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.To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia.
Xiao Shuai ZHANG ; Bing Cheng LIU ; Xin DU ; Yan Li ZHANG ; Na XU ; Xiao Li LIU ; Wei Ming LI ; Hai LIN ; Rong LIANG ; Chun Yan CHEN ; Jian HUANG ; Yun Fan YANG ; Huan Ling ZHU ; Ling PAN ; Xiao Dong WANG ; Gui Hui LI ; Zhuo Gang LIU ; Yan Qing ZHANG ; Zhen Fang LIU ; Jian Da HU ; Chun Shui LIU ; Fei LI ; Wei YANG ; Li MENG ; Yan Qiu HAN ; Li E LIN ; Zhen Yu ZHAO ; Chuan Qing TU ; Cai Feng ZHENG ; Yan Liang BAI ; Ze Ping ZHOU ; Su Ning CHEN ; Hui Ying QIU ; Li Jie YANG ; Xiu Li SUN ; Hui SUN ; Li ZHOU ; Ze Lin LIU ; Dan Yu WANG ; Jian Xin GUO ; Li Ping PANG ; Qing Shu ZENG ; Xiao Hui SUO ; Wei Hua ZHANG ; Yuan Jun ZHENG ; Qian JIANG
Chinese Journal of Hematology 2023;44(9):728-736
Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult
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Humans
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Adolescent
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Imatinib Mesylate/adverse effects*
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Incidence
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Antineoplastic Agents/adverse effects*
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Retrospective Studies
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Pyrimidines/adverse effects*
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
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Treatment Outcome
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Benzamides/adverse effects*
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Leukemia, Myeloid, Chronic-Phase/drug therapy*
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Aminopyridines/therapeutic use*
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Protein Kinase Inhibitors/therapeutic use*
3.Prediction of Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma by Evaluation Index of Liver Fibrosis
Shui-rong LIN ; Hao-zhong LIN ; Bai-feng QIAN ; Mu-qi LI ; Hong PENG ; Yun-peng HUA ; Bao-gang PENG ; Shun-li SHEN
Journal of Sun Yat-sen University(Medical Sciences) 2021;42(6):874-882
ObjectiveThe aspartate aminotransferase-to-platelet ratio index (APRI) and liver fibrosis-4 index (FIB-4) have been used for noninvasive prediction of liver fibrosis and cirrhosis and both indexes exhibit a high degree of accuracy in the the prediction of the prognosis of hepatocellular carcinoma(HCC)patients after hepatectomy.. This study aims to explore the predictive values of APRI and FIB-4 in the occurrence of posthepatectomy liver failure (PHLF) in HCC patients. MethodsThe clinical data of 426 patients with HCC who underwent hepatectomy in our hospital were retrospectively analyzed. Laboratory data were collected from patients within 2 weeks prior to hepatectomy. APRI, FIB-4 and Child-Pugh scores were calculated. Receiver operating characteristic (ROC) curves were used to determine the AUC values and optimal cut-off values of APRI, FIB-4 and Child-Pugh scores. Univariate and multivariate logistic regression analyses were employed to identify the independent risk factors for PHLF, and the predictive values of APRI and FIB-4 on PHLF were compared. ResultsA total of 48 patients (11.3%) developed PHLF. Multivariate analysis showed that major hepatectomy (≥3 segments resection), blood loss >400 mL, total bilirubin (TBIL), platelet (PLT), fibrinogen (Fib), APRI and FIB-4 were independent risk factors for PHLF. ROC curve analysis revealed that APRI (AUC = 0.816) and FIB-4 (AUC = 0.728) had better ability to predict PHLF than Child-Pugh score (AUC = 0.566; P<0.001). ConclusionsPreoperative APRI and FIB-4 are independent predictors of PHLF in HCC patients after hepatectomy and have good predictive values.
4.Status Quo and Development of Hope Houses for Individuals with Spinal Cord Injury in Shanghai from Perspective of Managers and Organizers
Hai-xia XIE ; Yu-hui YANG ; Ai-rong WU ; Chen SHEN ; Long-jun HU ; Jia ZHANG ; Pei-pei LIN ; Gang CHEN ; Jun LÜ ; Feng-shui CHANG
Chinese Journal of Rehabilitation Theory and Practice 2019;25(10):1221-1227
Objective:To analyze the status quo and development of the Hope Houses for individuals with spinal cord injury (SCI) in Shanghai. Methods:In June, 2018, the organizers and managers of Hope Houses from 16 districts in Shanghai were investigated with the self-designed questionnaires, which covered the personal characteristics, knowledge of related policy, development of projects and obstacles, and rehabilitation recognition. The descriptive analysis and correlational analyses were conducted. Results:Totally, eleven organizers and 16 managers were investigated. The knowledge of related policy for organizers was not good enough. Eight Hope Houses in 16 districts in Shanghai were operated by social organizations. The average implementation rate of projects in Hope Houses was 60.6%, and the highest was rehabilitation knowledge education (96.3%). There was insufficient provision in legal services, job skills training, rehabilitation nursing guidance, job referral, medical referral and education referral, etc. The main related factors limiting the development of the Hope Houses were lacks of budgets, social consensus and professionals. The rehabilitation cognition of organizers and managers was generally good, but the cognition of rehabilitation principles and rehabilitation value needed to be strengthened. Conclusion:The Hope Houses for individuals with SCI in Shanghai work well, and the rehabilitation cognition of organizers and managers is satisfactory. It should be strenghened in resource input, comprehensive rehabilitation and standard of management, to expand the service timely.
5.Rapid identification of geographical origins and determination of polysaccharides contents in Ganoderma lucidum based on near infrared spectroscopy and chemometrics.
LAI CJS ; Rong-Rong ZHOU ; Yi YU ; Wen ZENG ; Ming-Hua HU ; Luo-di FAN ; Lin CHEN ; Zi-Dong QIU ; Chuan SONG ; Shui-Han ZHANG ; Lan-Ping GUO ; Lu-Qi HUANG
China Journal of Chinese Materia Medica 2018;43(16):3243-3248
Near infrared spectroscopy combined with chemometrics methods was used to distinguish Ganoderma lucidum samples collected from different origins, and a prediction model was established for rapid determine polysaccharides contents in these samples. The classification accuracy for training dataset was 96.87%, while for independent dataset was 93.33%; as for the prediction model, 5-fold cross-validation was used to optimize the parameters, and different signal processing methods were also optimized to improve the prediction ability of the model. The best square of correlation coefficients for training dataset was 0.965 4, and 0.851 6 for validation dataset; while the root-mean-square deviation values for training dataset and validation dataset were 0.018 5 and 0.023 6, respectively. These results showed that combining near infrared spectroscopy with suitable chemometrics approaches could accuracy distinguish different origins of G. lucidum samples; the established prediction model could precious predict polysaccharides contents, the proposed method can help determine the activity compounds and quality evaluation of G. lucidum.
Fungal Polysaccharides
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analysis
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Geography
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Least-Squares Analysis
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Reishi
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chemistry
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Spectroscopy, Near-Infrared
6.Discussion on scientific problems in standard decoction of traditional Chinese medicine.
Shui-Han ZHANG ; Xue-Juan LIANG ; Hao LIU ; Dan WAN ; Toda KOIN ; Lin CHEN ; Rong-Rong ZHOU ; Lu-Qi HUANG
China Journal of Chinese Materia Medica 2017;42(17):3275-3281
Based on the reviewing of development and disadvantages of Chinese medicine formula granules, the concept of standard decoction of traditional Chinese medicine was proposed in this study, and it was used as the standard mode of Chinese medicine formula granules to standardize the production process and quality standards of formula granules. The standard was unified according to the principles of "standardization of medicinal materials, standardization of process, intellectualization of production, standardization of quality, normalization of packaging, and informatization of storage"; and consistency evaluation was carried out by the analysis of chemical components, pharmacological activities and clinical efficacy of the standardized decoction and the traditional decoction, interpreting the scientific questions to ensure the stability and uniformity of Chinese medicine formula granule as well as the safety and effectiveness of its clinical application.
7.Apoptosis of Lewis Lung Carcinoma Cells Induced by Microwave via p53 and Proapoptotic Proteins In vivo
Zhang KOU-DONG ; Tong LIN-RONG ; Wang SHUI-MING ; Peng RUI-YUN ; Huang HAI-DONG ; Dong YU-CHAO ; Zhang XING-XING
Chinese Medical Journal 2017;130(1):15-22
Background:Microwave therapy is a minimal invasive procedure and has been employed in clinical practice for the treatment of various types of cancers.However,its therapeutic application in non-small-cell lung cancer and the underlying mechanism remains to be investigated.This study aimed to investigate its effect on Lewis lung carcinoma (LLC) tumor in vivo.Methods:Fifty LLC tumor-bearing C57BL/6 mice were adopted to assess the effect of microwave radiation on the growth and apoptosis of LLC tumor in vivo.These mice were randomly assigned to 10 groups with 5 mice in each group.Five groups were treated by single pulse microwave at different doses for different time,and the other five groups were radiated by multiple-pulse treatment of a single dose.Apoptosis of cancer cells was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay.Western blotting was applied to detect the expression of proteins.Results:Single pulse of microwave radiation for 5 min had little effect on the mice.Only 15-min microwave radiation at 30 mW/cm2 significantly increased the mice body temperature (2.20 ± 0.82)℃ as compared with the other groups (0.78 ± 0.29 ℃,1.24 ± 0.52 ℃,0.78 ± 0.42 ℃,respectively),but it did not affect the apoptosis of LLC tumor cells significantly.Continous microwave radiation exposure,single dose microwave radiation once per day for up to seven days,inhibited cell division and induced apoptosis of LLC tumor cells in a dose-and duration-dependent manner.It upregulated the protein levels of p53,Caspase 3,Bax and downregulated Bcl-2 protein.Conclusions:Multiple exposures of LLC-bearing mice to microwave radiation effectively induced tumor cell apoptosis at least partly by upregulating proapoptotic proteins and downregulating antiapoptotic proteins.Continuous radiation at low microwave intensity for a short time per day is promising in treating non-small-cell lung cancer.
8. miR-218 expression in osteosarcoma tissues and its effect on cell growth in osteosarcoma cells
Hong-Tai WANG ; Ai-Gang LIU ; Zhang-Nan ZHOU ; Hong-Guang LIN ; Rong-Zi CHEN ; Kun CHEN ; Dao-Shu LUO ; Jin-Shui HE
Asian Pacific Journal of Tropical Medicine 2014;7(12):1000-1004
Objective: To investigate the expression of miR-218 and its clinical significance in osteosarcoma tissues and explore its effect on proliferation and apoptosis in osteosarcoma cells. Methods: miR-218 expression was detected in 76 samples of surgically resected osteosarcoma and matched normal tumor-adjacent tissues using quantitative reverse transcription polymerase chain reaction (qRT-PCR). MiR-218 was over-expressed by exogenous miR-218 plasmids in Saos-2 cells, and then BrdU cell proliferation assay and flow cytometry were used to determine cell proliferation and apoptosis. Results: The expression of miR-218 in osteosarcoma tissues was significantly lower than those in normal tumor-adjacent tissues (t=8.735, P<0.001). MiR-218 expression in tumor tissues was significantly correlated with tumor size (χ
9.Serial (18)F-FDG PET-CT imaging during radiotherapy for nasopharyngeal carcinoma: a prospective clinical study.
Qin LIN ; Rong-shui YANG ; Long SUN ; Yi-min LI ; Li-chen WANG ; Ming-ming DAI ; Zuo-ming LUO ; Long ZHAO ; Hua WU
Chinese Journal of Oncology 2012;34(5):356-359
OBJECTIVEThe primary aim of this prospective study was to use serial (18)F-FDG PET-CT imaging to evaluate the trend of the tumor's maximum standardized uptake value (SUVmax) during radiotherapy (RT) for patients with nasopharyngeal carcinoma (NPC), and to explore the possibility of early evaluation of the tumor bio-metabolic response during radiotherapy.
METHODSSixty patients with biopsy-proven primary NPC were prospectively enrolled into the study. All patients underwent four (18)F-FDG PET-CT scans: one initial scan before RT/cisplatin based concurrent chemoradiotherapy, at the point of 50 Gy during RT, the end of RT, and one month after RT, respectively. Tumor (18)F-FDG uptake was analyzed according to the World Health Organization pathological type.
RESULTSThere was a significant difference (P < 0.001) of the mean of SUVmax of the primary site among pretreatment (11.20 ± 5.37) and posttreatment at the dose of 50 Gy (3.50 ± 1.59), at the end of RT (3.05 ± 1.56) and one month after RT (2.52 ± 1.46). There was also a significant difference (P < 0.001) of the mean of SUVmax of neck node site. However, there was a significant difference of the SUVmax between histological WHO type IIb and type IIa in the primary site (P = 0.046) [(67 ± 19)% reduction at dose 50 Gy for type IIb vs. (55 ± 24)% for type IIa] but not in the lymph nodes.
CONCLUSIONSEarly PET scan during or right after RT instead of conventional 3 months interval after RT is indicated to evaluate the tumor response and to develop individualized adaptive radiotherapy in NPC. Our next study will attempt to demonstrate the results based on long-term follow-up data.
Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Squamous Cell ; diagnosis ; drug therapy ; pathology ; radiotherapy ; Chemoradiotherapy ; Cisplatin ; administration & dosage ; Female ; Fluorodeoxyglucose F18 ; Humans ; Lymphatic Metastasis ; Male ; Nasopharyngeal Neoplasms ; diagnosis ; drug therapy ; pathology ; radiotherapy ; Neoplasm Staging ; Positron-Emission Tomography ; methods ; Prospective Studies ; Radiopharmaceuticals ; Radiotherapy Dosage ; Radiotherapy, High-Energy ; Radiotherapy, Intensity-Modulated ; Tomography, X-Ray Computed
10.Complete genomic sequence of a watermelon isolate of cucumber green mottle mosaic virus in northern China.
Hong-yun CHEN ; Shi-ming LIN ; Qing CHEN ; Wen-jun ZHAO ; Fu-rong LIAO ; Hong-jun CHEN ; Shui-fang ZHU
Chinese Journal of Virology 2009;25(1):68-72
The complete genomic sequence of a watermelon isolate of Cucumber green mottle mosaic virus (CGMMV-LN) in Liaoning province was determined and compared with other cucurbit-infecting tobamoviruses. The genomic RNA of CGMMV-LN comprised 6422 nt, and 5'- and 3'- noncoding regions consisted of 59 nt and 175 nt, respectively. The encoded four proteins were two replicase proteins of 186 kD and 129 kD, move protein of 29 kD and coat protein of 17.4 kD. The alignment results of complete nucleotide sequence showed that CGMMV-LN shared identities of 97.6%-99.3% with four other CGMMV isolates, but only shared identities of 61.7%-62.8% with three other tobamoviruses. Homology trees generated from replicase proteins of 186 kD and coat proteins suggested that cucurbit-infecting tobamoviruses could be separated into two subgroups: subgroup I comprising all the isolates of CGMMV and subgroup II comprising Cucumber fruit mottle mosaic virus, Kyuri green mottle mosaic virus and Zucchini green mottle mosaic virus.
Base Sequence
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China
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Citrullus
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virology
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Genome, Viral
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genetics
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Molecular Sequence Data
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Tobamovirus
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genetics

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