Search

This study was performed to test the hypothesis that neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker would be helpful for differentiation acute kidney injury (AKI) from chronic kidney disease (CKD) in kidney malfunction patients from the nephrology department.This retrospective study included 355 patients admitted from the nephrology department with modification of diet in renal disease estimated glomerular filtration rate (MDRD eGFR) 60 ml/min/1.73 mUrinary NGAL (uNGAL) level in the AKI group was higher than in the CKD group (372.10 (170.10-690.63) vs 88.10 (52.00-238.80), P 0.001), but there was no significant difference in serum NGAL (sNGAL). Both sNGAL and uNGAL had a correlation with MDRD eGFR in total patients, AKI patients, and CKD patients. The propensity-matched analysis enrolled 75 patients in each group. In matched AKI group, sNGAL was lower (401.20 (239.10-616.00) vs 468.50 (305.00-709.40), P = 0.049) and uNGAL was elevated (284.00 (136.90-690.90) vs 203.70 (69.20-596.00), P = 0.032), compared with the matched CKD group. In all patients (n = 355), the ratio of uNGAL and sNGAL (u/s NGAL), fractional excretion of NGAL (Fe NGAL) discriminated AKI from CKD (area under the curve, 0.803 and 0.790, respectively). After stratified kidney function, the sub-analyses found that u/s NGAL and Fe NGAL were shown to differ substantially between the AKI group and CKD group (all P 0.01). The u/s NGAL ratio always had the highest AUC area in the sub-analyses.u/s NGAL might be helpful to discriminate AKI from CKD in kidney malfunction patients admitted to the nephrology department. Further confirmatory studies might be warranted.

Calciphylaxis is a rare cutaneous vascular disease with clinical manifestations of intolerable pains, non-healing skin wounds, histologically characterized by calcification, fibrointimal hyperplasia, and thrombosis in microvessels. Currently, there are no approved guidelines for this disease. High prevalence of thrombophilias and hypercoagulable conditions in calciphylaxis patients have been recognized in recent years. Here, we report a case of uremic calciphylaxis patient whom was refractory to conventional treatments and then received a salvage strategyviahuman amnion-derived mesenchymal stem cell (hAMSC) intravenous combined with local application. In order to investigate the therapeutic mechanism of hMASCs from the novel perspective of hypercoagulability, coagulation-related indicators, wound status and quality of life were followed up. Improvement of hypercoagulable condition involving correction of platelet, D-dimer and plasminogen levels, skin regeneration and pain alleviation were revealed after hAMSC administration for one year. We propose that hypercoagulability is the therapeutic target of calciphylaxis patients which can be improved by hAMSC treatment.

Ovarian follicle is the basic functional unit of female reproduction, and is composed of oocyte and surrounding granulosa cells. In mammals, folliculogenesis strictly rely on gonadotropin regulations to determine the ovulation and the quality of eggs. However, the dynamic changes of protein-expressing profiles in follicles at different developmental stages remain largely unknown. By performing mass-spectrometry-based quantitative proteomic analysis of mouse follicles, we provide a proteomic database (~3000 proteins) that covers three key stages of gonadotropin-dependent folliculogenesis. By combining bioinformatics analysis with in situ expression validation, we showed that our proteomic data well reflected physiological changes during folliculogenesis, which provided potential to predict unknown regulators of folliculogenesis. Additionally, by using the oocyte structural protein zona pellucida protein 2 as the internal control, we showed the possibility of our database to predict the expression dynamics of oocyte-expressing proteins during folliculogenesis. Taken together, we provide a high-coverage proteomic database to study protein-expression dynamics during gonadotropin-dependent folliculogenesis in mammals.

Purpose The combination of vancomycin and piperacillin/tazobactam (VAN + PTZ) provides a broad spectrum of activity against multiple pathogens. However, a major issue in previous research concerned significant nephrotoxicity associated with this drug combination, and most studies have been conducted in American and European countries, with no similar data available from China. Therefore, this study evaluated the nephrotoxic effects of VAN + PTZ in a large-scale Chinese cohort to determine the prevalence of acute kidney injury (AKI) in this population by comparing PTZ and vancomycin monotherapies and the combined use of vancomycin and β-lactam antibiotics. Methods This retrospective cohort study identified adult patients who received vancomycin either as monotherapy or in combination with PTZ or carbapenem (VAN + CAR) for at least 48 hours at Jiangsu Province Hospital from January 1, 2017, to December 31, 2018. Patients were also evaluated for the development of AKI, defined according to the Kidney Disease Improving Global Outcome criteria. Duration of vancomycin exposure, steady-state trough vancomycin concentrations, and other risk factors for AKI were assessed. A Bayesian network meta-analysis was conducted to validate our results and comparatively evaluate the nephrotoxicity of β-lactam antibiotics in combination with vancomycin. Findings In all, 752 patients were included in the present study. The prevalence of AKI was higher in the VAN + PTZ group than in the VAN and VAN + CAR groups (15.2% vs 4.0% and 6.0%, respectively). After adjustment for confounding factors, VAN + PTZ was still related to AKI (odds ratio [OR] = 4.37; 95% CI, 1.65–11.59; P = 0.003). The network meta-analysis indicated that VAN + PTZ was associated with a significantly higher risk for AKI than was VAN (OR = 3.23; 95% CI, 2.50–4.35), PTZ (OR = 2.86; 95% CI, 1.92–4.12), VAN + cefepime (FEP) (OR = 2.37; 95% CI, 1.80–3.19), or VAN + CAR (OR = 2.28; 95% CI, 1.64–3.21). However, there was no significant difference with respect to AKI prevalence among the VAN, PTZ, VAN + FEP, and VAN + CAR groups. Implications The prevalence of AKI was higher with VAN + PTZ therapy than with VAN or PTZ monotherapy or with the concurrent use of VAN and FEP or CAR in our study. Clinicians should adequately assess renal function and consider this differential risk for nephrotoxicity when choosing empiric antibiotics in hospitalized patients to minimize the rates of AKI.

Immune checkpoint inhibitor (ICI) therapy is now the stand of care for lung cancer. Due to the low incidence, the study of acute kidney injury (AKI) in lung cancer patients treated with ICIs was hardly reported. We focused on the incidence, characteristics, risk factors, and mortality of AKI in advanced lung cancer patients receiving PD-1 inhibitors.We reviewed advanced lung cancer patients receiving PD-1 inhibitors between January 2018 to August 2020 at Jiangsu Province Hospital. Patients were followed up for 6 months. We used the logistic regression model to evaluate risk factors for AKI, and Kaplan-Meier method to assess the association between AKI and mortality.A total of 305 advanced lung cancer patients treated with PD-1 inhibitors. The median age was 64 years and 80.6% of patients were male. The incidence of AKI was 10.2%, and the incidence of ICI-AKI was 4.6%. Multivariate analysis showed that concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) (OR 2.509; 95% CI 1.053-5.974) and renin-angiotensin-aldosterone system (RAAS) inhibitors (OR 2.656; 95% CI 1.091-6.466) were risk factors for AKI. In addition, concomitant use of NSAIDs (OR 5.170; 95% CI 1.087-24.595) and RAAS inhibitors (OR 5.921; 95% CI 1.871-18.737), and the occurrence of extra-renal immune-related adverse events (OR 4.726; 95% CI 1.462-15.280) were significantly associated with ICI-AKI. ICI-AKI was not associated with mortality while severe AKI was associated with higher risk of mortality.AKI is common in advanced lung cancer patients treated with PD-1 inhibitors. The characteristics and risk factors of ICI-AKI were similar to those previously reported in other solid organ malignancies treated with ICIs. Severe AKI may indicate higher mortality.

Objective: The objective of this study is to investigate the association between the serum sclerostin, the coronary artery calcification (CAC), and patient outcomes in maintenance dialysis patients. Methods: We performed a prospective cohort study of 65 maintenance dialysis patients in 2014, including 39 patients on peritoneal dialysis and 26 on hemodialysis, and followed up for 5 years. Parameters of mineral metabolism including bone-specific alkaline phosphatase, fibroblast growth factor 23, sclerostin, and other biochemical factors were determined at the baseline. Meanwhile, the CAC score was analyzed by cardiac computed tomography. Results: Serum sclerostin in hemodialysis patients was significantly higher than that in peritoneal dialysis patients (632.35 ± 369.18 vs. 228.85 ± 188.92, p < 0.001). The patients with CAC were older, receiving hemodialysis, lower Kt/V, and had longer dialysis vintage, as well as higher levels of serum 25-(OH)-vit D and sclerostin. In multivariate logistic regression analysis, older age and lower Kt/V were risk factors for CAC. The area under the receiver operating characteristic curves for prediction of CAC by sclerostin was 0.74 (95% confidence interval 0.605–0.878, p = 0.03), and the cutoff value of sclerostin is 217.55 pg/mL with the sensitivity 0.829 and specificity 0.619. After 5 years of follow-up, 51 patients survived. The patients in the survival group had significantly lower age, sclerostin levels, and low CAC scores than the nonsurvival group. Old age (≥60 years, p < 0.001) and high CAC score (≥50 Agatston unit, p = 0.031) were significant risk factors for the patient survival. Conclusions: Sclerostin is significantly elevated in dialysis patients with CAC. But sclerostin is not a risk factor for CAC. After 5 years of follow-up, patients in the survival group are younger and have lower sclerostin levels and CAC scores. But sclerostin levels are not independent risk factors for high mortality in dialysis patients.

Patients with pre-existing chronic diseases are more susceptible to coronavirus disease 2019 (COVID-19), yet the underlying causes of increased risk are of infection remain unclear. Angiotensin-converting- enzyme 2 (ACE2), the cell surface receptor that recognizes the coronavirus spike protein has protective effects against inflammation and chronic hyperglycemia in animal models. The roles of ACE2 in severe SARS-CoV-2 infections remains ambiguous due to contradictory findings. In this study, we aimed to investigate the relationship between human plasma ACE2 levels in diabetics and the high risk of severe SARS-CoV-2 infection. First, the medical records of 245 patients with SARS-CoV-2-positive who have chronic diseases were analyzed. We also recruited 404 elderly subjects with comorbid chronic diseases such as diabetes mellitus, coronary heart disease, cerebrovascular disease, hypertension and obesity, and investigated the ACE2 plasma levels. Plasma concentrations of ACE2 were much lower (2973.83±2196.79 pg/mL) in diabetics with chronic disease than in healthy controls (4308.21±2352.42 pg/ml), and the use of hypoglycemia drugs was associated with lower circulating concentrations of ACE2 (P=1.49E-08). Diabetics with lower plasma levels of ACE2 may be susceptible to severe COVID-19. Our findings suggest that the poor prognosis in patients with diabetes infected with SARS-CoV-2 may be due to low circulating ACE2 levels.

BackgroundIgG4-related kidney disease (IgG4-RKD) can affect multiple organs, which was first reported as a complication or extra-organ manifestation of autoimmune pancreatitis in 2004. It is characterized by abundant IgG4-positive plasma cells infiltration in tissues involved.Case presentationA 69-year-old man presented with cough and renal dysfunction with medical history of hypertension and diabetes. Pathological findings revealed interstitial nephritis and he was initially diagnosed with IgG4-RKD. Prednisone helped the patient to get a remission of cough and an obvious decrease of IgG4 level. However, he developed invasive pulmonary fungal infection while steroid theatment. Anti-fungal therapy was initiated after lung puncture (around cavitary lung lesion). Hemodialysis had been conducted because of renal failure and he got rid of it 2 months later. Methylprednisolone was decreased to 8 mg/day for maintenance therapy. Anti-fungal infection continued for 4 months after discharge home. On the 4th month of follow-up, Chest CT revealed no progression of lung lesions.ConclusionsThe corticosteroids are the first-line therapy of IgG4-RD and a rapid response helps to confirm the diagnosis. This case should inspire clinicians to identify IgG4-related lung disease and secondary pulmonary infection, pay attention to the complications during immunosuppressive therapy for primary disease control.

We compared the prognostic value of nutritional or volumetric parameters measured by body composition in hospitalized patients on maintenance hemodialysis. We conducted a cohort study to assess the association of different parameters of body composition with all-cause mortality in inpatients admitted to our nephrology department from January 2014 to December 2016. Of the 704 study patients, 160 (22.7%) died during a median follow-up of 33 months. In multivariate adjusted Cox models, higher ratio of extracellular water to body cell mass (ECW/BCM) (adjusted HR per 1-SD, 1.49; 95% CI, 1.19 to 1.85), lower lean tissue index (LTI) (adjusted HR per 1-SD, 0.70; 95% CI, 0.57 to 0.86) and lower body cell mass index (BCMI) (adjusted HR per 1-SD, 0.70; 95% CI, 0.58 to 0.85) were associated with a significantly greater risk of death. When these parameters were added to the fully adjusted model, BCMI performed best in improving the predictability for all-cause mortality (integrated discrimination improvement = 0.02, P = 0.04; net reclassification index = 0.11, P = 0.04). Among body composition indexes, ECW/BCM was the most relevant fluid volume indices to mortality and BCMI and LTI were the most relevant nutritional status indices to mortality in maintenance hemodialysis patients.

Immune checkpoint inhibitors (ICIs) have been more and more commonly used in patients with cancer. Therefore, it is important to understand the immune-related adverse events (irAEs), including immune-related renal adverse events, caused by ICIs. In this article, the authors explore the incidence, clinical features, risk factors and overall outcome of immune checkpoint inhibitor related-acute kidney injury (ICI-AKI) in Chinese patients treated with PD-1 inhibitors for the first time. Among 551 patients treated with PD-1 inhibitors, 65 patients experienced AKI and 31 patients experienced ICI-AKI. Patients with ICI-AKI may be more likely to receive nonsteroidal anti-inflammatory drugs, to receive PD-1 inhibitors for longer cycles or to experience extrarenal immune-related adverse events prior to or concomitant with ICI-AKI. The occurrence of ICI-AKI may not affect the survival time or disease progression of patients with cancer.

Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis, with high mortality and no proven therapy. Here, we reported a severe uremic calciphylaxis patient with progressive skin ischemia, large areas of painful malodorous ulcers, and mummified legs. Because of the worsening symptoms and signs refractory to conventional therapies, treatment with human amnion-derived mesenchymal stem cells (hAMSCs) was approved. Preclinical release inspections of hAMSCs, efficacy, and safety assessment, including cytokine secretory ability, immunocompetence, tumorigenicity, and genetics analysis in vitro, were introduced. We further performed acute and long-term hAMSC toxicity evaluations in C57BL/6 mice and rats, abnormal immune response tests in C57BL/6 mice, and tumorigenicity tests in neonatal Balbc-nu nude mice. After the preclinical research, the patient was treated with hAMSCs by intravenous and local intramuscular injection and external supernatant application to the ulcers. When followed up to 15 months, the blood-based markers of bone and mineral metabolism improved, with skin soft tissue regeneration and a more favorable profile of peripheral blood mononuclear cells. Skin biopsy after 1-month treatment showed vascular regeneration with mature noncalcified vessels within the dermis, and 20 months later, the re-epithelialization restored the integrity of the damaged site. No infusion or local treatment-related adverse events occurred. Thus, this novel long-term intravenous combined with local treatment with hAMSCs warrants further investigation as a potential regenerative treatment for uremic calciphylaxis due to effects of inhibiting vascular calcification, stimulating angiogenesis and myogenesis, anti-inflammatory and immune modulation, multidifferentiation, re-epithelialization, and restoration of integrity.

Description, Unique model of adult ovarian angiogenesis implies a strategy to extend female reproductive life span., Robust angiogenesis is continuously active in ovaries to remodel the ovary-body connections in mammals, but understanding of this unique process remains elusive. Here, we performed high-resolution, three-dimensional ovarian vascular imaging and traced the pattern of ovarian angiogenesis and vascular development in the long term. We found that angiogenesis was mainly active on ovarian follicles and corpus luteum and that robust angiogenesis constructs independent but temporary vascular networks for each follicle. Based on the pattern of ovarian angiogenesis, we designed an angiogenesis-blocking strategy by axitinib administration to young females, and we found that the temporary suppression of angiogenesis paused ovarian development and kept the ovarian reserve in the long term, leading to postponed ovarian senescence and an extension of the female reproductive life span. Together, by uncovering the detailed model of physiological ovarian angiogenesis, our experiments suggest a potential approach to delay female reproductive aging through the manipulation of angiogenesis.

Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis, with high mortality and no proven therapy. We reported a severe uremic calciphylaxis patient with progressive skin ischemia, large areas of painful malodorous ulcers and mummified legs. Because of her rapid progression and refractory to conventional therapy, human amnion-derived mesenchymal stem cells (hAMSCs) treatment was approved. Establishment and release inspection of hAMSCs, efficacy and safety assessment including cytokines secretory ability, immunocompetence, tumorigenicity and genetics analysisin vitrowere introduced. We further performed acute and long-term hAMSC toxity evaluations in C57BL/6 mice/rats, abnormal immune response tests in C57BL/6 mice and tumorigenic tests in the neonatal NU nude mice. After pre-clinical research, she was treated by hAMSCs with intravenous and local intramuscular injection and external supernatants application to her ulcers. When followed up to 15 months, her blood-based markers of bone and mineral metabolism were improved, with regeneration of skin soft tissue and a more favorable profile of peripheral blood mononuclear cells. Skin biopsy after 1 month treatment showed vascular regeneration with mature non-calcified vessels within dermis and 20 months later re-epithelialization restored the integrity of damaged site. No infusion or local treatment related adverse events occurred. To the best of our knowledge, this is the first evidence for the clinical use of hAMSCs. These findings suggest hAMSCs warrant further investigation as a potential regenerative treatment for uremic calciphylaxis with effects of inhibiting vascular calcification, stimulating angiogenesis and myogenesis, anti-inflammatory and immune modulation, multi-differentiation, re-epithelialization and restorage of integrity.

Continuous renal replacement therapy (CRRT) has become an important multiple organ support therapy and it is widely used in the intensive care unit (ICU). The aim of this study was to clarify the association between CRRT and 28-day mortality in critically ill coronavirus disease 2019 (-COVID-19) patients receiving mechanical ventilation.112 respiratory decompensated critically ill adult patients with COVID-19 admitted to a COVID-19-designated ICU were included in this retrospective cohort study. Data on demographic information, comorbidities, laboratory findings upon ICU admission, and clinical outcomes were collected. The Kaplan-Meier method and Cox proportional hazard model were applied to determine the potential risk factors associated with 28-day mortality.The median age was 65.7 years, 67.8% were males, and 58.9% patients had at least one comorbidity. The median scores of the Charlson Comorbidity Index and Sequential Organ Failure Assessment (SOFA) were 3 and 7, respectively. Acute kidney injury (AKI) occurred in 57 critically ill patients upon ICU admission; 43 patients were classified as stage 2 - 3 AKI, and 36 patients were treated with CRRT. Age 65 years, high SOFA score, damaged cardiac function, poor nutrition, and severe infection were significantly associated with increased 28-day mortality. AKI patients receiving CRRT had lower 28-day mortality compared with those not receiving CRRT (HR = 0.35, 95% CI: 0.21 - 0.58, p 0.001). Initiating CRRT within 72 hours after mechanical ventilation did not improve survival after CRRT initiation.AKI prevalence and 28-day mortality are high in critically ill patients with COVID-19 receiving mechanical ventilation. CRRT plays a part in decreasing the mortality of critically ill COVID-19 patients with AKI receiving mechanical ventilation.

Aims Acute kidney injury (AKI) can limit the clinical use of cisplatin in cancer treatment. The drivers of cisplatin-induced AKI include oxidative stress, mitochondrial dysfunction and apoptosis. Previous studies showed renalase protected cultured human renal proximal tubular cell (HK-2) against cisplatin induced necrosis, and renalase-knockout mice subjected to cisplatin showed exacerbated kidney injury. Therefore, it is necessary to determine the exact mechanisms of renalase in cisplatin-induced nephrotoxicity. Main methods To study the protective effect of renalase on cell viability, renal function, apoptosis, reactive oxygen species (ROS) production and mitochondrial dynamics, cultured HK-2 cells and male mice were subjected to cisplatin. Signaling proteins related to apoptosis, survival, and mitochondrial fission were analyzed by Western blot. Key findings In this study, we showed that the protective effect of recombinant renalase in cisplatin-induced AKI was associated with the regulation of ROS production, mitochondrial dynamics and sirtuin-3 (Sirt3) levels in vivo and in vitro. After cisplatin treatment, recombinant renalase restored Sirt3 expression, reduced mitochondrial fission and ROS generation. In HK-2 cells, downregulation of endogenous Sirt3 expression by siRNA transfection abrogated the renalase cytoprotection. Significance Our study suggests that renalase protects against cisplatin-induced AKI by improving mitochondrial function and inhibiting oxidative stress, and in vitro, it functions in a Sirt3-dependent manner.

BackgroundImmune checkpoint inhibitors (ICIs) have brought a paradigm shift to cancer treatment. However, little is known about the risk of renal adverse events (RAEs) of ICI-based regimens, especially ICI combination therapy.MethodsWe carried out a network meta-analysis of randomized controlled trials (RCTs) to compare the risk of RAEs between ICI-based regimens and traditional cancer therapy, including chemotherapy and targeted therapy. Subgroup analysis was conducted based on tumor types.ResultsNinety-five eligible RCTs involving 40,552 participants were included. The overall incidence of RAEs, grade 3–5 RAEs, acute kidney injury (AKI), and grade 3–5 AKI was 4.3%, 1.2%, 1.3%, and 0.8%, respectively. Both ICI-based treatment regimens and traditional cancer therapy showed significantly higher risk of RAEs and AKI than the placebo. Among ICI monotherapy, anti-PD-1 (RR: 0.51, 95%CI: 0.29–0.91) was significantly safer than anti-CTLA-4 in terms of RAEs. Anti-CTLA-4 showed significantly higher toxicity than anti-PD-1 (RR: 0.33, 95%CI: 0.14-0.77), anti-PD-L1 (RR: 0.38, 95%CI:0.16-0.91), and anti-PD-1 plus anti-CTLA-4 (RR: 0.32, 95%CI: 0.12-0.87) in terms of grade 3-5 RAEs. The difference was not significant between ICI monotherapy and traditional cancer therapy, except that targeted therapy seemed the least toxic therapy in terms of the incidence of AKI. Anti-CTLA-4 plus anti-PD-1 were associated with higher risk of RAEs than anti-PD-1 (RR: 1.61, 95%CI: 1.02–2.56). The difference was not significant between other dual ICI regimens and ICI monotherapy in terms of RAEs and AKI. ICI plus chemotherapy showed increased risk of both RAEs and AKI compared with ICI monotherapy, chemotherapy, and targeted therapy. The overall results remained robust in the meta-regression and sensitivity analyses.ConclusionsAmong ICI monotherapy, anti-CTLA-4 appeared to be associated with increased toxicity, especially in terms of grade 3–5 RAEs. Anti-CTLA-4 plus anti-PD-1 were associated with higher risk of RAEs than anti-PD-1. However, the difference was not significant between other dual ICI regimens and ICI monotherapy in terms of RAEs and AKI. ICIs plus chemotherapy seemed to be the most toxic treatment regimen in terms of RAEs, AKI, and grade 3–5 AKI.Systematic Review RegistrationPROSPERO, identifier CRD42020197039.

Introduction: Acute kidney injury has been identified as a common complication of cardiac surgery. To date, the effect of the time interval from coronary angiography to cardiac surgery on postoperative acute kidney injury is still controversial. The aim of this study was to investigate the relationship between the timing of coronary angiography and cardiac surgery associated acute kidney injury.Methods: Eight hundred thirteen patients who underwent coronary angiography and cardiac surgery successively from January 2017 to December 2018 were included in this retrospective cohort study. We applied multivariate logistic regression, propensity score analysis, and subgroup analysis to evaluate the association between the time interval and postoperative acute kidney injury incidence and prognosis. Meta-analysis was conducted to verify the results.Results: The overall incidence of the cardiac surgery associated acute kidney injury was 28.8%. Age (OR = 1.046, 95%CI: 1.017–1.075), cardiopulmonary bypass (OR = 3.439, 95%CI: 1.316–8.986) and diabetes (OR = 2.522, 95%CI: 1.439–4.417) were found to be independent risk factors of postoperative acute kidney injury in multivariate logistic regression and propensity score analysis. Undergoing cardiac surgery within 7 days after coronary angiography was not associated with increased incidence of postoperative acute kidney injury or worse prognosis. Meta-analysis obtained consistent results.Conclusions: The time interval shorter than 7 days had no influence on cardiac surgery associated acute kidney injury incidence and prognosis. The decision of delaying the surgery should be made after comprehensive evaluation of the patient.

BACKGROUND The predictive value of Doppler-based renal resistive index (RRI) for acute kidney injury (AKI) has not been fully elucidated. The present meta-analysis was carried out to disclose the correlation between AKI and RRI, and to investigate the predictive value of RRI for the onset of AKI and its recovery. MATERIALS AND METHODS We searched PubMed, Embase, and Cochrane Library databases from inception to March 2019. The weighted mean difference (WMD) with a 95% confidence interval (CI) was used to assess the difference in RRIs between AKI and non-AKI patients. Moreover, the sensitivity and specificity were calculated, and summary receiver operating characteristic (SROC) curves were constructed. Meta-Disc and STATA were used for all statistical analyses. RESULTS A total of 20 studies (14 for prediction of the onset of AKI and 6 for prediction of AKI short-term non-recovery) were included in our meta-analysis. The values of RRI (WMD = 0.07; 95% CI: 0.05 - 0.09; p < 0.0001) were significantly higher in AKI patients compared with non-AKI patients. The overall sensitivity and specificity of RRI for prediction of the onset of AKI were 72% (95% CI, 64 - 80%) and 79% (95% CI, 71 - 85%), respectively. As for prediction of AKI short-term non-recovery, the pooled sensitivity was 81% (95% CI: 64 - 91), and the pooled specificity was 80% (95% CI: 72 - 85). For the onset of AKI, the best predictive performance was observed for the RRI measured immediately after major surgery, and a cut-off value ≥ 0.715 also achieved superior predictive value. CONCLUSION This study showed that the elevation of RRI may be related to the progression of AKI, and RRI could have good overall predictive value for the onset of AKI and its short-term non-recovery. Further studies in different clinical settings and patient groups are warranted before it could be widely used in clinical practice.

The aim of this study is to investigate the association between body composition, measured by bioelectrical impedance analysis, and outcomes in patients with acute kidney injury (AKI) receiving kidney replacement therapy (KRT).Patients with severe AKI treated with KRT in our hospital between September 2016 and August 2018 were enrolled. These patients were assessed by body composition analysis before KRT, and on the 3rd day and the 7th day after initiation of KRT. The predictors included lean tissue index (LTI), fat tissue index, and body cell mass index (BCMI). The association between all-cause mortality and predictors was analyzed using Cox regression.A total of 152 patients were included in this study, with a 28-day mortality of 46.7% and 1-year mortality of 60.5%. LTI (adjusted hazard ratio per standard deviation: 0.37; 95% confidence interval = 0.21-0.66, P .001) and BCMI (adjusted hazard ratio per standard deviation: 0.37; 95% confidence interval = 0.21-0.67, P .001) on day 7 after initiation of KRT, rather than before KRT, were associated with mortality during follow-up. LTI and BCMI before KRT were associated with 28-day mortality rather than 1-year mortality.LTI and BCMI before KRT were associated with short-term prognosis, and those on day 7 after KRT initiation were associated with intermediate mortality in patients with AKI requiring KRT.

The Src homology and collagen A (ShcA) adaptor protein that binds to tyrosine kinase receptors. ShcA plays a role in insulin signaling, stress resistance and energy metabolism. The 66-kDa Src homology 2 domain-containing protein (p66shc) belongs to the ShcA family and has been associated with reactive oxygen species (ROS); increased ROS is involved in the pathology of lupus nephritis (LN). However, whether ShcA can act as a biomarker for oxidative injury in LN is unknown. This study is aimed to investigate the ShcA expression in kidney tissues from patients presenting with LN and the association between ShcA expression and clinical parameters. Renal biopsy tissues were obtained from 62 LN, 20 primary membranous nephropathy (MN) and 10 other secondary MN patients. ShcA was measured by immunofluorescence. The expression of ShcA in the membranous lupus nephritis (class V) group showed a higher trend but there were no significant differences compared with pure mesangial disease (class II) and proliferative (Class III/IV) lupus nephritis. ShcA deposits were negative in primary and other secondary MN. ShcA might act as a new biomarker and a diagnostic tool to identify membranous lupus nephritis with other MN.

Podocytes play an important role in the pathogenesis and progression of glomerulosclerosis. Recent studies indicate that aldosterone/mineralocorticoid receptor (MR) is a major contributor of chronic kidney disease (CKD) progression. Aldosterone/MR induces glomerular podocyte injury, causing the disruption of the glomerular filtration barrier and proteinuria. The present study investigated the mechanisms by which aldosterone/MR mediated podocyte injury, focusing on the involvement of oxidative stress, endoplasmic reticulum (ER) stress, and autophagy. We observed that aldosterone/MR induced ER stress and podocyte injury both in vivo and in vitro. Blockade of ER stress significantly reduced aldosterone/MR-induced podocyte injury. In addition, we found that ER stress-induced podocyte injury was mediated by CCAAT/enhancer-binding protein (C/EBP) homologous protein (Chop). Interestingly, autophagy was also enhanced by aldosterone/MR. Pharmacological inhibition of autophagy resulted in increased apoptosis. Inhibition of ER stress significantly reduced aldosterone/MR-induced autophagy. In addition, the activation of ER stress increased the formation of autophagy, which protected podocytes from apoptosis. Moreover, we observed that the addition of ROS scavenger, N-acetyl cystein (NAC), blocked both ER stress and autophagy by aldosterone/MR. Collectively, these results suggest that oxidant stress-mediated aldosterone/MR-induced podocyte injury via activating ER stress, which then triggers both Chop-dependent apoptosis and autophagy to cope with the injury. These findings may guide us to therapeutic strategies for glomerular diseases.

This paper introduces that the department of the Diagnostics of The First School of Clinical Medicine at Nanjing Medical University use network information technology to conduct online teaching during the novel coronavirus epidemic. Objectives: To share the experience of comprehensive online teaching, and to investigate students’ use of Fanya. Chaoxing online learning during the Diagnostics course under the COVID-19. Methods: We randomly selected Diagnostics as the course which we investigated and analyzed through using questionnaires. Results: 94.24% of students use smart phones to study online. 86% of students spend 1-6 hours per week studying Diagnostics. 79% of students have access to obtain the majority of online teaching resources. 86.3% of students expressed that they could achieve the learning objectives and meet the learning requirements of online learning content. The fluency score for watching instructional videos reached 87.13%. 92% of students believed course materials were helpful to them. There were many difficulties such as unclear assessment method, overwhelmed and unable to maintain learning progress, lack of learning resources. Conclusions: Chinese network can basically meet the needs of comprehensive online teaching. The materials for online teaching can basically meet the needs of teaching. Making a clear assessment method timely, assigning appropriate homework and preparing the learning materials as more as possible are necessary. Organizing student learning at different times and supporting by the National Information Network Department are important.

Summary Background and objectives Lower heart rate variability implies increased risk of cardiovascular disease. This study aimed to evaluate the relationship between mineral metabolism and heart rate variability and longitudinal changes of heart rate variability after parathyroidectomy in stage 5 CKD patients. Design, setting, participants, & measurements This cross-sectional study included 118 stage 5 CKD patients, 87 controls, and a prospective study in two subgroups classified as successful ( n =17) and unsuccessful ( n =4) parathyroidectomy follow-up enrolled from March of 2011 to December of 2012. Blood examination and 24-hour Holter for heart rate variability were measured. Results Most heart rate variability indices were lower in stage 5 CKD patients. In multivariate stepwise regression models, serum intact parathyroid hormone was correlated with mean normal-to-normal R–R intervals, mean heart rate, and very low frequency, serum calcium was correlated with SD of 5-minute average of normal R–R intervals, and serum phosphorus was correlated with very low frequency and low frequency/high frequency. Compared with baseline, the successful parathyroidectomy subgroup had significant improvements in mean normal-to-normal R–R intervals, mean heart rate, SD of normal-to-normal R–R intervals, SD of 5-minute average of normal R–R intervals, very low frequency, high frequency, and low frequency/high frequency. There was no significant change of heart rate variability in patients after unsuccessful parathyroidectomy. Conclusions Disorders of mineral metabolism are associated with decreased heart rate variability in stage 5 CKD. Successful parathyroidectomy may contribute to reverse this cardiovascular disease risk in severe secondary hyperparathyroidism patients.

Cisplatin often causes acute kidney injury (AKI) in the treatment of a wide variety of malignancies. Mitochondrial dysfunction is one of the main reasons for cisplatin nephrotoxicity. Previous study showed that Pink1 and Parkin play central roles in regulating the mitophagy, which is a key protective mechanism by specifically eliminating dysfunctional or damaged mitochondria. However, the mechanisms that modulate mitophagy in cisplatin induced nephrotoxicity remain to be elucidated. The purpose of this study was to investigate the effects of Pink1/Parkin pathway in mitophagy, mitochondrial dysfunction and renal proximal tubular cells injury during cisplatin treatment. In cultured human renal proximal tubular cells, we found that knockdown of Pink1/Parkin induced the aggravation of mitochondrial function, leading to the increase of cell injury through inhibition of mitophagy. Additionally, the overexpression of Pink1/Parkin protected against cisplatin-induced mitochondrial dysfunction and cell injury by promoting mitophagy. Our results provide clear evidence that Pink1/Parkin-dependent mitophagy has identified potential targets for the treatment of cisplatin-induced AKI.

Leptin is an adipokine that regulates various metabolism, but its association with secondary hyperparathyroidism (SHPT), a clinical manifestation of chronic kidney disease-mineral and bone disorder (CKD-MBD), remains obscure. Parathyroidectomy (PTX) is recommended for severe SHPT patients. Here, the associations between circulating leptin and clinical characteristics in CKD patients were investigated. Effects of PTX on leptin production were analyzed in vivo and in vitro. Controls and CKD patients had approximate serum leptin levels in that a larger proportion of CKD patients with body mass index (BMI) 2. Serum leptin was related to anemia, albumin, and bone metabolism disorders in CKD patients. Lower intact parathyroid hormone (PTH) was related with higher leptin in PTX patients group. Severe SHPT inhibited uremia-enhanced leptin production in 3T3-L1 adipocytes, which was attenuated after PTX. High levels of PTH were found to reduce Akt phosphorylation and leptin production in vitro but high levels of calcium and phosphorus were not. Successful PTX was found to improve anemia and malnutrition in severe SHPT patients, and this was correlated with increased circulating leptin levels via up-regulated Akt signaling in adipocytes. These findings indicated the therapeutic potential of leptin and related target pathway for improving survival and quality of life in CKD.

This article applies the index of multiple deprivations to measuring the dimensions of deprivation in the city of Guangzhou, China. The study uses both population census data and information on minimum living standard support. The spatial pattern shows the concentration of highly deprived areas in old areas as well as in ex-industrial districts on the outskirts. The deprivation in old areas is characterized by underprivileged living conditions, while ex-industrial areas present a more income-based poverty. The authors suggest that this spatial pattern has resulted from underinvestment in old areas before economic reform and economic restructuring of industrial districts under postreform policies.

The article analyzed the spatial division of industries of the Pearl River Delta (PRD) in the 1990s, a period that witnessed the deepening of the reform and opening policies and continued rapid development of the region. By adopting the index of specialization, the extent of specialization, its change and its spatial distribution in the region are measured and demonstrated. The research revealed that, despite the trend of more balanced development of the secondary sector between the PRD and the rest of the province, in the PRD, it is the unbalanced development that dominated and the spatial division of the secondary sector has been shaped. The tertiary industry has also been experiencing unbalance development and the spatial division of the tertiary sector has been emerging, its extent of concentration appearing even more evident than that of the secondary sector. The author also discussed the linkage between the spatial division of the two sectors. In the end of the paper, the trends of the spatial division of the industries in the PRD are forecasted.

Population density in Guangzhou City is characterized by a main single center and considerable differences throughout the 8 districts and 112 neighborhoods and towns. Historically, population density in Guangzhou City rose sharply, and population distribution was mainly influenced by the attraction of the port. After the founding of the People’s Republic of China (PRC), a series of large-sized factories were built in suburban areas, which drew in a large amount of population from the areas outside of Guangzhou. A small part of this population lived in the suburban areas while most resided within the city centre. As the natural increase rate of population was very high, the population density of both the city centre and suburban areas rose, the former rose at higher rates. Since reform and the opening up to the outside world, Chinese economy has grown quickly, the total population of Guangzhou has also increased quickly. Meanwhile, changes in population density within the city is becoming more and more obvious. Population density in the city centre is falling and in city periphery is rising. From the analysis of the population density model, it is found that population distribution of Guangzhou is in the process of transition from an early stage to a mature stage. Population decline within the centre city of Guangzhou City, which reflects a prosperous economy of the city, is significantly different from the recession of in the western countries.

Principal components analysis and cluster analysis we used to analyze the urban social spatial structure of socialist China, using the city proper of Guangzhou in 1984 as the study area. Unlike the urban social spatial structure in Western cities, which are commonly differentiated by socioeconomic status, family status, and ethnicity, it was found that the main components of social space in Guangzhou are population density, educational level, employment, housing quality, and household composition. Five types of social areas are identified: (i) high density, mixed function areas, (2) cadre (government worker) areas, (3) worker areas, (4) intellectual areas, and (5) scattered agricultural areas. The spatial pattern of the social areas of Guanghou has a concentric elliptical shape. The city is composed of a high-density, mixed-function center surrounded by consecutive rings of workers' residences and agricultural land, with a cadre sector abutting the northeastern edge of the city center and two intelectual ...

The city-size structure and spatial distribution of the urban system reflect socioeconomic development and its spatial distribution. By tracking the development of the urban system we can not only monitor the development of the society but also reveal problems in the process of development and thereby provide a basis for policymaking....Since 1978 a series of new policies has been introduced including rural reform urban reform establishment of the socialist market system the opening to the outside world and emphasis on the development of the coastal region of China. All have contributed to Chinas emergence as the most rapidly growing economy in the world and have dramatically changed its economic structure and pattern of regional development....This paper focuses on new trends in Chinas urban system between 1978 and 1990 and their relationships with economic development during this period. (EXCERPT)

Since 1978, rural urbanization has been accelerated in the Zhujiang (Pearl) River Delta because of the rapid development of commodity agriculture, industrialization and tertiary industry. Its natural urban population increase had been mostly mechanical before now, and the towns have been transformed from traditional centers into those serving various functions, particularly industrial ones.

Objective To investigate the effects of coupled plasma filtration adsorption (CPFA) on the immune function of patients with multiple organ dysfunction syndrome (MODS). Methods This study was a prospective, pilot, before-and-after self-crossover, clinical trial. Seven patients diagnosed with MODS and severe infection were randomly allocated to both 10 hours of CPFA and 10 hours of high-volume hemofiltration (HVHF) with a 12-hour interval and in random order. Serum concentrations of 7 cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-10 (IL-10), interleukin-1 receptor antagonist (IL-1Ra), and soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) were measured during each treatment. The HLA-DR expression by the blood monocytes and the TNF-α production by the patients’ blood (both spontaneous and lipopolysaccharide stimulated) were tested before and after the treatment. TNF-α production of normal human monocytes (THP-1 cells) incubated in vitro with the patient plasma was also measured. Results During CPFA, the fall in serum TNF-α and rise in serum IL-1Ra coincided with the rise in ratios of sTNFR2/TNF-α and IL-1Ra/IL-1β (p0.05). Spontaneous and lipopolysaccharide-induced TNF-α production increased over time with CPFA (p=0.038, p=0.034, respectively), but did not change with HVHF (p>0.05). Patient plasma suppressed the production of TNF-α by cultured normal monocytes. This effect decreased over time with CPFA (p=0.041), but there was no effect with HVHF (p>0.05). Conclusions CPFA was superior to HVHF in increasing the ratios of antiinflammatory to proinflammatory mediators, improving antigen presentation ability, and restoring leukocyte responsiveness. These findings suggest a potential role for CPFA in the treatment of MODS.

A Chinese megalopolis is currently forming around the Peari River delta. The population densities, transport infrastructures and local economic growth rates all contribute to the emergence of a vast urban region. Two towns, Hong Kong and Macao, give the delta international presence. The continental urban network offers a complete hierarchy of towns. It is the interrelations between these urban and economic poles which have produced the outstanding development of the coastal region in the eighties., Une mégalopolis chinoise se forme actuellement à l'échelle du delta de la Rivière des Peiles. Les densités de populations, les infrastructures de transports, les taux locaux de croissance économique, tout concourt à l'émergence d'une région urbaine de large ampleur. Grâce à Hong Kong et Macao, le delta dispose de métropoles de rayonnement international. Le réseau urbain continental offre, quant à lui, une hiérarchie complète de villes. Ce sont les interrelations entre ces pôles urbains et économiques qui ont permis l'exceptionnel développement de la région côtière dans les années quatre-vingt., Xu Xueqiang, Zhou Chunshan. Une mégalopolis en formation : le delta de la Rivière des Perles. In: Villes en parallèle, n°23-24, décembre 1996. Villes chinoises. pp. 168-179.