Background/Aims: This study assessed the long-term efficacy and safety of tenofovir alafenamide (TAF) in real-world settings. Methods: Patients who were candidates for TAF treatment and were followed up at 12-week intervals over 192 weeks were enrolled in this study. Results: One hundred and forty-four patients (50 treatment-naive and 94 treatment-experienced) were included in this study. The cumulative incidence rates of cirrhosis and hepatocellular carcinoma at 192 weeks were 3.9% and 0.7%, respectively. In treatment-naive patients, the rates of a virological response, HBeAg conversion, and HBsAg loss at 192 weeks were 100%, 33.3%, and 2%, respectively. The treatment-naive patients exhibited higher baseline HBsAg levels than the treatment-experienced patients (4.31 log10IU/mL vs. 3.97 log10IU/mL). A significant decrease in the HBsAg levels from the baseline was observed at 144 and 192 weeks in the treatment-naive patients (p=0.01). The baseline body mass index (BMI) <25 kg/m2 (p=0.02) and HBsAg <3.3 log10IU/mL (p=0.04) were identified as predictive factors for a decrease in HBsAg ≥0.5 log10IU/mL at 48 weeks. The eGFR levels were consistently lower in the treatment-experienced patients throughout the study. Although the treatment-naive patients showed no abnormal increases in urinary URBP, the treatment-experienced patients showed elevated urinary β2MG and NAG levels at the baseline, which decreased over the treatment course. The total cholesterol, triglyceride, and low-density lipoprotein levels were similar in both groups. Conclusions Prolonging the TAF treatment duration enhances the virological response rate. The decline in HBsAg levels was more significant in the treatment-naive patients than in the treatment-experienced patients. The baseline BMI <25 kg/m2 and HBsAg <3.3 log10IU/mL were predictive factors for a significant decline in HBsAg at 48 weeks. TAF has high renal safety and no significant impact on lipid levels.

Background/Aims: This study assessed the long-term efficacy and safety of tenofovir alafenamide (TAF) in real-world settings. Methods: Patients who were candidates for TAF treatment and were followed up at 12-week intervals over 192 weeks were enrolled in this study. Results: One hundred and forty-four patients (50 treatment-naive and 94 treatment-experienced) were included in this study. The cumulative incidence rates of cirrhosis and hepatocellular carcinoma at 192 weeks were 3.9% and 0.7%, respectively. In treatment-naive patients, the rates of a virological response, HBeAg conversion, and HBsAg loss at 192 weeks were 100%, 33.3%, and 2%, respectively. The treatment-naive patients exhibited higher baseline HBsAg levels than the treatment-experienced patients (4.31 log10IU/mL vs. 3.97 log10IU/mL). A significant decrease in the HBsAg levels from the baseline was observed at 144 and 192 weeks in the treatment-naive patients (p=0.01). The baseline body mass index (BMI) <25 kg/m2 (p=0.02) and HBsAg <3.3 log10IU/mL (p=0.04) were identified as predictive factors for a decrease in HBsAg ≥0.5 log10IU/mL at 48 weeks. The eGFR levels were consistently lower in the treatment-experienced patients throughout the study. Although the treatment-naive patients showed no abnormal increases in urinary URBP, the treatment-experienced patients showed elevated urinary β2MG and NAG levels at the baseline, which decreased over the treatment course. The total cholesterol, triglyceride, and low-density lipoprotein levels were similar in both groups. Conclusions Prolonging the TAF treatment duration enhances the virological response rate. The decline in HBsAg levels was more significant in the treatment-naive patients than in the treatment-experienced patients. The baseline BMI <25 kg/m2 and HBsAg <3.3 log10IU/mL were predictive factors for a significant decline in HBsAg at 48 weeks. TAF has high renal safety and no significant impact on lipid levels.

Background/Aims: This study assessed the long-term efficacy and safety of tenofovir alafenamide (TAF) in real-world settings. Methods: Patients who were candidates for TAF treatment and were followed up at 12-week intervals over 192 weeks were enrolled in this study. Results: One hundred and forty-four patients (50 treatment-naive and 94 treatment-experienced) were included in this study. The cumulative incidence rates of cirrhosis and hepatocellular carcinoma at 192 weeks were 3.9% and 0.7%, respectively. In treatment-naive patients, the rates of a virological response, HBeAg conversion, and HBsAg loss at 192 weeks were 100%, 33.3%, and 2%, respectively. The treatment-naive patients exhibited higher baseline HBsAg levels than the treatment-experienced patients (4.31 log10IU/mL vs. 3.97 log10IU/mL). A significant decrease in the HBsAg levels from the baseline was observed at 144 and 192 weeks in the treatment-naive patients (p=0.01). The baseline body mass index (BMI) <25 kg/m2 (p=0.02) and HBsAg <3.3 log10IU/mL (p=0.04) were identified as predictive factors for a decrease in HBsAg ≥0.5 log10IU/mL at 48 weeks. The eGFR levels were consistently lower in the treatment-experienced patients throughout the study. Although the treatment-naive patients showed no abnormal increases in urinary URBP, the treatment-experienced patients showed elevated urinary β2MG and NAG levels at the baseline, which decreased over the treatment course. The total cholesterol, triglyceride, and low-density lipoprotein levels were similar in both groups. Conclusions Prolonging the TAF treatment duration enhances the virological response rate. The decline in HBsAg levels was more significant in the treatment-naive patients than in the treatment-experienced patients. The baseline BMI <25 kg/m2 and HBsAg <3.3 log10IU/mL were predictive factors for a significant decline in HBsAg at 48 weeks. TAF has high renal safety and no significant impact on lipid levels.

Background/Aims: This study assessed the long-term efficacy and safety of tenofovir alafenamide (TAF) in real-world settings. Methods: Patients who were candidates for TAF treatment and were followed up at 12-week intervals over 192 weeks were enrolled in this study. Results: One hundred and forty-four patients (50 treatment-naive and 94 treatment-experienced) were included in this study. The cumulative incidence rates of cirrhosis and hepatocellular carcinoma at 192 weeks were 3.9% and 0.7%, respectively. In treatment-naive patients, the rates of a virological response, HBeAg conversion, and HBsAg loss at 192 weeks were 100%, 33.3%, and 2%, respectively. The treatment-naive patients exhibited higher baseline HBsAg levels than the treatment-experienced patients (4.31 log10IU/mL vs. 3.97 log10IU/mL). A significant decrease in the HBsAg levels from the baseline was observed at 144 and 192 weeks in the treatment-naive patients (p=0.01). The baseline body mass index (BMI) <25 kg/m2 (p=0.02) and HBsAg <3.3 log10IU/mL (p=0.04) were identified as predictive factors for a decrease in HBsAg ≥0.5 log10IU/mL at 48 weeks. The eGFR levels were consistently lower in the treatment-experienced patients throughout the study. Although the treatment-naive patients showed no abnormal increases in urinary URBP, the treatment-experienced patients showed elevated urinary β2MG and NAG levels at the baseline, which decreased over the treatment course. The total cholesterol, triglyceride, and low-density lipoprotein levels were similar in both groups. Conclusions Prolonging the TAF treatment duration enhances the virological response rate. The decline in HBsAg levels was more significant in the treatment-naive patients than in the treatment-experienced patients. The baseline BMI <25 kg/m2 and HBsAg <3.3 log10IU/mL were predictive factors for a significant decline in HBsAg at 48 weeks. TAF has high renal safety and no significant impact on lipid levels.

Background/Aims: This study assessed the long-term efficacy and safety of tenofovir alafenamide (TAF) in real-world settings. Methods: Patients who were candidates for TAF treatment and were followed up at 12-week intervals over 192 weeks were enrolled in this study. Results: One hundred and forty-four patients (50 treatment-naive and 94 treatment-experienced) were included in this study. The cumulative incidence rates of cirrhosis and hepatocellular carcinoma at 192 weeks were 3.9% and 0.7%, respectively. In treatment-naive patients, the rates of a virological response, HBeAg conversion, and HBsAg loss at 192 weeks were 100%, 33.3%, and 2%, respectively. The treatment-naive patients exhibited higher baseline HBsAg levels than the treatment-experienced patients (4.31 log10IU/mL vs. 3.97 log10IU/mL). A significant decrease in the HBsAg levels from the baseline was observed at 144 and 192 weeks in the treatment-naive patients (p=0.01). The baseline body mass index (BMI) <25 kg/m2 (p=0.02) and HBsAg <3.3 log10IU/mL (p=0.04) were identified as predictive factors for a decrease in HBsAg ≥0.5 log10IU/mL at 48 weeks. The eGFR levels were consistently lower in the treatment-experienced patients throughout the study. Although the treatment-naive patients showed no abnormal increases in urinary URBP, the treatment-experienced patients showed elevated urinary β2MG and NAG levels at the baseline, which decreased over the treatment course. The total cholesterol, triglyceride, and low-density lipoprotein levels were similar in both groups. Conclusions Prolonging the TAF treatment duration enhances the virological response rate. The decline in HBsAg levels was more significant in the treatment-naive patients than in the treatment-experienced patients. The baseline BMI <25 kg/m2 and HBsAg <3.3 log10IU/mL were predictive factors for a significant decline in HBsAg at 48 weeks. TAF has high renal safety and no significant impact on lipid levels.

AIM: To understand the publication status, research trends, and cutting-edge and hot topics in this field by conducting a bibliometrics analysis of relevant literatures on the pathogenesis of primary open angle glaucoma(POAG)in the past 30 a.METHODS:A total of 986 relevant literatures on the pathogenesis of POAG published on the core databases of China National Knowledge Infrastructure(CNKI)and Web of Science(WOS)from 1 September 1993 to 1 September 2023 were retrieved. CiteSpace(6.2.R.4)and VOSviewer(1.6.18)software were used to conduct knowledge graph analysis on the retrieved literature, including publication volume, author, research institution, country/region, and keywords.RESULTS:The United States(243 articles)has the highest number of publications, followed by China(121 articles). The foreign institution with the highest number of publications is Harvard University(37 articles), while domestic institutions such as Zhongshan Ophthalmic Center, Sun Yat-sen University, ophthalmology department of Xuanwu Hospital of Capital Medical University, and Peking University First Hospital tied for the highest number of publications. Louis R. Pasquale(21 articles)is the most prolific English author. Wang Ningli is the most active Chinese researcher in this field. Keywords include trabecular meshwork, intraocular pressure, aqueous humor, glucocorticoid, hemorheology, etc.CONCLUSION: The research on the pathogenesis of POAG is in a period of vigorous development. The United States has the largest number of publications in this field, and Harvard University is a leading institution in this field. The research focus in the field of POAG has shifted from the structural aspect to the genetic level, and gene research and traditional Chinese medicine treatment have broad application prospects in this field.

Objective To investigate the effects of Optimized New Shengmai Powder on myocardial fibrosis in rats with heart failure based on the β1-AR/cAMP/PKA/CREB signaling pathway.Methods Totally 50 SD rats were randomly divided into sham-operation group(10 rats)and operation group(40 rats).The left anterior descending coronary artery was ligated to establish a rat model of heart failure.The modeling rats were randomly divided into the model group,the captopril group,and TCM low-and high-dosage groups,with 8 rats in each group.The administration groups received relevant medicine for gavage for 4 weeks.LVEF and LVFS in rats were detected by echocardiography,and measurement of heart and lung mass and calculation of heart and lung organ coefficients were performed,myocardial fibrosis degree was observed by histopathology,serum NT-ProBNP and cAMP,Col Ⅰ,and Col Ⅲcontent in myocardial tissue were detected by ELISA,immunohistochemical was used to detect β1-AR,cAMP positive expression,and Western blot was used to detect the expression of β1-AR/cAMP/PKA/CREB signaling pathway related proteins.Results Compared with the sham-operation group,the LVEF and LVFS of the model group rats were significantly decreased(P<0.01),and the heart and lung organ coefficient significantly increased(P<0.01);the number of myocardial cells decreased,collagen volume fraction increased,and the proportion of type Ⅰ/Ⅲcollagen fibers increased(P<0.01),the contents of serum NT-ProBNP and myocardial tissue Col Ⅰ and Col Ⅲincreased significantly,while the cAMP content in myocardial tissue decreased significantly(P<0.01),the positive expressions of β1-AR and cAMP were significantly decreased(P<0.01),the expressions of β1-AR,AC1,cAMP,p-PKA,and p-CREB proteins were significantly decreased,while protein expressions of p-Smad2,Col Ⅰ,Col Ⅲ,and α-SMA significantly increased(P<0.05,P<0.01).Compared with the model group,the administration groups could increase LVEF and LVFS and decrease heart and lung organ coefficient to different degrees in rats;increase the number of myocardial cells,decrease collagen volume fraction and the proportion of type Ⅰ/Ⅲ collagen fibers,down-regulate serum NT-ProBNP and the content of Col Ⅰ and Col Ⅲ in myocardial tissue,up-regulate the content of cAMP,increase the positive expressions of β1-AR and cAMP in myocardial tissue,up-regulate β1-AR,AC1,cAMP,p-PKA,p-CREB protein expression,and inhibit p-Smad2,Col Ⅰ,Col Ⅲ,and α-SMA protein expression,in which the effects of the TCM high-dosage group and captopril group were more pronounced(P<0.01,P<0.05).Conclusion Optimized New Shengmai Powder can effectively reduce myocardial fibrosis in heart failure rats,improve myocardial hypertrophy and remodeling,and increase left ventricular contractility,and the mechanism may be related to the activation of the β1-AR/cAMP/PKA/CREB signaling pathway.

Objective:To evaluate the role of neuronal nitric oxide synthase (nNOS)-nitric oxide synthase 1 adaptor protein (NOS1AP) coupling in remifentanil-induced hyperalgesia in rats.Methods:Forty clean-grade healthy adult male Sprague-Dawley rats, weighing 240-260 g, aged 2-3 months, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), remifentanil group (group R), nNOS-NOS1AP inhibitor ZLc002 group (group C+ Z) and remifentanil + ZLc002 group (group R+ Z). Normal saline was intravenously infused at a rate of 0.1 ml·kg -1·min -1 for 60 min in C group. Remifentanil was intravenously infused at a rate of 1.0 μg·kg -1·min -1 for 60 min in R group. ZLc002 10 mg/kg was intraperitoneally injected for 3 consecutive days, and then normal saline 0.1 ml·kg -1·min -1 and remifentanil 1.0 μg·kg -1·min -1 were intravenously infused for 60 min in C+ Z group and R+ Z group. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before intravenous infusion and 6, 24 and 48 h after intravenous infusion (T 0-3). All the rats were sacrificed after the last measurement of pain thresholds, and the L 4-6 segments of the spinal cord were removed for determination of the expression of nNOS, NOS1AP and Dexamethasone-induced Ras-related protein 1 (Dexras1) protein and mRNA using the real-time polymerase chain reaction. Nitrosylated proteins were extracted by biotin conversion for determination of the expression of nNOS, NOS1AP and total and nitrosylated Dexras1 (by Western blot) and co-expression of nNOS-NOS1AP (by co-immunoprecipitation). The content of NO in the spinal cord was measured. Results:Compared with group C, the MWT was significantly decreased, and the TWL was shortened at T 1-3, the expression of nNOS and NOS1AP protein and mRNA was up-regulated, the co-expression of nNOS-NOS1AP and NO production were increased, and the expression of nitrosylated Dexras1 was up-regulated in group R ( P<0.05), and no significant change was found in each aforementioned parameter in group C+ Z ( P>0.05). Compared with group R, the MWT was significantly increased, and the TWL was prolonged at T 1-3, the co-expression of nNOS-NOS1AP and NO production were decreased, the expression of nitrosylated Dexras1 was down-regulated ( P<0.05), and no significant change was found in the expression of nNOS and NOS1AP protein and mRNA in group R+ Z ( P>0.05). There were no significant differences in total Dexras1 protein and mRNA expression among the four groups ( P>0.05). Conclusions:The mechanism by which remifentanil induces hyperalgesia may be related to up-regulating the expression of nNOS and NOS1AP in the spinal cord, promoting interaction between nNOS and NOS1AP and mediating NO generation and Dexras1 nitrosylation modification in rats.

Objective:To evaluate the effect of Salvianolic acid B (Sal B) on the inflammatory responses of vascular smooth muscle cells (VSMCs) in septic mice and the role of circACTA2.Methods:In vivo experiment Eighty-one healthy male C57BL/6 mice, aged 6-8 weeks, were divided into 3 groups ( n=27 each) by a random number table method: sham operation group, sepsis group and Sal B group. Sepsis model was developed by cecal ligation and puncture. After sucessful preparation of the model, Sal B 7 mg/kg/d was intraperitoneally injected once a day for 2 consecutive days in Sal B group. Twenty mice in each group were randomly selected to measure systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and whole blood lactic acid (Lac) and to record the survival within 7 days after developing the model. Seven mice in each group were randomly selected at 48 h after developing the model, and the arterial vascular tissues were collected for determination of the expression of interleukin-1beta (IL-1β) (by immunofluorescence staining), expression of IL-1β, tumor necrosis factor-alpha (TNF-α) and IL-6 protein and mRNA (by Western blot and quantitative real-time polymerase chain reaction, respectively), and expression of circACTA2 (by quantitative real-time polymerase chain reaction). Cell experiment Mouse VSMCs were cultured and divided into 6 groups ( n=3 each) by a random number table method: control group (C group), lipopolysaccharide (LPS) group, Sal B group, si-circACTA2+ C group, si-circACTA2+ LPS group, and si-circACTA2+ Sal B group. The cells were incubated for 24 h with LPS (final concentration 1 μg/ml) in LPS group and with LPS (final concentration 1 μg/ml) and Sal B (final concentration 5 μmol/L) in Sal B group. VSMCs were transfected with si-circACTA2 only in si-circACTA2+ C group. At 24 h after transfection of si-circACTA2 into VSMCs, the cells were incubated with LPS (final concentration 1 μg/ml) in si-circACTA2+ LPS group and with LPS (final concentration 1 μg/ml) and Sal B (final concentration 5 μmol/L) for 24 h in si-circACTA2+ Sal B group. The expression of IL-1β, TNF-α and IL-6 protein and mRNA was detected using Western blot and quantitative real-time polymerase chain reaction, and the expression of circACTA2 was determined by the quantitative real-time polymerase chain reaction. Results:In vivo experiment Compared with sham operation group, SBP, DBP and MAP were significantly decreased, the concentrations of whole blood Lac were increased, 7-day survival rate was decreased, the expression of IL-1β, TNF-α and IL-6 protein and mRNA in arterial vascular tissues was up-regulated, circACTA2 expression was down-regulated ( P<0.05), and the fluorescence of IL-1β was enhanced in sepsis group. Compared with sepsis group, SBP, DBP and MAP were significantly increased, whole blood Lac concentrations were decreased, 7-day survival rate was increased, the expression of IL-1β, TNF-α and IL-6 protein and mRNA in arterial vascular tissues was down-regulated, the expression of circACTA2 was up-regulated ( P<0.05), and the fluorescence of IL-1β was weakened in Sal B group. Cell experiment Compared with group C, the expression of IL-1β, TNF-α and IL-6 protein and mRNA was significantly up-regulated, and the expression of circACTA2 was down-regulated in LPS group ( P<0.05). Compared with LPS group, the expression of IL-1β, TNF-α and IL-6 protein and mRNA was significantly down-regulated, and the expression of circACTA2 was up-regulated in Sal B group ( P<0.05). Compared with si-circACTA2+ C group, the expression of IL-1β, TNF-α and IL-6 protein and mRNA was significantly up-regulated in si-circACTA2+ LPS group ( P<0.05). There were no significant differences in the expression of IL-1β, TNF-α and IL-6 protein and mRNA between si-circACTA2+ LPS group and si-circACTA2+ Sal B group ( P>0.05). Conclusions:Sal B can reduce the inflammatory responses of VSMCs, and the mechanism may be related to promoting the expression of circACTA2 in septic mice.

Objective:To evaluate the incidence of arrhythmias and electrocardiographic (ECG) characteristics in cancer patients treated with immune checkpoint inhibitors (ICIs).Methods:This was a cohort study conducted in the Fourth Hospital of Hebei Medical University. Cancer patients initiating ICIs treatments from November 2020 to September 2022 were included in this study. Baseline 12-leads ECG before ICIs initiation and post-treatment ECG were analyzed. An abnormal ECG was defined as the presence of any of the following changes: sinus arrhythmias, atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, ventricular tachycardia, premature contractions, conduction disorder, and ST-T changes.Results:A total of 87 patients were enrolled, aged 63 (57, 68) years, with 66 (75.9%) males. And 44.8% (39/87) of patients presented with at least one confirmed cardiovascular disease or cardiovascular risk factor at baseline. The incidence of abnormal ECG increased from 31.0% (27/87) at baseline to 65.5% (57/87) after receiving (5.0±2.7) cycles of ICIs treatment ( P<0.001). The incidence of sinus arrhythmias was significantly increased after ICIs treatment (23.0% (20/87) vs. 9.2% (8/87), P=0.023), of which only the incidence of sinus tachycardia was significantly increased (11.5% (10/87) vs. 2.3% (2/87), P=0.039). There was also a significantly increased incidence of ST-T changes after ICIs treatment (31.0% (27/87) vs. 17.2% (15/87), P=0.012), which mainly attributed to the T wave changes (29.9% (26/87) vs. 13.8% (12/87), P=0.001). The incidence of premature contractions was also significantly increased after ICIs treatment (9.2% (8/87) vs. 0, P=0.008). Additionally, compared with baseline, the P wave axis was significantly increased after ICIs treatment ((56.94±21.01)° vs. (52.00±22.69)°, P=0.043). After ICIs treatment, the heart rate was significantly increased ((79.07±15.37) beats/min vs. (75.64±13.37) beats/min, P=0.029). Sokolow-Lyon index ((2.21±0.81)mV vs. (2.33±0.75)mV, P=0.138), QTc interval ((431.44±36.04)ms vs. (428.00±30.05)ms, P=0.415) all showed signs of change after treatment, but did not reach the traditional significant level. Conclusions:The incidence of abnormal ECG is significantly increased after ICIs treatment, especially for sinus tachycardia, premature contractions and T wave changes; the P wave axis and heart rate is also significantly increased after treatment. It is important to perform regular ECG monitoring in patients receiving ICIs treatment.