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Introduction AL amyloidosis has become a common secondary cause in elderly male patients presenting with nephrotic syndrome. Daratumumab-CyBorD regimen is approved as the standard first-line regimen for AL-amyloidosis. We aim to analyze the prognosis of patients treated with bortezomib-based regimen and other alternative regimens. Method We retrospectively collected the baseline and follow up data of newly diagnosed AL amyloidosis patients. Hematological and renal response rate were compared among different regimens and overall survival and renal survival were analyzed. Subgroup analysis of Mayo stage III patients was also performed. Results 72 cases were included, 48.6% of whom had cardiac involvement. Overall response rate in patients treated with bortezomib-based regimen was 67.4%, including 27.9% complete response (CR). Renal outcomes such as proteinuria response rate and incidence of end stage renal disease (ESRD) were not different between bortezomib and thalidomide-based therapy.Median follow up for whole cohort was 22 months,and 13(18.1%) patients died at the end of follow-up, while 7 patients(9.7%) progressed to dialysis. Median overall survival (OS) was not reached in both regimens and 1 year survival rates were 90.4% and 80.0% respectively in bortezomib and thalidomide based therapy(P = 0.127). Patients treated with bortezomib-based treatment had longer organ deterioration progression-free survival (MOD-PFS).There was no difference in response rate and OS between patients treated with cyclophosphamide, bortezomib,dexamethasone(CVD) and bortezomib, dexamethasone (VD). Mayo stage III patients who were treated with VD regimen had longer OS compared with TD or CTD regimen. Conclusion Bortezomib-based regimen had high efficacy in promoting rapid hematologic responses and reducing the risk of major organ deterioration in AL amyloidosis, which was also effective among patients with cardiac insufficiency. Addition of cyclophosphamide into VD regimen could not further improve the overall remission or survival of AL amyloidosis.

Kidney international 103(2), 391-402 (2022). doi:10.1016/j.kint.2022.09.017, Published by Elsevier, New York, NY

Understanding the rules of genetic recombination in controlled pollination directly related to the selection of parental genotypes and the utilization of heterosis, and genotype identification is a primary study of the genetic rules. The aims of this study were to investigate the ability of near infrared (NIR) spectroscopy to accurately and efficiently discriminate pure species and hybrids within the genus of Eucalyptus, to evaluate the transmission of genetic pedigree in control pollination, and reveal the genetic variation within the genotypes studied. NIR spectra were collected both from fresh leaves and dried, milled leaves of seedlings from pure species E. urophylla and E. grandis, and their F1 hybrids. Principal component analysis (PCA) scores plots of NIR spectra from fresh leaves and dry, milled powder from pure species showed clear segregation, although the species clusters were scattered, suggesting different base genetics and high genetic variation within families of the two pure species. Classification using soft independent modelling of class analogy of the NIR spectra of dried leaves was significantly better than using spectra acquired on fresh leaves, meaning the water content had an effect on the analysis. The projections and orthogonal distance between hybrids and parents, as calculated using PCA models, demonstrated the visualized spectral distance between each hybrid and the parents was very different. Clouds of individuals within a hybrid clusters varied from tightly packed to scattered, which reflected the genetic additive effects inherited from female and male parents were different, and their genetic variation was also different after genetic recombination. The varying response values for partial least squares discriminant analysis prediction verified the conclusions shown by projections and orthogonal distance. The results of this study demonstrate the potential of using NIR spectroscopy to rapidly discriminate taxon. The application of NIR spectroscopy to non-destructively confirm taxonomic identity will greatly facilitate the evaluation of the genetic basis and genetic variation available within breeding populations and for accessing the levels of contamination by non-target pollen in control pollination.

Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Complement factor H related protein 5 (CFHR5) may contribute to dysfunctional complement activation, thus predisposing to SLE. The expression levels of anti-dsDNA, C3 and CFHR5 in blood samples from 50 SLE patients and 50 healthy individuals were evaluated, and also their expression levels were measured in an MRL/lpr mouse model and control MRL/MPJ mice. The results showed that CFHR5 expression increased in SLE patients together with the increase of anti-dsDNA in comparison with the healthy control. Furthermore, CFHR5 expression was inversely correlated with C3, down-regulation of which was associated with worse SLE. Previous studies indicated that long noncoding RNA (lncRNA) regulates mRNA synthesis via microRNA (miRNA) inhibition. The present bioinformatics analysis revealed that the target miRNA (miR-222) was combined with both lncRNA MIAT and mRNA CFHR5. H&E staining of the kidney tissues of the MRL/lpr mice revealed that lncRNA MIAT, as a competitive inhibitor of miR-222, enhanced SLE by upregulating CFHR5 expression through the degradation of miR-222 in vivo . Thus, our study revealed for the first time the role of lncRNA MIAT in regulating CFHR5 expression in SLE in vivo and provided new insights into the role of lncRNA in regulation and complement function of SLE pathogenesis.

Hyperglycemia-induced podocyte damage contributes to the onset of diabetic nephropathy, a severe complication of diabetes. Perilipin 5 (Plin5) exerts a vital role in numerous pathological conditions via affecting cell apoptosis, oxidative stress, and inflammation. However, whether Plin5 plays a role in regulating podocyte damage of diabetic nephropathy has not been fully determined. This work aimed to explore the role of Plin5 in mediating high glucose (HG)-induced injury of podocytes in vitro. Our results demonstrated that Plin5 expression was markedly decreased in mouse podocytes challenged with HG. Plin5 overexpression markedly suppressed HG-induced apoptosis, reactive oxygen species (ROS) production, and the pro-inflammatory response in podocytes. On the contrary, Plin5 silencing produced the opposite effects. Further mechanistic analysis demonstrated that Plin5 upregulation remarkably increased the levels of phospho-Akt and phospho-glycogen synthase kinase-3β (GSK-3β) in HG-exposed podocytes. Moreover, Plin5 overexpression increased the levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and enhanced the activation of Nrf2 signaling. Akt inhibition markedly blocked Plin5-mediated activation of Nrf2, while GSK-3β inhibition reversed Plin5-silencing-induced suppressive effects on Nrf2 activation. Notably, Nrf2 suppression significantly blocked Plin5-mediated protective effects against HG-induced podocyte injury. In summary, our work indicates a vital role for Plin5 in protecting against HG-induced apoptosis, oxidative stress, and inflammation in podocytes via modulation of Akt/GSK-3β/Nrf2 signaling. This study suggests that Plin5 may participate in modulating podocyte damage in diabetic nephropathy.

The CesA proteins are key players in cellulose synthesis. Eucalyptus is well-known for cellulose synthesis, although the mechanism of cellulose synthesis is largely unknown. In this study, 11 CcCesA genes were identified by comprehensive bioinformatics analysis in Corymbia citriodora, a eucalypt species. CcCesA genes were generally conserved in each subfamily. Among them, four genes lacked a transmembrane domain in the N-terminal. We showed that genes of CesA2, 4, 5, and 8 may regulate the synthesis of secondary cell walls (SCWs) through phylogenetic trees analysis. Two pairs of segmental duplication and one pair of tandem duplication were detected in CcCesAs. Analysis of Ka/Ks ratios revealed that the duplicated genes were under negative or purifying selection. Numerous cis-acting elements related to plant hormones and light reactions were identified in the promoters of CcCesAs. Expression analysis confirmed that genes of CesA2, 4, and 8 regulate the synthesis of SCWs, and CesA8, in particular, had the highest expression compared with other genes. The results will help us understand the complexity of the CcCesAs in different diameters at breast height and provide valuable information for future functional characterization of specific genes in C. citriodora.

Peritoneal dialysis (PD) first policy has been established in Hong Kong since 1985. After 35 years of practice, the PD first policy in Hong Kong has influenced many countries around the world including governments, health ministries, nephrologists and renal nurses on the overall health policy structure and clinical practice in treating kidney failure patients using PD as an important dialysis modality. In 2021, the International Association of Chinese Nephrologists and the Hong Kong Society of Nephrology jointly held a symposium celebrating the 35 years of PD first policy in Hong Kong. In that symposium, experts and opinion leaders from around the world have shared their perspectives on how the PD first policy has grown and how it has affected PD and home dialysis practice globally. The advantages of PD during COVID-19 pandemic were highlighted and the use of telemedicine as an important adjunct was discussed in treating kidney failure patients to improve the overall quality of care. Barriers to PD and the need for sustainability of PD first policy were also emphasized. Overall, the knowledge awareness of PD as a home dialysis for patients, families, care providers and learners is a prerequisite for the success of PD first. A critical mass of PD regional hubs is needed for training and mentorship. Importantly, the alignment of policy and clinical goals are enablers of PD first program.

Diabetic nephropathy (DN), a common cardiovascular disease, has been a global health threat. MicroRNAs (miRNAs) have been proposed to frequently participate in the occurrence and development of DN, however, the role of miR-325-3p in DN remains uncharacterized. Our research aimed to explore the function and mechanism of miR-325-3p in DN. Bioinformatics analysis (Targetscan, http://www.targetscan.org) and a wide range of experiments including RT-qPCR, CCK-8 assay, western blot, luciferase reporter assay, RNA immunoprecipitation (RIP) assays, urine protein and blood glucose assays, histology analysis and morphometric analysis were used to explore the function and mechanism of miR-325-3p and C-C motif chemokine ligand 19 (CCL19). CCL19 could facilitate the progression of DN by inhibiting cell viability and promoting inflammation and fibrosis in HK-2 and HMC cells. In addition, CCL19 was confirmed to be targeted and negatively regulated by miR-325-3p. Rescue assays validated that the impacts of miR-325-3p mimics on the viability, inflammation and fibrosis of HK-2 and HMC cells were recovered by CCL19 overexpression. To sum up, miR-325-3p inhibits renal inflammation and fibrosis by targeting CCL19 in a DN cell model and mice model, implying miR-325-3p as a possible therapeutic target for DN treatment.

Background Cardiac involvement frequently occurs in patients with renal light chain (AL) amyloidosis, which predisposes these patients to heart failure, arrhythmia, or infarction with poor prognosis. Hypothesis Twelve‐lead electrocardiogram (ECG) parameters may be associated with prognosis in renal AL amyloidosis. Methods A retrospective single‐center cohort study was performed. Biopsy‐proven renal AL amyloidosis patients from January 2014 to December 2018 at the First Affiliated Hospital of Xi'an Jiaotong University were enrolled. The baseline demographic information, laboratory tests, 12‐lead ECG parameters at the time of diagnosis were obtained from medical records. The endpoint was defined as the time to all‐cause death from baseline for all deceased patients and time to censor date (June 2019) for all other patients. Univariate and multivariate Cox proportional hazard models were conducted to identify the relationship between ECG parameters and all‐cause mortality. Results A total of 69 patients with a mean age of 61.5 ± 11.4 years were enrolled in this study. The median PR interval and QTc interval were 160 (140, 186) and 417 ± 42 ms. The mean follow‐up duration was 15.9 ± 13.8 months. Multivariate Cox regression analysis showed that regardless of adjustment for age, gender and serum creatinine, PR interval (HR 1.022, 95% CI: 1.007‐1.038, P = .005), and QTc interval (HR 1.012, 95% CI: 1.004‐1.021, P = .004) were independently associated with all‐cause mortality. Conclusions PR interval and QTc interval were independently associated with all‐cause mortality in renal AL amyloidosis patients. ECG parameters may provide prognostic potential of renal AL amyloidosis patients and promote the management of patients with renal AL amyloidosis.

In 2018, Kidney Disease: Improving Global Outcomes (KDIGO) published a clinical practice guideline on the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in chronic kidney disease (CKD). The guideline synthesized recent advances, especially in HCV therapeutics and diagnostics, and provided clinical recommendations and suggestions to aid healthcare providers and improve care for CKD patients with HCV. To gain insight into the extent that the 2018 guideline has been adopted in Asia, KDIGO convened an HCV Implementation Summit in Hong Kong. Participants included nephrologists, hepatologists, and nurse consultants from 8 Southeast Asian countries or regions with comparable high-to-middle economic ranking by the World Bank: mainland China, Hong Kong, Japan, Malaysia, Singapore, South Korea, Taiwan, and Thailand. Through presentations and discussions, meeting participants described regional practice patterns related to the KDIGO HCV in CKD guideline, identified barriers to implementing the guideline, and developed strategies for overcoming the barriers in Asia and around the world.

Background: The role of monitoring serum vancomycin levels during treatment of peritoneal dialysis (PD)–associated peritonitis is controversial. Substantial inter-individual variability may result in suboptimal serum levels despite similar dosing of vancomycin. The published predictors of suboptimal serum vancomycin levels remain limited. Methods: Data were retrospectively collected from 541 patients on continuous ambulatory peritoneal dialysis between 1 January 2018 and 31 December 312019. For gram-positive cocci and culture-negative peritonitis, we adopted a vancomycin administration and monitoring protocol. Short-term adverse outcomes of PD-associated peritonitis, including transfer to haemodialysis, death, persistent infection beyond planned therapy duration and relapse, were observed. The association between trough serum vancomycin levels and short-term adverse outcomes was evaluated. Results: Intraperitoneal vancomycin was used in 61 gram-positive cocci or culture-negative peritonitis episodes in 56 patients. Fourteen episodes of short-term adverse outcomes occurred in 12 patients, whose average trough serum vancomycin levels on day 5 of treatment were significantly lower than those who didn’t experience any adverse outcomes (8.4 ± 1.7 vs 12.5 ± 4.3 mg/L, p = 0.003). In gram-positive cocci or culture-negative peritonitis patients, those with higher day 5 trough serum vancomycin levels had a lower risk of short-term adverse outcomes (odds ratio: 0.6, 95% confidence interval: 0.4 to 0.9, p = 0.011). Receiver operating charecteristic curve (ROC) analyses showed that the day 5 trough serum vancomycin levels diagnostic threshold value for short-term adverse outcomes was 10.1 mg/L. After adjustments for gender, exchange volume and residual kidney function (RKF), baseline higher peritoneal transport was associated with a suboptimal (Conclusions: Serum vancomycin levels are correlated with short-term adverse outcomes of PD-associated peritonitis, and higher peritoneal solute transport status is associated with suboptimal trough serum vancomycin levels on day 5.

Large-scale, contemporary studies assessing the spectrum of kidney diseases in northwest China are lacking. Therefore, we aimed to assess the profile of 30-year temporal changes in biopsy-proven kidney diseases in northwest China.This cross-sectional study included all patients with a native kidney biopsy specimen in the First Affiliated Hospital of Xi'an Jiaotong University between 1989 and 2018. Data on demographic characteristics and pathological diagnosis were extracted from medical records and pathological reports. Changing patterns of kidney diseases over the study period and disease distributions in different gender and age groups were examined.This study included 13,620 patients with a mean age of 38.5 ± 16.5 years and included 58.2% of men. Primary glomerulonephritis (PGN), second glomerulonephritis (SGN), tubulointerstitial disease, and other renal diseases accounted for 79.1, 18.3, 2.4, and 0.2% of all kidney diseases, respectively. In PGN, IgA nephropathy (IgAN) (25.1%) was the most common type, followed by non-IgA mesangial proliferative glomerulonephritis (MsPGN) (24.9%) and membranous nephropathy (MN) (17.4%). The frequency of MN dramatically increased (p 0.001) over the course of the study. Lupus nephritis (6.2%) and Henoch-Schönlein purpura nephritis (HSPN) (4.9%) were leading SGN diagnosis. The frequencies of IgAN, non-IgA MsPGN, and HSPN declined, while those of ANCA/pauci-immune glomerulonephritis and diabetic nephropathy significantly increased.PGN continues to be the predominant kidney disease in northwest China, and IgAN is the most common type. The frequencies of MN and diabetic nephropathy significantly increased. These findings might be explained by behavioral and environmental exposures and provide implications on future hypothesis-driven research.

Aims/Introduction Type 2 diabetes mellitus has been a leading cause of chronic kidney disease (CKD), with a heterogeneous distribution worldwide. Optimal healthcare planning requires an understanding of how the burden of CKD as a result of type 2 diabetes mellitus has changed over time and geographic location, as well as the potential roles of sociodemographic, clinical and behavioral factors in these changes. Materials and Methods We used the Global Burden of Disease data from 1990 to 2017 at the global, regional and national levels to investigate changes in the incidence, death and disability‐adjusted life years of CKD as a result of type 2 diabetes mellitus, incorporating both epidemiological research and risk factor monitoring. Results The incident cases of CKD as a result of type 2 diabetes mellitus worldwide in 2017 had increased by 74% compared with 1990; total disability‐adjusted life years had increased by 113%, mainly attributable to population expansion and demographic transition. The Sociodemographic Index was significantly and negatively correlated with overall CKD as a result of type 2 diabetes mellitus burden. However, in 82 countries and territories, the burden was not alleviated in parallel with socioeconomic development. Conclusions CKD as a result of type 2 diabetes mellitus has been the main contributor to the increasing burden of CKD over the past several decades. We suggest a more pragmatic approach focusing on early diagnosis, primary care and adequate follow up to reduce mortality and the long‐term burden in low‐to‐middle Sociodemographic Index regions. Interventions should address high systolic blood pressure, as well as overweight and obesity problems, especially in high‐income regions., On a global scale, a modest decrease in the age‐standardized incidence rate of chronic kidney disease as a result of type 2 diabetes mellitus has been observed. Low‐ to middle‐income countries are suffering from a disproportionally higher burden of mortality rather than of morbidity compared with relatively more affluent counties. From 1990 to 2017, 82 of 195 countries failed to alleviate the burden of chronic kidney disease in patients with type 2 diabetes mellitus in parallel with sociodemographic development. Meanwhile, there are potential opportunities for countries across the entire development spectrum. High body mass index is accounting for an increasingly greater proportion of the age‐standardized disability‐adjusted life years rate globally.

With the widespread use combination antiretroviral therapy, there has been a dramatic decrease in HIV-associated nephropathy. However, although the patients living with HIV have low or undetectable viral load, the prevalence of chronic kidney disease (CKD) in this population remains high. Additionally, improved survival is associated with aging-related comorbidities such as diabetes and cardiovascular disease. A faster progression of CKD is associated with concurrent HIV infection and diabetes than with HIV infection or diabetes alone. To explore the potential pathogenic mechanisms that synergistically drive CKD progression by diabetes and HIV infection, we generated a new mouse model with a relatively low expression of HIV-1 proviral genes specifically in podocytes (pod-HIV mice) to better mimic the setting of kidney injury in patients living with HIV. While no apparent kidney phenotypes were observed at baseline in pod-HIV mice, the induction of mild diabetic kidney disease with streptozotocin led to significant worsening of albuminuria, glomerular injury, podocyte loss, and kidney dysfunction as compared to the mice with diabetes alone. Mechanistically, diabetes and HIV-1 synergistically increased the glomerular expression of microRNA-34a (miR-34a), thereby reducing the expression of Sirtuin-1 (SIRT1) deacetylase. These changes were also associated with increased acetylation and activation of p53 and p65 NF-κB and with enhanced expression of senescence and inflammatory markers. The treatment of diabetic pod-HIV mice with the specific Sirtuin-1 agonist BF175 significantly attenuated albuminuria and glomerulopathy. Thus, our study highlights the reduction in Sirtuin-1 as a major basis of CKD progression in diabetic patients living with HIV and suggests Sirtuin-1 agonists as a potential therapy.

Renal ischaemia/reperfusion (I/R) is a major cause of acute renal failure with increased morbidity, mortality, and prolonged hospitalizations. Clematichinenoside (AR), a triterpenoid saponin isolated from the roots of Clematis chinensis, was reported to possess a protective effect against I/R injury. However, the effect of AR on renal I/R injury has not been evaluated. This study aims to examine the effect of AR on an in vitro I/R model in human proximal tubular epithelial cells HK-2. HK-2 cells were subjected to hypoxia/reoxygenation (H/R) stimulation to mimic I/R in vitro. The results showed that AR improved cell viability of H/R-stimulated HK-2 cells. AR pretreatment resulted in decreased production of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as increased in superoxide dismutase (SOD) activity in H/R-stimulated HK-2 cells. In addition, AR also presented an anti-inflammatory activity, as evidenced by decreased secretion of pro-inflammatory cytokines including IL-6, IL-1β, and TNF-α. Moreover, apoptotic rate was markedly decreased in HK-2 cells pretreated with AR. The bax expression was decreased, while bcl-2 expression was increased by AR pretreatment. Furthermore, AR enhanced the H/R-stimulated activation of the Nrf2/HO-1 signalling pathway in HK-2 cells. In conclusion, these findings indicated that AR protected HK-2 cells from H/R-induced cell injury via regulating the Nrf2/HO-1 signalling pathway.

The innate immune response contributes to hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). However, the pathogenic mechanism of NAFLD is still poorly understood. The costimulatory molecule V-set and immunoglobulin domain-containing protein-4 (Vsig4), which is exclusively expressed on macrophages, shows significant role in regulating macrophage-mediated inflammation. Here, we attempted to explore if Vsig4 expression was involved in high fat diet (HFD)-induced NAFLD. The results indicated that Vsig4 expression was markedly down-regulated in fatty livers of NAFLD patients and obese mice. Vsig4 knockout accelerated HFD-induced metabolic dysfunction. In addition, the loss of Vsig4 significantly promoted insulin resistance and lipid deposition in liver samples of HFD-challenged mice. Furthermore, HFD-induced inflammation was apparently accelerated in Vsig4 knockout mice by further activating nuclear factor-κB (NF-κB) signaling pathway. Also, Vsig4 deficient mice exhibited greater collagen accumulation in hepatic samples in HFD-challenged mice compared to the WT mice, which was through promoting transforming growth factor-β1 (TGFβ1) signaling. Importantly, we found that lipopolysaccharide (LPS)- or TGFβ1-stimulated inflammation and fibrosis in primary hepatocytes and hepatic stellate cells, respectively, were markedly exacerbated by co-culture with condition medium from bone marrow-derived macrophages (BMDMs) with Vsig4 deficiency. Finally, transplantation of bone marrow cells from control mice to Vsig4-knockout mice restored the severity of steatosis, inflammation and fibrosis after HFD feeding. Therefore, loss of Vsig4 accelerated the severity of lipid deposition, fibrosis and the inflammatory response. Vsig4 could be a therapeutic target for NAFLD treatment.

Background: Peritoneal dialysis (PD) is a kind of renal replacement therapy (RRT), which can be employed to treat pediatric acute kidney injury (AKI) as it is safe, simple, and cost-effective. The studies of PD treatment in pediatric AKI in China have rarely been reported in English literature. Objective: To investigate the efficacy and the outcome of PD in pediatric patients with AKI. Methods: We performed a retrospective study of children who received PD as RRT for AKI in a teaching hospital in northwest China from 2003 to 2013. Demographic characteristics and laboratory data were collected, and the prognostic factors of renal recovery were identified. Results: There were 24 children (62.5% male) identified, with the mean age of 22.4 ± 18.7 months (3 months to 5 years old). The most common causes of AKI were drug induced (25.0%), glomerulonephritis (20.9%), and obstructive nephropathy (16.7%). The mean duration of PD was 11.3 ± 7.8 days (2–39 days). PD treatment was highly effective in attenuation of toxics, improvement of fluid overload, and correction of electrolyte disturbances (p < 0.001). One catheter outflow obstruction was noted, and no major complication was identified. In total, 18 children (75.0%) recovered and had the catheter successfully removed, 2 (8.3%) needed further PD treatment, and 4 (16.7%) died. The albumin level was significantly higher in patients who recovered with PD treatment (33.7 ± 6.2 vs. 21.5 ± 4.8 g/L, p = 0.002). Conclusions: PD can be performed safely and efficiently for the treatment of pediatric AKI. Low albumin level may be associated with poor prognosis of pediatric AKI.

Background: Type 2 diabetes mellitus (T2DM) has been a leading cause of chronic kidney disease (CKD) with a heterogeneous distribution worldwide. Optimal health-care planning requires an understanding how the burden of CKD due to T2DM has changed over time and geographic location, as well as the potential roles of sociodemographic, clinical, and behavioral factors in these changes. Methods: We used the Global Burden of Disease data from 1990 to 2017 at the global, regional, and national levels to investigate changes in the incidence, death, and disability-adjusted life years (DALYs) of CKD due to T2DM, incorporating both epidemiological research and risk-factor monitoring. Findings: The incident cases of CKD due to T2DM worldwide in 2017 had increased by 74% compared to 1990, and DALYs had increased by 113%. The SDI was significantly and negatively correlated with ASIR, ASDR, and the age-standardized DALY rate. However, in 82 countries and territories the burden was not alleviated in parallel with socioeconomic development. High systolic blood pressure was the leading risk factor for CKD due to T2DM, while high body mass index represented a growing threat globally across the entire SDI spectrum. Interpretation: We suggest a more-pragmatic approach focusing on early diagnosis and primary care to reduce the risk of death in low-SDI regions. Our findings indicate that sociodemographic prosperity is far from a decisive factor. Interventions for the increasing burden should address high systolic blood pressure as well as overweight and obesity problems, especially in high-income regions. Funding: National Social Science Foundation of China. Declaration of Interest: The authors declare no conflicts of interest that pertain to this work. Ethical Approval: Not required.

Peritoneal protein clearance has been suggested to be a marker of peritoneal inflammation and systemic endothelial dysfunction. We enrolled 711 consecutive incident PD patients. Baseline peritoneal protein clearance and other clinical information were reviewed. All patients were followed for at least 1 year for all-cause and cardiovascular mortality. The average PD effluent protein loss was 6.41 ± 2.16 g/day; peritoneal protein clearance was 97.15 ± 41.55 mL/day. The average duration of follow-up was 50.8 ± 36.2 months. Multivariate linear regression analysis showed that serum albumin, C-reactive protein, and mass transfer area coefficients of creatinine were independently associated with peritoneal protein clearance. By multivariate Cox regression analysis, age, Charlson comorbidity score, volume of overhydration and peritoneal protein clearance were independent predictors of all-cause mortality. Every 10 mL/day increase in peritoneal protein clearance confers 10.4% increase in risk of all-cause mortality (95% confidence interval 2.6–18.7%, p = 0.008). Peritoneal protein clearance was also associated with cardiovascular mortality by univariate analysis, but the association became insignificant after adjusting for confounding factors Cox regression analysis. Baseline peritoneal protein clearance is an independent predictor of all-cause mortality in incident PD patients. Routine measurement of peritoneal protein clearance may facilitate patient risk stratification.

Background Pseudomonas peritonitis is a serious complication of peritoneal dialysis (PD). However, the clinical course of Pseudomonas peritonitis following the adoption of international guidelines remains unclear. Methods We reviewed the clinical course and treatment response of 153 consecutive episodes of PD peritonitis caused by Pseudomonas species from 2001 to 2015. Results Pseudomonas peritonitis accounted for 8.3% of all peritonitis episodes. The bacteria isolated were resistant to ceftazidime in 32 cases (20.9%), and to gentamycin in 18 cases (11.8%). In 20 episodes (13.1%), there was a concomitant exit site infection (ESI); in another 24 episodes (15.7%), there was a history of Pseudomonas ESI in the past. The overall primary response rate was 53.6%, and complete cure rate 42.4%. There was no significant difference in the complete cure rate between patients who treated with regimens of 3 and 2 antibiotics. Amongst 76 episodes (46.4%) that failed to respond to antibiotics by day 4, 37 had immediate catheter removal; the other 24 received salvage antibiotics, but only 6 achieved complete cure. Conclusions Antibiotic resistance is common amongst Pseudomonas species causing peritonitis. Adoption of the treatment guideline leads to a reasonable complete cure rate of Pseudomonas peritonitis. Treatment with three antibiotics is not superior than the conventional two antibiotics regimen. When there is no clinical response after 4 days of antibiotic treatment, early catheter removal should be preferred over an attempt of salvage antibiotic therapy.

Genomic loci related with resistance to gall-inducing insects have not been identified in any plants. Here, association mapping was used to identify molecular markers for resistance to the gall wasp Leptocybe invasa in two Eucalyptus species. A total of 86 simple sequence repeats (SSR) markers were screened out from 839 SSRs and used for association mapping in E. grandis. By applying the mixed linear model, seven markers were identified to be associated significantly (P ≤ 0.05) with the gall wasp resistance in E. grandis, including two validated with a correction of permutation test (P ≤ 0.008). The proportion of the variance in resistance explained by a significant marker ranged from 3.3% to 37.8%. Four out of the seven significant associations in E. grandis were verified and also validated (P ≤ 0.073 in a permutation test) in E. tereticornis, with the variation explained ranging from 24.3% to 48.5%. Favourable alleles with positive effect were also mined from the significant markers in both species. These results provide insight into the genetic control of gall wasp resistance in plants and have great potential for marker-assisted selection for resistance to L. invasa in the important tree genus Eucalyptus.

AIM Previous genome-wide association studies have identified multiple susceptibility loci for IgA nephropathy (IgAN); however, validation of these findings is still needed. METHODS We performed a case-control study among 347 Chinese Han IgAN patients and 310 ethnicity-matched controls. Twenty-two single nucleotide polymorphisms (SNPs) were genotyped and association analysis was performed. RESULTS We found three alleles for IgAN in patients: the allele "C" of rs2188404 in the CCDC132 gene by recessive model (odds ratio (OR), 1.65; 95% confidence interval (CI), 1.10-2.48; P = 0.014) and additive model (OR, 1.29; 95% CI, 1.03-1.61; P = 0.024) analysis, respectively, the allele "A" of rs10488764 in FDX1 gene by additive model (OR, 1.27; 95% CI, 1.00-1.61; P = 0.048) analysis, the allele "A" of rs3803800 in TNFSF13 gene by recessive model (OR, 2.05; 95% CI, 1.16-3.62; P = 0.010) and additive model (OR, 1.35; 95% CI, 1.06-1.72; P = 0.013) analysis, respectively. However, the associations between these SNPs and the risk of IgAN were not significant when adjusted for age and sex. Additionally, we found polymorphisms of rs2188404, rs10488764 and rs3803800 were correlated with urine protein (UPRO), human serum albumin (HSA), total cholesterol (TC) and Lee's pathological grades. CONCLUSION We did not find any positive association between these SNPs and the risk of IgAN after adjustment by age and sex, but did find a significant and strong correlation with relevant clinical pathological parameters. Our study may provide a new perspective to understanding the aetiology of IgAN.

Backgrounds Syngeneic or autologous hematopoietic stem cells transplantation (HSCT) has been proposed to treat autoimmune diseases because of its immunosuppressive and immunomodulatory effects, which can also contribute to posttransplant antirejection therapy. In this study, we explored the tolerogenic effect of syngeneic HSCT on prolonging islet allograft survival. Methods C57BL/6 mice received syngeneic HSCT plus preconditioning with sublethal irradiation. Then islets of BALB/c mice were transplanted into the renal subcapsular of C57BL/6 mice after chemically induced into diabetes. Results HSCT mice exhibited improved islet allograft survival and increased serum insulin compared to control mice. Islet allografts of HSCT mice displayed lower level lymphocyte infiltration and stronger insulin staining than control mice. T cells of HSCT mice proliferated poorly in response to allogeneic splenocytes compared to control mice. Mice appeared reversed interferon-γ (IFN-γ)/interleukin-4 (IL-4) ratio to a Th2 immune deviation after syngeneic HSCT. The percentage of CD8+ T cells was lower, while percentage of CD4+ CD25+ Foxp3+ T regulatory cells (Tregs) was higher in HSCT mice than control mice. HSCT mice showed higher percentage of CTLA-4+ T cells and expression of CTLA-4 mRNA than control mice. Targeting of CTLA-4 by intraperitoneal injection of anti-CTLA-4 mAb abrogated the effect of syngeneic HSCT on prolonging islet allograft survival, inhibiting activity of T cells in response to alloantigen, promoting Th1 to Th2 immune deviation and up regulating CD4+ CD25+ Foxp3+ Tregs. Conclusions Syngeneic HSCT plus preconditioning of sublethal irradiation induces tolerance and improves islet allograft survival in fully mismatched mice model. Th1 to Th2 immune deviation, increased CD4+ CD25+ Foxp3+ Tregs and up-regulation of CTLA-4 maybe contribute to the tolerogenic effect induced by syngeneic HSCT.

Objective This study aimed to investigate the effect of nicotinamide on differentiation of mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) in vivo in mice and on homing of MSCs to the pancreas after being intravenously infused. Methods Streptozotocin (STZ)–induced diabetic Balb/c mice received syngeneic transplantation of carboxyfluorescein succinimidyl ester (CFSE)–labeled bone marrow MSCs into the liver or tail vein. Nicotinamide was intraperitoneally injected into mice at a dose of 500 mg/kg body weight per day after STZ administration. Mice who received saline solution injection instead of nicotinamide were involved as control. Results Mice that received nicotinamide injection showed lower blood glucose, higher serum insulin, and more improved glucose tolerance compared with the control group. Immunohistochemistry analysis showed that higher levels of insulin staining and higher percentages of CFSE+/insulin+ cells were observed in the liver and pancreas sections of mice who received nicotinamide injection compared with the control group. The percentage of CFSE+/insulin+ cells was positively correlated with serum insulin level. Real-time polymerase chain reaction results showed that the implanted MSCs in mice who received nicotinamide injection exhibited higher levels of β-cell–related gene expression than the control group. More CFSE-labeled MSCs appeared in the pancreas of mice who received nicotinamide injection compared with the control group after being intravenously infused, whereas the amount of CFSE-labeled MSCs in the liver was not affected by nicotinamide injection. Conclusions Nicotinamide facilitates MSCs differentiating into functional IPCs in vivo in diabetic mice and promotes intravenously infused MSCs to home to the pancreas.

The receptor for activated C-kinase 1 (RACK1) is a member of the WD40-repeat family of proteins and has been reported to be implicated in the development of liver fibrosis. However, the role of RACK1 in renal fibrosis remains unclear. Therefore, in this study, we investigated the effects of RACK1 on transforming growth factor-β1 (TGF-β1)-treated human proximal tubular epithelial cells and aimed to elucidate the possible mechanisms responsible for its anti-fibrotic effects. Our results revealed that RACK1 was highly expressed in the renal fibrotic tissues and TGF-β1-treated HK-2 cells. RACK1 silencing inhibited TGF-β1‑induced α-smooth muscle actin and connective tissue growth factor expression in the HK-2 cells. Furthermore, RACK1 silencing inhibited the expression of phosphorylated Smad3 in the TGF-β1-treated HK-2 cells. To the best of our knowledge, these data demonstrate for the first time the role of RACK1 in renal fibrosis. The present findings indicate that RACK1 silencing attenuates renal fibrosis by suppressing the activation of TGF-β1/Smad3 signaling pathway in HK-2 cells. Thus, RACK1 may serve as a novel regulator of renal fibrosis.

The gall wasp Leptocybe invasa is a major insect pest on plantation Eucalyptus in many countries. Since appearing in China in 2007 it has had major impacts on commercial plantations—some commonly planted Eucalyptus varieties have proven particularly susceptible, including hybrids involving Eucalyptus camaldulensis and E. tereticornis parent species. Intra-specific variation within each species for L. invasa susceptibility was examined in two seed source and family trials in southwest of Guangdong. The E. camaldulensis trial included 101 seedlots representing five natural stand and six seed orchard sources which also represented three sub-specific taxa. The E. tereticornis trial included 143 seedlots representing 11 natural stand and four seed orchard sources, including breeding seed orchards in China. Both trials were assessed for susceptibility to L. invasa along with height at age 9 months. Sub-specific taxa within E. camaldulensis differed significantly (P

Aim Treatment of idiopathic membranous nephropathy (IMN) remains a controversial issue. While clinical trials have shown that some immunosuppressants combined with glucocorticoid have a good efficacy on IMN patients. However, there is little data on leflunomide (LEF) in treatment of IMN. Methods Records of every patient with biopsy-proven IMN in Department of Nephrology, the First Affiliated Hospital, Xi'an Jiaotong University from January 2005 to December 2011 (n = 194) were retrospectively analyzed. Patients with nephrotic IMN were treated with LEF plus oral prednisone (n = 32) for at least 12 months, whereas 31 patients who did not receive any immunosuppressants were used as controls. Results Remission rates in the LEF group were 31.3%, 59.4%, 68.8% and 71.9% at 6, 9, 12 and 15 months, respectively, which were significantly higher than those in controls. In the LEF group, proteinuria decreased from 6.79 g/24 h at baseline to 5.63 g/24 h (P

Previous genome-wide association studies have identified multiple susceptibility loci for IgA nephropathy (IgAN); however, validation of these findings is still needed.We performed a case-control study among 347 Chinese Han IgAN patients and 310 ethnicity-matched controls. Twenty-two single nucleotide polymorphisms (SNPs) were genotyped and association analysis was performed.We found three alleles for IgAN in patients: the allele "C" of rs2188404 in the CCDC132 gene by recessive model (odds ratio (OR), 1.65; 95% confidence interval (CI), 1.10-2.48; P = 0.014) and additive model (OR, 1.29; 95% CI, 1.03-1.61; P = 0.024) analysis, respectively, the allele "A" of rs10488764 in FDX1 gene by additive model (OR, 1.27; 95% CI, 1.00-1.61; P = 0.048) analysis, the allele "A" of rs3803800 in TNFSF13 gene by recessive model (OR, 2.05; 95% CI, 1.16-3.62; P = 0.010) and additive model (OR, 1.35; 95% CI, 1.06-1.72; P = 0.013) analysis, respectively. However, the associations between these SNPs and the risk of IgAN were not significant when adjusted for age and sex. Additionally, we found polymorphisms of rs2188404, rs10488764 and rs3803800 were correlated with urine protein (UPRO), human serum albumin (HSA), total cholesterol (TC) and Lee's pathological grades.We did not find any positive association between these SNPs and the risk of IgAN after adjustment by age and sex, but did find a significant and strong correlation with relevant clinical pathological parameters. Our study may provide a new perspective to understanding the aetiology of IgAN.

To determine the imaging characteristics of basilar artery hypoplasia (BAH).From October 2009 to August 2013, 10 193 magnetic resonance angiogram (MRA) and 31 716 magnetic resonance imaging (MRI) consecutive cases were retrospectively retrieved from our institutional Picture Archiving and Communication System (PACS) database. BAH was defined as a continuous diameter reduction all over artery and a basilar artery diameter ≤ 2 mm. The same cut-off value was applied for vertebral artery hypoplasia (VAH). We measured the diameters of basilar and vertebral arteries with PACS in all patients according to source imaging and IMP construction of MRA. The carotid arterial computed tomography angiogram (CTA) profiles were reviewed in 50 patients. The fetal-type posterior circle of Willis (FTP) was assessed. The diagnosis of acute cerebral infarction was based on clinical symptoms, signs and a high signal on diffusion-weighted imaging (DWI). Acute cerebral infarction was divided into anterior circulation stroke (ACS) and posterior circulation stroke (PCS).A total of 210 BAH were identified among 10 193 consecutive patients. BAH was more common in females (56.7%) than males (43.3%) in the patient group. They had a fetal-type of posterior cerebral artery (FTP) (175 bilateral (83.3%), 35 unilateral (16.7%)). 99.5% patients had V4 VAH and 56.0% (28/50) V1-V3 VAH. Among 210 BAH, there are 74 patients (mean age 64 years, average 25-91 years, 44 males) with a diagnosis of acute cerebral infarction (ACI). The males were predominant in ACI (59.5% in males vs 40.5% in females, P = 0.021). The frequency of BAH was detected in 74 (2.2%) among 3 294 ACI patients.As a relatively rare vascular abnormality, BAH has always unilateral or bilateral FTP and V4 VAH.

The development of the first solution-phase molecular assembly comprising over 100 molecular logic gates, which more than quadruples the complexity performed by any previous system. “MAYA-II” is a second generation molecular automaton capable of playing a complete game of tic-tac-toe against a human opponent, and encompasses 76 permissible game plays. MAYA-II is more user-friendly than MAYA-I, as it signals both players move in a two-color output system and imposes no constraints on the position of the human player's first move. MAYA-II is constructed from three classes of stem-loop controlled deoxyribozyme-based logic gates that are allosterically modulated by input oligonucleotides to produce fluorescent output signals.