1.Efficacy, safety, and pharmacokinetics of capsid assembly modulator linvencorvir plus standard of care in chronic hepatitis B patients
Jinlin HOU ; Edward GANE ; Rozalina BALABANSKA ; Wenhong ZHANG ; Jiming ZHANG ; Tien Huey LIM ; Qing XIE ; Chau-Ting YEH ; Sheng-Shun YANG ; Xieer LIANG ; Piyawat KOMOLMIT ; Apinya LEERAPUN ; Zenghui XUE ; Ethan CHEN ; Yuchen ZHANG ; Qiaoqiao XIE ; Ting-Tsung CHANG ; Tsung-Hui HU ; Seng Gee LIM ; Wan-Long CHUANG ; Barbara LEGGETT ; Qingyan BO ; Xue ZHOU ; Miriam TRIYATNI ; Wen ZHANG ; Man-Fung YUEN
Clinical and Molecular Hepatology 2024;30(2):191-205
Background/Aims:
Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients.
Methods:
This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks.
Results:
68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported.
Conclusions
48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.
2.Saw palmetto fruit extract improves LUTS in type ⅢA prostatitis patients.
Yun-Peng SHAO ; Hao-Liang XUE ; Bai-Xin SHEN ; Liu-Cheng DING ; Zheng-Seng CHEN ; Zhong-Qing WEI
National Journal of Andrology 2017;23(5):417-421
Objective:
To assess the clinical efficacy of the saw palmetto fruit extract (SPFE) in the treatment of lower urinary tract symptoms (LUTS) in patients with type ⅢA prostatitis.
METHODS:
This retrospective study included 54 cases of type ⅢA prostatitis treated in the Outpatient Department of our hospital from January to December 2015. The patients were aged 35.06 ± 5.85 years, with a mean disease course of 3.8 ± 2.1 years, and all received oral medication of SPFE Capsules at the dose of 320 mg qd for 12 weeks. We assessed the therapeutic effects by comparing the NIH-chronic prostatitis symptom indexes (NIH-CPSI), voiding diary, International Prostate Symptom Scores (IPSS), and results of urodynamic examination before and after treatment.
RESULTS:
Compared with the baseline, both NIH-CPSI and IPSS were significantly decreased after medication (27.61 ± 3.76 vs 18.6 ± 5.34, P <0.01; 20.44 ± 4.51 vs 10.96±4.62, P <0.01), and urodynamic examination and voiding diary showed dramatic post-medication improvement in the average urinary flow rate ([8.05±1.42] vs [12.05±2.60] ml/s, P <0.01 ), maximum urinary flow rate ([14.22±1.74] vs [21.32±4.51] ml/s, P <0.01), residual urine volume ([46.15±16.57] vs [14.55±10.21] ml, P <0.01), maximum urethral closure pressure ([76.52±3.53] vs [65.32±4.75] cm H2O, P <0.01), mean urinary volume ([124.63±40.55] vs [285.93±58.68] ml, P <0.01), urination frequency (16.96±4.17 vs 8.96±2.50, P <0.01), and nocturia frequency (8.94±3.23 vs 3.15±1.90, P <0.01). No apparent adverse reactions were observed in any of the patients.
CONCLUSIONS
SPFE Capsules can safely and effectively improve LUTS and thus the quality of life of patients with type ⅢA prostatitis.
Adult
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Chronic Disease
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Humans
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Lower Urinary Tract Symptoms
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drug therapy
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etiology
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Male
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Plant Extracts
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therapeutic use
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Prostatitis
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complications
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Quality of Life
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Retrospective Studies
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Treatment Outcome
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Urination
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Urological Agents
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therapeutic use
3.Expression Levels of JARID1B, Hes1 and MMP-9 Genes in CML Patients Treated with Imatinib Mesylate.
Zhi-Kai HE ; Seng XUE ; Yong-Hong ZHANG ; Lin LI ; Yun-Jin XIA ; Xiang WANG ; Xin SHI ; Yu LIU ; Zheng XU ; Chen LI ; Jing-Xuan ZHANG
Journal of Experimental Hematology 2019;27(4):1071-1076
OBJECTIVE:
To explore the relationship between the expression levels of JARID1B,Hes1 and MMP-9 genes and the stages of chronic myelogenous leukemia(CML) and the curative effect of imatinib mesylate (IM).
METHODS:
Peripheral blood samples of 15 cases of CML in chronic phase and 10 cases of CML in progressive phase were collected from the Hematology Department of Taihe Hospital affiliated to Hubei University of Medicine and 15 cases of healthy people in the Physical Examination Center. CML patients were divided into effective group and ineffective group based on the efficacy after treatment with IM, then real-time PCR was used to detect the expression levels of JARID1B, Hes1 and MMP-9 mRNA, finally, the differences in the level of gene expression and their correlations with CML stages and IM curative efficacy were analysed.
RESULTS:
The expression levels of Hes1 and MMP-9 in initially diagnosed patients in chronic and progressive phase without IM treatment were significantly higher than those of health people(P<0.05). There was no significant difference in the expression level of JARID1B between chronic phase patients and health people(P>0.05), but the expression level of JARID1B in the progressive phase patients was higher than that of health people (P<0.05). The expression levels of JARID1B and Hes1 in the IM-effective group were not significantly different from those in the IM-ineffective group (P=0.85,P=0.82), while the expression level of MMP-9 in the IM-effective group [JP2]was significantly lower than that in the IM-ineffective group(P<0.05).
CONCLUSION
The expression levels of JARID1B Hes1 and MMP-9 relate with the different phase of CML; The expression levels of JARID1B and Hes1 have not significant relationship with IM curative efficacy, the MMP-9 gene expression level relates with IM curative efficacy.
Antineoplastic Agents
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therapeutic use
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Humans
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Imatinib Mesylate
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therapeutic use
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Jumonji Domain-Containing Histone Demethylases
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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drug therapy
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Matrix Metalloproteinase 9
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Nuclear Proteins
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Repressor Proteins
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Transcription Factor HES-1