OBJECTIVETo explore the mechanism of Astragalus polysaccharides (APS) for improving the cardiac function of Sjogren's syndrome (SS) model rats based on Keapl-Nrf2/ARE signaling pathway.

METHODSTotally 48 male Wistar rats were randomly divided into four groups by random digit table, i.e., the blank control group,the model control group,the APS group, and the hydroxychloroquine group, 12 in each group. Except those in the blank control group, 0. 1 mL mixed antigen protein of sufficiently emulsified Freund's complete adjuvant and submandibular gland protein was injected from two feet plantar to induce SS model. The intervention was started from 19th day after inflammation induction. Equal volume of normal saline was given to rats in the blank control group (1 mL/100 g), APS was administered to those in the APS group (1 mg/100 g), and hydroxychloroquine (0.03 125 g/kg) was administered to those in the hydroxychloroquine group. All rats were intervened once per day for 30 consecutive days. Changes of rats' body mass and drinking water quantity, submandibular gland index, spleen index, histological changes of glands were observed. Changes of the heart function were monitored using invasive hemodynamics. Serum reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (TAC), tumor necrosis factor alpha (TNF-alpha), and interleukin-35 (IL-35)were detected using ELISA method. The pathological changes were observed using HE staining. The protein expression of ROS, reactive nitrogen species (RNS), glutathione (GSH), and thioredoxin (TRX) were observed by immunohistochemical staining. The mRNA expression of Keap1, Nrf2, and ARE was detected using real time fluorescent quantitative PCR. The protein expression levels of gamma-glutamic acid and a half long glycine synthetase (gamma-GCS) and heme oxygenase 1 (HO-1) in the myocardial tissue were determined by Western blot method. Results Compared with the blank control group, the quantity of drinking water, submandibular gland index, spleen index, heart rate (HR), cardiac index (HI), left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVEDP), MDA, ROS, TNF-alpha, ROS protein expression, RNS protein expression, Keap 1 mRNA expression, Maf mRNA expression, Nfr2 mRNA expression, and HO-1 protein expression, and gamma-GCS protein expression significantly increased (P <0.01); body mass, +/-dp/dtmax, SOD, TAC, IL-35, GSH, and TRX significantly decreased (P <0.01) in the model group. Compared with the model group, the quantity of drinking water, submandibular gland index, spleen index, LVEDP, MDA, ROS, TNF-alpha, ROS protein expression, RNS protein expression, Keap1 mRNA expression, Maf mRNA expression, Nfr2 mRNA expression, and HO-1 protein expression, and gamma-GCS protein expression significantly decreased (P<0.05); body mass, +/-dp/dtmax, SOD, TAC, IL-35, GSH protein expression, and TRX protein expression significantly increased (P < 0.05, P <0.01) in the AR group and the hydroxychloroquine group. In the hydroxychloroquine group HR increased (P <0.05). In the AR group HR and LVSP decreased (P <0. 05, P <0. 01). Compared with the hydroxychloroquine group, HR, LVEDP, - dp/dtmax, y-GCS protein expression significantly decreased (P <0. 05, P <0. 01); SOD, TAC, GSH, TRX, HO-1 protein expression increased (P <0.01 )in the AR group. HI was positively correlated with ROS (P <0. 05). LVSP and LVEDP were positively correlated with Keap1 -Nrf2/ARE signaling pathways (P <0. 01) , and negatively correlated with TAC (P <0. 05, P <0. 01 ). +/-dp/dtmax was negatively correlated with Keap1-Nrf2/ARE signaling pathways(P <0.05), and positively correlated with TNF alpha (P <0. 05).

CONCLUSIONSDeclined heart function exists in SS rats. The mechamechanism of APS for improving the heart function might be closely correlated with activating Keap1-Nrf2/ARE signaling pathway.

Animals ; Astragalus Plant ; Blotting, Western ; Carboxylic Ester Hydrolases ; metabolism ; Heme Oxygenase-1 ; metabolism ; Hydroxychloroquine ; Male ; Malondialdehyde ; metabolism ; Myocardium ; enzymology ; NF-E2-Related Factor 2 ; metabolism ; Plant Extracts ; therapeutic use ; Polysaccharides ; metabolism ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; metabolism ; Signal Transduction ; Sjogren's Syndrome ; Submandibular Gland ; Superoxide Dismutase ; metabolism ; Thioredoxins ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

Objective To explore the effect and indication of splenectomy in liver transplantation.Methods From January 2001 to April 2006,260 patients underwent piggyback orthotopic liver transplantation(PBOLT),and 28 patients had undergone combined PBOLT and splenectomy(splenectomy group).These patients were compared to 56 randomly selected non-splenectomy patients from the same transplant period,meaningly two controls were se- lected for every non-spleneetomy case.Two groups were analyzed with respect to rate of infection and survival rate, as well as biopsy-proven acute allograft rejection within 30 days after transplantation.Results Rate of infection in the splenectomy group was higher than that in the non-splenectomy patients(85.7% vs 55.4%,P

OBJECTIVETo assess the recovery of the reproductive endocrine function in rats following orthotopic transplantation of fetal ovarian allograft.

METHODSNinety female SD rats (50-60 days old) were randomized into graft recipient group (n=50), positive control group (n=20), and negative control group (n=20) to receive orthotopic transplantation of fetal (17-19 gestational days) ovaries following bilateral oophorectomy, sham abdominal surgery, and bilateral oophorectomy, respectively. At 45 days after the surgeries, serum estradiol and progesterone levels were measured and the ovaries were removed for evaluation of the ovarian volume and follicle development.

RESULTSOn day 45 after the operations, the estradiol or progesterone levels showed no significant difference between the recipient group and positive control group (P>0.05), but both were significantly lowered in the negative control group (P<0.05). The ovarian volume was comparable between the recipient group and positive control group (P>0.05), and optical microscopy showed follicles in different stages of development and formation of corpus luteum in the ovaries in both groups.

CONCLUSIONFetal rat ovary allografts can develop into functional ovaries capable of ovulation to restore the reproductive endocrine function of recipient female rats.

Animals ; Estradiol ; blood ; Female ; Fetus ; Ovariectomy ; Ovary ; physiology ; transplantation ; Ovulation ; physiology ; Pregnancy ; Progesterone ; blood ; Rats ; Rats, Sprague-Dawley ; Transplantation, Homologous

OBJECTIVETo study the incidence, clinicopathological characteristics, diagnosis, treatment, and prognosis of synchronous or metachronous primary cancers in patients with gastric cancer.

METHODSClinical data of 4426 patients with gastric cancer in our hospital from 1996 to 2007 were reviewed.

RESULTSSeventy-four (1.7%) patients had synchronous or metachronous primary cancer of other organ, of whom 10 were synchronous and 64 were metachronous. Colorectal cancer was the most common type of primary cancer in other organs (43.8%), followed by breast cancer (16.3%). The mean time interval between gastric cancer and metachronous primary cancer was 82.2 (3-354) months. The mean age at the diagnosis of gastric cancer was 61.2 (33-84) years. The 5-year overall survival rate was 42.3%. The 5-year survival rates in patients with synchronous cancer, pre-metachronous cancer or post-metachronous cancer were 15.2%, 42.9% and 51.3%, respectively. Causes of death were primary cancers of other organ in 11 patients, gastric cancer in 24, and renal failure in 1 patient.

CONCLUSIONSPrimary cancer of other organ should be considered in the management of gastric cancer. Aggressive treatment should be used for the second primary cancer. Gastric cancer is the main cause of death in these patients.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; Colorectal Neoplasms ; Female ; Humans ; Male ; Middle Aged ; Neoplasms, Multiple Primary ; diagnosis ; Prognosis ; Stomach Neoplasms ; diagnosis

OBJECTIVETo evaluate the clinicopathological characteristics and prognosis of poorly differentiated neuroendocrine carcinoma of the stomach.

METHODSTwenty-three poorly differentiated neuroendocrine carcinomas of the stomach were treated in the Department of Abdominal Surgery at the Cancer Hospital, Fudan University between January 1996 and December 2007. Clinicopathological characteristics and survival data were analyzed.

RESULTSPoorly differentiated neuroendocrine carcinomas of the stomach accounted for 0.52% of all the gastric carcinomas. The tumor occurred more often in males (18 of 23), older patients (mean age of 62 years), upper third of the stomach (16 of 24,one patient had more than one lesion) with large size (mean diameter of 6.8 cm). TNM stages were as follows: stage II in 3 patients, stage III in 12, and stage IIII in 8. Thirteen patients underwent curative resection, while 8 underwent palliative resection and 2 others underwent exploratory laparotomy with biopsy. Of the 21 surgical resection specimens, vascular invasion was found in 18 patients (85.7%), perineural invasion in 16 patients (76.2%), and regional lymph node metastasis in 17 patients (81.0%). Follow up time ranged from 3 to 63 months. Mean overall survival time was 17.7 months. The 1-year, 2-year, and 5-year survival rates were 47.8%, 19.1%, and 4.3%, respectively. Statistically significant differences in survival curves were observed which were related to tumor staging and surgery type, but not related to gender, age, tumor location, or diameter.

CONCLUSIONSPoorly differentiated neuroendocrine carcinomas of the stomach are rare and with poor prognosis. Tumor stage and surgical type have potential impact on survival.

Adult ; Aged ; Carcinoma, Neuroendocrine ; diagnosis ; pathology ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; diagnosis ; pathology

The concept of "ischemic postconditioning" was first raised in 2002, and the following 5 year research shows that it can protect organs from reperfusion injury. Although the mechanism of ischemic postconditioning is similar to ischemic preconditioning in many ways, it still has its own characteristics. Reperfusion injury is an inevitable problem in organ transplantation. It may accelerate the function recovery of the transplants to lessen the reperfusion injury. So ischemic postconditioning may have a fine prospect in organ transplantation for its good controllability during reperfusion. This article is going to briefly introduce the distinct mechanisms of ischemic postconditioning to protect organs from reperfusion injury and approach the possibilities of its application in organ transplantation.
Animals ; Humans ; Ischemic Preconditioning ; Ischemic Preconditioning, Myocardial ; Myocardial Reperfusion Injury ; pathology ; prevention & control ; Organ Transplantation ; adverse effects ; methods ; Reperfusion Injury ; prevention & control

BACKGROUNDDelayed graft function (DGF) is common in kidney transplants from organ donation after cardiac death (DCD) donors. It is associated with various factors. Determination of center-specific risk factors may help to reduce the incidence of DGF and improve the transplantation results. The aim of this study is to define risk factors of DGF after renal transplantation.

METHODSFrom March 2010 to June 2012, 56 cases of recipients who received DCD kidneys were selected. The subjects were divided into two groups: immediate graft function (IGF) and DGF groups. Transplantation factors of donors and recipients as well as early post-transplant results of recipients were compared between the two groups.

RESULTSOn univariate analysis, preoperative dialysis time of recipients (P < 0.001), type of dialysis (P = 0.039), human leucocyte antigen (HLA) mismatch sites (P < 0.001), the cause of brain death (P = 0.027), body mass index (BMI) of donors (P < 0.001), preoperative infection (P = 0.002), preoperative serum creatinine of donors (P < 0.001), norepinephrine used in donors (P < 0.001), cardiopulmonary resuscitation (CPR) of donors (P < 0.001), warm ischemia time (WIT) (P < 0.001) and cold ischemia time (CIT) (P < 0.001) showed significant differences. Recipients who experienced DGF had a longer hospital stay, and higher level of postoperative serum creatinine.

CONCLUSIONMultiple risk factors are associated with DGF, which had deleterious effects on the early post-transplant period.

Adolescent ; Adult ; Aged ; Case-Control Studies ; Death ; Delayed Graft Function ; etiology ; Female ; Humans ; Kidney Transplantation ; adverse effects ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Tissue Donors

AIM To explore the effect of Heidihuang Pills on renal fibrosis in a rat model of chronic renal failure(CRF)and its mechanism.METHODS Wistar rats were randomly divided into the blank group for normal feeding and the model group for the establishment of CRF rat models by 5/6 nephrectomy.Subsequently,the successfully established rat models were randomly divided into the model group,the Heidihuang Pills group(10.43 g/kg),and the Heidihuang Pills+IGF-1R blocker(JB1)group for a regimen of 7-day subcutaneous injection of 18 μg/kg JB1 followed by gavage of 10.43 g/kg Heidihuang Pills.Eight weeks after the administration,the rats had their serum levels of Scr and BUN detected;their pathological changes of renal tissue observed by HE and Masson staining;their renal protein expressions of TGF-β,HIF-1α and α-SMA detected by immunohistochemistry;their renal protein expressions of IGF-1R and TGF-β detected by Western blot;and their renal mRNA expressions of IGF-1R and TGF-β detected by RT-qPCR.RESULTS Compared with the blank group,the model group displayed increased serum levels of Scr and BUN(P＜0.05);increased,degree of renal fibrosis,and renal fibrosis area(P＜0.05);increased renal expressions of TGF-β,HIF-1α,α-SMA proteins and TGF-β mRNA(P＜0.05);and decreased expressions of IGF-1R mRNA and protein(P＜0.05).Compared with the model group,the Heidihuang Pills group displayed decreased serum Scr and BUN levels(P＜0.05);decreased inflammatory cells in renal interstitium and the fibrosis degree(P＜0.05);decreased renal expressions of TGF-β,HIF-1α,α-SMA proteins and TGF-β mRNA(P＜0.05);and increased expressions of IGF-1R mRNA and protein(P＜0.05).However,the administration of JB1 could weaken the improvement effect of Heidihuang Pills on renal fibrosis in CRF rats(P＜0.05).CONCLUSION Heidihuang Pills can inhibit the renal fibrosis in CRF rats,and the inhibition process is related to up-regulated IGF-1 expression and promoted combination of IGF-1 and IGF-1R.

OBJECTIVETo explore the role of surgery and its long-term outcome in patients with advanced gastrointestinal stromal tumor(GIST) treated with imatinib preoperatively.

METHODSThirteen patients receiving imatinib therapy preoperatively, were retrospectively assessed for completeness of surgical resection and for disease-free and overall survival after resection.

RESULTSThirteen patients, including 3 patients with locally advanced primary GIST and 10 patients with recurrent or metastatic GIST, underwent surgery after preoperative treatment with imatinib. Complete resections were accomplished in 4 of the 5 responsive disease(RD) patients, and in 1 of the 8 progression disease(PD) patients (38.5%). The progression-free survival(PFS) time for patients with RD and PD were 24.8 months and 2.8 months respectively. The difference of PFS between patients with RD and those with PD was significant(P<0.01). Median overall survival(OS) was not reached in both patients with RD and PD. The difference of OS between patients with RD and those with PD was not significant(P>0.05).

CONCLUSIONSurgical intervention following imatinib is feasible and can be considered for patients with advanced GIST responsive to imatinib.

Antineoplastic Agents ; administration & dosage ; Benzamides ; Disease-Free Survival ; Female ; Gastrointestinal Stromal Tumors ; drug therapy ; surgery ; Humans ; Imatinib Mesylate ; Male ; Middle Aged ; Piperazines ; administration & dosage ; Prognosis ; Pyrimidines ; administration & dosage ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo characterize oncogenic KIT signaling mechanisms in gastrointestinal stromal tumor(GIST), and to determine which signaling pathway might be of potential relevance to imatinib acquired resistance.

METHODSThe mutations of KIT and PDGFRa gene were evaluated and KIT downstream signaling profiles were evaluated in 8 specimen from 5 GIST patients who were evaluated treated between 2003 and 2008 in our hospital. Biochemical inhibition of the expression of related proteins in Ras/Raf/MAPK and PI3-K/AKT pathways, such as KIT, mitogen-activated protein kinase(MAPK),mammalian target of rapamycin(MTOR), AKT, Proliferating cell nuclear antigen (PCNA) and BCL-2, were determined by Western blotting for protein activation.

RESULTSThree cases who showed response to imatinib carried primary mutations in KIT gene, with 2 cases possessing mutation in exon 11, 1 case in exon 13. One case with imatinib-resistance developed KIT secondary mutation, but all the cases had no PDGFRa mutation. p-KIT and p-AKT expressions were higher in the samples of imatinib-resistant GIST than those of imatinib-responsive GIST. Total KIT, MAPK, p-MAPK, p-MTOR expressions were strong and comparable in all varied GISTs, which had no significant difference between imatinib-resistant and imatinib-responsive samples. PCNA and BCL-2 expression varied in samples of different therapy cycles and different location.

CONCLUSIONSRas/Raf/MAPK and PI3-K/AKT/MTOR pathways are essential to GIST pathogenesis. The KIT secondary mutation and PI3-K/AKT/MTOR pathway are particularly relevant for therapeutic targeting in imatinib-resistant GIST.

Benzamides ; Drug Resistance, Neoplasm ; drug effects ; genetics ; Gastrointestinal Stromal Tumors ; drug therapy ; genetics ; metabolism ; Humans ; Imatinib Mesylate ; Mutation ; Piperazines ; pharmacology ; Proto-Oncogene Proteins c-kit ; genetics ; Pyrimidines ; pharmacology ; Signal Transduction ; drug effects ; genetics