1.Protective effect of extracorporeal membrane oxygenation on Maastricht type Ⅱ donation after cardiac death liver transplantation in pigs
Lei LIU ; Ning MA ; Yuan SHI ; Yan LIU ; Jing CHEN ; Sinan GAO ; Jianfeng FU ; Minghao SUI ; Zhongyang SHEN
Chinese Journal of Organ Transplantation 2016;37(11):682-685
Objective To detect the protective effect of extracorporeal membrane oxygenation (ECMO) on Maastricht type Ⅱ donation after cardiac death (DCD) liver transplantation in pigs.Methods Twenty mini-pigs were randomized into ECMO group (n =10) and control group (n =10).Then 10 pigs in each group were randomized into donors and recipients.Maastricht type Ⅱ DCD model was induced in all of the 10 donors.Donors of ECMO group received 2-h ECMO after cardiac death,then underwent liver graft procurement.The donors of control group underwent liver procurement directly after cardiac death.Recipients of two groups underwent orthotopic liver transplantation without venovenous bypass.During this procedure,vital signs were monitored continuously,lactate and liver biochemistry were tested,and 5-day survival rate was observed.Results Maastricht type Ⅱ DCD model was successfully built in all of the donors with consequent dark liver.For donors of ECMO group,liver turned sanguinous and soft quickly after treatment of ECMO.There were no significant differences in operation time,anhepatic time and anhepatic hemodynamic changes between these two groups (P > 0.05).As compared with control group,ECMO group had better hemodynamic parameters 30 min after reperfusion,lower lactate,ALT and AST levels 30 min after reperfusion and before closing the abdomen,and higher 5-day survival rate (P < 0.05).Conclusion ECMO may improve the quality of Maastricht type Ⅱ DCD liver graft,and increase the survival rate of DCD liver transplantation.
2.Successful management of hyperammonemia syndrome in a patient after skin transplantation: a case report and a literature review on 41 patients.
Weili WANG ; Sinan GAO ; Yisheng KANG ; Lixin YU ; Yihe LIU ; Zhongyang SHEN
Chinese Critical Care Medicine 2019;31(3):367-370
Hyperammonemia syndrome (HS) is a comparatively rare but often fatal clinical syndrome characterized by progressive respiratory alkalosis and abrupt mental status alteration associated with markedly elevated plasma ammonium levels. Although the exact mechanism of HS remains unclear, infection with urease producing microbes is proposed as the main etiology of HS recently. A patient with HS after repeated autologous skin transplantation was admitted to Tianjin First Center Hospital in March 2018, presented with fever, coma and epilepsy. The infection of Mycoplasma hominis was confirmed in blood sample by high throughput gene detection. The patient was survived after multimodal management including antimicrobial treatment, aggressive ammonia removal by continuous renal replacement therapy in combination with lactulose, and mechanical ventilation. She was successfully discharged from intensive care unit (ICU) with clear consciousness, normal temperature and smooth breath. In view of the experience of the case treatment, a review of literature was conducted to discuss the epidemiology and clinical characteristics, possible etiologies and mechanisms, and outcomes with emphasis on treatment strategies of HS and to promote more clinicians to recognize this rare disease.
Female
;
Humans
;
Hyperammonemia/therapy*
;
Intensive Care Units
;
Review Literature as Topic
;
Skin Transplantation/adverse effects*
;
Treatment Outcome
3.Complex congenital heart disease and pediatric liver transplantation: case reports and a brief review
Weili WANG ; Sinan GAO ; Yisheng KANG ; Lixin YU ; Jinzhen CAI ; Wei GAO ; Yihe LIU ; Zhongyang SHEN
Chinese Journal of Organ Transplantation 2018;39(6):359-363
Objective To discuss the surgical strategy for children with complex congenital heart disease (CHD) and end-stage liver disease (ESLD).Methods We reported two eases of pediatric liver transplantation in patients with complex CHD and ESLD.Medical data including operation procedure,ICU management and outcomes were reviewed retrospectively.Also we reviewed the literature on the topic of clinical outcomes resulted from different surgery options.Results The first case was a seven-month-old male patient with biliary atresia and complex CHD (unroofed coronary sinus syndrome,persistent left superior vena cava,patent foramen ovale,and peripheral pulmonary stenosis).Liver transplantation was successfully performed without corrective heart surgery.The operation time was 6 h and 35 min.The patient suffered acute cardiac dysfunction and significant hypoxemia after extubation,then pneumonia developed,and eventually the patient died on post-operative day 12.The second case was a seven-month-old male patient with biliary atresia and complex CHD (ventricular septal defect,patent foramen ovale,patent ductus arteriosus,pulmonary stenosis).Liver transplantation was performed on the same day following total correction of cardiac defects by open-heart surgery.The operation time was 16 h and 15 min.The patient was extubated after 60 h ventilation,and was transferred to ward from ICU on post-operative day 6 with stable cardiopulmonary function.However,hepatic artery occlusion occurred on early postoperative stage,and consequently the patient received the second liver transplantation for ischemic biliary complication on post-operative day 40.The second liver transplantation procedure was uneventful.The liver graft recovered smoothly with stable hemodynamics.Conclusion Children with complex CHD undergoing liver transplantation are at an increased perioperative risk.The surgical strategy for each patient must be tailored individually according to specific cardiovascular status and limited hepatic reserve.
4.Protective Mechanism of Zhuluan Decoction in Rats with Premature Ovarian Insufficiency Based on PI3K/Akt/mTOR Pathway
Li TANG ; Zhenni MU ; Sinan SHEN ; Lei LEI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(4):52-59
ObjectiveTo observe the effect of Zhuluan decoction on the ovarian reserve function of rats with cyclophosphamide-induced premature ovarian insufficiency, and explore the protective mechanism of Zhuluan decoction in the rat model of premature ovarian insufficiency based on the phosphatidylinositol-3-kinases/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. MethodSixty female SD rats were randomly divided into normal group (n=10) and model group (n=50). The model group was given intraperitoneal injection of cyclophosphamide (50 mg·kg-1 loading dose on the 1st day+8 mg·kg-1 low-dose maintenance on the 2nd–15th days). After successfully modeling, the rats were randomly divided into model group, positive drug (progynova) group (0.1 mg·kg-1·d-1), and low-, medium-, and high-dose Zhuluan decoction groups (14, 28, 56 g·kg-1·d-1 ), with 10 rats in each group. The model group and the normal group were given equal volume of distilled water by gavage, once a day, continuous administration for 21 d. The estrous cycle and body weight of rats in each group were detected, and the ovarian organ index and uterine organ index were calculated. The ovarian tissue pathology and ovarian follicle counts at all levels were determined by hematoxylin-eosin (HE) staining. The content of the serum antimullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and inhibin-B (INH-B) of rats was determined by enzyme-linked immunosorbent assay (ELISA), and the protein expression levels of PI3K, Akt, mTOR in the rat ovarian tissue were determined by Western blot. The microtubule-associated protein 1 light chain 3B (LC3B) protein expression in the rat ovarian tissue was determined by immunohistochemistry. ResultAs compared with the blank group, the estrous cycle of rats in the model group was disordered, the body weight, ovarian organ index, and uterine organ index decreased, the number of primordial follicles decreased, and the number of secondary follicles and atretic follicles increased. In the model group, FSH increased (P<0.01), LH increased (P<0.05), AMH level decreased (P<0.05), the protein expression levels of PI3K, Akt, and mTOR in the ovarian tissue decreased (P<0.01), and the protein expression level of LC3B increased significantly (P<0.01). As compared with the model group, the above indexes were improved in the progynova group and different doses of Zhuluan decoction groups, the content of AMH increased (P<0.05), and FSH decreased (P<0.05). In the progynova group and different doses of Zhuluan decoction groups, the protein expression level of LC3B decreased obviously (P<0.01), and the protein expression levels of PI3K, Akt, and mTOR all showed an increasing trend. Moreover, there was a statistically significant difference in the progynova group and low- and medium-dose Zhuluan decoction groups (P<0.05). ConclusionZhuluan decoction may inhibit the occurrence of excessive autophagy in ovarian granulosa cells by activating the PI3K/Akt/mTOR pathway, thereby reversing the effect of modeling on ovarian reserve in rats.
5.Shoutaiwan Regulate Lipopolysaccharide-induced Oxidative Stress and Pyroptosis in Human Extravillous Trophoblast Cells
Zonghui QIAO ; Sinan SHEN ; Dun DENG ; Shuqing ZHANG ; Lei LEI
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(17):17-24
ObjectiveTo investigate the regulatory effect of Shoutaiwan on oxidative stress and pyroptosis in lipopolysaccharide (LPS)-induced human extravillous trophoblast (HTR-8/SVneo) cells and provide a new direction for deciphering the mechanism of action of Shoutaiwan. MethodLPS (100 μg∙L-1) was used to induce the injury of HTR-8/SVneo cells (modeling). Five groups were designed in this study, including a blank group, a model group, a Shoutaiwan (10% Shoutaiwan-containing serum) group, an antioxidant (1 mmol·L-1 NAC) group, and NOD like receptor thermoprotein domain 3 (NLRP3) inhibitor (50 μmol·L-1 MCC950) group. Cell viability was detected by cell counting kit-8 (CCK-8) kit. Hochest 33342/PI double fluorescence staining and flow cytometry were employed to observe cell death. The levels of interleukin-18 (IL-18), interleukin-1β (IL-1β), malondialdehyde (MDA), and superoxide dismutase (SOD) in cell supernatant was determined by enzyme-linked immunosorbent assay (ELISA). DCFH-DA probe was used to measure the level of intracellular reactive oxygen species (ROS). Western blot was employed to determine the protein levels of NLRP3, Caspase-1, gastermin D (GSDMD), and IL-1β in cells, and Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) to measure the mRNA levels of NLRP3 and Caspase-1 in cells. ResultCompared with the blank group, the modeling decreased the cell viability (P<0.01), elevated the levels of IL-1β, IL-18, ROS, and MDA, and weakened the activity of SOD (P<0.01). Furthermore, it up-regulated the protein levels of NLRP3, Caspase-1, GSDMD, and IL-1β and the mRNA levels of NLRP3 and Caspase-1 (P<0.01). Compared with the model group, Shoutaiwan, NAC, and MCC950 increased the cell viability (P<0.01). Further, Shoutaiwan and NAC lowered the levels of MDA and ROS and increased the activity of SOD (P<0.01). Shoutaiwan and MCC950 reduced the IL-1β and IL-18 in cell supernatant (P<0.01), and down-regulated the protein levels of NLRP3, Caspase-1, GSDMD, and IL-1β and the mRNA levels of NLRP3, Caspase-1, and IL-1β (P<0.05,P<0.01). ConclusionShoutaiwan can regulate oxidative stress and pyroptosis to attenuate the LPS-induced damage of HTR-8/SVneo cells, which may be the mechanism of Shoutaiwan in preventing recurrent spontaneous abortion.
6.Shoutaiwan Ameliorates Oxidative Damage of Human Chorionic Trophoblast Cells by Regulating Nrf2 Signaling Pathway to Treat Recurrent Abortion
Sinan SHEN ; Zhenni MU ; Li TANG ; Lei LEI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(3):44-51
ObjectiveTo study the protective effect of Shoutaiwan-containing serum on the human chorionic trophoblast cells (HTR-8/Svneo) exposed to hydrogen peroxide (H2O2) via the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and to decipher the underlying mechanism. MethodThe H2O2 solutions of 25, 50, 100, 200, 400 μmol·L-1 were used to treated the HTR-8/Svneo cells. The cell counting kit-8 (CCK-8) was employed to measure the proliferation of the cells and further determine the optimal concentration of H2O2 solution for modeling and the drug-containing serum. The cells were divided into a blank group, a model group, a dydrogesterone group, and a Shoutaiwan group. The effect of drug-containing serum on H2O2-induced proliferation of HTR-8/Svneo cells was detected by CCK-8 assay. The intracellular reactive oxygen species (ROS) in each group was determined by enzyme-linked immunosorbent assay (ELISA). Western blot was employed to determine the protein levels of Nrf2, heme oxygenase-1 (HO-1), quinone oxidoreductase 1 (NQO1), cysteine-containing aspartate-specific protease-3 (Caspase-3), and B cell lymphoma/leukemia-2 (Bcl-2). Cellular immunofluorescence was employed to detect the expression of Nrf2 and Bcl-2. Real-time quantitative polymerase chain reaction (Real-time PCR) was carried out to examine the mRNA level of Nrf2, Caspase-3, and Bcl-2 associated X protein (Bax). ResultThe optimal concentration of H2O2 for modeling was 50 μmol·L-1, and the optimal concentration of drug-containing serum was 10%. Compared with the blank group, the modeling decreased the proliferation of cells (P<0.01), increased the intracellular ROS (P<0.01), down-regulated the protein levels of Nrf2, HO-1, NQO1, and Bcl-2 (P<0.05, P<0.01), up-regulated the protein levels of Caspase-3 and Bax (P<0.01), down-regulated the mRNA level of Nrf2 (P<0.01), and up-regulated the mRNA levels of Caspase-3 and Bax (P<0.05, P<0.01). Compared with the model group, Shoutaiwan-containing serum increased the proliferation of cells (P<0.01), reduced the intracellular ROS (P<0.01), up-regulated the protein levels of Nrf2, HO-1, NQO1, and Bcl-2 (P<0.01), down-regulated the protein levels of Caspase-3 and Bax (P<0.05, P<0.01), up-regulated the mRNA level of Nrf2 (P<0.05), and down-regulated the mRNA levels of Caspase-3 and Bax (P<0.05, P<0.01). ConclusionShoutaiwan-containing serum can inhibit H2O2-induced apoptosis by activating the Nrf2 signaling pathway and has protective effect on human chorionic trophoblast cells.