Abstract?AIM: To observe the effects of different antidiabetic therapies on macular thickness in diabetes patients without fundus complication.?METHODS: The macular thickness was measured by optical coherence tomography ( OCT) .The retina volume on the center of macula was scanned, and it generated automatically the average thickness data of three rings and nine areas of 1mm, 3mm and 6mm.The data were statistically analyzed.?RESULTS: Healthy control group, oral hypoglycemic drug group and insulin treatment group were enrolled. Each group included 22 cases 22 eyes.The macular retinal thickness of healthy control group is 268.09±17.97μm (the 1st ring), 340.41 ±22.25μm ( the 2nd ring) and 298.14 ± 12.90μm ( the 3 rd ring ) , respectively. The macular thickness of oral hypoglycemic drug group is 260.00 ± 18.17μm (the 1st ring), 335.44±21.12μm (the 2nd ring) and 295.63 ±15.92μm ( the 3rd ring), respectively.The macular thickness of insulin therapy group is 271.01 ± 26.09μm (the 1st ring), 340.86±17.10μm (the 2nd ring) and 298.57 ±12.14μm ( the 3rd ring ), respectively. Comparison of the macular thickness of the 1st ring among 3 groups was insignificant (F=1.21, P=0.31), neither the comparison of the 2nd ring (F=0.35, P=0.71), neither the comparison of the 3rd ring (F=0.22, P=0.81).? CONCLUSION: Compared with healthy individuals, both oral antidiabetic medicines and insulin therapy don't alter the macular thickness of patients with diabetes while without fundus complication.

Objective To study the clinical effect of Shenkang injection combined with valsartan in the treat-ment of patients with early stage diabetic nephropathy,and its influence on the expression changes of homocysteine ( Hcy) ,transforming growth factor β1 ( TGF -β1 ) , the inflammatory cytokines high sensitive C -reactive protein (hs-CRP),and interleukin-6 (IL-6).Methods 138 cases of early stage diabetic nephropathy were randomly divided into control group ( conventional treatment, valsartan act as antihypertensive drug ) and treatment group ( treated with Shenkang injection combined with valsartan) by digital table.The total effective rate,glycemic index, renal function,levels of Hcy and TGF-β1,expression levels of inflammatory cytokines of two groups were compared. Results The total effective rate of the treatment group (91.30%) was significantly higher than the control group (76.81%) (χ2 =5.004,P<0.05).The values of FPG,2h PG,HbAlc,UAER,CysC and Scr were lower in the treat-ment group compared with the control group (t=4.514,3.743,4.754,6.214,3.925,3.777,all P<0.05).Com-pared with the control group,the concentrations of Hcy,TGF-β1,hs-CRP and IL-6 decreased significantly[ (11. 78 ±1.95)μmol/L vs (9.21 ±1.64)μmol/L,(71.32 ±14.88) mg/L vs (60.04 ±11.75) mg/L,(7.07 ±1.25) mg/L vs (5.81 ±1.14)mg/L,(50.24 ±21.86)pg/mL vs (32.55 ±17.01)pg/mL],the differences were statistical-ly significant (t=8.378,4.942,6.187,5.305,all P<0.05).Conclusion Shenkang injection combined with val-sartan for the treatment of early stage diabetic nephropathy has significant clinical efficacy.It can improve patients're-nal function and reduce blood sugar levels.The effects may be related with inflammatory response inhibition and Hcy, TGF-β1 levels reduction.

ObjectiveTo investigate the clinical effects of androgen blockade combined treatment for the elderly with middle and late prostate cancer.Methods 63 patients (average age of 69.3 years) with middle and late prostate cancer (above stage T3 ) were studied retrospectively from June 2001 to August 2009.21 cases were treated by operation of bilateral orchidectomy independently.15 cases were treated by castration independently (enantone 3.75 mg or zoladex 3.6 mg/month,hypodermic injection for one year).27 cases were treated by bilateral orchidectomy plus maximum androgen blockade (MAB) (bicalutamide 50 mg,qd,fulutimad 250 mg,rid,po.)Results The survival rates of 1,2,3 years were 100.0％,90.0％,75.0％ in operation group,100.0％,86.7 ％,73.3％ in drug group,and 100.0％,96.2％,84.6％ in MAB group,respectively.The survival rates of 3 years was higher in MAB group than the other groups(x2 =4.460,P＜0.05).The levels of PSA within 3 months decreased and urinary flow rates in three groups increased after treatment than before treatment (t =2.641,3.074,6.703,P ＜ 0.01 ) with no differences among the groups.The relieve period of validity was longer in MAB group than in other groups (F=16.57,P＜0.01 ).Conclusions MAB may be more effective for the elderly with middle and late prostate cancer than castration therapy independently.

Objective To explore the changes in β-catenin expression and their significance in ultraviolet ray (UV)-induced development of skin tumor in mice.Methods The back of 60 mice was irradiated for various durations to establish tumor models.Ten mice receiving no irradiation served as the control.Fifteen mice were sacrificed respectively on week 2,4,6 and 8 after the beginning of irradiation and skin tissue specimens were resected from the back of these mice.Hematoxylin and eosin staining was conducted to observe the histopathological changes of skin,and immunohistochemistry and real time fluorescence PCR were carried out to detect the expression of β-catenin.Results Along with the UV irradiation,the exposed skin experienced a series of histological changes.The β-catenin expression was located in cell membrane in unirradiated mice and those irradiated for 2 weeks.There was an attenuation in the expression of β-catenin in cell membrane but an increment in the ectopic expression of β-catenin in 7,9 and 9 of the 15 mice receiving 4-,6- and 8-week irradiation respectively.Compared with the control mice,a significant increase was observed in the ectopic expression rate of β-catenin in mice receiving 4,6 and 8 weeks of irradiation (all P ＜ 0.045).The relative expression level of β-catenin mRNA was 4.893,7.857,10.452,12.481 and 14.702 in unirradiated mice,mice receiving 2,4,6 and 8 weeks of irradiation,respectively,with statistical differences between the 5 groups (all P ＜ 0.05).Conclusions There is an ectopic nuclear expression of β-catenin in cells of UV-irradiated mouse skin,which may be involved in the initiation and progression of skin tumors.

Objective To observe the effect of intravenous low intensity laser radiation (ILLLI) combined with traditional Chinese medicine on TXB2, 6-Keto-PGF1? and Ang II of the rabbits of experimental diabetic stroke. Method 35 successfully modeled rabbits, after alloxian injection for diabetes and photochemical radiation for stroke, were randomized into four treatment group-control group (B), ILIB group (C), a group with compound treatment of ILIB and TCH (D), TCM treatment group (E), and 7 unmodeled rabbits were made as the normal group (A). TXB2, 6-Keto-PGF1? and Ang II level were observed and compared. Result Compared with group B, group C and E can significantly rectify the disorderly TXB2, 6-Keto-PGF1? and Ang II, Group D was better than C and E. Conclusion ILLLI combined with TCM can effectively rectify the TXB2, 6-Keto-PGF1? and Ang II level, reduce nervous injury, cure diabetes cerebral infarction.

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.

Aim To discuss the repairing mechanism of Qinbai Qingfei Concentrated pellets to lung tissue of rats infected by mycoplasma. Method 60 Wistar rats weighting 80~100 g, male to female:1 ∶ 1) were di-vided into six groups randomly ( 10 rats in each group): blank group, model group, positive group, the high、middle and low dose groups of Qinbai Qingfei Concentrated pellets. Rats were infected through nasal intubation drip of MP. After 10 days of administration, concentrations of IL-6 , IL-8 AND TNF-α in serum of MPP rats were detected. Left pulmonary tissues of rats were collected to observe the lung tissue pathological change by HE staining and right pulmonary tissues were used to detect the transforming growth factor-beta ( TGF-β) and surface activity related protein A( SP-A) mRNA expression level by real-time quantitative PCR ( RT-PCR) and TGF-βand SP-A protein expression by (Western blot. Result Qinbai Qingfei Concentrated) pellets significantly inhibited inflammation of lung tis-sue, reduced the expression of TGF-β and increased the expression of SP-A in the lung tissue of rats infec-ted by mycoplasma. Conclusion Qinbai Qingfei Con-centrated pellets can inhibit epithelial-mesenchymal transition ( EMT ) , of alveolar type Ⅱ epithelial cells by reducing the content of TGF-β and restore the nor-mal morphology and function of the lung by increasing the expression of SP-A.

Small molecule covalent inhibitors, or called as irreversible inhibitors, are a type of inhibitors that exert their biological functions by irreversibly binding to target through covalent bonds. Compared with non-covalent inhibitors, covalent inhibitors have obvious advantages in bioactivity. Nevertheless, these agents may also exhibit larger toxicity once off-target effects arise. This "double-edged swords" property often leads drug researchers to avoid attaching them. In recent years, some problems such as drug resistance are difficult to be solved with reversible inhibitors leading researchers to pay more attention on the covalent inhibitors. In this review, we shall make a short summary to the recent research progress of covalent inhibitors and the interaction modes between covalent inhibitors and their target protein residues.
Amino Acids ; chemistry ; Antineoplastic Agents ; chemical synthesis ; chemistry ; therapeutic use ; Antiviral Agents ; chemical synthesis ; chemistry ; therapeutic use ; Drug Discovery ; Drug Resistance ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; therapeutic use ; Hepatitis C ; drug therapy ; Humans ; Molecular Structure ; Neoplasms ; drug therapy ; Protein Binding ; Protein Kinase Inhibitors ; chemical synthesis ; chemistry ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; Serine Proteinase Inhibitors ; chemical synthesis ; chemistry ; therapeutic use

Bronchi ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Middle Aged ; Pneumonectomy ; Pulmonary Sclerosing Hemangioma ; pathology ; surgery