Animals ; Intestines ; cytology ; drug effects ; physiology ; Meperidine ; pharmacology ; Mice ; Mice, Inbred Strains ; Muscle, Smooth ; drug effects ; physiology ; Rabbits

Objective:To analyze the effect of nucleos(t)ide analog (NAs) antiviral treatment on the clinical features and prognosis of patients with hepatitis B virus-related hepatocellular carcinoma (HBV-HCC).Methods:A retrospective analysis was performed on the data of 450 HBV-HCC patients first diagnosed and treated in the Third Hospital of Hebei Medical University from January 2015 to January 2021, including 193 patients in the continuous NAs treatment group and 257 patients in the NAs treatment after hepatocellular carcinoma (HCC) group. The baseline data of the two groups were balanced by propensity score matching. The relapse-free survival rate of HCC was estimated by Kaplan-Meier method, and the risk factors for HCC recurrence were analyzed by Cox proportional risk models. Spearman correlation analysis was used to explore the association between clinical features of HCC and hepatitis B virus (HBV) DNA load in patients receiving continuous NAs treatment.Results:Before matching, the proportions of liver cirrhosis, body mass index≥25.0 kg/m 2, single tumor, maximum tumor diameter ≤5 cm, Child-Pugh grade A, China liver cancer staging Ⅰ in the continuous NAs treatment group were 93.8%(181/193), 45.1%(87/193), 70.5%(136/193), 82.4%(159/193), 74.6%(144/193) and 74.6%(144/193), respectively. All of them were higher than those in the NAs treatment after HCC group (87.5%(225/257), 44.0%(113/257), 61.1%(157/257), 55.3%(142/257), 63.8%(164/257) and 56.0%(144/257), respectively). The proportions of drinking history and portal vein tumor thrombi in the continuous NAs treatment group were 12.4%(24/193) and 3.1%(6/193), respectively, which were lower than 33.9%(87/257) and 10.5%(27/257) in the NAs treatment after HCC group.The differences were all statistically significant ( χ2=4.86, 7.58, 4.27, 36.63, 8.15, 21.05, 27.21 and 8.88, respectively, all P<0.05). After matching, the median relapse-free survival time of the patients in the continuous NAs treatment group and the NAs treatment after HCC group were 388 days and 277 days, respectively. The five-year cumulative relapse-free survival rates were 50.0% and 37.5%, respectively, with statistically significant difference ( χ2=5.30, P=0.021). Multivariate analysis showed that no antiviral therapy before diagnosis of HCC, multiple tumors, maximum tumor diameter ≥5 cm and palliative treatment were independent risk factors for HBV-HCC recurrence (hazard ratio ( HR)=1.509, 1.491, 0.446 and 1.472, respectively, all P<0.05). After matching, the maximum tumor diameter ( r=0.175, P=0.042), incidence of portal vein tumor thrombi ( r=0.210, P=0.014) and recurrence of HBV-HCC ( r=0.178, P=0.038) in the continuous NAs treatment group were positively correlated with HBV DNA load. Conclusions:Early initiation of NAs antiviral treatment can improve the tumor characteristics when the disease progresses to HBV-HCC, and improve the relapse-free survival rate of HBV-HCC patients. No antiviral therapy before diagnosis of HCC, multiple tumors, maximum tumor diameter ≥5 cm and palliative treatment are independent risk factors for HBV-HCC recurrence.

Molecular targeted drugs are one of the treatments for hepatocellular carcinoma (HCC), the primary factor influencing their therapeutic efficacy is drug resistance. Diminished drug intake, greater efflux, improved DNA damage repair capacity, aberrant signal pathways, hypoxia, epithelial-mesenchymal cell transition, and the cellular autophagy system are summarized herein as aspects of the drug resistance mechanism. Simultaneously, effective strategies for addressing drug resistance are elaborated, providing ideas for better clinical treatment of HCC.

Systemic treatment, including molecular targeted therapy, immunotherapy, and chemotherapy, is an important means of achieving long-term survival in patients with intermediate-and advanced-stage liver cancer. However, some patients are insensitive to treatment and even develop drug resistance. Mitochondria are the center of cellular energy metabolism and, at the same time, are the priority targets for systemic therapy. Mitochondrial homeostasis plays an important role in the treatment of liver cancer. The relationship between the two advances is elucidated so as to provide better ideas for the clinical treatment of liver cancer.

Hepatocellular carcinoma is one of the most common malignant tumors in the world, which is a serious threat to human health. HBV infection is one of the most common causes of hepatocellular carcinoma.The diagnosis of most hepatocellular carcinoma has progressed to the middle and late stage, and the prognosis is poor. Early detection, diagnosis and treatment are important supports to improve the clinical outcome of hepatocellular carcinoma. In recent years, scholars at home and abroad have established various hepatocellular carcinoma risk prediction models, which are conducive to improving the early diagnosis rate of hepatocellular carcinoma and reducing the mortality rate. This article reviews the risk factors and risk prediction models of chronic hepatitis B associated hepatocellular carcinoma, in order to provide reference for HBV-associated liver cancer risk monitoring and management decision.

Objective:To understand the common viral infection among the surveillance cases of fever respiratory syndrome (FRS) in nine provinces in China.Methods:The research data were obtained from nine provinces (Anhui, Beijing, Guangdong, Hebei, Hunan, Jilin, Shandong, Shaanxi and Xinjiang) in the "Infectious Disease Surveillance Technology Platform Information Management System" of the Chinese Center for Disease Control and Prevention from January 2009 to June 2021. Finally, 8 243 FRS cases with nucleic acid detection results of eight viruses [human influenza virus (HIFV), human respiratory syncytial virus (HRSV), human adenovirus (HAdV), human parainfluenza virus (HPIV), human rhinovirus (HRV), human metapneumovirus (HMPV), human coronavirus (HCoV) and human Boca virus (HBoV)] were included in the study. The χ 2 test/Fisher exact probability method was used to analyze the difference of virus detection rate in different age groups, regions and seasons. Results The M ( Q1, Q3) age of 8 243 FRS cases was 4 (1, 18) years old, and 56.56% (4 662 cases) were children under 5 years old. Males accounted for 58.1% (4 792 cases) of all cases. All cases were from outpatient/emergency department (2 043 cases) and inpatient department (6 200 cases). The virus detection rates of FRS cases from high to low were HRSV, HIFV, HPIV, HRV, HAdV, HMPV, HCoV and HBoV. Two or more viruses were detected simultaneously in 524 cases, accounting for 15.66% of virus-positive cases. The difference of the virus detection rate in different age groups was statistically significant (all P values<0.05), and the virus detection rate in children<5 years old was higher (49.96%). The positive rate of any virus in south China was higher than that in north China ( P<0.001). The virus-positive FRS cases were detected throughout the year. The detection rate of HRSV was higher in autumn and winter. The detection rate of HIFV was higher in winter. The detection rate of HMPV was higher in winter and spring. The detection rates of HPIV, HRV, HCoV and HBoV were higher in summer and autumn, while there was no significant difference in the detection rate of HAdV in different seasons. Compared with 2009-2019, the detection rate of any virus in 2020-2021 decreased from 41.37% to 37.86%. The detection rate of HIFV decreased sharply from 10.62% to 1.37%. The detection rate of HPIV decreased from 8.24% to 5.88%. The detection rate of HRV and HBoV increased from 5.43% and 1.79% to 9.67% and 3.19%, respectively. Conclusion:HRSV and HIFV infections are more common among FRS cases in nine provinces in China from 2009 to 2021, and the epidemiological characteristics of eight common respiratory viruses vary in different age groups, regions and seasons.

Objective:To understand the common viral infection among the surveillance cases of fever respiratory syndrome (FRS) in nine provinces in China.Methods:The research data were obtained from nine provinces (Anhui, Beijing, Guangdong, Hebei, Hunan, Jilin, Shandong, Shaanxi and Xinjiang) in the "Infectious Disease Surveillance Technology Platform Information Management System" of the Chinese Center for Disease Control and Prevention from January 2009 to June 2021. Finally, 8 243 FRS cases with nucleic acid detection results of eight viruses [human influenza virus (HIFV), human respiratory syncytial virus (HRSV), human adenovirus (HAdV), human parainfluenza virus (HPIV), human rhinovirus (HRV), human metapneumovirus (HMPV), human coronavirus (HCoV) and human Boca virus (HBoV)] were included in the study. The χ 2 test/Fisher exact probability method was used to analyze the difference of virus detection rate in different age groups, regions and seasons. Results The M ( Q1, Q3) age of 8 243 FRS cases was 4 (1, 18) years old, and 56.56% (4 662 cases) were children under 5 years old. Males accounted for 58.1% (4 792 cases) of all cases. All cases were from outpatient/emergency department (2 043 cases) and inpatient department (6 200 cases). The virus detection rates of FRS cases from high to low were HRSV, HIFV, HPIV, HRV, HAdV, HMPV, HCoV and HBoV. Two or more viruses were detected simultaneously in 524 cases, accounting for 15.66% of virus-positive cases. The difference of the virus detection rate in different age groups was statistically significant (all P values<0.05), and the virus detection rate in children<5 years old was higher (49.96%). The positive rate of any virus in south China was higher than that in north China ( P<0.001). The virus-positive FRS cases were detected throughout the year. The detection rate of HRSV was higher in autumn and winter. The detection rate of HIFV was higher in winter. The detection rate of HMPV was higher in winter and spring. The detection rates of HPIV, HRV, HCoV and HBoV were higher in summer and autumn, while there was no significant difference in the detection rate of HAdV in different seasons. Compared with 2009-2019, the detection rate of any virus in 2020-2021 decreased from 41.37% to 37.86%. The detection rate of HIFV decreased sharply from 10.62% to 1.37%. The detection rate of HPIV decreased from 8.24% to 5.88%. The detection rate of HRV and HBoV increased from 5.43% and 1.79% to 9.67% and 3.19%, respectively. Conclusion:HRSV and HIFV infections are more common among FRS cases in nine provinces in China from 2009 to 2021, and the epidemiological characteristics of eight common respiratory viruses vary in different age groups, regions and seasons.

Objective: To analyze the epidemiological characteristics and the molecular types of human adenovirus (HAdV) from influenza-like illness (ILI) samples with negative influenza virus in Xi'an from January 2013 to December 2015. Methods: Samples from patients with ILI were collected from two national influenza sentinel surveillance hospitals during 2013—2015 in Xi′an. HAdV was detected by real-time PCR, and then the positive samples were inoculated into Hep-2 cells to isolate the viruses. The amplified products were purified and sequenced of hexon gene, and the sequences were compared with the Genebank data and phylogenetic trees were constructed. Results: In 2367 samples, 88 samples were positive for HAdV, the positive rate was 3.72%. There were 7 subtypes detected, and the rates of each subtype are as follows: HAdV-1 was 9.09%, HAdV-2 was 22.73%, HAdV-3 was 23.86%, HAdV-4 was 5.68%, HAdV-5 was 7.95%, HAdV-6 was 3.41% and HAdV-7 was 1.14%. Males had higher infection rate than females, but there was no significant difference. The patients were divided into 6 groups according to age. There were 3 positive samples among those under 1 year of age, 36 positive samples among those 1 to 3 years old, 26 positive samples among those 4 to 6 years old, 16 positive samples in those 7 to 18 years old, 5 positive samples in 19 to 59 years old and 2 positive samples in those older than sixty years of age. HAdV infection was primarily confined to children under 7 years of age. Conclusions HAdV-3 and HAdV-2 were the dominant epidemic strains during 2013—2015 in Xi′an. Children younger than 7 years were the main susceptible population. HAdV infections circulate all year-round and there was no considerable seasonal variation.

Objective: To explore the risk factors for prognosis in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), and to establish a prognostic model. Methods: A total of 193 patients diagnosed with HBV-ACLF who were admitted to the Department of Infectious Diseases of the Third Hospital of Hebei Medical University were collected from 1st January 2013 to 1st November 2018 as a derivation cohort. Thirty-five patients diagnosed with HBV-ACLF who were admitted to the Fifth Hospital of Shijiazhuang during the period from 1st July 2017 to 1st November 2018 were collected as a validation cohort. The survival condition of all patients at week 12 of admission was observed. The risk factors associated with short-term prognosis were analyzed by using multivariate logistic regression analysis, and a logistic regression equation prediction model was established and verified. The diagnostic performance of the prognostic model was evaluated using the receiver operating characteristic (ROC) curve, and was compared with model for end-stage liver disease (MELD) scoring system, Child-Turcotte-Pugh (CTP) scoring system, sequential organ failure assessment (SOFA) scoring system and chronic liver failure (CLIF)-SOFA scoring system. Results: Multivariate logistic regression analysis showed that age (odds ratio(OR)=2.133, 95% confidence interval(CI)1.033-4.405), total bilirubin (OR=3.371, 95%CI 1.610-7.060), serum creatinine (OR=4.448, 95%CI 1.697-11.661), hepatic encephalopathy (OR=5.313, 95%CI 2.463-11.461), and ascites (OR=2.959, 95%CI 1.410-6.210) were independent risk factors for predicting the short-term prognosis of patients with HBV-ACLF. The newly established logistic regression model (LRM)=-1.726+ 0.757×age+ 1.215×total bilirubin+ 1.049 2×serum creatinine+ 1.670×hepatic encephalopathy (with=1, without=0) + 1.085×ascites (with=1, without=0). The area under the ROC curve of the LRM for predicting the short-term prognosis of patients with HBV-ACLF was 0.82 (95%CI 0.76-0.88). Furthermore, the areas under the ROC curve of the models of MELD, CTP, SOFA, CLIF-SOFA were 0.67 (95%CI 0.60-0.75), 0.73 (95%CI 0.66-0.80), 0.77 (95%CI 0.70-0.83) and 0.72 (95%CI 0.65-0.80), respectively. The ROC-area under curve of the validation cohort was 0.81 (95%CI 0.65-0.97). Conclusions Age, total bilirubin, serum creatinine, hepatic encephalopathy, and ascites are independent risk factors for the prognosis of HBV-ACLF. The prognostic model established based on these factors can accurately predict the patients′ short-term prognosis, which is superior to MELD, CTP, SOFA and CLIF-SOFA.