VDR regulates mitochondrial function as a protective mechanism against renal tubular cell injury in diabetic rats.

PURPOSE: To investigate the regulatory effect and mechanism of Vitamin D receptor (VDR) on mitochondrial function in renal tubular epithelial cell under diabetic status. METHODS: The diabetic rats induced by streptozotocin (STZ) and HK-2 cells under high glocose(HG)/transforming growth factor beta (TGF-ß) stimulation were used in this study. Calcitriol was administered for 24 weeks. Renal tubulointerstitial injury and some parameters of mitochondrial function including mitophagy, mitochondrial fission, mitochondrial ROS, mitochondrial membrane potential (MMP), mitochondrial ATP, Complex V activity and mitochondria-associated ER membranes (MAMs) integrity were examined. Additionally, paricalcitol, 3-MA (an autophagy inhibitor), VDR over-expression plasmid, VDR siRNA and Mfn2 siRNA were applied in vitro. RESULTS: The expression of VDR, Pink1, Parkin, Fundc1, LC3II, Atg5, Mfn2, Mfn1 in renal tubular cell of diabetic rats were decreased significantly. Calcitriol treatment reduced the levels of urinary albumin, serum creatinine and attenuated renal tubulointerstitial fibrosis in STZ induced diabetic rats. In addition, VDR agonist relieved mitophagy dysfunction, MAMs integrity, and inhibited mitochondrial fission, mitochondrial ROS. Co-immunoprecipitation analysis demonstrated that VDR interacted directly with Mfn2. Mitochondrial function including mitophagy, mitochondrial membrane potential (MMP), mitochondrial Ca2+, mitochondrial ATP and Complex V activity were decreased dramatically in HK-2 cells under HG/TGF-ß ambience. In vitro pretreatment of HK-2 cells with autophagy inhibitor 3-MA, VDR siRNA or Mfn2 siRNA negated the activating effects of paricalcitol on mitochondrial function. Pricalcitol and VDR over-expression plasmid activated Mfn2 and then partially restored the MAMs integrity. Additionally, VDR restored mitophagy was partially associated with MAMs integrity through Fundc1. CONCLUSION: Activated VDR could contribute to restore mitophagy through Mfn2-MAMs-Fundc1 pathway in renal tubular cell. VDR could recover mitochondrial ATP, complex V activity and MAMs integrity, inhibit mitochondrial fission and mitochondrial ROS. It indicating that VDR agonists ameliorate renal tubulointerstitial fibrosis in diabetic rats partially via regulation of mitochondrial function.

Mitofusin2 Ameliorated Endoplasmic Reticulum Stress and Mitochondrial Reactive Oxygen Species Through Maintaining Mitochondria-Associated Endoplasmic Reticulum Membrane Integrity in Cisplatin-Induced Acute Kidney Injury.

Aims: This study investigated the regulatory effect of Mitofusin2 (Mfn2) on mitochondria-associated endoplasmic reticulum membrane (MAM) integrity and cellular injury in cisplatin-induced acute kidney injury (CP-AKI). Results: CP-AKI mice exhibited decreased expression of Mfn2, increased expression of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), abnormal mitochondrial morphology, and reduced MAMs integrity, accompanied by the activation of mitochondrial reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress (inositol-requiring enzyme 1 [IRE1] and PERK pathways). In in vitro studies, CP-induced mitochondrial ROS, ER-stress activation, and increased apoptosis were accompanied by the downregulation of Mfn2 and MAMs integrity reduction in Boston University mouse proximal tubular cells (BUMPT) and human proximal tubular epithelial cells (HK-2). Pretreatment of BUMPT cells with the Mfn2 plasmid partially restored the integrity of MAMs, negatively controlled IRE1 and PERK pathways, and inhibited cell apoptosis. In contrast, ER-stress and MAMs integrity violations were increased after Mfn2 small-interfering RNA (siRNA) treatment in HK-2 cells under CP treatment. Coimmunoprecipitation analysis demonstrated that Mfn2 interacted with PERK and IRE1. Furthermore, the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), acadesine (AICAR), had a similar effect to Mfn2 plasmid in the regulation of ER stress and MAMs. Conversely, the ER-stress inhibitor, 4-phenylbutyric acid (4-PBA), had no effect on the expression of Mfn2 and MAMs integrity. Innovation and Conclusion: This is the first study to explore the association between MAMs, ER stress, and Mfn2 in CP-AKI. Downregulation of Mfn2 expression abolished the MAMs integrity, and induced ER stress, mitochondrial ROS, and tubular cell apoptosis. This suggests that the Mfn2-MAMs pathway is a potential therapeutic target in CP-AKI. Antioxid. Redox Signal. 40, 16-39. The Ethical Registration number of animal experiment in this study was CSU-2022-01-0095.

Association of vitamin D metabolites with arteriovenous fistula function in hemodialysis patients: A single center study.

INTRODUCTION: Arteriovenous fistula (AVF) is a primary dialysis vascular access commonly used for maintaining hemodialysis (MHD) patients. Vitamin D (VD) is a fat-soluble steroid hormone that is closely related to vascular endothelial function. This study aimed to investigate the association between VD metabolites and AVF failure in patients undergoing HD. METHODS: This study included 443 HD patients using AVF between January 2010 and January 2020. The AVF operations in these patients were newly created by the same physician. We analyzed the AVF patency rates using the chi-square test. Univariate and multivariate logistic regression analyses were performed to explore risk factors for AVF failure. Survival analysis was performed to explore AVF survival at different serum 25-hydroxyvitamin D (25(OH)D) concentrations. RESULTS: Logistic regression analyses showed that male sex; age; BMI; serum albumin, triglyceride, phosphorus, 25(OH)D, iPTH and hemoglobin levels, history of hypertension, CHD, diabetes, stroke, and antiplatelet drug use; and smoking habits were not risk factors for AVF failure. The failure incidence rates of AVF in subjects in the VD deficiency and non VD deficiency group were not statistically significant (25.0% vs. 30.8%, p = 0.344). The AVF failure incidence rates at 1, 3, and 5 years in the patients with 25(OH)D levels more than 20 ng/mL were 26%, 29%, and 37%, respectively, and the one-year AVF failure incidence rates were 27% in the patients with 25(OH)D levels less than 20 ng/mL. In addition, the Kaplan-Meier analysis suggested that the no significant differences were noted when calculating the cumulative survival rates of AVF between the two groups within 50 months of AVF using. CONCLUSION: Our findings suggest that 25(OH)D deficiency is not associated with AVF failure incidence rates, and that 25(OH)D deficiency has no significant impact on long-term cumulative AVF survival rate.

Iron metabolism and chronic inflammation in IgA nephropathy.

IgA nephropathy (IgAN), an immune-mediated chronic inflammatory kidney disease, is the most common primary glomerular disease in Asia, especially in China and Japan. The pathogenesis of IgAN is complex, and the main cause of IgAN is explained by the 'multiple hit' theory, which states that the deposition of immune complexes in renal mesangial cells induces chronic inflammation that leads to kidney damage. Chronic inflammation is associated with iron metabolism, which also plays an essential role in the pathogenesis, progression, diagnosis and prognosis of IgAN. Overall, this review aimed to explore the application of iron metabolism in IgAN by systematically elaborating the relationship between iron metabolism and chronic inflammation in IgAN to speculate on the possible diagnostic and therapeutic significance of iron metabolism indicators in IgAN.

Prognostic value of low-density lipoprotein cholesterol in IgA nephropathy and establishment of nomogram model.

Background: Dyslipidemia is closely related to kidney disease. We aimed to investigate the relationship between low-density lipoprotein cholesterol (LDL-C) and prognosis of IgA nephropathy (IgAN) and build a nomogram prognostic model. Methods: 519 IgAN patients with 61 months median follow-up were enrolled and divided into two groups based on the cut-off value of baseline LDL-C (2.60 mmol/L): the high group (n=253) and the low group (n=266). Renal survival was assessed by Kaplan⁃Meier (KM) survival curve. Risk factors were identified by COX regression analysis. The area under the receiver operating characteristic (ROC) curves (AUC), concordance index (C-index), and calibration curves were applied to evaluate the nomogram model. Results: KM survival curve analysis showed that the high LDL-C group had worse renal survival than the low LDL-C group (χ2 = 8.555, p=0.003). After adjusting for confounding factors, Cox regression analysis showed the baseline LDL-C level was an independent risk factor of end-stage renal disease (ESRD) in IgAN (HR=3.135, 95% CI 1.240~7.926, p =0.016). LDL-C, segmental sclerosis, tubular atrophy/interstitial fibrosis, the prevalence of cardiovascular disease, 24-hour proteinuria were identified and entered into the nomogram models, with AUC of 0.864, 0.827, and 0.792 respectively to predict the 5-, 8-, and 10-year risk of ESRD in IgAN. The C-index of this prediction model was respectively 0.862, 0.838, and 0.800 and was well-calibrated. Conclusion: Elevated LDL-C level is a predictive factor for the prognosis of IgAN. We developed a nomogram model that can predict the risk of ESRD in IgAN by using LDL-C ≥ 2.60 mmol/L.

Prevalence and prevention and control effects of malaria in Huangshi, Hubei, 1951-2021 / 中国热带医学

@#Abstract: Objective To analyze the epidemiological characteristics, prevention and control strategies, measures and the effects achieved of malaria in Huangshi City from 1951 to 2021, and to offer a reference for further strengthening malaria eradication and control successes. Methods　Descriptive epidemiological methods were used to assess the prevalence, measurements, and impacts of malaria in different time periods based on data for malaria control in Huangshi City from 1951 to 2021, and we created "semi-log" line graphs and charts to display the prevalence of disease and the effort done in prior years in terms of prevention and control. Results　Between 1951 and 2021, 527 780 cases of malaria were recorded in Huangshi, with an average annual incidence rate of 40.07/10 000. The prevention and control of malaria has gone through four stages, namely, the high prevalence of malaria stage (1951-1979), the basic elimination stage (1980-1999), the consolidation stage (2000-2010), and the eradication stage (2011-2021). Different strategies and measures have been adopted in different epidemic periods. During the high epidemic period, great efforts have been made to carry out general surveys and treatments, and strengthen the management of symptomatic patients; during the eradication stage, prominent and classified prevention and control strategies were adopted. When the incidence rate dropped to below 1/10 000, the main measures adopted were malaria monitoring, including timely discovery and standardization of infectious sources, disposal of epidemic points, management of migrant population malaria and vector monitoring. Through active prevention and control, remarkable results were achieved, and the incidence rate of malaria fell to below 1/10 000 in 1989, reaching the level of "basic elimination of malaria" issued by the Ministry in 1999, and passed the provincial malaria elimination acceptance in 2015. In recent years, with the increasing labor exports and foreign exchanges, imported malaria has been on the rise. African countries are the main sources of imported malaria, and the main species is P.falciparum. Conclusions　Malaria was once one of the main infectious diseases endangering the health of people in Huangshi City. The preventive and control methods and procedures adopted in different epidemic periods are effective. Currently, we have entered the consolidation phase of malaria elimination, with the focus of work being to monitor, report, and timely and effectively respond to imported malaria cases, thus reducing the risk of local transmission.

AMPK agonist alleviate renal tubulointerstitial fibrosis via activating mitophagy in high fat and streptozotocin induced diabetic mice.

Renal tubulointerstitial fibrosis was a crucial pathological feature of diabetic nephropathy (DN), and renal tubular injury might associate with abnormal mitophagy. In this study, we investigated the effects and molecular mechanisms of AMPK agonist metformin on mitophagy and cellular injury in renal tubular cell under diabetic condition. The high fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice model and HK-2 cells were used in this study. Metformin was administered in the drinking water (200 mg/kg/d) for 24 weeks. Renal tubulointerstitial lesions, oxidative stress and some indicators of mitophagy (e.g., LC3II, Pink1, and Parkin) were examined both in renal tissue and HK-2 cells. Additionally, compound C (an AMPK inhibitor) and Pink1 siRNA were applied to explore the molecular regulation mechanism of metformin on mitophagy. We found that the expression of p-AMPK, Pink1, Parkin, LC3II, and Atg5 in renal tissue of diabetic mice was decreased obviously. Metformin reduced the levels of serum creatinine, urine protein, and attenuated renal oxidative injury and fibrosis in HFD/STZ induced diabetic mice. In addition, Metformin reversed mitophagy dysfunction and the over-expression of NLRP3. In vitro pretreatment of HK-2 cells with AMPK inhibitor compound C or Pink1 siRNA negated the beneficial effects of metformin. Furthermore, we noted that metformin activated p-AMPK and promoted the translocation of Pink1 from the cytoplasm to mitochondria, then promoted the occurrence of mitophagy in HK-2 cells under HG/HFA ambience. Our results suggested for the first time that AMPK agonist metformin ameliorated renal oxidative stress and tubulointerstitial fibrosis in HFD/STZ-induced diabetic mice via activating mitophagy through a p-AMPK-Pink1-Parkin pathway.

HRD1 attenuates the high uptake of [18F]FDG in hepatocellular carcinoma PET imaging.

INTRODUCTION: Due to individual deviations in tumor tissue uptake, the role of [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) in hepatocellular carcinoma (HCC) diagnosis is limited. ß-Hydroxy ß-methylglutaryl-CoA reductase degradation 1 (HRD1) plays a key role in clearing misfolded proteins. This study is aimed to investigate the role and mechanism of HRD1 in [18F]FDG uptake for the diagnosis of HCC. METHODS: HRD1 expression level was detected using immunohistochemical (IHC) staining in 9 HCC patients. [18F]FDG PET/CT scans were conducted before treatment. [18F]FDG uptakes in HRD1 overexpressed and knockdown transgenic models were measured by γ-counter and microPET imaging. The GLUT1-HRD1 complex was examined by co-immunoprecipitation and IHC assays. GLUT1 expression in different cell lines, xenograft models and HCC patients was evaluated by Western blot and IHC assays. RESULTS: HRD1 was highly expressed in the HCC tumors of patients with low [18F]FDG uptake, while the HRD1 expression was obviously low in the higher [18F]FDG uptake group. Both in vitro and in vivo studies found that HRD1 significantly inhibited [18F]FDG uptake in HCC Huh7 cell lines and animal models. Furthermore, the co-location and interaction of HRD1 with GLUT1 were detected, and the results also indicate that HRD1 could induce the degradation of GLUT1 in vitro and in vivo. CONCLUSION: HRD1 inhibits the high uptake of [18F]FDG in HCC tumor cells by inducing degradation of GLUT1, which leads to decreased diagnostic efficiency of [18F]FDG PET imaging for HCC. ADVANCES IN KNOWLEDGE: This study suggests that HRD1 inhibits the high uptake of [18F]FDG in HCC tumor by inducing degradation of GLUT1. IMPLICATIONS FOR PATIENT CARE: HCC diagnosis with [18F]FDG PET should be accompanied by determination of HRD1 expression, and patients with high tumor HRD1 expression might be unsuitable for [18F]FDG PET.

Mitochondria targeted peptide SS-31 prevent on cisplatin-induced acute kidney injury via regulating mitochondrial ROS-NLRP3 pathway.

OBJECTIVE: This study aimed to assess the effect and mechanism of SS31 on cisplatin-induced acute kidney injury (CP-AKI) both in vivo and in vitro. METHOD: Male mices and HK-2 cells were treated using cisplatin to establish models of CP-AKI. 32 C57BL/6 mices were randomly divided into four groups (control group, CP group, CP + normal saline group, CP + SS-31 group). Cisplatin was intraperitoneally injected once to the mice (25 mg/kg). SS31 was administrated for 10 days at dosages of 10 mg/kg per day. Kidney histological changes and level of reactive oxygen species(ROS) were detected. In vitro studies, HK-2 cells were incubated with cisplatin (50 u M) or combimed with SS-31(100 u M), the level of mitochondrial ROS, apoptosis rate and the the expression of NLRP3, Caspase-1 and IL-1ß were tested. RESULTS: Renal tubulointerstitial apoptosis and oxidative stress were significantly increased in CP-AKI mice. Cisplatin caused elevation of serum creatinine (Scr), blood urea nitrogen (BUN) levels and enhanced IL-1ß, caspase1 and NLRP3 expression, the electron microscopy examination showed mitochondria cristae swelling, mitochondrial spheres and partial ridge breakdown in renal tubular cell of CP-AKI mice. SS31 treatment could effectively suppress mitochondrial ROS, ameliorate these lesions and decrease the expression of NLRP3, IL-1ß and Caspase1. In vitro studies, SS31 could restored the level of mitochondrial ROS and downregulate apoptosis rate in HK-2 cells, moreover, the elevated expression of NLRP3, IL-1ß and Caspase-1were restored. CONCLUSION: SS31 could protect CP-AKI in mices, which might be due to an anti-oxidative and anti-apoptotic action via regulating mitochondrial ROS-NLRP3 pathway. NLRP3 inflammasome might be considered as a novel therapeutic target of CP-AKI.

Early Departure, Early Revival: A ''Free From Care'' Account of Negative Temporal Discounting.

According to the positive temporal discounting theory and our relevant observations, when faced with future losses, people should, and do, prefer delayed negative events (e.g., deferring paying taxes, debts, or tickets), which can lead to substantial individual and societal costs. However, a counterexample has been identified and it appears to depart from the prediction of positive temporal discounting when faced with negative events. This study proposed and investigated the novel free from care account for the reverse preference. Results of five laboratory and field studies showed that students preferred an immediate negative event (i.e., an English oral exam) when "something tying one up" was imposed, in which coping with a distraction induced by such a situation could play a mediating role. In particular, the addition of "something tying one up" was found to be an effective behavioral nudge in terms of reliability and reproducibility and should be simple for potential users to follow. Specifically, the association between being tied up and undergoing a negative event immediately in the present studies mirrored the association between outgroup threat and intergroup cooperation in the Robbers Cave experiment.

Comparison of 99mTc-DTPA and serum creatinine, cystatin C in detection of glomerular filtration rate: a retrospective clinical data analysis of 744 Chinese subjects.

BACKGROUND: To compare the accuracy of various equations for estimating glomerular filtration rate. METHODS: Chronic kidney disease was classified by Tc-DTPA scintigraphy (reference glomerular filtration rate), estimating glomerular filtration rate was estimated using various formulas. The similarity to reference glomerular filtration rate decide the accuracy of estimating glomerular filtration rate. RESULTS: Overall, the Fengscr-cys equation had significantly higher accuracy and correct proportion in chronic kidney disease stage classification than other equations. The subgroup analysis showed that Fengscr-cys equation was slightly more precise than other equations both in the male and female patients. Moreover, in patients older than 60 years or whose reference glomerular filtration rate was above 60 ml/min, Fengscr-cys equation also showed better accuracy. CONCLUSION: Our data suggest that estimating glomerular filtration rate equations evaluated by serum cystatin C were better than serum creatinine-based equations, estimating glomerular filtration rate equations evaluated by both serum creatinine and cystatin C were better than those evaluated by serum creatinine or cystatin C alone. Among all enrolled equations, Fengscr-cys equation might be the best one to evaluate glomerular filtration rate in general Chinese paticipants.

Activation of vitamin D receptor attenuates high glucose-induced cellular injury partially dependent on CYP2J5 in murine renal tubule epithelial cell.

AIMS: Vitamin D and its receptor, vitamin D receptor (VDR), have renoprotection effect against diabetic nephropathy (DN). But the exact mechanism has not been fully elucidated. Epoxyeicosatrienoic acids (EETs) are cytochrome P450 (CYP) epoxygenase-derived metabolites of arachidonic acid, protecting against diabetes and DN. Herein, we hypothesized that activation of VDR attenuated high glucose-induced cellular injury in renal tubular epithelial cells partially through up-regulating CYP2J5 expression. MAIN METHODS: Streptozotocin (STZ) was injected to induce diabetic in wild type and Vdr-/- mice. The effects of VDR knockout and an activator of VDR, paricalcitol, on the renal injury were detected. In vitro, a murine kidney proximal tubule epithelial cell line BU.MPT induced by high glucose were treated with or without paricalcitol (30 mM) for 12 h or 24 h. KEY FINDINGS: The expression of CYP2J5 was significantly decreased both in wild type and Vdr-/- diabetic mice induced by STZ. The STZ-induced kidney architecture damage and apoptosis rate in Vdr-/- mice were more severe. In vitro, high glucose treatment strongly reduced the CYP2J5 expression and the synthesis of 14,15-EET in BU.MPT cells. Supplement of 14,15-EET significantly reduced the lactate dehydrogenase (LDH) release induced by high glucose in BU.MPT cells. Furthermore, treatment with paricalcitol attenuated cellular injury and restored the expression of CYP2J5 reduced by high glucose in BU.MPT cells. SIGNIFICANCE: We conclude that activation of VDR attenuates high glucose-induced cellular injury partially dependent on CYP2J5 in murine renal tubule epithelial cells and paricalcitol may represent a potential therapy for DN.

Mitochondria-Targeted Peptide SS31 Attenuates Renal Tubulointerstitial Injury via Inhibiting Mitochondrial Fission in Diabetic Mice.

OBJECTIVE: Renal tubular injury is an early characteristic of diabetic nephropathy (DN) that is related to mitochondrial dysfunction. In this study, we explore the effects and mechanisms of mitochondria-targeted peptide SS31 on renal tubulointerstitial injury in DN. METHOD: 40 C57BL/6 mice were randomly divided into control group, STZ group, STZ+SS31 group, and STZ+normal saline group. SS31 was intraperitoneally injected to the mice every other day for 24 weeks. Renal lesions and the expression of Drp1, Mfn1, Bcl-2, Bax, Caspase1, IL-1ß, and FN were detected. In in vitro studies, HK-2 cells were incubated with different concentrations of D-glucose (5, 30 mM) or combined with SS31 and Drp1 inhibitor Midivi1. Mitochondrial ROS, membrane potential, and morphology have been detected to evaluate the mitochondrial function. RESULTS: Compared with diabetic mice, the levels of serum creatinine and microalbuminuria were significantly decreased in the SS31 group. Renal tubulointerstitial fibrosis, oxidative stress, and apoptosis were observed in diabetic mice, while the pathological changes were reduced in the SS31-treatment group. SS31 could decrease the expression of Drp1, Bax, Caspase1, IL-1ß, and FN in the renal tissue of diabetic mice, while increasing the expression of Mfn1. Additionally, mitochondria exhibit focal enlargement and crista swelling in renal tubular cells of diabetic mice, while SS31 treatment could partially block these changes. An in vitro study showed that pretreatment with SS31 or Drp1 inhibitor Mdivi1 could restore the level of mitochondrial ROS, the membrane potential levels, and the expressions of Drp1, Bax, Caspase1, IL-1ß, and FN in HK-2 cells under high-glucose conditions. CONCLUSION: SS31 protected renal tubulointerstitial injury in diabetic mice through a decrease in mitochondrial fragmentation via suppressing the expression of Drp1 and increasing the expression of Mfn1.

Association of Vitamin D Receptor Gene Polymorphism With the Risk of Nephrolithiasis.

This study aimed to explore the relationship between vitamin D receptor (VDR) gene polymorphisms and the risk of nephrolithiasis. All relevant trials were searched from multiple databases according to predefined criteria, the pooled OR and corresponding 95% CI were analyzed using Stata software. Seventeen studies involving 2441 cases and 2296 controls were included. The pooled analysis showed that VDR BsmI, FokI, and ApaI gene polymorphisms were not associated with nephrolithiasis susceptibility either in Asian and in Caucasians populations. VDR TaqI gene polymorphism was associated with nephrolithiasis in the overall populations (T vs. t: OR = 0.84, 95% CI: 0.73-0.95, P = 0.006; TT vs. Tt + tt: OR = 0.79, 95% CI: 0.66-0.95, P = 0.010). In Asian population, VDR TaqI gene polymorphism also was associated with nephrolithiasis susceptibility (TT vs. Tt + tt: OR = 0.72, 95% CI: 0.55-0.93, P = 0.012; Tt vs. TT + tt: OR = 1.43, 95% CI: 1.00-2.05, P = 0.048). But TaqI gene polymorphism was not associated with nephrolithiasis risk in Caucasian populations (T vs. t: OR = 0.85, 95% CI: 0.72-1.00, P = 0.051; TT vs. Tt + tt: OR = 0.87, 95% CI: 0.68-1.10, P = 0.245; tt vs. Tt + TT: OR = 1.32, 95% CI: 0.86-2.01, P = 0.206; Tt vs. TT+ tt: OR = 0.98, 95% CI: 0.70-1.38, P = 0.931). VDR BsmI, FokI, and ApaI gene polymorphisms were not associated with the risk of nephrolithiasis either in Asian and Caucasians populations, but VDR TaqI gene polymorphism was associated with nephrolithiasis in the Asian subjects.

Vitamin D Receptor Down-Regulation Is Associated With Severity of Albuminuria in Type 2 Diabetes Patients.

CONTEXT: Inflammation plays an important role in albuminuria in type 2 diabetes mellitus (T2DM). The vitamin D receptor (VDR) has potent anti-inflammatory activities. OBJECTIVE: To investigate the correlation between VDR expression and albuminuria in T2DM. DESIGN/SETTING/PATIENTS: Renal biopsies from T2DM patients with albuminuria (n = 8) and nondiabetic subjects (n = 4) were compared for VDR expression by immunohistochemistry. Recruited T2DM patients (n = 242; estimated glomerular filtration rate > 60 mL/min/1.73 m2) were divided into three groups based on urinary albumin-to-creatinine ratio (uACR): normal albuminuria (uACR < 30 mg/g; n = 85), microalbuminuria (30 mg/g ≤ uACR < 300 mg/g; n = 84), and macroalbuminuria (uACR ≥ 300 mg/g; n = 73), with healthy individuals (n = 72) as controls. Peripheral blood mononuclear cells (PBMCs) from these subjects were analyzed for VDR mRNA (n = 314), TNF-α mRNA (n = 314), microRNA (miR)-346 (n = 120; 30 for each group), and VDR protein (n = 80; 20 for each group). PBMCs from randomly selected subjects (n = 6 for each group) were cultured ex vivo to evaluate the effect of TNF-α on miR-346 and VDR, and miR-346-mediated VDR suppression was further explored in HK2 cells. RESULTS: VDR expression was down-regulated in PBMCs and renal tubular epithelial cells from T2DM patients with albuminuria. VDR mRNA and protein levels were both negatively correlated with uACR, and VDR mRNA was inversely correlated with TNF-α and miR-346 in PBMCs from T2DM patients. TNF-α reduced VDR while inducing miR-346 in cultured PBMCs. TNF-α suppressed VDR by up-regulating miR-346 in HK2 cells. CONCLUSIONS: VDR down-regulation in PBMCs is independently associated with the severity of albuminuria in T2DM. TNF-α suppression of VDR in PBMCs and HK2 cells is mediated by miR-346.

Pain now or later: an outgrowth account of pain-minimization.

The preference for immediate negative events contradicts the minimizing loss principle given that the value of a delayed negative event is discounted by the amount of time it is delayed. However, this preference is understandable if we assume that the value of a future outcome is not restricted to the discounted utility of the outcome per se but is complemented by an anticipated negative utility assigned to an unoffered dimension, which we termed the "outgrowth." We conducted three studies to establish the existence of the outgrowth and empirically investigated the mechanism underlying the preference for immediate negative outcomes. Study 1 used a content analysis method to examine whether the outgrowth was generated in accompaniment with the delayed negative events. The results revealed that the investigated outgrowth was composed of two elements. The first component is the anticipated negative emotions elicited by the delayed negative event, and the other is the anticipated rumination during the waiting process, in which one cannot stop thinking about the negative event. Study 2 used a follow-up investigation to examine whether people actually experienced the negative emotions they anticipated in a real situation of waiting for a delayed negative event. The results showed that the participants actually experienced a number of negative emotions when waiting for a negative event. Study 3 examined whether the existence of the outgrowth could make the minimizing loss principle work. The results showed that the difference in pain anticipation between the immediate event and the delayed event could significantly predict the timing preference of the negative event. Our findings suggest that people's preference for experiencing negative events sooner serves to minimize the overall negative utility, which is divided into two parts: the discounted utility of the outcome itself and an anticipated negative utility assigned to the outgrowth.

Effects of vitamin E-coated dialysis membranes on anemia, nutrition and dyslipidemia status in hemodialysis patients: a meta-analysis.

BACKGROUND: This was controversial whether vitamin E-coated dialyzer therapy was beneficial for the complications associated with hemodialysis. Therefore, we performed this systematic review to evaluate the effects of vitamin E-coated dialyzer. METHODS: Related trials were searched from multiple electronic databases. We conducted meta-analysis to assess changes in the predefined outcomes using RevMan 5.3 software. RESULTS: Meta-analysis showed vitamin E-coated dialyzer therapy could decrease erythropoietin (EPO) resistance index (SMD, -0.24; 95% CI, -0.47 to -0.01; p = 0.04). However, pooled-analysis showed vitamin E-coated dialyzer therapy could not decrease weekly EPO dose (SMD, -0.11; 95% CI, -0.32 to 0.09; p = 0.28) and intima-media thickness (IMT) of the carotid artery (MD, -0.09; 95% CI, -0.2 to 0.01; p = 0.09), and vitamin E-coated dialyzer therapy did not improve the serum hemoglobin (MD, -0.03; 95% CI, -0.18 to 0.13; p = 0.74), albumin levels (SMD, -0.64; 95% CI, -1.62 to 0.34; p = 0.2), in addition, there was no significant difference in serum cholesterol (SMD, -0.07; 95% CI, -0.45 to 0.31; p = 0.71), triglycerides (MD, -2.77; 95% CI, -32.42 to 26.87; p = 0.85), high density lipoprotein (HDL) (SMD, 0.24; 95% CI, -0.14 to 0.62; p = 0.22) and low density lipoprotein (LDL) (SMD, 0.00; 95% CI, -0.38 to 0.37; p = 0.98) levels. CONCLUSIONS: Vitamin E-coated dialyzer may reduce the EPO resistance, but there is no conclusive evidence that vitamin E-coated dialyzer can improve the renal anemia, malnutrition, dyslipidemia and atherosclerosis status in hemodialysis (HD) patients. However, high-quality trials with hard clinical endpoints are required to fully elucidate the clinical value of vitamin E-coated dialyzer therapy.

Application of blunt dissection in ESD of a gastric submucosal tumor.

We performed endoscopic submucosal dissection of a gastric fundus tumor. It was difficult to strip the tumor completely due to space limitation, and we used blunt dissection to remove the tumor quickly and safely. Firstly, the basal area of the 2.5 cm submucosal tumor located in the gastric fundus was cut open, and the mucosa was dissected. The tumor was difficult to peel, therefore, a snare was used and the tumor was pulled and tightened slightly. Short electronic coagulation was used during the procedure. The tumor was then bluntly dissected. This method ensured rapid and complete removal of the tumor.

A parallel study of careHPV and Hybrid Capture 2 human papillomavirus DNA testing for cervical cancer screening in rural China.

Hybrid Capture 2 (HC2) has been demonstrated to be a feasible screening method for cervical cancer. Based upon HC2 technology, careHPV is a simple, rapid, accurate, and inexpensive screening test for women in low-resource settings. This study aims to characterize both the careHPV test and HC2 test, and to compare careHPV results of specimens stored in careHPV test collection medium (TCM) to HC2 results from partner specimens stored in Qiagen specimen transport medium and TCM. The positive rates of high-risk HPV in careHPV, HC2, and HC2 (TCM) were 13.2% (108/818), 13.2% (108/818), and 13.6% (111/818), respectively. The agreement rates of pairwise tests were 95.8% (95% CI: 94.5-97.2%), 96.7% (95% CI: 95.5-97.9%), and 97.2% (95% CI: 96.1-98.3%), respectively. The Kappa values of the pairwise tests were 0.82 (95% CI: 0.76-0.88), 0.86 (95% CI: 0.81-0.91), and 0.88 (95% CI: 0.83-0.93), respectively. Based on these findings, although careHPV is demonstrated to be a viable alternative to the HC2 test, improvements on the careHPV test are still required prior to its implementation as a suitable screening method for women in low-resource settings. Further studies on the significance and applicability of the careHPV test must be performed.