Sulfonylureas are widely used oral anti-diabetic drugs. However, its long-term usage effects on patients' lifespan remain controversial, with no reports of influence on animal longevity. Hence, the anti-aging effects of chlorpropamide along with glimepiride, glibenclamide, and tolbutamide were studied with special emphasis on the interaction of chlorpropamide with mitochondrial ATP-sensitive K⁺ (mitoK-ATP) channels and mitochondrial complex II. Chlorpropamide delayed aging in Caenorhabditis elegans, human lung fibroblast MRC-5 cells and reduced doxorubicin-induced senescence in both MRC-5 cells and mice. In addition, the mitochondrial membrane potential and ATP levels were significantly increased in chlorpropamide-treated worms, which is consistent with the function of its reported targets, mitoK-ATP channels. Increased levels of mitochondrial reactive oxygen species (mtROS) were observed in chlorpropamide-treated worms. Moreover, the lifespan extension by chlorpropamide required complex II and increased mtROS levels, indicating that chlorpropamide acts on complex II directly or indirectly via mitoK-ATP to increase the production of mtROS as a pro-longevity signal. This study provides mechanistic insight into the anti-aging effects of sulfonylureas in C. elegans.

Objective To investigate the incidence of abnormalities and adverse reactions of intrauterine device ( IUD) by three‐dimensional transvaginal ultrasound ,and guide the correct selection of IUD . Methods Female volunteers who came to our hospital for health check‐up from July 2016 to February 2018 were selected as subjects to obtain information of the belt loop time and number of loops . T hree‐dimensional transvaginal ultrasound was used to observe and record the IUD types and positions . T he incidence of location abnormalities ,adverse reactions and cervical lesions of differnet types of IUD were retrospectively analyzed . Results T wo thousand one hundred and thirteen eligible subjects were included in the study ,including 423 cases of McuIUD ,506 cases of circular ring ,405 cases of uterine ring ,372 cases of T‐ring and 407 cases of γ ring . T he statistical analysis showed that the incidence of adverse reactions after wearing rings was as high as 34 .07% ,and the adverse reaction rate of different IUD was different . McuIUD had the highest incidence of adverse reactions ,compared with the circular ring ,the uterine ring ,the T‐ring , and the γ ring ( 47 .99% vs 25 .88% ,27 .41% ,37 .10% ,33 .66% ; all P ＜ 0 .05 ) . Different IUD had different incidence of adverse reactions . T he low back pain rate in McuIUD and γ ring were higher than the other 3 IUDs . T he low back pain rate of McuIUD was higher than the circular ring ,the uterine ring and the T‐ring ( 23 .4% vs 15 .71% ,14 .07% ,13 .7 1% ; all P ＜ 0 .01 ) . Different types of IUD had different incidence of location anomalies . T he descending rate of the circular ring was higher than that of the McuIUD and γ ring ( 6 .32% vs 3 .30% ,3 .19% ; all P＜ 0 .05 ) ,and no statistically significant difference compared with the uterine ring and T‐ring ( 6 .32% vs 3 .45% ,4 .30% ; all P ＞0 .05 ) . T he incarceration rate of the mother ring was higher than that of the circular ring ,uterine ring and T‐ring ( 3 .07% vs 0 ,0 .25% ,0 .54% ;all P ＜0 .01) . T he intrauterine rotation rate of uterine ring and γ ring were higher than that of McuIUD , circular ring and T‐ring ( all P ＜0 .01) . Pregnancy ＞1 and ring times ≥2 were related with the occurrence of adverse reactions of IUD ( P ＜ 0 .05 ) . T he incidence of cervical erosion in the T‐ring was the highest compared with the McuIUD ,circular ring ,uterine ring ,and γ ring ( 30 .65% vs 16 .78% ,16 .80% ,18 .02% , 17 .69% ; all P ＜0 .01) . Conclusions The incidence of adverse reactions is higher in women with different types of IUD . T he incidence of different types of abnormal IUD position is different . T he frequency of pregnancy and band ring are related to the occurence of adverse veactions to IUD .

To evaluate the changes of myocardial viability and systolic function in rabbits with different ischemic periods by layer‐specific strain of ultrasound speckled tracking imaging ( ST I) and low dose dobutamine stress echocardiography ( LDDSE ) . Methods T hirty‐six rabbits were randomly divided into 3 groups( n ＝12) : ①myocardial infarction group Ⅰ :coronary artery occlusion for 45 min ; ②myocardial infarction group Ⅱ :coronary artery occlusion for 60 min ; ③ myocardial infarction group Ⅲ :coronary artery occlusion for 90 min . Echocardiography examinations were performed at baseline ,after ligation and low dose dobutamine stress . After the experiment ,rabbits were killed and the hearts were taken to assess viable or nonviable mycardium , triphenyl tetrazolium chloride and Evans blue staining were applied . Results ①After coronary artery ligation ,left ventricular ejection fraction( LVEF) decreased in 3 groups ( all P ＜ 0 .05 ) , the ventricular global endocardial longitudinal strain ( GSLsys‐endo ) , global myocardial longitudinal strain( GSLsys‐mid) ,and global epicardial longitudinal strain( GSLsys‐epi) decreased in 3 groups ( all P ＜ 0 .05 ) ,the longitudinal strain of endocardium ( SLsys‐endo ) ,longitudinal strain of myocardium ( SLsys‐mid) ,longitudinal strain of epicardium ( SLsys‐epi) decreased in viable myocardial ( all P＜0 .05) ; ②While low dose dobutamine stressing ,the GSLsys and SLsys increased in each groups ,and the GSLsys‐endo ,GSLsys‐mid ,GSLsys‐epi and SLsys‐endo of viable segments in each group were increased ( P＜0 .05) ; ③After ligation and low dose dobutamine stress ,the GSLsys in endocardium in three groups were different( P ＜0 .05) ,and the SLsys in endocardium of viable segments in three groups were different ( P＜0 .05) . Conclusions Layer‐specific strain of STI combined with LDDSE can accurately evaluate the changes of myocardial viability and systolic function in different ischemic periods ,and the longitudinal strain of endocardium is more sensitive ;moreover ,with the increase of coronary artery occlusion time ,the infarcted myocardium increases ,myocardial viability and systolic function decrease .

Objective To assess the diagnostic performance of Mainz ultrasound scoring system combined with 3D-power Doppler ultrasound(PDU) and CA125 in differentiating benign and malignant pelvic tumors.Methods The randomly selected patients were divided into two groups according to the pathological results,the benign group ( n =61) and malignant group ( n =79).Mainz scoring system was used to evaluate the tumor score of 150 pelvic masses,3D-PDU scan was performed to obtain vascular index (VI),blood flow index (FI),and vascular flow index (VFI) by two doctors with more than 5 years working experience in double-blind.The VI,FI,VFI and serum markers of two groups were compared to evaluate the value of Mainz scoring system and in combination with 3D-PDU and CA125 in the differential diagnosis of benign and malignant tumors. Results Compared with benign group,VI,FI and VFI increased significantly in malignant group(all P < 0.01). The Kappa indices of using Mainz ultrasound scoring system and using Mainz ultrasonic scoring system combined with 3D-PDU to distinguish benign and malignant pelvic masses were 0.79 and 0.83,respectively.The sensitivity,specificity and accuracy of Mainz score to evaluate benign and malignant pelvic tumors were 85.1%,78.2% and 82.0%,respectively,the sensitivity,specificity and accuracy were 89.2%,86.3% and 88.0% when combined with 3D-PDU. As compared with 3D-PDU and serum markers,the sensitivity was 96.4%,specificity was 90.9% and accuracy was 94.0%,respectively. Conclusions Mainz ultrasound scoring system has important clinical value in distinguishing benign and malignant pelvic masses,when combined with 3D-PDU its sensitivity,specificity can be improved significantly.The sensitivity and specificity are further improved after combining of clinical serological markers.

BACKGROUND: Individual three-dimensional (3D) scaffolds can be constructed by 3D printing via Computer Aided Design based on the given anatomical measurements of related tissues. A rapid and accurate reconstruction of bone, cartilage, muscle and vessel also can be achieved by 3D printing; however, many problems still remain unsolved.OBJECTIVE: To summarize the principle and classification of 3D printing, the classification, characteristics and histocompatibility of scaffolds through reviewing the articles addressing 3D printing applied in bone tissue engineering,thereby providing theoretical foundation for the study on the construction of tissue-engineered bone.METHODS: PubMed and CNKI databases were retrieved for the literatures regarding the application of 3D printing technology in bone tissue engineering published from January 2001 to January 2017 using the keywords of three-dimensional printing, rapid prototyping manufacturing, bone tissue engineering in English and Chinese,respectively. Finally, 30 articles were reviewed and discussed in accordance with the inclusion and exclusion criteria.RESULTS AND CONCLUSION: The microstructures of normal tissues can be reconstructed and seed cells are printed on the 3D scaffolds synchronously by 3D printing technology. Moreover, the scaffold degradation and cell differentiation are synchronous, which contributes to tissue repair. Biological ceramics have been widely used in bone tissue engineering because of its good biocompatibility and mechanical properties. However, the urgent problems such as angiogenesis and cellular signal transduction still need to be addressed.

Objective To evaluate the effect of pharmacological postconditioning on longitudinal myocardial function in rabbits' model of myocardial inshemia-reperfusion using layer-specific strain of ultrasound speckle tracking imaging.Methods Forty healthy rabbits were randomly divided into two groups:ischemia-reperfusion group (IR) and pharmacological postconditioning group (ATP-PPost). Echocardiography examinations were performed at baseline,45 min after ligation and 30 min,60 min,120 min after reperfusion.Pathological examinations were applied in two rabbits randomly selected from each group at 45 min after ligation and 30 min,60 min after reperfusion and at the end of experiment.Results①After coronary artery ligation,left ventricular ejection fraction (LVEF) decreased in two groups(P <0.05) and longitudinal systolic strain(SLsys) of 3 myocardial layers decreased in two groups (P <0.01). And the SLsys in the endocardium had greater variation than that in the epicardium.②Compared with that after ligation,the SLsys of all myocardial layers increased at 30 min after reperfusion in ATP-PPost group (P <0.01),and the SLsys in endocardial layer kept increasing with the time of reperfusion(P <0.05). And the SLsys of 3 myocardial layers were significantly higher in ATP-PPost group than those in IR group (P <0.01).③ In two groups,the values of SLsys were decreasing from endocardial layer to epicardial layer.They were higher in the endocardium than those in the epicardium at any time(P <0.01 and P <0.05).Conclusions Layer-specific strain of STI can evaluate exactly the regional myocardial function of rabbit myocardial pharmacological-postconditioning model.SLsys of endocardial layer is more sensitive to myocardial ischemia than that of epicardial layer.

Objective: To identify the role of interferon (IFN)-γ during respiratory syncytial virus (RSV) re-infection in mice. Method: Female wild type C57BL/6 mice and IFN-γ knockout mice (IFN-γ^-/- mice) at the age of 6 to 8 weeks were randomly divided into two groups: control group and RSV group, according to random number table.Each group was further divided into primary infection group and re-infection group.There were 8 groups.Mice were sacrificed on days 5, 7, 14 to collect samples.There were 5-8 mice in each group at each time point.And experiment was repeated twice. Leukocytes in bronchoalveolar lavage fluid (BALF) were counted, left lung tissues were stained with HE and histopathological scoring (HPS) was performed.The concentrations of IFN-γ, IL-5, IL-13 were determined with ELISA.T test or single factor analysis of variance was used to compare between groups. Result: (1) Mice infected or reinfected with RSV showed pale hair, weight loss, decreased activity and anorexia.(2) IFN-γ levels significantly increased on days 5 and 7 following RSV primary infection and reinfection as compared to control groups in wild type mice ((192±44) vs.(36±8) and (531±161) vs.(23±4) pg/ml on day 5, (100±23) vs.(36±8) and (862±186) vs.(23±4) pg/ml on day 7, t=2.654, 2.513, 2.654, 3.968, all P<0.05). (3) Compared to the RSV-reinfected IFN-γ^-/- mice, RSV-reinfected wild type mice had less body weight loss ((13.6±2.6)% vs.(22.7±2.9)% on day 5, (18.0±3.1)% vs.(26.5±1.8)% on day 7, t=2.314, 2.308, both P<0.05), lower lung tissue histopathological score ((1.50±0.09) vs.(2.07±0.11) on day 5, (1.53±0.11) vs.(2.08±0.09) on day 7, (1.10±0.06) vs.(1.59±0.08) on day 14, t=3.916, 3.890, 4.837, all P<0.01), less BALF inflammatory cells count ((11.6±2.0) vs.(44.2±10.6)×10⁵/ml on day 5, (18.2±3.9) vs.(38.3±2.2)×10⁵/ml on day 7, t=2.818, 4.786, both P<0.05), and lower levels of IL-5 and IL-13 ((24±3) vs.(148±23), (23±4) vs.(169±26) pg/ml on day 5, (30±8) vs.(233±44), (20±5) vs.(182±19) pg/ml on day 7, (91±6) vs.(129±19), (62±8) vs.(132±5) pg/ml on day 14, t=5.252, 5.445, 4.517, 7.326, 3.816, 7.577, all P<0.01). Conclusion IFN-γ can alleviate airway inflammation following RSV reinfection in mice.

Objective To investigate the relationship between single nucleotide polymorphisms (SNPs) of UGT1 A6 and aspirin response in a cohort of Chinese Han population.Methods A total of 323 ischemic stroke patients consecutively registered in Nanjing Stroke Registry Program from September 2011 to October 2014 were enrolled.Three SNPs (rs6759892,rs2070959 and rs1105879) of UGT1A6 were genotyped in these ischemic stroke patients.Association of genotypes and aspirin response was evaluated by generalized linear model.Indicated with the inhibition rate of platelets,aspirin response was assessed by thromboelastograph.Results The mutation allele (G) of rs2070959 was positively related to platelets inhibition (β =0.084,P =0.010,Pcorrected =0.029),especially in male (β =0.098,P =0.006,Pcorrected =O.019).The dominant models of rs6759892,rs1105879 were also modestly related to aspirin response (P=0.015,Pcorrected=0.046 in both SNPs) in male.Thus the polymorphisms of UGT1A6 showed a relationship with aspirin response,especially in males.Conclusions The results indicated that genetic polymorphism of UGT1A6 might have an effect on individuals' aspirin response,especially in males.These findings can help clinicians to optimize the antiplatelet therapy for ischemic stroke patients.

Stroke has become the leading cause of death in Chinese residents. As the cornerstone of the primary and secondary prevention of ischemic stroke, aspirin can prevent the occurrence and recurrence of ischemic stroke in a certain extent. However, some patients stil have vascular events after taking aspirin regularly or higher platelet aggregation rate. This phenomenon is caled aspirin resistance or aspirin low reactivity. This article reviews the occurrence, detection methods, and treatment measures of aspirin resistance in patients with ischemic stroke.

Objective Hypertension is a leading modifiable risk factor for cardiovascular disease .However , a lot of hyper-tension patients hold inactive attitudes to hypertension treatment .The purpose of this study was to investigate the relationship between previous treatment of hypertension and stroke severity in acute ischemic stroke . Methods We retrospectively analyzed the clinical data of 653 in-hospital ischemic stroke patients with hypertension between January 2011 and December 2014 .According to the National Institutes of Health Stroke Scale (NIHSS) at admission, the stroke patients were divided into a mild group (NIHSS≤3) and a severe group (NIHSS >3) and, based on their history of hypertension treatment , allocated to a regular treatment, an irregular treatment, a non-treatment , and an unawareness group .We studied the relationship of previous hypertension treatment with stroke severity by Spearman correlation analysis and identified the potential factors associated with stroke severity by multivariate logistic regression anal-ysis. Results Previous treatment of hypertension was positively correlated with stroke severity (r=0.146, P=0.000 2).Compared with the patients of the regular treatment group , those in the irregular treatment group (OR: 2.21; 95%CI:1.39 -3.52; P =0.001), non-treatment group ( OR: 2.18; 95%CI: 1.41 -3.36; P =0.0004) and unawareness group (OR:1.80;95%CI:1.12-2.88; P=0.015) tended to have more severe stroke. Conclusion Previous treatment of hypertension is closely related to the severity of ischemic stroke .