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.Value of preoperative quantitative quadriceps muscle ultrasound measures in predicting postoperative delirium in elderly patients undergoing gastrointestinal surgery
Lan CAO ; Wenxuan JI ; Cunjin WANG ; Ju GAO
Chinese Journal of Anesthesiology 2024;44(7):791-796
Objective:To evaluate the value of preoperative quantitative quadriceps muscle ultrasound measures in predicting postoperative delirium (POD) in elderly patients undergoing gastrointestinal surgery.Methods:This was a prospective study. A total of 277 elderly patients of both sexes, aged 65-88 yr, with American Society of Anesthesiologists Physical Status classification ≤ Ⅳ and body mass index of≤30 kg/m 2, undergoing elective gastrointestinal surgery with general anesthesia at the Northern Jiangsu People′s Hospital from March to December 2023, were included in the study. The quadriceps femoris thickness and echo intensity were measured using ultrasound before induction of anesthesia. Delirium was assessed using the Confusion Assessment Method score at 1-7 days after operation. The patients were divided into 2 groups based on the occurrence of POD: POD group and non-POD group. Factors with statistically significant differences between groups were included in the logistic regression analysis to identify the independent risk factors for POD, and then a visual risk Nomogram prediction model for POD risk factors was developed based on this analysis in elderly patients undergoing gastrointestinal surgery. The receiver operating characteristic curve was plotted, and the area under the receiver operating characteristic curve (AUC) and 95% confidence interval ( CI) were used to evaluate the predictive value of each independent risk factor and Nomogram prediction model for POD. The Youden Index was used to determine the critical value for predicting POD, and the sensitivity and specificity were calculated. Results:The results of logistic regression analysis revealed that age, preoperative Mini-Mental State Examination scores, quadriceps femoris thickness and echo intensity of quadriceps femoris were independent risk factors for POD in elderly patients undergoing gastrointestinal surgery ( P<0.05). The AUC of preoperative quadriceps femoris thickness was 0.695 (95% CI 0.614-0.746), the critical value 2.465 cm, the sensitivity 73.7% and the specificity 78.2%. The AUC of preoperative quadriceps femoris echo intensity was 0.717 (95% CI 0.662-0.773), the critical value 59.985, the sensitivity 81.9% and the specificity 48.5%. Conclusions:Preoperative ultrasound measurement of quadriceps femoris thickness and echo intensity is an independent risk factor for POD and has some predictive value for POD in elderly patients undergoing gastrointestinal surgery.
5.Clinical effects of Bushen Quyu Decoction combined with conventional treatment on patients with postmenopausal osteoporosis due to Kidney Deficiency and Blood Stasis
Li XIAO ; Ju-Ying XIE ; Yun LIU ; Li-Ping HU ; Xia CAO ; Jun-Lin SHI
Chinese Traditional Patent Medicine 2024;46(8):2601-2605
AIM To investigate the clinical effects of Bushen Quyu Decoction combined with conventional treatment on patients with postmenopausal osteoporosis due to Kidney Deficiency and Blood Stasis.METHODS One hundred and six patients were randomly assigned into control group(53 cases)for 6-month intervention of conventional treatment,and observation group(53 cases)for 6-month intervention of both Bushen Quyu Decoction and conventional treatment.The changes in clinical effects,TCM syndrome scores,bone metabolism indices(β-CTX,PINP,BGP),bone mineral density,oxidative stress indices(SOD,AOPP,MAOA)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P<0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,β-CTX,BGP,AOPP,MAOA(P<0.05),and increased PINP,bone mineral density,SOD(P<0.05),especially for the observation group(P<0.05).No significant difference in incidence of adverse reactions was found between the two groups(P>0.05).CONCLUSION For the patients with postmenopausal osteoporosis due to Kidney Deficiency and Blood Stasis,Bushen Quyu Decoction combined with conventional treatment can safely and effectively improve bone mineral density,bone metabolism indices,and alleviate oxidative stress responses.
6.Application of highly selective arterial indocyanine green angiography in the design of anterolateral thigh free flap
Shi WANG ; Shuai DONG ; Yang CAO ; Guiyang WANG ; Chengpeng YANG ; Fengwen SUN ; Yongtao HUANG ; Liping GUO ; Liang YANG ; Rong ZHOU ; Jihui JU
Chinese Journal of Burns 2024;40(10):948-954
Objective:To introduce the application of highly selective arterial indocyanine green angiography (hereinafter referred to as highly selective arterial angiography) in the design of anterolateral thigh free flap.Methods:This study was a retrospective observational study. From November 2023 to April 2024, 29 patients with wounds in extremities which were repaired by anterolateral thigh free flaps designed under the assistance of highly selective arterial angiography and met the inclusion criteria were admitted to the Department of Hand Surgery and Department of Wound Repair Surgery of Suzhou Ruihua Orthopedic Hospital, including 26 males and 3 females, aged 16 to 71 years. The wound area after debridement ranged from 8.0 cm×4.5 cm to 27.0 cm×16.0 cm. During the surgery, highly selective arterial angiography was used to assist in flap design. The fluorescence development range of the source arteries or perforators of flaps was observed. The blood supply range of the source arteries or perforators of flaps was determined based on the fluorescence development of the skin, and the excision position of the flap was adjusted. The flap incision area ranged from 9.0 cm×6.0 cm to 29.0 cm×16.0 cm. During the surgery, the number of highly selective arterial angiography, the type of source artery of perforators for puncture, and changes in the excision position of flaps were observed and recorded. After surgery, the blood supply and survival of flaps, the healing of wounds and the survival of skin grafts in the flap donor sites, and the angiography-related complications were observed.Results:All the 32 flaps of 29 patients were successfully excised. The highly selective arterial angiography was performed 37 times, including 13 cases of puncture of the oblique branch of the lateral circumflex femoral artery, 6 cases of puncture of the descending branch, 8 cases of double puncture of the oblique and descending branches, and 2 cases of puncture of arteries from other branches. During the surgery, the excision position of 28 flaps did not change, the excision position of 3 flaps moved towards proximal extremity of the thigh, and the excision position of 1 flap moved towards distal extremity of the thigh. All the flaps survived successfully after the surgery, and there was no partial necrosis of the flaps at the proximal or distal ends. The wounds in the flap donor sites healed, and all skin grafts survived. No angiography-related complications occurred.Conclusions:Highly selective arterial angiography can be used to determine the blood supply range of the source artery and perforators of the anterolateral thigh free flaps during the surgery. It can evaluate the blood supply of flaps more intuitively and objectively. Its application in assisting flap design can avoid partial flap necrosis caused by unreasonable preoperative design to a certain extent, and it is safe and reliable.
7.Association between the structure of intestinal flora and inflammatory response in children with sepsis:a prospective cohort study
Zhao-Yi LYV ; Liu-Ju WANG ; Mei-Xian XU ; Xin-Feng BAI ; Li-Jing CAO
Chinese Journal of Contemporary Pediatrics 2024;26(6):567-574
Objective To investigate the structural characteristics of intestinal flora in children with sepsis and its association with inflammatory response.Methods A prospective cohort study was conducted.The children with sepsis who were admitted from December 2021 to January 2023 were enrolled as the sepsis group,and the children with non-sepsis who were admitted during the same period were enrolled as the non-sepsis group.The two groups were compared in terms of the distribution characteristics of intestinal flora,peripheral white blood cell count(WBC),C reactive protein(CRP),and cytokines,and the correlation of the relative abundance of fecal flora with WBC,CRP,and cytokines was analyzed.Results At the genus level,compared with the non-sepsis group,the sepsis group had significantly lower relative abundance of Akkermansia,Ruminococcus,and Alistipes and significantly higher relative abundance of Enterococcus,Streptococcus,and Staphylococcus(P<0.05).At the phylum level,Proteobacteria was the dominant phylum(37.46%)in the group of children with a score of≤70 from the Pediatric Critical Illness Score(PICS),and Firmicutes was the dominant phylum in the group of children with a score of 71-80 or 81-90 from the PICS(72.20%and 43.88%,respectively).At the genus level,among the 18 specimens,5 had a relative abundance of>50%for a single flora.Compared with the non-sepsis group,the sepsis group had significant higher levels of WBC,CRP,interleukin-6(IL-6),interleukin-10(IL-10),and tumor necrosis factor-α(P<0.05).The Spearman's rank correlation analysis showed that at the genus level,the relative abundance of Ruminococcus,Alistipes,and Parasutterella in the sepsis group was negatively correlated with the levels of WBC,CRP,and IL-6(P<0.05);the relative abundance of Enterococcus was positively correlated with the CRP level(P<0.01);the relative abundance of Streptococcus and Staphylococcus was positively correlated with the levels of CRP and IL-6(P<0.05);the relative abundance of Streptococcus was positively correlated with WBC(P<0.05).Conclusions Intestinal flora disturbance is observed in children with sepsis,and its characteristics vary with the severity of the disease.The structural changes of intestinal flora are correlated with inflammatory response in children with sepsis.
8.Evidence-Based Dampness-Heat ZHENG (Syndrome) in Cancer: Current Progress toward Establishing Relevant Animal Model with Pancreatic Tumor.
Ju-Ying JIAO ; Chien-Shan CHENG ; Zhang-Qi CAO ; Lian-Yu CHEN ; Zhen CHEN
Chinese journal of integrative medicine 2024;30(1):85-95
Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG (syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG (DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted animal model to study this core syndrome in vivo. The shortage of animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer animal model.
Animals
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Humans
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Medicine, Chinese Traditional
;
Hot Temperature
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Pancreatic Neoplasms/therapy*
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Models, Animal
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Syndrome
9.Experimental study on regulation of immune effect of brain glioma cells by NKG2D mediated by miR-10b
Gang YUAN ; Hu JU ; Zongyu XIAO ; Wenhui LI ; Lixin CAO ; Chaojie HUI
Chinese Journal of Immunology 2024;40(3):507-512
Objective:To observe the regulatory effect of microRNA-10b(miR-10b)on the immune effect of glioma cells and explore its mechanism.Methods:Human glioma cell U251 was cultured to obtain cells in logarithmic growth stage.The cell suspen-sion was prepared according to the concentration of 1.0×105 cells/ml,and the control group,overexpression group,low expression group and blank group were set up,with 6 wells in each group.The negative control,miR-10b mimics and miR-10b inhibitor were transfected by liposome transfection in control group,overexpression group and low expression group,respectively.The blank group was given the same amount of sterile normal saline.Natural killer(NK)cells from peripheral blood of a healthy volunteer was isolated and cultured.The killing activity of NK cells was detected by MTT method.The expression of NK cell activated receptor(NKG2D)on the surface of NK cells in each group were detected by flow cytometry,and the expression of major histocompatibility complex class Ⅰ chain-related gene A(MICA),UL16 binding protein 2(ULBP2)and UL16 binding protein 3(ULBP3)on the surface of U251 hu-man glioma cells in each group were detected.Results:The transfection efficiency of control group,overexpression group and low ex-pression group were(93.55±2.05)%,(95.67±3.14)%,(94.18±3.26)%,respectively.Compared with control group and blank group,the expression of miR-10b increased in overexpression group and decreased in low expression group,and the difference were statisti-cally significant(P<0.05).There was no significant difference in the expression of miR-10b between control group and blank group(P>0.05).Compared with control group and blank group,the killing activity of NK cells with different effect target ratios in overex-pression group decreased,the expression of NKG2D decreased,the killing activity of NK cells with different effect target ratios in low expression group increased,and the expression of NKG2D increased,and the difference were statistically significant(P<0.05).The killing activity of NK cells in each group increased with the increase of effect target ratio,and the difference were statistically signifi-cant(P<0.05),and there was no significant difference in NK cell killing activity and NKG2D expression between control group and blank group(P>0.05).Compared with control group and blank group,the expression of MICA,ULBP2 and ULBP3 on the surface of human glioma cell U251 in overexpression group decreased,and the expression of MICA,ULBP2 and ULBP3 on the surface of human glioma cell U251 in low expression group increased,the difference were statistically significant(P<0.05),and there was no signifi-cant difference in the expression of MICA,ULBP2 and ULBP3 on the surface of U251 glioma cells between control group and blank group(P>0.05).Conclusion:Inhibiting the expression of miR-10b can increase the expression of NKG2D on the surface of NK cells and MICA,ULBP2 and ULBP3 on the surface of human glioma cell U251,and enhance the killing activity of NK cells against human glioma cell U251.
10.Analysis of amino acid and protein components of commercial swim-bladders
Jin-Ju ZHANG ; Yi-Hong LU ; Qing HE ; Meng-Hua WU ; Zhi-Guo MA ; Ying ZHANG ; Hui CAO
Chinese Traditional Patent Medicine 2024;46(2):499-506
AIM To study the amino acids and proteins in 16 batches of commercial fish swim-bladders with different origins.METHODS A high performance liquid chromatography method based on pre-column derivatization using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate(AQC)was developed for the determination of contents and components of 17 amino acids in fish swim-bladders.Sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)was performed to analyze the molecular weight distribution of proteins from different fish swim-bladders,and proteins in fish swim-bladders were identified by proteomics method.RESULTS The result showed that the determination of 17 amino acids had a good linear relationship(R2≥0.998 0).The average recovery rate was 85.62%-109.60%and the relative standard deviations of precision,stability and repeatability were less than 3.5%.The total content of the 17 amino acids in 16 batches of fish swim-bladders ranged from 468.31 mg/g to 620.05 mg/g.A total of 688 proteins including 11 collagens were identified from 16 batches of fish swim-bladder samples and a plenty of low-abundance proteins at 52-95 kDa were also detected in fish swim-bladders by SDS-PAGE.CONCLUSION This study provides a good reference for the quality evaluation and further utilization of fish swim-bladders.

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