Objective To study the protective effects of rosiglitazone against early skin changes in experimental diabetic rats. Methods Diabetic models were established in male Wistar rats aged 8 to 10 weeks by using streptozotocin (STZ). Then, 39 experimental diabetic rats were equally divided into insulin-treated diabetic group (DI group), rosiglitazone-treated diabetic group (DR group), diabetic control group (DC group),and 13 normal rats served as the control (C group). The rats were given subcutaneous insulin (1 - 2 U) twice daily in DI group, intragastric rosiglitazone (5 mg/kg) once daily in DR group, and intragastric sterile water in DC and C groups. Sixteen weeks later, heart blood samples were collected from all the rats for the measurement of tumor necrosis factor (TNF)-α, interleukin (IL)-6, C reactive protein (CRP), superoxide dismutase (SOD) and P substance (SP) levels, then the rats were killed and tissue samples were obtained from the medial area of the dorsal skin and subjected to pathological observation, measurements of skin as well as dermal thickness, and immunohistochemical examinations for the expression of advanced glycation end products(AGEs) and peroxisome proliferator activated receptor-γ (PPAR-γ). Results The levels of IL-6, TNF-α and CRP in the DC group were significantly higher than those in the C group (135.05 ± 43.39 ng/L vs. 99.92 ±32.36 ng/L, 1.45 ± 0.67 μg/L vs. 0.86 ± 0.60 pg/L, 3.51 ± 0.62 mg/L vs. 2.54 ± 1.31 mg/L, all P < 0.05),while no significant difference was found between C group and DI group or DR group (all P> 0.05). Decreased levels of SOD and SP were noted in the DC group (70.71 ± 37.52 U/ml, 22.22 ± 7.93 ng/L), compared withthe C group (137.76 ± 27.6 U/mL, 29.57 ± 3.74 ng/L, both P< 0.01), DI group (149.96 ± 13.25 U/mL, P<0.01; 29.79 ± 5.21 ng/L, P< 0.05) and DR group (128.50 ± 38.27 U/mL, P< 0.01; 33.35 ± 15.0 ng/L, P<0.05 ). Micrometer measurements indicated that the skin thickness was significantly lower in the DC group than in the C group, DI group and DR group (0.77 ± 0.18 mm vs. 1.59 ± 0.26 mm, 1.47 ± 0.50 mm and 1.22 ±0.47 mm, P < 0.01, 0.01, 0.05 respectively). Histological observation found a mild disarrangement of epidermal cells, shrinkage, swelling and degeneration of dermal collagen as well as progressive atrophy or disappearance of subcutaneous fat in the DC group. No obvious histological changes appeared in the DI or DR group. Immunohistochemistry indicated that AGEs and PPAR-γ proteins, which were stained into brown granules, were located in the vascular basement membrane, stromal cells, etc, of skin. The DC group showed the highest expression of AGEs but lowest expression of PPAR-γ. Conclusions There is an accumulation of AGEs and elevated expressions of inflammatory factors in the skin of experimental diabetic rats, and rosigLItazone shows a protective effect against the early skin changes.

Objective To observe the histopathological features of early skin lesions and serum inflammatory mediators changes in the diabetes mellitus(DM) rats.Methods A total of 50 Wistar rats at 8 to 10 weeks of age were divided into normal control group(C group,n=25) and diabetic group(DC group,n=25).The rats of DC group were given a high-glucose and high-fat diet for 2 weeks to induce insulin resistance and then an intraperitoneal injection of 35 mg/kg streptozotocin.All 25 rats were identified to be diabetic models with their fasting blood glucose over ≥7.0 mmol/L.Four rats of C group or DC group were killed to take the skin tissues in the 4th,8th and 12th weekend.In the 16th week,the heart blood samples of the left 13 rats of C group and 10 rats of DC group were collected to measure TNF-?,IL-6 and C-RP levels,and the skin samples were also taken for pathological observation and full-thickness and dermal thickness measurement.Results In the 16th week,the TNF-?,IL-6 and C-RP levels of DC group were significantly higher than the normal group(P

Objective To investigate the effects of rosiglitazone on serum levels of tumor necrosis factor-? (TNF-?),interleukin-6 (IL-6),C-reactive protein (C-RP) and superoxide dismutase (SOD),and early skin changes in the diabetic rats.Methods The rats were divided into normal control group (C group,n=13),diabetic control group (DC group,n=13),diabetes and insulin treatment group (DI group,n=13),diabetes and rosiglitazone treatment group (DR group,n=13).The diabetic rat models were established with high-fat diet for 2 weeks followed by intraperitoneal injection of 35 mg/kg streptozotocin injection,the rats were idenfied as diabetic when their fasting blood glucose (FBG) over 7.0 mmol/L.The living rats were given corresponding treatment,subcutaneous injection of 1 to 2 U/d insulin,intragastric injection of 5 mg/(kg?d) rosiglitazone,or sterile water.Heart blood samples of rats from each group were collected to measure TNF-?,IL-6,C-RP and SOD levels in the 16th weekend.Also the skin was taken for pathological observation and full-thickness as well as dermal thickness measurements.Results The serum levels of IL-6,TNF-? and C-RP in diabetic group were significantly higher than those in normal group (P

Objective To explore the mechanism of therapeutic action of needle knife “regulating sinews and treating bones” on knee osteoarthritis (KOA) by observing the effect of needle knife intervention on KOA rabbit behaviors, mechanical characteristics of patellar ligament (PL), and expressions of interleukin-4 (IL-4), matrix metalloproteinase-3 (MMP-3) and aggrecan in knee cartilages.Methods Forty New Zealand rabbits were randomly allocated to blank, model, needle knife and electroacupuncture groups, 10 rabbits each. A rabbit model of KOA was made by the modified Videman method of immobilization in extension position. After model making, the needle knife and electroacupuncture groups received needle knife and electroacupuncture treatments, respectively. A behavioral assessment was made using the modified Lequesne MG knee grade evaluation method in every group after model making and treatment. The samples were taken after treatment. PL tension, stress relaxation and creep state were tested using a Bose Electro Force 3300 protracted test machine. Cartilage cell IL-4 expression was examined by ELISA. MMP-3 mRNA and aggrecan mRNA expressions were detected by real-time PCR.Results After model making, there was a statistically significant difference in the Lequesne MG score between the model and blank groups (P<0.01); there was no statistically significant difference in the Lequesne MG score between the needle knife or electroacupuncture group and the model group (P>0.05). There was a statistically significant post-treatment difference in the Lequesne MG score between the needle knife or electroacupuncture group and the model group (P<0.01,P<0.05) and between the needle knife and electroacupuncture groups (P<0.05). There were statistically significant post-treatment differences in PL maximum stress, maximum displacement, elastic modulus, stress relaxation rate and creep rate between the model and blank groups (P<0.01,P<0.05). There were statistically significant post-treatment post-treatment differences in PL maximum stress, maximum displacement, elastic modulus, stress relaxation rate and creep rate between the needle knife and model groups (P<0.01,P<0.05). There was a statistically significant post-treatment difference in elastic modulus between the electroacupuncture and model groups (P<0.01). The IL-4 content and aggrecan mRNA expression decreased significantly and MMP-3 mRNA expression increased significantly in the model group after model making and there were statistically significant differences compared with the blank group (P<0.01,P<0.05). After treatment, the IL-4 content increased significantly in the needle knife and electroacupuncture groups compared with the model group (P<0.01,P<0.05) and aggrecan mRNA expression tended to increase in the two groups. The regulation of aggrecan mRNA and MMP-3 mRNA expressions was better in the needle knife group than in the electroacupuncture groups, but there was no statistically significant difference compared with the model group (P>0.05).Conclusion The mechanism of action of needle knife treatment on KOA may be that it improves ligament mechanical characteristics, regulates intra-articular stress environment, and modulates aggrecan mRNA and MMP-3 mRNA expressions and inhibits cartilage degeneration through IL-4 mechanical signal pathway, to produce the therapeutic effect of “regulating sinews and treating bones”.

Objective To study dynamic changes of T cell subsets and CD3＋HLA-DR＋T cells in peripheral blood of composite tissue transplantation-hand allograft recipients. Methods The levels of CD3＋、CD3＋CD4＋、CD3＋CD8＋、CD3＋HLA-DR＋T cells and ratio of CD4/CD8 in peripheral blood of hand allograft recipients in different periods were examined by using flow cytometry.The recipients before transplantation were as the control groups.Results The first day after transplantation,the levels of CD3＋、CD3＋CD4＋、CD3＋CD8＋、CD3＋HLA-DR＋T cells and ratio of CD4/CD8 all began to descend.The 3th to 5th day after transplantation,the levels were the lowest.The 8th day,the levels of CD3＋、CD3＋CD4＋、CD3＋CD8＋、CD3＋HLA-DR＋T cells and ratio of CD4/CD8 were eventually rised and go to stable 15th day after transplantation.But the levels of CD3＋、CD3＋CD4＋and value of CD4/CD8 were still lower than those of the contols,and the levels of CD3＋CD8＋、CD3＋HLA-DR＋T cells were higher distinctly.Conclusion Dynamic changes of T cell subsets and active T cells in peripheral blood of composite tissue transplantation-hand allograft recipients were accordant with that of renal allograft recipients with stable period and with stable clinical state of the hand transplantation recipients.

Objective:To dynamically describe the drug concentration change in different time in vivo to understand the in vivo be-havior patterns and rules of drugs, provide reference for performing individual treatment and avoiding adverse drug reactions and lay foundation for dynamic description of physiological pharmacokinetic model. Methods:A two-compartment model was established using Simulink dynamic simulation and used in curve fitting and parameter estimation. The results from the model were compared with those from 3P97 software. Results:There was no significant difference between the results from the dynamic model and those from 3P97 soft-ware. Conclusion:The dynamic model can be used to dynamically simulate two-compartment model for oral administration. The re-sults from the dynamic simulation are more direct, and can correct the fitting error in 3P97 software.

OBJECTIVE:To provide reference for promoting the prior usage of essential medicines and scientifically selecting of antitumor medicines in the national and local drug reimbursement list. METHODS:Entering the Human Resources and Social Se-curity Bureau websites in 10 cities(Beijing,Shanghai,Guangzhou,Nanjing,Wuhan,Xi’an,Chengdu,Shenyang,Jinan and Gui-yang),drug reimbursement list was downloaded to statistically analyze the containing of antitumor medicines(including 24 essential medicines). RESULTS:In antitumor medicines,there were 5 cities with more than 100 varieties,of which Shanghai had 255 vari-eties,which was far more than other cities;the numbers of medicines in class A were near 30 in all the cities except Beijing(67 va-rieties),and the number of class B was highest in Shanghai and lowest in Beijing. All the drug reimbursement lists in 10 cities con-tained 24 antitumor essential medicines,however,the classification was different according to the dosage forms,among which, parts of formulations of cytarabine(injections),doxorubicin(injections),busulfan (often release oral dosage forms),fluorouracil (often release oral dosage forms,injections),cyclophosphamide(often release oral dosage forms,injections),methotrexate(often release oral dosage forms,injections)and cisplatin were classified as class A medicines in all cities;oxaliplatin(injections)and pa-clitaxel (injections) were classified as class B medicines;busulfan,fluorouracil,cyclophosphamide and methotrexate were classi-fied as class B in Shanghai only. CONCLUSIONS:There are some differences in the distribution of antitumor essential medicines in drug reimbursement list in each city,the varieties in developed cities are relatively more,and developing cities are less. It is sug-gested to consider the tumor epidemiology characteristics and economic situations,reasonably select antitumor essential medicines into drug reimbursement list and reasonably adjust the proportion of class A and B to ensure the basic medication and drugs’reim-bursement.

Objective The purpose of the present study is to compare the pharmacokinetic and biodistribution properties of 99Tcm N-mercaptopyridine-N-oxide (99 Tcm N-MPO) with 99 Tcm-sestamibi (99 Tcm-MIBI) in normal dogs, and to investigate the potential of 99TcmN-MPO as a myocardial perfusion agent in canines with acute myocardial infarction. Methods Twelve healthy mongrel dogs were injected intravenously with 99TcmN-MPO (n = 6) or 99Tcm-MIBI (n = 6). Tracer kinetics in body fluids were determined by collecting blood of 1 ml via a femoral vein catheter at 30 s, 1,2,3,4,5, 10, 20, 30, 40, 60and 90 min post-injection (p. i.). The collected blood samples were weighed and counted for radioactivity in a γ-counter. Anterior and posterior planar γ-camera images were collected at 10, 20, 30, 60, 90, and 120 min after injection, with organ uptake quantified by region-of-interest (ROIs) analysis. For comparison, 99Tcm-MIBI was also evaluated in the same twelve dogs. Canine infarct models were set up by micro-invasive interventional embolization. SPECT images in the canine infarct model were collected 24 hours after myocardial infarction at 30 min and 60 min after the administration of 99Tcm N-MPO (n = 5) or 99Tcm-MIBI (n = 5). Results Both of 99Tcm N-MPO and 99Tcm-M1BI had a rapid blood clearance with less than 50% of initial radioactivity remaining at 1 min [99TcmN-MPO: (35. 77 ± 6. 31)% ID/mg ,99Tcm-MIBI (34. 46 ± 6. 83) % ID/mg] and less than 5% at 30 min p. i. [99Tcm N-MPO(3. 11 ± 1.44) % ID/mg,99Tcm-MIBI (2.93 ±0. 39)% ID/mg] . After injection, 99TcmN-MPO showed significant accumulation in the myocardium and prolonged retention. This rapid liver clearance of 99TcmN-MPO led to favorable heart-to-liver ratios, reaching values of 0. 54 ±0. 06 at 10 min, 1.02 ±0. 06 at 30 min, and 1.38 ±0. 06 at 60 min p. i.In contrast, the heart/liver ratio of 99Tcm-MIBI remained low at all time points (0. 46 ± 0. 03 at 10 min,0. 63 ±0. 03 at 30 min, and 0. 62 ± 0. 12 at 60 min p. i.). SPECT imaging studies in canines with acute myocardial infarction indicated that good visualization of the left ventricular wall and perfusion defects could be achieved at 30 min after administration of 99TcmN-MPO, but not 99Tcm-MIBI. Conclusion The combination of high heart uptake and rapid liver clearance makes 99TcmN-MPO a promising new radiotracer for myocardial perfusion imaging.

Objective To investigate the differences of various two-stent techniques in vitro and virtual bench testing. Methods Stent implantation with classic crush, double kissing ( DK) crush and culotte stenting techniques were performed in the silicone simulation model of bifurcation vessels with various distal bifurcation angles. The whole processes were recorded by a micro-focus camera. Results Distal side branch (SB) re-crossing in classical crush technique left a significant gap without stent coverage near the carina in T type bifurcation model after final kissing balloon inflation (FKBI) . The gap was also noted in either classic crush with proximal SB re-crossing or DK crush with two times proximal SB re-crossing in T type bifurcation model. The size of the gap in DK crush technique was smaller than that of classic crush. In Y type bifurcation model, both DK crush and culotte stenting left no gap compared to T type bifurcation model. Two times proximal SB re-crossing in culotte stenting resulted in a new stent carina formation after FKBI. Conclusions Distal bifurcation angle was an anatomatic predictor of gap formation in two-stent technique. In T type bifurcation model, the size of gap in DK crush technique was smaller than that of classic crush. It was suggested to perform two times proximal SB re-crossing for DK crush technique and distal SB re-crossing for culotte stenting.

Objective To determine the effectiveness and safety of stereotactic body radiotherapy (SBRT)-CyberKnife for oligometastatic prostate cancer.Methods From May 2012 to February 2017,31 patients treated by CyberKnife were retrospectively reviewed,with a median age of 67 years(range 52 to 83 years),including 50 oligometastatic and 2 primary prostate cancer patients.The median PSA level was 8.4 ng/ml(range 0 to 300.0 ng/ml) and PSA test was performed every month.PSA progression-free survival (PSA-PFS),time to initiation of androgen deprivation therapy (ADT) and local control rate (LCR) were measured as the main outcomes.Results SBRT was well tolerated and were performed as planned in all patients.No SBRT related acute or late toxicities were observed.No bone fracture was observed in patients treated by bony targeted radiotherapy.The median follow-up after SBRT was 20.7.months (range 1.2-58.3 months).The median PSA-PFS was 5.3 months (range 0-58.3 months).1-year,2-year,and 4-year PSA-PFS was 52.0％,36.7％ and 36.7％ respe ctively.PSA level decrease was observed in 21 oligometastatic prostate cancer patients after SBRT,with median PSA-PFS of 12.3 months (range 1.2-58.3 months).PSA level increase was observed in 29 oligometastatic prostate cancer patients after SBRT.Six local recurrence were observed resulting in an actuarial 1-year,2-year and 3-year LCR of 90.4％,86.9％ and 82.6％,respectively.Twelve patients treated without ADT after SBRT,with median follow-up of 8.6 months (range 2.9-58.3 months) in this subgroup.Seven patients were added ADT after SBRT,with the median time from SBRT to initiation of ADT of 13.3 months (range 3.0-24.0 months) in this subgroup.Twelve patients were treated with ADT continuously after SBRT.Conclusions CyberKnife seems to be a safe and effective treatment with tolerated adverse events and good local control for patients with oligometastatic prostate cancer.