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.Mortality from cerebrovascular diseases in China: Exploration of recent and future trends
Bin LV ; Ge SONG ; Feng JING ; Mingyu LI ; Hua ZHOU ; Wanjun LI ; Jiacai LIN ; Shengyuan YU ; Jun WANG ; Xiangyu CAO ; Chenglin TIAN
Chinese Medical Journal 2024;137(5):588-595
Background::Cerebrovascular disease (CVD) ranks among the foremost factors responsible for mortality on a global scale. The mortality patterns of CVDs and temporal trends in China need to be well-illustrated and updated.Methods::We collected mortality data on patients with CVD from Chinese Center for Disease Control and Prevention’s Disease Surveillance Points (CDC-DSP) system. The mortality of CVD in 2020 was described by age, sex, residence, and region. The temporal trend from 2013 to 2019 was evaluated using joinpoint regression, and estimated rates of decline were extrapolated until 2030 using time series models.Results::In 2019, the age-standardized mortality in China (ASMRC) per 100,000 individuals was 113.2. The ASMRC for males (137.7/10 5) and rural areas (123.0/10 5) were both higher when stratified by gender and urban/rural residence. The central region had the highest mortality (126.5/10 5), the western region had a slightly lower mortality (123.5/10 5), and the eastern region had the lowest mortality (97.3/10 5). The age-specific mortality showed an accelerated upward trend from aged 55-59 years, with maximum mortality observed in individuals over 85 years of age. The age-standardized mortality of CVD decreased by 2.43% (95% confidence interval, 1.02-3.81%) annually from 2013 to 2019. Notably, the age-specific mortality of CVD increased from 2013 to 2019 for the age group of over 85 years. In 2020, both the absolute number of CVD cases and the crude mortality of CVD have increased compared to their values in 2019. The estimated total deaths due to CVD were estimated to reach 2.3 million in 2025 and 2.4 million in 2030. Conclusion::The heightened focus on the burden of CVD among males, rural areas, the central and western of China, and individuals aged 75 years and above has emerged as a pivotal determinant in further decreasing mortalities, consequently presenting novel challenges to strategies for disease prevention and control.
5.Exploration and practice of building a disciplinary inspection management platform in public hospitals
Jianchun YU ; Huimin LV ; Jin YAN ; Jia ZHANG
Modern Hospital 2024;24(10):1515-1517
The second plenary session of the 20th Central Commission for Discipline Inspection proposed the"develop-ment of a five-year plan for information technology construction to establish a digital disciplinary inspection and supervision system that covers the entire process and all elements."This provides guidance and momentum for disciplinary inspection agencies at all levels to implement the strategic deployment of the Party's 20th National Congress regarding comprehensive and strict governance of the Party.In this context,utilizing information technology to enhance the efficiency of supervision,discipline enforcement,and accountability while ensuring the high-quality development of public hospitals has become a key task for their disciplinary inspec-tion departments.The Disciplinary Inspection Commission of a public hospital has explored the establishment of a disciplinary in-spection management platform to achieve modular management of inspection tasks.By utilizing functions such as task allocation,statistical analysis,data migration,and early warning reminders,the platform aims to improve the efficiency of disciplinary in-spection work.This approach helps address the challenges of heavy workloads and limited inspection resources in hospitals,enab-ling real-time supervision,early warning correction,and time-bound oversight,thereby providing strong support for the construc-tion of integrity in the hospital.
6.Cost control and structural optimization of medical consumables in a public hospital:a case study on the management of drug-loaded embolic microspheres in transcatheter Hepatic Artery Embolization
Jiawen TAN ; Zhilun YANG ; Jiaqing MIAO ; Xiaohui LV ; Lihua WU ; Donglan YU
Modern Hospital 2024;24(11):1694-1698,1701
Effective cost control and structure optimization of medical consumables in public hospitals can facilitate a shift from extensive cost control to scientific and refine management.On the premise of ensuring medical quality,reducing the burden of patients'diagnosis and treatment and meeting the actual needs of hospital management,this approach aims to realize valuable healthcare outcomes.This study was conducted in a tertiary hospital,which balanced both the medical and economic val-ue of medical consumables.Using an integrated approach to specialty capacity building and disease structure optimization,the hospital restructured the use of medical consumables in Transcatheter Arterial Embolization(TAE)procedures.It developed standardized pathways and usage protocols tailored to specific diseases and surgical requirements.A targeted consumable usage policy framework was introduced,comprising"one department,one policy;one surgery type,one policy;and one consumable,one policy."This included initiatives such as validating the use of drug-loaded embolic microspheres,conducting multi-depart-mental review meetings,strictly regulating indications for these microspheres,limiting personnel involvement,and negotiating re-duced pricing on imported microspheres.Following implementation,the average case-mix index(CMI)for discharged patients undergoing TAE increased from 2.23 to 2.34(P<0.001),while the average per-case cost of consumables decreased from 19 600 to 15 600(P<0.001).These measures offer valuable decision-making and operational reference for hospitals nation-wide,supporting efficient,quality-focused consumables management.
7.Small molecule deoxynyboquinone triggers alkylation and ubiquitination of Keap1 at Cys489 on Kelch domain for Nrf2 activation and inflammatory therapy
Linghu KE-GANG ; Zhang TIAN ; Zhang GUANG-TAO ; Lv PENG ; Zhang WEN-JUN ; Zhao GUAN-DING ; Xiong SHI-HANG ; Ma QIU-SHUO ; Zhao MING-MING ; Chen MEIWAN ; Hu YUAN-JIA ; Zhang CHANG-SHENG ; Yu HUA
Journal of Pharmaceutical Analysis 2024;14(3):401-415
Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.
8.PD-1 inhibitors plus chemotherapy for refractory EBV-positive DLBCL:a retrospective analysis
Youli LI ; Yonghe WU ; Sufen CAO ; Baohua YU ; Qunling ZHANG ; Zuguang XIA ; Junning CAO ; Fangfang LV ; Guang‑Liang CHEN
Blood Research 2024;59():36-
Background:
Immunochemotherapy has demonstrated a promising efficacy for a variety of B-cell lymphoma but has limited efficacy for Epstein–Barr virus-positive (EBV +) diffuse large B-cell lymphoma (DLBCL) that is refractory or relapsed to conventional chemotherapy regimens. Considering higher programmed death-ligand 1 (PD-L1) expres‑ sion in the subset of patients with DLBCL with positive EBV, we speculated that PD-1 inhibitors plus chemotherapy may be an alternative regimen in patients with refractory/relapsed EBV + DLBCL.
Methods:
This retrospective study included six adult patients diagnosed with refractory EBV + DLBCL resistant to first-line immunochemotherapy regimens (R-CHOP). These patients received PD-1 inhibitors plus chemotherapy as second-line treatment.
Results:
The final analysis included six patients (four men and two women (median age, 50 years; range, 39–83 years)). Four patients were diagnosed with Epstein–Barr virus (EBV) + DLBCL, and two had DLBCL associated with chronic inflammation. Over a median follow-up of 20 months (range, 2–31 months), the objective response rate was 83% (5/6) and the complete remission rate was 67% (4/6). No severe immune-related adverse reactions occurred, and only a mild rash was reported, which did not necessitate the discontinuation of therapy.
Conclusion
The combination of PD-1 inhibitors and chemotherapy offers promising results as a second-line treat‑ ment for patients with refractory EBV + DLBCL that is resistant to first-line immunochemotherapy regimens. These preliminary findings warrant further investigation in larger clinical trials to validate the efficacy and safety of this therapeutic approach.
9.PD-1 inhibitors plus chemotherapy for refractory EBV-positive DLBCL:a retrospective analysis
Youli LI ; Yonghe WU ; Sufen CAO ; Baohua YU ; Qunling ZHANG ; Zuguang XIA ; Junning CAO ; Fangfang LV ; Guang‑Liang CHEN
Blood Research 2024;59():36-
Background:
Immunochemotherapy has demonstrated a promising efficacy for a variety of B-cell lymphoma but has limited efficacy for Epstein–Barr virus-positive (EBV +) diffuse large B-cell lymphoma (DLBCL) that is refractory or relapsed to conventional chemotherapy regimens. Considering higher programmed death-ligand 1 (PD-L1) expres‑ sion in the subset of patients with DLBCL with positive EBV, we speculated that PD-1 inhibitors plus chemotherapy may be an alternative regimen in patients with refractory/relapsed EBV + DLBCL.
Methods:
This retrospective study included six adult patients diagnosed with refractory EBV + DLBCL resistant to first-line immunochemotherapy regimens (R-CHOP). These patients received PD-1 inhibitors plus chemotherapy as second-line treatment.
Results:
The final analysis included six patients (four men and two women (median age, 50 years; range, 39–83 years)). Four patients were diagnosed with Epstein–Barr virus (EBV) + DLBCL, and two had DLBCL associated with chronic inflammation. Over a median follow-up of 20 months (range, 2–31 months), the objective response rate was 83% (5/6) and the complete remission rate was 67% (4/6). No severe immune-related adverse reactions occurred, and only a mild rash was reported, which did not necessitate the discontinuation of therapy.
Conclusion
The combination of PD-1 inhibitors and chemotherapy offers promising results as a second-line treat‑ ment for patients with refractory EBV + DLBCL that is resistant to first-line immunochemotherapy regimens. These preliminary findings warrant further investigation in larger clinical trials to validate the efficacy and safety of this therapeutic approach.
10.Effect of internal fixation with mini plate and cannulated screw on postoperative recovery of joint function in patients with large fracture of posterior malleolus
Junjie FAN ; Xiao YU ; Feng LV ; Weidong WU ; Jun SHEN ; Li SUN
The Journal of Practical Medicine 2024;40(18):2571-2577
Objective To analyze the impact of mini plate and cannulated screw internal fixation on joint function recovery in patients with posterior malleolus fracture.Methods A total of 150 patients with posterior malleolus fractures,treated at our hospital from March 2021 to June 2023,were included in this study.They were divided into two groups using the odd-even number method.The control group consisted of 75 patients who underwent cannulated screw internal fixation,while the study group comprised 75 patients who received mini plate internal fixation.Clinical indicators,ankle range of motion,ankle function,and health status were compared and analyzed between the two groups.Additionally,levels of inflammatory factors,postoperative complications,and clinical efficacy were assessed.Results In terms of operation time and intraoperative blood loss,there was no statistically significant difference between the two groups(P>0.05).However,the study group exhibited shorter ambulation days,fracture healing time,and hospitalization days compared to the control group(P<0.05).Moreover,the study group demonstrated significantly improved ankle dorsiflexion,ankle plantar flexion,foot varus and foot valgus range of motion compared to the control group(P<0.05).Additionally,higher AOFAS score and KPS score were observed in the study group as compared to the control group(P<0.05).Furthermore,levels of IL-6,IL-8 and CRP were lower in the study group than in the control group(P<0.05).The incidence of postoperative complica-tions was also lower in the study group than in the control group(P<0.05).Conclusion Mini plate internal fixa-tion for posterior malleolus fracture yields ideal outcomes by promoting improvement in clinical indicators and ankle range of motion while effectively enhancing ankle function,reducing inflammatory reaction as well as minimizing postoperative complications.

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