1.Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)
Chuan LIU ; Hong YOU ; Qing-Lei ZENG ; Yu Jun WONG ; Bingqiong WANG ; Ivica GRGUREVIC ; Chenghai LIU ; Hyung Joon YIM ; Wei GOU ; Bingtian DONG ; Shenghong JU ; Yanan GUO ; Qian YU ; Masashi HIROOKA ; Hirayuki ENOMOTO ; Amr Shaaban HANAFY ; Zhujun CAO ; Xiemin DONG ; Jing LV ; Tae Hyung KIM ; Yohei KOIZUMI ; Yoichi HIASA ; Takashi NISHIMURA ; Hiroko IIJIMA ; Chuanjun XU ; Erhei DAI ; Xiaoling LAN ; Changxiang LAI ; Shirong LIU ; Fang WANG ; Ying GUO ; Jiaojian LV ; Liting ZHANG ; Yuqing WANG ; Qing XIE ; Chuxiao SHAO ; Zhensheng LIU ; Federico RAVAIOLI ; Antonio COLECCHIA ; Jie LI ; Gao-Jun TENG ; Xiaolong QI
Clinical and Molecular Hepatology 2025;31(1):105-118
Background:
s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model.
Methods:
Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort.
Results:
In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM).
Conclusions
Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.
2.Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)
Chuan LIU ; Hong YOU ; Qing-Lei ZENG ; Yu Jun WONG ; Bingqiong WANG ; Ivica GRGUREVIC ; Chenghai LIU ; Hyung Joon YIM ; Wei GOU ; Bingtian DONG ; Shenghong JU ; Yanan GUO ; Qian YU ; Masashi HIROOKA ; Hirayuki ENOMOTO ; Amr Shaaban HANAFY ; Zhujun CAO ; Xiemin DONG ; Jing LV ; Tae Hyung KIM ; Yohei KOIZUMI ; Yoichi HIASA ; Takashi NISHIMURA ; Hiroko IIJIMA ; Chuanjun XU ; Erhei DAI ; Xiaoling LAN ; Changxiang LAI ; Shirong LIU ; Fang WANG ; Ying GUO ; Jiaojian LV ; Liting ZHANG ; Yuqing WANG ; Qing XIE ; Chuxiao SHAO ; Zhensheng LIU ; Federico RAVAIOLI ; Antonio COLECCHIA ; Jie LI ; Gao-Jun TENG ; Xiaolong QI
Clinical and Molecular Hepatology 2025;31(1):105-118
Background:
s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model.
Methods:
Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort.
Results:
In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM).
Conclusions
Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.
3.Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)
Chuan LIU ; Hong YOU ; Qing-Lei ZENG ; Yu Jun WONG ; Bingqiong WANG ; Ivica GRGUREVIC ; Chenghai LIU ; Hyung Joon YIM ; Wei GOU ; Bingtian DONG ; Shenghong JU ; Yanan GUO ; Qian YU ; Masashi HIROOKA ; Hirayuki ENOMOTO ; Amr Shaaban HANAFY ; Zhujun CAO ; Xiemin DONG ; Jing LV ; Tae Hyung KIM ; Yohei KOIZUMI ; Yoichi HIASA ; Takashi NISHIMURA ; Hiroko IIJIMA ; Chuanjun XU ; Erhei DAI ; Xiaoling LAN ; Changxiang LAI ; Shirong LIU ; Fang WANG ; Ying GUO ; Jiaojian LV ; Liting ZHANG ; Yuqing WANG ; Qing XIE ; Chuxiao SHAO ; Zhensheng LIU ; Federico RAVAIOLI ; Antonio COLECCHIA ; Jie LI ; Gao-Jun TENG ; Xiaolong QI
Clinical and Molecular Hepatology 2025;31(1):105-118
Background:
s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model.
Methods:
Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort.
Results:
In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM).
Conclusions
Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.
4.Clinical Significance of Genetic and Molecular Changes in Primary Myeloid Sarcoma
Ya-Jun JIANG ; Chun-Fang ZHANG ; Hong-Xia WANG ; Lan ZHAO ; Fei-Fei ZHANG ; Xiu-Hua HAN
Journal of Experimental Hematology 2024;32(1):27-32
Objective:To investigate the clinical significance of genetic and molecular changes in primary myeloid sarcoma(MS).Methods:Fourteen patients with primary MS were selected in Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences,The First People's Hospital of Lianyungang from September 2010 to December 2021.AML1-ETO fusion,PML-RARα fusion and CBFβ breakage were detected by fluorescence in situ hybridization(FISH),and the mutations of NPM1,CEBPA,FLT3,RUNX1,ASXL1,KIT and TP53 genes were detected by new generation sequencing(NGS).Results:Among 14 patients,the MS occurred in bone,breast,epididymis,lung,chest wall,cervix,small intestine,ovary,lymph nodes and central nervous system.The tumor cells expressed MPO(13 cases),CD34(7 cases),CD43(8 cases),CD68(7 cases),CD99(8 cases)and CD117(6 cases).Cytogenetic abnormalities were observed in 4 cases,including 3 cases of AML1-ETO fusion and 1 case of CBF β breakage,while no PML-RAR α fusion was detected.There were no significant differences in overall survival(OS)and leukemia-free survival(LFS)between patients with and without AML1-ETO fusion/CBFβ breakage(both P>0.05).Among the 14 patients,the number of NPM1,CEBPA,FLT3-ITD,RUNX1,ASXL1,KIT and TP53 gene mutations was 5,3,5,3,2,2,1.respectively,of which 7 cases had at least one mutation in FLT3-ITD,RUNX1,ASXL1 and TP53 gene.The OS and LFS of patients with FLT3-ITD,RUNX1,ASXL1 or TP53 mutation were shorter than those without mutations(both P<0.01).Conclusion:The genetic and molecular abnormalities of primary MS can be detected by FISH and NGS techniques.FLT3-ITD,RUNX1,ASXL1 or TP53 mutation indicates a worse prognosis,but further clinical studies are needed to confirm it.
5.Analysis on Medication Rule of Ruan Yan in the Treatment of Children with Allergic Rhinitis Based on Data Mining
Weizhen XU ; Simin WANG ; Caishan FANG ; Wanning LAN ; Yan RUAN ; Yajie YAN ; Yu MENG ; Ruizhi WANG ; Jinxiang ZHU ; Jiajun ZHANG ; Qindong LIU ; Weiping HE ; Huixian XU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(6):896-903
Objective To analyze and discuss the medication rule of professor Ruan Yan in the treatment of children with allergic rhinitis by using data mining method,and to provide reference for the clinical research and patented drugs development for the treatment of children with allergic rhinitis.Methods The outpatient medical records of professor Ruan Yan for the treatment of children with allergic rhinitis were collected.Microsoft Excel 2010 software was used for frequency statistics.SPSS Clementine 12.0 software was used for association rule analysis,cluster analysis and factor analysis to obtain the data.The frequency of use of various drugs and the association rules between drugs were obtained.Then the medication rules in professor Ruan Yan's prescription were analyzed.Results A total of 308 Chinese medicine compounds were included,involving 80 kinds of Chinese medicines,among which relieving drugs and qi-invigorating herbs were high-frequently used.The distribution of traditional Chinese medicine syndrome types was mainly characterized by lung-qi deficiency-cold syndrome and lung-spleen qi deficiency syndrome.The medicinal properties were mainly spicy,warm and sweet,and most of them belonged to the lung,spleen and stomach meridians.Five core prescriptions were extracted by factor analysis.Four drug combinations were obtained by systematic cluster analysis.Conclusion Ventilating lung and opening the orifices,expelling wind and removing cold,strengthening the spleen and replenishing qi are basic therapeutic principles for professor Ruan Yan in the treatment of children with allergic rhinitis.The treatment mainly focused on dispelling evil,ventilating lung and opening the orifices,expelling wind and removing cold during the acute stage of allergic rhinitis.In the remission period,according to the principle of"treating disease must be based on its origin",the treatment should enhance children's physical fitness,tonify lung and strengthen spleen,thereby reducing recurrence.
6.The clinical effect of the whole process blood glucose management on improving postoperative vision in T2DM cataract patients with non-diabetic retinopathy based on visual electrophysiology and OCTA study
Juan TANG ; Fen LAN ; Linxia MENG ; Qinqin ZHANG ; Chuanqiang DAI ; Zheng LEI ; Qilin FANG ; Ying LI ; Xiaoli WU ; Tao LI
The Journal of Practical Medicine 2024;40(20):2888-2899
Objective Visual electrophysiology and optical correlation tomography angiography(OCTA)were used to investigate differences in preoperative retinal function in patients with type 2 diabetic cataract(DC)without obvious retinopathy(NDR)and to determine the clinical application of whole-process blood glucose man-agement(WBGM)for improving postoperative vision in DC patients.Methods This study investigated the preop-erative and postoperative visual electrophysiology(N75,P100,photopic FERG,and scotopic FERG),peripapil-lary retinal nerve fiber layer(pRNFL)and peripapillary capillary vessel density(ppVD)data,as well as trends in these data changes during blood glucose management intervention.Results As the course of T2DM progressed,FBG and HbA1c increased,the N75 and P100 lategraduancy periods of patients gradually lengthened,and the photopic FERG,scotopic FERG,pRNFL,and ppVD values decreased at each postoperative time point.At the same time,the best corrected visual acuity(BCVA)of patients after surgery gradually decreased(P<0.05).Compared with that at 1 week after surgery,the BCVA of Group A(without whole-process blood glucose manage-ment)gradually increased at 1 month and 3 months after surgery but showed a downward trend at 1 year after sur-gery.The BCVA of Group B(with whole-process blood glucose management)gradually stabilized at 1 month after surgery,and at all time points after surgery,the BCVA of Group B was better than that of Group A.The results showed that N75 and P100 in Group A were greater than those in Group B,while the photopic and scotopic FERG,pRNFL,and ppVD(%)in Group A were lower than those in Group B.In addition,N75 and P100 in Group A showed a gradual prolongation trend at various time points after surgery,while photopic FERG,scotopic FERG,pRNFL,and ppVD(%)showed a gradually decreasing trend.However,the above data in Group B gradu-ally stabilized at 3 months after DC surgery,approaching the preoperative level of the group(P<0.05).In the state of whole blood glucose management,although N75 and P100 both reached their longest durations at 1 week af-ter surgery,N75,P100,photopic FERG,scotopic FERG,and pRNFL showed a gradually decreasing trend at 1 month and 3 months after surgery,while ppVD(%)gradually increased(P<0.05).At various time points from 3 months to 1 year after surgery,the overall trend of the above indicators remained stable and close to the preoperative values(P>0.05).Conclusion According to the results of the quantitative analysis of visual electrophysiology and OCTA,in DC patients without obvious retinopathy and with the worsening of diabetes,retinal function decreased,but whole-process blood glucose management effectively restored retinal function and improved visual quality after surgery.
7.Effects and Mechanism of Lithocarpus litseifoliu on Improving Hyperuricemia Nephropathy in Mice
Zhenzhen SONG ; Fang LIANG ; Jia CHEN ; Renna FENG ; Yuan PAN ; Chendong LIAO ; Changhua ZHANG ; Lan CAO
Herald of Medicine 2024;43(6):855-861
Objective To investigate the ameliorative effects and potential mechanism of Lithocarpus litseifoliu on renal function and inflammation in mice with hyperuricemic nephropathy(HN).Methods The HN model was established by the combined administration of adenine and potassium oxyzate.The mice were randomly divided into normal control group,model control group,benzbromarone group,and high,medium and low dose groups of Lithocarpus litseifoliu.Different drugs were given to the mice,and their body mass was recorded once a week.The levels of uric acid(UA),creatinine(Cr),urine protein(UP),blood urea nitrogen(BUN)and urine urea nitrogen(UUN)as well as the levels of tumor necrosis factor α(TNF-α)and interleukin 6(IL-6)in serum or urine of each group were collected and measured on the 21st day.Hematoxylin-eosin(HE)staining was performed to observe kidney tissue injury in mice;real-time PCR(RT-PCR)was performed to determine ATP-binding cassette subfamily G member 2(ABCG2),urate transporter protein(URAT1),glucose transporter protein 9(GLUT9),and cytosolic factor NF-κB p50(κB p50)in kidney tissues.Results Compared with the normal control group,the body mass of mice in the model control group was significantly lower after the second weeks of modeling(P<0.05),and the levels of UA,Cr,UP,BUN,UUN,TNF-α,IL-6 contents and GLUT9 mRNA and κB p50 mRNA expression contents of kidney tissues were significantly higher(P<0.01,P<0.05).Compared with the model control group,the levels of Cr,UP,BUN and UUN contents and renal tissue nuclear cytokine κB p50 mRNA expression were significantly lower in the high,medium and low dose groups of Lithocarpus litseifoliu(P<0.01,P<0.05).The UA levels were significantly lower in the high dose group of Lithocarpus litseifoliu(P<0.05),and renal ABCG2 mRNA expression was significantly higher in the medium dose group(P<0.01).The renal URAT1 mRNA expression was significantly decreased in the low dose group(P<0.01).Conclusion Lithocarpus litseifoliu has shown ameliorative effects on HN mice,and the mechanism may be related to the modulation of renal uric acid transporters,improvement of renal function and anti-inflammation effects.
8.Excavation and evaluation of tocilizumab and infliximab for adverse drug event signals among children
Yue TAN ; Ning-Ning GE ; Jing PENG ; Wen-Shuang QIU ; Xin ZHANG ; Lan-Fang LI
The Chinese Journal of Clinical Pharmacology 2024;40(5):732-736
Objective To analyze the risk of adverse drug events in pediatric clinical applications of tocilizumab versus inflixima.Methods Adverse event(AE)reporting data for tocilizumab versus infliximab in the U.S.Food and Drug Administration Adverse Event Reporting System database for the pediatric population from Q1 2013 to Q1 2023 were collected.AE risk signal mining was performed using the reporting odds ratio(ROR)method and the proportional reporting ratio(PRR)method.AEs were also classified and statistically analyzed according to the preferred system organ classification and preferred terminology(PT)of the International Dictionary of Medical Terminology.Results Data were extracted and cleaned to include 1 052 AE reports with 198 positive PT signals for tocilizumab as the suspected drug and 9 1 39 AE reports with 387 positive PT signals for infliximab as the suspected drug.The analyses suggested that the stronger positive risk signals for both drugs were focused on gastrointestinal disorders,infectious and invasive diseases,laboratory tests,musculoskeletal and connective tissue disorders,and blood,vascular,and lymphatic disorders.The risk signals for infliximab were focused on gastrointestinal disorders,infections,and infectious diseases,while the risk signals for tocilizumab were focused on the musculoskeletal muscle system.Conclusion Clinical use of both drugs in children has multi-system effects,tocilizumab may have effects on growth and development,and infliximab has effects on the gastrointestinal tract in children.
9.Effects of radiation on pharmacokinetics
Jie ZONG ; Hai-Hui ZHANG ; Gui-Fang DOU ; Zhi-Yun MENG ; Ruo-Lan GU ; Zhuo-Na WU ; Xiao-Xia ZHU ; Xuan HU ; Hui GAN
The Chinese Journal of Clinical Pharmacology 2024;40(13):1996-2000
Radiation mainly comes from medical radiation,industrial radiation,nuclear waste and atmospheric ultraviolet radiation,etc.,radiation is divided into ionizing radiation and non-ionizing radiation.Studying the effects of ionizing and non-ionizing radiation on drug metabolism,understanding the absorption and distribution of drugs in the body after radiation and the speed of elimination under radiation conditions can provide reasonable guidance for clinical medication.This article reviews the effects of radiation on the pharmacokinetics of different drugs,elaborates the changes of different pharmacokinetics under radiation state,and discusses the reasons for the changes.
10.Cost-effectiveness analysis of chemical treatment with drones for Oncomelania hupensis control in marshland and lake areas
Yong CHEN ; Xiaojuan XU ; Daolong WEN ; Bo DAI ; Lan GAO ; Rong ZHANG ; Qingqing HUANG ; Linlin LI ; Fan ZHA ; Liang FANG ; Ping ZHANG ; Shiqing ZHANG ; Chunli CAO
Chinese Journal of Schistosomiasis Control 2024;36(5):502-506
Objective To evaluate the molluscicidal effect and cost of spraying molluscicides with drones against Oncomelania hupensis snails in marshland and lake areas, so as to provide new insights into field snail control in China. Methods A marshland and lake setting measuring approximately 12 000 m2 was selected in Wanzhi District, Wuhu City on June 2023 as the test field, and assigned to four groups, of 3 000 m2 in each group. Environmental cleaning was not conducted in groups A or B, which were given 5% niclosamide ethanolamine salt granules sprayed with knapsack-type sprayers and drones at a dose of 40 g/m2, and environmental cleaning was conducted in groups C and D, which were given 5% niclosamide ethanolamine salt granules sprayed with drones and knapsack-type sprayers at a dose of 40 g/m2, respectively. O. hupensis snails were surveyed before chemical treatment and 1, 3, 5, 7, 14 days post-treatment. The uniformity of chemicals was determined on the day of treatment, and the snail mortality, corrected snail mortality and density of living snails were calculated and compared among groups. The cost of molluscicides, labor fees of environmental cleaning and chemical treatment and cost of equipment were calculated, and the cost for a 1% reduction in the mean density of living snails was calculated 14 days post-treatment. Results The mean densities of living snails and mortality rates of snails were 1.82 to 2.85 snails/0.1 m2 and 1.41% to 2.94% in groups A, B, C and D before chemical treatment, and the mortality and corrected mortality of snails were 55.75%, 49.32%, 85.94% and 87.50%, and 55.00%, 48.47%, 85.70% and 87.29% in groups A, B, C and D 14 days post-treatment. There was a significant difference in the mortality of snails among the four groups 14 days post-treatment (χ2 = 38.735, P < 0.005), and there was a higher snail mortality in Group D than in Group A (χ2 = 16.876, P < 0.005), and higher in Group C than in Group B (χ2 = 20.508, P < 0.005). The density of living snails reduced by 55.00%, 43.94%, 90.43% and 87.14% 14 days post-treatment relative to pre-treatment in groups A, B, C and D, respectively. The test for uniformity of chemicals showed that the mean dose of molluscicides were 57.34, 55.21, 40.19 g/m2 and 32.37 g/m2 in groups A, B, C and D, respectively, and the minimal standard deviation (7.07) and coefficient of variation (0.18) of mean doses were seen in Group C. The costs for chemical treatment were 0.33 Yuan in groups A and B and 1.53 Yuan in groups C and D, respectively. The costs for a 1% reduction in the mean density of living snails were 17.82, 22.47, 50.73 Yuan and 52.56 Yuan in groups A, B, C, and D 14 days post-treatment, respectively. Conclusions The molluscicidal effect and cost of spraying 5% niclosamide ethanolamine salt granules with drones are comparable to manual spraying, and chemical treatment with drones are high in uniformity of molluscicides, time- and labor-saving, and feasible for applications in complex environments, which deserves widespread applications in the field of snail control.

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