1.Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TORCH-B trial
Yao-Chun HSU ; Chi-Yi CHEN ; Cheng-Hao TSENG ; Chieh-Chang CHEN ; Teng-Yu LEE ; Ming-Jong BAIR ; Jyh-Jou CHEN ; Yen-Tsung HUANG ; I-Wei CHANG ; Chi-Yang CHANG ; Chun-Ying WU ; Ming-Shiang WU ; Lein-Ray MO ; Jaw-Town LIN
Clinical and Molecular Hepatology 2025;31(1):213-226
Background/Aims:
Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population.
Methods:
This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019).
Results:
Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg.
Conclusions
In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.
2.Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TORCH-B trial
Yao-Chun HSU ; Chi-Yi CHEN ; Cheng-Hao TSENG ; Chieh-Chang CHEN ; Teng-Yu LEE ; Ming-Jong BAIR ; Jyh-Jou CHEN ; Yen-Tsung HUANG ; I-Wei CHANG ; Chi-Yang CHANG ; Chun-Ying WU ; Ming-Shiang WU ; Lein-Ray MO ; Jaw-Town LIN
Clinical and Molecular Hepatology 2025;31(1):213-226
Background/Aims:
Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population.
Methods:
This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019).
Results:
Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg.
Conclusions
In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.
3.Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TORCH-B trial
Yao-Chun HSU ; Chi-Yi CHEN ; Cheng-Hao TSENG ; Chieh-Chang CHEN ; Teng-Yu LEE ; Ming-Jong BAIR ; Jyh-Jou CHEN ; Yen-Tsung HUANG ; I-Wei CHANG ; Chi-Yang CHANG ; Chun-Ying WU ; Ming-Shiang WU ; Lein-Ray MO ; Jaw-Town LIN
Clinical and Molecular Hepatology 2025;31(1):213-226
Background/Aims:
Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population.
Methods:
This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019).
Results:
Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg.
Conclusions
In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.
4.Survival Analysis and Prognostic Factors for Peri-ocular Malignancies in Malaysia
Dhashani Sivaratnam ; Radzlian Othman ; Navin Kumar Devaraj ; Yap Ming Teck ; Vincent Ng Teng Fung ; Ew Shao Chen ; Ramizah Md Rozi ; Nur Najlaa Baharudin ; Kirbashini Kanasan ; Abdul Hanif Khan Yusof Khan ; Vasudevan Ramachandran ; Siew Moi Ching
Malaysian Journal of Medicine and Health Sciences 2024;20(No.1):60-69
Introduction: This study aims to determine the prognostic factors and survival outcomes of patients that underwent
this surgery. Method: A retrospective review of 43 patients who underwent exenteration for periocular malignancies
over a 14-year period was carried out. Patient demographics, tumour histology, treatment details, surgical margins’
status and post-operative survival were recorded. The survival outcome examined was the overall survival (OS)
rate. Cox regression and Kaplan-Meier analysis were used to evaluate post-exenteration survival. Results: In total,
20 females and 23 males with a median age of 62 ± 17.3 years were identified. The most common indication for
exenteration was basal cell carcinoma (20.9%), followed by squamous cell carcinoma (18.6%), adenocystic carcinoma (14%), malignant melanoma (14%) and sebaceous gland carcinoma (11.6%). The independent predictors for
worse OS on multivariate analysis were Chinese ethnicity (adjusted hazard ratio [aHR] 4.95, p =0.017), sebaceous
gland carcinoma (aHR 57.61 p=0.006), adenocystic carcinoma (aHR 45.87, p=0.008), clear surgical margins (aHR
5.41, p=0.025), receiving only chemotherapy (aHR 169.13, p=0.004), and receiving both adjuvant chemotherapy
and radiotherapy (aHR 41.51, p=0.010). Conclusion: We recommend targeted public health initiatives for Chinese
patients due to their increased mortality risk from peri-ocular malignancies. In addition, we advise comprehensive
adjuvant therapy for all patients regardless of whether a clear surgical margin is achieved. Basal cell carcinoma and
adenocystic carcinoma may also benefit from genetic research. We advocate more training for ophthalmologists to
identify periocular malignancies earlier for better treatment options and increased chances of survival.
5.Assessment of the clinical efficacy of surgical treatment for cervical lymph node tuberculosis
Tanwei FANG ; Teng LIU ; Ming FAN ; Xun WU
Chinese Journal of Geriatrics 2024;43(2):187-191
Objective:To assess the effectiveness and practical value of surgery in clinical treatment of cervical lymph node tuberculosis.Methods:110 patients receiving surgical treatment for tuberculosis at Hunan Provincial Chest Hospital between January 2020 and December 2022 were selected, all of whom were diagnosed with cervical lymph node tuberculosis.According to patient preferences, they were divided into two groups, a drug treatment group consisted of 60 patients receiving conventional Western medicine treatment and a surgical treatment group of 50 patients receiving surgical treatment.Statistical analysis was made to compare the clinical efficacy, recurrence rate, complications, quality of life, and patient satisfaction between the two groups.Results:The overall clinical effectiveness rate was higher in the surgical treatment group than in the drug treatment group(94.00% vs.70.00%, χ2=10.170, P=0.001), with the rate higher in the surgical treatment group than in the drug treatment group for patients under 60 years of age(64.29% vs.40.00%, χ2=-6.996, P=0.035), but there was no difference in therapeutic efficacy between the two groups for patients aged 60 and above(54.55% vs.40.00%, Z=3.842, P=0.146). Compared with the drug treatment group, the surgical treatment group had a lower recurrence rate(8.00% vs.46.67%, χ2=19.767, P<0.001)and a lower rate of complications(8.00% vs.21.67%, χ2=3.899, P=0.048), but higher scores of quality of life in all four domains(physical function: 64.02±4.49 vs.76.11±4.47, t=14.090, P<0.001; material life: 66.50±2.39 vs.81.03±2.28, t=32.417, P<0.001; psychological function: 62.98±2.51 vs.79.24±2.50, t=33.892, P<0.001; social function: 63.12±3.39 vs.76.08±3.51, t=19.645, P<0.001)and a higher level overall patient satisfaction(90.00% vs.66.67%, χ2=8.455, P=0.004). Conclusions:Surgical treatment for cervical lymph node tuberculosis patients has better efficacy, fewer complications and better prognosis and is clinically practical and highly valuable.
6.Application of metal cushion block combined with Jumbo cup in reconstruction of acetabular bone defect in revision of artificial hip joint
Feng-Zhen LI ; Wen-Teng SI ; Ai-Li TIAN ; Yu ZHOU ; Ming-Wei CHEN
China Journal of Orthopaedics and Traumatology 2024;37(5):464-469
Objective To investigate the application effect and imaging changes of metal cushion block combined with Jumbo cup in the reconstruction of acetabular bone defect after revision of artificial hip joint.Methods Retrospective analysis was made on the clinical data of 83 patients who underwent revision acetabular bone defect reconstruction of the artificial hip joint in our hospital from September 2019 to October 2021.They were divided into group A and group B according to different surgical methods.There were 42 patients in group A,including 26 males and 16 females,aged from 44 to 72 years old with an average of(60.57±4.62)years,who underwent revision with metal cushion block and Jumbo cup.There were 41 patients in group B,including 22 males and 19 females,aged from 42 to 71 years old with an average of(58.74±4.25)years,who under-went revision with metal cushion block and bone cement mortar cup.The operation related indexes,Harris hip function score and visual analogue scale(VAS)of pain before operation,1 month and 12 month after operation were compared between two groups.The results of X-ray imaging examination(hip rotation center height,acetabular abduction angle,femoral eccentricity and imaging standard qualification rate)before and 12 month after operation were evaluated,and the incidence of complica-tions was compared between two groups.Results There was no significant difference in operation time,intraoperative bleeding volume and postoperative drainage volume between two groups(P>0.05).Both groups were followed up for 12 to 36 months with an average of(25.36±3.59)months.The scores of pain,function,deformity and Harris'total score in the two groups at 1 month after operation were higher than those before operation(P<0.05),and the scores of pain,function,deformity,joint activ-ity and Harris'total score in two groups at 1 year after operation were higher than those before operation and 1 month after op-eration(P<0.05),and the above scores in group A were higher than those in group B at 1 year after operation(P<0.05).The VAS of two groups decreased successively at 1 month and 1 year after operation(P<0.05),but there was no significant differ-ence in both groups at each time point(P>0.05).The femoral eccentricity increased in both groups at 1 year after operation(P<0.05),and group A was higher than group B(P<0.05).The height of rotation center and acetabular abduction angle de-creased in both groups at 1 year after operation(P<0.05),and the height of rotation center in group A was lower than that in group B(P<0.05),but there was no significant difference in acetabular abduction angle between two groups(P>0.05).The imaging qualification rate of group A was higher than that of group B(P<0.05).There was no significant difference in the inci-dence of adverse reactions between two groups(P>0.05).Conclusion Metal cushion block combined with Jumbo cup in the treatment of acetabular bone defects can provide the hip joint function,and restore the hip joint rotation center,femoral eccen-tricity and acetabular abduction angle,with obvious clinical effect.
7.Analysis of Genes Related to Platelet Activation in Essential Thrombocythemia Based on Transcriptomics
Yan SUN ; Er-Peng YANG ; Yu-Meng LI ; Ji-Cong NIU ; Pei ZHAO ; Wei-Yi LIU ; Zhuo CHEN ; Ming-Jing WANG ; Teng FAN ; Xiao-Mei HU
Journal of Experimental Hematology 2024;32(6):1814-1821
Objective:To analyze the genes related to platelet activation in essential thrombocythemia (ET)based on transcriptome sequencing technology (RNA-seq ),and to explore the potential targets related to ET thrombosis. Methods:Blood samples from ET patients and healthy individuals were collected for RNA-seq,and differentially expressed lncRNAs,miRNAs,and mRNAs were selected to construct a lncRNA-miRNA-mRNA regulatory network. Differential mRNAs in the regulatory network were enriched and analyzed using Gene Ontology (GO ) and Kyoto Encyclopedia of Genes and Genomes (KEGG).The real-time PCR method was applied to validate differential mRNAs on crucial signaling pathways.Results:A total of 32 lncRNAs (3 up-regulated,29 down-regulated),16 miRNAs (8 up-regulated,8 down-regulated),and 35 mRNAs (27 up-regulated,8 down-regulated)were identified as differentially expressed.Among them,5 lncRNAs,12 miRNAs,and 19 mRNAs constituted the regulatory network.KEGG enrichment analysis showed that the differential mRNAs were related to the platelet activation signaling pathway,and there were 6 differential mRNAs related to platelet activation,namely F2R,ITGA2B,ITGB1,ITGB3,PTGS1,and GP1 BB,which were all up-regulated in their expression.RT-PCR results showed that the expression of five mRNAs including F2R,ITGA2B,ITGB1,ITGB3,and GP1BB were upregulated in ET patients compared with healthy subjects,and consistent with RNA-seq results,while PTGS1 expression was not significantly different.Conclusion:Differential mRNAs in ET patients are related to the platelet activation pathway,and F2R,ITGA2B,ITGB1,ITGB3,and GP1BB mRNAs may serve as novel targets associated with platelet activation in ET.
8.Effect of RNF113A on the malignant biological behavior of hepatocellular carcinoma cells
Hai-Jie DAI ; Xia HUANG ; Li-Jun DONG ; Ming-Xuan XING ; Teng-Yue ZOU ; Wen-Xiao LI
Chinese Journal of Current Advances in General Surgery 2024;27(4):275-281
Objective:To explore the effects of RNF113A on the proliferation,migration,in-vasion,apoptosis,and autophagy of hepatocellular carcinoma cells.Methods:Hep3B cells were divided into control group and RNF113A overexpression group(RNF113A-OE),HepG2 was divided into control group and RNF113A knockdown group(si-RNF113A),CCK-8 assay was used to detect changes in cell viability,clone formation assay was used to detect changes in cell proliferation abili-ty,Transwell assay was used to detect changes in cell invasion ability,wound healing assay was used to detect changes in cell migration ability,and flow cytometry was used to detect changes in cell apoptosis ability,Western blot experiments were used to detect changes in protein expression of autophagy related genes and AMPK signaling pathway related genes.Results:Compared with the control group,the proliferation,cloning,invasion,and migration abilities of Hep3B cells in the RNF113A-OE group were improved,while apoptosis and autophagy abilities were decreased,and the AMPK signaling pathway was inhibited;In the si-RNF113A group,the proliferation,cloning,in-vasion,and migration abilities of HepG2 cells were significantly reduced,while apoptosis and au-tophagy abilities were increased,and the activation of the AMPK signaling pathway was promoted.Conclusion:RNF113A promotes the proliferation,cloning,invasion,and migration of hepatocel-lular carcinoma cells,and inhibited apoptosis and autophagy by inhibiting the AMPK signaling path-way.
9.Determination of tryptophan metabolite levels in serum and urine from adolescents with depression by liquid chromatogra-phy-tandem mass spectrometry
Mengmeng MA ; Xiaoming TENG ; Liu LU ; Zhihan YE ; Ming ZONG
Chinese Journal of Clinical Laboratory Science 2024;42(8):561-566
Objective To observe and compare the concentrations of tryptophan-kynurenine pathway metabolites in serum and urine of adolescents with depression individuals using liquid chromatography-tandem mass spectrometry(LC-MS/MS).Methods The major metabolites in this pathway,such as tryptophan(TRP),kynurenine(KYN),kynurenic acid(KYNA),and 3-hydroxykynurenine(3-HK)were quantitatively analyzed using isotope-labeled internal standards.The separation was achieved using a Shimadzu C18 col-umn with gradient elution of 0.2%aqueous acid and acetonitrile.The detection was performed within 7 minutes using positive ion mode and multiple reaction monitoring(MRM).The parameters,such as linear range and precision were evaluated to assess reliability of the method.Subsequently,this method was applied to detect and compare the results in the samples of serum and urine from 143 adoles-cents with depression and 110 healthy controls.Results Taking TRP as the example,the linear ranges for serum and urine were 0.54 to 107.84 μmol/L and 0.74 to 147.06 μmol/L,respectively.The intra-batch coefficient of variation(CV)was ≤6.3%,the inter-batch CV was ≤3.22%,and the total laboratory CV was ≤6.5%.The results showed the KYNA,KYN and TRP levels were lower in the de-pression group compared to the control group,while 3-HK levels were higher in the depression group with statistical significance(P<0.01).Apart from TRP,the levels of other metabolites were significantly higher in urine than those in serum,with statistical signifi-cance(P<0.01).Conclusion Compared to the results of serum,the concentrations of TRP metabolites,including KYN,KYNA and 3-HK were higher than those in urine.The concentrations of TRP-KP metabolites in urine,i.e.,KYN,KYNA and 3-HK were higher than those in serum,and the detection of TRP-KP metabolites in urine may offer a greater advantage because the urine collection process is non-invasive.
10.Several key and difficult issues related to the grading of urothelial carcinoma of urinary bladder
Ming ZHAO ; Xiaodong TENG ; Huiying HE ; Liang CHENG
Chinese Journal of Pathology 2024;53(8):773-776
Grading and staging are the most important prognostic factors for both non-invasive and invasive urothelial carcinomas, and are also one of the most common difficulties encountered by pathologists in the daily diagnostic practice of urothelial carcinoma. Recently, the International Society of Urological Pathology organized a survey and questionnaire conference on various issues related to the diagnosis, grading, and staging of urothelial carcinoma, and ultimately formed a series of consensus opinions. This article briefly summarizes the consensus opinions of this series, and combines them with the current pathological diagnosis status of urothelial carcinoma in China. It briefly comments on how to apply this series of consensus opinions in the daily diagnostic practice of pathologists, deeply understand relevant diagnostic problems, and carry out relevant clinical pathological research to further solve problems.


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