Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Immune response occurs in a variety of cellular stresses that severely disrupt function of endoplasmic reticulum(ER),leading to accumulation of misfolded or unfolded protein in ER lumen,resulting in endoplasmic reticulum stress(ERS).ERS triggers unfolded protein response to restore ER homeostasis,but its duration is too long and can lead to cell apoptosis.Although sus-tained ERS can lead to an increase in pro-inflammatory cytokines that induce inflammatory responses and activate immune responses,causal relationship between ERS and immune responses has not been established.This review summarizes role of ERS in inducing im-mune cell differentiation,cytokine expression and immune function,and further illustrates regulatory role of ERS in pathogenesis of immune disorders,which is helpful to explore new therapies for ERS-related diseases.

Hepatogenous diabetes (HD) is a common complication of end-stage liver disease, and many studies have confirmed its adverse effect on prognosis. In recent ten years, a great number of studies have been conducted on the pathogenesis of HD and some progress has been made. This article reviews the research advances in the pathogenesis of HD, in order to provide a reference for the diagnosis and treatment of HD by clinicians.

Both diabetes mellitus and liver cirrhosis have high incidence rate and mortality rate around the world, and in recent ten years, scholars in China and globally have conducted many studies on the association between diabetes mellitus and liver cirrhosis. This article systematically reviews the advances in the basic and clinical research on the influence of diabetes mellitus on liver cirrhosis and its complications and summarizes possible mechanisms. The results show that diabetes mellitus can accelerate the process of liver fibrosis, increase the risk of complications and progression to liver cancer in patients with liver cirrhosis, and reduce their survival rate.

OBJECTIVE: To analyze the clinical phenotype of a Chinese pedigree affected with Tuberous sclerosis complex (TSC) and explore pathogenic mutations of TSC1 and TSC2 gene. METHODS: Unique clinical phenotypes，the results of imaging, examination of the proband and special family history, collectively, made the constellation of features of TSC. Genomic DNA was obtained from six affected and eight unaffected members of the family and potential mutations of the TSC1 and TSC2 genes were detected by PCR-amplification of the exons and exon-intron boundaries and direct sequencing. A total of 150 normal unrelated individuals were used as controls. RESULTS: Genetic analysis documented the presence of a heterozygous mutation, c.1781_1782delTG (p.Val594GlyfsX11), in the exon 15 of TSC1 gene within all the patients of the family. This mutation was not observed in the eight unaffected family members or in the 150 unrelated control subjects from the same population , or the Human Gene Mutation Database (HGMD) and had completely co-segregated with the disease phenotype in the family. CONCLUSION The c.1781_1782delTG mutation of TSC1 gene may be responsible for the tuberous sclerosis complex in this family. The data presented in the present study are of significance to clinicians, as well as genetic counselors, and may provide new clues for molecular diagnosis of this disease．.
DNA Mutational Analysis ; Humans ; Mutation ; Pedigree ; Tuberous Sclerosis ; genetics ; Tuberous Sclerosis Complex 1 Protein ; genetics ; Tuberous Sclerosis Complex 2 Protein

Objective: To analyze the clinical phenotype of a Chinese pedigree affected with Tuberous sclerosis complex(TSC) and explore pathogenic mutations of TSC1 and TSC2 gene. Methods: Unique clinical phenotypes, the results of imaging, examination of the proband and special family history, collectively, made the constellation of features of TSC.Genomic DNA was obtained from six affected and eight unaffected members of the family and potential mutations of the TSC1 and TSC2 genes were detected by PCR-amplification of the exons and exon-intron boundaries and direct sequencing.A total of 150 normal unrelated individuals were used as controls. Results: Genetic analysis documented the presence of a heterozygous mutation, c. 1781_1782delTG (p.Val594GlyfsX11), in the exon 15 of TSC1 gene within all the patients of the family. This mutation was not observed in the eight unaffected family members or in the 150 unrelated control subjects from the same population , or the Human Gene Mutation Database(HGMD)and had completely co-segregated with the disease phenotype in the family. Conclusions The c. 1781_1782delTG mutation of TSC1 gene may be responsible for the tuberous sclerosis complex in this family. The data presented in the present study are of significance to clinicians, as well as genetic counselors, and may provide new clues for molecular diagnosis of this disease.

Objective To investigate the preoperative risk factors of occurrence of intra-operative ventricular fibrillation (VF) in patients with acute inferior myocardial infarction undergoing emergency percutaneous coronary intervention(PCI). Methods A retrospective approach was conducted, 572 patients with acute inferior myocardial infarction admitted to Cangzhou City People's Hospital from May 2016 to May 2018 were enrolled, and they were divided into VF group (50 cases) and non-VF group (520 cases) according to whether the intra-operative complication of VF occurred. The clinical data of the two groups of patients were collected, and the related risk factors were analyzed by univariate and multivariate analyses to explore the preoperative risk factors related to VF intra-operative occurrence in patients with acute inferior myocardial infarction undergoing emergency PCI; the receiver operating characteristic (ROC) curve was drawn to evaluate the test efficiencies of all kinds of risk factors. Results The univariate analysis showed that the ratio of Killip > Ⅰ grade, infarct area size/blood potassium concentration (IS/[K]) and symptom onset to balloon dilatation time (SOTBT) in the VF group were significantly higher than those in the non-VF group [Killip > Ⅰ grade:36.5% (19/52) vs. 24.0% (125/520), IS/[K]: 3.2±0.3 vs. 2.5±0.8, SOTBT (hours): 6.3 (2.1, 8.0) vs. 4.6 (1.8, 6.5)], the differences were statistically significant (all P < 0.05); the T wave peak to T end interval/QT interval (Tp-e/QT) and blood potassium level of the VF group were significantly lower than those of the non-VF group [Tp-e/QT: 0.3±0.1 vs. 0.4±0.1; blood potassium (mmol/L): 2.8±0.5 vs. 4.1±1.2, both P < 0.05]. Multivariate logistic regression analysis showed that the SOTBT > 6 hours [odds ratio (OR) = 8.337], Killip >Ⅰ grade (OR = 1.721), hypokalemia (OR = 1.031) and high IS/[K] (OR = 9.167) were independent risk factors for intra-operative occurrence of VF in patients with acute inferior myocardial infarction during emergency PCI (all P < 0.05). ROC curve analysis showed that the area under the ROC curve (AUC) of serum potassium, IS/[K], SOTBT > 6 hours and Killip > Ⅰ grade for predicting the intra-operative occurrence of VF during emergency PCI for patients with acute inferior myocardial infarction had certain values, their AUC were 0.633, 0.837, 0.821, 0.682, respectively, suggesting that IS/[K] and SOTBT > 6 hours had moderate predictive values, and serum potassium, Killip > Ⅰ grade had relatively low predicative values; when the optimal cut-off value of IS/[K] was 2.8, the sensitivity was 85.5% and the specificity was 80.0%. Conclusion SOTBT > 6 hours, Killip > Ⅰ grade, hypokalemia, and high IS/[K] are independent risk factors of intra-operative occurrence of VF in patients with acute inferior myocardial infarction undergoing emergency PCI.

Objective To explore the possible causative factors of appearance of ventricular fibrillation (VF) during emergency percutaneous coronary intervention (PCI) in patients with acute inferior myocardial infarction. Methods Five hundred and seventy two patients with acute inferior myocardial infarction who underwent emergency PCI 24 hours after onset from May 2016 to May 2018 in Cangzhou People's Hospital were enrolled, they were divided into a VF group (52 cases) and a non-VF group (NVF, 520 cases) according to whether VF occurred or not during PCI. The differences in clinical data, characteristics of coronary artery disease and coronary artery score (Gensini score) between the two groups were compared; multivariate Logistic regression analysis was used to analyze the risk factors related to the occurrence of VF during emergency PCI; the receiver operating characteristic curve (ROC) was drawn to evaluate the efficacy of each risk factor. Results There were no statistical significant differences in sex, age, past histories of drinking alcohol, smoking, hypertension, diabetes, previous use of β blockers, aspirin, the peak values at admission of systolic blood pressure, heart rate, creatine kinase isoenzyme (CK-MB) and cardiac troponin I (cTnI), etc between the two groups (all P > 0.05). The proportions of patients with grade 0 blood flow in myocardial infarction thrombolysis (TIMI) before recanalization, with high thrombus load, criminal vessels being right coronary artery (RCA) and proximal segment of RCA, Gensini score in VF group were significantly higher than those in NVF group [TIMI 0: 80.8% (42/52) vs. 58.1% (302/520), high thrombus load: 71.2% (37/52) vs. 58.1% (302/520), criminals being RCA: 84.6% (44/52) vs. 73.7% (383/520), the occlusion site of infarction-related artery (IRA) being the proximal segment of RCA: 61.5% (32/52) vs. 41.2% (214/520), Gensini scores: 93.84±16.48 vs. 61.37±20.01, all P < 0.05]. The multiple logistic regression analysis showed that the risk factors for VF occurrence during emergency PCI for patients with acute inferior myocardial infarction included the criminals being RCA [odds ratio (OR) = 1.967, 95% confidence interval (95% CI) = 1.696-3.015, P =0.032], TIMI blood flow grade 0 before re-canalization (OR = 3.032, 95%CI = 1.248-3.675, P = 0.043), the occlusion site of infarction-related artery (IRA) being the proximal segment of RCA (OR = 2.288, 95%CI = 1.458-3.895, P =0.024), Gensini score (OR = 6.558, 95%CI = 2.168-13.359, P = 0.001] and high thrombus load (OR = 1.781, 95%CI =1.016-3.017, P = 0.033); they all were risk factors of occurrence of ventricular fibrillation during emergency PCI in patients with acute inferior myocardial infarction (all P < 0.05). ROC curve analysis showed that TIMI blood flow grade 0 before re-canalization, Gensini score and higher thrombus load had certain predictive value for VF occurrence during emergency PCI for acute inferior wall myocardial infarction; the area under ROC curve (AUC) was 0.613, 0.869 and 0.605, and 95% CI was 0.540-0.687, 0.787-0.969 and 0.521-0.675, the P value was 0.007, 0.000 and 0.012, respectively, suggesting that Gensini score had moderate predictive value for intra-operative VF, while the predictive values of TIMI blood flow grade 0 before re-canalization and higher thrombus load were relatively low. When the Gensini score had an optimal cutoff value of 96.50, the sensitivity was 85.50% and the specificity was 81.20%. Conclusion The risk factors of VF occurrence in emergency PCI for patients with acute inferior myocardial infarction are criminal vessel RCA, TIMI blood flow grade 0 before re-canalization, IRA occlusion site being proximal segment of RCA, Gensini score and high thrombus load; pre-recanalization TIMI blood flow grade 0, Gensini score and higher thrombus load all have certain predictive value for the occurrence of VF in emergency PCI for acute inferior myocardial infarction.

Objective To investigate the prognostic risk factors of patients with acute inferior myocardial infarction and intra-operative occurrence of ventricular fibrillation (VF) when undergoing emergency percutaneous coronary intervention (PCI). Methods The data of 52 patients with acute inferior myocardial infarction treated in Cangzhou City People's Hospital from May 2016 to May 2018 were retrospectively analyzed, and they were divided into poor prognosis group (19 cases) and good prognosis group (33 cases) according to whether cardiovascular events occurred during 1 year of follow-up. The patients' gender, age, smoking or not, histories of diabetes, hypertension, hyperlipidemia, and the results of well performed color echocardiography within recent 3 days, such as left ventricular ejection fraction (LVEF), cardiac infarction size (IS), and coronary Gensini score were recorded in the two groups; the indicators with statistical significance in univariate analysis were included in the multivariate logistic regression analysis to screen out the prognostic risk factors of patients with acute inferior wall myocardial infarction undergoing emergency PCI and occurrence of intra-operative VF; Receiver operating characteristic (ROC) curve was drawn to evaluate the values of coronary Gensini score and IS in predicting intraoperative occurrence of VF in patients with acute inferior wall myocardial infarction undergoing emergency PCI. Results During 1-year follow-up, 19 of 52 patients with acute inferior myocardial infarction occurred VF, the incidence being 36.5%. The univariate analysis showed that the IS and Gensini score in poor prognosis group were significantly higher than those in the good prognosis group [IS: (3.2±0.2)% vs. (2.5±0.4)%, Gensini score: 98.8±12.5 vs. 85.7±8.4, both P < 0.05], the LVEF level was significantly lower in the poor prognosis group than that in the good prognosis group (0.37±0.08 vs. 0.46±0.11, P < 0.05). The multivariate Logistic regression analysis showed that IS [odds ratio (OR) = 5.016] and coronary Gensini score (OR = 2.415) were the risk factors of occurrence of cardiovascular events after surgery in patients with acute inferior myocardial infarction and intra-operative VF when undergoing PCI (P < 0.05). The ROC curve analysis showed that IS and coronary Gensini scores had certain predictive values for the prognosis of patients with acute inferior myocardial infarction and occurrence of intra-operative VF when undergoing emergency PCI, the area under the ROC curve (AUC) was 0.863 and 0.597, respectively, indicating that IS had a medium predictive value, while the value of coronary Gensini score was lower, when the IS optimal cut off value was 3.0, the sensitivity was 89.4% and the specificity was 88.0%. Conclusion High IS and Gensini score are the risk factors of prognosis of patients with acute inferior myocardial infarction and intra-operative occurrence of VF when undergoing emergency PCI.