AUP1 regulates lipid metabolism and induces lipid accumulation to accelerate the progression of renal clear cell carcinoma.

Lipid metabolic reprogramming is a prominent feature of clear cell renal cell carcinoma (ccRCC). Lipid accumulation affects cellular energy homeostasis, biofilm synthesis, lipid signal transduction, and phenotypic transformation in ccRCC. Herein, a prognostic-related model was constructed, and the prognostic utility of AUP1, a lipid droplet-regulating very low-density lipoprotein assembly factor, in ccRCC was determined through multiparameter analysis. AUP1 expression was significantly higher in clinical samples than in normal tissues and was closely associated with the clinical stage. The inhibition of AUP1 expression impaired the proliferation, migration, and invasion of ACHN and A498 ccRCC cells in vitro and in vivo. RNA-seq analysis revealed that AUP1 inhibition can significantly reduce the contents of intracellular triglyceride and cholesterol and regulate cell growth by cell cycle arrest, promoting apoptosis and reversing epithelial-mesenchymal transition. AUP1 regulated the synthesis of cholesterol esters and fatty acids (FAs) in ccRCC cells by targeting sterol O-acyltransferase 1 and partially promoted the progression of ccRCC. AUP1 also induced lipid accumulation in ccRCC by promoting the de novo synthesis of FAs (inhibiting protein kinase AMP-activated catalytic subunit alpha 2), inhibiting the rate-limiting enzyme of FA ß oxidation (carnitine palmitoyltransferase 1A), regulating the key enzyme of lipolysis (monoglyceride lipase, MGLL), and inhibiting the lipid transporter StAR-related lipid transfer domain containing 5 (STARD5). However, it did not affect the intracellular cholesterol synthesis pathway. The differential expression and prognostic significance of MGLL and STARD5 in ccRCC should be further studied. AUP1 may serve as a new and effective potential target and prognostic marker for ccRCC.

Combination of Soxhlet extraction and catalytic hydrodebromination for remediation of tetrabromobisphenol A contaminated soil.

As a widely used brominated flame retardants (BFRs), tetrabromobisphenol A (TBBPA) has been detected in various environmental matrices and is known to cause negative effects on both the environment and human health. In this study, a combined method was developed for the abatement of TBBPA contaminated soil based on successive steps of solvent extraction (SE) and catalytic hydrodebromination (HDB) over Pd/C. The results showed that TBBPA could be efficiently extracted from the TBBPA contaminated soil with polar solvents. Subsequently, TBBPA could be completely hydrodebrominated over Pd/C in ethanol, via multistep ultimately yielding bisphenol A. Moreover, NaOH, NH3H2O, and Et3N were more favorable to promote the HDB of 4-TBBPA over Pd/C, and 100% bromide atom removal ratio of TBBPA was achieved within 40 min when [NaOH]0/[organic-Br]0 was more than 1.10 in ethanol. However, the catalytic activity of Pd/C decreased with the repeated use in ethanol. To study the mechanism for this phenomenon, fresh and used catalysts were analyzed by characterization techniques including scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), and energy dispersive X-ray spectrometer (EDS). It was found that the deactivation of Pd/C catalyst caused by the gradual accumulation of NaBr could be recovered by washing with water. On the basis of these studies, an effective and practical system for the combined method of SE and catalytic HDB over Pd/C was developed to dispose BFRs contaminated soils.

Downregulation of CIP2A inhibits cancer cell proliferation and vascularization in renal clear cell carcinoma.

BACKGROUND: CIP2A has been proved to play a role as an oncogene in various types of malignancies while its functionality in renal clear cell carcinoma has not been investigated. Our study aimed to investigate the role of CIP2A in renal clear cell carcinoma and to explore the possible mechanisms. METHODS: A total of 80 patients with renal clear cell carcinoma and 32 healthy people were included in the study. Expression of CIP2A was detected by qRT-PCR. CIP2A silencing renal clear cell carcinoma cell line was established. Its effects on cell proliferation and migration were verified by CCK-8 assay and Transwell cell assay, respectively. The effects of CIP2A overexpression on AKT and VEGF were investigated. RESULTS: CIP2A expression level was increased in tumor tissues compared to adjacent healthy tissues. Serum levels of CIP2A protein were higher in cancer patients than in healthy controls, and serum levels of CIP2A protein were increased with increased stage of primary tumor. Serum CIP2A protein can be used to accurately predict renal clear cell carcinoma and its prognosis. CIP2A siRNA silencing inhibited tumor cell proliferation, and treatment with Akt activator reduced this inhibitory effect. CIP2A siRNA silencing decreased the expression level of VEGF and phosphorylation levels of AKT in renal clear cell carcinoma cells, while AKT activator treatment showed no significant effects on CIP2A expression. CONCLUSION: Downregulation of CIP2A can inhibit cancer cell proliferation and vascularization in renal clear cell carcinoma through inactivation of the Akt pathway and its downstream VEGF.

Expression of autophagy-related genes in cerebrospinal fluid of patients with tuberculous meningitis.

The expression of autophagy-related genes in cerebrospinal fluid of patients with tuberculous meningitis (TBM) and their clinical significance in patients with TBM was investigated. Sixty patients with TBM (observation group) and twenty healthy volunteers during the same period (control group) were selected and the cerebrospinal fluid was collected. The expression levels of p62, Beclin1 and LC3-II genes in cerebrospinal fluid were detected via semi-quantitative reverse transcription-polymerase chain reaction and patients in observation group were divided into high expression and normal or low expression group on the basis of LC3-II expression levels. On the other hand, the contents of inflammatory factors interleukin-6, -10 (IL-6, -10), and tumor necrosis factor-α (TNF-α) were detected using the enzyme-linked immunosorbent assay kit. The mRNA levels of p62, Beclin1 and LC3-II in cerebrospinal fluid of patients in observation were significantly higher than those in the control group (P<0.01). TUNEL assay showed that the apoptosis level of cerebro-spinal fluid in high expression was obviously lower than that in normal or low expression group (P<0.01); the content of IL-6 and TNF-α in cerebrospinal fluid in high expression was significantly lower than those in normal or low expression group (P<0.01); the content of IL-10 in cerebrospinal fluid in high expression was obviously higher than that in normal or low expression group (P<0.01). Correlation analysis revealed that LC3-II was positively correlated with IL-10, but negatively correlated with IL-6 and TNF-α. The mRNA levels of p62, Beclin1 and LC3-II in cerebrospinal fluid of patients with TBM are increased, there is a correlation between expression levels of autophagy-related genes and inflammatory factors, and the high expression of autophagy-related genes may have a protective effect on patients with TBM.

Evaluation of daily ginger consumption for the prevention of chronic diseases in adults: A cross-sectional study.

OBJECTIVES: The aim of this study was to assess daily ginger consumption and explore its correlation with chronic diseases among adults and to analyze further how different levels of ginger intake affect the prevalence of chronic diseases. METHODS: We examined the prevalence rate of chronic diseases (diabetes, hypertension, coronary heart disease [CHD], hyperlipidemia, cerebrovascular disease, fatty liver, anemia, and tumor), as well as the daily ginger intake in a large cross-sectional study. In all, 4628 participants (1823 men and 2805 women) ages 18 to 77 y completed face-to-face dietary and health questionnaires. We extracted diagnoses and investigation results from the participants' health records. The association between the level of ginger intake (0-2 g/d, 2-4 g/d, and 4-6 g/d) and the prevalence of chronic diseases was analyzed by using χ2 statistical test and unconditional logistic model. RESULTS: Overall, daily ginger consumption was associated with decreased risk for hypertension (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.86-0.98) and CHD (OR, 0.87; 95% CI, 0.78-0.96) in adults ages ≥18 y. Differences were also observed in adults ages ≥40 y: hypertension (OR, 0.92; 95% CI, 0.87-0.99), CHD (OR, 0.87; 95% CI, 0.78-0.97). However, after 20 y, no association was seen for hypertension but there was still a difference between ginger consumption and CHD in adults ages ≥60 y (OR, 0.84; 95% CI, 0.73-0.96). Again, the probability of illness (hypertension or CHD) decreased when the level of daily ginger intake increased. CONCLUSIONS: These data indicate that ginger has a potential preventive property against some chronic diseases, especially hypertension and CHD, as well as its ability to reduce the probability of illness.

Ineffectiveness of remote ischemic renal preconditioning in a porcine solitary-kidney model.

PURPOSE: Our study sought to demonstrate the effects of remote ischemic preconditioning (R-IPC) on renal function in a large animal (porcine) solitary-kidney model. METHODS: Twelve pigs were assigned to two groups: Each underwent a right nephrectomy followed by a week of recovery. Group 1 (No-IPC) underwent left renal hilar clamping for 90 minutes. Group 2 underwent right and left iliac artery clamping for 10 minutes each (R-IPC), followed by left hilar clamping for 90 minutes. Serum creatinine was drawn for both groups before ischemia (preoperative), then at 6 hours, 24 hours, 3 days, and 7 days after. Kidneys were harvested at 24 hours or 7 days for histologic analysis, and the degree of acute tubular necrosis (ATN) or lymphocyte invasion was quantified. RESULTS: Paired serum creatinine values were analyzed between time points. For Group 1, paired differences existed at 24 hours (P=0.008) but not at 3 days or 7 days. For Group 2, paired differences existed at 24 hours (P=0.006) but not at 3 days or 7 days. The mean preoperative serum creatinine level was similar between groups (P>0.05). The change in serum creatinine level was not significantly different between groups at any time point. Histologic analysis revealed rare evidence of ATN at 24 hours in Group 2, but not in Group 1. At 7 days, neither group showed ATN, and both showed 1-2+evidence of lymphocytic infiltrates. CONCLUSION: R-IPC in a solitary-kidney porcine model does not confer renal protection from warm ischemia either as evidenced by renal function measures or on histologic analysis.

Long-term outcomes in healthy adults after radiofrequency ablation of T1a renal tumours.

OBJECTIVE: To report the long-term oncological and renal function outcomes in healthy adults treated with radiofrequency ablation (RFA) for small renal masses. MATERIALS AND METHODS: We retrospectively analysed the medical records of otherwise healthy patients (those with American Society of Anesthesiologists symptom score 1 or 2) with clinical T1a renal tumours who underwent RFA at our institution between March 2001 and July 2012. Radiographic follow-up with contrast imaging was performed at 6 weeks, 6 months, 1 year and annually thereafter. Local recurrence was defined as any new enhancing lesion (>10 HU) after the initial negative post-treatment computed tomography results. The estimated glomerular filtration rates (eGFRs) before and after RFA were calculated using the Cockgroft-Gault equation. RESULTS: We performed RFA on 58 renal tumours in 52 patients. The mean tumour size was 2.2 cm with a median (interquartile range) follow-up of 60 (48-90) months. Three (5.1%) of the treated masses had tumour recurrence after initial RFA. The 5- and 10-year recurrence-free survival rate was 94.2%. There were no recurrences after 3 years. Three (5.1%) patients died during the follow-up, which gave 5- and 10-year overall survival rates of 95.7% and 91.1%. No patient developed metastatic renal cell carcinoma (RCC) and none died from RCC. Paired analysis showed that the eGFR values at a median follow-up of 40 months did not differ significantly from those before RFA. CONCLUSION: With long-term follow-up, RFA provides durable oncological and functional outcomes for selected T1a renal tumours in otherwise healthy patients.

Laparoscopic radiofrequency ablation of small renal tumors: long-term oncologic outcomes.

INTRODUCTION: Unlike percutaneous radiofrequency ablation (RFA) of small renal tumors, there are limited data assessing the long-term efficacy of laparoscopic RFA. Although the ablation cannot be visualized as reliably as with cryoablation, laparoscopic RFA allows for improved mobilization and placement of probes under direct vision. We reviewed our experience with laparoscopic RFA to assess long-term oncologic outcomes. METHODS: We performed a retrospective study of all patients who had undergone laparoscopic RFA for pT1a renal tumors from April 2000 to April 2010. Demographic, clinical, and radiologic data were assessed to determine indications and evidence for recurrence of disease. Radiologic recurrence was defined as any new enhancement (>10 HU) after absence of enhancement on initial negative 6-week computed tomography. RESULTS: Data were available for 79 patients who had 111 small renal masses treated over the 10-year period. The median tumor diameter was 2.2 cm and intraoperative biopsy identified renal cell carcinoma in 77%. The median follow-up was 59 months with an estimated 5-year recurrence-free survival of 93.3%. The overall rate of complications was 8.8% with a 3.8% rate of major complications. CONCLUSIONS: Long-term experience with laparoscopic RFA demonstrates that it is a safe and effective option for the treatment of small renal tumors. Five-year oncologic outcomes appear to be comparable to extirpation.

Prevalence of type 2 diabetes among newly detected pulmonary tuberculosis patients in China: a community based cohort study.

BACKGROUND: Patients with type 2 diabetes (DM) have a higher risk of developing pulmonary tuberculosis (PTB); moreover, DM co-morbidity in PTB is associated with poor PTB treatment outcomes. Community based prevalence data on DM and prediabetes (pre-DM) among TB patients is lacking, particularly from the developing world. Therefore we conducted a prospective study to investigate the prevalence of DM and pre-DM and evaluated the risk factors for the presence of DM among newly detected PTB patients in rural areas of China. METHODS AND FINDINGS: In a prospective community based study carried out from 2010 to 2012, a representative sample of 6382 newly detected PTB patients from 7 TB clinics in Linyi were tested for DM. A population of 6674 non-TB controls from the same community was similarly tested as well. The prevalence of DM in TB patients (6.3%) was higher than that in non-TB controls (4.7%, p<0.05). PTB patients had a higher odds of DM than non-TB controls (adjusted OR 3.17, 95% CI 1.14-8.84). The prevalence of DM increased with age and was significantly higher in TB patients in the age categories above 30 years (p<0.05). Among TB patients, those with normal weight (BMI 18.5-23.9) had the lowest prevalence of DM (5.8%). Increasing age, family history of DM, positive sputum smear, cavity on chest X-ray and higher yearly income (≥10000 RMB yuan) were positively associated and frequent outdoor activity was negatively associated with DM in PTB patients. CONCLUSIONS: The prevalence of DM in PTB patients was higher than in non-TB controls with a 3 fold higher adjusted odds ratio of having DM. Given the increasing DM prevalence and still high burden of TB in China, this association may represent a new public health challenge concerning the prevention and treatment of both diseases.

A comparison of long term renal functional outcomes following partial nephrectomy and radiofrequency ablation.

INTRODUCTION: To compare long term glomerular filtration rate (GFR) outcomes of partial nephrectomy and radiofrequency ablation performed for renal malignancy. MATERIALS AND METHODS: Renal function of 347 patients undergoing radiofrequency ablation (n = 142) or partial nephrectomy (n = 205) for renal malignancy between 1994 and 2011 were compared from a retrospective database at a single tertiary care center. Minimum 1 year of follow up was required, resulting in a mean follow up of 48.2 (SD +/- 28.2) months. Renal function was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The primary study outcome was progression of Chronic Kidney Disease (CKD) stage, calculated using the Kaplan-Meier life table method. Multivariate analysis was also conducted to determine the level of association between GFR decline and treatment modality. RESULTS: The 5 year freedom from CKD stage progression for radiofrequency ablation and partial nephrectomy was 85.4% (95% CI 76.8%-91.1%) versus 82.1% (95% CI 73.7%-88.1%) (p = 0.06). A longer follow up interval was associated with greater GFR decline, although hypertension, diabetes, age, and tumor size were not. CONCLUSION: Radiofrequency ablation provides similar long term renal function preservation benefit as partial nephrectomy.

The spatial epidemiology of tuberculosis in Linyi City, China, 2005-2010.

BACKGROUND: Tuberculosis (TB) remains a major public health burden in many developing countries. China alone accounted for an estimated 12% of all incident TB cases worldwide in 2010. Several studies showed that the spatial distribution of TB was nonrandom and clustered. Thus, a spatial analysis was conducted with the aim to explore the spatial epidemiology of TB in Linyi City, which can provide guidance for formulating regional prevention and control strategies. METHODS: The study was based on the reported cases of TB, between 2005 and 2010. 35,308 TB cases were geo-coded at the town level (n = 180). The spatial empirical Bayes smoothing, spatial autocorrelation and space-time scan statistic were used in this analysis. RESULTS: Spatial distribution of TB in Linyi City from 2005 to 2010 was mapped at town level in the aspects of crude incidence, excess hazard and spatial smoothed incidence. The spatial distribution of TB was nonrandom and clustered with the significant Moran's I for each year. Local G(i)* detected five significant spatial clusters for high incidence of TB. The space-time analysis identified one most likely cluster and nine secondary clusters for high incidence of TB. CONCLUSIONS: There is evidence for the existence of statistically significant TB clusters in Linyi City, China. The result of this study may assist health departments to develop a better preventive strategy and increase the public health intervention's effectiveness.