MAGI2 ameliorates podocyte apoptosis of diabetic kidney disease through communication with TGF-ß-Smad3/nephrin pathway.

Podocytes, the key component of the glomerular filtration barrier (GFB), are gradually lost during the progression of diabetic kidney disease (DKD), severely compromising kidney functionality. The molecular mechanisms regulating the survival of podocytes in DKD are incompletely understood. Here, we show that membrane-associated guanylate kinase inverted 2 (MAGI2) is specifically expressed in renal podocytes, and promotes podocyte survival in DKD. We found that MAGI2 expression was downregulated in podocytes cultured with high-glucose in vitro, and in kidneys of db/db mice as well as DKD patients. Conversely, we found enforced expression of MAGI2 via AAV transduction protected podocytes from apoptosis, with concomitant improvement of renal functions. Mechanistically, we found that MAGI2 deficiency induced by high glucose levels activates TGF-ß signaling to decrease the expression of anti-apoptotic proteins. These results indicate that MAGI2 protects podocytes from cell death, and can be harnessed therapeutically to improve renal function in diabetic kidney disease.

What is the prognosis of ANCA-associated glomerulonephritis with immune deposition?

OBJECTIVES: This study aimed to analyze histological and clinical characteristics of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) showing renal involvement to investigate the associations between immune complexes (IC) and clinicopathological indicators, and explore the renal outcomes of AAV. METHODS: We retrospectively evaluated the histopathological features and clinical characteristics of 80 renal biopsies of patients with AAV with renal involvement. Renal morphology was classified into two (with and without the presence of IC and complement deposition). Endpoints included end-stage kidney disease (ESKD) and death. RESULTS: Compared with patients without IC, patients with immune deposition had lower complement C3 (0.80 ± 0.27 vs. 0.93 ± 0.20, p = 0.024), more severe hematuria [133 (46-299) vs. 33 (15-115), p = 0.001] but had milder chronic pathology, including chronic tubular atrophy (p = 0.03), chronic interstitial fibrosis (p = 0.049). Patients in the immune deposition group showed a tendency to have more severe crescent formation and less glomerulosclerosis, but the difference was not statistically significant. Endpoints such as death and ESKD were not significantly different between the two groups. CONCLUSIONS: Immune deposition may indicate lower complement C3, more severe hematuria and glomerular lesions, milder tubular atrophy, and interstitial fibrosis, but it cannot predict the renal outcome.

Development and internal validation of machine learning algorithms for end-stage renal disease risk prediction model of people with type 2 diabetes mellitus and diabetic kidney disease.

AIMS: Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD) and is associated with increased morbidity and mortality in patients with diabetes. Identification of risk factors involved in the progression of DKD to ESRD is expected to result in early detection and appropriate intervention and improve prognosis. Therefore, this study aimed to establish a risk prediction model for ESRD resulting from DKD in patients with type 2 diabetes mellitus (T2DM). METHODS: Between January 2008 and July 2019, a total of 390 Chinese patients with T2DM and DKD confirmed by percutaneous renal biopsy were enrolled and followed up for at least 1 year. Four machine learning algorithms (gradient boosting machine, support vector machine, logistic regression, and random forest (RF)) were used to identify the critical clinical and pathological features and to build a risk prediction model for ESRD. RESULTS: There were 158 renal outcome events (ESRD) (40.51%) during the 3-year median follow up. The RF algorithm showed the best performance at predicting progression to ESRD, showing the highest AUC (0.90) and ACC (82.65%). The RF algorithm identified five major factors: Cystatin-C, serum albumin (sAlb), hemoglobin (Hb), 24-hour urine urinary total protein, and estimated glomerular filtration rate. A nomogram according to the aforementioned five predictive factors was constructed to predict the incidence of ESRD. CONCLUSION: Machine learning algorithms can efficiently predict the incident ESRD in DKD participants. Compared with the previous models, the importance of sAlb and Hb were highlighted in the current model.HighlightsWhat is already known? Identification of risk factors for the progression of DKD to ESRD is expected to improve the prognosis by early detection and appropriate intervention.What this study has found? Machine learning algorithms were used to construct a risk prediction model of ESRD in patients with T2DM and DKD. The major predictive factors were found to be CysC, sAlb, Hb, eGFR, and UTP.What are the implications of the study? In contrast with the treatment of participants with early-phase T2DM with or without mild kidney damage, major emphasis should be placed on indicators of kidney function, nutrition, anemia, and proteinuria for participants with T2DM and advanced DKD to delay ESRD, rather than age, sex, and control of hypertension and glycemia.

The C2H2 Transcription Factor SltA Contributes to Azole Resistance by Coregulating the Expression of the Drug Target Erg11A and the Drug Efflux Pump Mdr1 in Aspergillus fumigatus.

The emergence of azole-resistant fungal pathogens has posed a great threat to public health worldwide. Although the molecular mechanism of azole resistance has been extensively investigated, the potential regulators of azole resistance remain largely unexplored. In this study, we identified a new function of the fungal specific C2H2 zinc finger transcription factor SltA (involved in the salt tolerance pathway) in the regulation of azole resistance of the human fungal pathogen Aspergillus fumigatus A lack of SltA results in an itraconazole hypersusceptibility phenotype. Transcriptional profiling combined with LacZ reporter analysis and electrophoretic mobility shift assays (EMSA) demonstrated that SltA is involved in its own transcriptional regulation and also regulates the expression of genes related to ergosterol biosynthesis (erg11A, erg13A, and erg24A) and drug efflux pumps (mdr1, mfsC, and abcE) by directly binding to the conserved 5'-AGGCA-3' motif in their promoter regions, and this binding is dependent on the conserved cysteine and histidine within the C2H2 DNA binding domain of SltA. Moreover, overexpression of erg11A or mdr1 rescues sltA deletion defects under itraconazole conditions, suggesting that erg11A and mdr1 are related to sltA-mediated itraconazole resistance. Most importantly, deletion of SltA in laboratory-derived and clinical azole-resistant isolates significantly attenuates drug resistance. Collectively, we have identified a new function of the transcription factor SltA in regulating azole resistance by coordinately mediating the key azole target Erg11A and the drug efflux pump Mdr1, and targeting SltA may provide a potential strategy for intervention of clinical azole-resistant isolates to improve the efficiency of currently approved antifungal drugs.

Advances allowing feasible pyrG gene editing by a CRISPR-Cas9 system for the edible mushroom Pleurotus eryngii.

For decades, the edible mushroom Pleurotus eryngii (P. eryngii) has been cultivated as important raw materials for food and pharmaceutical industries in most of Asian countries, especially in China. Unfortunately, the generation and improvement of new cultivars are very difficult since there are many barriers which have not been solved thoroughly by gene editing tools, even though the CRISPR-Cas9 technique has been widely applied in other species. In this study, we identified the point-mutated variant of the endogenous sdhB gene (cbxr) as a more stable selection marker than hygromycin B resistance gene (hph) in P. eryngii. Furthermore, using a codon-optimized Cas9, a predicted native U6 promoter-guided sgRNA, as well as an optimized protoplast transformation system, a highly efficient pyrG gene editing system was established in P. eryngii, that incorporated varied insertions and deletions (indels) by non-homologous end joining (NHEJ) and homology-directed repair (HDR). Findings for a successful targeted gene editing strategy in the edible mushroom P. eryngii may open a new chapter for the improvement of edible mushroom cultivars.

Association between atherosclerotic cardiovascular diseases risk and renal outcome in patients with type 2 diabetes mellitus.

AIMS: Chronic kidney disease (CKD) and diabetes mellitus increase atherosclerotic cardiovascular diseases (ASCVD) risk. However, the association between renal outcome of diabetic kidney disease (DKD) and ASCVD risk is unclear. METHODS: This retrospective study enrolled 218 type 2 diabetic patients with biopsy-proven DKD, and without known cardiovascular diseases. Baseline characteristics were obtained and the 10-year ASCVD risk score was calculated using the Pooled Cohort Equation (PCE). Renal outcome was defined as progression to end-stage renal disease (ESRD). The association between ASCVD risk and renal function and outcome was analyzed with logistic regression and Cox analysis. RESULTS: Among all patients, the median 10-year ASCVD risk score was 14.1%. The median of ASCVD risk score in CKD stage 1, 2, 3, and 4 was 10.9%, 12.3%, 16.5%, and 14.8%, respectively (p = 0.268). Compared with patients with lower ASCVD risk (＜14.1%), those with higher ASCVD risk had lower eGFR, higher systolic blood pressure, and more severe renal interstitial inflammation. High ASCVD risk (>14.1%) was an independent indicator of renal dysfunction in multivariable-adjusted logistic analysis (OR, 3.997; 95%CI, 1.385-11.530; p = 0.010), though failed to be an independent risk factor for ESRD in patients with DKD in univariate and multivariate Cox analysis. CONCLUSIONS: DKD patients even in CKD stage 1 had comparable ASCVD risk score to patients in CKD stage 2, 3, and 4. Higher ASCVD risk indicated severe renal insufficiency, while no prognostic value of ASVCD risk for renal outcome was observed, which implied macroangiopathy and microangiopathy in patients with DKD were related, but relatively independent.

CLINICOPATHOLOGIC FEATURES AND PROGNOSIS OF TYPE 2 DIABETES MELLITUS AND DIABETIC NEPHROPATHY IN DIFFERENT AGE GROUPS: MORE ATTENTION TO YOUNGER PATIENTS.

Objective: Our study sought to investigate the clinicopathologic features and renal prognosis of patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) in different age groups. Methods: A total of 315 patients with T2DM and biopsy-proven DN were enrolled and divided into three groups by age: the Youth group (≤44 years old), the Middle-aged group (45 to 59 years old), and the Elderly group (≥60 years old). Results: The Youth group, Middle-aged group, and Elderly group accounted for 19.05% (60/315), 59.37% (187/315), and 21.59% (68/315) of the patients in our study, respectively. The patients in the Youth group had a higher estimated glomerular filtration rate (calculated using the Chronic Kidney Disease-Epidemiology collaboration formula) (P<.001), a higher incidence of diabetic retinopathy (P = .044), and a higher incidence of being in the lower-risk chronic kidney disease heat map category (P = .046) but lower duration of diabetes (P = .016). Histologically, patients in the Youth group had the highest incidence of glomerular classification in class I (P = .006) and arteriolar hyalinosis score of 0 (P = .005). The renal survival among the three groups was comparable (P>.05). Conclusion: This study indicated that there were different clinicopathologic features among Chinese DN patients in different age groups. Although the Youth group had a relatively lower rapid kidney disease progression rate, there were no significant differences in renal survival rate among the three groups, which calls more attention to early supervision and prevention for younger DN patients. Abbreviations: CKD = chronic kidney disease; DN = diabetic nephropathy; DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease; G&Y&O = green and yellow and orange; IFTA = interstitial fibrosis and tubular atrophy; T2DM = type 2 diabetes mellitus.

THE ASSOCIATION OF SERUM BILIRUBIN ON KIDNEY CLINICOPATHOLOGIC FEATURES AND RENAL OUTCOME IN PATIENTS WITH DIABETIC NEPHROPATHY: A BIOPSY-BASED STUDY.

Objective: To explore the relationship between serum bilirubin concentration and clinicopathologic features and renal outcome in biopsy-diagnosed diabetic nephropathy (DN) in patients with type 2 diabetes mellitus. Methods: In this retrospective study, 118 patients with DN were enrolled. Participants were divided into two groups according to their median baseline serum bilirubin concentration: Group 1 (serum bilirubin ≤7.5 µmol /L); Group 2 (serum bilirubin >7.5 µmol /L). Basic clinical parameters were measured at the time of renal biopsy, and the relationships between serum bilirubin and the clinicopathologic features and renal outcome were analyzed. Results: Patients in Group 1 often had inferior renal function. Compared with Group 2, the glomerular classification and interstitial inflammation were more severe in subjects of Group 1, while arteriolar hyalinosis and interstitial fibrosis and tubular atrophy (IFTA) were comparable between the groups. Serum bilirubin was negatively correlated with the severity of the glomerular classification, interstitial inflammation, and IFTA. In the prognostic analysis, higher serum bilirubin level was associated with a lower risk of progression to end-stage renal disease, which was independent of the effects of age, gender, duration of diabetes, anemia, serum glucose, and hypertension but not of estimated glomerular filtration rate (hazard ratio, 0.406; 95% confidence interval, 0.074 to 2.225; P = .299). Conclusion: Our study showed a negative correlation between serum bilirubin level and renal pathologic lesions in patients with DN; serum bilirubin showed an inverse association with DN progression, but this was not independent. Abbreviations: CI = confidence interval; CKD = chronic kidney disease; DM = diabetes mellitus; DN = diabetic nephropathy; DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease; HbA1c = glycated hemoglobin; HO-1 = heme oxygenase 1; HR = hazard ratio; IFTA = interstitial fibrosis and tubular atrophy; log-BIL = log-transformed baseline serum bilirubin; T2DM = type 2 diabetes mellitus.

Thyroid hormones and diabetic nephropathy: An essential relationship to recognize.

AIMS: Although abnormal thyroid hormone metabolism is common in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN), the relationship between thyroid hormones and DN is unclear and has been ignored during clinical practice. This study aimed to investigate the relationship between thyroid hormones and clinicopathologic changes in biopsy-proven DN patients. METHODS: Clinical and pathological data for 146 biopsy-proven DN patients were collected. The patients were divided into four groups: euthyroid group, high-thyroid stimulating hormone (TSH) group (SCH), low-free triiodothyronine (FT3) group (with normal levels of TSH and FT4), and high-TSH + low-FT3 group (with normal levels of FT4). The clinicopathologic features among the four groups were investigated. We evaluated the risks of abnormal thyroid hormone levels on DN by logistic regression with multivariable adjustments for other risk factors. We also performed quarterback and eight-point analyses of TSH and FT3 levels to determine their influences on DN. RESULTS: The overt proteinuria (>5 g/24 h) (P = 0.008) and severity of glomerular lesions (P = 0.011) differed between euthyroid group and high-TSH group significantly. Moreover, the levels of estimated glomerular filtration rate (P =0.019), serum creatinine (P =0.014), and severity of glomerular lesions (P =0.003) differed between the euthyroid group and low-FT3 group significantly. There were also significant differences between high-TSH, low-FT3 and high-TSH + low-FT3 patients, respectively. Respective correlations between high-TSH, low-FT3 and renal clinicopathologic changes were found to be significant according to logistic regression analyses. Quarterback and eight-point analyses indicated that patients with TSH levels of 4.54-5.67 mU/L had the most severe renal clinicopathologic changes, and the severity of renal changes decreased with increased FT3 levels. CONCLUSIONS: Diabetic nephropathy patients with high-TSH and/or low-FT3 had more severe proteinuria, renal insufficiency, and glomerular lesions, suggesting that regulating thyroid hormones might have a renoprotective effect.

Effects of neutrophil-lymphocyte ratio on renal function and histologic lesions in patients with diabetic nephropathy.

AIM: Chronic low-grade inflammation related to diabetic nephropathy (DN) may affect the serum neutrophil-lymphocyte ratio (NLR). We aimed to examine the cross-sectional relationships of NLR with renal function and structural lesions of DN in patients with type 2 diabetes mellitus (T2DM). METHODS: The study retrospectively included 247 patients with T2DM and biopsy-proven DN. The severity of different pathological lesions was evaluated based on the criteria of Renal Pathology Society. The patients were divided into two groups based on the median (2.42) of NLR level, group 1: NLR < 2.42 (n = 122) and group 2: NLR ≥ 2.42 (n = 125). Renal dysfunction was defined by estimated glomerular filtration rate less than 60 mL/min per 1.73 m2 . The influence of NLR on renal dysfunction was evaluated using logistic regression analysis. RESULTS: The spearman's rank-correlation test indicted that NLR was positively correlated with interstitial fibrosis and tubular atrophy (r = 0.170, P = 0.007) and serum fibrinogen (r = 0.261, P < 0.001), whereas negatively related with estimated glomerular filtration rate (r = -0.233, P < 0.001). However, the NLR level demonstrated no association with glomerular lesions, interstitial inflammation and arteriolar hyalinosis. A multivariate logistic regression analysis showed that higher level of NLR (≥2.42) was significantly associated with renal dysfunction when adjusting for some important baseline clinical and pathological variables (odds ratio, 2.46; 95% confidence interval, 1.21-4.97; P = 0.012). CONCLUSION: Increased NLR affects renal function and histologic lesions in patients with T2DM and may be an important factor for the progression of DN.

The association between the red cell distribution width and diabetic nephropathy in patients with type-2 diabetes mellitus.

BACKGROUND: Red cell distribution width (RDW) has been reported to be involved in metabolic syndrome and cardiovascular events. Patients with diabetic nephropathy (DN) are often found to be with high level of RDW. The aim of this study was to explore whether RDW was associated with DN severity and progression in patients with type-2 diabetes mellitus (T2DM). METHODS: A total of 175 T2DM patients with biopsy-proven DN were enrolled. The baseline clinical and pathologic data of these patients was extracted from the medical records. The patients then were divided into two groups based on the median (13.6%) of RDW level; group 1: <13.6% and group 2: ≥13.6%. The effect of RDW level on the renal outcomes was evaluated by using cox regression analysis. RESULTS: Compared with the patients with lower RDW level, the patients with higher level of RDW had higher proportions of female, longer DM duration, lower levels of eGFR, albumin and hemoglobin, and more serious glomerular damage. Moreover, the RDW levels were negatively corrected with eGFR (r = -0.283, p < 0.001), but positively related with proteinuria (r = 0.227, p = 0.003). In the follow-up period, 81(46.3%) patients had reached ESRD from baseline. Importantly, the Cox regression analyses showed that the levels of RDM had a significant effect on the risk of progression to ESRD (HR = 1.92, p < 0.01), albeit not emerged as an independent predictor. CONCLUSIONS: These data indicated that the levels of RDW were significantly associated with increased risk of progression to ESRD in patients with DN, despite did not an independent predictor.

[Evaluation of the application of regional citrate anticoagulation in sustained low efficiency hemodialysis].

OBJECTIVE: To compare the anticoagulation effect of regional citrate and heparin in patients with sustained low-efficiency hemodialysis (SLED). METHOD: This study was conducted in the teaching hospital of Sichuan University between November 2011 and January 2013.Sixty-three patients suffering from acute kidney injury or end-stage renal diseases (ESRD) were enrolled and further randomized to 2 groups: citrate and heparin anticoagulation treatment groups in SLED. SLED was conducted by Fresenius 4008sARrTplus dialyzer for 8 hours each session, and blood flow was set at 150 ml/min. Prothrombin time (PT), activated partial thromboplastin time (APTT) and platelet (PLT) count were analyzed. RESULT: Sixty-three patients underwent 118 sessions of SLED. Among them, 59 patients (93.7%) was discharged after treatment or converted to outpatient intermittent hemodialysis, and 4 patients died of multiple organ failure during hospitalization. Compared with that in the citrate group, both PT and APTT in heparin group was significantly higher [PT: (15.5 ± 2.0) s vs (12.3 ± 2.7) s, P < 0.001; APTT: (56.0 ± 10.9) s vs (32.8 ± 6.1) s, P < 0.001;respectively] at 2 h during SLED.However, the PT and APTT levels in heparin group decreased afterwards and were similar with those in the citrate groups at 5 h during treatment. There is no difference on PLT counts between these two groups after treatment. CONCLUSION: The anticoagulation effect of regional citrate and heparin was similar in patients when receiving SLED.Regional citrate may be an alternative anticoagulant approach for the patients at high risk of bleeding who require the treatment of SLED.

Nephrotic proteinuria and hematuria with newly diagnosed IgA nephropathy after liver transplant: A case report.

BACKGROUND: IgA nephropathy is a renal lesion in patients with end-stage liver disease, called hepatic IgA nephropathy. The common manifestation of hepatic IgA nephropathy is microscopic hematuria. Sirolimus, often used to prevent organ rejection, has been reported to induce proteinuria after organ transplantation. But few cases of nephrotic proteinuria and hematuria are reported. CASE PRESENTATION: In this case, a 45-year-old male with a long history of hepatic B virus infection and liver cirrhosis, received liver transplant and was taking sirolimus as one of his immunosuppression drugs. Overt proteinuria and hematuria occurred. With no proteinuria history before, renal biopsy was performed, which indicated IgA nephropathy. CONCLUSION: We reported a liver recipient, who was taking sirolimus, developing nephrotic proteinuria and hematuria with IgA nephropathy. Further studies need to be carried out to disclose mechanism behind this phenomenon.

[The safety and efficacy of regional citrate anticoagulation in sustained low efficiency dialysis].

OBJECTIVE: To evaluate the safety and efficacy of regional citrate anticoagulation in sustained low efficiency dialysis (SLED). METHODS: A total of 45 patients with acute kidney injury (AKI) or end stage renal disease (ESRD) admitted in our hospital from August 2011 to September 2012 were prospectively enrolled in this study. All the patients received SLED treatment by Fresenius 4008sARrTplus dialyzer through either femoral or internal jugular venous catheter, with each session of SLED treatment lasting for 8 hours. All the patients were pumped in 4% tri-sodium citrate solution through the arterial line at 130 ml/hour and 10% calcium gluconate through the venous line at 40 ml/hour. The blood flow was 150 ml/minute while the calcium-free dialysate was delivered at 200 ml/minute. Systemic citrate concentration, peripheral and post dialyzer ionized calcium levels at 0, 2 and 5 hour were recorded. RESULTS: All the 45 patients underwent 162 sessions of SLED with 2 were discontinued due to III° dialyzer coagulation, and other 160 SLED sessions (98.8%) were all successfully performed. The systemic citrate concentration at 0 hour was (0.14 ± 0.06) mmol/L, the systemic citrate concentrations at 2 and 5 hour were slightly increased while no statistical difference was found[(1.08 ± 0.12) mmol/L vs (1.11 ± 0.17) mmol/L, P > 0.05]. The 0, 2, 5 hour peripheral blood ionized calcium levels were (1.04 ± 0.13) mmol/L, (1.07 ± 0.23) mmol/L and (1.04 ± 0.24) mmol/L, respectively, with no significant difference (P > 0.05). The post dialyzer ionized calcium levels were (0.31 ± 0.04) mmol/L at 2 hour and (0.29 ± 0.03) mmol/L at 5 hour. The transmembrane pressure at 2 hour was (104.5 ± 17.8) mm Hg(1 mm Hg = 0.133 kPa), and (109.3 ± 20.1) mm Hg at 5 hour, however the increase was not of statistical significance (P > 0.05). At 5 hour, prothrombin time and activated partial thrombin time were identified to be similar to those before SLED. During the treatments, no bleeding complication, thrombocytopenia, cardiac arrhythmia, hypernatremia, metabolic alkalosis or hypotension was observed. CONCLUSION: SLED under regional citrate anticoagulation is safe and effective. Citrate achieves satisfying regional anticoagulation effect without interfering systemic clotting function, thus this study provides a new option of SLED anticoagulation for clinicians.

Emerging Liquid Metal Catalysts.

Catalysts serve pivotal roles in facilitating the development of sustainable energy systems on a global scale. Liquid metal usually refers to metal that is liquid below 330 °C, also known as low melting point metal. Liquid metal has emerged as an intriguing catalyst due to its commendable electrical conductivity, favorable fluidity, solubility in metals, phase transition capabilities, and modifiable oxide surface, thereby presenting a plethora of prospects for diverse catalytic reactions. In this Perspective, we elucidate the four primary merits of liquid metal catalysts: resistance to coking, the ability to tune elemental composition, the potential for structural transformation, and the capacity to inhibit coalescence. In light of this, a comprehensive summary is presented on the research advancements pertaining to liquid metal in methane pyrolysis, alkane dehydrogenation, carbon dioxide reduction, alcohol oxidation, and various other catalytic reactions. Finally, the challenges and prospects of liquid metal catalysts are elucidated.

Metabolic-associated fatty liver disease increases the risk of end-stage renal disease in patients with biopsy-confirmed diabetic nephropathy: a propensity-matched cohort study.

AIMS: To investigate the relationship between metabolic-associated fatty liver disease (MAFLD) and end-stage renal disease (ESRD) in patients with biopsy-confirmed diabetic nephropathy (DN). METHODS: A total of 316 participants with biopsy-confirmed DN between January 2008 and December 2019 were retrospectively assessed. Kaplan-Meier curve and Cox proportional hazard models were used to compare the risk of incident ESRD in 50 patients with MAFLD and 50 patients without MAFLD, after using propensity score matching (PSM) to address the imbalances of sex, age, baseline-estimated glomerular filtration rate, serum albumin, 24-h urine protein, hemoglobin and systolic blood pressure. RESULTS: During the median follow-up period of 3 years, there were 19 ESRD outcome events (19%) in PSM cohort. Kaplan-Meier curve analysis suggested that renal survival significantly deteriorated in patients with MAFLD versus those without MAFLD (p = 0.021). Additionally, the hazard ratios (95% confidence interval) of MAFLD were 3.12 (1.09-8.95, p = 0.035), 3.36 (1.09-10.43, p = 0.036), 3.66 (1.22-10.98, p = 0.021), 4.25 (1.34-13.45, p = 0.014), 3.11 (1.08-8.96, p = 0.035) and 5.84 (1.94-18.5, p = 0.003) after adjustment for six models, including demographic, clinical and pathological characteristics as well as medication use at the time of renal biopsy, respectively. Besides, patients with higher liver fibrosis score had a greater possibility of ESRD, comparing to those with lower liver fibrosis score (p = 0.002). CONCLUSIONS: MAFLD increases the risk of incident ESRD in patients with biopsy-proven DN. Further research is needed to determine whether treatment targeting MAFLD improves the prognosis of DN.

[Sustained low efficiency dialysis on patients with multiple organ failure resulted from diabetic kidney disease].

OBJECTIVE: To investigate the effect of sustained low efficiency dialysis (SLED) on patients with multiple organ failure resulted from diabetic kidney disease (DKD). METHODS: Five DKD patients who developed MOF between Nov. 2011 and Jan. 2012 were recruited for SLED treatment (dose: 200 ml/min, for 8 to 12 hours every other day) in the West China Hospital. Meanwhile, other therapeutic measures, such as underlying disease management, infection control and nutritional support were applied. Biochemical changes and progress of disease were observed. RESULTS: One patient died unexpectedly 12h after admission to hospital. The main cause of death was multiple organ failure. The other four patients had sharp improvements in high potassium concentration and (or) metabolic acidosis after SLED therapy, with obvious amelioration of main organs functions and oxygenation index [PO2 (103.3 +/- 25.7) mm Hg]. Two ventilator dependent patients successfully weaned from mechanical ventilation 3 to 5 days after the treatment. BNP of the patients decreased from > 35,000 ng/mL before the treatment to (13,312 +/- 3,537) pg/mL after the treatment (P < 0.05). APACHE II decreased by 10.3%, 41.9% and 67.8% within 24 hours, three days and five days respectively. CONCLUSION: SLED as early intervention can bring significant benefits to DKD patients with multiple organ failure (MOF). SLED has the same efficacy as continuous renal replacement therapy (CRRT) in the treatment of MOF for patients with DKD.

Therapeutic carrier based on solanesol and hyaluronate for synergistic tumor treatment.

The administration of nanodrugs can lead to metabolism related systemic toxicity due to the use of inert carriers in large quantities. Carrier materials that offer therapeutic effects are therefore a promising means of addressing this limitation. Herein, a hyaluronate-based nanocarrier was prepared from hyaluronic acid (HA) and solanesol. Solanesyl thiosalicylate (STS) derived from solanesol has certain antitumor effects and was used to modify HA. The conjugate (HA-STS) self-assembled into nanoparticles acting as a drug carrier. The synthesis of the conjugates was confirmed by 1H NMR spectroscopy. Doxorubicin (DOX) was loaded into the HA-STS nanoparticles with a relatively high content of 6.0%. pH-sensitive drug release behavior was achieved by introducing a hydroazone bond between STS and HA. A cytotoxicity assay indicated that the blank nanoparticles had an antitumor effect, which was enhanced by loading with an additional drug. Moreover, in vivo antitumor experiments indicated that the HA-STS-DOX showed superior tumor inhibition compared with free DOX, as well as lower cardiotoxicity and hepatotoxicity, demonstrating the advantages of the bioactive drug vehicles in cancer therapy.

Dual Self-Built Gating Boosts the Hydrogen Evolution Reaction.

Optimizing the intrinsic activity of active sites is an appealing strategy for accelerating the kinetics of the catalytic process. Here, a design principle, namely "dual self-built gating", is proposed to tailor the electronic structures of catalysts. Catalytic improvement is confirmed in a model catalyst with a ReS2 -WS2 /WS2 hybridized heterostructure. As demonstrated in experimental and theoretical results, the dual gating can bidirectionally guide electron transfer and redistribute at the interface, endowing the model catalyst with an electron-rich region. The tailored electronic structures balance the adsorption of intermediates and the desorption of hydrogen synergistically to enhance the reaction kinetics for the hydrogen evolution reaction. Interestingly, the effect of dual gating can be easily amplified by the electric field. The overpotential and Tafel slope (49 mV, 35 mV dec-1 ) obtained under the electric field for ReS2 -WS2 /WS2 catalyst with the dual self-built gating effect are far below than those (210 mV, 116 mV dec-1 ) of the pure WS2 catalyst, which exhibits nearly four times improvement. The concept of dual gating can be applied to more systems, offering a new guideline for designing advanced electrocatalysts.

Whether Renal Pathology Is an Independent Predictor for End-Stage Renal Disease in Diabetic Kidney Disease Patients with Nephrotic Range Proteinuria: A Biopsy-Based Study.

Aims: To investigate whether renal pathology is an independent predictor for end-stage renal disease (ESRD) in diabetic kidney diseases (DKD) with nephrotic range proteinuria. Methods: A total of 199 DKD patients with nephrotic range proteinuria underwent renal biopsy and were divided into an ESRD group and a non-ESRD group. A Kaplan−Meier analysis was used to compare renal survival rate, and univariate and multivariate Cox proportional hazard analyses were used to determine the predictors of the ESRD. Results: The mean age of included patients was 51.49 ± 9.12 years and 113 patients (56.8%) progressed to ESRD. The median follow-up period was 16 (12−28) months. The glomerular pathology class III is the most common type (54.3%). In the Kaplan−Meier analysis, compared with patients without ESRD, patients with ESRD had a longer duration of diabetes (≥6 years), lower eGFR (<60 mL/min/1.73 m2), lower albumin (<30 g/L), lower hemoglobin (<120 g/L), and a higher grade of glomerular stage (class III + IV vs. class I + II) (p < 0.05). The hemoglobin and e-GFR, but not the histopathological damage, were significantly associated with a higher risk of ESRD in both the univariate and multivariate Cox analyses. Conclusions: In patients with diabetic kidney disease characterized by nephrotic range proteinuria, histopathological damage (glomerular alterations, interstitial fibrosis and tubular atrophy (IFTA), interstitial inflammation, and arteriolar hyalinosis) is not associated with poor renal outcomes, but hemoglobin and e-GFR could predict poor renal outcomes.