Objective To evaluate the therapeutic effects,acute and late side-effects of cisplatin plus 5-fluorouracil (PF) schemed chronomodulated chemotherapy combined with concurrent intensitymodulated radiotherapy(IMRT) for nasopharyngeal carcinoma.Methods A total of 48 nasopharyngeal carcinoma patients treated with chronomodulated chemotherapy plus concurrent IMRT were retrospectively studied.The radiation doses prescribed to the gross target volume GTVnx of nasopharyngeal,to the positive neck lymphnodes GTVnd,to the clinical target volume CTV1,and to CTV2 were 73.92-77.88,69.96,60.06-66.00 and 50.96-56.00 Gy respectively.The Kaplan-Meier survival analysis was used to calculate the local-regional progression-free rate.The acute and late side-effects were graded according to RTOG radiation morbidity scoring criteria.Results The complete remission (CR) rate was 41.6％(20/48) ; the partial remission (PR) rate was 47.9％ (23/48) ; the stable disease (SD) rate was 4.2％(2/48) ; and the local tumor control rate was 89.6％.Most of the patients had grade 1 to 2 acute side effects and grade 0 to 1 late side-effects.No grade 4 acute and late toxicity was observed.1,2,4-year survival rates were 93.8％,79.2％ and 64.5％,respectively.The DVH analysis showed that IMRT improved the total dose and dose per-fraction to the target volume with considerable dose reduction of the normal structures at the same time.Conclusions PF chronomodulated chemotherapy plus concurrent intensity-modulated radiotherapy for NPC could improve therapeutic effects with satisfactory tolerance of the side effects.

ObjectiveTo investigate the delineation of gross tumor volume (GTV) in locally advanced nasopharyngeal carcinoma (LANC) according to imageological changes before and after induction chemotherapy (IC) in order to decrease high dose area and protect normal tissue better.MethodsBetween Mar 2010 to Jan 2011,11 patients with LANC were enrolled and treated with TPF regimen followed by intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy,target volumes were delineated based on fused CT imaging before and after IC following project determination.Tumor target volumes after and before IC were respectively delineated according to imaging tumor residues and were overlaid by CTVnx in order to ensure radical doses for the imaging tumor volume before IC,the resulting differences of tumor target volumes of IC before and after were measured and analyzed by paired t-test.ResultsBefore and after IC,the average volumes of GTVnx were respectively 44.72 cm3 and 28.87 ( t =3.89,P =0.003 ),the average volumes of GTVnd were respectively 32.76 cm3 and 19.82 cm3 ( t =2.47,P =0.033 ),the volumes of maximum dose area in brainstem and spinal cord as well as eyeball decreased ( t =2.93-4.59,all P ＜0.05).ConclusionsLANC treated by 3 cycle TPF regimen followed by IMRT with concurrent chemotherapy showes significant shrinkage of tumor volume.The volume of high dose region which caused by normally recovered tissues were decreased by re-delineation of target volume in brainstem and spinal cord as well as eyeball of CT images after IC.

Objective To analyze the clinical outcome of concurrent ehemo-radiotherapy in stage Ⅳ non-small cell lung cancer(NSCLC).Methods From Jan.1997 to Dec.2006,214 patients with patho logically or cytologically proven stage Ⅳ NSCLC were included in this analysis.Of those patients,98 re ceived radiotherapy concurrently with 3-week cycle chemotherapy(group A),18 received radiotherapy con currently with weekly chemotherapy(group B) ,44 received chemotherapy alone,37 received radiotherapy a lone and 13 received sequential chemo-radiotherapy.The primary tumor was treated by three-dimensional conformal radiotherapy(3DCRT) or conventional radiotherapy with conventional fraefionation or late-course accelerated hyperfraction (LA H RT).Group A received 21-28 days cycle cisplatin-based chemotherapy (cis platin combined with PTX,DTY,NVB or Vp-16) ,and group B received weekly DDP combined with PTX or topteeon for 4-6 weeks.Results The follow-up rate was 99%.The 1-and 2-year overall survival rates of group A,group B,chemotherapy alone,radiotherapy alone and sequential chemo-radiotherapy were 41% and 11% ,16% and 0,31% and 7% ,34% and 10% ,26% and 3% ,respectively(x2 = 11.18,P=0.025).The patients with concurrent 3DCRT,LAHRT and radiotherapy dose≥70 Gy had better survival in group A than those in chemotherapy alone group.Patients who received≥2 cycles chemotherapy with concurrent radio therapy had longer survival time than those who had ≥2 cycles chemotherapy alone. Conclusions Con current chemotherapy and 3DCRT,LAHRT with the dose ≥70 Gy can improve the overall survival of patients with stage Ⅳ non-small cell lung cancer.

OBJECTIVE: To determine the correlation of serum soluble CD14 (sCD14) level with the injury of vascular endothelial cells and chronic low grade inflammation in newly diagnosed Type 2 diabetes (T2DM). METHODS: ELISA was used to examine serum sCD14 and serum soluble E-selectin (sE-selectin) level, while immunoturbidimetric assay was used to detect serum high sensitivity C reactive protein (hsCRP). RESULTS: The levels of serum sCD14, sE-selectin, and hsCRP in newly diagnosed T2DM group were higher than those in the euglycemic group [sCD14: (300.7+/-136.6) ng/mL vs. (273.3+/-86.0) ng/mL); sE-selectin: (21.3+/-7.7) ng/mL vs. (32.9+/-11.4) ng/mL; hsCRP: (1.45+/-1.21) mg/L vs. (2.37+/-1.45)mg/L], and there was a significant difference in the latter two parameters between the 2 groups(P<0.01). In the patients with newly diagnosed T2DM, after matching blood pressure, blood sugar, and blood lipid, the levels of serum sCD14, sE-selectin, and hsCRP in the obese group were higher than those in the non-obese group. There was no significant difference in the former 2 parameters between the 2 groups. The serum sE-selectin was correlated with fasting blood sugar (r=0.369, P<0.001), 2-hour postprandial blood sugar (r=0.421, P<0.001), glycosylated hemoglobin (r=0.291, P=0.005), sCD14(r=0.312, P=0.002), and homeostasis model assessment-insulin resistance(r=0.247, P=0.018) in the newly diagnosed T2DM group. Stepwise regression ana-lysis showed that the serum sCD14 was one of the chief influencing factors on serum sE-selectin. CONCLUSION Serum sCD14 levels tend to increase in newly diagnosed T2DM patients, especially in the obese diabetic patients, which is one of the chief influencing factors to induce the injury of vascular endothelial cells. The innate immunity mediated by Toll-like receptor 4 may take part in the injury of vascular endothelial cells in newly diagnosed T2DM patients.
Aged ; C-Reactive Protein ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; immunology ; E-Selectin ; blood ; Female ; Humans ; Lipopolysaccharide Receptors ; analysis ; blood ; Male ; Middle Aged ; Regression Analysis ; Solubility ; Toll-Like Receptor 4 ; immunology

Objective To evaluate the differences of toxicities,therapeutic efficacy and immune function between induction chemotherapy followed by sinusoidal chrono-modulated infusion and flat intermittent infusion of cisplatin (DDP)with intensity-modulated radiotherapy (IMRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC).Methods Seventy patients with biopsydiagnosed stages Ⅲ and Ⅳ B NPC (according to the 2010 UICC staging system) were treated with two-cycle induction chemotherapy before chemoradiotherapy in Guizhou Cancer Hospital.The TPF chemotherapy regimen was administered as follows:The TXT and DDP with the dose of 75 mg/m2 was carried out by bolus infusing for the first day,the 5-FU with 750 mg · m-2 · d-1 was carried out by continuous intravenous pumping for the first day to fifth day(120 h).The induction chemotherapy was 21 days per cycle,for two cycles.After that all patients were randomly treated with 2-3 cycles of sinusoidal chronomodulated infusion or flat intermittent constant rate infusion of DDP with IMRT.Using a multi-channel programmed pump,the patients were given 12 h continuous infusions of DDP (100 mg/m2) for day one,repeated every 3 weeks for 2-3 cycles.DDP was administered from 10:00 am to 10:00 pm.Concurrent radiotherapy regimen was administered as follows:GTVnx 69.96-73.92 Gy/33 f,PTVnx 69.96 Gy/33 f,PTVnd 69.96 Gy/33 f,PTV1 60.06 Gy/33 f,PTV2 50.96 Gy/28 f.Results The main toxicities of chemoradiotherapy in the group of sinusoidal chrono-modulated infusion were bone marrow suppression:leukocytes,and then nausea,oral mucositis and hemoglobin.The main toxicities of chemoradiotherapy in the group of flat intermittent constant rate infusion were bone marrow suppression:hemoglobin,leukocytes,and then nausea,oral mucositis.No significant differences were observed for toxicities(P ＞ 0.05).After concurrent chemoradiotherapy,the complete response rate (CR),partial response rate (PR),stable disease rate(SD),progressive disease rate (PD) and overall response rate (ORR) were 11.4％,85.7％,2.9％,0 and 97.1％ in the group of sinusoidal chrono-modulated infusion.The CR,PR,SD,PD,ORR in the group of flat intermittent constant rate infusion were 22.9％,74.2％,2.9％,0,97.1％,respectively.However,there was no significant differences of effect in the two Arms (P ＞ 0.05).For sinusoidal ehrono-modulated infusion and flat intermittent infusion group,the 2-year overall survival(OS) were 82.9％ and 94.3％ respectively,the 2-year progression-free survival(PFS) were 77.1％,91.4％ respectively,and the 2-year distant metastasis free survival (DMFS) were 82.9％,91.4％ respectively.The value of CD3 + in the group of sinusoidal chrono-modulated infusion was higher than the group of flat intermittent constant rate infusion after therapy (Z =3.254,P ＜ 0.05).The value of CD4 +,CD8 +,CD16 + CD56 +,CD19 +,and CD4 +/CD8 + had no differences in two Arms (P ＞ 0.05).Conclusions No significance differences on the toxicities,therapeutic efficacy and survival were observed between the two groups,but immune function might be improved in the sinusoidal chrono-modulated infusion group.

Objective:To investigate the protective effect and possible mechanism of Tangshenbao on renal damage in diabetic nephropathy (DN) rats.Methods:Totally 36 SPF male SD rats were randomly divided into normal group ( n=6) and model group ( n=30). The DN rat model was prepared by single high-dose intraperitoneal injection of STZ. According to the random number table method, the rats were divided into model group, irbesartan group and Tangshenbao low-, medium- and high-dosage groups, with 6 rats in each group. Drug intervention lasted for 8 weeks. The general condition and body weight of rats in each group were recorded. The blood glucose, kidney index, 24 h urine protein (24 h UTP), SCr and BUN levels were detected. The pathological morphology of renal tissue was observed by PAS staining and transmission electron microscopy. The mRNA and protein expressions of Ets-1, TGF-β1, Smad2 and Smad3 in renal tissue were detected by real-time fluorescence quantitative PCR and Western blot. Results:Compared with model group, the body weight of Tangshenbao low, medium and high dose groups and irbesartan group significantly increased ( P<0.01). The kidney index decreased ( P<0.05 or P<0.01). The contents of 24 hUTP, BUN and SCr significantly decreased ( P<0.05 or P<0.01). Glomerular volume was significantly reduced ( P<0.05 or P<0.01), the mRNA expressions of Ets-1 (1.59 ± 0.06, 1.47 ± 0.04, 1.31 ± 0.03, 1.39 ± 0.03 vs. 1.64 ± 0.04), TGF-β1 (1.65 ± 0.05, 1.59 ± 0.03, 1.38 ± 0.05, 1.49 ± 0.04 vs. 1.77 ± 0.08), Smad2 (1.48 ± 0.05,1.39 ± 0.05, 1.22 ± 0.03, 1.31 ± 0.04 vs. 1.54 ± 0.05), Smad3 (1.57 ± 0.04, 1.48 ± 0.03, 1.28 ± 0.03, 1.39 ± 0.02 vs. 1.64 ± 0.05) in renal tissue of rats significantly decreased ( P<0.05 or P<0.01), the protein expressions of Ets-1 (1.33 ± 0.32, 1.16 ± 0.38, 0.77 ± 0.06, 0.84 ± 0.06 vs. 1.97 ± 0.43), TGF-β1 ( 1.35 ± 0.14, 1.24 ± 0.22, 0.94 ± 0.13, 1.07 ± 0.06 vs. 1.63 ± 0.20), Smad2 (1.24 ± 0.26, 1.14 ± 0.31, 0.77 ± 0.28, 0.85 ± 0.19 vs. 1.72 ± 0.34) and Smad3 (1.29 ± 0.14, 1.19 ± 0.21, 0.85 ± 0.39, 0.90 ± 0.37 vs. 1.76 ± 0.21) decreased ( P<0.05 or P<0.01). Conclusion:Tangshenbao can improve renal damage in DN rats, and its mechanism may be related to the inhibition of Ets-1 expression and TGF-β1/Smads signaling pathway.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a group of systemic small vasculitis characterized by the detection of ANCA in serum. Bactericidal permeability enhancing protein (BPI) is one of the target antigens of ANCA. BPI-ANCA-associated vasculitis is not common clinically, and the combination of bronchiectasis is not accidental. The paper reported a case of BPI-ANCA-associated vasculitis with renal damage combined with bronchiectasis. We reviewed relevant literature to explore the characteristics of BPI-ANCA-associated vasculitis and the correlation between bronchiectasis and ANCA-associated vasculitis, so as to improve the clinician's understanding on this disease.

Objective: To compare the adverse events, immune status, and short-term efficacy between chronomodulated chemotherapy (CCR) and routine chemotherapy (RCR) combined with intensity modulated radiotherapy (IMRT)in the treatment of patients with locally advanced nasopharyngeal carcinoma. Methods: A total of 159 patients with newly diagnosed locally advanced nasopharyngeal carcinoma were randomized into the CCR group and the RCR group to evaluate the short-term efficacy and adverse events. Results: No significant difference was found in CR, PR, SD, and PD between the CCR group and the RCR group (P>0.05), and no significant difference was observed in the response rate (CR+ PR) between the two groups (P>0.05). The incidence of leukopenia(Z=-2.222, P<0.05), neutropenia(Z=-1.999, P<0.05), vomiting(Z=-2.298, P<0.05), and oral mucositis(Z=-3.571, P<0.05)of the CCR group was lower than those of the RCR group with statistical significance. The CD16+ 56+ lymphocyte cell count was higher in the CCR group than that in the RCR group(Z=-2.332, P<0.05). Conclusions As a novel invention, CCR combined with IMRT can reduce the incidence and severity of treatment-related adverse events and improve immune status without diminishing clinical efficacy, therefore deserving clinical application.

Objective: To evaluate the long-term effect and safety of chrono-chemotherapy combined with intensity modulated radiotherapy (IMRT) in locally advanced nasopharyngeal carcinoma (NPC). Methods: 160 patients with locally advanced NPC were randomly divided into a chrono group and conventional group according to random number table. In the first stage, all patients underwent two cycles of induced chemotherapy, consisting of docetaxel, cisplatin and 5-Fu every 21 days. Notably, patients received chrono-moduated chemotherapy according to circadian rhythm in the chrono group, and conventional chemotherapy in the conventional group. Then, 21 days after the completion of first stage, three cycles of concurrent cisplatin chemotherapy every 21 days were given to all patients during IMRT. The median follow-up after the completion of radiotherapy was 31 months. Long-term side effects and the survival of patients were observed. Results: Patients in the chrono group had significantly lower rates of hearing loss (22.72%), dysphagia (0) and neck fibrosis (4.54%) compared with those in the conventional group (39.13%、8.69%, 15.94%, respectively, all P<0.05). Meanwhile, the 1- year overall survival rates (97.0% vs 92.8%), 3-year overall survival rates (80.3% vs 81.2%), 1-year progression free survival rates (95.5% vs 87.0%), 3-year progression free survival rates (71.2% vs 73.9%), 1-year locoregional relapse-free survival rates (97.0% vs 95.7%), 1-year locoregional relapse-free survival rates (92.4% vs 92.8%), 1-year distant metastasis-free survival rates (97.0% vs 98.6%) and 3-year distant metastasis-free survival rates (90.9% vs 91.3%) between the chrono group and the conventional group were not statistically significant (all P>0.05). Conclusions Compared with conventional chemotherapy, chrono-chemotherapy combined with IMRT didn′t affect long-term survival, but reducing the incidence of adverse events in patients with locally advanced NPC.