Background and purpose:Advanced and metastatic colorectal cancer is the second leading cause of cancer death. In the past ,the standard treatment for patients with advanced CRC was fluorouracil(5-FU) biochemically modulated by leucovorin(LV), which demonstrated a response rate of about 23% .In 1990s, a number of new treatment options have been available. In particular, one new cytotoxic agent ,irinotecan (CPT-11), which is a specific inhibitor of topoisomerase I, have been proven to have efficacy in the tretment of CRC .Furthermore, several first-line phase Ⅲ trials show a significant improvement in result with the addition of CPT-11 to FU-LV combination therapy (FOLFIRI).We observed the survival situation, efficacy and safety of irinotecan plus 5-FU/LV after first-line chemotherapy failure for Chinese patients with advanced or/and metastatic colorectal cancer. Methods:Twenty-four patients with metastatic colorectal cancer whose disease had progressed after treatment with first-line oxaliplatin or other chemotherapeutics were included to receive biweekly FOLFIRI regimen (irinotecan 180mg/m~ 2 on day 1,with LV 200mg/m~ 2 adiministrated as a 2-hour infusion before 5-FU 400mg/m~ 2 administrated as an intravenous bolus injection and FU⒉4g/m~ 2 as 46-hour infusion immediately after 5-FU bolus ).All the patients were planned to receive at least 6 cycles of chemotherapy .They were assessed on the basis of WHO evaluation standard of objective therapeutic effect for solid tumor.Results:24 patients were assessable to observe the efficacy and safety. No case was CR.5 case were PR, response rate was 20% (5/24). 17 case were SD , rate was 70% (17/24). 2 case were PD, rate was 8%(2/24). Median time to progression (TTP) were 6.6 months (6 to 24 months ),median overall survival was 10.7 months. The majority of adverse reaction were nausea, vomiting, anorexia, diarrhea, leucopenia, alopecie. Most of them were Ⅰ/Ⅱ degree, only 6 cases reached III/IV degree. 3 cases had diarrhea with leucopenia and fever.Conclusions:The biweekly regimen of irinotcan in combination with 5-FU/LV results in significant and clinically meaningful improvement in survival and quality of life among patients with metastatic colorectal cancer. Toxicity is manageable.

Objective To analyze the impact of allograft category on the result of living related donor kidney transplantation (LRKT)and to evaluate the predominant donors. Methods A retrospective analysis of 104 recipients receiving LRKT from Apr. 2004 to Mar. 2008 was performed. Based on donor resource, all the recipient-donor pairs were divided into four groups: spousal donation group,parental donation group, sibling donation group and cousinly donation group. The observational parameters were selected for analysis, such as average post-transplant hospitalization dates, time for serum creatinine (Scr) back to normal level, Scr levels of every observational time point, incidence of major complications (infection, rejection, DGF) and recipient/graft survival rate. Results Recipient/graft survival rate of sibling donation group seemed higher. Recipients of sibling donation group seemed to have fewer post-transplant hospitalization dates, but higher rates of infection, while those of parental donation group seemed to have higher rates of rejection. Rates of rejection and infection of spousal donation group were lower than supposed. There was no statistically significant difference in time for Scr back to normal level and Set levels of every observational time point among these four groups. Conclusions The result of sibling donor renal transplantation is better, while short-term outcome of spouse donor renal transplantation is ideal, which is similar with parent or cousin donor renal transplantation. Except for human leukocyte antigen, aspects such as quality of donor kidney, predominance during operation and self-administration post-transplant are also the guarantee for the success.

Objective To develop a flow cytometrie assay to for diagnosis of X-Linked Hyper.1gM Syndrome(XHIM).Methods Heparinized peripheral blood obtained from patient,mother and a healthy control was diluted with RPMI- 1640(unstimulated control)or with RPMI-1640 containing 15μl PMA(1 rig/μl)and 6 trl ionomycin(50 ng/μl)(stimulated cell).Using directly labeled antibodies,we have examined CD40 ligand levels on CD3+ CD8- lymphocyte surface,and CD69 levels on CD;lymphocyte Surface to determine whether the cells were activated.Results CD69 levels on CD3+ lymphocyte surface from stimulated group and from unstimulated group were above 96% and below 3%,respectively.CD40L levels Oil CD3 CDs-T lymphocyte surface from stimulated group were 0.8% (patient),60.04%(mother) and 62.87%(healthy contr01).CD40L levels on CD3+ CD8-T lymphocyte surface from unstimulated group were 0.88% (patient),4.15%(mother)and 5.51%(healthy contr01).Conclusion This flow cytometric assayis accurate and convenient,which Can be used in neonatal screening.

Objective To analyze the relationship between the genetic polymorphisms of organic anion transporting polypeptide (SLCO1B1 and SLCO1B3) and mycophenolic acid ( MPA)pharmacokinetics in Chinese kidney transplant recipients. Methods Gene mutations (SLCO1B3T334G, SLCO1B1 A338G) were detected in 68 recipients by PCR-LDR. The plasma samples were collected and blood concentration of MPA was measured on the 28 th day after transplantation. The area under the curve (AUC)0-12 of MPA in different genotype recipients was compared to analyze the correlation between single nucleotide polymorphisms (SNPs) and MPA pharmacokinetics. Results MPA AUC0-12 was higher in SLCO1B3 T334G GG carriers group than in TT carriers [(54. 54 ±14.40)vs(37.30±12.88)mg·h·L-1,(P=0.052)].However,there was no difference in MPA AUC0-12 among each genotype of SLCO1B1 A338G (P>0. 05). Conclusion Genetic polymorphisms of SLCO1B3 affect interindividual variety in plasma MPA concentration in Chinese kidney transplantation recipients.

Objective T o observe the expression changes of hypoxia inducible factor-1α (H IF-1α) and vascular endothelial grow th factor-A (V E G F-A ) in rats w ith arrhythm ias, and to explore the differences of the expression pattern in the tw o indicators of acute m yocardial ischem ia caused by arrhythm ias and coronary insufficiency. Methods T he arrhythm ia w as induced by C aC l2, and the expression changes of H IF-1α and V E G F-A w ere detected by im m unohistochem istry, W estern blotting and real-tim e PC R w ithin 6 h after the arrhythm ia in rats. Results T he expression of H IF-1α and V E G F-A show ed diffuse in the m yocardial tissue of rats died from arrhythm ias. B oth of them increased in the early arrhythm ia, then decreased. E xtensive m yocardial ischem ia happened at the beginning of arrhythm ia occurrence and its range didn't expand w ith tim e. Conclusion T he expressions of H IF-1α and V E G F-A in m yocardium of the rats w ith arrhythm ia can provide evidence for the differential diagnosis of acute m yocardial is-chem ia caused by fatal arrhythm ia and coronary insufficiency.

Objective To investigate the change and implication of plasma osteopontin (OPN) levels in renal allograft rejection.Methods The clinical data and biological samples of 46 renal transplant recipients were analyzed rerrospecnvely,including 16 patiens with stable allograft function and no evidence of biopsy-proved rejection (Non-R),22 patients with biopsy-proved acute cellular rejection (ACR),and 8 paients with biopsy-proved chronic allograft nephropathy (CAN).Six living related donors served as healthy controls (HC).Plasma OPN level was determined by using the human OPN ELISA kit.Type and grade of ACR were diagnosed based on Banff 03 classification criteria of renal allograft pathology.The plasma OPN levels were compared among different groups.The assistant diagnostic value of plasma OPN levels in differentiating rejection patients were also evaloated.Results The plasma OPN level in HC,Non-R,CAN and ACR groups was ( 12.23 ±5.95),(19.38±8.23),(27.77± 12.27) and (41.84± 18.51) μg/L,respectively.There was no significant difference in plasma OPN levels among HC,Non-R and CAN groups (P＞0.05),but the OPN levels in ACR group were decreased significantly as compared with Non-R and CAN groups (P＜0.05 ).OPN levels were positively correlated with Banff grading of ACR (P＜0.05).OPN levels were significantly different between grade Ia and grade IIb (P＜0.05).Conclusion The change in plasma OPN level has a relationship with acute rejection.Besides,the plasma OPN levels were also positively correlated with the severity of ACR.Monitoring plasma OPN levels should be useful in predicting and evaluating the severity of ACR in renal transplant recipients.

Objective To observe the protection and distribution of bone marrow mesenchymal stem cells (MSCs) by distinct intravenous infusion time on renal ischemia reperfusion injury (IRI) in rats.Methods We used unilateral nephrectomy and contralateral vascular occlusion method to establish renal IRI model in rats.The experimental groups which received 2 × 106 MSCs infusion through the tail vein,were subsequently divided into 3 subgroups:2 h pre-reperfusion (PreOp,n =16),immediately after reperfusion (Op,n =16),6 h post-reperfusion (PostOp,n - 16).The control groups included sham operation group (n =16) and ischemia group (n =16).Chemotaxis of DAPI-labeled MSCs was detected 6 h after administration in the IR kidney.Renal function was detected at 6,24,and 48 h respectively after operation. Forty eight h after operation,the renal tissues were harvested to observe the pathological changes by HE staining and the tubular epithelial cell apoptosis via TUNEL assay.Results MSCs were found in the experimental groups after IR in the kidney,most in PostOp group.Twenty-four and 48 h after reperfusion,there was no significant difference in Cr and BUN between the experimental groups and sham operation group (P＞0.05),but the levels of Cr and BUN in the experimental groups were significantly lower than in the IR group (P＜ 0.05). As compared with IR group,the renal pathological injury was alleviated,the number of apoptotic cells was decreased in the experimental group,most significantly in PostOp group (P＜0.05).Conclusion MSCs can reduce the inflammatory response and inhibit renal tubular cell apoptosis in rat renal IRI.Post-reperfusion administration of MSCs leads to the best chemotaxis efficiency and protection.

Objective To compare the clinical effect of ifosfamide in combination with liposomal doxorubicin and dexamethasone (CDD) in the treatment of relapsed/refractory multiple myeloma (MM) with or without extramedullary plasmacytoma (EMP). Methods The clinical data of 71 relapsed/refractory MM patients treated with CDD regimen from January 2011 to December 2016 were retrospectively analyzed, including 48 patients with EMP(group A)and 23 patients without EMP (group B).One cycle of the CDD treatment was 21 d or 28 d and efficacy analysis was performed after every two cycles.Results The overall response rate in group A was 43.8%(21/48)and the complete remission and near complete remission rate was 8.3%(4/48);the overall response rate in group B was 65.2%(15/23)and the complete remission and near complete remission rate was 13.0% (3/23). There were no statistically significant differences between the two groups(χ2=1.203,0.659,P>0.05).The progression-free survival (PFS)time in group A was(8.6 ± 3.3)months, while the PFS time in group B was(7.9 ± 2.5)months and there was no significant difference between the two groups(t=1.009,P>0.05).There was no significant difference about incidence rate of adverse effects between the two groups(P>0.05).Conclusions CDD regimen can be used for the treatment of relapsed/refractory MM with or without EMP, the PFS and drug related adverse effects are similar, especially in patients with EMP.

Objective To explore the protective effect of ETaR siRNA on renal ischemia reperfusion injury (IRI) by changing the immuno-microenvironment in rats .Methods A total of 40 male Sprague-Dawley (SD) rats were randomized into four groups of sham ,IR ,negative siRNA and ETaR siRNA .A renal IRI model was generated by clamping left renal artery .ETaR siRNA was delivered into kidney through renal vein by a retrograde 'hydrodynamic' injection .Blood samples were collected for detecting renal function and kidney tissue harvested for Hematoxylin & Eosin (HE) staining , TdT-mediated dUTP Nick-End Labeling (TUNEL) staining ,polymerase chain reaction (PCR) and Western blot at 48 h post-reperfusion .Results Serum creatinine ,blood urea nitrogen and renal apoptotic cells increased and renal tissue was injured after IR . The changes were inhibited by ETaR siRNA . PCR showed that ETaR siRNA treatment significantly down-regulated the expressions of inflammatory factors TNF-α , IFN-γ and IL-6 and transcription factor NF-κB induced by IR .Conclusions ETaR siRNA can effectively improve the immunomicroenvironment and thereby alleviate renal ischemia reperfusion injury .

BACKGROUND:Currently, hematopoietic stem celltransplantation mainly depends on unrelated donors. Mental state of the unrelated donors is very important to ensure the successful celltransplantation. OBJECTIVE:To compare mental and physical health status of relative and unrelated donors during the hematopoietic stem cellcol ection. METHODS:We compared the mental (Symptom Checklist-90) and physical (temperature, breath, pulse, and blood pressure) health status of relative and unrelated donors at admission, 1 day before cellcol ection, and 1-2 days after cellcol ection.RESULTS AND CONCLUSION:At admission, there was no difference in the mental health status of relative and unrelated donors (P>0.05), while the scores on Symptom Checklist-90 were significantly higher in the unrelated donors than the relative donors, including total score, forced, depression, anxiety, hostility, and fear (P<0.05). The physical signs were steady in the unrelated and relative donors, but the difference in breath and systolic blood pressure was of great significance before and after cellcol ection in the two groups. These findings indicate that during cellcol ection, the unrelated donors exhibit heavier mental load than the relative donors, and psychological counseling and health guidance are necessary.