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).

OBJECTIVE To investigate the implementation effects of the national centralized drug volume-based procurement policy （abbreviated as “national centralized procurement policy”） in Guangxi Zhuang Autonomous Region prefecture， and to provide a reference for the future centralized drug procurement work of the medical institution. METHODS Drug procurement data before and after policy implementation were included in the study. The six secondary indicators （such as availability， affordability， and drug safety） and eighteen third-level indicators （such as completion rate of agreed purchase volume， affordability level， drug revenue proportion） were introduced， guided by the policy objectives and issues of concern to policy beneficiaries. Descriptive statistics was adopted to analyze the data before and after policy implementation （in 2019 and 2020） in terms of differences and change trends. RESULTS In terms of accessibility， the participation rate of medical institutions in Guangxi Zhuang Autonomous Region was 92.55%， the proportion of diseases involved and median completed procurement rate were 40.16%， and 287.82% respectively， and the total centralized delivery rate was 97.20%. In terms of affordability， the total reduction amplitude in drug price was 74.80% from 2019 to 2022； the charge for medicine per capita in hospitalization， the proportion of medicine used for outpatient service and hospitalization， decreased by 17.61%， 10.22%， and 20.10% in order； the burden levels on medical fares for patients were all below 1 in addition to chronic diseases， and anti-tumor drugs. In terms of the impact on medicine， the ratio of adverse drug reaction event cases in 2022 was 66.00%， an increase of 1.29% compared to the previous； since the implementation of the policy， 12 drugs from local pharmaceutical enterprises from Guangxi Zhuang Autonomous Region had passed the consistency evaluation， and the market concentration rate of the top 8 pharmaceutical companies was less than 20.00%. In terms of the impact on healthcare and medical insurance， the public medical institutions achieved generic substitution for originator drugs mostly until 2022； about 9.12% of drugs that were non- centrally purchased in the same category were used； 63.39% of people under investigation did not show a need for a second dressing change； drug expenditure decreased by 2.459 billion yuan. CONCLUSIONS The national centralized procurement policy achieves a significant effect in Guangxi Zhuang Autonomous Region. On the other hand， attention should be paid to these suggestions as follows: expanding the category of drugs used in clinic， conducting clinically comprehensive evaluation of selected drugs， and improving reasonable allocation strategy， etc.

Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPARα is highly expressed in the small intestine and regulates the absorption of dietary lipids. However, as a key mediator of inflammation, the impact of intestinal PPARα signaling on cell death pathways is unknown. Here, we show that Pparα deficiency of intestinal epithelium up-regulates necroptosis signals, disrupts the gut vascular barrier, and promotes LPS translocation into the liver. Intestinal Pparα deficiency drives age-related hepatic steatosis and aggravates hepatic fibrosis induced by a high-fat plus high-sucrose diet (HFHS). PPARα levels correlate with TRIM38 and MLKL in the human ileum. Inhibition of PPARα up-regulates necroptosis signals in the intestinal organoids triggered by TNF-α and LPS stimuli via TRIM38/TRIF and CREB3L3/MLKL pathways. Butyric acid ameliorates hepatic steatosis induced by intestinal Pparα deficiency through the inhibition of necroptosis. Our data suggest that intestinal PPARα is essential for the maintenance of microenvironmental homeostasis and the spread of inflammation via the gut-liver axis.

Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N⁶-methyladenosine (m⁶A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m⁶A methylation. We then indicate that SRSF7 is a novel m⁶A regulator, which specifically facilitates the m⁶A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m⁶A methyltransferase. The two m⁶A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m⁶A and validates the presence and functional importance of temporal- and spatial-specific regulation of m⁶A mediated by RNA-binding proteins (RBPs).
Humans ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics* ; Methyltransferases/metabolism* ; RNA Splicing Factors/metabolism* ; RNA, Messenger/genetics* ; RNA-Binding Proteins/metabolism* ; Serine-Arginine Splicing Factors/metabolism* ; RNA Methylation/genetics*

Objective: Computed tomography (CT)-guided percutaneous lung biopsy is difficult for small nodules and lesions that are adjacent to large blood vessels. This study investigated the validity of CT-guided percutaneous lung biopsy in the diagnosis of pulmo-nary nodules with a digital angle instrument. Methods: This study was a retrospective analysis of 35 patients with lung mass≤60 mm, who underwent CT-guided percutaneous lung biopsy from January 2018 to September 2018. Patients were assigned in to three groups. Group A and B were patients with pulmonary nodules≤30 mm. Biopsy of group A was performed with the help of a digital an-gle instrument, and group B didn’t use digital angle instrument. Group C had lung mass of>30 mm, and the biopsy was performed without using the instrument. The size of the mass, frequency of punctures, distance of the puncture, and complication of pneumotho-rax after puncture were compared among the three groups. Results: The maximum diameter of pulmonary nodules in group A (18.4 ± 2.1) mm was significantly lower than that in groups B (28.3 ± 2.0) mm and C (43.2 ± 3.6) mm, and their P value were 0.0034 and 0.0028, respectively. Some patients in group A were at risk because of severe chronic obstructive pulmonary disease and proximity of lesions to large blood vessels. The puncture distance in group A was also significantly more than groups B (P<0.039). However, the probability of puncture success in group A was 100%, which was significantly higher than groups B and C. The postoperative complica-tions in group A were also significantly fewer than in other two groups. Conclusions: CT-guided percutaneous lung biopsy with a digital angle instrument is a safe, simple, and accurate diagnostic method, especially in patients with pulmonary nodular lesions.

Objective To investigate the distribution of LAP+CD4+T cells in gastric carcinoma microenvironment and the correlation of LAP + CD4 + T cells with the progression of gastric tumor. Methods Forty gastric tumor patients and 20 healthy donors were enrolled in this study. The percentage of LAP+CD4+T cells in the peripheral blood and tumor tissue was detected by flow cytometry. The correlation of LAP+CD4+T cells with the progression of gastric tumor was analyzed. Results The percentage of LAP+CD4+T cells in the peripheral blood of gastric tumor patients was higher than that of health donors:(10.9±3.3)%vs. (4.3 ± 1.2)%;the percentage of LAP+CD4+T cells from tumor tissue was higher than that from non-tumor tissue:(13.5 ± 5.3)%vs. (4.7 ± 1.4)%. The percentage of LAP+CD4+T cells in peripheral blood from metastasis patients was higher than that from non-metastasis patients and health donors: (10.1 ± 6.4)% vs. (4.5 ± 1.3)% and (4.3 ± 1.2)%. Conclusions LAP+ CD4+ T cells accumulates in gastric carcinoma microenvironment and the percentage of LAP+CD4+T cells increases along with the progression of gastric tumor.

Objective To understand the management status quo of migrant workers with chronic hepatitis B (CHB) to ex‐plore the management countermeasures and improve the survival quality for tamping the foundation of the healthy project .Methods Totally 300 migrant workers with CHB were performed the living quality evaluation and investigation on the service needs ,com‐pliance ,economic condition ,categories and proportion of reimbursement by adopting the supplementary revision of SF‐36 living quality scale and general information questionnaire ;the influencing factors of their living quality were performed the univariate anal‐ysis and multivariate stepwise regression analysis .Results The statistical analysis found that whether convenient for outside visit‐ing hospital ,categories and proportion of reimbursement ,whether normalized antiviral therapy ,whether conducting examination and follow up at regular intervals and liver disease specific symptoms were the influencing factors of living quality in the migrant work‐ers with CHB(P<0 .05);the living quality in the patients with outside convenient visiting hospital ,high reimbursement proportion , normalized antiviral therapy and examination and follow up at regular intervals was significantly higher than that in the patients with inconvenient outside visiting hospital ,low reimbursement proportion ,non‐normalized anti‐viral therapy and examination and follow up without regular intervals(P<0 .05);the liver disease specific symptom score showed the positive correlation trend with the living quality score (B=7 .657 ,SD=2 .650 ,t=2 .889 ,P=0 .004) .Conclusion It is necessary to improve the patient′s medical needs ,reimbursement type and proportion ,increase the compliance of patient′s normalized examination and follow‐up at regular in‐tervals and standard antiviral treatment ,thus to realize the standardized examination and treatment in CHB patients ,prevent or de‐lay the disease progression ,avoid liver cirrhosis and decompensated hepatopathy ,reduce the occurrence of HCC ,improve the quality of life and prolong the survival period .

Objective To compare the therapeutic effects of bone marrow stem treatment by different bone marrow mobilization,distinct separation methods or cell suspension density, and to explore the optimal treatment plan of autologous bone marrow stem cell transplantation for decompensated cirrhosis.Methods Twenty three patients with decompensated cirrhosis were studied.100 ~200 mL bone marrow from each patient was harvested in aseptic condition, after isolation and purification by density gradient centrifugation,the stem cells were obtained and transplanted into the liver via hepatic artery.The serum glutamic acid alanine aminotransferase (ALT), albumin (ALB), prothrombin time (PT) and total bilirubin (TBIL) were checked before and l, 2, 3 months after therapy respectively,changes in these indicators of each group were compared by different bone marrow mobilization, distinct separation methods, or cell suspension density.Results After transplantation, levels of albumin increased significantly 1, 2, 3 months after treatment compared with baseline(P<0.05).Patients in bone marrow mobilization group obtained higher stem cell density (P<0.05), which had no significant difference in improving liver function ( ALT, TBIL, ALB, PT) compared with non-bone marrow mobilization group.Patients using the kit significantly improved their albumin (3 months after treatment, P<0.05), which had no significant difference in improving liver function (ALT, TBIL, ALB, PT) compared with using ordinary lymphocyte isolation method group.There was no significant difference in improving liver function ( ALT, TBIL, ALB, PT) between lower magnitude stem cell density group(≤1 ×1010/L) and higher magnitude stem cell density group(1 ×1010/L).Conclusion The treatment for decompensated cirrhosis by transplantation of autologous bone nlarrow stem cells is safe and effective, which can significantly increase the level of albumin in patients with decompensated cirrhosis.Preoperative bone marrow mobilization can increase the rate of stem cells obtained, and the method using the kit improves the leves of protein respectively.They are helpful to improve the efficacy.

OBJECTIVETo observe the clinical efficacy of shensong yangxin capsule (SYC) on ventricular premature beat (VPB) differentiated in TCM as palpitation of Qi-yin deficiency syndrome or Xin collateral stagnation syndrome, and cardiovascular autonomic nervous function in patients with coronary heart disease (CHD).

METHODSThe randomized, double-blind, parallel contrast method was adopted, patients were randomly assigned by 3:1 ratio into two groups. One hundred and sixty-five patients in SYC treated group and 56 in the control group (treated with Xinlvning tablet), and the therapeutic course for both groups was 4 weeks.

RESULTSThe clinical efficacy on VPB and in improving TCM syndromes was better in SYC group than that in the control group (P < 0.01). After treatment, the heart rate variability (HRV) and QT dispersion in the two groups were improved in a certain degree. The changes of SDNN, SDANN, SDNN Index and PNN50 in the two groups were significantly different (P < 0.05, P < 0.01), the efficacy in the treated group was superior to that in the control group.

CONCLUSIONSYC has definite effect on VPB and TCM Syndromes, it can obviously meliorate the activity of cardiovascular autonomic nervous system in the patients with CHD.

Adult ; Aged ; Autonomic Nervous System ; drug effects ; physiopathology ; Capsules ; Coronary Disease ; complications ; drug therapy ; Double-Blind Method ; Drug Administration Schedule ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Heart ; innervation ; Humans ; Male ; Middle Aged ; Phytotherapy ; Ventricular Premature Complexes ; drug therapy ; etiology