Risk factors related to the severity of COVID-19 in Wuhan.

Objective: To evaluate the characteristics at admission of patients with moderate COVID-19 in Wuhan and to explore risk factors associated with the severe prognosis of the disease for prognostic prediction. Methods: In this retrospective study, moderate and severe disease was defined according to the report of the WHO-China Joint Mission on COVID-19. Clinical characteristics and laboratory findings of 172 patients with laboratory-confirmed moderate COVID-19 were collected when they were admitted to the Cancer Center of Wuhan Union Hospital between February 13, 2020 and February 25, 2020. This cohort was followed to March 14, 2020. The outcomes, being discharged as mild cases or developing into severe cases, were categorized into two groups. The data were compared and analyzed with univariate logistic regression to identify the features that differed significantly between the two groups. Based on machine learning algorithms, a further feature selection procedure was performed to identify the features that can contribute the most to the prediction of disease severity. Results: Of the 172 patients, 112 were discharged as mild cases, and 60 developed into severe cases. Four clinical characteristics and 18 laboratory findings showed significant differences between the two groups in the statistical test (P<0.01) and univariate logistic regression analysis (P<0.01). In the further feature selection procedure, six features were chosen to obtain the best performance in discriminating the two groups with a linear kernel support vector machine. The mean accuracy was 91.38%, with a sensitivity of 0.90 and a specificity of 0.94. The six features included interleukin-6, high-sensitivity cardiac troponin I, procalcitonin, high-sensitivity C-reactive protein, chest distress and calcium level. Conclusions: With the data collected at admission, the combination of one clinical characteristic and five laboratory findings contributed the most to the discrimination between the two groups with a linear kernel support vector machine classifier. These factors may be risk factors that can be used to perform a prognostic prediction regarding the severity of the disease for patients with moderate COVID-19 in the early stage of the disease.

Correction to: High sensation seeking is associated with behavioral and neural insensitivity to increased negative outcomes during decision-making under uncertainty.

The original article unfortunately had "?" in place of "훥 "on few lines and those are corrected below.

Circulating sex hormone levels in relation to male sperm quality.

BACKGROUND: Although sex hormones play critical roles in spermatogenesis and sperm maturation, it remains inconclusive whether circulating sex hormones can serve as non-invasive biomarkers to improve the assessment of sperm quality. METHODS: We systematically evaluated the association of various sex hormones in serum with sperm quality among 338 men in subfertile couples. Concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), total estradiol (E2), and sex hormone-binding globulin (SHBG) were detected by chemiluminescent immunoassay. Free testosterone and estradiol were calculated using a validated algorithm. A generalized liner regression model controlling for lifestyle factors was used to evaluate the associations with sperm count, concentration, motility, and morphology. RESULTS: After adjusting for age, body mass index, current smoking and alcohol drinking, LH, FSH, and TT levels were all inversely associated with sperm motility (all P for trend < 0.05); however, in mutual adjustment analysis, only LH remained an inverse association with sperm motility after adjusting for FSH and TT levels (P for trend = 0.04). Higher concentrations of LH were also associated with lower sperm progressive motility (P for trend = 0.04). Moreover, LH and FSH levels were both inversely associated with normal sperm morphology (P for trend = 0.04 and 0.02, respectively). CONCLUSIONS: Increased levels of LH are associated with poor sperm motility and morphology, suggesting that LH may play a central role in sperm maturation. Future studies are warranted to assess potential clinical utility of LH for risk stratification and tailed prevention of male infertility.

High sensation seeking is associated with behavioral and neural insensitivity to increased negative outcomes during decision-making under uncertainty.

High-level sensation seeking (HSS) has been linked to a range of risky and unhealthy behavior; however, the neural mechanisms underlying such linkage remain unclear. In the present study, we used event-related potential (ERP) with a Balloon Analogue Risk Task (BART) to investigate how sensation seeking modulates brain responses to sequential decision-making with variable reward/loss outcome magnitudes. Behavior data showed that decision-making behavior was significantly affected by the large compared with the small magnitude of monetary outcome in the BART for individuals with low-level sensation seeking (LSS), but not for individuals with HSS. Similarly, HSS individuals displayed no changes in feedback-related negativity (FRN) in response to negative outcomes from decision-making with large or small reward/loss magnitudes, whereas LSS individuals showed greater FRN in response to decision-making with large loss magnitude than those with small loss magnitude. In addition, FRN amplitude differences correlated with decision-making behavior changes from small to large outcome magnitude for LSS, while such correlation was not observed for HSS. These findings suggest that a high-level of sensation seeking is associated with behavioral and neural insensitivity to increased negative outcome during decision-making under uncertainty, which may lead to greater risky behavior in these individuals when facing potential loss.

[Correlation of serum anti-Müllerian hormone with semen parameters].

OBJECTIVE: To investigate the relationship between the serum anti-Müllerian hormone (AMH) level and semen parameters. METHODS: We collected the data about 726 outpatients at the Male Infertility Clinic of Jinling Hospital from September 2015 to November 2016, including 72 with non-obstructive azoospermia, 123 with oligospermia, and 531 with normal sperm concentration. We obtained the semen volume, total sperm count, sperm concentration, sperm motility, the percentages of progressively motile sperm (PMS) and morphologically normal sperm (MNS), and the levels of serum AMH, inhibin B (INH-B), total testosterone (TT) and follicle - stimulating hormone (FSH) of the patients, analyzed the correlation of the serum AMH level with the other parameters, and compared the AMH level among different groups. RESULTS: The serum AMH level was found to be correlated positively with the total sperm count (r = 0.227, P <0.001), sperm concentration (r = 0.215, P <0.001), sperm motility (r = 0.111, P = 0.003), the percentage of PMS (r = 0.120, P = 0.001), and the levels of INH-B (r = 0.399, P <0.001) and TT (r = 0.184, P = 0.002), negatively with the FSH level (r = －0.283, P <0.001), but insignificantly with age, time of abstinence, semen volume, and the percentage of MNS (P >0.05). There was a statistically significant difference in the serum AMH level among the patients with non-obstructive azoospermia, oligozoospermia, and normal sperm concentration (ï¼»6.33 ± 4.26ï¼½ vs ï¼»8.26 ± 3.98ï¼½ vs ï¼»9.8 ± 5.19ï¼½ ng/ml, P <0.001). CONCLUSIONS: Serum AMH is a biomarker reflecting the function of Sertoli cells and its level is significantly correlated with sperm concentration and motility, suggesting that AMH may be involved in spermatogenesis and sperm maturation.

The administration of erythropoietin attenuates kidney injury induced by ischemia/reperfusion with increased activation of Wnt/ß-catenin signaling.

BACKGROUND/PURPOSE: Understanding the mechanisms of protecting the kidneys from injury is of great importance because there are no effective therapies that promote repair and the kidneys frequently do not repair adequately. Evidence has shown that erythropoietin (EPO) has a vital renoprotective role, independent of its erythropoietic effect. However, whether EPO can contribute to kidney repair after injury and the potential mechanisms are not fully understood. METHODS: To investigate the renoprotective mechanism of EPO, a kidney ischemia/reperfusion injury (IRI) model was induced in adult male Sprague-Dawley rats. The rats were subsequently randomly treated with EPO or a vehicle 6 hours after the kidney IRI. The rats were sacrificed on Day 3, Day 5, and Day 7 post kidney IRI. Renal function and histological alterations were examined. Renal interstitial macrophage infiltration, cell proliferation, apoptosis, and angiogenesis were evaluated by immunostaining. Furthermore, the effects of EPO on the Wnt/ß-catenin pathway and IRI-related micro-RNAs were investigated. RESULTS: The administration of EPO significantly improved renal function and reduced tubular injury. Furthermore, EPO treatment significantly prevented tubular cell apoptosis and promoted cell proliferation after IRI. Erythropoietin significantly suppressed macrophage infiltration, compared to the vehicle. In addition, treatment with EPO markedly prevented the loss of microvasculature. We have also demonstrated that, compared to the vehicle, EPO administration enhanced the expression of Wnt7b and ß-catenin, and downregulated miR-21, -214, -210, and -199a. CONCLUSION: Erythropoietin protects the kidneys against IRI by attenuating injury of the renal microvasculature and tubule epithelial cells, by promoting Wnt/ß-catenin pathway activation, and by regulating miRNA expression.

Recent Research Progress of Mn4+-Doped A2MF6 (A = Li, Na, K, Cs, or Rb; M = Si, Ti, Ge, or Sn) Red Phosphors Based on a Core-Shell Structure.

White light emitting diodes (WLEDs) are widely used due to their advantages of high efficiency, low electricity consumption, long service life, quick response time, environmental protection, and so on. The addition of red phosphor is beneficial to further improve the quality of WLEDs. The search for novel red phosphors has focused mainly on Eu2+ ion- and Mn4+ ion-doped compounds. Both of them have emissions in the red region, absorption in blue region, and similar quantum yields. Eu2+-doped phosphors possess a rather broad-band emission with a tail in the deep red spectral range, where the sensitivity of the human eye is significantly reduced, resulting in a decrease in luminous efficacy of WLEDs. Mn4+ ions provide a narrow emission band ~670 nm in oxide hosts, which is still almost unrecognizable to the human eye. Mn4+-doped fluoride phosphors have become one of the research hotspots in recent years due to their excellent fluorescent properties, thermal stability, and low cost. They possess broad absorption in the blue region, and a series of narrow red emission bands at around 630 nm, which are suitable to serve as red emitting components of WLEDs. However, the problem of easy hydrolysis in humid environments limits their application. Recent studies have shown that constructing a core-shell structure can effectively improve the water resistance of Mn4+-doped fluorides. This paper outlines the research progress of Mn4+-doped fluoride A2MF6 (A = Li, Na, K, Cs, or Rb; M = Si, Ti, Ge or Sn), which has been based on the core-shell structure in recent years. From the viewpoint of the core-shell structure, this paper mainly emphasizes the shell layer classification, synthesis methods, luminescent mechanism, the effect on luminescent properties, and water resistance, and it also gives some applications in terms of WLEDs. Moreover, it proposes challenges and developments in the future.

The effect of intravenous granisetron on prophylactic ephedrine for preventing hypotension after general anaesthesia induction in elderly patients: a randomized controlled trial.

Serotonin 3 receptor antagonists, a commonly used drug for preventing postoperative nausea and vomiting, have recently been reported to decrease the incidence of hypotension and the need for vasoactive drugs after spinal anaesthesia in obstetric surgery. However, it remains unknown whether they could also prevent hypotension after induction of general anaesthesia. In the current study, we aimed to investigate the effect of intravenous granisetron on prophylactic ephedrine for preventing hypotension after general anaesthesia induction in elderly patients. Sixty elderly patients were randomly assigned to receive granisetron or saline control 30 min before induction of general anaesthesia. The first patient in each group received a prophylactic dose of ephedrine (0.15 mg kg-1) to prevent hypotension. The prophylactic dose for each patient was increased or decreased by 0.05 mg/kg based on the efficacy results of the previous patient. The up-down sequential allocation analysis and probit regression was used to calculate the effective dose for 50% of patients (ED50) with prophylactic ephedrine. In the up-down sequential allocation analysis, the ED50 of ephedrine was significantly lower in group granisetron (0.08 mg kg-1 [95% CI, 0.06-0.11 mg kg-1]) when compared with group control (0.14 mg kg-1 [95% CI, 0.13-0.16 mg kg-1]) (P < 0.001). The conclusion was further supported by probit regression analysis (0.09 mg kg-1 [95% CI, 0.05-0.12 mg kg-1] in group granisetron and 0.14 mg kg-1 [95% CI, 0.12-0.16 mg kg-1] in group control). Intravenous granisetron reduced the requirement of prophylactic ephedrine in preventing hypotension after general anaesthesia induction in elderly patients.

Angiotensin receptor blockade attenuates glomerulosclerosis progression by promoting VEGF expression and bone marrow-derived cells recruitment.

BACKGROUND: Previous studies have demonstrated that angiotensin Type I receptor blockade (ARB) reduces proteinuria, reverses glomerular injury and glomerulosclerosis in rat models of diabetic nephropathy and glomerulonephritis. However, the cellular and molecular mechanisms are unclear. To investigate the role of cells of the bone marrow (BM) in glomerular repair seen during ARB administration, we induced progressive glomerulosclerosis in enhanced green fluorescent protein BM chimeric rats by a single injection of anti-Thy 1.1 monoclonal antibody, followed by unilateral nephrectomy. METHODS: Cohorts of rats received valsartan or no treatment from Week 2 to Week 8 after induction of disease. Renal function, urinary protein excretion and histological changes were examined 8 weeks after anti-Thy-1.1 monoclonal antibody injection. RESULTS: Valsartan administration improved renal function, reduced severity of glomerulosclrosis and markedly reduced mortality. Valsartan administration promoted regeneration of the glomerular tuft, lowered proteinuria and resulted in enhanced vascular endothelial growth factor (VEGF) expression in the cortex and glomerular tuft. In addition, valsartan promoted increased recruitment of BM-derived cells (BMDCs) many of which expressed VEGF and likely contributed directly to glomerular repair. Nearly all BMDCs recruited to the glomerulus expressed the monocyte/macrophage marker CD68. CONCLUSIONS: In conclusion, the data shows that ARB by valsartan prevents glomerulosclerosis progression by enhancing glomerular capillary repair which is associated with the recruitment of VEGF producing 'reparative' monocytes and macrophages from the BM.

Self-reported daily sleep quality modulates the impact of the framing effect on outcome evaluation in decision-making under uncertainty: An ERP study.

A growing body of research has largely confirmed and supported the idea that experimental sleep loss, such as sleep deprivation or sleep restriction, could affect individuals' risk-taking behavior and brain activity. However, whether self-reported sleep quality resulting from daily life modulates how feedback is evaluated during decision-making is still unclear. In this study, we used event-related potentials (ERPs) with a Balloon Analogue Risk Task (BART) to investigate how self-reported daily sleep quality modulates the brain's response to feedback from decision-making in the gain and loss frames. Behavioral data showed an increased aversion to uncertainty in the gain frame relative to the loss frame for individuals with higher sleep quality. However, this was not true for individuals with lower voluntary sleep quality. Similarly, the ERP data demonstrated that individuals with lower self-reported daily sleep quality displayed no changes in feedback-related negativity (FRN) in response to outcomes from decision-making in the gain and loss frames; however, individuals with higher self-reported daily sleep quality showed a greater FRN in response to decision-making in the gain frame than that in the loss frame. A Pearson correlation analysis showed that self-reported daily sleep quality was positively related to the variance of the FRN amplitude in response to the gain and loss frames. These findings suggest that framing effects on decision-making under uncertainty may depend on self-reported daily sleep quality and that the effects disappear when the sleep quality declines.

The impact of pegylated recombinant human growth hormone replacement therapy on glucose and lipid metabolism in children with growth hormone deficiency.

BACKGROUND: This study aimed to investigate the impact of pegylated recombinant human growth hormone (PEG-rhGH) replacement therapy on glucose and lipid metabolism in children with growth hormone deficiency (GHD). METHODS: A total of 17 children with a growth hormone deficiency were treated with PEG-rhGH (trade name Juyi' Erchun) via subcutaneous injection once a week before sleep for 3 months. The doses given were 0.2 and 0.15 mg/(kg·week). The injection sites included the upper arm, the front of the thigh, and the periumbilical area of the abdominal wall. Follow-ups were conducted every 3 months after the treatment to detect the metabolic indexes of the children's blood glucose and blood lipids. Growth and development indexes, thyroid function, and other indexes were also detected regularly. The glucose and lipid metabolism indexes of each child, including fasting blood glucose, glycosylated hemoglobin, fasting insulin, total cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL), were measured before the treatment and every three months after the treatment. The total detection time was 3-30 months. RESULTS: No significant differences in fasting blood glucose, glycosylated hemoglobin, fasting insulin, total cholesterol, triglycerides, HDL, and LDL were detected after the treatment when compared with measurements taken before the treatment (P>0.05). CONCLUSIONS: PEG-rhGH replacement therapy may have no significant impact on glucose and lipid metabolism in children with GHD. However, this conclusion needs to be verified through studies with larger samples and long-term follow-up periods.

Electroacupuncture Reduces Oocyte Number and Maintains Vascular Barrier Against Ovarian Hyperstimulation Syndrome by Regulating CD200.

Ovarian hyperstimulation syndrome (OHSS) is a common complication caused by ovulatory stimulation therapy, which manifests as an increase in ovarian volume, an increase in the number of oocytes retrieved, and increased vascular permeability throughout the body and especially in ovarian tissue. In our previous study, we found that electroacupuncture (EA) could prevent the progression of OHSS, by mainly affecting ovary. However, the specific molecules and the mechanism of this process were still unknown. In order to explore the underlying mechanism, OHSS rat model was established and EA treatment was performed, which was followed by proteomic analysis of ovaries. Results showed a significant increase in the expression level of CD200 in the ovaries of OHSS group treated with EA than those of OHSS group. Clinical data showed that the level of CD200 in follicular fluid was negatively correlated with the number of oocytes retrieved and serum E2 level. Further in vitro experiments showed a concentration-dependent role of human chorionic gonadotropin (hCG) in reducing CD200 and CD200R levels, and increasing inflammatory cytokine levels in cultured KGN cells. In human umbilical vein endothelial cells (HUVECs), the vascular barrier function was improved by CM (cultural medium from KGN cell) which treated with CD200Fc (CD200R agonist). Meanwhile, the results of in vivo experiments indicated that EA reduced the number of ovarian corpora lutea, decreased inflammatory response, and improved the vascular barrier function by increasing the expression of CD200 and CD200R in rat ovaries. These findings suggest that EA treatment may reduce oocyte number and maintain vascular barrier against OHSS through ovarian anti-inflammatory response mediated by CD200. Therefore, this study is the first to identify CD200 as a main of EA in the ovary and elucidate the possible mechanism of EA on preventing and treating OHSS, which provide a scientific basis for CD200 as an effector and indicator in EA treatment.

Gender-associated difference following COVID-19 virus infection: Implications for thymosin alpha-1 therapy.

Gender influences clinical presentations, duration and severity of symptoms, and therapy outcome in coronavirus disease 2019 (COVID-19) infection. Whether the immune response to Tα1 treatment for SARS-CoV-2 differs between the sexes, and whether this difference explains the male susceptibility to COVID-19, is unclear. This study aimed to investigate the efficiency and safety of Tα1 treatment and provide a basis for practically identifying gender differences characteristics and features of COVID-19. One hundred twenty-seven patients had COVID-19 symptoms and tested COVID19-positive (female 42.52%) in Wuhan union hospital were enrolled for medication. They were randomly divided into groups Control and Tα1 intervention. Seventy-eight patients received a subcutaneous injection of 1.6 mg Tα1, based on supportive treatment for 15 days. The control group included untreated 49 COVID19 patients closely matched for gender and age and received regular supportive treatment. In this retrospective analysis, we found that COVID-19-infected males reported more symptoms than COVID-19-infected females. A high degree of gender differences-related variability was observed in CRP and PCT levels and the cell counts of many lymphocyte subpopulations in the COVID-19 patients after Tα1 intervention. Levels of CRP and IL-6 were higher in Tα1-treated male group than Tα1-treated female group, while the level of PCT was significantly lower in Tα1-treated male group. Gender differences may be a factor in sustaining COVID-19 immunity responded to Tα1, male and female show statistically significant differences in relevance to cytokine production associated with the development of a more significant number of symptoms. This leaves the question of identifying gender-specific risk factors to explain these differences.

Paying out one versus paying out all trials and the decrease in behavioral and brain activity in the Balloon Analogue Risk Task.

Both pay out for all the trials (pay-all) and pay out for only one randomly selected trial (pay-one), are widely used in economics experiments to elicit choices from study participants. However, whether pay-all and pay-one payments modulate risk-taking and decision-making in the same manner remains controversial. In the present study, we used event-related potentials (ERPs) with the Balloon Analogue Risk Task (BART) to investigate the effects of the pay-all and pay-one payments on dynamic sequential decision-making behavior under uncertainty and brain activity. Behavioral data showed an increased uncertainty aversion, especially after negative feedback (balloon explosion) during the BART in the pay-all condition, as compared to those in the pay-one condition. The ERP data demonstrated a larger feedback-related negativity (FRN) in response to the balloons that exploded during decision-making in the pay-all condition, as compared to those in the pay-one condition. In addition, in the pay-all condition, the FRN amplitude elicited by the explosion of the balloon correlated with the future decision-making behavior, although this correlation was not observed in the pay-one condition. In contrast, the P300 component was unresponsive to payment method manipulation. These findings demonstrate the differential effects of the pay-all versus the pay-one payments on decision-making behavior under uncertainty and brain activity, suggesting that the payment method plays an important role in dynamic decision-making studies.

Exploring the valence-framing effect: Gain frame enhances behavioral and brain sensitivity to the failure of decision-making under uncertainty.

The framing effect, which is one of the cognitive biases, can play a major role in changing preferences and the decision-making process. However, whether the gain and loss frames modulate the evaluation of feedback during decision-making is still unclear. In this study, we used event-related potentials (ERPs) with a Balloon Analogue Risk Task (BART) paradigm to examine the effects of a gain and loss frame on the evaluation of feedback during the decision-making process of the brain. Behavioral data showed an increased uncertainty-aversion, especially after receiving negative feedback (balloon explosion) during the completion of the BART in the gain frame relative to the loss frame. The ERP data demonstrated a more negative feedback-related negativity (FRN) after receiving negative feedback in the gain frame relative to the loss frame. Additionally, the FRN amplitude elicited by the negative feedback correlated with the future decision-making behavior in both the gain and loss frames. These findings demonstrated that, in comparison to the loss frame, the gain frame increased behavior and brain sensitivity to the failure of decision-making under uncertainty.

Potential function of CTLA-4 in the tumourigenic capacity of melanoma stem cells.

Extensive clinical evidence supports that cytotoxic T lymphocyte antigen-4 (CTLA-4) is expressed in a variety of human malignant tumour cells in addition to T cells. In certain types of cancer, the overexpression of CTLA-4 is associated with poor patient prognosis. However, few studies have demonstrated the effects of tumour-intrinsic CTLA-4 in cancer stem cells, including melanoma stem cells (MSCs). In the present study, it was demonstrated that melanoma cell-intrinsic CTLA-4 induced tumour cell proliferation in vitro and suppressed tumour cell apoptosis. Furthermore, CTLA-4 was expressed in aldehyde dehydrogenase (ALDH)+ MSCs. CTLA-4 inhibited MSCs proliferation in vitro by blocking antibodies and significantly downregulated ALDH1A1, ALDH1A3 and ALDH2 mRNA expression (P<0.01). Functionally, blocking CTLA-4 in melanoma cell lines suppressed the properties of stem-like cells, including ALDH activity and significantly suppressed the ability of these cells to form spheres in vitro (P<0.05). In addition, the blocking of CTLA-4 in melanoma cells suppressed the properties of stem-like cells in vivo, including the capacity for tumourigenesis. The presence of residual ALDH+ MSCs within the tumour was observed, and the blocking CTLA-4 significantly decreased the number of residual ALDH+ MSCs in vivo (P<0.01). Altogether, these results indicate the identification of a novel mechanism underlying melanoma progression in the present study and that CTLA-4-targeted therapy may benefit candidate CTLA-4-targeted therapy by improving the long-term outcome for patients with advanced stages of melanoma.

Effects of saturated palmitic acid and omega-3 polyunsaturated fatty acids on Sertoli cell apoptosis.

Obesity is believed to negatively affect male semen quality and is accompanied by dysregulation of free fatty acid (FFA) metabolism in plasma. However, the implication of dysregulated FFA on semen quality and the involvement of Sertoli cells remain unclear. In the present study, we report obesity decreased Sertoli cell viability through dysregulated FFAs. We observed an increased rate of apoptosis in Sertoli cells, accompanied with elevated FFA levels, in the testes of obese mice that were provided a high-fat diet (HFD). Moreover, the levels of reactive oxygen species were elevated. Furthermore, we demonstrated by in vitro assays that saturated palmitic acid (PA), which is the most common saturated FFA in plasma, led to decreased cell viability of TM4 Sertoli cells in a time- and dose-dependent manner. A similar finding was noted in primary mouse Sertoli cells. In contrast to saturated FFA, omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) protected Sertoli cells from PA-induced lipotoxicity at the physiologically relevant levels. These results indicated that the lipotoxicity of saturated fatty acids might be the cause of obesity-induced Sertoli cell apoptosis, which leads to decreased semen quality. In addition, ω-3 PUFAs could be classified as protective FFAs. ABBREVIATIONS: FFA: free fatty acid; HFD: high-fat diet; SD: standard diet; PA: palmitic acid; PUFA: polyunsaturated fatty acid; AI: apoptotic index; MTT: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide; ROS: reactive oxygen species; HE: Hematoxylin and eosin; WT1: Wilm Tumor 1; NAFLD: non- alcoholic fatty liver disease; DCFH-DA: 2', 7' dichlorofluorescin diacetate; 36B4: acidic ribosomal phosphoprotein P0; SD: standard deviation; EPA: eicosapentaenoic acid; PI: propidium iodide; DHA: docosahexenoic acid.

Wnt4 is significantly upregulated during the early phases of cisplatin-induced acute kidney injury.

Wnt4 is a secreted growth factor associated with renal tubulogenesis. Our previous studies identified that renal and urinary Wnt4 are upregulated following ischemia-reperfusion injury in mice, but the roles of Wnt4 in other forms of acute kidney injury (AKI) remain unclear. Here, we investigated the changes in Wnt4 expression using a cisplatin-induced AKI model. We found that renal and urinary Wnt4 expression increased as early as 12 hours, peaked at day 4 following cisplatin-induced AKI and was closely correlated with histopathological alterations. By contrast, the serum creatinine level was significantly elevated until day 3, indicating that Wnt4 is more sensitive to early tubular injury than serum creatinine. In addition, renal Wnt4 was co-stained with aquaporin-1 and thiazide-sensitive NaCl cotransporter, suggesting that Wnt4 can detect both proximal and distal tubular injuries. These data were further confirmed in a clinical study. Increased urinary Wnt4 expression was detected earlier than serum creatinine and eGFR in patients with contrast-induced AKI after vascular intervention. This study is the first to demonstrate that increased expression of renal and urinary Wnt4 can be detected earlier than serum creatinine after drug-induced AKI. In particular, urinary Wnt4 can potentially serve as a noninvasive biomarker for monitoring patients with tubular injury.

Urine anti-PLA2R antibody is a novel biomarker of idiopathic membranous nephropathy.

Since urine samples more directly reflect kidney alterations and damage than blood samples, we investigated whether urine anti-PLA2R antibody (uPLA2R-Ab) could be utilized similarly to serum anti-PLA2R antibody (sPLA2R-Ab) as a noninvasive biomarker of idiopathic membranous nephropathy (IMN). In this study, we performed a qualitative analysis using an indirect immunofluorescence test (IIFT) and measured uPLA2R-Ab and sPLA2R-Ab concentrations using an enzyme-linked immunosorbent assay (ELISA) in 28 patients with biopsy-proven IMN and 12 patients with secondary membranous nephropathy (SMN). Overall, 64.3% (n=18) of patients with IMN had IIFT-positive sPLA2R-Ab, 67.9% (n=19) of patients with IMN had IIFT-positive uPLA2R-Ab, and none of the SMN patients had IIFT-positive sPLA2R-Ab or uPLA2R-Ab. The titers of the anti-PLA2R antibody from the IMN patients in the urine (10.72±22.24 RU/µmol, presented as uPLA2R-Ab/urine creatinine) and serum (107.36±140.93 RU/ml) were higher than those from the SMN patients (0.51±0.46 RU/µmol, 0.008±0.029 RU/ml, respectively, p<0.05). Statistical analyses indicated that there were positive correlations between uPLA2R-Ab and gPLA2R, sPLA2R-Ab or urinary protein and negative correlations between uPLA2R-Ab and serum albumin in patients with IMN. In conclusion, uPLA2R-Ab is a novel biomarker of IMN. sPLA2R-Ab combined with uPLA2R-Ab might be more helpful for diagnosis and activity in PLA2R associated MN.