1.TIPS with bare stents and covered stents for the treatment of portal hypertension:analysis of its long-term efficacy
Shengli YANG ; Linqiang LAI ; Jingjing SONG ; Dengke ZHANG ; Zhongwei ZHAO ; Jianfei TU ; Jiansong JI ; Yingjun BAO ; Junpeng GU ; Weixin REN
Journal of Interventional Radiology 2024;33(3):295-299
Objective To evaluate the long-term efficacy of transjugular intrahepatic portosystemic shunt(TIPS)with bare stents and Fluency covered stents in the treatment of portal hypertension,and to discuss its clinical value.Methods The clinical data of 29 patients with intractable ascites or esophagogastric fundus varices rupture and hemorrhage caused by cirrhotic portal hypertension,who received TIPS with bare stents and covered stents at the First Affiliated Hospital of Xinjiang Medical University of China(25 patients)and the Lishui Municipal Central Hospital of China(4 patients)between August 2012 and December 2017,were retrospectively analyzed.The patients were regularly followed up to check the survival status.The postoperative cumulative shunt patency rate and cumulative survival rate of the patients were analyzed by Kaplan-Meier method.Results The technical success rate of TIPS was 100%.The mean portal vein pressure was decreased from preoperative(40.21±3.24)cmH2O to postoperative(24.55±3.55)cmH2O(P<0.05).The patients were followed up for 5.1-10.5 years.The postoperative 1-,3-,5-,7-year primary cumulative patency rates of the shunt were 89.7%,75.9%,75.9% and 52.5%,respectively.The postoperative 5-,7-,9-and 10-year cumulative survival rates were 100%,66.9%,66.9% and 33.4%,respectively.The incidence of hepatic encephalopathy was 13.8%(4/29).Conclusion Using bare stents combined with Fluency covered stents for TIPS is clinically safe and effective in the treatment of portal hypertension.This technique carries higher long-term shunt patency rate and low incidence of hepatic encephalopathy.Therefore,it can be used as a substitute for Viatorr stent when necessary.(J Intervent Radiol,2024,33:295-299)
2.Technical details and latest progress of bronchial artery chemoembolization
Dengke ZHANG ; Liai LV ; Linqiang LAI ; Jianfei TU ; Risheng YU
Journal of Interventional Radiology 2024;33(3):330-334
At present,bronchial arterial chemoembolization(BACE)is a well-established,local minimally-invasive palliative treatment technique for mid-to-advanced primary lung cancer.However,its technical details are still controversial,and it is difficult to standardize each technical detail.Through reviewing the literature,this paper provides a detailed review of BACE,focusing on the source of lung cancer blood supply,embolization materials,particle size of embolization materials,number of treatments,embolization endpoints,selection of anti-tumor drugs,complications,therapeutic effect,etc.(J Intervent Radiol,2024,33:330-334)
3.Perioperative Animal Care for Xenotransplantation from Genetically Edited Pigs to Monkeys
Chan ZHU ; Dongliang ZHANG ; Deli ZHAO ; Xueqin SHI ; Lei QIAN ; Xuan ZHANG ; Yan JIN ; Wei DUAN ; Ruocheng QI ; Chaohua LIU ; Xuekang YANG ; Juntao HAN ; Dengke PAN
Laboratory Animal and Comparative Medicine 2024;44(5):495-501
Objective To discuss the perioperative care and wound protection of xenotransplantation from genetically edited pigs to monkeys, with the goal of improving the success rate of such experimental procedures. Methods From October 2022 to October 2023, perioperative care and wound protection were performed on 7 recipient rhesus monkeys undergoing xenotransplantation of genetically edited pig tissues and organs. Customized wound protective garments were designed based on monkeys' size and surgical area to protect the wounds, alongside meticulous perioperative care. This included preoperative preparation and medication, intraoperative monitoring of physiological indicators and anesthesia management, and postoperative care comprising wound protection, observation and monitoring, and nutritional support. Results All seven monkeys successfully underwent xenotransplantation. With the aid of protective garments and detailed care, all surgical wounds healed by first intention, and postoperative recovery was satisfactory. Conclusion Proper care and wound protection during xenotransplantation from genetically edited pigs to monkeys not only promote wound healing, but also alleviate pain and harm to animals. This has significant implications for advancing experimental research in pig-monkey xenotransplantation and enhancing animal welfare.
4.Clinical efficacy of carrellizumab combined with albumin-bound paclitaxel in patients with locally advanced esophageal cancer
Dingqian ZHANG ; Kefeng GAO ; Luyao XIONG ; Xue BAI ; Dengke NIE
Tianjin Medical Journal 2024;52(12):1256-1261
Objective To explore the clinical effect and safety of carrellizumab combined with albumin-bound paclitaxel on the treatment of patients with locally advanced esophageal cancer.Methods Ninety-eight patients with locally advanced esophageal cancer were randomly divided into the study group and the reference group,with 49 cases in each group.The reference group was treated with albumin-bound paclitaxel,while the study group was treated with camrelizumab+albumin-bound paclitaxel.After treatment,the overall efficacy was evaluated,and the disease control rate was calculated.Serum tumor markers[high mobility group protein B1(HMGB1),squamous cell carcinoma associated antigen(SCCA)],PD-1 and PD-L1 levels were detected by enzyme-linked immunosorbent assay(ELISA)before and after treatment.Immunohistochemistry was used to detect the microvascular density(MVD)and the expression levels of PD-1 and PD-L1 in esophageal carcinoma tissue.The percentages of CD3+,CD4+and CD8+cells were detected by flow cytometry.Patients were followed up and adverse reactions and survival were recorded.Results The disease control rate was higher in the study group than that of the control group(P<0.05).There were no significant differences in all indexes between the groups before treatment(P>0.05).After treatment,HMGB1 level,SCCA level,MVD,serum PD-1 level and tumor tissue high expression rate of PD-1 were all decreased in the two groups,while serum PD-L1 level,PD-L1 high expression rate and percentages of CD3+,CD4+and CD8+cells were all increased(P<0.05).Except there was no significant difference in MVD between groups,the other indexes were significantly changed in the study group compared with the control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).The progression-free survival rate was higher in the study group than that of the control group(P<0.05).Conclusion Carrellizumab combined with albumin-bound paclitaxel in the treatment of locally advanced esophageal cancer can help control lesion progression and inhibit angiogenesis,with good safety.
5.Study of Ctsk knockout regulating type H blood vessel formation and tooth extraction socket healing in mice
Wuyang ZHANG ; Dengke LI ; Yiming WANG ; Yuan LI ; Yuzhe CHEN ; Xueni ZHENG ; Hongzhi ZHOU ; Kaijin HU ; Yang XUE
Journal of Practical Stomatology 2024;40(3):330-336
Objective:To study the effects of cathepsin K(CTSK)on the healing process of tooth extraction socket and type H blood vessel angiogenesis in mice.Methods:Ctsk knockout(Ctsk-/-)mice were generated by CRISPR/Cas9 technology,and genotype sequen-cing,general observation,Micro-CT and immunohistochemistry were performed to confirm successful knockout of Ctsk.Then 8 week-old WT and Ctsk-/-mice were used to establish the tooth extraction modle by extracting the left maxillary first molars,and the mice were sac-rificed at the day 7,10,14,21,28 and 35 respectively(n=3)after tooth extraction.Then samples were subjected to stereo microscope and Micro-CT examination.Immunofluorescence staining was used to study the effect of Ctsk knockout on type H blood vessel angiogene-sis.Results:Ctsk knockout did not affect the soft tissue healing of tooth extraction socket,but significantly promoted the bone healing process,and Ctsk deficency significantly enhanced type H blood vessel angiogenesis in the tooth extraction socket.Conclusion:Ctsk knockout can enhance type H vessel angiogenesis,and promote bone healing process of tooth extraction socket in mice.
6.Report of 5 gene-edited pig-rhesus monkey heterotopic heart xenotransplantation experiment
Gen ZHANG ; Huan WANG ; Yulong GUAN ; Jie YAN ; Ji LI ; Xiaoliang LI ; Xianhua LI ; Rong ZHOU ; Xianzhi WANG ; Zhipeng REN ; Dongsheng HE ; Xin LI ; Dengke PAN ; Dianyuan LI
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(6):379-384
Objective:To investigate the changing trends in cardiac function following xenogeneic heterotopic heart transplantation of multi-gene edited pig hearts and assess the impact of recipient immune responses on donor heart, laying experimental groundwork for the clinical application of gene editing technology.Methods:On December 16, 2023, xenogeneic heterotopic heart transplantation was performed between pigs and rhesus monkeys. Functional status of the graft under post-transplantation load conditions and recipient immune indicators were observed.Results:The recipient monkeys survived for 40 days with satisfactory functionality of both donor and recipient hearts, and no hyperacute or acute immune rejection reactions were observed.Conclusion:Multi-gene editing technology provides potential for xenotransplantation, yet further exploration is needed for its clinical application.
7.MLL4 Regulates the Progression of Non–Small-Cell Lung Cancer by Regulating the PI3K/AKT/SOX2 Axis
Yang YANG ; Rongfang QIU ; Qiaoyou WENG ; Ziwei XU ; Jingjing SONG ; Siyu ZHAO ; Miaomiao MENG ; Dengke ZHANG ; Chunli KONG ; Hailin WANG ; Min XU ; Zhongwei ZHAO ; Jiansong JI
Cancer Research and Treatment 2023;55(3):778-803
Purpose:
Mixed-lineage leukemia protein 4 (MLL4/KMT2D) is a histone methyltransferase, and its mutation has been reported to be associated with a poor prognosis in many cancers, including lung cancer. We investigated the function of MLL4 in lung carcinogenesis.
Materials and Methods:
RNA sequencing (RNA-seq) in A549 cells transfected with control siRNA or MLL4 siRNA was performed. Also, we used EdU incorporation assay, colony formation assays, growth curve analysis, transwell invasion assays, immunohistochemical staining, and in vivo bioluminescence assay to investigate the function of MLL4 in lung carcinogenesis.
Results:
We found that MLL4 expression was downregulated in non–small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues and tended to decrease with disease stage progression. We analyzed the transcriptomes in control and MLL4- deficient cells using high-throughput RNA deep sequencing (RNA-seq) and identified a cohort of target genes, such as SOX2, ATF1, FOXP4, PIK3IP1, SIRT4, TENT5B, and LFNG, some of which are related to proliferation and metastasis. Our results showed that low expression of MLL4 promotes NSCLC cell proliferation and metastasis and is required for the maintenance of NSCLC stem cell properties.
Conclusion
Our findings identify an important role of MLL4 in lung carcinogenesis through transcriptional regulation of PIK3IP1, affecting the PI3K/AKT/SOX2 axis, and suggest that MLL4 could be a potential prognostic indicator and target for NSCLC therapy.
8.Preliminary report of perioperative monitoring of six-gene-edited pig-to-cynomolgus monkey kidney xenotransplantation
Shujun YANG ; Hao WEI ; Yong XU ; Heng'en WANG ; Xiangyu SONG ; Zhibo JIA ; Jiang PENG ; Mengyi CUI ; Boyao YANG ; Leijia CHEN ; Aitao GUO ; Xiaoli ZHANG ; Dengke PAN ; Jiaxiang DU ; Panfeng SHANG ; Shengkun SUN
Organ Transplantation 2023;14(4):521-
Objective To investigate the establishment of a six-gene-edited pig-to-non-human primate kidney xenotransplantation model. Methods The kidney of humanized genetically-edited pig (GTKO/β4GalNT2KO/CMAHKO/hCD55/hCD46/hTBM) was transplanted into a cynomolgus monkey. The survival of the recipient and kidney condition after blood perfusion were observed. The parenchymal echo, blood flow changes, and size of the kidney were monitored on a regular basis. Routine blood test, kidney function test and electrolyte assessment were carried out. Dynamic changes of urine, feces and body mass were monitored. At the end of life, the transplant kidney, heart, liver, spleen, lung, and cecum were collected for pathological examination. Results The recipient died at postoperative 7 d. After blood flow was restored, the kidney was properly perfused, the organ was soft and the color was normal. At the end of the recipient's life, a slight amount of purulent secretion was attached to the ventral side of the kidney, with evident congestion and swelling, showing the appearance of "red kidney". Postoperatively, the echo of renal parenchyma was increased, blood flow was decreased, the cortex was gradually thickened, and a slight amount of effusion surrounded the kidney and abdominal cavity over time. In the recipient, the amount of peripheral red blood cells, hemoglobin, albumin, and platelets was progressively decreased, and serum creatinine level was increased to 308 μmol/L at postoperative 7 d, whereas the K+ concentration did not significantly change. Light yellow urine was discharged immediately after surgery, diet and drinking water were resumed within postoperative 3 h, and light yellow and normal-shape stool was discharged. The reddish urine was gradually restored to normal color within postoperative 1 d, which were consistent with the results of the routine urine test. A large amount of brown bloody stool was discharged twice in the morning of 2 d after surgery. Omeprazole was given for acid suppression, and the stool returned to normal at postoperative 4 d. The β2-microglobulin level was increased to 0.75 mg/L at postoperative 7 d. The body mass was increased by 1.7 kg. Autopsy pathological examination showed interstitial edema and bleeding of the transplant kidney, a large amount of infiltration of lymphocytes and macrophages, infiltration of lymphocytes in the arteriole wall and arterial cavity, accompanied by arteritis changes, lymphocyte infiltration in the cecal stroma and congestion in the spleen tissues. No significant abnormal changes were observed in other organs. Conclusions The humanized genetically-edited pig-to-non-human primate kidney xenotransplantation model is successfully established, and postoperative survival of the recipient is 1 week.
9.Coptidis Rhizoma Crude Polysaccharide and Berberine Synergistically Restore Intestinal Mucosal Barrier Damage in Ulcerative Colitis
Mingsong XUE ; Yuyu ZHENG ; Yufeng ZHANG ; Quan TAO ; Ye YANG ; Dengke YIN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(13):71-76
ObjectiveTo investigate the synergistic effect of Coptidis Rhizoma crude polysaccharide (CCP) and berberine (BBR) in treating ulcerative colitis (UC) model mice. MethodThirty male BALB/c mice were randomized into five groups. Except the 6 mice in the normal group, the rest were given 5% dextran sodium sulfate in their daily drinking water to establish the UC model. After modeling, the mice were administrated with corresponding agents by gavage once daily for 4 days: BBR (100 mg·kg-1) group, BBR (100 mg·kg-1) + low-dose (22.8 mg·kg-1) CCP group, BBR (100 mg·kg-1) + high-dose (45.6 mg·kg-1) CCP group. The mice in the model group and normal group were administrated with the same volume of normal saline. At the end of the experiment, the mice were sacrificed for the collection of colon, and the expression of tight junction proteins zonula occluden-1 (ZO-1), Claudin-1, and Occludin in colon tissue was detected by Western blot. With the normal group as the control, the disease activity index (DAI) score, colon length, colon histomorphology, and expression levels of tight junction proteins in other groups were evaluated. ResultCompared with the normal group, the modeling down-regulated the protein levels of ZO-1, Claudin-1, and Occludin (P<0.01). Compared with the model group, BBR did not significantly change the protein level of Claudin-1 and up-regulated those of ZO-1 and occludin (P<0.01). The expression levels of Claudin-1, ZO-1, and Occludin were up-regulated in BBR + CCP groups (P<0.01). The expression levels of tight junction proteins in BBR + CCP groups were significantly higher than those in the BBR group (P<0.05). ConclusionThe administration of CCP combined with BBR can effectively ameliorate intestinal mucosal barrier damage in the mice with UC.
10.Timing of radiofrequency ablation in treatment of complicated pyogenic liver abscesses
Shan KE ; Shaohong WANG ; Xiangtao WANG ; Pu ZHANG ; Dengke LI ; Jun GAO ; Xuemei DING ; Jian KONG ; Xinliang KONG ; Wenbing SUN
Chinese Journal of Hepatobiliary Surgery 2020;26(6):422-425
Objective:To study the timing of radiofrequency ablation (RFA) in treatment of complicated pyogenic liver abscesses (PLA).Methods:A retrospective analysis was performed on 49 patients with complicated PLA who were treated with the RFA-based treatment modality from August 2010 to January 2020 at Beijing Chaoyang Hospital, West Campus, Capital Medical University, Institute of Hepatobiliary, Pancreas and Spleen Surgery and the Second Hospital, Binzhou. The patients were divided into the early RFA group (≤ 72 h, n=27) and the delayed RFA group (>72 h, n=22) according to the timing of RFA. RFA was guided by laparoscopy combined with Ultrasound or CT. The safety and effective rates of RFA, and the total expenses were evaluated. Results:All patients in both the early and the delayed RFA groups were successfully cured (100%). No serious complications, including biliary leakage and massive hemorrhage, happened in the 2 groups. Significantly longer operating time and hospital stays [(8.1±1.6)d vs. (9.5±1.5)d], and higher hospital costs [(3.4±0.2) ten thousand yuan vs. (3.8±0.4) ten thousand yuan] were found in the delayed RFA group when compared with the early RFA group ( P<0.05). Conclusion:RFA treatment of complicated PLA should be completed within 72 hours of onset of PLA.

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