1.High-dose estrogen impairs demethylation of H3K27me3 by decreasing Kdm6b expression during ovarian hyperstimulation in mice.
Quanmin KANG ; Fang LE ; Xiayuan XU ; Lifang CHEN ; Shi ZHENG ; Lijun LOU ; Nan JIANG ; Ruimin ZHAO ; Yuanyuan ZHOU ; Juan SHEN ; Minhao HU ; Ning WANG ; Qiongxiao HUANG ; Fan JIN
Journal of Zhejiang University. Science. B 2025;26(3):269-285
Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female
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Mice
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Demethylation/drug effects*
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Embryonic Stem Cells
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Estrogens/administration & dosage*
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Gene Expression/drug effects*
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Histones/metabolism*
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Jumonji Domain-Containing Histone Demethylases/metabolism*
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Mice, Inbred C57BL
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Oocytes
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Ovary/drug effects*
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Reproductive Techniques, Assisted
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Animals
2.Investigating the effects and mechanisms of Yiqi Jiedu Decoction in protecting against ionizing radiation—induced small intestinal functional damage in mice based on ferroptosis
Yan WANG ; Minhao XU ; Wenyan ZHANG ; Yuankai GAO ; Qing XU ; An WANG ; Wenhui XU ; Sumin HU
Space Medicine & Medical Engineering 2025;36(5):389-395
Objective To observe the protective effects of Yiqi Jiedu Decoction on ionizing radiation-induced small intestinal functional injury in mice,and explore whether it alleviates such injury by inhibiting small intestinal ferroptosis,thereby providing scientific support for the discovery and development of intestinal radiation protection drugs in aerospace medicine.Methods A total of 378 male Balb/c mice were randomly divided into 7 groups:blank control group,model group,positive drug group,high-dose Yiqi Jiedu Decoction group,low-dose Yiqi Jiedu Decoction group,Liproxstatin-1 pre-irradiation administration group,and Liproxstatin-1 post-irradiation administration group,with 54 mice in each group.Each group was further divided into 3 batches,with 18 mice per batch.Seven days after preventive administration,all groups except the blank control group were subjected to a single whole-body irradiation with 2.0 Gy 60Co γ-rays.The general condition and morphological structure of the small intestine were observed at 1,3,and 7 days post-irradiation.The small intestinal charcoal propulsion rate,serum D-xylose content,and lactic acid content were measured,along with the levels of Fe,LPO,MDA,GSH,and SOD activity in the small intestine.Results Yiqi Jiedu Decoction could mitigate the decrease in body weight of mice after 2.0 Gy 60Co γ-ray irradiation,improve the morphological structure of the small intestine,reduce the small intestine charcoal propulsion rate,increase serum D-xylose levels,and decrease total serum lactate levels.It also alleviated mitochondrial shrinkage in the small intestine and reduced the contents of Fe and MDA in small intestine tissues.Conclusion Yiqi Jiedu Decoction may alleviate ionizing radiation-induced small intestinal functional injury by inhibiting ferroptosis in the small intestine,providing a new strategy for intestinal radiation injury in deep space exploration missions such as manned spaceflight.
3.Development of a radiolabeled site-specific single-domain antibody positron emission tomography probe for monitoring PD-L1 expression in cancer
Yinfei CHEN ; Shiyu ZHU ; Jiayu FU ; Jianguo LIN ; Yan SUN ; Gaochao LV ; Minhao XIE ; Tao XU ; Ling QIU
Journal of Pharmaceutical Analysis 2022;12(6):869-878
Despite advances in immunotherapy for the treatment of cancers,not all patients can benefit from programmed cell death ligand 1(PD-L1)immune checkpoint blockade therapy.Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level;hence,accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects.Therefore,based on the high affinity antibody Nb109,a new site-specifically radiolabeled tracer,68Ga-NODA-cysteine,aspartic acid,and valine(CDV)-Nb109,was designed and synthesized to accurately monitor PD-L1 expression.The tracer 68Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95%and radiochemical purity of 97%.It showed high affinity for PD-L1 with a dissociation constant of 12.34±1.65 nM.Both the cell uptake assay and positron emission tomography(PET)imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells.Meanwhile,dynamic PET imaging of a NC1-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression,allowing timely interventional immunotherapy.In conclusion,this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.
4.Meta-analysis of β-blockers for the primary prevention of liver cirrhosis with clinically significant portal hypertension with no or small esophageal varices
Xin SU ; Wenjie LI ; Zhe CHEN ; Qibiao WU ; Minhao YIN ; Xu HAN ; Danping ZHANG ; Xiqiao ZHOU ; Hong ZHU
Chinese Journal of Hepatology 2022;30(11):1237-1245
Objective:To explore whether NSBB is suitable for the primary prevention of liver cirrhosis accompanied by CSPH with no or small esophageal varices.Methods:Relevant literatures were retrieved from Cochrane library, PubMed, EMBASE, SinoMed, CNKI and Wanfang databases until December 12, 2020. All randomized controlled trials (RCTs) on NSBB use for primary prevention of cirrhosis accompanied by CSPH with no or small esophageal varices were collected. The literature was strictly screened according to the established inclusion and exclusion criteria, odds ratio (OR), and 95% confidence interval (CI) combined effect size. The development of esophageal varices and the initial upper gastrointestinal bleeding were the primary outcome measures. Death (with a maximum average follow-up of about five years) and adverse events (adverse drug reactions, etc.) were the secondary outcome measures.Results:A total of 9 RCTs with 1396 cases were included. Meta-analysis results showed that, compared with placebo, NSBB significantly reduced the incidence of liver cirrhosis accompanied by CSPH with no or small esophageal varices to large esophageal varices progression ( OR=0.51, 95% CI: 0.29-0.89, P=0.02), and mortality (with maximum average follow-up of about five years) ( OR=0.64, 95% CI: 0.44-0.92, P=0.02); however, there was no statistically significant difference in the initial upper gastrointestinal bleeding rate between the two groups ( OR=0.82, 95% CI: 0.44-1.52, P=0.53). Adverse event incidence was greater in the NSBB than the placebo group ( OR=1.74, 95% CI: 1.27-2.37, P=0.0005). Conclusions:NSBB use cannot reduce the initial upper gastrointestinal bleeding rate or adverse event incidence in patients with liver cirrhosis accompanied by CSPH with no or small esophageal varices, but it can delay the progression of gastroesophageal varices and reduce patient mortality.
5.Construction and validation of the physical fitness age model for community-dwelling elderly people
Jing XU ; Jiaojiao LI ; Ya CHEN ; Dan XU ; Yufei CHEN ; Minhao SHI ; Hongyan MENG ; Li WANG
Chinese Journal of Modern Nursing 2022;28(34):4725-4731
Objective:To construct and validate the physical fitness age model for community-dwelling elderly people, so as to provide new methods and reference for the health assessment and rehabilitation guidance of the elderly.Methods:From March to September 2021, 794 community-dwelling health people in six districts of Suzhou (Wuzhong District, Gusu District, Xiangcheng District, Wujiang District, Huqiu District and Industrial Park) were selected by multi-stage stratified sampling. Postgraduates who received unified training used unified monitoring tools to assess the physical function and physical fitness of the subjects in the designated community health service centers. Principal component analysis was used to construct a physical fitness age model. According to the scores of Short Physical Performance Battery, people with high physical function and people with low physical function were divided to verify the effectiveness of the model evaluation.Results:A total of four indicators, including 2-min step test, 30 s chair stand test, biceps flexion and lift test, and time up and go test (TUGT) , were finally included to build a physical fitness age model. The model formula was physical fitness age=-0.126×2-min step test-0.612×biceps flexion and lift test-0.625×30 s chair stand test+1.855×TUGT+0.51×age+55.29. The model validation showed that the physical fitness age of the community-dwelling elderly people of the high physical function group was lower than the age, and the difference was statistically significant ( P<0.01) . The physical fitness age of the community-dwelling elderly people of the low physical function group was higher than that of the age, and the difference was also statistically significant ( P<0.01) . The research results were consistent with the research assumptions, suggesting that the model was reasonable and effective. Conclusions:The construction of the physical fitness age model for community-dwelling elderly people can reflect the decline of the elderly's physical function, can be used for the elderly's health assessment and rehabilitation guidance, and can provide evaluation indicators for the elderly to provide community and home medical care services.
6. High Expression of GADD45B Induced by Acid and Bile Acid is A Potential Prognostic Marker for Barrett's Esophagus-associated Adenocarcinoma
Xin SU ; Danping ZHANG ; Zhe CHEN ; Xu HAN ; Peichen XIA ; Minhao YIN ; Wenjie LI ; Shuo LI ; Guoqin ZHU ; Hong ZHU
Chinese Journal of Gastroenterology 2021;26(11):647-655
Background: Esophageal mucosal injury induced by gastroesophageal reflux is a key link to the development of Barrett's esophagus-associated adenocarcinoma. However, the molecular mechanism is still not elucidated. Aims: To investigate the role of differentially expressed genes (DEGs) after stimulating esophageal cells with acid and bile acid in the development of esophageal adenocarcinoma (EAC). Methods: The DEGs were obtained through bioinformatics methods after stimulating esophageal cells with low pH and deoxycholic acid, and GO, KEGG enrichment analysis were performed. Protein-protein interaction (PPI) network was performed to screen the hub genes, and their relationships with prognosis and tumor stage of EAC patients were analyzed. The role of co-expressed genes of GADD45B in EAC was also analyzed. Results: Thirty-one overlapping DEGs were obtained after stimulating esophageal cells with low pH and deoxycholic acid, which mainly enriched in the cytokine-cytokine receptor interaction, transcription factors activity, and regulation of cell proliferation and apoptotic process. High expression of GADD45B was correlated with the survival prognosis and tumor stage of EAC patients. GADD45B and its co-expressed genes were involved in the production of tumor necrosis factor. Conclusions: The high expression of GADD45B induced by acid and bile acid is correlated with the prognosis and tumor stage of EAC patients, and is a potential diagnosis and treatment target for Barrett's esophagus-associated adenocarcinoma.
7.Application value of three-dimensional visualization technology in management of middle hepatic vein processing in associating liver partition and portal vein ligation for staged hepatectomy
Mingqi WEI ; Ling ZHANG ; Jilong WANG ; Banghao XU ; Weilin HUANG ; Yanjuan TENG ; Ya GUO ; Minhao PENG ; Zhang WEN
Chinese Journal of Digestive Surgery 2020;19(11):1217-1223
Objective:To investigate the application value of three-dimensional visualization technology in management of middle hepatic vein (MHV) processing in associating liver partition and portal vein ligation for staged hepatectomy(ALPPS).Methods:The retrospective and descriptive study was conducted. The clinical data of 40 patients with right massive liver cancer or multiple right liver lesions who underwent ALPPS in the First Affiliated Hospital of Guangxi Medical University from November 2017 to August 2019 were collected. There were 34 males and 6 females, aged (44±9)years, with a range from 26 to 64 years. All patients underwent multi-slice computed tomography (CT) plain and enhanced scan of superior abdominal region before operation, and the data were transmitted to the liver visualization analysis software IQQA system with 1.5 mm thin-layer images to complete the three-dimensional reconstruction of the liver and its blood vessels. Patients were performed ALPPS based on results of three-dimensional reconstruction and intraoperative findings. Observation indicators: (1) results of preoperative three-dimensional reconstruction; (2) surgical situations; (3) follow-up. Follow-up was conducted using outpatient examinations and telephone interview to detect postopeartive survival of patients up to March 2020. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were described as M (range). Count data were represented as absolute numbers. Results:(1) Results of preoperative three-dimensional reconstruction: 40 patients underwent three-dimensional reconstruction successfully, of which 37 clearly showed MHV, tumor location and relationship between them, 3 patients showed unclearly MHV and were classified based on two-dimensional images. Of the 40 patients, 12 had MHV classified as type A, 13 as type B, 9 as type C, and 6 as type D. Three-dimensional reconstruction of vessels showed 22 with umbilical veins and 9 with anterior veins. Of the 40 patients, 35 were predicted to preserve MHV, and 5 were predicted to resect MHV. Total estimated liver volume, tumor volume, and reserved liver volume were (1 012±119)cm 3, 600 cm 3(8-2 055 cm 3), (346±80)cm 3. The ratio of future liver remnant to standard liver volume was 34%±8%. (2) Surgical situations : 40 patients underwent the first-stage ALPPS, including 35 with preservation of MHV and 5 with resection of MHV, which was accorded with preoperative prediction. Thirty-four patients underwent the second-stage ALPPS, and 6 patients had failure to receive the second-stage ALPPS due to undificiency future liver remnant. The operation time and volume of intraoperative blood loss for 40 patients undergoing first-stage ALPPS were (350±79)minutes and 300 mL(range, 100-2 600 mL). Three patients received blood transfusion and no perioperative death occurred. There were 24 patients with grade A heptic insufficiency according to criteria of International StudyGroup of Liver Surgery (ISGLS) and 16 patients with grade B heptic insufficiency after the first-stage ALPPS. Twenty-eight patients had grade Ⅰ complications of Clavien-Dindo classification, including 17 with a small pleural effusion, 10 with a small pleural and abdominal effusion, 1 with hypoproteinemia; 8 patients had grade Ⅱ complications of Clavien-Dindo classification, including 5 with pneumonia, 1 with pneumonia combined with pleural and abdominal effusion, 1 with coagulation disorders, 1 with biliary fistula; 3 patients had grade Ⅲ complications of Clavien-Dindo classification, including 2 with pneumothorax and pneumonia, 1 with pneumothorax, pneumonia and coagulation disorders; 1 patient had grade Ⅳ complications of Clavien-Dindo classification as systemic inflammatory response syndrome. All patients with complications were improved after symptomatic treatment, anti infection, transfusion of fresh frozen plasma or drainage. For the 34 patients undergoing the second-stage ALPPS, the operation time and volume of intraoperative blood loss were (320±83)minutes and 500 mL(range, 200-6 000 mL). Twelve patients received blood transfusion. There were 12 patients with grade A heptic insufficiency according to criteria of ISGLS and 22 with grade B heptic insufficiency after the second-stage ALPPS. Eighteen patients had grade Ⅰ complications of Clavien-Dindo classification, including 11 with a small pleural effusion, 7 with a small pleural and abdominal effusion; 12 patients had grade Ⅱ complications of Clavien-Dindo classification, including 4 with pneumonia, 4 with coagulation disorders, 3 with massive abdominal effusion, 1 with biliary fistula; 3 patients had grade Ⅲ complications of Clavien-Dindo classification, including 1 with pneumothorax and pneumonia, 1 with massive pleural effusion, 1 with obstructive jaundice; 1 patient had grade Ⅳ complications of Clavien-Dindo classification as pneumonia and anemia. All patients with complications were improved after symptomatic treatment, anti infection, transfusion of fresh frozen plasma or drainage. (3) Follow-up: 40 patients were followed up for 2-35 months, with a median follow-up time of 17 months. The 6-month, 1-, and 2-year survival cases were 35, 26, 21 cases. Conclusion:Three-dimensional visualization technology can clearly show the MHV classification and its relationship with tumor location, which has an important guiding significance in the decision-making of MHV management in ALPPS.
8.Lateral rectus abdominis approach combined with presacral decompression for old Denis type II sacral fractures complicated with upper sacral plexus injury
Minhao WU ; Keke XU ; Zimeng CHEN ; Huowen LIU ; Yuanlong XIE ; Feifei YAN ; Ansong PING ; Zhouming DENG ; Xiaobin ZHU ; Yongjian QI ; Jun LEI ; Lin CAI
Chinese Journal of Trauma 2020;36(5):421-427
Objective:To investigate the clinical effect of lateral rectus abdominis approach combined with presacral decompression for surgical treatment of old Denis type II sacral fractures complicated with upper sacral plexus injury.Methods:A retrospective case series study was performed on the clinical data of 9 patients with old Denis type II sacral fractures complicated with upper sacral plexus injury (L 4-S 1) admitted to Zhongnan Hospital of Wuhan University from June 2010 to December 2016. There were 6 males and 3 females, aged (33.1±7.5)years (range, 15-58 years). Embolization of internal iliac artery and preimplantation of abdominal aortic balloon were performed 2 hours before operation under the guidance of digital subtraction angiography (DSA). Surgery was performed using a single lateral rectus abdominis approach combined with presacral decompression. The operation time, intraoperative blood loss and full weight-bearing time were recorded. The visual analogue scale (VAS) and European QOL Five Dimensional health scale (EQ-5D) were compared before and after operation. The Gibbons' impairment scale was used to assess neurological function. X-ray and CT scan were used to observe internal fixation and fracture healing. The complications during and after operation were recorded. Results:The patients were followed up for 24-52 months [(35.2±5.2)months]. The operation time was (2.9±0.6)hours. The intraoperative bleeding was (573±138)ml, and the full weight-bearing time was (11.6±1.2)weeks. X-ray and CT scan showed bone healing in all patients at the latest follow-up. The VAS and EQ-5D scale improved from preoperative (7.8±0.6)points and (0.34±0.07)points to the final follow-up of (0.8±0.3)points and (0.81±0.05)points ( P<0.05). According to Gibbons classification, 8 patients were grade I and 1 patient was grade II one year after operation ( P<0.01). Namely, the radiation pain of lower extremities was significantly improved in all patients, among which 8 patients showed pain disappeared and completely returned to normal and 1 patient showed residual numbness and hypoesthesia of the affected limbs. No major complications (eg, iatrogenic lumbosacral plexus injury, vital blood vessels or pelvic organs injury) occurred during the operation. During the follow-up period, only one patient developed traumatic hip arthritis and underwent total hip arthroplasty 6 months after operation. Fractures of the remaining patients were healed well without complications like infection, pressure ulcer or implant failure. Conclusions:For old Denis type II sacral fractures complicated with upper sacral plexus injury, lateral rectus abdominis approach combined with presacral decompression can fully decompress the upper sacral plexus nerve, relieve pain, and promote functional rehabilitation, with low incidence of complications. It is an alternative surgical method for the treatment of old Denis type II sacral fractures complicated with upper sacral plexus injury.
9.Clinical efficacy of hepatic artery ringed and restriction operation-associating liver partition and portal vein ligation for staged hepatectomy in the treatment of giant hepatocellular carcinoma
Zhang WEN ; Banghao XU ; Jilong WANG ; Chunhui YE ; Kaiyi LU ; Tingting LU ; Ling ZHANG ; Jingjing ZENG ; Ya GUO ; Yanjuan TENG ; Minhao PENG
Chinese Journal of Digestive Surgery 2019;18(5):489-498
Objective To investigate the clinical efficacy of hepatic artery ringed and restriction operation-associating liver partition and portal vein ligation for staged hepatectomy (HARO-ALPPS) in the treatment of giant hepatocellular carcinoma.Methods The retrospective and descriptive study was conducted.Clinical data of a 45-year-old male patient with giant hepatocellular carcinoma who was admitted to the First Affiliated Hospital of Guangxi Medical University in July 2018 were collected.In the first stage operation,right portal vein ligation+ in situ liver partition + right hepatic artery ringed operation was performed on the patient.In the second stage operation,right hemihepatectomy was performed on the patient.Observation indicators:(1) surgical and postoperative situations of the first stage operation;(2) surgical and postoperative situations of the second stage operation;(3) postoperative pathological examination;(4) changes in future liver remnant (FLR) and tumor volume;(5) perioperative hemodynamic changes of right hepatic artery,proper hepatic artery and left hepatic artery;(6) perioperative hemodynamic changes of left-portal vein and main portal vein;(7) follow-up.Follow-up using outpatient examination was performed to detect the prognosis of patients up to February 2019.Count data were described as absolute number.Results (1) Surgical and postoperative situations of the first stage operation:the patient underwent right portal vein ligation+ in situ liver partition+ right hepatic artery ringed operation successfully.The operation time and volume of intraoperative blood loss were 376 minutes and 400 mL.Inflammatory indicators including body temperature,white blood cells (WBC),C-reactive protein,procalcitonin,and liver function indices including total bilirubin (TBil),albumin (Alb),alanine aminotransferase (ALT),aspartate aminotransferase (AST),ascites,indocyanine green retention rate at15 min (ICG R15),score of model for end-stage liver disease (MELD) before the second stage operation were improved after symptomatic supportive treatment.Prothrombin time (PT) was in the normal range after the first stage operation.There was no complication of Clavien-Dindo classification Ⅱ or above.(2) Surgical and postoperative situations of the second stage operation:the patient underwent right hemihepatectomy successfully.The operation time and volume of intraoperative blood loss were 322 minutes and 900 mL.The patient received 300 mL of fresh frozen plasma infusion.Inflammatory indicators including body temperature,C-reactive protein,and liver function indices including Alb,ALT,AST,ascites,were recoved to normal level after symptomatic supportive treatment.WBC,procalcitonin,TBil,and PT were in the normal range.There was no complication of Clavien-Dindo classification Ⅱ or above.(3) Postoperative pathological examination:① Ⅱ stage hepatocellular carcinoma was confirmed,mass-like type,with tissue necrosis and microvascluar invasion.There was no distal metastasis and tumor did not invade liver capsule or surgical margin.Ishak score of surrounding tissues was 3 in the inflammation and 2 in the fibrosis.② Chronic inflammation was detected in the gallbladder mucosa.③ Reactive hyperplasia was found in the 2 lymph nodes of the group 8.④ One in the group 12 lymph nodes showed reactive hyperplasia.Immunohistochemistry showed positive Glypican-3,Hepatocyte,Arginase-1,NM23,weakly positive vascular endothelial growth factor,and negative Ki-67,vascular endothelial cell marker CD34,biliary epithelial marker CK19 and CK 7,tumor suppressor gene P21 and P23.(4) Changes in FLR and tumor volume:FLR was 565 mL and 580 mL at the 5th and 14th day after the first stage operation respectively,accounting for 54% and 57% of total liver volume.The FLR to body weight ratio was 0.96 and 0.98,and the growth rate of FLR was 194% and 202%.Tumor volume was 1 210 mL and 1 297 mL at the 5th and 14th day after the first stage operation respectively.Tumor necrosis volume was 635 mL and 500 mL at the 5th and 14th day after the first stage operation respectively.At the 5th and 14th day after the first stage operation,the liver CT examination showed that HARO was successfully underwent and the blood supply of remnant liver was good.Preoperative CT aothgraphy (CTA) examination showed that the right hepatic tumor had rich arterial blood supply.At the 5th day after the first stage operation,the CTA examination confirmed the ringed site of right hepatic artery,and the blood supply of the tumor gradually decreased.At the 14th day after the first stage operation,CTA examination showed significant decrease in the blood supply of liver tumors.Liver CT examination showed rich supply of the remnant liver and the liver volume of 829 mL at the 7th day after the second stage operation.(5) Perioperative hemodynamic changes of the right hepatic artery,proper hepatic artery and left hepatic artery.① Blood flow of right hepatic artery was 224.3,574.7,827.5,222.7,153.0,282.5,279.1,247.9 and 150.2 mL/min before the first stage operation,before right portal vein ligation,after right portal vein ligation and before right hepatic artery ringed and restriction,after right portal vein ligation and right hepatic artery ringed and restriction,at the 1st,3th,5th and 7th day after the first stage operation.Blood flow of right hepatic artery in the second stage operation was 505.0 mL/min.② Blood flow of proper hepatic artery was 399.7,793.5,830.5,1 075.4,784.7.5,821.2,722.8,467.4 and 555.4 mL/min before the first stage operation,before right portal vein ligation,after right portal vein ligation and before right hepatic artery ringed and restriction,after right portal vein ligation and right hepatic artery ringed and restriction,at the 1st,3th,5th and 7th day after the first stage operation.Blood flow of proper hepatic artery was 505.0,473.3,158.5,627.0,103.8 and 139.8 mL/min before right hepatectomy in the second stage operation,after right hepatectomy,at the 1st,3th and 5th day after the second operation,respectively.③ Blood flow of left hepatic artery was 147.5,13.8,19.4,16.2,62.1,93.9,67.1,30.8 and 106.1 mL/min before the first stage operation,before right portal vein ligation,after right portal vein ligation and before right hepatic artery ringed and restriction,after right portal vein ligation and right hepatic artery ringed and restriction,at the 1st,3th,5th,7th and 10th day after the first stage operation.Blood flow ot left hepatic artery was 52.0,43.2,112.4,103.6,80.7 and 56.1 mL/min before right hepatectomy in the second stage operation,after right hepatectomy,at the 1st,3th and 5th day after the second operation,respectively.(6) Perioperative hemodynamic changes of left-portal vein and main portal vein.① Blood flow of left portal vein was 552.6,181.2,412.2,320.0,1 777.7,1 284.7,749.5 and 484.2 mL/min before the first stage operation,before right portal vein ligation,after right portal vein ligation and right hepatic artery ringed and restriction,at the 1st,3th,5th,7th and 10th day after the first stage operation,respectively.Blood flow of left portal vein was 793.3,979.0,485.2,1 042.5,803.5 and 548.3 mL/min before right hepatectomy in the second stage operation,after right hepatectomy,at the 1st,3th,5th and 7th day after the second operation respectively.② Blood flow of main portal vein was 1 186.0,696.7,833.7,431.7,1 319.1,668.4,890.7,550.8 mL/min before the first stage operation,before right portal vein ligation,after right portal vein ligation and right hepatic artery ringed and restriction,at the 1st,3th,5th,7th and 10th day after the first stage operation,respectively.Blood flow of main portal vein was 846.4,937.4,891.2,1 671.0,2 697.8,and 1 230.0 mL/min before right hepatotectomy in the second stage operation,after right hepatectomy,at the 1st,3th,5th and 7th day after the second stage operation,respectively.(7) Follow up:the patient was followed up for 6 months and survived well,with Child A of liver function and normal alpha fetoprotein level.Liver contrast CT examination showed increase in the remnant liver,good blood supply,and no tumor recurrence.The FLR was 727 mL at the 2 months after operation.Conclusion For patients with giant hepatocellular carcinoma,HARO-ALPPS can be performed to decrease blood supply of tumor,increase tumor necrosis area,and reduce the incidence of intrahepatic arteriovenous fistula,which ensure blood supply of remnant liver hyperplasia.
10.Correlation between interleukin-6 and future liver remnant growth after associating liver partition and portal vein ligation for staged hepatectomy
Chunhui YE ; Banghao XU ; Zhang WEN ; Ling ZHANG ; Tingting LU ; Jingjing ZENG ; Meifang OU ; Yanjuan TENG ; Ya GUO ; Minhao PENG
Chinese Journal of Digestive Surgery 2018;17(12):1187-1192
Objective To investigate the correlation between interleukin-6 (IL-6) and future liver remnant (FLR) growth after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS).Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 15 patients who underwent ALPPS at the First Affiliated Hospital of Guangxi Medical University between March 2017 and May 2018 were collected.Observation indicators:(1) intraoperative situations in the first staged ALPPS and the second staged ALPPS;(2) postoperative situations:① postoperative complications and duration of hospital stay,② results of pathological examination;(3) IL-6 concentration in the peripheral blood before and after operation;(4)follow-up situations.Follow-up using outpatient examination,telephone interview and internet was performed to detect life quality and survival of patients.Imaging examination was done to detect tumor recurrence and metastasis.Follow-up was done up to May 2018.Measurement data with normal distribution or similar normal distribution were represented as (x)±s.Measurement data with skewed distribution were described as M (range).Repeated measures data were analyzed by the repeated measures ANOVA.Correlation comparison was done using Pearson bivariate correlation test.Results (1) Intraoperative situations.① The first staged ALPPS:15 patients had liver parenchymal transection via anterior approach combined with selective hepatic vascular exclusion,without allogenic blood transfusion.The operation time,volume of intraoperative blood loss,FLR at postoperative 16 days,interval time to the second staged ALPPS,growth rate of liver volume,ratio of FLR and standard liver volume (SLV) were respectively 324 minutes (range,240-387 minutes),356 mL (range,200-600 mL),(582± 134) cm3,24 days (range,9-34 days),35%±20% and 53%±7%.② The second staged ALPPS:of 15 patients,13 underwent the second staged ALPPS successfully including 11 undergoing middle hepatic vein preserved right hepatectomy and 2 undergoing expanded right hemihepatectomy or right trisegmentectomy,1 underwent transcatheter arterial chemoembolization (TACE) due to FLR/SLV =31%,1 was detected yellow-white nodules at left lobe and confirmed as hepatocellular carcinoma by frozen section pathological examination,and then improved and discharged after 5-FU abdominal local chemotherapy combined with postoperative TACE.The operation time,volume of intraoperative blood loss of 13 patients undergoing the second staged ALPPS were 324 minutes (range,140-515 minutes) and 639 mL(range,100-1 400 mL).Two patients had blood transfusion including 1 with 800 mL of fresh frozen plasma and 4.0 U of red cells and 1 with 600 mL of plasma and 9.5 U of de-leucocytes and red cells.(2) Postoperative situations.① Postoperative complications and duration of hospital stay:15 patients had no perioperative death,9 and 6 were detected grade A and grade B liver failure respectively,15 had grade Ⅰ complications of Clavien-Dindo classification and no patient had grade Ⅱ and above complications,10 had pleural effusion including 1 with volume of effusion >500 mL.Of 13 patients undergoing the second staged ALPPS,4 and 9 were detected grade A and grade B liver failure respectively,8 and 5 had grade Ⅰ and Ⅱ complications of Clavien-Dindo classification and no patient had grade Ⅲ and above complications,11 had few pleural effusion with volume of effusion <500 mL.Patients with grade B liver failure and grade Ⅱ complications were recovered and discharged after treatments of liver protection,gastric protection,reinforced dressing change,continuous use of Alb,fresh frozen plasma transfusion.The patient with volume of pleural effusion > 500 mL was improved after closed thoracic drainage and other patients with pleural effusion were improved after symptomatic and supportive treatment.Duration of total hospital stay was 31 days (range,22-49 days) in 15 patients.② Results of pathological examination:13 patients undergoing complete ALPPS were diagnosed as hepaticocellular carcinoma with R0 resection and without cancer cells involving surgical margin,including 7 with grade Ⅱ portal vein tumor thrombus.Ishak score for postoperative pathological fibrosis and liver cirrhosis was 7.7±1.4 in 15 patients,including 1 case of 5,1 case of 6,2 case of 7,6 case of 8,5 case of 9.(3) IL-6 concentration in the peripheral blood before and after operation:IL-6 concentration in the peripheral blood before surgery was (8±3)ng/L in 15 patients,and (207±150)ng/L,(104±65)ng/L,(45±38)ng/L,(26±9)ng/L,(18±10)ng/L at 1,3,5,7,10 days after the first staged ALPPS,showing a statistically significant difference in changing trend before and after surgery (F=25.877,P<0.05) and statistically significant differences in paired comparison between 1,3,5,7,10 days after the first staged ALPPS and before surgery respectively (P<0.05).There was correlation between IL-6 concentration in the peripheral blood at 1,3 days after the first staged ALPPS and growth of FLR (r=0.766,0.881,P<0.05),and also between IL-6 concentration in the peripheral blood at 1,3 days after the first staged ALPPS and growth rate of FLR (r =0.810,0.879,P< 0.05).(4) Follow-up:15 patients were followed up for 1-14 months with a median time of 7 months.Of the 15 patients,1 without the second staged ALPPS died of multiple organ dysfunction syndrome at 7 months after the first staged ALPPS,14 survived and took care of theirselves in daily life during follow-up with improved life quality,including 1 detected multiple lung metastases at 12 months after complete ALPPS with mild increased AFP and 13 undetected new lesions in the remnant liver on contrast-enhanced CT and liver contrast-enhanced ultrasonography with normal AFP.Conclusion The peak of IL-6 concentration in peripheral blood at 1,3 days after the first staged ALPPS is significantly correlated with the hyperplasia of FLR,which may be used to predict the hyperplasia of FLR.

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