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Objective To observe the protective effects of Diazoxide (DZ) on myocardial ischemia and reperfusion (I/R) in non-diabetic rats with stressed hyperglycemia and to explore its possible mechanism. Methods The stressed hyperglycemia (SHG) myocardical I/R model was prepared by ligation of the left anterior descending branch of the coronary artery for 30 minutes and reperfusion for 120 minutes on the healthy adult Sprague-Dawley (SD) rats. Blood sugar was required up to 10 mmol/L in the qualified animal model after ischemia for 30 minutes. The 48 successful model rats were randomly divided into 4 groups (12 in each group): I/R group, low, medium and high dose DZ treated group (LIPO group, MIPO group, HIPO group). Sham-operated group (sham group) was only threaded without deligation. I/R group, LIPO group, MIPO group and HIPO group were challenged to 0.1% dimethyl sulfoxide (DMSO), DZ (0.1% DMSO dissolved) 4, 7, 10 mg/kg for 2 mL, respectively after ischemia for 25 minutes. Hemodynamics indicators were continuously monitored. After reperfusion for 120 minutes, blood glucose, serum creatine kinase (CK) concentration and lactate dehydrogenase (LDH) activity were detected, myocardial infarction area was analyzed by triphenyltetrazolium chloride (TTC) staining, myocardial ultrastructure was observed by electron microscope, expressions of phosphorylated protein kinase B (p-Akt) and phosphorylated glycogen synthase kinase-3β (p-GSK-3β) were detected by Western Blot. Results Compared with sham group, I/R group had an elevated blood glucose, decreased heart rate (HR), systolic diastolic dysfunction, increased myocardial enzymes. Obvious necrosis of myocardium, myocardial tissue edema, mitochondria swelling, cristae, disappearing glycogen granules were observed under electron microscope with TTC staining. After reperfusion for 120 minutes, comparing with I/R group, blood glucose of HIPO group was significantly increased (mmol/L: 16.93±3.22 vs. 14.65±3.61, P < 0.05); the maximum rate of left ventricle internal pressure drop (-dp/dt max) of LIPO group was improved (mmHg/s: -1 055±16 vs. -982±10, P < 0.05) and the infarct size was evidently shrunk [(32.45±3.54)% vs. (41.30±3.21)%, P < 0.05]; left ventricular systolic pressure (LVSP) of MIPO group and HIPO group [LVSP (mmHg, 1 mmHg = 0.133 kPa): 60±2, 74±4 vs. 54±4], left ventricular end-diastolic pressure [LVEDP (mmHg): 24.6±1.5, 18.9±1.3 vs. 27.9±1.6], the maximum rate of left ventricle internal pressure were increased [+dp/dt max (mmHg/s): 1 049±37, 1 262±75 vs. 975±17], and -dp/dt max (mmHg/s: -1 068±21, -1 321±63 vs. -982±10) were improved in different degrees (all P < 0.05); CK (kU/L: 10.7±0.5, 11.0±1.3 vs. 12.9±1.0), LDH (kU/L: 6.8±0.2, 7.8±0.1 vs. 8.8±0.1) was evidently decreased (all P < 0.05), infarct size was smaller [(31.24±2.45)%, (30.81±2.68)% vs. (41.3±3.21)%, all P < 0.05], electron microscope showed that the myocardial injury was repaired. After reperfusion for 120 minutes, compared with sham group, expressions of p-Akt and p-GSK-3β in I/R group have obviously reduced (grey value: 0 vs. 0.187±0.018, 0.110±0.045 vs. 0.200±0.081, both P < 0.05). Compared with I/R group, expressions of p-Akt in HIPO group and p-GSK-3β in LIPO group, MIPO group and HIPO group were obviously increased (grey value: 0.101±0.009 vs. 0; 0.180±0.057, 0.270±0.062, 0.280±0.039 vs. 0.110±0.045, all P < 0.05). But there were significant increase in MIPO group and HIPO group. There was no significant difference in HR among different treatment groups. Conclusions I/R with SHG can significantly inhibit the activity of PI3K/Akt-GSK-3β signaling pathways, middle and high dose of DZ has a protective effect on I/R myocardium complicating with SHG, and middle dose will not lead to evident increase of blood glucose; DZ may act on GSK-3β through PI3K/Akt-GSK-3β signaling pathways, phosphorylate it and inhibit its activity, so as to develop the cardioprotective effect.

[ ABSTRACT] AIM: To observe the effect of circadian rhythms on wound healing of mouse corneal epithelium. METHODS:The C57BL/6 male mice were used in the study.A part of corneal epithelium (2 mm in diameter) was struck off by a golf-like knife to form a round wound area.The dynamics of epithelial healing in the wound area were ob-served under microscope with fluorescein staining.In addition, with related antibodies and DAPI, the dynamic changes of the neutrophils, platelets and dividing cells were also investigated.RESULTS:The healing rates in LL group (12 h light/12 h light) and DD group (12 h dark/12 h dark) were obviously slower than that in LD group (12 h light/12 h dark), mainly showing delayed re-epithelialization, decreased epithelial cells, increased diameter of blood vessel, and delayed re-cruitment of neutrophils and platelets, but more cell number.CONCLUSION:Disruption of circadian rhythms significant-ly inhibits the wound healing of corneal epithelium, mainly through delaying the inflammation and re-epithelialization, but aggravating the inflammatory responses.

OBJECTIVETo explore the reason, key diagnosic point and therapeutic method of the incisions fat colliquation or infections at early stage after operation of lumbar disc herniation.

METHODSFrom July 2007 to May 2012, clinical data of 11 patients with incision fat liquefaction or early infection after lumbar discectomy were retrospectively analyzed. There were 5 males and 6 females with an average age of 43.1 years, and the mean time of incisions fat colliquation or infection was 5 days and a half after operation. The main clinical features included local wound pain aggravating, fervescence, fresh seepage in the wound, and blood inflammatory index increased, etc. The wound could heal at the first treatment stage or not was an evaluation standard of curative effect.

RESULTSAll patients were followed up with an average period of 21 months. The wounds of 10 cases healed at the first stage without recurrence and complications. In 1 case infected by staphylococcus aureus, distal part of the wound present local red, swelling and with wave motion at 2 months after operation, staphylococcus aureus infection was confirmed after puncture and bacterial culture, and 1 thrum was found after local incision. The wound healed after change dressings for 1 week, without recurrence after followed up for 13 months.

CONCLUSIONPreventing the risk factors before operation, minimizing invasive technique during operation reasonable antibiotics application for the lumbar operation reguiring placement objects, and correctly handling with wound after operation could prevent and reduce the incidence of incisions fat liquefaction or infection after operation of lumbar disc herniation. For incision fat liquefaction or infection, early diagnosis, debridement, VSD negative pressure irrigation and drainage, to choosing sensitive antibiotics according to the results of drug sensitivity, may contribute to wound early healing and decrease complication.

Adipose Tissue ; pathology ; Adult ; Aged ; Female ; Humans ; Intervertebral Disc Displacement ; surgery ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Staphylococcal Infections ; pathology ; therapy ; Surgical Wound Infection ; pathology ; therapy ; Time Factors

OBJECTIVETo analyze and evaluate the fatigue of shoulder skeletal muscle caused by different lifting loads with surface electromyography (sEMG).

METHODSAccording to the loading standard of1 Repetition Maximum (1RM), ten male volunteers performed 3 tasks of upper limb flexion, i.e. 10%, 50% and 90%-1RM. During action process, the signals of Upper Trapezius (UT), Lower Trapezius (LT), Serratus Anterior (SA) and Anterior Deltoid (AD) were recorded by sEMG. The Mean Amplitude (MA) served as an index to evaluate the changes in skeletal muscle fatigue.

RESULTSThe scores of Borg were 15.6, 15.9 and 15.2 for 3 loads of 10%-1RM, 50%-1RM and 90%-1RM, respectively (P > 0.05). The mean amplitudes (MAs) of Upper Trapezius, Lower Trapezius, Anterior Deltoid and Serratus Anterior in shoulders increased obviously. Under the load intensity of 10%-1RM, the MAs of Upper Trapezius and Anterior Deltoid increased significantly (P < 0.05), which were 0.898 and 0.736, respectively. After the exhaustion, the contribution of mean amplitude in shoulder muscle did not change significantly (P > 0.05).

CONCLUSIONThe low-load action for long time can induce easily the fatigue of upper trapezius and anterior deltoid.

Adult ; Electromyography ; Humans ; Lifting ; Male ; Muscle Fatigue ; physiology ; Muscle, Skeletal ; physiology ; Shoulder ; physiology ; Workload

To investigate the effect of recombinant human growth hormone (rhGH) on JAK2-STAT3 pathway and the growth of gastric cancer cell lines at different GHR expression status, the eukaryotic expression vector targeting human GHR (pGPU6/GFP/Neo-shGHR and pGPU6/GFP/Neo-scramble) was constructed and transfected into MGC803 cells by Lipofectamine 2000. Stable expressive cell lines were obtained by G418 screening. The expression of GHR was analyzed by Western blotting. After being stimulated with rhGH, cell growth was detected by MTT assay. Cell cycle and apoptosis were examined by flow cytometry. The components of JAK2/STAT3 signaling pathway were detected by Western blotting. There is no significant difference of GHR expression between MGC803 and pGPU6/GFP/Neo-scramble-transfected cells (named as MGC803-NC) (P > 0.05). Compared with MGC803, the GHR expression in pGPU6/GFP/Neo-shGHR-transfected cells (named as MGC803-shGHR) decreased significantly (protein decreased 50%). The cells were treated with rhGH at 0, 150 and 300 ng x mL(-1), the growth rate of MGC803 and MGC803-NC increased significantly, PI and the number of G2/M phase cells all increased significantly, and apoptosis decreased significantly. Western blotting revealed that the expression of pJAK2 and pSTAT3 was up-regulated after being treated with rhGH in MGC803 and MGC803-NC cells. In contrast, similar change was not observed in MGC803-shGHR cells. Knockdown of GHR gene may decrease the sensitivity of gastric cancer cells to rhGH, and down-regulating of components of the expression of JAK2/STAT3 signaling pathway may be the potential mechanisms.
Apoptosis ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Down-Regulation ; Human Growth Hormone ; genetics ; pharmacology ; Humans ; Janus Kinase 2 ; metabolism ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Receptors, Somatotropin ; genetics ; metabolism ; Recombinant Proteins ; genetics ; pharmacology ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; Stomach Neoplasms ; metabolism ; pathology ; Transfection

Worldwide sales of biologic drugs exceeded 100 billion USD in 2011. About 32% is from therapeutic monoclonal antibody (mAb). With many blockbuster biopharmaceutical patents expiring over the next decade, there is a great opportunity for biosimilar to enter the worldwide especially emerging market. Both European Medicines Agency (EMA) and Food and Drug Administration (FDA) have introduced regulatory frameworks for the potential approval of biosimilar mAb therapeutics. Rather than providing a highly abbreviated path, as in the case for small molecule chemical drug, approval for biosimilar mAb will require clinical trial and the details will be very much on a case-by-case basis. Since mAb is the dominant category of biologic drugs, mAb will be the focus of this review. First, the United States (US) and European Union (EU) approved mAb and those in phase 3 trials will be reviewed, then strategies on how to win biosimilar competition will be reviewed.
Animals ; Antibodies, Bispecific ; therapeutic use ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Biosimilar Pharmaceuticals ; standards ; Clinical Trials, Phase III as Topic ; Drug Approval ; European Union ; Humans ; United States ; United States Food and Drug Administration

Chronic kidney disease (CKD) is a serious chronic disease with high incidence, poor prognosis, and a variety of complications. Indoxyl-sulfate (IS) and p-cresol sulfate (PCS) are two typical gut-derived uremic toxins, which are produced by the co-metabolism of intestinal microbes and the host. With the progression of CKD, gut-derived uremic toxins such as IS and PCS accumulate in patients with CKD and thereafter accelerate the progression of CKD. Gut microbiota is closely related with CKD, and targeting gut microbiota to regulate gut-derived uremic toxins synthesis and metabolic pathways may be a promising strategy to delay the progression of CKD. In this paper, the relationship between gut microbiota, gut-derived uremic toxins, and CKD was analyzed, and the strategy to delay the progression of CKD by targeting gut microbiota and uremic toxins metabolism pathway was proposed.

Objective To comparatively analyze the preoperative value of the size of primary breast cancer presenting as a mass by ultrasonography and by mammography.Methods The tumor size data obtained preoperatively by mammography and by ultrasonography were retrospectively analyzed in all the patients pathologically diagnosed with primary breast cancer in our hospital from July 2006 to July 2009.The Pearson correlation coefficient was calculated for the size of tumors between with pathological method and with each of the imaging modalities.Results A total of 57 patients with breast cancers took both of imaging modalities including 51 cases of infiltrating ductal cancer,4 cases of infiltrating lobular cancer,and 2 of ductal carcinoma in situ.The ranges of the maximum diameter of tumor was 0.6-11.8 cm and mean value was (2.3±2.1) cm by pathological examination,0.6-12.6 cm and mean value was (3.4±2.9)cm by mammography and 0.7-10.2 cm and mean value was (2.4±1.8)cm by ultrasonography,respectively.The Pearson correlation coefficient in the accuracy of imaging assessments was superior to those by ultrasonography (r=0.744,P＜0.05) than those by mammography (r=0.544,P＜0.05).Conclusion Ultrasonography is more accurate than mammography for size assessment of primary breast cancer.

Objective To comparatively analyze the changes of environmental risk factors in 9 years in an area polluted by arsenic coal-burning in Xingren County of Guizhou Province,in order to provide evidence for reasoning the occurrence and development as well as its effective prevention and control.Methods Epidemiological sampling methods was used to conduct follow-up investigation on 181 arsenism patients who were diagnosed in 1998 in arsenic polluted area.Control group included 65 residents who lived far from polluted area of 12 km.The follow up investigation included age,sexuality,family economic situation,time of use or stop use of arsenic coal, ventilation of the room,desiccation of food etc.Diethyl dithiocarbamate silver(Ag-DDC)method was used to detect arsenic content of coal,soil,air,water and rice,corn,chili;Single factor and multivariate factors non-conditional Logistic regression models were used to analyze exposure factors of patients and related environmental risk factom, and the differences of those in 1998 and 2006 were compared. Results The arsenic content in indoor and outdoor air,coal,chili and corn went down from 0.0880 and 0.0220 mg/m3,397.20,45.07 and 2.64 mg/kg in 1998 to 0.0790 and 0.0070 mg/m3,93.01,3.46 and 1.50 mg/kg in 2006. Arsenic contents of other samples were less than national standard. The analysis of single factor and multivariate factors non-conditional Logistic regression showed that time of using high arsenic coal,age,fluorosis and smoking(x2 = 50.159,12.195,37.69,6.358,P ＜ 0.05 or ＜ 0.01 ) were still the main risk factors for arsenism,while family economic situation was still influential factors (X2 = 4.614,P ＜ 0.05);Ventilation of the room changed from a risk factors at 1998 to an influencing factors at 2006(X2 = 38.093,P ＜ 0.01 ). Single factor non-conditional Logistic regression model analysis showed that food desiccation by arsenic coal-burning and educational level were no longer risk and influencing factors,while food preservation and gender had become influencing factors(x2 = 17.463,11.004,all P ＜ 0.01 ) nine years after. Conclusions Environmental arsenic pollution in arsenism area in Guizhou Province has been obviously improved after nine years. However,the continued existence of low doses of arsenic pollution is still a major cause of failure of controlling arsenism. Time of using high arsenic coal,age,smoking,fluorosis,family economic situation and ventilating room are closely related to the occurrence and the development of arsenism. Prohibition of use of high arsenic coal,furnace improvement,health education and economic development are effective measures