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.Effects of Rhizosphere Organic Acids on Metabolism of Hairy Roots of Salvia miltiorrhiza
Xinyu FU ; Wenying HAN ; Jidong JU ; Bingqian ZHOU ; Guohong YANG ; Xiao WANG ; Lanping GUO ; Wei LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):166-174
ObjectiveTo investigate the effects of rhizosphere organic acids secreted by the roots of Salvia miltiorrhiza on continuous cropping obstacles. MethodsThe mixed solution of organic acids in the rhizosphere of S. miltiorrhiza in continuous cropping and rotation cropping was added to the hairy roots subcultured for 21 days, and samples were collected on days 0, 2, 4, 6, 8, and 10. The changes of biomass, effective components, primary metabolites, secondary metabolites, antioxidant enzymes, and hormones in hairy roots of S. miltiorrhiza were observed and determined. ResultsCompared with the rotation cropping group and the blank control group, the simulation of organic acid secretion from the roots of S. miltiorrhiza had a significant inhibitory effect on the growth of hairy roots and decreased the content of effective components as well as total sugar and total protein in primary metabolites. Compared with the blank control group, the rotation cropping group and the continuous cropping group showed total sugar and total protein content decreases of 33.9% and 5.1%, respectively. On the other hand, the secretion of organic acids from S. miltiorrhiza roots significantly promoted the accumulation of total phenolic acids and total tanshinone, which showed increases of 14.6% and 1.6%, respectively, in continuous cropping group and rotation cropping group compared with the blank control group. ConclusionThe organic acid environment under continuous cropping significantly inhibited the growth of hairy roots and the accumulation of primary metabolites, while promoting the synthesis and accumulation of secondary metabolites of S. miltiorrhiza.
5.Upregulation of NR2F1 Induces Dormancy in Ovarian Cancer Cells and Promotes Their Resistance to Chemotherapeutic Agents
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(5):794-805
ObjectiveTo explore the molecular mechanism of the chemo-resistance in NR2F1-mediated dormant ovarian cancer(OC) cells. MethodsThe expression of the NR2F1 molecule in OC patients and its relationship with the overall survival of patients were analyzed using the GEPIA database. Nuclear receptor subfamily 2 group F member 1(NR2F1) overexpressed OC cell and control cell were constructed by lentivirus in vitro transfection. The proliferation of OC cells was analyzed by CCK-8 method. Real-time fluorescent quantitative PCR(qRT-PCR) was used to analyze the mRNA expression of dormancy-related molecular genes in OC cells. Western blot was performed to analyze the protein expression levels of related molecules. The viability of OC cells treated with different chemotherapy drugs was analyzed by trypan blue exclusion method. Annexin V-FITC/PI double-staining assay was used to detect the apoptosis of OC cells treated by different chemotherapy drugs. Transcriptome sequencing technology was used to analyze the differentially expressed genes in NR2F1 overexpressed SKOV3 cell line, and the relevant signaling pathways were screened through KEGG enrichment analysis. qRT-PCR was performed to verified the mRNA expression level of drug resistance-related molecules in OC cells. The GEPIA database was used to further verify the correlation between the expression of NR2F1 and the drug resistance-related genes. ResultsThe NR2F1 expression is low in the tumor tissues and the high expression of NR2F1 correlates with poor overall survival in the OC patients. Compared with the control group, the proliferation ability of the NR2F1 overexpressed OC cell lines was significantly reduced. The expression of dormancy-related molecules, cyclin-dependent kinase inhibitor 1B(p27), differentiated embryonic cartilage gene-2(DEC2) and transforming growth factor-β2(TGF-β2), increased significantly in the NR2F1 overexpressed OC cell lines, and anti-apoptotic molecule B-cell lymphoma gene-2(BCL-2) also increased. In contrast, the expression of the proliferation-related molecule KI67 was decreased. In addition, the NR2F1 overexpressed OC cell lines significantly enhanced the resistance to chemotherapy drugs. Transcriptome sequencing and KEGG enrichment analysis showed that the upregulated genes in NR2F1 overexpressed OC cells were enriched in phosphatidylinositol-3-kinase-protein kinase(PI3K-Akt) signaling pathway, focal adhesion pathway, extracellular matrix-receptor interactions and signaling pathways regulating pluripotency of stem cells, and the downregulated genes in NR2F1 overexpressed OC cells were mainly enriched in cell cycle pathway. The results of qRT-PCR verification showed that drug resistance-related molecules kinesin family member 26B(KIF26B), secreted protein acidic and rich in cysteine(SPARC), collagen type Ⅵ alpha 1(COL6A1), collagen type Ⅴ alpha 2 chain(COL5A2), frizzled homolog 1(FZD1) and inhibin subunit beta A gene(INHBA) were up-regulated in NR2F1 overexpressed OC cells. GEPIA database analysis showed that the expression of NR2F1 in OC tumor tissues was positively correlated with the expression of drug resistance-related genes KIF26B, SPARC, COL6A1, COL5A2, FZD1 and INHBA. ConclusionsThis study shows that upregulation of NR2F1 may induce dormancy in OC cells and enhance their resistance to chemo-drugs. The NR2F1-mediated drug resistance of dormant OC cells might be associated with the PI3K-Akt signaling pathway and signaling pathways regulating pluripotency of stem cells, and closely related to the upregulation of KIF26B, SPARC, COL6A1, COL5A2, FZD1 and INHBA.
6.Value of target blood pressure management based on cerebral oximetry index during CPB in preventing postoperative delirium in patients with acute type A aortic dissection
Weiwei LI ; Songqing GUO ; Shunyan LIN ; Xin CHEN ; Yang ZHANG ; Chao LUO ; Ju GAO
Chinese Journal of Anesthesiology 2024;44(5):543-547
Objective:To evaluate the value of target blood pressure management based on cerebral oximetry index (COx) during cardiopulmonary bypass (CPB) in preventing postoperative delirium (POD) in patients with acute type A aortic dissection (ATAAD).Methods:One hundred and fifty-seven patients with ATAAD, aged 18-64 yr, regardless of gender, were divided into 2 groups by a random number table method: traditional experience group (group C, n=81) and COx management group (group M, n=76). The mean arterial pressure in group C was maintained in the traditional range of 60-80 mmHg during CPB. In group M, the mean arterial pressure range was obtained based on the COx and maintained within this range during CPB. The primary outcome assessed was the development of delirium within 7 days after surgery. Secondary outcomes included other postoperative complications, tracheal extubation time, and duration of cardiac intensive care unit stay. Results:Compared with group C, the incidence and severity scores of POD were significantly decreased, the duration of POD was shortened, the duration of POD was shortened, the extubation time and duration of cardiac intensive care unit stay were shortened, and the incidence of postoperative cerebral infarction and acute kidney injury was decreased in group M ( P<0.05). Conclusions:Target blood pressure management based on COx during CPB is helpful in reducing the occurrence of POD and improving the prognosis of patients undergoing surgery for ATAAD.
7.Advances in mechanical circulatory support therapy after acute type A aortic dissection surgery
Ju GUO ; Yunlin SONG ; Xiangyou YU
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(5):311-315
Aortic dissection (AD) is a condition in which high-velocity, high-pressure blood flow in the aortic lumen enters the mesentery through a tear in the aortic intima, forming a coarctation hematoma that expands and dissociates in the aortic mesentery, resulting in pathological changes in both the true and pseudolumen. Aortic dissection has a high morbidity and mortality rate, especially in acute type A aortic dissection. Once diagnosed, type A aortic dissection should be actively treated surgically. Surgery is still the gold standard of treatment for type A aortic dissection. Despite surgical advances, the postoperative mortality rate for type A aortic dissection remains high. When conventional treatment fails and patients develop postoperative cardiopulmonary dysfunction and circulatory collapse, in severe cases leading to death. The use of mechanical circulatory assist devices for the treatment of postoperative cardiogenic shock after aortic dissection has been reported on a constant schedule, and the latest developments are described in this review.
8.Effects of anterolateral femoral perforator flaps pedicled with oblique branch of lateral circumflex femoral artery and carrying fascia lata in repairing destructive wounds and rebuilding function of hands or feet
Chengwei GE ; Guodong JIANG ; Junnan CHENG ; Liping GUO ; Zhigang CHE ; Song YUAN ; Jihui JU
Chinese Journal of Burns 2024;40(9):842-848
Objective:To investigate the effects of anterolateral femoral perforator flaps pedicled with oblique branch of lateral circumflex femoral artery and carrying fascia lata in repairing destructive wounds and rebuilding function of hands or feet.Methods:This study was a retrospective observational study. From January 2022 to March 2023, 16 patients with destructive wounds in hands or feet combined with extensor tendon defects who met the inclusion criteria were admitted to Suzhou Ruihua Orthopedic Hospital, including 12 males and 4 females, aged 3 to 63 years. The wounds were located on the hands in 12 cases and on the feet in 4 cases. The number of defective extensor tendon ranged one to five, and the length of the defect ranged from 2.5 to 6.0 cm. The wound area was 11.0 cm×5.5 cm to 29.0 cm×9.5 cm after debridement. The wounds were repaired with anterolateral femoral perforator flaps pedicled with oblique branch of lateral circumflex femoral artery and carrying fascia lata, and the flap area was 12.0 cm×6.5 cm to 30.0 cm×11.0 cm. The fascia lata was used to repair the extensor tendon defects, and the harvesting area of fascia lata was 8.0 cm×3.0 cm to 12.0 cm×8.0 cm. The wounds in flap donor areas in 15 patients were sutured directly, and the wound in flap donor area in 1 patient was covered with medium-thickness skin graft from lower abdomen. The survival of flaps and the wound healing in donor and recipient areas of flaps were observed within 1 week after operation. The number of patients who underwent thinning and plastic surgery or tenolysis was recorded during postoperative follow-up. At the last follow-up, the recovery of sensory function of the transplanted flaps on hands or feet was evaluated, the efficacy of flap repair was evaluated according to the comprehensive flap evaluation scale, and the function of hands was evaluated according to the trial standards for evaluation of partial function of upper extremity by the Hand Surgery Society of Chinese Medical Association. The following two indexes were compared, including the measured total active motion of the injured fingers and the foot function assessed using Maryland foot function scale between before surgery and at the last follow-up.Results:Arterial crisis occurred in flaps in 2 patients after operation, and the flaps survived after timely exploration; the flaps in the rest patients survived well after operation. No obvious scar hyperplasia or ulceration was observed in donor and recipient areas of flaps after operation. All patients were followed up for 8 to 16 months, of which 6 patients underwent flap thinning and plastic surgery 6 to 7 months after operation, and 4 patients underwent tenolysis 3 to 6 months after operation. At the last follow-up, the recovery of sensory function of flaps reached S1 level in 5 cases and S2 level in 11 cases, and the two-point discrimination only had 1 point. The efficacy of flap repair scored 80 to 91, which were evaluated as excellent in 5 cases, good in 9 cases, and acceptable in 2 cases. The hand function was evaluated as excellent in 5 cases, good in 5 cases, and acceptable in 2 cases. The active extension function of the injured finger/toe was reconstructed successfully, and the total active motion of the injured finger was (225±22)° at the last follow-up, which was significantly higher than (117±20)° before surgery ( t=119.59, P<0.05); the foot function score was 86±7 at the last follow-up, which was significantly higher than 29±7 before surgery ( t=222.68, P<0.05), and the foot function was evaluated as excellent in 2 cases, good in 1 case, and acceptable in 1 case. Conclusions:The operation of harvesting the anterolateral femoral perforator flap pedicled with oblique branch of lateral circumflex femoral artery is relatively simple. After the wounds on hands or feet being repaired with the flaps, the appearance and function are good, with no obvious scar hyperplasia in donor and recipient areas of flaps. The fascia lata carried by the flap can repair the extensor tendon defect at the same time and improve the movement of the finger/toe.
9.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.
10.Analysis of Helicobacter pylori infection in the natural population of Sanya City
Shi-Mei HUANG ; Lian-Guo LAN ; Da-Ya ZHANG ; Run-Xiang CHEN ; Xiao-Dong ZHANG ; Chen CHEN ; Fan ZENG ; Da LI ; Xian-Feng HUANG ; Qi WANG ; Shi-Ju CHEN ; Lei GAO ; Jun-Tao ZENG ; Fei-Hu BAI
Modern Interventional Diagnosis and Treatment in Gastroenterology 2024;29(2):141-145
Objective To explore the current status of H.pylori infection in the natural population of Sanya City,analyze its influencing factors,and provide a reference basis for the prevention and control of H.pylori infection.Methods A total of 677 residents from four districts of Sanya City were selected by overall stratified random sampling method,and were subjected to urea 14C breath test and questionnaire survey to calculate the positive rate of H.pylori in the natural population and analyze the influencing factors of H.pylori infection.Results A total of 606 residents were included,and the number of H.pylori positive detections was 261,with a positive detection rate of 38.5%.Among them,different ethnicity,marital status,smoking,eating vegetables and fruits,and literacy level were associated with H.pylori infection(P<0.05);gender,age,BMI,alcohol consumption,drinking water source,betel quid chewing,and the number of cohabitants were not significantly associated with H.pylori infection(P>0.05).Family infection was an independent risk factor for H.pylori infection in the natural population of Sanya City,and Li ethnicity,frequent consumption of fruits and vegetables,and college and higher education level were independent protective factors for H.pylori infection in the natural population of Sanya City.Conclusion The rate of H.pylori infection in the natural population of Sanya City is lower than the national average.Consuming more fruits and vegetables and improving the awareness of hygiene protection are conducive to the prevention of H.pylori infection;and the promotion of the family and related members with the same examination and treatment is important to avoid aggregation of infection within the family.

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