Small cell lung cancer(SCLC) is a type of neuroendcorine cancer with high growth fraction, early metastatic spread and poor prognosis, accounting for approximately 15％ of all newly diagnosed lung cancer cases.Patients with SCLC are generally treated with platinum-based chemotherapy in combination with radiotherapy.Despite good responses to chemotherapy in the early stage of treatment, patients develop drug resistance and recurrence soon.There has been limited success with the targeted approaches in clinical trials completed in the past several years.Novel targeted and more effective treatment strategies for SCLC are in urgent need With increasing translational research and a better understanding of the molecular basis of small cell lung cancer, a number of new targeted drugs such as kinase inhibitors, angiogenesis inhibitors, apoptosis inducers, proteasome inhibitors, epigenetic regulators, immune checkpoint inhibitors have been developed and investigated in various preclinical studies.Some of them have entered clinical trials.At the same time, a number of novel treatment strategies such as immunotherapy and combination treatment receive attention.This review summarizes potentially molecular targeted therapies that have been developed and employed recently, and ongoing and future clinical trials in attempt to improve patient outcomes in SCLC, and meanwhile to invite future potential SCLC new treatment strategies.

Objective The aim of this study was to investigate the distribution and clinical significance of CD8+ T cells in bladder cancer tissues in situ.Methods Immunohistochemistry were used to examine the distribution of CD8+ T cells in bladder cancer tissues,which were obtained from January 2003 to December 2009 from 302 patients.Among all the patients,262 were male while 40 were female;mean age is 60 years;tumor size ≤ 3 cm was in 235 and tumor size ＞ 3 cm was in 67;Unifocal tumor was in 214 and multifocal tumors were in 88.Amount of tumor stage Ta-T1 was 212 and T2-T4 was 90.Sixteen patients have lymph node metastasis.Histological low grade was diagnosed in 175 and histological high grade was diagnosed in 127.According to the differences between anatomic structure and cellular composition,bladder tumor tissues can be classified to two localization patterns:(1) intratumoral regions,defined as tumor cell nests;(2) stromal regions,defined as stromal areas that lack direct contact with tumor cells.Therefore,we divided 302 bladder cancer patients into two groups based on the median frequency of intratumoral CD8+ T cells (median,3/× 400 high resolution) and stromal CD8+ T cells (median,37/× 400 high resolution),respectively.x2 analysis was used to evaluated the correlation between CD8+ T cell density and clinicalpathological variables.Kaplan-Meier analysis and Cox proportional hazards regression models were applied to estimate overall survival (OS).Results CD8+ T cells were predominantly located in the intratumoral regions (mean,14 ± 2/× 400 high resolution) rather than in associated stromal regions (mean,50 ± 3/× 400 high resolution,P ＜ 0.05).The density of intratumoral CD8+ T cells was inversely associated with age (P =0.026),tumor size (P ＜ 0.05) and tumor stage (P ＜ 0.05),and could represent a favorable prognostic predictor of OS (HR =0.427,P =0.003).However,the density of stromal CD8+ T cells was positively associated with age (P =0.004) and histological grade (P ＜ 0.01),and could represent an adverse prognostic predictor of OS (HR =2.206,P =0.009).Conclusions Our findings suggest that intratumoral/ stromal CD8+ T cells could potentially serve as favorable/ adverse prognostic markers for bladder cancer patients,respectively.

Objective To investigate the effects of mesenchymul stem cells(MSCs) transfected with human home oxygenase- 1 gene on the inflammatory cytokines and the ventricular remodeling after myocardial infarction in rats.Method MSCs were acquired from the hone marrow of adults rats.They were isolated,purified cultured,and transfected with Adv-HO-1,or Adv-GFP in vitro before transplantation.At 1 hours after left coronary artery ligation,Adv-HO-1-MSCs or Adv-GFP-MSCs marked with DAPI were directly injected into the horder of cardiac infarction in rats.At 4 days after transplantation,western blot analysis was used to measure HO-1 protein expression in the the horder of cardiac infarction.The levels of VEGF,bFGF,HGF protein expression were measured by ELISA,and the levels of TNF-α,IL-1β,IL-6,IL-10 mRNA expression were measured by RT-PCR.The rat heart function was measured by echocardiography.At 4 weeks after transplantation,ventricular remodeling and pathological changes were measured by HE and Masson staining.Results The Adv-HO-1-MSCa treated group showed marked increase of HO-1 rotein (P<0.05),and displayed significant increase of montioned cytokines above,P <0.05,compared with other groups.The Adv-HO-1-MSCs treated group displayed significant reduction of mRNAs expreesion of TNF-α,IL-1β,IL-6,and significant increase in IL-10 mRNA expression,with P<0.05,compared with others.Conclusions HO-1-MSCs could secrete multiple cytokines in infarction hearts,and had beneficial effects on inflammatory cytokines,remodeling processes and cardiac function.

ObjectiveTo assess the safety and clinical values of video-laryngoscope in spontaneous respiration tracheal intubation for emergency patients. Methods Seventy-nine patients,who needed the endotracheal intubation,were recruited in our department between January 2010 and December 2010,and were randomly ( random number) divided into two groups according to consultative sequence.Forty patients (group A ) were operated with traditional laryngoscope and thirty-nine patients (group B ) with videolaryngoscope.The operative time and success rate of tracheal intubation,Cormack-Lehane classification,as well as adverse events,were recorded.The heart rate ( HR ),mean arterial blood pressure ( MAP),respiratory rate ( RR ),and saturation of pulse oxygen ( SpO2 ) were observed pre-operation,during operation and 2 min post-operation.Results( 1 ) The Cormack-Lehane classification in group A were significantly lower than in group B. (2) The operative time of tracheal intubation in group B was significantly less than that in group A [(35.6+12.7) svs. (58.3 ± 13.5) s; P＜0.05] ; and one-time success rate of tracheal intubation in group B was higher than that in group A ( 84.6％ vs.52.5％ ; P ＜0.05).(3) Compared to group B,the HR and MAP in Group A were significantly increased at t2 and t3 ( P ＜ 0.05 ). ( 4 ) The adverse events,including restlessness,bucking and injury,were significantly decreased in group B than those in group A ( P ＜ 0.05 ).ConclusionsThe video-laryngoscope used in spontaneous respiration tracheal intubation,could improve Cormack-Lehane classification,short operative time,enhance one-time success rate and reduce adverse evevnts.

Aim To establish a model of the vascular endothelial cell (VEC) injury in SDrats.Methods SD rats were randomly divided into the control and the modelgroups. The model rats were injected with adrenaline diluted to 2. 5 times 0. 05 mg?100 g-1 (tid) for 5 d continously. From the 4th d, they were irritated for 5 min in the0℃ cold-water in the middle between adrenaline injections.The control rats weregiven 0. 9% NS as above. At 6th d, blood samples were taken from carotid arteries ofthe rats and the CEC counts, t - PA、PAI activities, 6-keto-PGF1? concentrations andthe platelet aggregation rate(max) were detected respectively. Results In the modelgroup, as compared with those in the control group, t - PA activity and 6-keto-PGF1?concentration decreased significantly(P

Deflazacort (DFZ, a prodrug) is well absorbed and rapidly metabolized into the active metabolite 21-hydroxydeflazacort (21-OH DFZ) after oral administration. The aim of this study is to evaluate the pharmacokinetic properties of 21-OH DFZ in healthy Chinese volunteers after a single and multiple oral administration of DFZ tablets under fed condition. Twelve volunteers (six males and six females) were administered a single dose of 6 mg or 12 mg or 24 mg of DFZ in three different periods separately, according to the 3 x 3 Latin square design. Between each administration period there was a washout period of one week. The multiple-dose study of 12 mg dose DFZ per day for 7 consecutive days was started after a 1 w washout period when the single-dose study completed. The pharmacokinetic parameters of 21-OH DFZ after the single oral administration of 6 mg, 12 mg and 24 mg DFZ tablets were as follows: (37.7 +/- 11.6), (61.5 +/- 17.7) and (123 +/- 23) ng x mL(-1) for C(max); (1.90 +/- 0.32), (1.96 +/- 0.27) and (2.13 +/- 0.34) h for t1/2; (96.6 +/- 25.9), (190 +/- 44) and (422 +/- 107) ng x h x mL(-1) for AUC(0-14 h), respectively. After the multiple dose administration, the mean plasma concentration at steady-state C(av) was (7.00 +/- 1.66) ng x mL(-1) and the degree of plasma concentration fluctuation DF was 7.7 +/- 1.2. The results showed that the pharmacokinetic characteristics of 21-OH DFZ in healthy Chinese volunteers were linear over the dose range of 6 to 24 mg. No significant gender differences were found in the pharmacokinetics of 21-OH DFZ in healthy Chinese volunteers. After the multiple dose administration of 12 mg DFZ for 7 d, no accumulation of 21-OH DFZ in healthy Chinese volunteers was observed.
Administration, Oral ; Area Under Curve ; Asian Continental Ancestry Group ; Female ; Healthy Volunteers ; Humans ; Male ; Pregnenediones ; pharmacokinetics ; Tablets

Objective To evaluate therapeutic ERCP in the treatment and preventing the recurrence of acute biliary pancreatitis(ABP).Methods One hundred and seventeen patients of ABP were randomly divided into two groups,ERCP treatment group(n=49)and non-ERCP control group(n=68).Changes of clinical symptoms and laboratory indexes were recorded accordingly.Follow-up study was for all the patients. Results Of the 117 with ABP,99 cases were mild(MABP)and 18 ones were severe(SABP).The days of relief of abdominal pains,normalization of hepatic function indexes and hospitalization were significantly shorter in ERCP treatment group than that in control group.The complications related to endoscopic therapy were not found.All patients had got followed-up visits for average 20(range 5-37)months(94.0%).The re- currence rate in the ERCP group 0(0/46)were significantly lower than that in the control group 46.8%(29/ 62)(P

BACKGROUND:Development of new coronary thrombolytic agents is hot in the market. A new drug, mutated recombinant tissue-type plasminogen activator (rtPAm), is the product of mutation of tPA by changing binding loci with plasminogen activator inhibitor (PAI)-1 to reduce the degradation. In vitro test has demonstrated that the activity of rtPAm is much higher than rtPA in the absence of PAI. The present study is to observe the efficacy of mutated recombinant tissue-type plasminogen activator (rtPAm) in coronary thrombolytic therapy. METHODS:A total of 30 adult beagles were equally divided into 5 groups after thrombi:vehicle group, urokinase group, rtPAm low-dose group, rtPAm medium-dose group, and rtPAm high-dose group. Thrombolytic effect and myocardial infarction were observed after thrombolytic therapy. RESULTS:In the urokinase group, time to reperfusion was (15.8±3.8) minutes. TIMI 2 flow was demonstrated in 4 beagles, TIMI 3 flow in 2, and re-occlusion in 4 after 90 minutes respectively. In the low-dose rtPAm group, time to reperfusion was (15±4.5) minutes; TIMI 2 flow was demonstrated in 2 beagles, TIMI 3 flow in 4, and re-occlusion in 2 after 90 minutes. In the high-dose rtPAm group, time to reperfusion was (7.5±2.6) minutes. None of the beagles showed re-occlusion after 90 minutes. The infarction areas were (2.1+0.9)％ in the medium-dose rtPAm group and (0.7+0.4)％ in the high-dose rtPAm group, which decreased significantly than those in the low-dose rtPAm group. The aggregation rate in the medium-dose and high-dose rtPAm groups decreased significantly than that in the urokinase group. CONCLUSION:rtPAm may serve as a thrombolytic agent with platelet-targeted fibrinolysis and antiplatelet aggregation activities.

OBJECTIVETo study the effect of peri-implantitis inflammatory microenvironment on the biological function of jaw bone osteoblasts.

METHODSPrimary mandible osteoblasts from peri-implantitis and normal tissue were isolated and cultured. Third-generation purified osteoblasts were identified and detected. The proliferative activity of osteoblasts was evaluated through MTT assay. Osteocalcin (OCN), Runx2, and collagen I (Col I) mRNA levels were examined by real-time quantitative polymerase chain reaction. OCN protein levels were determined by Western blot.

RESULTS: After 4 d of culture, the proliferative activity of osteoblasts from peri-implantitis became lower than that of normal tissue ( P <0.05). After 7 d of culture, OCN, Runx2, and Col I mRNA expression decreased ( P <0.05). The OCN protein levels also decreased ( P <0.05).

CONCLUSIONPeri-implantitis inflammatory microenvironment can decrease the proliferation and differentiation activity of mandible osteoblasts.

Bone and Bones ; Cell Differentiation ; Humans ; Mandible ; Osteoblasts ; Osteocalcin ; Peri-Implantitis ; RNA, Messenger

OBJECTIVETo investigate the efficacy mechanisme of chicory extract interventing abdominal obesity rat from the aspect of gut bacteria.

METHODMale SD rats were randomly divided into five groups, namely the normal group, model group, large and small dose group of chicory and the fenofibrate group. Normal group was given deionized water, the other group was given fructose water and give the medical treatment of chicory and fenofibrate. Assay triglycerides, total cholesterol, LDL and HDL by biochemical methods and measure body weight and abdominal circumference and microscopicly observe the count changes of gut bacteria through real-time PCR method.

RESULTCompared with normal group, the triglyceride level and abdominal circumference were significantly higher (P < 0.05), weight and high-density lipoprotein increased but no significant changes and E. coli, lactobacillus increased significantly. Compared with model group, chicory extract large and small dose group and the fenofibrate group can significantly reduce triglyceride levels (P < 0.05), reduce the number of E. coli and Lactobacillus and increase the number of bifidobacteria. The fenofibrate group can significantly reduce total cholesterol and high-density lipoprotein levels.

CONCLUSIONThe chicory's treatment effect on abdominal obesity is significant. The efficacy mechanisme intervention abdominal obesity may be related to the reduction of the number of lactic acid bacteria and E. coli and the increase of bifidobacteria.

Animals ; Bacteria ; classification ; genetics ; isolation & purification ; Biodiversity ; Chicory ; chemistry ; metabolism ; Cholesterol ; metabolism ; Gastrointestinal Tract ; microbiology ; Humans ; Male ; Microbiota ; Obesity, Abdominal ; metabolism ; microbiology ; Plant Extracts ; metabolism ; Rats ; Rats, Sprague-Dawley ; Triglycerides ; metabolism