 24 h of BE incubation.⑤The grouping was the same as in②,and qPCR assay was used to detect the mRNA expression levels of Toll-like receptor 4 (TLR4),myeloid differentiation factor 88 (MYD88) and TNF receptor-associated factor 6 (TRAF6) after 24 h of BE incubation,Western blot assay was used to detect the expression levels of MYD88,IκBα,NF-κB p65,and p-NF-κB p65 after 24 h of BE incubation.RESULTS ① The maximum non-toxic concentration of BE towards MA104 cells was 1 μmol·L-1,and TC50 was 5.795 μmol·L-1.The concentrations of BE in the anti-RV experiments ranged from 0.03125μmol·L-1 to 1μmol·L-1.② In the anti-RV biosynthesis experiment,the inhibition rates of BE for RV-Wa between 0.0625 and 1 μmol·L-1 exceeded 50％,EC50 was 0.0485 μmol·L-1,and the value of TI was 119.48.The inhibition rates of BE for RV-SA-11 between 0.25 and 1 μmol·L-1 were above 50％,EC50 was 0.1226 μmol·L-1,and the value of TI was 47.27.In contrast,the effects of BE on anti-RV adsorption and direct inhibition of RV were not obvious.③ Compared with the RV group,BE inhibited the expression of VP6 (P＜0.01).④ Compared with the RV group,BE reduced the concentrations of IL-6,IL-1β and TNF-α(P＜0.01),but increased the concentrations of IL-10 and IFN-γ(P＜0.01).⑤Compared with the RV group,BE reduced the mRNA levels of TLR4,MYD88 and TRAF6 (P＜0.01),decreased the protein expression levels of MYD88 and p-NF-κB p65,and increased those of IκBα and NF-κB p65 (P＜0.01).CONCLUSION BE has anti-RV biosynthesis effect,and it may reduce inflammatory response caused by RV infection via TLR4/MYD88/NF-κB signaling pathway.

A 66-year-old female patient with infiltrating adenocarcinoma in left lung received anlotinib 12 mg orally once daily (2-week medication followed by 1-week discontinuation, 3 weeks was a cycle). After 14 months of regular medication, the patient developed palpitation and chest tightness. Laboratory tests showed that the N-Terminal pro-brain natriuretic peptid (NT-proBNP) was 1 698 ng/L; echocardiography showed decreased apical wall motion and left ventricular diastolic dysfunction. Heart failure was condsidered, which was suspected to be related to anlotinib. Anlotinib was stopped and symptomatic treatments were given. Eight days later, her symptoms above-mentioned were alleviated and NT-proBNP was 485 ng/L. Because of the illness condition, the patient took anlotinib again at original dose according to the doctor′s instructions. Three months later, the above symptoms recurred and ventricular fibrillation occurred suddenly. Considering that the heart failure in the patient might be caused by anlotinib. Anlotinib was stopped again. After 11 days of treatments with diuretics, cardiac function improvement, myocardial nutrition, and potassium supplement, the patient′s condition was improved obviously. After that, the patient did not take anlotinib again.

Objective:To investigate the risk factors for hepatocellular carcinoma (HCC) after sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection.Methods:Patients with chronic HCV infection who were treated in Tianjin Second People′s Hospital from January 2012 to April 2019 were enrolled and the incidence of new HCC was retrospectively analyzed. Cox proportional hazards model was used to analyze the risk factors for HCC.Results:Among the 644 patients with chronic HCV infection, 421 cases (65.4%) had chronic hepatitis C(CHC), 223 cases (34.6%) had hepatitis C cirrhosis, and 34 cases had new HCC. No patient without cirrhosis developed HCC. Cox proportional hazards multivariate analysis showed that Child-Pugh grade B or above (hazard ratio ( HR)=6.050, 95% confidence interval ( CI) 2.658 to 13.771, P<0.001), drinking history ( HR=3.077, 95% CI 1.428 to 6.634, P=0.004), family history of cancer ( HR=2.376, 95% CI 1.155 to 4.888, P=0.019), age≥60 years old ( HR=3.301, 95% CI 1.563 to 6.974, P=0.002), controlled attenuation parameter>292 dB/m ( HR=3.842, 95% CI 1.543 to 9.565, P=0.004) were risk factors for HCC. Conclusions:Patients with CHC, especially cirrhosis, are still at risk of HCC post-SVR. HCC monitoring should be strengthened for individuals over 60 years of age, Child-Pugh grade B or above, with severe fatty liver disease, drinking history or family history of malignancy.

A 66-year-old female patient with infiltrating adenocarcinoma in left lung received anlotinib 12 mg orally once daily (2-week medication followed by 1-week discontinuation, 3 weeks was a cycle). After 14 months of regular medication, the patient developed palpitation and chest tightness. Laboratory tests showed that the N-Terminal pro-brain natriuretic peptid (NT-proBNP) was 1 698 ng/L; echocardiography showed decreased apical wall motion and left ventricular diastolic dysfunction. Heart failure was condsidered, which was suspected to be related to anlotinib. Anlotinib was stopped and symptomatic treatments were given. Eight days later, her symptoms above-mentioned were alleviated and NT-proBNP was 485 ng/L. Because of the illness condition, the patient took anlotinib again at original dose according to the doctor′s instructions. Three months later, the above symptoms recurred and ventricular fibrillation occurred suddenly. Considering that the heart failure in the patient might be caused by anlotinib. Anlotinib was stopped again. After 11 days of treatments with diuretics, cardiac function improvement, myocardial nutrition, and potassium supplement, the patient′s condition was improved obviously. After that, the patient did not take anlotinib again.

Objective To analyze the pathogenic characteristics of sepsis in patients with hepatic failure, and to explore the risk factors for sepsis in patients with liver failure. Methods The data of 221 patients with hepatic failure admitted to Tianjin Second People's Hospital from January 2014 to December 2018 were retrospectively collected. The patients were divided into two groups according to whether they suffered from sepsis or not. The pathogeny results of blood culture in patients with sepsis were observed. The levels of white blood cell (WBC), neutrophil (Neut), platelet (PLT), lactic acid (Lac), C-reactive protein (CRP) and procalcitonin (PCT) were compared between the two groups. The risk factors for sepsis in patients with hepatic failure were analyzed by multivariate Logistic regression analysis. Results Among 221 patients, 27 cases had incomplete data and were excluded. Finally, 194 cases were enrolled in the analysis, including 52 in sepsis group and 142 in non-sepsis group. From 2014 to 2018, there were 11, 12, 11, 11 and 8 positive cases of sepsis in patients with liver failure. The positive rate of Gram-positive (G+) bacteria increased year by year (2, 3, 4, 5 and 4 cases of G+ bacteria from 2014 to 2018). There was no significant difference in demographic and medical history data, such as gender, age and history of diabetes mellitus between the two groups. Compared with non-sepsis group, Neut, Lac, CRP and PCT in sepsis group were significantly increased [Neut:0.81±0.09 vs. 0.74±0.15, Lac (mmol/L): 3.04±0.61 vs. 2.00±0.43, CRP (mg/L): 44.09±8.37 vs. 40.54±8.37, PCT (μg/L): 0.34±0.12 vs. 0.31±0.11], with significant differences (all P < 0.05). But there was no statistical difference in WBC or PLT between the two groups. The multivariate Logistic regression model incorporated the indicators with statistical significance in univariate analysis. The results showed that Lac was an independent factor of sepsis in patients with hepatic failure [odds ratio (OR) = 58.286, 95% confidence interval (95%CI) = 16.633-204.247, P =0.000]. Conclusions For patients with hepatic failure infection, the ratio of G+ bacteria increased year by year. Elevated Lac is an independent risk factor for sepsis in patients with liver failure.

Objective To investigate the effects of cardioplegic solution containing different concentrations of emulsified isoflurane on myocardial ischemia-reperfusion injury in isolated rat hearts. Methods Fifty-six male SD rats, weighing 180-250 g, were anesthetized with intraperitoneal 20% urethane 1 g/kg and heparin 1 000 U/kg. Their hearts were excised and perfused in a Langendorff apparatus. Fifty-six isolated hearts were randomly divided into 7 groups ( n = 8 each) : St. Thomas cardioplegic solution group (group C) and St. Thomas cardioplegic solution containing 6 different concentrations of emulsified isoflurane groups (group E1-6 ). After 20 min equilibration, cardiac arrest was induced with St. Thomas cardioplegic solution 20 ml and St. Thomas cardioplegic solution containing 0.28, 0.56, 1.12, 1.68, 2.24 and 2.80 mmol/L emulsified isoflurane 20 ml at 4℃for 45 min followed by 60 min reperfusion in group C and E1-6 respectively. HR, left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP) and + dp/dtmax were recorded at the end of 20 min equilibration, 20, 40 and 60 min of reperfusion. Coronary effluent 1.5 ml was collected for determination of LDH and SOD activity and the concentration of cTnI. At the end of 60 min reperfusion, the area of myocardial infarction was calculated. Results Compared with group C, HR, LVDP, + dp/dtmax and SOD activity were significantly higher, LVEDP, LDH activity and cTnI concentration lower, and the area of myocardial infarction lower in group E4, and HR, LVDP, + dp/dtmax and SOD activity were significantly lower, LVEDP, LDH activity and cTnI concentration higher, and the area of myocardial infarction higher in group E6 and E6 ( P < 0.05) , but there was no significant difference in the above indices between group E1-3 and group C ( P > 0.05) . HR, LVDP, + dp/dtmax and SOD activity were significantly lower, LVEDP, LDH activity and cTnI concentration higher, and the area of myocardial infarction higher in group E1-3-5-6 than in group E4 (P < 0.05 ). Conclusion St. Thomas cardioplegic solution containing 1.68 mmol/L emulsified isoflurane can attenuate myocardial ischemia-reperfusion injury in isolatede rat hearts.