The causal relationship between COVID-19 and estimated glomerular filtration rate: a bidirectional Mendelian randomization study.

BACKGROUND: Previous Mendelian studies identified a causal relationship between renal function, as assessed by estimated glomerular filtration rate (eGFR), and severe infection with coronavirus disease 2019 (COVID-19). However, much is still unknown because of the limited number of associated single nucleotide polymorphisms (SNPs) of COVID-19 and the lack of cystatin C testing. Therefore, in the present study, we aimed to determine the genetic mechanisms responsible for the association between eGFR and COVID-19 in a European population. METHODS: We performed bidirectional Mendelian randomization (MR) analysis on large-scale genome-wide association study (GWAS) data; log-eGFR was calculated from the serum levels of creatinine or cystatin C by applying the Chronic Kidney Disease Genetics (CKDGen) Meta-analysis Dataset combined with the UK Biobank (N = 1,004,040) and on COVID-19 phenotypes (122,616 COVID-19 cases and 2,475,240 controls) from COVID19-hg GWAS meta-analyses round 7. The inverse-variance weighted method was used as the main method for estimation. RESULTS: Analyses showed that the genetically instrumented reduced log-eGFR, as calculated from the serum levels of creatinine, was associated with a significantly higher risk of severe COVID-19 (odds ratio [OR]: 2.73, 95% confidence interval [CI]: 1.38-5.41, P < 0.05) and significantly related to COVID-19 hospitalization (OR: 2.36, 95% CI: 1.39-4.00, P < 0.05) or infection (OR: 1.24, 95% CI: 1.01-1.53, P < 0.05). The significance of these associations remained when using log-eGFR based on the serum levels of cystatin C as genetically instrumented. However, genetically instrumented COVID-19, regardless of phenotype, was not related to log-eGFR, as calculated by either the serum levels of creatinine or cystatin C. CONCLUSIONS: Our findings suggest that genetical predisposition to reduced kidney function may represent a risk factor for COVID-19. However, a consistent and significant effect of COVID-19 on kidney function was not identified in this study.

Lower serum irisin levels are associated with the increasing mortality of cardiovascular and cerebrovascular diseases in hemodialysis patients.

BACKGROUND: Irisin is a recently discovered myokine/adipokine and lower levels of irisin were proved to be associated with adverse outcomes of cardiovascular and cerebrovascular diseases (CCVD) in general population. A significant decrease of irisin concentrations were also detected in patients with chronic kidney disease (CKD). In the present study, we investigated whether the serum irisin levels were associated with cardiovascular and cerebrovascular mortality in hemodialysis (HD) patients. METHODS: This retrospective cohort study enrolled 152 HD patients. Kaplan-Meier analysis was used to estimate the cumulative mortality of CCVD. The differences between the survival curves were compared by log-rank test. A multivariable Cox regression analysis was employed to identify the predictors of CCVD related deaths. RESULTS: Among 152 HD patients, 55 patients died and 18 of them died of CCVD, 97 HD patients survived. Compared with the survival group, patients died of CCVD had significantly lower serum irisin levels [23.6 (2.2, 319.4) vs. 45.7 (2.1, 367.8) ng/mL, P<0.05]. The Kaplan-Meier survival curves showed that patients with lower levels of irisin had higher CCVD mortality. The Cox regression analysis indicated lower irisin level as an independent risk factor for CCVD mortality in HD patients but not for all-cause mortality. CONCLUSIONS: Our results provided an association between lower irisin level and CCVD mortality in HD patients. Lower levels of irisin increased the mortality of CCVD in HD patients.

Frequent DYSF rare variants/mutations in 152 Han Chinese samples with ovarian endometriosis.

PURPOSE: Endometriosis is a common chronic gynecological disease greatly affecting women health. Prior studies have implicated that dysferlin (DYSF) aberration might be involved in the pathogenesis of ovarian endometriosis. In the present study, we explore the potential presence of DYSF mutations in a total of 152 Han Chinese samples with ovarian endometriosis. METHODS: We analyze the potential presence of DYSF mutations by direct DNA sequencing. RESULTS: A total of seven rare variants/mutations in the DYSF gene in 10 out of 152 samples (6.6%) were identified, including 5 rare variants and 2 novel mutations. For the 5 rare variants, p.R334W and p.G941S existed in 2 samples, p.R865W, p.R1173H and p.G1531S existed in single sample, respectively; for the two novel mutations, p.W352* and p.I1642F, they were identified in three patients. These rare variants/mutations were absent or existed at extremely low frequency either in our 1006 local control women without endometriosis, or in the China Metabolic Analytics Project (ChinaMAP) and Genome Aggregation Database (gnomAD) databases. Evolutionary conservation analysis results suggested that all of these rare variants/mutations were evolutionarily conserved among 11 vertebrate species from Human to Fox. Furthermore, in silico analysis results suggested these rare variants/mutations were disease-causing. Nevertheless, we find no significant association between DYSF rare variants/mutations and the clinical features in our patients. To our knowledge, this is the first report revealing frequent DYSF mutations in ovarian endometriosis. CONCLUSION: We identified a high frequency of DYSF rare variants/mutations in ovarian endometriosis for the first time. This study suggests a new correlation between DYSF rare variants/mutations and ovarian endometriosis, implicating DYSF rare variants/mutations might be positively involved in the pathogenesis of ovarian endometriosis.

Interleukin-1ß Promotes Ox-LDL Uptake by Human Glomerular Mesangial Cells via LOX-1.

The aim of this study was to determine whether interleukin-1ß (IL-1ß) promotes oxidised low-density lipoprotein (Ox-LDL) uptake by human glomerular mesangial cells (HMCs) and its effect on the expression of lectin-like Ox-LDL receptor 1 (LOX-1) and to identify pathways through which IL-1ß affects lipid uptake. Confocal laser scanning microscopy and flow cytometry were used to observe the effect of IL-1ß on lipid uptake by HMCs and the pathway by which IL-1ß may mediate lipid uptake. Real-time polymerase chain reaction (PCR) and western blotting were used to evaluate the effect of IL-1ß on LOX-1 expression. Confocal laser scanning microscopy and flow cytometry revealed that IL-1ß promoted uptake of fluorescent Dil-labelled Ox-LDL(Dil-Ox-LDL) by HMCs and the enhanced uptake of Dil-Ox-LDL was partially inhibited by an anti-LOX-1 antibody evaluated by flow cytometry. Further, IL-1ß promoted LOX-1 mRNA and protein expression of HMCs in a dose- and time-dependent manner. Thus, Ox-LDL is ingested by HMCs under basic conditions. Inflammatory cytokine IL-1ß promotes Ox-LDL uptake by HMCs. Furthermore, IL-1ß promotes the mRNA and protein expression of LOX-1, a specific receptor of Ox-LDL, suggesting that the enhancement of Ox-LDL uptake may be mediated by LOX-1 pathway. Anti-LOX-1 therapy may be a promising option for treatment of glomerulosclerosis.

Infrared-assisted extraction followed by high performance liquid chromatography to determine angoroside C, cinnamic acid, and harpagoside content in Scrophularia ningpoensis.

BACKGROUND: Angoroside C, cinnamic acid, and harpagoside are bioactive constituents in Scrophularia ningpoensis. Currently, an infrared-assisted extraction (IRAE) method coupled with high-performance liquid chromatography with ultraviolet detection (HPLC-UV) for the analysis of bioactive constituents in this plant is lacking. METHODS: A method based on HPLC following IRAE has been developed for quantifying angoroside C, cinnamic acid, and harpagoside in Scrophularia ningpoensis. Four main factors, namely, extraction solvent, solid/liquid ratio, illumination time, and distance between the infrared lamp and the round-bottom flask, were optimized for extraction. Furthermore, conventional ultrasonic extraction (USE) and microwave-assisted extraction (MAE) were also investigated to validate the developed method. RESULTS: The optimal extraction conditions were as follows: ethanol concentration, 37.5%; solid/liquid ratio, 1:25; illumination time, 10 min; and distance between infrared lamp and round-bottom flask, 3 cm. The results of method validation demonstrated that the developed method meets the requirement of analysis. CONCLUSION: The results show that the IRAE-HPLC is a simple, accurate, and green analytical preparatory method for the potential extraction and quantification of angoroside C, cinnamic acid, and harpagoside in Scrophularia ningpoensis.

Expression of LOX-1 in human mesangial cells is increased by Ox-LDL and IL-1ß treatment.

The present study aimed to determine whether the expression of lectin-like oxidized LDL receptor 1 (LOX-1) could be induced by oxidized low-density lipoprotein (Ox-LDL) and interleukin 1ß (IL-1ß) in human mesangial cells (HMCs). Oil Red O staining was used to observe the uptake of Ox-LDL by HMCs stimulated with IL-1ß, and reverse transcription-quantitative polymerase chain reaction analysis and western blotting were used to examine the expression of LOX-1 in HMC following Ox-LDL and IL-1ß treatment. Uptake of Ox-LDL by HMCs was upregulated upon stimulation with IL-1ß. Furthermore, Ox-LDL (10-40 µg/ml) treatment induced LOX-1 mRNA and protein expression in a dose-dependent manner. In addition, when HMCs were treated with IL-1ß and Ox-LDL, the expression of LOX-1 was enhanced further. These results indicated that inhibiting LOX-1 expression or inhibiting the Ox-LDL/LOX-1 signaling axis may be a potential novel method for treating renal disease.

Efficacy of Intravenous Iron Sucrose in Hemodialysis Patients with Restless Legs Syndrome (RLS): A Randomized, Placebo-Controlled Study.

BACKGROUND Restless legs syndrome (RLS) is a common disorder in hemodialysis (HD) patients that causes sleep disturbances and diminished quality of life. Because iron deficiency has been implicated in the pathogenesis of RLS, we sought to investigate the effects of intravenous (IV) iron sucrose on symptoms of RLS in HD patients. MATERIAL AND METHODS The study was a randomized, placebo-controlled study of 1000 mg iron sucrose versus normal saline as placebo. Patients were evaluated at baseline and 2 weeks after the last injection. The severity of RLS was assessed using the International RLS Study Group rating scale (IRLS). Blood samples were taken to measure iron parameters reflecting the iron status, including serum ferritin (SF) concentration, percentage transferrin saturation (TSAT%) and hemoglobin (Hb), and other biochemical parameters as safety assessments, including creatinine (Cr), urea, intact parathyroid hormone (iPTH), and the index of urea clearance (Kt/V). Adverse events were monitored in all subjects during the period of infusion. RESULTS After 2 weeks, IRLS scores decreased more in the IV-iron group (-7.38±2.03) than in the placebo group (-0.81±2.61) (P=0.000). Serum ferritin, TSAT, and hemoglobin increased more in the IV-iron group (227.63±77.64 µg/L; 26.06±7.77%; 13.98±3.62g/L, respectively) than in the placebo group (SF, p=0.000; TSAT, p=0.000; Hb, p=0.000, respectively). There were no significant differences between IV-iron and placebo groups in Cr, urea, iPTH, and Kt/V. No adverse effects were observed in the study. CONCLUSIONS IV iron sucrose is a safe and effective treatment for reducing RLS symptoms in HD patients over the short-term.

Immunophenotypic and prognostic analysis of PAX8 and TTF-1 expressions in neuroendocrine carcinomas of thymic origin: A comparative study with their pulmonary counterparts.

OBJECTIVES: To investigate the immunoreactivity of TTF-1 and PAX8 in neuroendocrine carcinoma of thymic (TNEC) and pulmonary origins (PNEC), and whether their immunophenotyping could be used to distinguish between NEC of the two sites, as well as prognosis of patients with TNEC. METHODS: Twenty-two cases of TNEC and 20 cases of PNEC were selected for immunohistochemical analysis using PAX8 and TTF-1. Clinical data and follow-up information were obtained for survival analyses. RESULTS: TTF-1 immunoreactivity was seen in 19 PNEC cases (95%) and 13 TNEC cases (59.1%). PAX8 was negative in all pulmonary tumors while positive in 19 thymic cases (86.4%). TTF-1 positivity was associated with high sensitivity but low specificity for PNEC, and adding PAX8 negativity significantly increased the specificity. PAX8 positivity alone showed essentially 100% specificity and 86.4% sensitivity for TNEC. Survival analysis showed lung metastasis as a significant prognostic factor in TNEC. CONCLUSION: Our study demonstrated that TTF-1/PAX8 immunophenotyping may be helpful for differential diagnosis of NECs of pulmonary and thymic origins. TTF-1+/PAX8- immunophenotyping showed high specificity for PNECs, while PAX8+ alone showed a good diagnostic accuracy for TNEC. Lung metastasis was a predictive factor that associated with survival of TNEC patients. J. Surg. Oncol. 2016;114:697-702. © 2016 Wiley Periodicals, Inc.

Patient-physician mistrust and violence against physicians in Guangdong Province, China: a qualitative study.

OBJECTIVE: To better understand the origins, manifestations and current policy responses to patient-physician mistrust in China. DESIGN: Qualitative study using in-depth interviews focused on personal experiences of patient-physician mistrust and trust. SETTING: Guangdong Province, China. PARTICIPANTS: One hundred and sixty patients, patient family members, physicians, nurses and hospital administrators at seven hospitals varying in type, geography and stages of achieving goals of health reform. These interviews included purposive selection of individuals who had experienced both trustful and mistrustful patient-physician relationships. RESULTS: One of the most prominent forces driving patient-physician mistrust was a patient perception of injustice within the medical sphere, related to profit mongering, knowledge imbalances and physician conflicts of interest. Individual physicians, departments and hospitals were explicitly incentivised to generate revenue without evaluation of caregiving. Physicians did not receive training in negotiating medical disputes or humanistic principles that underpin caregiving. Patient-physician mistrust precipitated medical disputes leading to the following outcomes: non-resolution with patient resentment towards physicians; violent resolution such as physical and verbal attacks against physicians; and non-violent resolution such as hospital-mediated dispute resolution. Policy responses to violence included increased hospital security forces, which inadvertently fuelled mistrust. Instead of encouraging communication that facilitated resolution, medical disputes sometimes ignited a vicious cycle leading to mob violence. However, patient-physician interactions at one hospital that has implemented a primary care model embodying health reform goals showed improved patient-physician trust. CONCLUSIONS: The blind pursuit of financial profits at a systems level has eroded patient-physician trust in China. Restructuring incentives, reforming medical education and promoting caregiving are pathways towards restoring trust. Assessing and valuing the quality of caregiving is essential for transitioning away from entrenched profit-focused models. Moral, in addition to regulatory and legal, responses are urgently needed to restore trust.

[Upper arm vein versus subclavian vein for totally implantable venous access ports for patients with gastrointestinal malignancy: a retrospective comparison of complications].

OBJECTIVE: To compare two different routes of totally implantable venous access ports (TIVPs) from the upper arm vein and the subclavian vein in terms of complications for patients with gastrointestinal malignancy. METHODS: Patients who underwent implantations of TIVPs from September 2013 to January 2015 were retrospectively evaluated. The outcome measurements were rates and types of postprocedural early-stage and long-term complications. RESULTS: A total of 208 patients(upper arm vein group, 86; subclavian vein group, 122) were included in this study. All TIVPs were implanted successfully. The rate of catheter displacement was higher in upper arm vein group(14.0% vs 5.7%, P=0.04), while other postprocedural early-stage complications had no significant difference between the two groups. The occurrence of transfusion obstacle and rates of overall postprocedural long-term complications were significantly lower in upper arm vein group than that in subclavian vein group(1.2% vs. 9.8%, P=0.02; 7.0% vs. 27.0%, P=0.01, respectively). CONCLUSION: Compared with subclavian vein group, upper arm vein group has lower postprocedural long-term complication rates and is recommended as a safe and comfortable choice for port implantation.

[Effects of erigeron injection on renal interstitial fibrosis in rats].

OBJECTIVE: To investigate the effect and mechanism of Erigeron Injection (EI) on renal interstitial fibrosis in rats. METHODS: Unilateral ureteral obstruction (UUO) model rats were taken as the subject of study. Thirty-six Sprague-Dawley rats were randomly divided into the control group (A), the UUO model group (B) and the treatment group (C) treated with intraperitoneal injection of EI 5 mL/kg per day from 24 h before to 9 days after the operation. On the 10th day of UUO, rats were killed and their kidneys were processed to paraffin sections with HE, PAS and picro-sirius-red staining. The pathological change of renal tubular interstitial tissue and relative cortical/interstitial volume (C/I) as well as the relative content of collagen (RC) were observed by light microscope. The expression of transforming growth factor beta1 (TGF-beta1), alpha-smooth muscle actin (alpha-SMA) and collagen I in the renal mesenchyma were examined by immunohistochemistry. RESULTS: Marked renal interstitial fibrosis changes were found in Group B and C, but the changes were milder in Group C. C/I and RC were higher in Groups B and C as compared with those in Group A (P < 0.01), but they were much lower in Group C than in Group B (P < 0.01). The expression of TGF-beta1, alpha-SMA and collagen I were higher in Group B and C than those in Group A (P < 0.05), but they were lower in Group C than in Group B (P < 0.05). CONCLUSION: EI could ameliorate renal interstitial fibrosis in rats, which might be partially realized by down-regulating the expression of TGF-beta1 to prevent the renal epithelial cell differentiation and reducing the synthesis of collagen I.