Summary The F-box protein S-phase kinase-associated protein 2 is frequently overexpressed in human cancers. Herein, we aimed to investigate the expression pattern, clinical significance, and ...biological function of S-phase kinase-associated protein 2 in hepatocellular carcinoma. Analysis by reverse transcriptase polymerase chain reaction, Western blot, and immunohistochemistry revealed that S-phase kinase-associated protein 2 was aberrantly overexpressed in hepatocellular carcinomas relative to adjacent nontumor liver tissues. This overexpression was significantly associated with advanced tumor stage, increased histologic grade, vascular invasion, and intrahepatic metastasis, as well as worse overall survival and higher early recurrence rate. Knockdown of the endogenous S-phase kinase-associated protein 2 expression in 1 hepatocellular carcinoma cell line, Huh7, by RNA interference reduced cell proliferation, blocked the cell cycle at G1 phase, and increased apoptosis. S-phase kinase-associated protein 2 silencing resulted in a deregulation of multiple cell-cycle regulatory proteins in Huh7 cells, as detected by quantitative real-time polymerase chain reaction arrays. Furthermore, high S-phase kinase-associated protein 2 immunoreactivity was found to be significantly correlated with reduced expression of P27, P21, and cell-cycle checkpoint kinase 2, as well as with increased expression of transcription factors Dp-1, cyclin D2, and cyclin D1 in hepatocellular carcinoma tissues. These data demonstrate that S-phase kinase-associated protein 2 expression is closely linked to tumor progression and represents an independent predictor of poor prognosis in hepatocellular carcinoma. S-phase kinase-associated protein 2 is involved in hepatocellular carcinoma cell proliferation through regulating numerous genes involved in cell-cycle progression, thereby providing a potential therapeutic target for this malignancy.
Background A prospective multicenter survey was conducted to assess the rational use of antibiotics in clean and clean-contaminated elective surgical procedures applied in 53 grade III first class ...hospitals in Shandong Province, China, from 2006 to 2011. The survey was designed to examine the prevalence of antibiotic prophylaxis, evaluate the quality of perioperative antibiotic prophylaxis (PAP) prescriptions, and investigate the risk factors associated with inappropriate indication for antibiotic prophylaxis. Methods Medication charts and medical, anesthetic, and nursing records were reviewed. Antibiotic prescriptions were compared with the Chinese National Antibiotic Guideline on indication, antibiotic combination, antibiotic choice, dose, dosing interval, route of administration, timing of first administration, and duration of prophylaxis. Results 14,261 of 14,525 procedures (98.2%) receiving antibiotic prophylaxis. The most frequently encountered noncompliance types were PAP indications (18.6%), duration of prophylaxis (26.7%), and timing of first administration (30.3%). The steps of PAP were justified and correct only in 9.4% of procedures. Risk factors independently associated with inappropriate indication for antibiotic prophylaxis were seen in age, hospital type, hospital size, surgical disciplines, and surgical duration. Conclusion Results showed a significantly high rate of antibiotic prophylaxis in clean and clean-contaminated elective surgery and also a high prevalence of inappropriate indication prescriptions. These findings suggest important areas for intervention and implementation of antibiotic stewardship policies in Shandong Province hospitals.
Introduction The prevalence of obesity in Chinese adults increased from 1991 to 2000; however, recent changes in this trend are unclear. This study aims to estimate the current prevalence of obesity ...and to assess trends in obesity and BMI distribution in Chinese adults from 1991 through 2011. Methods Height and weight measurements of 12,249 Chinese adults from the 2011 China Health and Nutrition Survey were analyzed (in 2013) together with China Health and Nutrition Survey data for 1991−2009. Obesity was defined as BMI≥28.0 kg/m2 based on the Working Group on Obesity in China criteria. Results In the 2011 survey, the age-adjusted mean BMI was 23.8 (95% CI=23.7, 23.9) for men and 23.4 (95% CI=23.2, 23.5) for women. The age-adjusted prevalence of obesity was 11.3% (95% CI=10.8%, 11.9%) overall, 11.8% (95% CI=10.8%, 12.6%) among men, and 11.0% (95% CI=10.3%, 11.8%) among women. Estimates of age-adjusted obesity prevalence among the Chinese population were significantly lower than those of the U.S. population (all p <0.05). Over the 20-year period, the prevalence of obesity increased from 2.88% to 11.8% among men (age-adjusted annual change in OR=1.08, 95% CI=1.07, 1.09, p <0.001) and from 4.55% to 11.0% among women (OR=1.05, 95% CI=1.05, 1.06, p <0.001). Similar significant findings were observed for both men and women based on WHO recommendations. Conclusions The prevalence of obesity among both Chinese men and women increased significantly from 1991 through 2011, particularly among men.
Summary Background On the basis of the results of the randomised clinical trial HPTN 052 and observational studies, WHO has recommended that antiretroviral therapy be offered to all HIV-infected ...individuals with uninfected partners of the opposite sex (serodiscordant couples) to reduce the risk of transmission. Whether or not such a public health approach is feasible and the outcomes are sustainable at a large scale and in a developing country setting has not previously been assessed. Methods In this retrospective observational cohort study, we included treated and treatment-naive HIV-positive individuals with HIV-negative partners of the opposite sex who had been added to the national HIV epidemiology and treatment databases between Jan 1, 2003 and Dec 31, 2011. We analysed the annual rate of HIV infection in HIV-negative partners during follow-up, stratified by treatment status of the index partner. Cox proportional hazards analyses were done to examine factors related to HIV transmission. Findings Based on data from 38 862 serodiscordant couples, with 101 295·1 person-years of follow-up for the seronegative partners, rates of HIV infection were 2·6 per 100 person-years (95% CI 2·4–2·8) among the 14 805 couples in the treatment-naive cohort (median baseline CD4 count for HIV-positive partners 441 cells per μl IQR 314–590) and 1·3 per 100 person-years (1·2–1·3) among the 24 057 couples in the treated cohort (median baseline CD4 count for HIV-positive partners 168 cells per μl 62–269). We calculated a 26% relative reduction in HIV transmission (adjusted hazard ratio 0·74, 95% CI 0·65–0·84) in the treated cohort. The reduction in transmission was seen across almost all demographic subgroups and was significant in the first year (0·64, 0·54–0·76), and among couples in which the HIV-positive partner had been infected by blood or plasma transfusion (0·76, 0·59–0·99) or heterosexual intercourse (0·69, 0·56–0·84), but not among couples in which the HIV-positive partner was infected by injecting drugs (0·98, 0·71–1·36). Interpretation Antiretroviral therapy for HIV-positive individuals in serodiscordant couples reduced HIV transmission across China, which suggests that the treatment-as-prevention approach is a feasible public health prevention strategy on a national scale in a developing country context. The durability and generalisability of such protection, however, needs to be further studied. Funding Chinese Government's 12th Five-Year Plan, the National Natural Science Foundation of China, and the Canadian International Development Research Centre.
Abstract Breast cancer remains one of the most common cancers for females. Drug delivery based on cancer nanotechnology could improve the performance of some chemotherapeutic medicines already used ...in clinic. The emergence of polymersomes provided the potential to encapsulate hydrophobic/hydrophilic drugs. By modifying the weight ratio of methoxy-poly (ethylene glycol) (mPEG) chain to ethyl-p-aminobenzoate (EAB) side group, a series of amphiphilic graft polyphosphazenes (PEPs) was prepared. PEP can be tuned from micelles to polymersomes with the decrease of mPEG content via dialysis. Either hydrophilic doxorubicin hydrochloride (DOX·HCl) or hydrophobic doxorubicin base (DOX) could be encapsulated into PEP polymersomes with high payload and high encapsulation efficiency due to the strong intermolecular interaction with PEP. Compared with free DOX·HCl administration, in vivo investigation in growth inhibition of MCF-7 xenograft tumors in nude mice demonstrated that PEP polymersomes could enhance life safety without compromise of therapeutic efficacy, especially DOX·HCl loaded delivery system. From the Clinical Editor In this preclinical study, polymerosomes based on PEPs were investigated as doxorubicin delivery systems, demonstrating similar efficacy but less toxicity compared to standard delivery methods.
Abstract Glypican 3 (GPC3) is a glycosylphosphatidylinositol-anchored membrane protein and plays an important role in regulation of cell growth, differentiation, and migration. The aims of this study ...were to investigate the expression of GPC3 in human liver, biliary tract, and pancreatic tumors and to evaluate its diagnostic role in differentiating hepatocellular carcinoma (HCC) from other hepatic mimickers. Immunohistochemistry was performed on a large collection of surgically resected samples from 941 primary liver tumors, 50 metastatic adenocarcinomas, and 30 normal livers as well as primary adenocarcinomas of the pancreas (n = 17), gallbladder (n = 30), and extrahepatic bile duct (n = 20). The relationship of GPC3 expression and clinicopathologic features in patients with HCC was determined. We found that 516 (52%) of the 991 liver neoplastic tissue samples demonstrated positive staining for GPC3. A high incidence of GPC3 expression (492/757; 65%) was observed in HCC, whereas intrahepatic cholangiocarcinomas, adenocarcinomas, and benign liver lesions displayed rare positive cases. There were significant correlations between GPC3 expression and clinicopathologic characteristics, including histologic grade ( P < .001), intrahepatic metastasis ( P = .007), and positive serum hepatitis B surface antigen ( P = .042), in patients with HCC. In conclusion, our results confirm the high expression of GPC3 in HCC and suggest its potential diagnostic value as a clinical marker for this disease.
Abstract Pseudomonas aeruginosa can cause major infection in immunocompromised patients, and successful antibiotic treatment of the infection relies on accurate and rapid identification of the ...infectious agents. Here, we reported a culture-free diagnostic method based on the surface-enhanced Raman spectroscopy (SERS) of pyocyanin (PCN), a major biomarker of P. aeruginosa . This platform can detect PCN as low as 5 ppb or 2.38×10 − 8 mol L − 1 in both aqueous solutions and spiked clinical sputum samples. It has also been used to dynamically monitor the excretion of PCN by P. aeruginosa during its growth. The presence of PCN has been detected by SERS in 15 clinical sputum samples, which indicates P. aeruginosa infection, with 95.6% sensitivity and 93.3% specificity. The system can advantageously process multiple specimens rapidly, overcomes the need for bacterial culture and diagnostic microbiology assays, and have widespread implications in the early detection of P. aeruginosa infection. From the Clinical Editor A surface enhanced Raman spectroscopy method optimized for the detection of P. aureginosa infections is presented in this paper. The presence of pyocyanin, a marker of this bacterium has been detected in 15 clinical sputum samples utilizing this method. A sensitivity of 95.6% and 93.3% specificity was reported, which suggests that the method may enable culture-free high throughput rapid detection of this infection.
AbstractPurposePropafenone hydrochloride has been widely used for the treatment of supraventricular and ventricular arrhythmias. We present a case report of an 81-year-old patient with ...propafenone-associated gross hematuria. MethodsThe Naranjo Adverse Drug Reaction Probability Scale was used to assess causality. We also performed a literature search to find publications that report propafenone-associated gross hematuria. FindingsThe Naranjo scale generated a score of 6, suggesting a probable association between gross hematuria and propafenone therapy. Thirteen publications that reported an association between gross hematuria and propafenone administration were found. ImplicationsA probable association exists between gross hematuria and propafenone.
Abstract Background Superparamagnetic iron oxide magnetic nanomaterials (SPIO) are tracers used for treatment of central nervous and cardiovascular system complications in animal models. The present ...study investigated survival and proliferation of SPIO-labeled bone marrow mesenchymal stem cells (BMSCs) to determine their potential therapeutic value in liver repair. Methods Surface antigens of BMSCs were measured using flow cytometry. BMSCs viability, growth curve, and SPIO (0–100 μg/mL) labeling rate were evaluated using trypan blue staining, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and Prussian blue staining, respectively. SPIO-labeled BMSCs were transplanted via liver or spleen injection in rats undergoing 70% hepatectomy. Distribution of SPIO-labeled BMSCs in liver and spleen, and liver repair were evaluated by magnetic resonance imaging (MRI), and serum alanine aminotransferase, aspartate aminotransferase, albumin, and total bilirubin levels. Results CD29+ /CD90+ /CD45− BMSCs were successfully isolated from rats. Labeling rate of SPIO in 25 μg/mLwas 94.9%. SPIO labeling did not affect BMSCs survival and proliferation. MRI showed that BMSCs colonized in the liver, whether via spleen or liver injection. Serum levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin in the transplanted rats were significantly lower than in the hepatectomy group at days 1, 3, and 7 after hepatectomy (all P < 0.05), whereas serum albumin levels were significantly higher in the transplanted rats on posthepatectomy day 3 (both P < 0.05). These indicators were not significantly different between the spleen and liver injection approaches. Conclusions BMSCs transplantation via liver or spleen injection could significantly accelerate liver healing. In vivo MRI of SPIO-labeled BMSCs can be used to trace real-time liver healing during clinical treatment after hepatectomy.
Our purpose was to investigate the relationship between oxygen saturation (SpO2) and dynamic interstitial glucose level (IGL) in patients with obstructive sleep apnea (OSA) along with type 2 diabetes ...mellitus (T2DM), and to investigate the potential mechanisms thereof.
A total of 130 patients with OSA and T2DM underwent polysomnography and oral glucose tolerance tests at the Sleep Medicine Center. Using the lowest (L) SpO2% tested, patients were divided into mild, moderate and severe LSpO2 groups. Polysomnography and continuous glucose monitoring systems were used to analyze the altered pattern of SpO2 and dynamic IGL in the 3 groups.
LSpO2 during sleep in patients with OSA and T2DM stimulated an increase in IGL. The moderate and severe levels were represented by IGL45 and IGL30, respectively. The average nocturnal and peak IGL after LSpO2 in the severe group were significantly higher than in the mild and moderate groups. Stepwise multiple regression analysis showed that the body mass index (β = 0.301, P < 0.001), homeostatic model assessment of insulin resistance (β = 0.260, P < 0.001), apnea-hypopnea index (β = 0.309, P < 0.001), average SpO2 (β = -0.423, P = 0.008), LSpO2 (β = -0.369, P < 0.001) and microarousal index (β = 0.335, P = 0.044) were probably related to nocturnal IGL in patients with OSA along with T2DM.
Severe and moderate OSA with T2DM is marked by a delayed IGL peak following LSpO2. Nocturnal hypoxemia causes hyperglycemia in patients with OSA along with T2DM.
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