Inhibitory Effect of PPARδAgonist GW501516 on Proliferation of Hypoxia-induced Pulmonary Arterial Smooth Muscle Cells by Regulating the mTOR Pathway

Objective This study aimed to investigate the effects of the peroxisome proliferator-activated receptorδ(PPARδ)agonist GW501516 on the proliferation of pulmonary artery smooth muscle cells(PASMCs)induced by hypoxia,in order to search for new drugs for the treatment and prevention of pulmonary vascular remodeling.Methods PASMCs were incubated with different concentrations of GW501516(10,30,100 nmol/L)under the hypoxic condition.The proliferation was determined by a CCK-8 assay.The cell cycle progression was analyzed by flow cytometry.The expression of PPARδ,S phase kinase-associated protein 2(Skp2),and cell cycle-dependent kinase inhibitor p27 was detected by Western blotting.Then PASMCs were treated with 100 nmol/L GW501516,100 nmol/L mammalian target of rapamycin(mTOR)inhibitor rapamycin and/or 2µmol/L mTOR activator MHY1485 to explore the molecular mechanisms by which GW501516 reduces the proliferation of PASMCs.Results The presented data demonstrated that hypoxia reduced the expression of PPARδin an oxygen concentration-and time-dependent manner,and GW501516 decreased the proliferation of PASMCs induced by hypoxia by blocking the progression through the G0/G1 to S phase of the cell cycle.In accordance with these findings,GW501516 downregulated Skp2 and upregulated p27 in hypoxia-exposed PASMCs.Further experiments showed that rapamycin had similar effects as GW501516 in inhibiting cell proliferation,arresting the cell cycle,regulating the expression of Skp2 and p27,and inactivating mTOR in hypoxia-exposed PASMCs.Moreover,MHY1485 reversed all the beneficial effects of GW501516 on hypoxia-stimulated PASMCs.Conclusion GW501516 inhibited the proliferation of PASMCs induced by hypoxia through blocking the mTOR/Skp2/p27 signaling pathway.

Rapid Detection of rpoB Gene Mutations in Rif-resistant M.tuberculosis Isolates by Oligonucleotide Microarray

Objective To detect the specific mutations in rpoB gene of Mycobacterium tuberculosis by oligonucleotide microarray. Methods Four wild-type and 8 mutant probes were used to detect rifampin resistant strains. Target DNA of M. tuberculosis was amplified by PCR, hybridized and scanned. Direct sequencing was performed to verify the results of oligonucleotide microarray Results Of the 102 rifampin-resistant strains 98 （96.1%） had mutations in the rpoB genes. Conclusion Oligonucleotide microarray with mutation-specific probes is a reliable and useful tool for the rapid and accurate diagnosis of rifampin resistance in M. tuberculosis isolates.

Cavernous hemangioma of the ileum in a young man:A case report and review of literature

BACKGROUND Small intestinal cavernous hemangioma is a rare disease,especially in the ileum.It is difficult to accurately diagnose due to its hidden location and nonspecific clinical symptoms.Here,we reported a case of ileal cavernous hemangioma with chronic hemorrhage in a 20-year-old man and review the literature to gain a better understanding of this disease.CASE SUMMARY The patient complained of intermittent melena and hematochezia for > 3 mo.The lowest hemoglobin level revealed by laboratory testing was 3.4 g/d L(normal range:12-16 g/dL).However,the gastroscopy,colonoscopy and peroral doubleballoon enteroscopy(DBE) showed no signs of bleeding.The transanal DBE detected a lesion at about 340 cm proximal to the ileocecal valve.Thus,we performed an exploratory laparoscopy and the lesion was resected.After the operation,the patient had no melena.Finally,the pathological examination identified the neoplasm as an ileal cavernous hemangioma,thereby resulting in gastrointestinal hemorrhage.CONCLUSION This report might improve the diagnosis and treatment of ileal cavernous hemangioma.

Simultaneously Improved Curing,Mechanical,Antioxidative Properties and Reduced ZnO Loading of Silica Filled NR Composites by Incorporation of Low-cost Crude Carbon Dots via Conventional Melt-milling Method

Rubbers or elastomers play an important role in hi-tech technology and civilian daily life because of their unique and strategical properties.Generally,the rubber additives are essential components for rubbers’practical application.Nowadays,developing novel multifunctional additives has attracted increasing research attention.In this work,low-cost crude carbon dots(CCDs)were used as multifunctional additives for natural rubber/silica system(without any additional modification)through industrial compatible melt-mixing method.The results revealed that the CCDs could disperse well in the NR/silica system,and they could not only endow the rubber compound with excellent anti-aging capability due to CCDs’radical scavenging activity because of their plenty of nitrogen-containing species,but also improve the curing rate and mechanical performance of the rubber composite.Also,the CCDs could reduce the rolling resistance of the rubber composites(tanδvalue at 7%strain of the rubber composite could be decreased by 34%),which is promising for the application of energy-saving tire industry.Lastly,the addition of CCDs could effectively reduce the ZnO dosage by at least 40%in the rubber composite without deteriorating its performance.Overall,this work provides valuable guidance to develop novel cheap yet effective additives for the elastomer.

Surgical complexity and prognostic outcome of small volume renal cell carcinoma with high-level venous tumor thrombus and large volume renal cell carcinoma with low-level thrombus

Background:Radical nephrectomy with thrombectomy is one of the most difficult and complicated urological operations.But the roles of renal tumor volume and thrombus level in surgical complexity and prognostic outcome are not clear.This study aimed to evaluate the surgical complexity and prognostic outcome between the volume of renal cell carcinoma (RCC) and the level of venous tumor thrombus.Methods:The clinical data of 67 RCC cases with renal vein or inferior vena cava (IVC) tumor thrombus from January 2015 to May 2018 were retrospectively analyzed.Among these 67 cases,21 (31.3%) were small tumors with high-level thrombus (tumor ≤7 cm in diameter and thrombus Neves Level Ⅱ-Ⅳ),while 46 (68.7%) were large tumors with low-level thrombus group (tumor >7 cm in diameter and thrombus Level 0-Ⅰ).Clinical features,operation details,and pathology data were collected.Univariable and multivariable logistic regression analyses were applied to evaluate the risk factors for small tumor with high-level thrombus.Results:Patients with small tumors and high-level thrombus were more likely to have longer operative time (421.9 ± 135.1 min vs.282.2 ± 101.9 min,t=4.685,P < 0.001),more surgical bleeding volume (1200 [325,2900] mL vs.500 [180,1000] mL,U =270.000,P =0.004),more surgical blood transfusion volume (800 [0,1400] mL vs.0 [0,800] mL,U =287.500,P =0.004),more plasma transfusion volume (0 [0,800] mL vs.0 [0,0] mL,U =319.000,P =0.004),higher percentage of open operative approach (76.2% vs.32.6%,x2 =11.015,P =0.001),higher percentage of IVC resection (33.3% vs.0%,x2 =17.122,P < 0.001),and higher percentage of post-operative complications (52.4% vs.19.6%,x2 =7.415,P =0.010) than patients with large tumors and low-level thrombus.In multivariate analysis,decreased hemoglobin (Hb)(odds ratio [OR]:0.956,95 % confidence interval [CI]:0.926-0.986,P =0.005) and non-sarcomatoid differentiation (OR:0.050,95% CI:0.004-0.664,P =0.023) were more likely to form small tumors with high-level tumor thrombus rather than large tumor with small tumor thrombus.The estimated mean cancerspecific survival times of small tumor with high-level thrombus and large tumor with low-level thrombus were 31.6 ± 3.8 months and 32.5 ± 2.9 months,without statistical significance (P =0.955).After univariate and multivariate Cox proportional hazard survival regression analyses,only distant metastasis (hazard ratio [HR]:3.839,P =0.002),sarcomatoid differentiation (HR:7.923,P < 0.001),alkaline phosphatase (HR:2.661,P =0.025),and severe post-operative complications (HR:10.326,P =0.001) were independent predictors of prognosis.Conclusions:The level of the tumor thrombus was more important than the diameter of the primary kidney tumor in affecting the complexity of surgery.In the same T3 stage,neither the renal tumor diameter nor the tumor thrombus level was an independent risk factor for prognosis.

Peking University Third Hospital score:a comprehensive system to predict intra-operative blood loss in radical nephrectomy and thrombectomy

Background:Radical nephrectomy and thrombectomy is the standard surgical procedure for the treatment of renal cell carcinoma (RCC) with tumor thrombus (TT). But the estimation of intra-operative blood loss is only based on the surgeon’s experience. Therefore, our study aimed to develop Peking University Third Hospital score (PKUTH score) for the prediction of intra-operative blood loss volume in radical nephrectomy and thrombectomy.Methods: The clinical data of 153 cases of renal mass with renal vein (RV) or inferior vena cava tumor thrombus admitted to Department of Urology, Peking University Third Hospital from January 2015 to May 2018 were retrospectively analyzed. The total amount of blood loss during operation is equal to the amount of blood sucked out by the aspirator plus the amount of blood in the blood-soaked gauze. Univariate linear analysis was used to analyze risk factors for intra-operative blood loss, then significant factors were included in subsequent multivariable linear regression analysis.Results: The final multivariable model included the following three factors: open operative approach (P < 0.001), Neves classification IV (P < 0.001), inferior vena cava resection (P = 0.001). The PKUTH score (0-3) was calculated according to the number of aforementioned risk factors. A significant increase of blood loss was noticed along with higher risk score. The estimated median blood loss from PKUTH score 0 to 3 was 280 mL (interquartile range [IQR] 100-600 mL), 1250 mL (IQR 575-2700 mL), 2000 mL (IQR 1250-2900 mL), and 5000 mL (IQR 4250-8000 mL), respectively. Meanwhile, the higher PKUTH score was, the more chance of post-operative complications (P = 0.004) occurred. A tendency but not significant overall survival difference was found between PKUTH risk score 0vs. 1 to 3 (P = 0.098).Conclusion: We present a structured and quantitative scoring system, PKUTH score, to predict intra-operative blood loss volume in radical nephrectomy and thrombectomy.

Identification of a novel mutation in the SRD5A2 gene of one patient with 46,XY disorder of sex development

Dear Editor, 46,XY disorder of sex development （DSD） is characterized by a female phenotype in an individual with a normal 46,XY karyotype.1 The clinical phenotTpe of 46,XY DSD is characterized by bilateral undescended testes and a normal female appearance, including breasts, female external genitalia, and other secondary sex characteristics, but the absence of a uterus or ovaries.2 Development of the male external genitalia in the fetal period depends on the biosynthesis of testosterone （T）, the conversion ofT into dihydrotestosterone （DHT） by steroid 5α-reductase type 2 （SRD5A2）, and the response of functionally active androgen receptors in genital tissues） The disruption of any of these stages will block the differentiation of internal and external genitalia and cause 46,XY DSD.