1.Toxoplasma gondii infection induces cell apoptosis via multiple pathways revealed by transcriptome analysis.
Kaige DU ; Fei LU ; Chengzuo XIE ; Haojie DING ; Yu SHEN ; Yafan GAO ; Shaohong LU ; Xunhui ZHUO
Journal of Zhejiang University. Science. B 2022;23(4):315-327
Toxoplasma gondii is a worldwide parasite that can infect almost all kinds of mammals and cause fatal toxoplasmosis in immunocompromised patients. Apoptosis is one of the principal strategies of host cells to clear pathogens and maintain organismal homeostasis, but the mechanism of cell apoptosis induced by T. gondii remains obscure. To explore the apoptosis influenced by T. gondii, Vero cells infected or uninfected with the parasite were subjected to apoptosis detection and subsequent dual RNA sequencing (RNA-seq). Using high-throughput Illumina sequencing and bioinformatics analysis, we found that pro-apoptosis genes such as DNA damage-inducible transcript 3 (DDIT3), growth arrest and DNA damage-inducible α (GADD45A), caspase-3 (CASP3), and high-temperature requirement protease A2 (HtrA2) were upregulated, and anti-apoptosis genes such as poly(adenosine diphosphate (ADP)-ribose) polymerase family member 3 (PARP3), B-cell lymphoma 2 (Bcl-2), and baculoviral inhibitor of apoptosis protein (IAP) repeat containing 5 (BIRC5) were downregulated. Besides, tumor necrosis factor (TNF) receptor-associated factor 1 (TRAF1), TRAF2, TNF receptor superfamily member 10b (TNFRSF10b), disabled homolog 2 (DAB2)-interacting protein (DAB2IP), and inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) were enriched in the upstream of TNF, TNF-related apoptosis-inducing ligand (TRAIL), and endoplasmic reticulum (ER) stress pathways, and TRAIL-receptor 2 (TRAIL-R2) was regarded as an important membrane receptor influenced by T. gondii that had not been previously considered. In conclusion, the T. gondii RH strain could promote and mediate apoptosis through multiple pathways mentioned above in Vero cells. Our findings improve the understanding of the T. gondii infection process through providing new insights into the related cellular apoptosis mechanisms.
Animals
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Apoptosis
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Chlorocebus aethiops
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Gene Expression Profiling
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Humans
;
Mammals/genetics*
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Toxoplasma/genetics*
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Toxoplasmosis/pathology*
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Vero Cells
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ras GTPase-Activating Proteins/genetics*
2.Toxoplasma gondii infection induces cell apoptosis via multiple pathways revealed by transcriptome analysis
DU KAIGE ; LU FEI ; XIE CHENGZUO ; DING HAOJIE ; SHEN YU ; GAO YAFAN ; LU SHAOHONG ; ZHUO XUNHUI
Journal of Zhejiang University. Science. B 2022;23(4):315-327
Toxoplasma gondii is a worldwide parasite that can infect almost all kinds of mammals and cause fatal toxoplasmosis in immunocompromised patients. Apoptosis is one of the principal strategies of host cells to clear pathogens and maintain organismal homeostasis, but the mechanism of cell apoptosis induced by T. gondii remains obscure. To explore the apoptosis influenced by T. gondii, Vero cells infected or uninfected with the parasite were subjected to apoptosis detection and subsequent dual RNA sequencing (RNA-seq). Using high-throughput Illumina sequencing and bioinformatics analysis, we found that pro-apoptosis genes such as DNA damage-inducible transcript 3 (DDIT3), growth arrest and DNA damage-inducible α (GADD45A), caspase-3 (CASP3), and high-temperature requirement protease A2 (HtrA2) were upregulated, and anti-apoptosis genes such as poly(adenosine diphosphate (ADP)-ribose) polymerase family member 3 (PARP3), B-cell lymphoma 2 (Bcl-2), and baculoviral inhibitor of apoptosis protein (IAP) repeat containing 5 (BIRC5) were downregulated. Besides, tumor necrosis factor (TNF) receptor-associated factor 1 (TRAF1), TRAF2, TNF receptor superfamily member 10b (TNFRSF10b), disabled homolog 2 (DAB2)-interacting protein (DAB2IP), and inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) were enriched in the upstream of TNF, TNF-related apoptosis-inducing ligand (TRAIL), and endoplasmic reticulum (ER) stress pathways, and TRAIL-receptor 2 (TRAIL-R2) was regarded as an important membrane receptor influenced by T. gondii that had not been previously considered. In conclusion, the T. gondii RH strain could promote and mediate apoptosis through multiple pathways mentioned above in Vero cells. Our findings improve the understanding of the T. gondii infection process through providing new insights into the related cellular apoptosis mechanisms.
3.PTCD combined with laparoscopic common bile duct exploration and primary duct closure in treating patients presenting with acute cholangitis due to common bile duct stones
Xueme DING ; Xiangtao WANG ; Xinliang KONG ; Shangsheng LI ; Jun GAO ; Shan KE ; Shaohong WANG ; Jian KONG ; Yinming ZHOU ; Qiang LI ; Wenbing SUN
Chinese Journal of Hepatobiliary Surgery 2021;27(7):513-516
Objective:To study the results of using a sequential menagement of conservative treatment, percutaneous transhepatic cholangial drainage(PTCD), laparoscopic cholecystectomy(LC) combined with laparoscopic common bile duct exploration(LCBDE) and primary duce closure(PDC) in patients with cholecystolithiasis and common bile duct stone(CBDS) who presented with acute cholangitis.Methods:The clinical data of 397 patients with CBDS and cholecystolithiasis who presented with acute cholangitis from January 2015 to August 2020 were retrospectively analyzed, including 230 patients from the West Campus, Beijing Chaoyang Hospital, Capital Medical University, 95 patients from the Second People's Hospital of Binzhou and 72 patients from Rizhao Central Hospital. Conservative treatment, PTCD and LC+ LCBDE+ PDC were used sequentially. The interval between PTCD and LCBDE, the decrease of serum total bilirubin and alanine aminotransferase after PTCD, the operative time of LC+ LCBDE+ PDC, and the intraoperative blood loss were analyzed. Postoperative indwelling time of abdominal drainage tube and PTCD tube time, postoperative hospital stay, postoperative complications, etc.Results:These were 15 males and 18 femals with the mean age of 57.5 years old. The mean serum total bilirubin and alanine aminotransferase levels decreased from (148.3±36.8) μmol/L and (172.6±26.9) U/L before PTCD to (32.6±5.9) μmol/L and (45.7±7.2) U/L after PTCD, respectively. The interval between PTCD and LCBDE was (25.3±2.6) d. The operation time of LC+ LCBDE+ PDC was (95.4±14.2) min. The intraoperative blood loss was (35.2±9.5 )ml and the mean postoperative hospital stay was (12.4±3.5) d. The postoperative indwelling time of abdominal drainage tubes and PTCD tubes were (10.6±2.3) d and (25.8±4.7) d, respectively. After surgery, bile leakage occurred in 3 patients (9.1%), abdominal hemorrhage in 1 patient (3.0%), biliary bleeding in 1 patient (3.0%), navel incision infection in 1 patient (3.0%), lower common bile duct stenosis in 2 patients (6.1%). All complications responded well to conservation treatment.Conclusions:Sequential treatment using conservative treatment, PTCD combined with LC+ LCBDE+ PDC in patients with cholecystolithiasis and CBDS who presented with acute cholangitis was safe, and efficacious using the minimally invasive approach. This approach is worth promoting to other centers.
4.The risk factors for long-term survival after radiofrequency ablation for hepatocellular carcinoma: a multi-center study
Xuemei DING ; Shuying DONG ; Changyu YAO ; Chunmin NING ; Shigang GUO ; Xiangtao WANG ; Shangsheng LI ; Jun GAO ; Shan KE ; Shaohong WANG ; Jian KONG ; Wenbing SUN
Chinese Journal of Hepatobiliary Surgery 2020;26(6):406-411
Objective:To explore the influencing factors of long-term survival for hepatocellular carcinoma (HCC) treated by radiofrequency ablation (RFA).Methods:A retrospective analysis of 255 patients who underwent RFA as the main treatment modality for HCC from May 1, 2004 to Feb 28, 2015 was performed. All patients were divided into two groups according to the postoperative survival time: the 5-year or more survival group and the less than 5-year survival group. Clinical indicators such as age, maximum tumor size and number, and frequency of radiofrequency ablation were compared between the two groups. Cox single factor and multiple factors were used to analyze the influencing factors of long-term survival.Results:The median overall survival of all the 255 patients was 4.3 years (range 0.5-15.5 years). There were 115 patients (45.1%) who survived for 5 years or more and 140 patients (54.9%) who survived for less than 5 years. The 1-, 3-, 5-, and 10-year survival rates of all the patients were 86.7%, 61.2%, 44.8% and 34.8%, respectively. There were no significant differences in gender, age, accompanying symptoms, aetiology of liver disease, level of alpha fetoprotein and treatment ( P>0.05), but there were significant differences in Child-Pugh class, liver cirrhosis, maximum diameter of tumor, tumor number, tumor stage, and frequency of RFA ( P<0.05) between the 2 groups of patients. Multivariate analysis showed that age ≥70 years old, Child-Pugh class B, maximum diameter of tumor >5.0 cm, multiple tumor were independent risk factors of long-term survival, but the number of sessions of RFA was a protective factor. Conclusions:For medium sized HCC and solitary large HCC, RFA combined with other therapeutic modalities could achieve satisfactory therapeutic results. Age, Child-Pugh class, maximum diameter of tumor, tumor number and RFA frequency were influencing factors for long-term survival of HCC patients.
5.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.
6.Early laparoscopic radiofrequency ablation for spontaneous rupture of hepatocellular carcinoma
Li XU ; Jun GAO ; Shan KE ; Xuemei DING ; Shaohong WANG ; Jian KONG ; Shuying DONG ; Wenbing SUN
International Journal of Surgery 2018;45(12):811-815,封3
Objective To evaluate the efficacy and clinical outcomes of early laparoscopic radiofrequency ablation(RFA) forspontaneously ruptured hepatocellular carcinoma (HCC).Methods A retrospective analysis was conducted on 12 patients with spontaneously ruptured HCC treated by laparoscopic RFA from April 2005 to June 2018 in the West Campus of Beijing Chao-yang Hospital,Capital Medical University.The successful rate,safety,peritoneal recurrence rate,complete ablation rate and survival rate of RFA were respectively analyzed.Results The median size of the 12 HCC cases was 5.85 cm (4.0-10.1 cm) in the maximal dimension.Procedures of laparoscopic RFA ablation were performed successfully for all patients.Complete ablation was achieved in 58.3%patients (7/12).Five patients with incompletely ablated tumors received repeated RF ablation to achieve completeablation.Four patients (33.3%) developed minor complications(Dindo-Clavien grade Ⅰ).The mean follow-up of 36.8 months,4 patients (33.3%) were alive and 8 (66.7%) died.Of the 12 patients,the 1-and 3-year survival rates were 90.0% and 60.0%,respectively.No patient had peritoneal recurrence.Conclusion Early laparoscopic RFA therapy is an minimally invasive,safety and effective treatment measure for spontaneouslyruptured HCC in selected patients,which presents an advantage of achieving simultaneous hemostasis,tumorelimination,and rinsing of peritoneal cavity to minimize the risk of peritoneal metastasis.
7.Current situation and progression of radiofrequency ablation therapy for benign space occupying lesion of the liver
Yingrui DU ; Shan KE ; Jun GAO ; Xuemei DING ; Shaohong WANG ; Jian KONG ; Wenbing SUN
Chinese Journal of Hepatobiliary Surgery 2018;24(4):283-286
Benign occupations of the liver (BOL) are a heterogeneous group of benign hepatic lesions,a minority of which may need active management.It's reported that radiofrequency ablation (RFA) can be used to treat BOL,such as hepatic haemangioma,focal nodular hyperplasia (FNH),hepatocellular adenoma,simple hepatic cyst,liver abscess and hepatic echinococcosis.RFA has exhibited a potentiality to replace resection as the first-line treatment option for hepatic haemangioma.For multiloculated intractable simple hepatic cyst or liver abscess,when patients are not suitable for or refuse surgical resection,RFA may be an alternative option for the resection;and it also has many advantages over resection,including effectiveness,safety,minimal invasiveness and repeatability in the treatment of FNH,hepatocellular adenoma,and hepatic echinococcosis.A review will be presented on the current situation and latest progression of RFA therapy for BOL in this article.
8.Efficacy of radiofrequency ablation in treatment of complicated pyogenic liver abscess
Shan KE ; Shaohong WANG ; Xinliang KONG ; Jun GAO ; Xuemei DING ; Qiang WANG ; Jian KONG ; Li XU ; Wenbing SUN
Chinese Journal of Hepatobiliary Surgery 2018;24(8):505-509
Objective To evaluate the efficacy of radiofrequency ablation (RFA) in treatment of complicated pyogenic liver abscess (PLA).Methods A retrospective analysis was conducted on 20 patients with complicated PLA treated from August 2010 to January 2018 in the West Campus of Beijing Chao-yang Hospital which is Affiliated to the Capital Medical University and Rizhao Central Hospital of Shandong Province.These patients were treated with RFA based treatment modalities using CT-guided or laparoscopy combined with Ultrasound-guided RFA.The successful rate,efficacious rate and safety of RFA were respectively analyzed.Routine follow-up was carried out after treatment.Results The successful rate of RFA was 100%.The median operation time was 45 minutes.All the 20 patients were cured by one session of RFA.The multilocular lesion in one patient was converted to a unilocular lesion after one session of RFA.The patient was then cured by percutaneous hepatic abscess drainage.No serious complications were observed.Conclusions RFA was safe and efficacious.It should be considered as an alternative treatment for patients with complicated PLA who were not responsive to,or not applicable to antibiotics treatment and radiological intervention.
9.A SWOT analysis and development thinking on the status of scientific research in county level public hospitals
Binying CHAI ; Hai GONG ; Heng GAO ; Dong XU ; Shaohong DING ; Lan LIU ; Hua ZHANG ; Jie LI ; Jie HOU
Chinese Journal of Medical Science Research Management 2018;31(3):239-240,封3-封4
Objective This thesis analyze the current situation of scientific research and the proposals of development of the county level public hospitals.Methods Questionnaires were used to collect the data of the scientific research situation of county-level public hospitals,and SWOT analysis was employed to develop a better understanding of the situation and development of scientific research of county-level public hospitals.Results The number of papers published by hospitals is bound up with the number of scientific and technical staff in the county-level public hospitals,the number of laboratories,tissue banks and the proportion of the postgraduate students to the public hospitals.The achievements above municipal level in scientific research are also strongly linked with the professional scientific and management personnel,the number of laboratories and tissue banks and the proportion of postgraduate students to the hospital.There are distinct features of the advantages,disadvantages,plans and challenges of the scientific research work of county-level public hospitals.Conclusions The most important ways of improving the ability of scientific research and the quality of service in country level public hospitals are that:attach great importance to scientific research,intensify the efforts for the introduction and cultivation of scientific research talents,formulate a reasonable reward system,enable professional scientific research management for its delicacy research etc.
10.Radiofrequency ablation for hepatic hemangiomas: a Chinese consensus statement
Jun GAO ; Ruifang FAN ; Jiayin YANG ; Yan CUI ; Jiansong JI ; Kuansheng MA ; Xiaolong LI ; Long ZHANG ; Chongliang XU ; Xinliang KONG ; Shan KE ; Xuemei DING ; Shaohong WANG ; Jingjing SONG ; Bo ZHAI ; Chunmin NING ; Shigang GUO ; Zonghai XIN ; Yonghong DONG ; Jun LU ; Huaqiang ZHU ; Wenbing SUN
Chinese Journal of Hepatobiliary Surgery 2017;23(5):289-295

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