Objective To define the maximum-tolerated dose (MTD) of lobaplatin (LBP) in a weekly regimen combined with concurrent radiotherapy in the treatment of locally advanced nasopharyngeal carcinoma (NPC).Methods A total of 18 cases with stage Ⅲ/Ⅳ A NPC were enrolled.Concurrent chemoradiotherapy was given to all the patients with a dose escalation of LBP.The initial dose of LBP was 15 mg/m2 with an escalating dose of 5 mg/m2.At least 3 patients were assigned into each group.Patients were proceeded into the next dose group if no dose-limiting toxicity (DLT) occurred until the MTD was achieved.Efficacy and toxicity were evaluated regularly.Results Three patients were assigned into the 10 mg/m2,3 into the 15 mg/m2,and 6 into the 20 mg/m2 and 25 mg/m2 groups,respectively.Two patients experienced DLT in the 25 mg/m2 group.Hence,the MTD was determined as 20 mg/m2.At 3 months after corresponding treatment,the remission rate of nasopharyngeal tumors and neck-positive lymph nodes of the patients was 100％.The most common toxicity was reversible bone marrow suppression.Conclusions The MTD of weekly lobaplatin plus concurrent IMRT is 20 mg/m2 for locally advanced NPC.This regimen is reliable and safe,which is worthy of further clinical study.

A patent cardiac support system which is used as a bridge treatment for acute myocardial infarction has been designed and tested in vitro and in two dogs in vivo. This is an easy-to-use intelligentized pulsatile flow cardiopulmonary bypass device to replace the function of heart. The device consists of two identical pumps and perfusion chambers, a sensing and control system, a gas exchanger between the vein and pump, two one way valves between pump and veins or arteries. Arterial pressure and EKG feedback mechanisms are used for maintaining blood pressure and coordinating the pumping activity with heart contraction. A prototype of the device was built to perform hydraulic in vitro tests with aims of verifying the new device's pumping behavior. Functional evaluation of the device was carried out by using it in a model circuit made with standard CPB components plus a mock hydraulic pipeline. This system demonstrated easy manipulation, good controllability, and provided a 65+/-2ml x beat(-1) flow volume. There was a linear correlation between peak pressure value and pulsatile frequency. In the two in vivo experiments, the primary objective was to determine whether the device could work well in dog, whether physiologic pulsatility could be achieved and whether the blood supply to heart should be sufficient during asystole status by drugs. The results suggest that all the goals have been achieved.
Animals ; Cardiopulmonary Bypass ; Computer-Aided Design ; Dogs ; Equipment Design ; Heart-Assist Devices ; Materials Testing ; Myocardial Infarction ; therapy

Objective:To investigate the changes in peripheral blood and liver-infiltrating natural killer-like B (NKB) cells in patients with primary hepatocellular carcinoma (HCC), and to assess the influence of IL-18 on NKB cells in vitro and the underlying mechanism. Methods:Forty-three HCC patients and 21 normal controls (NC) were enrolled in the study. Peripheral blood samples were collected to isolate plasma and peripheral blood mononuclear cells (PBMC). Intrahepatic lymphocytes (IHL) were isolated from tumor tissues and para-tumor tissues obtained from 16 HCC patients who received surgery. IL-12, IL-18 and IL-18 binding protein (IL-18BP) levels in plasma were measured by enzyme linked immunosorbent assay. The percentages of CD3 -NKp46 + CD19 + NKB cells and IL-18 + NKB cells in PBMC and IHL were analyzed by flow cytometry. Changes in the percentages of NKB cells and IL-18 + NKB cells were measured after stimulating PBMC and IHL with recombinant human IL-18 (1 ng/ml and 10 ng/ml). Changes in IL-18BP levels in the culture supernatants and phosphorylated nuclear factor-κB (NF-κB) in NKB cells were also assessed. Student′s t test, one-way analysis of variance or LSD-t test was used for statistical analysis. Results:There was no significant difference in plasma IL-12 level between HCC patients and NC ( P=0.245). Compared with NC, HCC patients had decreased IL-18 level in plasma [(224.3±58.89) pg/ml vs (327.0±52.27) pg/ml, P<0.000 1], but increased IL-18BP level [(4.421±0.97) ng/ml vs (0.92±0.18) ng/ml, P<0.000 1]. The percentages of peripheral blood NKB cells and IL-18 + NKB cells were lower in HCC patients than in NC [(2.68±1.23)% vs (8.88±2.95)% and (54.42±12.60)% vs (69.74±12.65)%, both P<0.000 1]. The percentage of NKB cells in IHL was reduced in tumor tissues as compared with that in para-tumor tissues [(2.89±0.86)% vs (4.66±1.17)%, P<0.000 1]. Moreover, the percentage of IL-18 + NKB cell was also down-regulated in tumor tissues as compared with that in para-tumor tissues [(51.50±13.18)% vs (62.13±9.24)%, P=0.013]. Recombinant human IL-18 stimulation reduced the IL-18BP level in the culture supernatants ( P<0.05). IL-18 stimulation at 1 ng/ml did not affect NKB cell percentage, IL-18 + NKB cell percentage or NF-κB phosphorylation in NKB cells from PBMC or IHL ( P>0.05), while 10 ng/ml of IL-18 not only elevated NKB cell percentage and IL-18+ NKB cell percentage, but also promoted NF-κB phosphorylation in NKB cells ( P<0.01). Conclusions:In vitro stimulation with high concentration of IL-18 might promote NF-κB phosphorylation by inhibition of IL-18BP expression. This process might play a positive feedback role to induce the activation of NKB cells and IL-18 secretion.

Objective To investigate the effect of thalidomide combined with infliximab(IFX)in treatment of refractory inflammatory bowel disease(IBD)and its effects on insulin-like growth fac-tor-1(IGF-1)and transforming growth factor-β1(TGF-β1).Methods A total of 120 patients with refractory IBD were randomly divided into experimental group and control group,with 60 cases in each group.The two groups were given conventional treatment(mesalazine),the control group was given IFX,and the experimental group was given IFX combined with thalidomide,continuous treat-ment for two months.The efficacy,intestinal flora disturbance rate,adverse reactions,Crohn's dis-ease activity index(CDAI),Lewis score,serum IGF-1,TGF-β1 levels and nutritional status indexes[albumin(ALB),transferrin(Tf)]before and after treatment for 1 month and 2 months of the two groups were compared.Results The total effective rate of the experimental group was significantly higher than that of the control group(P＜0.05).After one month and two months of treatment,CDAI and Lewis scores of the experimental group were significantly lower than those of the control group(P＜0.05);the serum levels of IGF-1,TGF-β1 as well as ALB and Tf in the experimental group were significantly higher than those in the control group(P＜0.05).The improvement of intestinal flora disturbance rate in the experimental group was significantly better than that in the control group(P＜0.05).There was no significant difference in the incidence of oral and nasal mucosa dryness,throat discomfort,nausea and vomiting between two groups(P＞0.05).Conclusion In the treat-ment of refractory IBD patients,thalidomide combined with IFX can regulate serum IGF-1 and TGF-β1 levels,effectively relieve clinical manifestations,inhibit inflammatory activities,and improve nutri-tional status and intestinal flora disorders of patients,and it has high safety.

Objective To investigate the effect of thalidomide combined with infliximab(IFX)in treatment of refractory inflammatory bowel disease(IBD)and its effects on insulin-like growth fac-tor-1(IGF-1)and transforming growth factor-β1(TGF-β1).Methods A total of 120 patients with refractory IBD were randomly divided into experimental group and control group,with 60 cases in each group.The two groups were given conventional treatment(mesalazine),the control group was given IFX,and the experimental group was given IFX combined with thalidomide,continuous treat-ment for two months.The efficacy,intestinal flora disturbance rate,adverse reactions,Crohn's dis-ease activity index(CDAI),Lewis score,serum IGF-1,TGF-β1 levels and nutritional status indexes[albumin(ALB),transferrin(Tf)]before and after treatment for 1 month and 2 months of the two groups were compared.Results The total effective rate of the experimental group was significantly higher than that of the control group(P＜0.05).After one month and two months of treatment,CDAI and Lewis scores of the experimental group were significantly lower than those of the control group(P＜0.05);the serum levels of IGF-1,TGF-β1 as well as ALB and Tf in the experimental group were significantly higher than those in the control group(P＜0.05).The improvement of intestinal flora disturbance rate in the experimental group was significantly better than that in the control group(P＜0.05).There was no significant difference in the incidence of oral and nasal mucosa dryness,throat discomfort,nausea and vomiting between two groups(P＞0.05).Conclusion In the treat-ment of refractory IBD patients,thalidomide combined with IFX can regulate serum IGF-1 and TGF-β1 levels,effectively relieve clinical manifestations,inhibit inflammatory activities,and improve nutri-tional status and intestinal flora disorders of patients,and it has high safety.