1.Pharmacokinetics of 188Re-HEDP in cancer patients with osseous metastases
Ai-ping, CHENG ; Shao-liang, CHEN ; Shu-guang, CHEN
Chinese Journal of Nuclear Medicine 2010;30(4):267-271
Objective To investigate the biodistribution,excretion and other pharmacokinetics,of 188Re-1-hydroxy-1,1-ethylidene disodium phosphonate (HEDP) in cancer patients with osseous metastases who were suffering form bone pain. Methods A single dose (20,30,40,and 50 MBq/kg,10 patients in every group) of 188Re-HEDP was administered as a bolus injection,meanwhile dynamic images on patient's chest were collected for 30 min. Anterior and posterior whole-body images were obtained at 1,2,4,5,12,24,36,48,60 and 72 h after injection of 188Re-HEDP. By region of interest (ROI) technology,the curve of time-background corrected counts of left cardiac ventricle could be generated,and the background-corrected counts of various organs and total whole body could be calculated as a geometric mean using the anterior and posterior scans,and transformed to the percentage injected dose ( % ID). Urine was collected after injection of 188Re-HEDP. Counts of urine were measured by γ counter. Analysis of variance and t-test were used. Results Linear relationship of metabolism of 188Re-HEDP was observed in the doses from 20 to 50 MBq/kg,with correlation coefficient r2 = 0. 9376. A two-compartment model was the best fit for metabolism of 188Re-HEDP with the parameters median area under curve (AUC) 3.32 × 105,3.97 × 105,7.83 × 105,8.58 ×105,respectively; median α 0.06,0.05,0.04,0.06 respectively; median β 1.16 ×10-3,1.16 × 10-3,1.03 × 10-3,1.15 × 10 -3 respectively; median A 3591.21,4858.23,5642. 48,4167.05 respectively; median B 293.97,352.95,614.41,1063.82 respectively; median T1/2(α) 12.51,12.83,15.41,12.02 min respectively; median T1/2(β) 595.47,596.50,673.09,600.93 min respectively in the doses of 20,30,40and 50 MBq/kg. 188Re-HEDP was taken up mainly by bone up to 40% ID at 4 h. Urine profile showed that 66.79 % ID was eliminated within 24 h,being its 74% collected along the first 5 h after-administration.Conclusions In the doses of 20,30,40 and 50 MBq/kg,metabolism of 188Re-HEDP presented linear model. Pharmacokinetics of 188 Re-HEDP followed a two-compartment model administrated by blood vessel.Following injection,188 Re-HEDP was taken up mainly by bone and excreted by uropoietic system.
2.Effects of intravenous infusion of bilirubin on the expression of myeloid differentiation factor 88 and in-terleukin-1 receptor associated kinase-4 in splenocytes with neonatal rats
Juan LUO ; Changhui CHEN ; Xiaoming LIANG ; Tianwei SHAO ; Fulan ZOU
Chinese Pediatric Emergency Medicine 2015;22(10):699-703
Objective To explore the effects of bilirubin on myeloid differentiation factor 88 (MyD88)and interleukin-1 receptor associated kinase-4(IRAK-4).Methods Seven-day-old Sprague Daw-ley rats (clean grade),male or female,weighing 12.0 to 15.0 g,were randomly assigned to 6 groups.There were normal saline group(Ⅰ),lipopolysaccharide(LPS)control group (LPS,Ⅱ),15 mg /kg bilirubin con-trol (free-LPS)group (Ⅲ),15 mg /kg group (Ⅳa),30 mg /kg group (Ⅳb)and 50 mg /kg group (Ⅳc), and then subsequently divided into 2 h,5 h and 24 h subgroups in each groups.Some of the 200 newborn rats died amid the experiment.Finally a total of 144 were involved in the analysis of results,and 8 rats in each subgroups.Newborn Sprague Dawley rats were administered at various doses of bilirubin (15 mg /kg, 30 mg /kg and 50 mg /kg respectively)intravenously;1 h after injection,the rats were administered LPS intrap-eritoneally at a dose of 1 mg /kg;MyD88 and IRAK-4 were detected by immunohistochemistry at 2 h,5 h and 24 h after the injection of bilirubin.Results (1 )LPS could stimulate the expression of MyD88 and IRAK-4 in spleen cells (qMyD88 2 h =49.89,qMyD88 5 h =139.54,qIRAK-4 2 h =7.93,qIRAK-4 5 h =24.30,qIRAK-4 24 h =6.97 ,P <0.01 ).(2)Low concentration of bilirubin could promote the expression of MyD88 and inhibit the ex-pression of IRAK-4 (qMyD88 2 h =0.76,qMyD88 5 h =5.05,qIRAK-4 2 h =6.43,qIRAK-4 5 h =22.37,qIRAK-4 24 h =1.50, P <0.01 ).(3)LPS stimulation MyD88 affected by low concentration of bilirubin was not obvious (q2 h =1.48,q5 h =1.45,q24 h =0.10,P >0.05).Effects of medium and high concentration of bilirubin on LPS stim-ulation MyD88 were inhibitory(qⅣb 2 h =42.87,qⅣc 2 h =51.38,qⅣb 5 h =103.61 ,qⅣc 5 h =1 15.44,qⅣb 24 h =1.18,qⅣc 24 h =1 1.66,P <0.01 ).(4)Effects of low,medium and high concentration of bilirubin on LPS stimulation IRAK-4 were inhibitory(qⅣa 2 h =9.52,qⅣb 2 h =14.39,qⅣc 2 h =25.55,qⅣa 5 h =38.83,qⅣb 5 h =54.62,qⅣc 5 h =60.51 ,qⅣa 24 h =2.41 ,qⅣb 24 h =1.47,qⅣc 24 h =7.61 ,P <0.01 ).(5)The inhibition of biliru-bin to MyD88 and IRAK-4 was observed at 2 h,strengthened at 5 h,disappeared at 24 h in low-mid concen-trations of bilirubin(P <0.01 )while still visible at 24 h in high concentration of bilirubin.(6)There was neg-atively correlation between the expression level of MyD88,IRAK-4 and bilirubin concentration(rsMyD88 2 h =-0.86, rsMyD88 5 h =-0.92,rsMyD88 24 h =-0.53,rsIRAK-4 2 h =-0.82,rsIRAK-4 5 h =-0.86,rsIRAK-4 24 h =-0.57,P <0.01).(7) Under the effect of bilirubin and LPS,there were positively correlation between the expression levels of MyD88 and IRAK-4 of spleen cells(r2 h =0.77,r5 h =0.9,r24 h =0.67,P <0.01).Conclusion Bilirubin could inhibit the expression of MyD88 and IRAK-4.As the concentration of bilirubin increasing,its inhibition is more obvious and prolonged.The mechanism that bilirubin affects immune function of newborn rat may be related to regulation of expression of MyD88 and IRAK-4 at toll-like receptor 4 signal pathway.
3.Survey of totally thoracoscopic anatomic segmentectomy for the peripheral stage ⅠA non small cell lung cancer
Weibing WU ; Liang CHEN ; Quan ZHU ; Yongfeng SHAO ; Shijiang ZHANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2013;29(7):399-401
Objective To evaluate the safety and feasibility of totally thoracoscopic anatomic pulmonary segmentectomy (TTAS) for the treatment of the peripheral stage ⅠA non small cell lung cancer(NSCLC).Methods The study involved 50 consecutive patients undergoing totally thoracoscopic anatomic segmentectomy (TTAS) from September 2010 to November 2012 in the First People's Hospital affiliatied to Nanjing Medical University.The diameter of the tumors were less than 2 cm [(mean diameter(1.35 ±0.48) cm].All lymph node sampling of N1 and N2 were neglive,All patients received symtematic lymph node dissection.The pulmonary vessels were individually ligated,and the bronchi were closed using an endoscopic stapler.The intersegmental plane was identified using the demarcation between the resected(inflated) and preserved(collapsed) lungs.Staplers were used for intersegmental dissection.Results The mean operative time and intraoperative bleeding were (191.5 ± 50.4) min and (49.2 ± 54.6) ml respectively.The chest tube drainage duration was (3 ± 1) days.The number of stapler cartridges used for intersegmental division was 3.9 ±0.8.The mean number of lymph nodes and nodal stations dissected were 12.6 ± 2.8 and 6.0 ± 1.5 respectively.No mortality and complications were observed 30 days after the surgery.Further,no local recurrence or metastases were observed during follow-up.Conclusion Totally thoracoscopic anatomic segmentectomy(TTAS) is a feasible and safe technique.With systematic lymph node dissection,TTAS can be a reasonable therapeutic option for stage ⅠA NSCLC.
5.Study on the Effect of Various Polarity Fractions Extracted from Sancaofang and Its Combination on Human Lung Adencarcinoma SPC-A-1 Cells
Zhenzhong SHAO ; Xiaobin JIA ; Yan CHEN ; Liang FENG ; Feng SHI
China Pharmacy 2001;0(07):-
OBJECTIVE: To study the effect of various polarity fractions extracted from Sancaofang (SCF) and its combination on proliferation of human lung adenocarciaoma SPC-A-1 cells for bolting the most effective position of anti-tumor and suitable compatibility regimes.METHODS: Ethanol extraction and water extraction were adopted to prepare 95%,60% and 30% ethanol extract portion,water extract portion of SCF and compound decoction.The MTT assay was used to determine the effect of various polarity fractions of SCF,decoction and its combination on SPC-A-1 cells proliferation.RESULTS: IC50 of 60% ethanol extract was the smallest for SPC-A-1 cells.60% ethanol extract combined with 95% ethanol extract acts as a stimulus to anti-tumor activity significantly.CONCLUSION: The best suitable compatibility regimes were 95% ethanol extract combined with 60% ethanol extract.The liposolubility extract of SCF can be applied for anti-tumor.
6.The tolerance to 188Re-HEDP treatment in patients with bone pain from osseous metastases
Ai-ping, CHENG ; Shao-liang, CHEN ; Wen-guan, LIU ; Xue-fen, CHEN ; Chang-de, XU
Chinese Journal of Nuclear Medicine 2011;31(2):77-81
Objective To study the tolerance to 188Re-1-hydroxy-1 ,1-ethylidene disodium phosphonate(HEDP) in patients with bone pain caused by osseous metastases. Methods Thirty-one patients(10with prostate cancer, 9 with breast cancer, 3 with lung cancer, 5 with liver cancer, 2 with rectal cancer, 1with esophageal cancer and 1 with renal cancer) received a single injection dose of 188Re-HEDP. The patients were divided into four groups according to the injection dose: 20 MBq/kg (6 patients), 30 MBq/kg(6 patients), 40 MBq/kg (9 patients), and 50 MBq/kg (10 patients). Haematological toxicity (WHO grading) of grade Ⅲ- Ⅳ was considered unacceptable. Vital signs and adverse effects after injection were recorded for 8 weeks. Blood counts were measured weekly during a period of 8 weeks. Biochemical parameters and electrocardiogram were assayed at week 4 and 8. Statistical analysis was performed for per-protocol (pp) population (t-test). Results Twenty-seven patients belonged to PP population with 5 in the group of 20 MBq/kg, 5 in the group of 30 MBq/kg, 8 in the group of 40 MBq/kg and 9 in the group of 50 MBq/kg.No obvious adverse effects and no significant change of vital signs, electrocardiogram, liver and renal function were found after injection. Alkaline phosphatase was slightly higher than baseline at week 4 and 8 after therapy, but the difference was not statistically significant. In the 20 MBq/kg group, reversible grade Ⅰ leucopenia was noted in 1 patient. In the 30 MBq/kg group, 2 patients showed reversible grade Ⅰ leucopenia including 1 alone with reversible grade Ⅲ thrombopenia. In the 40 MBq/kg group, reversible grade Ⅰ leucopenia and thrombopenia was observed in 1 patient and reversible grade Ⅱ leucopenia and thrombopenia in another patient. In the .50 MBq/kg group, 3 patients showed reversible grade Ⅱ leucopenia. The lowest level of thrombopenia was at week 4(143.5 × 109/L), leucopenia at week 6 (5.4 × 109/L) and anaemia at week 8(t = 3.1325, 3.3156, 3.4917, all P < 0. 05 compared with baseline). At week 8, the mean level of platelet and leucocyte recovered to baseline. "Bounce pain" was found in 2 of 27 patients (7.41%).Conclusions The dose of 20 MBq/kg, 30 MBq/kg, 40 MBq/kg or 50 MBq/kg of 188Re-HEDP do not cause significant side effects on cancer patients with bone metastases, though there is a tendency that the haematological toxicity may increase as the dose of 188Re-HEDP increases.
7.Laparoscopic high ligation of spermatic vein in the treatment of critical varicocele
Shao-Lin ZHANG ; Bo-Chuan CHEN ; Yong-Hua CHEN ; Wei-Dong LIANG ; Liang BAI ; Yu-Xiang ZHONG ;
Chinese Journal of Primary Medicine and Pharmacy 2006;0(12):-
Objective To probe into the clinical curative effect of laparoscopic high ligation of spermatic vein in the treatment of critical varicocele.Methods The clinical data of the 26 eases of laparoscopic high ligation of apermatic vein in the treatment of critical varicocde were reviewed and analyzed in the last two years in this hospi- tal.Results All the 26 cases had been conducted smoothly with the operation time 25~50min,an average of(28?3)min.After 3~24 months being followed-up,all the symptoms and signs disappeared with no relapse and testicle a- trophy.Eight wives of the patients who had been operated on got pregnant.Conclusion With soon recovery and small wound,it was safe to adopt laparoscopic high ligation of spermatic vein in the treatment of critical varicocele, especially for critical two-sided varicocde.
8.Effect of tumor length on clinicopathologied and prognosis of node-negative esophageal carcinoma patients
Mingwen SHAO ; Liang CHEN ; Hongxia LI ; Lan MA ; Yongqian SHU ; Lianke LIU
China Oncology 2014;(11):846-851
Background and purpose:At present, the relationship between tumor length and prognosis of esophageal carcinoma patients has been a controversial topic, and there have been few studies describing the effect of tumor length on clinicopathology and prognosis of node-negative esophageal carcinoma patients. The purpose of this study was to investigate the effect of the tumor length on clinicopathology and prognosis of node-negative esophageal carcinoma patients.Methods:The clinicopathological characteristics and survival time of 686 node-negative esophageal carcinoma patients, conifrmed by surgical pathology specimens in the First Afifliated Hospital of Nanjing Medical University from Jan. 2008 to Dec. 2010, were retrospectively analyzed. The optimal cut-off value was determined by decision tree model. Univariate and multivariate methods were used to analyze the prognostic factors of node-negative esophageal carcinoma patients.Results:In decision tree analysis, esophageal tumor length was correlated with an increasing hazard ratio for death with a cut-off value at 3 cm. No signiifcant differences were found in gender, onset age, lesion site and pathological type between 2 groups which were patients with tumor length≤3 cm and tumor length >3 cm (P>0.05). The only 1 difference between 2 groups was T stage (P<0.001), and tumor length had a positive correlation with T stage (r=0.373). The 1-, 3- and 5-year survival rates of patients with tumor length≤3 cm and tumor length >3 cm were 95.7%, 84.4%, 76.1% and 88.3%, 57.8%, 46.5% respectively, and the difference was statistically signiifcant (P<0.001). Tumor length was signiifcantly associated with overall survival in univariate and multivariate analyses.Conclusion:Tumor length has close relationship with T stage in node-negative esophageal carcinoma patients. Tumor length≤3 cm could be considered as T1-2 and >3 cm as T3. Tumor length is an important prognostic factor for esophageal carcinoma patients without lymphatic metastasis.
9.The effects of family feeding pattern on the physical growth of infants
Jinchan LIU ; Yan LUO ; Liang CHEN ; Yan WANG ; Ziyu SHAO ; Li LI ; Chuanlai HU
Chinese Journal of Primary Medicine and Pharmacy 2014;(9):1302-1304
Objective To explore the relationship between physical growth of infants and family feeding be -havior.Methods Demographic information was collected from 516 objects.Height,weight,head circumference,chest circumference were measured and feeding behavior was evaluated using prospective observational study method . Results (1) Feeding behavior score was positively associated with infant physical development indicators ,the be-tween groups differences of infant age ,body weight,body length were statistically significant (P<0.05).(2)The re-sults of Pearson correlation analysis showed that weight , head circumference of infants at 18 months and length at 24 months were significantly correlated with feeding behavior score (P<0.05).(3)The analysis of feeding behavior factors found that food preparation was associated with weight infants at 18 months(P<0.05);behavior of infants and height,weight,head circumference,chest circumference of children in the 18 months of age were related(P<0.05);infant feeding environment in the 18-month-old was related with their height,weight,head circumference(P<0.05). Conclusion It is suggested that well family feeding pattern might be a certain stimulative role in young children ′s physical growth and development .
10.Effects of intravenous infusion of bilirubin on the expression of phospho-p38 mitogen-activated protein kinase and the apoptosis in splenocytes of neonatal rats
Xiaoming LIANG ; Changhui CHEN ; Tianwei SHAO ; Juan LUO ; Fulan ZOU ; Maojun LI ; Binzhi TANG
Chinese Journal of Applied Clinical Pediatrics 2014;29(12):931-935
Objective To explore the effects of bilirubin on myeloid differentiation factor phospho-p38 mitogen-activated protein kinase (p-p38MAPK) and apoptosis in splenocytes of neonatal rats.Methods Seven-day-old Sprague Dawley rats (clean grade),male or female,weighting 12.0-15.0 g,were randomly assigned to 6 groups.There were blank control group (Ⅰ),lipopolysaccharide (LPS) control group (Ⅱ),15 mg/kg bilirubin control (free-LPS) group (Ⅲ),15 mg/kg group (Ⅳa),30 mg/kg group (Ⅳb) and 50 mg/kg group (Ⅳc),and then subsequently divided into 2 h,5 h and 24 h subgroups in each groups.Some of the 200 newborn rats died amid the experiment,tinally,a total of 144 cases were involved in the analysis of results,and 8 rats in each subgroups.Newborn Sprague Dawley rats were administered at various doses of bilirubin (15 mg/kg,30 mg/kg and 50 mg/kg,respectively) intravenously; 1 h after injection,the rats were administered LPS intraperitoneally at a dose of 1 mg/kg;p-p38MAPK were detected by immunohistochemistry;Apoptosis in splenocytes was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling methods at 2 h 5 h and 24 h after the injection of bilirubin.Results 1.Expression of p-p38MAPK in each group:bilirubin in low-mid concentrations of range inhibited LPS-induced p38MAPK activation (qⅣa =20.93,10.37,respectively at 2 h,and 5 h,all P < 0.01 ;qⅣ b =79.97,14.79,all P < 0.01).The inhibition strengthened with increasing concentration of bilirubin.The effect was observed at 2 h,strengthened at 5 h,disappeared at 24 h.Bilirubin in the high concentrations of range stimulated the expression of p-p38MAPK (qⅣc =32.55,19.23,27.72,respectively at 2 h,5 h and 24 h,all P <0.01),observed at 5 h,reduced at 24 h.2.Effects of bilirubin on apoptosis in splenocytes:LPS could increased the apoptosis index (AI) of splenocytes(q =54.62,P < 0.01);The AI of splenocytes had no significant change in low concentrations of range of bilirubin (q =43.92,P > 0.05).Low-mid concentration of bilirubin with LPS reduced the AI of splenocytes (q Ⅳ a =4.48,P < 0.01 ;q Ⅳ b =2.07,P < 0.05),while high concentration of bilirubin with LPS increased the AI of splenocytes (q =5.08,P < 0.01).Conclusions Bilirubin in low-mid concentrations of range could inhibit the expression of LPS-induced p38MAPK,while bilirubin in high concentrations of range stimulated the expression.As the concentration of bilirubin elevated,its inhibition was prolonged.Bilirubin in high concentrations of range bilirubin could induce apoptosis in splenocytes.The immune dysfunction in neonatal hyperbilirubinemia may have something to do with the regulation of phosphorylation of p38MAPK and activation of apoptotic pathways.