[The relationship between the expression of amplified in breast cancer 1、androgen receptor and tamoxifen resistance in breast cancer].

Objective: To discuss the value of amplified in breast cancer 1(AIB1) and androgen receptor (AR) for the resistance of adjuvant tamoxifen in estradiol receptor (ER) positive breast cancer. Methods: A total of 188 cases with breast cancer after receiving tamoxifen treatment in the Tianjin Medical University Cancer Institute and Hospital from June 2008 to July 2013 were enrolled in this study.Using immunohistochemical SP method to detect AIB1and AR expression in breast cancer tissue, analyzing the relationship of AIB1 and AR expression and the effect of tamoxifen.And verify the results of the experiment through the GEPIA database. Results: The response of tamoxifen was 80.3%. The response rate in AR positive group and AR negative group was 79.6% and 82.4%, with no significant difference (P=0.669). The response rate in AIB1 High expression group and AIB1 Low expression group was 68.4% and 93.3%, respectively, with a significant difference (P<0.001).The response rate in AR negative and AIB1 Low expression group, AR negative and AIB1 High expression group, AR positive and AIB1 Low expression group, AR positive and AIB1High expression group was 89.7%, 71.4%, 96.7%, 66.2%respectively, with a significant difference (P<0.001). Conclusions: The expression level of AIB1 is correlated with the therapeutic effect of tamoxifen in breast cancer. Its high expression can cause tamoxifen resistance, while AR positive and High expression of AIB1 are more likely to cause tamoxifen resistance, and AIB1 can be used as an independent influencing factor for breast cancer tamoxifentreatment.

[Effect of jejunal feeding tube placement on complications after laparoscopic radical surgery in patients with incomplete pyloric obstruction by gastric antrum cancer].

Objective: To assess the effect of jejunal feeding tube placement on early complications of laparoscopic radical gastrectomy in patients with incomplete pyloric obstruction by gastric cancer. Methods: This was a retrospective cohort study. Perioperative clinical data of 151 patients with gastric antrum cancer complicated by incomplete pyloric obstruction who had undergone laparoscopic distal radical gastrectomy from May 2020 to May 2022 in the First Affiliated Hospital of Nanchang University were collected. Intraoperative jejunal feeding tubes had been inserted in 69 patients (nutrition tube group) and not in the remaining 82 patients (conventional group). There were no statistically significant differences in baseline characteristics between the two groups (all P>0.05). The operating time, intraoperative bleeding, time to first intake of solid food, time to passing first flatus, time to drainage tube removal, and postoperative hospital stay, and early postoperative complications (occurded within 30 days after surgery) were compared between the two groups. Results: Patients in both groups completed the surgery successfully and there were no deaths in the perioperative period. The operative time was longer in the nutritional tube group than in the conventional group [(209.2±4.7) minutes vs. (188.5±5.7) minutes, t=2.737, P=0.007], whereas the time to first postoperative intake of food [(2.7±0.1) days vs. (4.1±0.4) days, t=3.535, P<0.001], time to passing first flatus [(2.3±0.1) days vs. (2.8±0.1) days, t=3.999, P<0.001], time to drainage tube removal [(6.3±0.2) days vs. (6.9±0.2) days, t=2.123, P=0.035], and postoperative hospital stay [(7.8±0.2) days vs. (9.7±0.5) days, t=3.282, P=0.001] were shorter in the nutritional tube group than in the conventional group. There was no significant difference between the two groups in intraoperative bleeding [(101.1±9.0) mL vs. (111.4±8.7) mL, t=0.826, P=0.410]. The overall incidence of short-term postoperative complications was 16.6% (25/151). Postoperative complications did not differ significantly between the two groups (all P>0.05). Conclusion: It is safe and feasible to insert a jejunal feeding tube in patients with incomplete outlet obstruction by gastric antrum cancer during laparoscopic radical gastrectomy. Such tubes confer some advantages in postoperative recovery.

Association between TP53 polymorphisms and chronic lymphocytic leukemia.

OBJECTIVE: The aim of this study was to explore the association between TP53 gene polymorphisms (rs8068934 A>G and rs218698 C>T) and chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: CLL patients who received treatment in our hospital were enrolled in this study as the disease group. Meanwhile, healthy subjects were taken as the control group. Peripheral blood samples were collected to detect TP53 gene polymorphisms at rs8068934 and rs218698, and the haplotype analysis was performed. The expression of TP53 was detected via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Furthermore, the survival conditions were analyzed. RESULTS: The allele distribution at rs8068934 (p=0.046) and rs218698 (p=0.028) of TP53 gene was different between control group and disease group. A allele frequency at rs8068934 and T allele frequency at rs218698 were significantly higher in disease group (p<0.05). The genotype distribution at rs218698 of TP53 gene in disease group was also different from that in control group (p=0.038). The results demonstrated that CC genotype frequency in disease group was significantly lower than that in control group (p<0.05). Besides, the distribution of dominant model at rs8068934 (p=0.042) and recessive model at rs218698 (p=0.033) in disease group exhibited remarkable differences from control group, in which AA+AG frequency (dominant model) at rs8068934 and CC+CT frequency (recessive model) at rs218698 in disease group were significantly higher. Meanwhile, the distribution of AT (p=0.029) and GC (p=0.007) haplotypes at rs8068934 and rs218698 in disease group was evidently different from that in control group. The results indicated that disease group showed significantly higher frequency of AT haplotype and lower frequency of GC haplotype (p<0.05). Moreover, TP53 gene polymorphisms at rs8068934 were significantly associated with the levels of white blood cells (WBC) (p=0.000) and platelets (PLT) (p=0.035). Patients with GG genotype had significantly higher level of WBC, while those with AG genotype showed significantly lower level of PLT (p<0.05). TP53 gene polymorphisms at rs218698 were associated with the level of red blood cells (RBC) (p=0.000). Patients with CT genotype had a remarkably lower level of RBC (p<0.05). There were significant correlations of TP53 gene polymorphisms at rs8068934 (p=0.000) and rs218698 (p=0.000) with the expression of TP53. The expression of TP53 was lower in people with AA genotype at rs8068934 but higher in people with TT genotype at rs218698 (p<0.05). Furthermore, TP53 gene polymorphisms at rs8068934 (p=0.000) and rs218698 (p=0.000) were markedly associated with patients' survival. CONCLUSIONS: TP53 polymorphisms are significantly correlated with the occurrence and progression of CLL.

MiR-373 promotes the osteogenic differentiation of BMSCs from the estrogen deficiency induced osteoporosis.

OBJECTIVE: This study aimed to investigate the expression of miR-373 in osteoporosis patients and rat models induced by estrogen deficiency and to detect whether miR-373 can regulate the ability of osteogenic differentiation of bone marrow mesenchymal stem cells in the osteoporosis microenvironment caused by estrogen deficiency. PATIENTS AND METHODS: Bone tissues and blood samples were collected from 20 osteoporotic patients and 20 controls. PCR analysis was used to detect the expression of miR-373 in bone tissue and serum from postmenopausal osteoporotic patients and normal patients. 120 SD rats were purchased and randomly divided into sham operation group and OVX group. Rat models of sham-operated and bilateral oophorectomy mice models were constructed. The expression of miR-373 in bone tissue, cells, and serum of the mice was tested. Then, bone marrow mesenchymal stem cells from sham-operated rats and bilaterally ovariectomized rats were isolated and cultured. After 10 days of osteogenic induction, alkaline phosphatase staining and alizarin red staining were performed to test the osteogenic differentiation ability of bone marrow mesenchymal stem cells, and whether miR-373 affects this ability. RESULTS: PCR results showed that the expression of miR-373 in the bone tissue and the serum of patients with postmenopausal osteoporosis was significantly reduced. The expression of miR-373 was markedly decreased in the bone tissue, cells, and serum from the rats of bilateral ovariectomy group. Alkaline phosphatase staining and alizarin red staining showed that miR-373 could promote the differentiation of bone marrow mesenchymal stem cells into osteoblasts and reverse the decreased osteogenic differentiation of bone marrow mesenchymal stem cells caused by osteoporosis. CONCLUSIONS: The expression of miR-373 is decreased in osteoporotic patients and rat models caused by estrogen deficiency, and it can promote the differentiation of bone marrow mesenchymal stem cells into the osteogenic direction. This work provides a new direction and experimental basis for clinical diagnosis and treatment of osteoporosis.

[Liver transplantation for polycystic liver disease: 11 cases report and literature review].

Objective: To explore the indications and safety of orthopedic liver transplantation for polycystic liver disease (PLD). Methods: Data of 11 patients with PLD who underwent orthotopic liver transplantation between 2004 and 2013 was retrospectively analyzed. Demographic, clinical and follow-up data were collected for statistical analysis. The survival rate was calculated by Kaplan-Meier method. Results: Over a period of 10 years, the patients received modified piggyback orthopedic liver transplantation (n=9) or combined liver-kidney transplantation (n=2) for PLD. The recipients' median age was 56 years. Seven patients were classified as Gigot type Ⅱ PLD, and four were classified as Gigot type Ⅲ PLD. Eight patients had severe decreased mobility (Eastern Cooperative Oncology Group, ECOG≥3). Only three cases were Child-Pguh Class C patients and the model for end-stage liver disease (MELD) score was>20. The mean hospitalization duration was (45.4±15.3) days, and the mean length of stay in intensive care unit was (4.1±1.9) days. The perioperative mortality was 18.2% and morbidity of complications was 63.6%. The median follow-up period was 111 months. Two patients died of severe complications after combined liver-kidney transplantation. One patient died of ischemia cholangitis during follow-up. The actuarial 1-, 5-and 10-year survival rate during the follow-up period was 82.2%, 81.8%, and 65.5%, respectively. Conclusions: Liver transplantation is the only curative and safe procedure for PLD, and it provides a good long-term prognosis and high quality of life for PLD patients. Liver transplantation could be a primary option in treating progressive or advanced PLD.

Capturing intracellular oncogenic microRNAs with self-assembled DNA nanostructures for microRNA-based cancer therapy.

Aberrantly overexpressed oncogenic microRNAs (miRNAs, miRs) are excellent targets for therapeutic interventions. Nevertheless, thus far, little progress has been made in developing miRNA-based drugs and techniques for clinical applications, especially for overexpressed miRNAs. In this study, we demonstrate that self-assembled DNA nanostructures bearing multiple DNA sequences that are complementary to a target miRNA can effectively capture the overexpressed oncogenic miRNA and subsequently inhibit cancer cell proliferation. Specifically, a DNA nanotube structure that carries functional DNA segments (single-stranded, duplex and hairpin forms) was designed and synthesized to capture two well-known overexpressed miRNAs, miR-21 and miR-155. It was found that all three DNA nanotubes significantly reduced both miRNA levels and inhibited cancer cell growth. Moreover, the capture efficiency was highly concentration dependent and was associated with the structural design of the DNA nanotube. These results demonstrate that through careful design, programmable DNA nanostructures can hijack the natural cellular machinery and can serve as nucleic acid drugs themselves. The concept of using self-assembled DNA nanostructures to disrupt the intracellular machinery for therapeutic purposes opens a new paradigm for exploiting self-assembled DNA nanostructures for miRNA-based anticancer therapy.

[Preoperative restricted versus liberal fluid administration on perioperative safety for pancreatic surgery: a Meta-analysis].

Objective: To assess the perioperative safety of preoperative restricted fluid administration and liberal fluid administration for pancreatic surgery. Methods: The randomized controlled trials comparing restricted and liberal in pancreatic surgery were collected by searching the databases of PubMed, Embase and the Cochrane Library.Two reviewers independently selected studies according to the inclusion and exclusion criteria, then extracted the data and assessed the quality of included studies.Meta-analysis was performed by RevMan 5.3 software. Results: A total of 4 studies involving 785 patients were finally included, with 396 cases in restricted group and 389 cases in liberal group.Results of Meta-analysis showed that there was no statistically significant difference between the two groups in terms of intraoperative blood loss, postoperative complications, mortality, reoperation in-hospital and length of stay(all P>0.05). Conclusion: With regard to pancreatic surgery, restricted fluid administration do not have outstanding advantages.

[Feasibility and value of index of microcirculatory resistance in patients with acute myocardial infarction after primary percutaneous coronary intervention].

Objective: To evaluate the feasibility of detecting index of microcirculatory resistance (IMR) and the relationship between IMR and left ventricular (LV) systolic function after acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI). Methods: The patients with first AMI received primary PCI in Peking University Third Hospital were enrolled from January 2014 to March 2016. IMR were measured immediately after PCI by using pressure/temperature wire. The relationship between IMR and left ventricular ejection fraction (LVEF) assessed by echocardiography at first day and 6 months after admission was evaluated. Results: Twenty-eight patients with anterior wall AMI were enrolled, with an average age (56±13) years. The success rate of IMR detection was 100%. The mean IMR was (33±18 )mmHg·s. There was no complication related to intravenous adenosine triphosphate (ATP) (140 µg· kg(-1)· min(-1)). The IMR was negatively correlated with TIMI blood flow grade after primary PCI (r=-0.386, P=0.043), and positively correlated with female gender, CK peak value and TnT peak value (r=0.430, P=0.022; r=0.431, P=0.025; r=0.434, P=0.024). After 6 months of follow-up, no adverse cardiovascular events (including cardiac death, nonfatal myocardial infarction, malignant arrhythmia, unplanned revascularization, hospitalization for unstable angina pectoris and severe heart failure requiring hospitalization) occurred. LVEF increased significantly compared with the first day after PCI (0.54±0.08 vs 0.47±0.06, P=0.001), and IMR was negatively correlated with LVEF after 6 months (r=-0.477, P=0.014). Multivariable linear regression analysis showed that CK peak and IMR were predictors of LVEF after six months ( ß=-0.595, t=-3.814, P=0.01; ß=-0.352, t=-2.26, P=0.036). Conclusions: Immediate detection of IMR in patients with anterior wall AMI after PCI is safe and feasible. The immediate IMR after PCI reflects the extent of myocardial necrosis and myocardial perfusion, and is a predictor of LVEF at 6 months after PCI.

Muscle pain, fever, cough, and progressive dyspnea in a woman with eosinophilic pneumonia.

The diagnosis of eosinophilic pneumonia (EP) is rare and challenging. This condition is frequently misdiagnosed as pulmonary tuberculosis, lymphoma, schistosomiasis, Wegener's granuloma, severe acute respiratory syndrome, or severe community-acquired pneumonia. Herein, we report a case in which computed tomography (CT)-guided percutaneous lung biopsy was used to diagnose EP without alveolar eosinophilia or peripheral eosinophilia. A roundworm identified in the patient's stool confirmed the precise diagnosis to be parasitic EP. This is, to our knowledge, the first reported case of EP confirmed by CT-guided percutaneous lung biopsy. CT-guided percutaneous lung biopsy may represent a new tool for the diagnosis of EP in patients without typical alveolar eosinophilia or peripheral eosinophilia.

[Myocardial protection of remote ischemic postconditioning during primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction].

OBJECTIVE: To evaluate the cardioprotection of remote ischemic postconditioning (RIPostC) in patients with acute ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). METHODS: Forty-six STEMI patients undergoing primary PCI at Peking University Third Hospital from January to April 2014 were randomized to RIPostC group (n=23) and control group (n=23).The RIPostC protocol was started within 1 min after reflow by thrombus aspiration or balloon inflation and consisted of 3 cycles of 5 min/5 min ischemia/reperfusion by cuff inflation/deflation of the lower left limb. The enzymatic infarct size, rate of complete ST segment resolution, corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) in infarct-related artery (IRA) and plasma levels of malondialdehyde(MDA), endothelin-1(ET-1), tumor necrosis factor α (TNFα) of the two groups were compared. RESULTS: There was no significant difference in enzymatic infarct size between the two groups (P>0.05). The rate of complete ST-segment resolution was significantly higher in RIPostC group than in control group (60.9%vs. 30.4%,P=0.04). There was a trend toward lower CTFC in RIPostC group than that in control group, but the difference was not statistically significant(28 ± 11 vs. 33 ± 11, P = 0.10). However, in the subgroup of anterior wall myocardial infarction CTFC in RIPostC group was significantly lower, compared with control group (25±9 vs. 39±10, P=0.01).There were lower plasma levels of MDA,ET-1,TNFα in RIPostC group than in control group at different time points after primary PCI (P<0.05). CONCLUSION: In STEMI patients undergoing primary PCI, RIPostC may improve myocardial perfusion and attenuate ischemia reperfusion injury with the underlying mechanisms involving reduction of oxidative stress, protection of endothelial function and inhibition of inflammatory response.

Influence of neural stem cell transplantation on angiogenesis in rats with spinal cord injury.

We examined the influence of neural stem cell transplantation on angiogenesis in rats with spinal cord injury. Sixty rats with spinal cord injury were divided into an experimental group and a control group and given neural stem cells or an equivalent amount of phosphate-buffered saline by intravenous transplantation, respectively. Basso, Beattie, and Bresnahan (BBB) motor function assessment was performed in rats at different times after transplantation, and von Willebrand factor (vWF) immunofluorescence and Western blot analysis of vascular endothelial growth factor (VEGF) protein were also performed. The BBB scores of rats in the 2 groups were both zero before transplantation. The BBB score gradually increased over time. The BBB score of the experimental group showed no significant difference compared with that of the control group (P > 0.05) 7 days after transplantation. The BBB score of the experimental group was significantly improved compared with that of the control group 14 days after transplantation (P < 0.05). vWF-positive cells and VEGF protein expression in the experimental group were significantly increased compared with those in the control group 7 and 14 days after transplantation, respectively (P < 0.05). Neural stem cell transplantation may promote angiogenesis by inducing VEGF expression as well as improve functional recovery of limb movements.

Elevated blood eosinophil count is a valuable biomarker for predicting late acute cellular rejection after liver transplantation.

BACKGROUND: Recent studies have indicated the value of increased blood eosinophil counts for the diagnosis of acute cellular rejection (ACR) after orthotopic liver transplantation (OLT). However, the relationship between eosinophil count and late ACR at more than 6 months after OLT is still unclear. METHODS: We sought to retrospectively analyzed the ACR predictive value of eosinophil counts. In the day before or the day of biopsy among 40 biopsies performed on 37 patients beyond 6 months after OLT. RESULTS: Relative eosinophil count was significantly higher in the ACR (n = 24) than the non-ACR cohort, albeit with no significant difference in absolute eosinophil count. Receiver operating characteristic (ROC) analysis showed an absolute eosinophil count of 0.145 × 10(9)/L and a relative eosinophil count of 2.3% to show the highest Youden index with area under the ROC curves of 0.746 and 0.813, respectively. When absolute eosinophil count ≥ 0.145 × 10(9)/L or relative eosinophil count ≥ 2.3% was defined to be elevated, the sensitivity and specificity to predict ACR were 45.8% and 87.5%, and 75% and 87.5%, respectively. When the absolute eosinophil count ≥ 0.285 × 10(9)/L or relative eosinophil count ≥ 3% was defined as elevated, the sensitivity and specificity were 25% and 100%, and 50% and 100%, respectively. All patients with an absolute eosinophil count ≥ 0.285 × 10(9)/L showed a relative eosinophil count ≥ 3%. CONCLUSIONS: Elevated blood eosinophil count was a valuable biomarker to predict late ACR after OLT.

The role of liver transplantation for intrahepatic cholangiocarcinoma: a single-center experience.

BACKGROUND/AIM: Intrahepatic cholangiocarcinoma (ICC) is not a widely accepted indication for liver transplantation (LT). The present study describes our institutional experience with patients who underwent transplantation for ICC. METHODS: A retrospective analysis was performed on 11 consecutive patients with ICC who underwent LT between October 2003 and November 2008 at our institution. RESULTS: At a median patient follow-up interval of 10 months (2-56), the median survival time was 9 months (2.5-53). The perioperative mortality and the recurrence rate were 0 and 45.5%, respectively. Five patients are currently alive 10, 12, 41, 51 and 53 months after LT, respectively. One patient died 3 months after LT as a result of bile leak and toxic shock, and 5 patients died of tumor recurrences at 2.5, 8, 8, 9 and 10 months post-LT, respectively. The 1-, 2-, 3- and 4-year disease-free survival rates and overall survival rates of all the patients were 51.9, 51.9, 51.9 and 51.9%, and 50.5, 50.5, 50.5 and 50.5%, respectively. CONCLUSION: With better and strict patient selection, the prognosis of LT for ICC could be improved. ICC patients with lymph node involvement, vascular or bile duct invasion are contraindicated for LT.

Effects of gene transfer CTLA4Ig and anti-CD40L monoclonal antibody on islet xenograft rejection in mice.

Blockade of a costimulatory pathway by adenovirus-mediated cytotoxic T lymphocyte associated antigen 4 immunoglobulin (CTLA4-Ig) gene transfer and anti-CD40L mAb(MR1) have been reported to enhance graft survival in several experimental transplantation models. In this study, we investigated the effects of gene transfer of CTLA4Ig and MR1 on islet xenograft rejection in mice. Recombinant adenovirus AdCTLA4Ig was constructed to express CTLA4Ig. Islet grafts from adult male DA rats transferred with AdCTLA4Ig were transplanted to streptozocin-induced diabetic Balb/c mice. The diabetic mice were treated with MR1 after transplantation. We evaluated the islet xenograft mean survival time as well as changes in interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) levels in transplanted mice. The mean survival of islet xenografts in the MR1 treatment group was 34.9 +/- 5.62 days, in the AdCTLA4Ig treatment group it was 56.5 +/- 10.64 days, and in the AdCTLA4Ig plus MR1 treatment group it was 112.9 +/- 19.26 days, all significantly prolonged compared with an untreated group (8.1 +/- 0.83 days). Within 1 week after transplantation the levels of IL-2 and TNF-alpha showed sharp increases in the untreated group, being significantly higher than those observed prior to transplantation. In conclusion, using both AdCTLA4Ig and MR1 can improve the islet xenograft survival. The beneficial effects of the combined use of the 2 reagents were superior to either 1 alone, possibly related to down-regulated expression of Th1 cell-related cytokines.

Ultraviolet B exposure of peripheral blood mononuclear cells of patients with systemic lupus erythematosus inhibits DNA methylation.

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease, in which sunlight (especially ultraviolet B (UVB) 290-320 nm) is known to induce exacerbation of disease. DNA methylation regulates gene expression, and hypomethylation is associated with abnormal cell function in SLE. The purpose of this study was to investigate the effect of UVB on DNA methylation in SLE and its significance in the pathogenesis of SLE. Forty-five patients with SLE and 20 healthy controls were enrolled in the study, which involved the investigation of DNA methylation and DNA methyltransferase 1 (DNMT1) of peripheral blood mononuclear cells with UVB irradiation. Our results demonstrate the following: The level of DNA methylation in patients with SLE was lower than that in the control group. DNA methylation was decreased after UVB irradiation at different dosages especially in patients with marlar rashes and leucopenia, but no significant difference was observed in the DNMT1 mRNA expression. DNA methylation levels in patients with active SLE were more sensitive to UVB. In conclusion, UVB exposure is able to inhibit DNA methylation, which subsequently takes part in the pathogenesis of SLE.

Single-center experience of therapeutic management of hepatic artery stenosis after orthotopic liver transplantation. Report of 20 cases.

BACKGROUND/AIMS: Hepatic artery stenosis (HAS) is a potentially life-threatening complication of liver transplantation because the associated mortality and morbidity rates are high. Surgical reconstruction was recommended as first choice of treatment and interventional radiologic techniques have been introduced recently. However, the mid- or long-term outcomes of HAS were unclear. The purpose of this study was to evaluate the efficacy of interventional therapy and clinical outcomes of HAS following liver transplantation. METHODS: A retrospective analysis was performed for 20 cases of HAS documented by angiography from October 2003 to August 2007 at the authors' institution. All patients underwent transluminal interventional therapy including percutaneous transluminal angioplasty and endovascular stent placement. The technical results, hepatic artery patency and clinical outcome were reviewed. RESULTS: All patients were treated with interventional management. Technical and immediate success was 100%. Of 8 patients with early HAS (within 1 month of transplantation), 1 underwent retransplantation due to deterioration of liver function. One died of acute liver failure waiting for retransplantation. Of 12 patients with late HAS (after 1 month of liver transplantation), 1 died of severe sepsis 38 days after transplantation. Five patients underwent late retransplantation due to ischemic-type biliary strictures or recurrent attacks of cholangitis. One of these patients died 11 days after retransplantation. The median follow-up of all 20 patients was 14.4 months after liver transplantation. The Kaplan-Meier curve of patency showed that cumulated primary patency of hepatic artery interventional treatment at 3, 6 and 12 months was 94, 87 and 79%, respectively. Two patients died of causes unrelated to HAS. Three patients developed recurrent HAS and were successfully treated with second interventional therapy. Eight patients (40%) developed ischemic-type biliary strictures and 7 underwent endoscopic treatment or percutaneous transhepatic cholangiodrainage. Graft function in 5 patients improved. The Kaplan-Meier curve of survival showed that the 1- and 2-year cumulated survival rates of early and late HAS were 87.5 and 43.8% and 81.5 and 61.1%, respectively. There was no significant difference in 1- and 2-year survival rates between early and late HAS (log-rank test, p = 0.928). CONCLUSION: Interventional therapy is an effective treatment for both early and late HAS with excellent short- and mid-term outcomes, while without irreversible graft dysfunction resulted from HAS. However, the patients have a high incidence of ischemic-type biliary lesions.

A single-center experience of retransplantation for liver transplant recipients with a failing graft.

With the accumulation of orthotopic liver transplantation (OLT) recipients, an increased number of patients with graft failure need retransplantation (re-OLT). This study was undertaken to examine our clinical experience of re-OLT for patients with poor graft function after primary transplantation at a single center. We analyzed retrospectively, the clinical data of 32 re-OLTs in 31 patients at our center from January 2004 to February 2007, including indications and causes of death, timing of retransplantation, and surgical techniques. The indications included bile leak (2 cases), biliary stricture (16 cases), recurrence of hepatocellular carcinoma (HCC) (5 cases), hepatic artery stenosis (4 cases), hepatic artery thrombosis (HAT) (2 cases), and hepatitis B recurrence (3 cases). The rate of re-OLT was 4.29%. All patients underwent modified piggyback liver transplantations with cadaveric allografts. No intraoperative mortality and acute rejection occurred. Overall, 17 of 31 patients (54.8%) died after re-OLT with survival times ranging from 2 weeks to 28 months. Another 14 patients were cured with survival times of 4 to 32 months. The perioperative mortality rate of patients who underwent re-OLT between 8 and 30 days after their initial transplantation was highest (66.7%). The most common cause of death after re-OLT was sepsis (47.1%), multiple-organ failure (17.6%), and recurrence of HCC (17.6%), whereas the majority of deaths posttransplantation were sepsis-related (54%) within 1 year. Re-OLT is the only therapeutic option for a failing liver graft. Proper indications and optimal operative time, advanced surgical procedures, reasonable individual immunosuppression regimens, and effective perioperative anti-infection treatments contribute to the improved survival of patients after re-OLT.

Alleviation of ischemia-reperfusion injury in rat liver transplantation by induction of small interference RNA targeting Fas.

BACKGROUND: Cellular apoptosis plays an important role in ischemia-reperfusion (I/R) injury during organ transplantation. Synthetic small interference RNA (siRNA) targeting apoptotic receptor Fas has proven effective to protect mice against hepatitis and renal I/R injury. The objective of this study is to investigate the silencing impact of Fas siRNA to alleviate I/R injury in rat liver transplantation. MATERIALS AND METHODS: Rat hepatocytes (BRL cells) were transfected with three pairs of synthesized Fas siRNA; cells untreated and treated with GFP siRNA were taken as blank and siRNA control. The most effective Fas siRNA was chosen for in vivo experiments. Syngeneic orthotopic liver transplantation was performed in Fas siRNA group, siRNA control group, and blank control group of Sprague-Dawley rats. There were 25 pairs of rats in each group. siRNA transfection of donor rats was done with hydrodynamic injection method 48 h before liver procurement. Blood and liver samples were collected for evaluation of serum ALT levels, Fas protein and mRNA expression, and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, 1, 3, 6, 12, and 24 h after liver transplantation. RESULTS: Fas siRNA2, which inhibited Fas gene expression much more than other siRNAs, was chosen for in vivo experiment. The serum ALT levels of Fas siRNA group were much less than those of blank and siRNA control groups 1, 3, 6, 12, and 24 h after blood reperfusion, indicating diminishing ischemia-reperfusion injury. Donor livers in Fas siRNA group had substantially less cell apoptosis. The expression of Fas mRNA and protein was reduced dramatically in the Fas siRNA group compared with the other two groups. CONCLUSION: Fas-mediated apoptosis play an important role in I/R injury of rat liver transplantation. Silencing Fas by hydrodynamic injection of siRNA holds therapeutic promise to limit I/R injury.

Increased mortality odds ratio of male liver cancer in a community contaminated by chlorinated hydrocarbons in groundwater.

AIMS: To investigate the association between cancer mortality risk and exposure to chlorinated hydrocarbons in groundwater of a downstream community near a contaminated site. METHODS: Death certificates inclusive for the years 1966-97 were collected from two villages in the vicinity of an electronics factory operated between 1970 and 1992. These two villages were classified into the downstream (exposed) village and the upstream (unexposed) according to groundwater flow direction. Exposure classification was validated by the contaminant levels in 49 residential wells measured with gas chromatography/mass spectrometry. Mortality odds ratios (MORs) for cancer were calculated with cardiovascular-cerebrovascular diseases as the reference diseases. Multiple logistic regressions were performed to estimate the effects of exposure and period after adjustment for age. RESULTS: Increased MORs were observed among males for all cancer, and liver cancer for the periods after 10 years of latency, namely, 1980-89, and 1990-97. Adjusted MOR for male liver cancer was 2.57 (95% confidence interval 1.21 to 5.46) with a significant linear trend for the period effect. CONCLUSION: The results suggest a link between exposure to chlorinated hydrocarbons and male liver cancer risk. However, the conclusion is limited by lack of individual information on groundwater exposure and potential confounding factors.

Induction of apoptosis by norcantharidin in human colorectal carcinoma cell lines: involvement of the CD95 receptor/ligand.

PURPOSE: Cantharidin, a natural toxin, is the active substance of mylabris and has antitumor effects in man. Norcantharidin, the demethylated analogue of cantharidin, has been used in the treatment of patients with primary hepatoma and those with leukopenia in China. The present study was designed to investigate whether norcantharidin exerts cytotoxic activity against colorectal cancer cells by inducing apoptosis and to examine the possible mechanism in the phenomenon. METHODS: Inhibition of proliferation of norcantharidin on Colo205, HT-29, and SW480 colorectal cancer cells was determined by the trypan blue dye exclusion test. Apoptosis of norcantharidin-treated cells was determined by morphological analysis, agarose gel DNA electrophoresis, and quantitated by flow cytometry after staining with propidium iodide. Cell cycle and the cell surface expression of the CD95/CD95 ligand were evaluated by flow cytometry. Caspase 8-like protease and protein phosphatase 1 and 2A activities were also analyzed. RESULTS: Treatment with norcantharidin of colorectal cancer cells not only inhibited cell proliferation, but also induced apoptosis. Norcantharidin induced apoptosis mainly in two phases: rapid apoptosis in S-phase cells and delayed apoptosis in G2/M arrested cells. Treatment with norcantharidin resulted in an upregulation of the CD95 receptor and CD95 ligand on the cell surface. Furthermore, stimulation with anti-CD95 monoclonal antibody (mAb) resulted in further induction of apoptosis after treatment with norcantharidin. In addition, the apoptosis-inducing effect of norcantharidin was almost completely inhibited by anti-CD95 ligand mAb. Norcantharidin-treated cells showed the activation of caspase 8. Both zVAD-FMK (a broad range caspase inhibitor) and IETD-FMK (a caspase-8 inhibitor) showed apparent inhibition of the apoptosis-inducing effect. Norcantharidin did not show an inhibitory effect on protein phosphatase. CONCLUSIONS: These results suggest that norcantharidin triggers apoptosis in colorectal cancer cell lines via the activation of the CD95 receptor/ligand system, and that this agent may be useful for developing new therapeutic regimens for the treatment of colorectal carcinoma.