1.Analysis of the efficacy and safety profile of sofosbuvir/velpatasvir/voxilaprevir in the treatment of patients with chronic hepatitis C with failed DAAs therapy
Yan GUO ; Songtao ZHAO ; Yan ZHU ; Cheng YANG ; Jianping LI ; Lihua ZHANG ; Changming YANG ; Huagang XIONG ; Dong ZHANG ; Guangjun TIAN ; Bihua GAO ; Li GUO ; Jie XIA
Chinese Journal of Hepatology 2024;32(S2):25-30
Objective:To explore the efficacy and safety profile of sofosbuvir/velpatasvir/voxilaprevir ± ribavirin (SOF/VEL/VOX±RBV) for salvage treatment of chronic hepatitis C patients who have failed direct-acting antivirals (DAAs).Methods:Patients with chronic hepatitis C who failed DAAs±RBV treatment and were treated in five hospitals in Chongqing, Guangdong, Guizhou, and Guangxi from January 2022 to December 2023 were included in this retrospective study. One or more courses of DAAs±RBV therapy were evaluated for all patients who had been previously treated. Virological rebound occurrence was observed during the follow-up. SOF/VEL/VOX±RBV was used for one course of salvage treatment. Virological and biochemical indicators were analyzed before salvage therapy, post-treatment, and drug discontinuation at 12 weeks. Adverse drug events were recorded during treatment. Data between groups were compared using t-tests or non-parametric tests.Results:A total of 26 cases of chronic hepatitis C who had failed DAAs±RBV were included in this study, with an age of (52.9±9.6) years. Twenty-one cases (80.8%) were male, sixteen (61.5%) had a history of drug abuse, two (7.7%) had combined human immunodeficiency virus infection, and fourteen (53.8%) had combined cirrhosis. The previous DAA regimen of 21 cases (80.8%) included SOF/VEL. The baseline HCV RNA load of salvage treatment was (5.8±1.6) log 10 IU/ml, and 16 cases (61.5%) were genotype 3. All patients completed the 12-week SOF/VEL/VOX±RBV salvage treatment and achieved sustained virological response (SVR) at the end of treatment. All 22 cases were followed up for 12 weeks following treatment completion and attained SVR12, including patients with genotype 3 and cirrhosis. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) had normalized return rates of 94.1% and 93.8%, respectively, following therapy. ALT, AST, FIB-4 index, APRI, and aPMAP scores were significantly lower than those before treatment ( Z=-3.980, -3.875, -3.461, -3.582, P<0.05). The proportion of patients in the high-risk group of liver cancer dropped (52.6% before treatment and 33.3% after treatment), and more patients were reclassified to medium-and low-risk groups. Two cases (7.7%) experienced nausea and diarrhea, one case (3.8%) had a headache, and one case (3.8%) had fatigue, all of which were well managed during treatment. There were no serious adverse events, deaths, or interruptions of treatment due to adverse reactions. Conclusions:SOF/VEL/VOX is a safe and effective salvage treatment option for chronic hepatitis C patients who have failed DAAs therapy, and may be particularly beneficial to refractory populations infected with genotype 3 and combined with cirrhosis.
2.Analysis of the efficacy and safety profile of sofosbuvir/velpatasvir/voxilaprevir in the treatment of patients with chronic hepatitis C with failed DAAs therapy
Yan GUO ; Songtao ZHAO ; Yan ZHU ; Cheng YANG ; Jianping LI ; Lihua ZHANG ; Changming YANG ; Huagang XIONG ; Dong ZHANG ; Guangjun TIAN ; Bihua GAO ; Li GUO ; Jie XIA
Chinese Journal of Hepatology 2024;32(S2):25-30
Objective:To explore the efficacy and safety profile of sofosbuvir/velpatasvir/voxilaprevir ± ribavirin (SOF/VEL/VOX±RBV) for salvage treatment of chronic hepatitis C patients who have failed direct-acting antivirals (DAAs).Methods:Patients with chronic hepatitis C who failed DAAs±RBV treatment and were treated in five hospitals in Chongqing, Guangdong, Guizhou, and Guangxi from January 2022 to December 2023 were included in this retrospective study. One or more courses of DAAs±RBV therapy were evaluated for all patients who had been previously treated. Virological rebound occurrence was observed during the follow-up. SOF/VEL/VOX±RBV was used for one course of salvage treatment. Virological and biochemical indicators were analyzed before salvage therapy, post-treatment, and drug discontinuation at 12 weeks. Adverse drug events were recorded during treatment. Data between groups were compared using t-tests or non-parametric tests.Results:A total of 26 cases of chronic hepatitis C who had failed DAAs±RBV were included in this study, with an age of (52.9±9.6) years. Twenty-one cases (80.8%) were male, sixteen (61.5%) had a history of drug abuse, two (7.7%) had combined human immunodeficiency virus infection, and fourteen (53.8%) had combined cirrhosis. The previous DAA regimen of 21 cases (80.8%) included SOF/VEL. The baseline HCV RNA load of salvage treatment was (5.8±1.6) log 10 IU/ml, and 16 cases (61.5%) were genotype 3. All patients completed the 12-week SOF/VEL/VOX±RBV salvage treatment and achieved sustained virological response (SVR) at the end of treatment. All 22 cases were followed up for 12 weeks following treatment completion and attained SVR12, including patients with genotype 3 and cirrhosis. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) had normalized return rates of 94.1% and 93.8%, respectively, following therapy. ALT, AST, FIB-4 index, APRI, and aPMAP scores were significantly lower than those before treatment ( Z=-3.980, -3.875, -3.461, -3.582, P<0.05). The proportion of patients in the high-risk group of liver cancer dropped (52.6% before treatment and 33.3% after treatment), and more patients were reclassified to medium-and low-risk groups. Two cases (7.7%) experienced nausea and diarrhea, one case (3.8%) had a headache, and one case (3.8%) had fatigue, all of which were well managed during treatment. There were no serious adverse events, deaths, or interruptions of treatment due to adverse reactions. Conclusions:SOF/VEL/VOX is a safe and effective salvage treatment option for chronic hepatitis C patients who have failed DAAs therapy, and may be particularly beneficial to refractory populations infected with genotype 3 and combined with cirrhosis.
3.Evaluation of Neurodevelopmental Toxicity of Dianhydrogalactitol in Zebrafish
PENG Xiaoli ; CAO Wen ; LI Cheng ; WEI Sijun ; LIU Huagang
Chinese Journal of Modern Applied Pharmacy 2023;40(15):2093-2099
OBJECTIVE To explore dianhydrogalactitol(DAG)-induced neurodevelopmental toxicity and mechanisms in zebrafish embryos and larvae. METHODS On the basis of general toxicity evaluation, zebrafish embryos were exposed to DAG in groups, and the effects of DAG on zebrafish nerves and behaviors were observed by means of autonomic locomotor response and light stimulation response of juvenile fish; the effects of DAG on zebrafish brain tissues were observed by means of histopathological examination of brain and acridine orange staining. The relative expression of dopamine neuron-related genes(DAT, TH, GCH1) and neural inhibition/promotion of apoptosis-related genes(Bax, Bcl-2) was determined by real-time fluorescence quantitative PCR in zebrafish larvae. RESULTS DAG inhibited the voluntary movement of zebrafish under the 20, 40, 75 mg·L-1, and the inhibition rate of voluntary movement showed obvious concentration correlation; DAG inhibited the reaction speed of zebrafish under the 20, 40, 75 mg·L-1, and the rate of decrease of reaction ability showed concentration correlation; the brain tissue became smaller, but the tissue structure of zebrafish did not show any significant abnormality in the various concentration groups of DAG; acridine orange staining was used to detect the apoptosis of the overall embryonic cells of zebrafish, and it was found that the administration of DAG inhibited the apoptosis of zebrafish. Acridine orange staining was used to detect apoptosis in the whole embryonic cells of zebrafish, and it was found that the green fluorescence in the head of the administered group was more obvious than that in the control group, indicating that apoptosis increased, and apoptosis increased in a dose-dependent manner, which was in accordance with the apparent observation; DAG in 75, 150, 300, 425, 600 mg·L-1 of the experimental condition could lead to a downward regulation of the relative expression of mRNA of the genes related to the zebrafish juvenile dopaminergic neuron, DAT, TH and GCH1. The Bax/Bcl-2 relative mRNA expression was up-regulated with increasing drug concentration. CONCLUSION The neurodevelopmental toxicity of DAG in zebrafish embryos and juveniles may be related to the inhibition of dopaminergic neurons.
4.Construction of a prognostic prediction model and scoring tool for severe trauma patients in the emergency department
Linfang LI ; Huagang HU ; Feng XU ; Lanfeng QIU ; Du CHEN ; Xiaoqin LI
Chinese Journal of Emergency Medicine 2022;31(5):592-597
Objective:To construct the prognostic prediction model and scoring tool by using severe trauma patients’ physiological indicators on admission, and to verify the clinical application effect and provide a reference for the early evaluation of severe trauma patients.Methods:This study was a retrospective study which adopted cluster sampling. Patients who met the inclusion and exclusion criteria in the emergency department of the First Affiliated Hospital of Soochow University from September 2019 to November 2020 were included. Patients were randomly assigned into the modeling group and the validation group in a ratio of 7:3 based on their outcome in the emergency department. Logistic regression analysis was performed to construct a prediction model, which was simplified as a scoring tool. The model was verified by using validation group and two months’ prospective validation. The efficiency of the simplified scoring tool was compared with that of the revised trauma score (RTS) and the injury severity score (ISS).Results:Totally 863 patients were included in this study, including 604 patients in the modeling group and 259 patients in the validation group. The model included systolic blood, SpO 2 and AVPU score. The AUC for predicting the death of severe trauma patients was 0.938. The AUC of the prediction model was 0.933, the best cut-off point was 5, the sensitivity was 86.7%, the specificity was 94.2%; the AUC of the validation was 0.885, the sensitivity was 83.3%, the specificity was 93.7%; and the AUC of prospective validation was 0.919, the sensitivity was 100%, and the specificity was 76.7%. The AUC of the RTS and ISS were 0.800 and 0.833, respectively. The AUC of RTS was lower than that of the simplified scoring tool constructed in this research. Conclusions:The prediction model and simplified scoring tool are better than RTS in predicting the outcome of emergency severe trauma patients, which are convenient for emergency medical staff to evaluate the severity of trauma patients.
5.Effect of Entacapone Plus Levodopa/Carbidopa on Anxiety, Depression, and Quality of Life in Patients with Parkinson Disease
Huagang LI ; Jinsong XIAO ; Hong ZHU
Journal of China Medical University 2019;48(2):164-169
Objective To investigate the effects of levodopa/carbidopa plus entacapone (LCE) and levodopa/carbidopa (LC) on anxiety, depression, and quality of life (QOL) between patients with Parkinson disease (PD). Methods In total, 120 patients with idiopathic PD were enrolled in this trial and randomized into the experimental (LCE) and control (LC) groups in a 1∶1 ratio to receive treatment for12 weeks. The Hamilton anxiety scale score (HAMA), Hamilton depression scale score (HAMD), 39-item PD QOL questionnaire score (PDQ-39), Unified PD rating scale score (UPDRS), "on" time (h/d), and "off" time (h/d) were measured at each visit (baseline 0, 4, 8, and 12 weeks). Results At the end point (12 weeks), the decrease in the HAMA score from baseline was higher in the LCE group compared with that in the LC group (3.6±1.3, 95% CI:3.3-3.9 vs 1.3±0.7, 95% CI:1.1-1.5, P<0.001), as well as the HAMD score (5.2±1.9, 95% CI:4.7-5.7 vs 1.2±0.7, 95% CI:1.0-1.4, P <0.001). Similarly, the changes in the PDQ-39 score were evaluated, and the change was compared between the LCE group and the LC group (14.1±7.8, 95% CI:12.1-16.1 vs 6.9±4.2, 95% CI:5.8-8.0, P<0.001). In addition, the LCE group presented better improvement in the UPDRS score (Ⅰ-Ⅳ), "on" time, and "off" time from the baseline than that in the LC group (P < 0.05). Conclusion Entacapone combined with levodopa/carbidopa could significantly improve anxiety, depression, and QOL in patients with PD experiencing wearing-off.
6.Simultaneous Determination of 8 Ingredients in Guizhijiashaoyao Decoction by HPLC
Zhenzhen HAN ; Changsen SHAO ; Yuanyuan ZHANG ; Shaohua WANG ; Li LIU ; Guitao LIN ; Huagang SHENG
China Pharmacy 2019;30(6):784-788
OBJECTIVE: To establish a method for simultaneous determination of albiflorin, paeoniflorin, liquiritin, liquiritigenin, cinnamic acid, cinnamaldehyde, ammonium glycyrrhetate and 6-ginger phenol in Guizhijiashaoyao decoction. METHODS: HPLC method was adopted. The determination was performed on Kromasil C18 column with mobile phase consisted of acetonitrile-0.1% phosphoric acid solution (gradient elution) at the flow rate of 1.0 mL/min. The detection wavelengths were 235 nm(0-35 min,albiflorin, paeoniflorin, liquiritin)、280 nm(35-65 min,liquiritigenin, cinnamic acid, cinnamaldehyde, ammonium glycyrrhetate and 6-ginger phenol). The column temperature was 25 ℃, and the sample size was 20 μL. RESULTS: The linear range of albiflorin, paeoniflorin, liquiritin, liquiritigenin, cinnamic acid, cinnamaldehyde, ammonium glycyrrhetate and 6-ginger phenol were 2.125-34.000 μg/mL(r=0.999 9), 28.700-459.200 μg/mL(r=0.999 7), 3.675-58.800 μg/mL(r=0.999 7), 1.235-19.760 μg/mL(r=0.999 8), 2.300-36.800 μg/mL(r=0.999 8), 0.955-15.280 μg/mL(r=0.999 7), 36.000-576.000 μg/mL(r=0.999 7) and 1.500-24.000 μg/mL(r=0.999 7), respectively. The quantitative limits were 0.135, 0.102, 0.096, 0.033, 0.013, 0.023, 0.663, 0.198 μg/mL; the detection limits were 0.041, 0.031, 0.029, 0.010, 0.004, 0.007, 0.201, 0.059 μg/mL. RSDs of precision, stability and reproducibility tests were all lower than 3% (n=6). The recovery rates were 97.47%-100.76%(RSD=1.33%,n=6), 98.15%-103.50%(RSD=1.82%,n=6), 95.65%-100.84%(RSD=2.38%,n=6), 96.75%-100.32%(RSD=1.31%,n=6), 95.88%-102.75%(RSD=2.52%,n=6), 95.63%-100.63%(RSD=2.00%,n=6), 96.78%-100.45%(RSD=1.35%,n=6), 95.71%-100.48%(RSD=1.80%,n=6). CONCLUSIONS: The method is accurate, reliable and exclusive, and suitable for simultaneous determination of 8 ingredients in Guizhijiashaoyao decoction.
7.Clinical significance and outcomes of pleural effusion in patients with type B aortic dissection treated by endovascular repair
Binshan ZHA ; Huagang ZHU ; Wentao XIE ; Zhigong ZHANG ; Yongsheng LI ; Yusheng YE ; Bin LIU ; Zhiyong CHEN ; Kangmin YU ; Meng WEI ; Jun LI
Chinese Journal of General Surgery 2017;32(12):1018-1021
Objective To explore clinical implications of pleural effusion in thoracic endovascular aorta repair (TEVAR) of type B aortic dissection.Methods Clinical data of 28 patients (23 males,5 females) hospitalized from Jan 2015 to Dec 2016 were analyzed retrospectively.There were ruptured aortic dissection (RAD) (n =7) and the contained aortic dissection (CAD) (n =21).26 patients underwent TEVAR,and two patients received conservative treatment.Results 26 patients received TEVAR and operations were successful.2 patients treated conservatively died.Six patients had bilateral pleural effusion,while 20 had left pleural effusion and two had right pleural effusion.The distribution of pleural effusion was significantly different between CAD and RAD group (x2 =10.4,P < 0.05),and the rupture risk was the highest in right sided pleural effusion.The median volume of pleural effusion on right side in RAD group are higher than that in CAD group (Z =-3.293,P =0.001).One patient died of sudden death on post-op 9th day.Pleural effusion disappeared in all 24 patients who were followed-up for more than 3 months.There were no ensuing pleural thickening,pulmonary atelectasis,and lung consolidation.Conclusious Pleural effusion on left side are common in type B aortic dissection,while bulk right pleural effusion may indicate impending rupture.Endovascular therapy is a feasible,safe and effective therapy for aortic dissection with pleural effusion.
8.Features of time distribution in the onset of aortic dissection of 476 patients
Yingfeng ZHANG ; Huagang ZHU ; Zhigong ZHANG ; Yongsheng LI ; Peng QIU
Chinese Journal of Digestive Surgery 2017;16(11):1113-1117
Objective To investigate the features of time distribution in the onset of aortic dissection (AD).Methods The retrospective cross-sectional study was conducted.The clinical data of 476 AD patients who were admitted to the First Affiliated Hospital of Anhui Medical University from January 2009 to June 2017 were collected.The patients were divided by the following criteria:gender,age [youth(<45 years),middle-age (45-59 years) and elderly (≥ 60 years)],Stanford types (type A and type B),with or without hypertension.All variables were analyzed by circular distribution statistics to illuminate the features of time distribution in the onset of AD (monthly rhythm and circadian rhythm).Observation indicators:(1) overall time distribution of AD;(2) time distribution of subgroups with different genders;(3) time distribution of subgroups with different age;(4) time distribution of subgroups with different Stanford types;(5) time distribution of subgroups with or without hypertension.Measurement data with normal distribution were represented as (x)±s and count data were described as constituent ratio.The circular distrbution statistics were used to calculate time data of onset after trigonometric function transformation.The monthly rhythm and circadian rhythm were done using the Rayleigh test (Z value).Results (1) Overall time distribution of AD:the AD patients had the monthly rhythm and circadian rhythm (Z=14.79,31.60,P<0.05).The months with the maximum and minimum cases were November (59 cases) and August (24 cases) respectively,the peak day was on January 12.AD often occurred from 16:00 to 17:00 (37 cases) but barely occurred from 3:00 to 4:00 (8 cases),with a peak of 14:55.(2) Time distribution of subgroups with different gender:male subgroup had the monthly rhythm and circadian rhythm (Z =11.28,27.81,P<0.05);female subgroup had the monthly rhythm and circadian rhythm (Z=3.48,4.37,P<0.05).(3) Time distribution of subgroups with different age:patients in the youth subgroup had no monthly rhythm (Z=1.33,P>0.05),and there was the circadian rhythm (Z=4.29,P<0.05);patients in the middle-age subgroup had the monthly rhythm and circadian rhythm (Z =7.48,17.41,P<0.05);patients in the old-age subgroup had the monthly rhythm and circadian rhythm (Z =6.62,11.04,P < 0.05).(4) Time distribution of subgroups with different Stanford type:patients inthe type A subgroup had no monthly rhythm (Z=1.60,P>0.05),and there was the circadian rhythm (Z=10.51,P<0.05);patients in the type B subgroup had the monthly rhythm and circadian rhythm (Z=13.94,21.70,P<0.05).(5) Time distribution of subgroups with or without hypertension:subgroups with hypertension had the monthly rhythm and circadian rhythm (Z =12.08,29.81,P< 0.05).Subgroups without hypertension had no monthly rhythm (Z=3.84,P>0.05),showing a statistically significant difference in the circadian rhythm (Z=4.78,P<0.05).Conclusion AD often occurs in cold months and afternoon.
9.Awareness on dangerous aortic dissection and its varied clinical manifestations
Chinese Journal of Digestive Surgery 2017;16(11):1098-1100
Aortic dissection (AD) is one of the disastrous cardiovascular diseases.Due to the uncertain,varied clinical manifestations of the AD,clinical misdiagnosis or missed diagnosis may occur occasionally.Doctors should carefully and thoroughly evaluate clinical manifestations,and raise awareness and vigilance on acute AD.After suspecting or diagnosing acute AD,specialists of vascular surgery should be contacted as soon as possible so that they could successfully treat patients.By briefly describing the different clinical manifestations of the AD in various human systems,this paper aims to promote the recognition of the atypical AD.
10.Preservation of Internal Iliac Artery after Endovascular Repair of Common Iliac Artery Dissection Using Modified Fenestrated Stent Graft.
Binshan ZHA ; Huagang ZHU ; Bin LIU ; Yusheng YE ; Jun LI
Korean Circulation Journal 2016;46(3):412-416
Standard endovascular repair of iliac/aortoiliac pathologies can lead to complications, such as buttock claudication, colon ischemia and erectile dysfunction. Branch grafts have been developed but require at least 6 weeks for customization and are not currently available in China; they are also quite expensive. To our knowledge, modified fenestrated stent grafts (MFSGs) are a safe and effective alternative for treating patients with juxtarenal aneurysms. Most MFSGs are used for the preservation of renal and left subclavian arteries. Few cases of MFSGs have been reported in the treatment of iliac pathologies. The use of an MFSG is decided on a case-by-case basis. This report presents our first clinical use of an MFSG for preservation of the internal iliac artery.
Aneurysm
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Blood Vessel Prosthesis*
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Buttocks
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China
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Colon
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Erectile Dysfunction
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Humans
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Iliac Artery*
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Ischemia
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Male
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Pathology
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Stents*
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Subclavian Artery
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Transplants


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