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.Improvement of Lung Function in Rats with Idiopathic Pulmonary Fibrosis by Shengxiantang via Regulating Cell Senescence Mediated by Wnt3a/β-catenin Signaling Pathway
Yanan YAN ; Yulei LIANG ; Jiepeng WANG ; Chaoyi FANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):31-38
ObjectiveTo observe the effect of Shengxiantang (SXT) on cell senescence mediated by wingless/integrated (Wnt)3a/β-catenin pathway in rats with idiopathic pulmonary fibrosis (IPF) and reveal the possible mechanism in improving lung function of IPF rats. MethodA total of 32 SPF level SD rats were randomly divided into sham group, model group, pirfenidone group, and SXT group. The IPF rat model was established by intratracheal instillation of bleomycin (0.005 g·kg-1). The following day after surgery, rats in the SXT group were given the aqueous solution of SXT granules (0.78 g·kg-1), and the pirfenidone group was given pirfenidone suspension (0.05 g·kg-1). The other groups were given deionized water (10 mL·kg-1) for 28 consecutive days. Lung tissue was collected after the lung function was measured. The pathological changes of the lung tissue were observed by hematoxylin-eosin (HE) and Masson staining, and then the Szapiel score and Ashcroft score were performed. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect telomere length. Western blot was applied to detect the expressions of epithelial-mesenchymal transformation (EMT) markers [α-smooth muscle actin (α-SMA) and E-cadherin], telomere reverse transcriptase (TRET), aging-related proteins (p53 and p21), senescence-associated secretory phenotype [interleukin-6 (IL-6) and matrix metalloproteinase-1 (MMP-1)], and key proteins of Wnt signaling pathway [Wnt3a, glycogen synthase kinase-3β (GSK-3β), β-catenin, Cyclin D1, and c-Myc]. ResultCompared with those in the Sham group, peak expiratory flow (PEF) and minute ventilation volume (MV) in the model group were significantly decreased (P<0.01), and the frequency of respiratory (f) was significantly increased (P<0.01). The Szapiel score, Ashcroft score, and protein expression of α-SMA, p53, p21, IL-6, MMP-1, Wnt3a, GSK3β, β-catenin, Cyclin D1, and c-Myc were increased (P<0.01). The expressions of E-cadherin and TERT, as well as telomere length were significantly decreased (P<0.01). Compared with those in the model group, PEF and MV in the SXT group were significantly increased (P<0.01), while f was significantly decreased (P<0.01). The Szapiel score, Ashcroft score, and protein expression of α-SMA, p53, p21, IL-6, MMP-1, Wnt3a, GSK3β, β-catenin, Cyclin D1, and c-Myc were significantly decreased (P<0.05, P<0.01). Nevertheless, the expression of E-cadherin and TERT, as well as telomere length were significantly increased (P<0.01). ConclusionSXT presents a significant protective effect on lung function in IPF rats, and the prescription may act on the Wnt3a/β-catenin signaling pathway to regulate cell senescence induced by TERT to inhibit EMT.
5.Robot-assisted femoral tunnel localization in reconstruction of the medial patellofemoral ligament
Zhaohe ZHANG ; Yushun FANG ; Yanan LI ; Shaohua ZHANG ; Hongfei TAN ; Qingsong ZHANG
Chinese Journal of Orthopaedic Trauma 2024;26(1):19-25
Objective:To investigate the efficacy of robot-assisted femoral tunnel localization in reconstruction of the medial patellofemoral ligament (MPFL).Methods:A retrospective study was conducted to analyze the 36 patients who had been admitted to Department of Sports Medicine, The Fourth Hospital of Wuhan between January 2019 and January 2022 due to recurrent patellar dislocation. There were 15 males and 21 females; age: 23.5 (18.3, 29.0) years; number of dislocations: 2.5 (2.0, 3.0). They were stratified into 2 cohorts based on utilization of robot-assistance. In the observation group (17 cases), the femoral tunnel localization was robot-assisted in MPFL reconstruction; in the control group (19 cases), the femoral tunnel localization was guided by C-arm fluoroscopy in MPFL reconstruction. The 2 groups were compared in terms of operation time, frequency of guide wire placement, visual analogue scale (VAS) at postoperative 1 d, patellar tilt angle (PTA) and the disparity between actual femoral tunnel insertion and ideal tunnel insertion point (Sch?ttle point) at postoperative 1 to 3 d, and Lysholm knee score and International Knee Documentation Committee (IKDC) score at the last follow-up.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). All patients were followed up for 12.0 (10.3, 13.0) months. In the observation group, the operation time [(64.1±16.7) min], frequency of guide wire placement [1.0 (1.0, 2.0) times], VAS [2.5 (2.0, 3.0) points], and disparity between actual femoral tunnel insertion and ideal tunnel insertion point [(4.7±1.2) mm] were significantly better than those in the control group [(84.2±19.7) min, 3.0 (2.0, 4.0) times, 3.5 (3.0, 4.0) points, and (6.1±1.2) mm] ( P<0.05). There was no statistical difference between the 2 groups in PTA, Lysholm knee score or IKDC score ( P>0.05). Conclusions:The short-term clinical efficacy of robot-assisted femoral tunnel localization is satisfactory in MPFL reconstruction. Compared with the intraoperative C-arm fluoroscopy, robot-assisted localization can decrease the frequency of guide wire placement, enhance femoral tunnel accuracy and efficiency, and alleviate more postoperative pain for the patients.
6.Treatment of Endometriosis from the Perspective of "Retention due to Deficiency Qi"
Yujuan ZHANG ; Youhua ZHU ; Jiajing ZHAO ; Yanan YANG ; Mengya BU ; Mengxin FANG ; Yuxiao HUANG
Journal of Traditional Chinese Medicine 2024;65(9):954-957
It is believed that retention due to deficient qi is an important pathogenesis of endometriosis (EMs). Deficient qi is the root of the disease, mainly manifested as spleen deficiency, while retention is the branch pathogenesis of the disease, mainly with blood stasis, complicated with constraint, phlegm, heat, toxin and other pathological factors. Therefore, it is proposed to follow the treatment principle of supplementing deficiency and unblocking stagnation, and take the methods of replenishing qi and fortifying the spleen, removing stasis and eliminating concretions. Self-made Fuzheng Huayu Formula (扶正化瘀方) is taken as the basic formula, and can be modified with the symptoms in menstrual and non-menstrual periods. Additionally, the methods of moving qi, dispelling phlegm, clearing heat, relieving toxin and others can be combined, and it is recommended to treat the root and the branch simultaneously.
7.Cost-utility analysis of trastuzumab deruxtecan versus trastuzumab emtansine in the second-line treatment for HER2-positive metastatic breast cancer
Yanan WU ; Fang WU ; Yanhong HOU
China Pharmacy 2024;35(2):204-209
OBJECTIVE To evaluate the cost-effectiveness of trastuzumab deruxtecan(T-DXd) versus trastuzumab emtansine (T-DM1) in the second-line treatment of HER2-positive metastatic breast cancer, and to provide a basis for the selection of clinical medication regimen and medical and health decisions. METHODS Based on the clinical trial DESTINY-Breast03, a partitioned survival model was constructed, with a cycle of 3 weeks as the simulation of patients’ lifetime. The incremental cost-effectiveness ratio (ICER) was calculated by using quality-adjusted life years (QALY) as output indicators, and sensitivity analysis was used to verify the robustness of the basic analysis results; the cost-effectiveness of the second-line treatment for HER2-positive metastatic breast cancer was compared between T-DXd and T-DM1. RESULTS Under the premise of taking 3 times China’s per capita gross domestic product (GDP) in 2022 as the willingness-to-pay threshold (257 094 yuan/QALY), the T-DXd group also needed to pay more cost compared with T-DM1 group while obtaining incremental utility (0.69 QALYs), and the ICER value was 1 850 478.40 yuan/QALY. The results of univariate sensitivity analysis showed that progression-free survival state utility value, T-DXd price, cost discount rate were factors that had a great influence on ICER value, but these parameters could not flip the basic analysis results within a reasonable range. In the probability sensitivity analysis, when the threshold of willingness-to-pay rose to 1 500 400 yuan/QALY, the probability of economic activity was 50% in the T-DXd regimen. The results of the scenario analysis also verified the robustness of the original research results. CONCLUSIONS Under the premise of 3 times China’s per capita GDP as the WTP threshold, compared with T-DM1, T-DXd is not cost-effective in the second-line treatment of HER2-positive metastatic breast cancer.
8.Prevalence and factors related to overweight, obesity and hypertension comorbidities among primary and secondary school students in Ningxia
WEI Rong, LI Yuan, MA Ning, WANG Xiaoli, JIN Yanan,MA Fang,YANG Yi,CHEN Yaogeng
Chinese Journal of School Health 2024;45(12):1807-1810
Objective:
To explore the prevalence and related factors of overweight, obesity and hypertension comorbidities among children and adolescents in Ningxia, so as to provide a scientific basis for effective early health intervention in children and adolescents.
Methods:
From September 2021 to June 2022, a total of 4 577 students aged 9-16 were selected from Jinfeng District of Yinchuan City, Shapotou District of Zhongwei City, Yanchi County of Wuzhong City and Pingluo County of Shizuishan City in Ningxia by multi stage cluster random sampling method for questionnaire survey and physical measurement. The influencing factors of overweight, obesity and hypertension comorbidities in children and adolescents were investigated by Chi square test and multivariate unconditioned Logistic regression analysis with weighted complex sampling design.
Results:
The prevalence of overweight and obesity among primary and secondary school students in Ningxia was 22.87%, the prevalence of hypertension was 1.30%, and the comorbity rate of overweight, obesity and hypertension was 1.07%. Multivariate Logistic regression analysis showed that students aged 13-16 ( OR =15.66,95% CI =3.84-63.96, P <0.05) were more likely to suffer from overweight, obesity and hypertension than students aged 9-12. The students of insufficient sleep duration ( OR =5.47, 95% CI =1.73-17.33, P <0.05) had higher levels of overweight, obesity and hypertension comorbidities than those of adequate sleep duration. Students who had breakfast 1 to 7 times a week ( OR =0.08, 95% CI =0.02-0.37) had lower incidence than those who had breakfast once a week ( P <0.05).
Conclusions
Age, sleep time and breakfast frequency are all related factors of overweight, obesity and hypertension co morbidity among primary and secondary school students in Ningxia. Close attention should be paid to students aged 9-12 years with insufficient sleep time and fasting in the morning, and carry out scientific education and prevention and control interventions should be carried out.
9.Effect of pre-infusion of hypertonic saline on postoperative cognitive function in elderly patients
Fang XU ; Xupeng WANG ; Yanan LI ; Yahui ZHANG ; Qi ZHOU ; Mingyang GAO ; Yufei HU ; Xiaoqin REN ; Qiujun WANG
Chinese Journal of Anesthesiology 2024;44(10):1186-1189
Objective:To evaluate the effect of pre-infusion of hypertonic saline on the postoperative cognitive function in elderly patients.Methods:This was a prospective study. Seventy-six patients of both sexes, aged≥60 yr, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, who underwent elective shoulder arthroscopic surgery under brachial plexus block combined with general anesthesia from June 2022 to January 2023 in our hospital, were selected and divided into 2 groups ( n=38 each) by the random number table method: hypertonic saline group and normal saline group. At 30 min before anesthesia induction, 3% hypertonic saline of 4 ml/kg was intravenously infused in hypertonic saline group, and normal saline 4 ml/kg was intravenously infused in normal saline group. The occurrence of intraoperative cerebral desaturation events was recorded. Venous blood samples were collected at 24 h postoperatively, and the plasma concentrations of interleukin-1beta (IL-1β), IL-6, tumor necrosis factor-alpha and S-100β were measured by enzyme-linked immunosorbent assay, and the expression of neutrophil CD11b was detected by flow cytometry. Rey auditory verbal learning test, trail making test, digit symbol substitution test, and stroop color-word test were performed at 1 day before surgery and 5 days after surgery, and the postoperative cognitive dysfunction was assessed using the Z-score method. Results:Compared with normal saline group, the concentrations of plasma IL-6, tumor necrosis factor-alpha and S-100β and expression of neutrophil CD11b were significantly decreased in hypertonic saline group, and the incidence of cognitive dysfunction and cerebral desaturation events was decreased in hypertonic saline group ( P<0.05). Conclusions:Pre-infusion of hypertonic saline can reduce inflammatory responses and improve postoperative cognitive function in elderly patients.
10.Exploring the mechanism by which acupuncture and moxibustion reduce colonic mucosal inflammation in rats with ulcerative colitis(UC)based on the P2X7R-NLRP3 inflammasome pathway
Zhenzhen FANG ; Huangan WU ; Luyi WU ; Yanan LIU ; Ling YANG ; Chen ZHAO ; Zhe MA ; Yan HUANG ; Wenjia WANG
Journal of Acupuncture and Tuina Science 2023;21(5):356-367
Objective:To explore the mechanism of acupuncture and moxibustion for ulcerative colitis(UC)from the perspective of the P2X7 receptor(P2X7R)-nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome pathway. Methods:Sprague-Dawley rats were randomly assigned to a normal(N)group,a model(M)group,a herb-partitioned moxibustion(HM)group,and an electroacupuncture(EA)group.For modeling,the rats drank 4%dextran sulfate sodium for 7 d.Rats in the HM group and EA group received 7 consecutive days of HM or EA at bilateral Tianshu(ST25),respectively.The histopathological change in colon tissue was observed by hematoxylin-eosin(HE)staining;immunofluorescence staining was used to detect the protein expression of related molecules in the colon tissue,and enzyme-linked immunosorbent assay was used to detect the concentrations or contents of related molecules in the serum and colon tissue.Wild-type(WT)and P2X7R gene knockout(KO)mice were used to construct UC models,histopathological changes in the colon tissue were observed by HE staining,and the NLRP3 protein expression in the colon tissue was observed by immunohistochemistry. Results:Compared with the N group,the colon histopathological score in the M group was significantly increased,and the protein expression of P2X7R,NLRP3,apoptosis-associated speck-like protein containing CARD(ASC),Caspase-1,interleukin-1β(IL-1β),and interleukin-18(IL-18)in the colon tissue and the protein levels of IL-1β and IL-18 in the serum were significantly increased(P<0.05).Compared with the M group,the histopathological scores of the colon in the HM group and the EA group were significantly decreased,and the protein expression levels of P2X7R,NLRP3,ASC,Caspase-1,IL-1β,and IL-18 in the colon tissue and the protein level of IL-18 in the serum were significantly decreased(P<0.05).After UC modeling,the colonic mucosal epithelial damage and inflammatory cell infiltration in P2X7R KO mice were less than those in WT mice,and the NLRP3 protein expression in the colon was also decreased compared with that in WT mice(P<0.05). Conclusion:HM and EA at Tianshu(ST25)may inhibit the protein activities of P2X7R,NLRP3,ASC,and Caspase-1 in the colon tissue of rats with UC,thereby reducing the downstream molecules IL-1β and IL-18 in the P2X7R-NLRP3 inflammasome pathway to relieve UC inflammation.


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