1.Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy
Pei-Chien TSAI ; Chung-Feng HUANG ; Ming-Lun YEH ; Meng-Hsuan HSIEH ; Hsing-Tao KUO ; Chao-Hung HUNG ; Kuo-Chih TSENG ; Hsueh-Chou LAI ; Cheng-Yuan PENG ; Jing-Houng WANG ; Jyh-Jou CHEN ; Pei-Lun LEE ; Rong-Nan CHIEN ; Chi-Chieh YANG ; Gin-Ho LO ; Jia-Horng KAO ; Chun-Jen LIU ; Chen-Hua LIU ; Sheng-Lei YAN ; Chun-Yen LIN ; Wei-Wen SU ; Cheng-Hsin CHU ; Chih-Jen CHEN ; Shui-Yi TUNG ; Chi‐Ming TAI ; Chih-Wen LIN ; Ching-Chu LO ; Pin-Nan CHENG ; Yen-Cheng CHIU ; Chia-Chi WANG ; Jin-Shiung CHENG ; Wei-Lun TSAI ; Han-Chieh LIN ; Yi-Hsiang HUANG ; Chi-Yi CHEN ; Jee-Fu HUANG ; Chia-Yen DAI ; Wan-Long CHUNG ; Ming-Jong BAIR ; Ming-Lung YU ;
Clinical and Molecular Hepatology 2024;30(3):468-486
Background/Aims:
Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients.
Methods:
We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development.
Results:
Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients.
Conclusions
Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.
2. Real-world study of ceftazidime-avibactam in the treatment of multidrug-resistant gram-negative bacterial infections
Daoli JIANG ; Xiaohua CHOU ; Zhidong LIU ; Wei LI ; Bo ZHANG ; Dongmei LV ; Tao WANG ; Sang XU ; Defei TAN ; Yi FANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(9):1008-1017
AIM: To describe and evaluate the clinical characteristics, treatment management and clinical outcomes of ceftazidime-avibactam (CZA) in the treatment of patients with multidrug-resistant gram-negative bacterial (MDR-GNB) infections. METHODS: A retrospective cohort study was performed on patients hospitalized in the Affiliated Hospital of Xuzhou Medical University from September 2019 to December 2021. Adult patients who received CZA for ≥ 72 hours consecutively were eligible for inclusion. The primary outcome was clinical failure, defined as a composite of 30-day all-cause mortality, microbiological failure and / or failure to resolve or improve signs and symptoms of infection during treatment with CZA. RESULTS: A total of 198 patients with MDR-GNB infections were described and evaluated, including 132 in the carbapenem-resistant Enterobatceriaceae (CRE) cohort and 66 in the Pseudomonas spp. cohort. The main infection sites were lung infection (92.42%), abdominal infection (10.61%), and intracranial infection (10.61%), among which 63 patients (31.82%) were positive for blood culture. Clinical failure, 30-day all-cause mortality and microbiological failure occurred in 61 (30.81%), 33(16.67%) and 11(5.56%) patients, respectively. Body mass index (BMI), acute physiology and chronic health evaluation scoring system (APACHE Ⅱ) and polymicrobial infections were positively associated with clinical outcome failureadjusted OR 1.109, 95%CI 1.017, 1.209; adjusted OR 1.071, 95%CI 1.015, 1.129; adjusted OR 2.844, 95%CI 1.391, 5.814, however, initiation of CZA within 48 hours of admission was protective (adjusted OR 0.424, 95%CI 0.205, 0.879). A total of 15 patients had adverse reactions possibly related to CZA, including 2 cases of rash, 6 cases of nausea and vomiting, and 7 cases of antibiotic-related diarrhea. CONCLUSION: CZA can be used to treat infections caused by a range of MDR-GNB, including Pseudomonas spp. and CRE.
3.Exploring loss and grief during the COVID-19 pandemic: A scoping review of qualitative studies.
Xinyu TAO ; Chou Chuen YU ; James Alvin LOW
Annals of the Academy of Medicine, Singapore 2022;51(10):619-628
INTRODUCTION:
The COVID-19 pandemic has brought about multiple losses to various groups, namely patients, families and healthcare professionals. Grief, which is the reaction to these losses, could cause strain on these individuals' physical and mental health if not identified and managed early. This scoping review analysed loss, grief and how they were managed among these groups during the pandemic.
METHOD:
This scoping review utilised the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement extension for Scoping Reviews (PRISMA-ScR) and the Joanna Briggs Institute framework for scoping reviews. Only qualitative studies relating to loss and grief and their management were included. Of 166 studies screened, 69 were included in the study. Qualitative analysis and data coding of each record were conducted through qualitative data analysis software.
RESULTS:
Losses included the death of family members, patients, colleagues and others. They also included the loss of usual routines, lifestyles and physical health. The grief experienced was multidimensional, affecting mainly the emotional, physical, social and existential realms. Anger, guilt and fear resulted from unsatisfactory farewells, issues with funerals, social isolation, financial strain and stigmatisation. Management strategies could be categorised into 5 themes: communication, finance, counselling, education and spiritual care.
CONCLUSION
Loss and grief identification and management among patients, family members and healthcare professionals are critically important during this COVID-19 pandemic. Current operating guidelines have proven insufficient in managing loss and grief. Innovative strategies are essential to tackle the many dimensions of loss and grief. Nevertheless, further research is necessary to better understand the effectiveness of implemented policies.
Humans
;
COVID-19
;
Grief
;
Health Personnel
;
Pandemics
;
Qualitative Research
4.Bibenzyls from Dendrobium officinale.
Yu-Juan ZHOU ; Jun-Hao WANG ; Hong XU ; Gui-Xin CHOU ; Zheng-Tao WANG
China Journal of Chinese Materia Medica 2021;46(15):3853-3858
Fifteen bibenzyls were isolated and purified from the ethyl acetate extract of the stems of Dendrobium officinale by macroporous resin, MCI, silica gel, Sephadex LH-20, and ODS column chromatographies, as well as preparative thin-layer chromatography and preparative HPLC. The structures of compounds were identified according to the spectra data of ~1H-NMR, ~(13)C-NMR, and MS, and the physical and physiochemical properties: dendrocandin X(1), 3,4'-dihydroxy-4,5-dimethoxybibenzyl(2), 6″-de-O-methyldendrofindlaphenol A(3), 3,4-dihydroxy-4',5-dimethoxybibenzyl(4), dendrosinen B(5), 3,4,4'-trihydroxy-5-methoxybibenzyl(6), 3,3'-dihydroxy-4,5-dimethoxybibenzyl(7), 3,4'-dihydroxy-5-methoxybibenzyl(8), moscatilin(9), gigantol(10), 4,4'-dihydroxy-3,5-dimethoxybibenzyl(11), 3,4',5-trihydroxy-3'-methoxybibenzyl(12), 3-O-methylgigantol(13), dendrocandin U(14), and dendrocandin N(15). Compound 1 was a novel compound. Compound 2 was isolated from Dendrobium species for the first time. Compounds 3-7 were isolated from D. officinale for the first time.
Bibenzyls
;
Chromatography, High Pressure Liquid
;
Dendrobium
;
Magnetic Resonance Spectroscopy
5.Genetic analysis of a child with recessive dystrophic epidermolysis bullosa due to compound heterozygous variants of (COL7A1 gene.
Xue LYU ; Hao LI ; Hongyan LIU ; Haiyan CHOU ; Tao LI ; Wu ZHOU
Chinese Journal of Medical Genetics 2020;37(4):445-448
OBJECTIVE:
To carry out genetic testing and prenatal diagnosis for a family affected with recessive dystrophic epidermolysis bullosa (RDEB).
METHODS:
All exons of the COL7A1 gene and their flanking regions were subjected to PCR and Sanger sequencing. Suspected variant was validated in family members, based on which prenatal diagnosis was provided.
RESULTS:
Sanger sequencing found that the proband has carried two variants of the COL7A1 gene, namely c.7289delC (p.Pro2430Glnfs*36) and c.7474C>T (p.Arg2492*), which were respectively derived from his mother and father. The same variants were not found among 100 healthy controls. By prenatal diagnosis, the fetus was found to have inherited the c.7474C>T (p.Arg2492*) variant from its father.
CONCLUSION
The pathogenic variants of the COL7A1 gene of the RDEB family were clarified, based on which prenatal diagnosis was provided.
Child
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Collagen Type VII
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genetics
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Epidermolysis Bullosa Dystrophica
;
genetics
;
Exons
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Female
;
Genes, Recessive
;
Genetic Testing
;
Humans
;
Male
;
Mutation
;
Pregnancy
;
Prenatal Diagnosis
;
Sequence Analysis, DNA
6.BRCA1/2 mutation status in patients with metachronous breast and ovarian malignancies: clues towards the implementation of genetic counseling
Angel CHAO ; Yi-Hao LIN ; Lan-Yan YANG ; Ren-Chin WU ; Wei-Yang CHANG ; Pi-Yueh CHANG ; Shih-Cheng CHANG ; Chiao-Yun LIN ; Huei-Jean HUANG ; Cheng-Tao LIN ; Hung-Hsueh CHOU ; Kuan-Gen HUANG ; Wen-Ling KUO ; Ting-Chang CHANG ; Chyong-Huey LAI
Journal of Gynecologic Oncology 2020;31(3):e24-
Objective:
The characteristics of patients with metachronous breast and ovarian malignancies and the pathogenic role of BRCA1/2 mutations remain poorly understood. We investigated these issues through a review of hospital records and nationwide Taiwanese registry data, followed by BRCA1/2 mutation analysis in hospital-based cases.
Methods:
We retrospectively retrieved consecutive clinical records of Taiwanese patients who presented with these malignancies to our hospital between 2001 and 2017. We also collected information from the Data Science Center of the Taiwan Cancer Registry (TCR) between 2007 and 2015. Next-generation sequencing and multiplex ligation-dependent probe amplification were used to identify BRCA1/2 mutations and large genomic rearrangements, respectively. When BRCA1/2 mutations were identified in index cases, pedigrees were reconstructed and genetic testing was offered to family members.
Results:
A total of 12,769 patients with breast cancer and 1,537 with ovarian cancer were retrieved from our hospital records. Of them, 28 had metachronous breast and ovarian malignancies. We also identified 113 cases from the TCR dataset. Eighteen hospital-based cases underwent BRCA1/2 sequencing and germline pathogenic mutations were detected in 7 patients (38.9%, 5 in BRCA1 and 2 in BRCA2). All BRCA1/2 mutation carriers had ovarian high-grade serous carcinomas. Of the 12 patients who were alive at the time of analysis, 5 were BRCA1/2 mutation carriers. All of them had family members with BRCA1/2-associated malignancies.
Conclusions
Our results provide pilot evidence that BRCA1/2 mutations are common in Taiwanese patients with metachronous breast and ovarian malignancies, supporting the clinical utility of genetic counseling.
7.Maintenance of pegylated liposomal doxorubicin/carboplatin in patients with advanced ovarian cancer: randomized study of an Asian Gynecologic Oncology Group
Chyong-Huey LAI ; Elizabeth VALLIKAD ; Hao LIN ; Lan-Yan YANG ; Shih-Ming JUNG ; Hsueh-Erh LIU ; Yu-Che OU ; Hung-Hsueh CHOU ; Cheng-Tao LIN ; Huei-Jean HUANG ; Kuan-Gen HUANG ; Jiantai QIU ; Yao-Ching HUNG ; Tzu-I WU ; Wei-Yang CHANG ; Kien-Thiam TAN ; Chiao-Yun LIN ; Angel CHAO ; Chee-Jen CHANG
Journal of Gynecologic Oncology 2020;31(1):e5-
Objectives:
An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer.
Methods:
Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m2, n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA/homologous recombination deficiency (HRD) genes, because BRCA/HRD mutations (BRCA/HRDm) are known to be associated with better prognosis.
Results:
Enrollment was slow, accrual was closed when 7+ years had passed. With a medianfollow-up of 88.9 months, the median PFS was significantly better in arm A (55.5 months) than arm B (9.2 months) (hazard ratio [HR]=0.40; 95% confidence interval [CI]=0.19–0.87; p=0.020), yet the median overall survival was not significantly different in arm A (not reached) than arm B (95.1 months) (p=0.148). Overall grade 3/4 adverse events were more frequent in arm A than arm B (60.9% vs 0.0%) (p<0.001). Quality of life was generally not significantly different. Distribution of BRCA1/2m or BRCA/HRDm was not significantly biased between the two arms. Wild-type BRCAon-HRD subgroup seemed to fare better with maintenance therapy (HR=0.35; 95% CI=0.11–1.18; p=0.091).
Conclusions
Despite limitations in small sample size, it suggests that maintenance carboplatin-PLD chemotherapy could improve PFS in advanced ovarian cancer.
8.Maintenance of pegylated liposomal doxorubicin/carboplatin in patients with advanced ovarian cancer: randomized study of an Asian Gynecologic Oncology Group
Chyong Huey LAI ; Elizabeth VALLIKAD ; Hao LIN ; Lan Yan YANG ; Shih Ming JUNG ; Hsueh Erh LIU ; Yu Che OU ; Hung Hsueh CHOU ; Cheng Tao LIN ; Huei Jean HUANG ; Kuan Gen HUANG ; Jiantai QIU ; Yao Ching HUNG ; Tzu I WU ; Wei Yang CHANG ; Kien Thiam TAN ; Chiao Yun LIN ; Angel CHAO ; Chee Jen CHANG
Journal of Gynecologic Oncology 2020;31(1):5-
9.Quality standard study on Tibetan medicine Gentianae Urnulae Herba.
Liu-liu ZONG ; Gui-fa LUO ; Li-hong WU ; Zheng-tao WANG ; Gui-xin CHOU ; Hai-qing LIU
China Journal of Chinese Materia Medica 2015;40(19):3878-3882
Gentianae Urnulae Herba, dried whole herb of Gentiana urnula,is a commonly used Tibetan medicine. However, only the character identification is used as quality control standard officially at present. As a part of project for the Chinese Pharmacopoeia (2015 edition), the quality standard of this species was established in this study. The tests of water content, total ash, acid-insoluble ash and ethanol-soluble extractives of the crude drugs were carried out following the methods recorded in appendix of Chinese Pharmacopeia (2010 edition, volume 1). The TLC identification method was established by using gentiournoside A as reference substance, and a mixture of ethyl acetate-methanol-water-formic acid(7:1. 5:1: 0. 2) as the developing solvent system on silica gel G TLC plate. The content of gentiournoside A was assayed by HPLC on an Agilent Zorbax SB-C18 (4.6 mm x 250 mm,5 μm) column, using acetonitrile-water (0.1% phosphoric acid) (26:74) as the mobile phase at a flow rate of 1.0 mL x min(-1). The column temperature is at 30 degrees C and the detection wavelength is at 240 nm. As a result, gentiournoside A and the other constituents were separated and presented the same fluorescence light comparing with the reference substance on TLC detected under the UV light(366 nm). The methodology validation for the assay of gentiournoside A showed that it was in a good linear correlation in the range of 0.009 95-0.398 g x L(-1) with the regression equation of Y = 1 467.1X +41.407(r = 0.999 9), and the average recovery was 98. 3% (RSD 2.2%). The mass fractions of gentiournoside A, water content, ethanol-soluble extractives of 15 batches samples were varied in the ranges of 0.175% -1.83%, 8.60% - 9.93% and 29.2% - 35.2%, respectively. Total ash and acid-insoluble ash were 10.2% - 17.2% and 5.26% - 10.8% detected from 10 batches samples. The recommended standards of quantitative indexes are that the mass fractions of gentiournoside A and extractives are not less than 0.80% and 26.0%, respectively; the water, total ash and acid-insoluble ash are not more than 12.0%, 15.0% and 8.0%, respectively.
China
;
Drugs, Chinese Herbal
;
chemistry
;
pharmacology
;
standards
;
Humans
;
Medicine, Tibetan Traditional
;
standards
;
Plants, Medicinal
;
chemistry
;
Quality Control
10.Separation and authentication of tilianin and quality standards of semen of Dracocephalum moldavia.
Xue-mei CHENG ; Ting-yun MA ; Su LEY-MAN ; Ha-Lik ; Dan-dan MU ; Tiann FANG ; Gui-Xin CHOU ; Zheng-tao WANG ; Chang-hong WANG
China Journal of Chinese Materia Medica 2015;40(10):1845-1849
Tilianin was separated and authenticated from the seeds of Dracocephalum moldavia, a Uygur medicine, by chromatographic technique and spectroscopic method. The purity of tilianin is more than 98% determined by HPLC area normalization method. Thin layer chromatography (TLC) method was used to separate tilianin from D. moldavia by mixture of chloroform-methanol (5: 1) as a developing solvent on high performance silicagel precoated plate (SGF254) and using aluminium trichloride as a chromogenic agent for qualitative identification of D. moldavia. To establish a HPLC method for quantitative analysis of D. moldavia, tilianin was used as a Quantitative marker and separated on a C18 (4.6 mm x 250 mm, 5 μm) column with acetonitrile-01% formic acid (25: 75) as the mobile phase and detected at 330 nm. The calibration curve of tilianin displayed ideal linearity over the range of 0.617 2-123.44 μg x mL(-1) with a regression equation of Y = 33.773X - 0.824 8 (r = 1). The average recovery of tilianin was 101.0% with RSD of 3.7%. The RSD values of intra-day and inter-day precision were less than 2%. The content of tilianin in 4 batches of the authenticated semen of D. Moldavia was between 0.016 and 0.187 mg x g(-1). The qualitative and quantitative method established is suitable for the quality evaluation and assessment of semen of D. Moldavia.
Chromatography, High Pressure Liquid
;
Chromatography, Thin Layer
;
Drugs, Chinese Herbal
;
chemistry
;
isolation & purification
;
standards
;
Flavonoids
;
chemistry
;
isolation & purification
;
standards
;
Glycosides
;
chemistry
;
isolation & purification
;
standards
;
Lamiaceae
;
chemistry
;
Magnetic Resonance Spectroscopy
;
Quality Control

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