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To screen transcription factor genes related to the prognosis of adult patients with sepsis.Twenty-three patients with sepsis and ten healthy individuals admitted for RNA-seq. Differential factors were enriched by four transcription factor databases, and survival analysis was adopted for core factors. Then, target genes were submitted to STRING to constitute the PPI network. Single-cell technology was used to localize cell lines. Finally, a transcription-target gene regulation network was constituted.A total of 4,224 DEGs were obtained between sepsis and NC groups. PPI results showed that FOXO3, NFKB1, SPI1, STAT5A, and PPARA were located in the center of the network. Target genes were related to cytokine-mediated signaling pathway and transcription regulator activity, etc. SPI1 was mainly located in monocyte cell lines, while FOXO3, PPARA, SP1, STAT3, and USF1 were expressed in monocyte cell lines, NK-T cell lines, and B cell lines. Compared with those in the control group, FOXO3, SP1, SPI1, STAT3, and USF1 were highly expressed in the sepsis group, while PPARA had low expression.Transcription factors such as FOXO3, PPARA, SP1, SPI1, STAT3, and USF1 are correlated with the prognosis of sepsis patients and thus may have a potential research value.Clinical Trial Registration: The clinical trial registration number is ChiCTR1900021261.

Gray system theory is a new field of control theory, which is the product of applying cybernetics and methods to social and economic systems, and is also the product of the combination of control theory and operations research. It takes the gray system as the research object. Whitening, desalination, quantification, modeling, and optimization are the core of the gray system, and it aims to predict and control the development of various gray systems. The purpose of this paper is to study how to analyze and study the impact of higher education cooperation projects with the help of multi-dimensional gray theory and describe the gray system theory. The problem of analyzing the impact of cooperation projects proposed in this paper is based on the gray theory, so it is elaborated around its concept and related algorithms, and a case design and analysis of the impact of higher education cooperation projects are carried out. The experimental results show that the institutions responsible for infrastructure at the top of the school have the greatest impact on infrastructure projects, accounting for about 70%, with 20% weight for communication with government agencies, and about 10% for communication with users.

A considerable amount of people succumbs to lung adenocarcinoma (LUAD) due to its high incidence and mortality. This study attempted to reveal the impacts of GOLM1 on LUAD. This work analyzed GOLM1 expression in LUAD and normal tissue and studied its prognostic value utilizing data from The Cancer Genome Atlas. RNA and protein levels were, respectively, determined utilizing qRT-PCR and western blot. Cell-aggressive behaviors were assessed employing Cell Counting Kit-8, scratch healing, and Transwell assays. The targetting relationship between GOLM1 and miR-30a-3p was assayed by dual-luciferase method. GOLM1 up-regulation in LUAD was found in TCGA and it was also a negative factor for survival in patients. GOLM1 overexpression promoted cell progression in LUAD. Down-regulated miR-30a-3p in LUAD was an upstream regulatory miRNA of GOLM1 in terms of molecular mechanism. Further, rescue assays illustrated that miR-30a-3p overexpression attenuated the GOLM1 facilitating impacts on LUAD progression. Finally, we proved that miR-30a-3p/GOLM1 regulated progression of LUAD cells via JAK-STAT pathway. Collectively, the inhibitory impacts of miR-30a-3p on LUAD growth may be mediated by GOLM1/JAK-STAT, which may contribute to the diagnosis of LUAD therapy and the development of therapeutic tools.

Objective To investigate the way that miR-136 regulated spleen tyrosine kinase (SYK) and transforming growth factor-β1 (TGF-β1)/Smad3 signaling pathways on renal fibrosis. Methods 100 male SD (Sprague-Dawley) rats were randomly divided into diabetic nephropathy (DN) group, normal control (NC) group, miR-136 mimics group, and control group. The renal fibrosis model of diabetic rats was established by streptozotocin (STZ) method. NRK-52E cells were transfected into six groups: HG group, HG + miR-136 group, HG + miR-NC group, miR-136 + SYK group, miR-136 + NC group, and control group. Histopathological examination, the expressions of miR-136 and SYK mRNA, the expression of mTOR, blood glucose, urine protein, body weight, creatinine level, blood urea nitrogen (BUN), and KW/BW were detected in each group. Transfection efficiency, the targeted binding, and regulation between miR-136 and SYK, as well as the expression level of related inflammatory factors, the expression levels of SYK, E-Cad (E-cadherin), Vimentin, Collagen I, α-smooth muscle actin (α-SMA), and vascular endothelial growth factor A (VEGFA) were detected. Results It was shown that the expression level of miR-136 in DN group significantly decreased. The blood glucose and urine protein concentrations in the DN group and miR-136 mimics group significantly increased and the body weight was decreased, but the blood glucose concentration in the miR-136 mimics group increased with time. The prolongation of the decline significantly decreased, and the growth rate of urinary protein reduced. Creatinine, BUN, and the kidney weight to body weight ratio (KW/BW) in DN group increased significantly. Cell culture results showed that SYK was a target gene of miR-136 and miR-136/SYK-mediated renal fibrosis by activating TGF-β1/Smad3 signal. Conclusion SYK activates TGF-β1/Smad3 signaling, while miR-136 inhibits TGF-β1/Smad3 signaling mediating tubular epithelial cell fibrosis by down-regulating SYK.

IntroductionIt remains unclear whether kidney transplantation (KT) from hepatitis B surface antigen (HBsAg) +donors to HBsAg− recipients (D(HBsAg+)/R(HBsAg−)) provides comparable transplant outcomes without hepatitis B virus (HBV) transmission compared with D(HBsAg−)/R(HBsAg−) KT. Moreover, no consensus has been reached for standardised prophylaxis regimens to prevent HBV transmission after D(HBsAg+)/R(HBsAg−) KT. We developed stratified prophylaxis regimens, including pretransplant antiviral treatment of donors, and pretransplant hepatitis B vaccination and post-transplant antiviral treatment of recipients, based on donors’ and recipients’ HBV serological characteristics. However, the safety and efficacy of stratified prophylaxis regimens remains unknown.Methods and analysisWe are conducting a prospective, multicentre, observational study. Between September 2020 and December 2023, 100 cases of (D(HBsAg+)/R (HBsAg−)) KT will be recruited from four university-affiliated hospitals with a follow-up at least 2 years. They will naturally receive stratified prophylaxis regimens or routine prophylaxis based on clinical experience to compare the efficacy and safety of these two regimens in (D(HBsAg+)/R(HBsAg−)) KT. The primary outcome will be post-transplant HBV infection to evaluate safety, defined as post-transplant HBsAg−→+or HBV DNA−→+. The composite endpoint of prevention failure will be also an endpoint of safety (any one of HBsAg−→+, HBV DNA−→+, HB e antigen−→+, HB e antibody−→+ and HB c antibody−→+). The efficacy will be evaluated by transplant outcomes, including death-censored graft survival, patient survival, acute rejection, delayed graft function and kidney graft function.Ethics and disseminationThis study will be registered as a clinical audit at each participating hospital and has obtained approval from the Ethics Committee of West China Hospital (reference: 2020-683, 8 September 2020).Trial registration numberNCT04562051.

N6-methyladenosine (m6A) modification is involved in diverse immunoregulation, while the relationship between m6A modification and immune tolerance post kidney transplantation remains unclear. Expression of Wilms tumor 1-associating protein (WTAP), an m6A writer, was firstly detected in tolerant kidney transplant recipients (TOL). Then the role of WTAP on regulatory T (Treg) cell differentiation and function in CD4sup+/supT cells from kidney transplant recipients with immune rejection (IR) was investigated. The potential target of WTAP and effect of WTAP on immune tolerance in vivo were subsequently verified. WTAP was upregulated in CD4sup+/supT cells of TOL and positively correlated with Treg cell proportion. In vitro, WTAP overexpression promoted Treg cell differentiation and enhanced Treg cell-mediated suppression toward naïve T cells. Forkhead box other 1 (Foxo1) was identified as a target of WTAP. WTAP enhanced m6A modification of Foxo1 mRNA in coding sequence (CDS) region, leading to up-regulation of Foxo1. Overexpression of m6A demethylase removed the effect of WTAP overexpression, while Foxo1 overexpression reversed these effects. WTAP overexpression alleviated allograft rejection in model mice, as evidenced by reduced inflammatory response and increased Treg population. Our study suggests that WTAP plays a positive role in induction of immune tolerance post kidney transplant by promoting Treg cell differentiation and function.

Bone marrow‐derived mesenchymal stem cell (BMSC)‐derived small extracellular vesicles (sEVs) are potent candidates for the suppression of acute rejection post‐renal allograft and have been reported to halt dendritic cells (DCs) maturation. However, whether BMSC‐derived sEVs mitigate acute rejection post‐renal allograft by targeting DCs is still unclear. In this study, donor BMSC‐derived sEVs (sEVs) relieved the inflammatory response and suppressed mature DCs (mDCs) location in kidney grafts, and increased regulatory T (Treg) cell population in the spleens of the rats that underwent kidney allograft. In lipopolysaccharide (LPS)‐stimulated immature DCs (imDCs), sEVs suppressed the maturation and migration of DCs and inactivated toll‐like receptor 4 (TLR4) signaling. Compared with LPS‐treated imDCs, imDCs treated with LPS+sEVs promoted CD4+T cells differentiated toward Treg cells. Subsequently, we found that Loc108349490, a long non‐coding RNA (lncRNA) abundant in sEVs, mediated the inhibitory effect of sEVs on DC maturation and migration by promoting TLR4 ubiquitination. In rats that underwent an allograft, Loc108349490 deficiency weakened the therapeutic effect of sEVs on acute rejection. The present study firstly found that sEVs alleviated acute rejection post‐renal allograft by transferring lncRNA to DCs and screened out the functional lncRNA loaded in sEVs was Loc108349490., This study reports that the administration of donor BMSC‐derived sEVs efficiently alleviates inflammatory response in kidney grafts post‐renal allograft by suppressing DC maturation and promoting the Treg cell population. The immunoregulatory effect of donor BMSC‐derived sEVs is attributed to Loc108349490, which mediated the maturation and migration of DCs by promoting TLR4 degradation.

The δ34S curve of sulfate from Members V–IV of the Jialingjiang Formation of the Sichuan Basin in the Early Triassic (T1j4−5) is highly consistent with global marine sulfate, and their trends are also similar, showing that the Early–Middle Triassic evaporites in the Sichuan Basin are comparable with those of the Early–Middle Triassic global evaporites and that the massive polyhalite deposit of the Early–Middle Triassic in the Sichuan Basin is related to global events, seawater composition and climate conditions. The sulfur isotopes of anhydrite with different symbiotic minerals at certain depths are steadily distributed, and the sulfur isotopes are not affected by recrystallization of gypsum (anhydrite). During the deposition of the Jialingjiang Formation, the Xuanhan–Dazhou area was the salinization center, accumulating a lot of the early residual brines with high δ34S values. In section V of the Jialingjiang stage, the volume of seawater entering the northeastern Sichuan Basin was integrally limited by basin uplift, the ancient Luzhou–Kaijiang uplift, and seawater with a low δ34S value slowly entered the Xuanhan area, leading to a gradual reduction in the δ34S value in the secondary basin until the basin was completely closed. Thus, the sulfur isotope value of sulfate from T1j4−5 in the ZK001 core gradually decreased (from 33.65 to 30.69 ‰) and then remained steady at 30.14 + 0.35 ‰, and the δ34S value of marine sulfate was slightly higher than the global average. The δ34S composition of the anhydrite sample from the Zk001 core is stable, and no abnormal fluctuation is found at the bottom of the new type of polyhalite potassium ore, implying that the provenance and sedimentary environment have not changed. The polyhalite fragment in the new type of polyhalite potassium ore is a kind of “non-in situ” polyhalite.

Determining the etiology of end-stage renal disease (ESRD) constitutes a great challenge in the context of renal transplantation. Evidence is lacking on the genetic findings for adult renal transplant recipients through exome sequencing (ES). Adult patients on kidney transplant waitlist were recruited from 2017 to 2019. Trio-ES was conducted for the families who had multiple affected individuals with nephropathy or clinical suspicion of a genetic kidney disease owing to early onset or extrarenal features. Pathogenic variants were confirmed in 62 from 115 families post sequencing for 421 individuals including 195 health family members as potential living donors. Seventeen distinct genetic disorders were identified confirming the priori diagnosis in 33 (28.7%) families, modified or reclassified the clinical diagnosis in 27 (23.5%) families, and established a diagnosis in two families with ESRD of unknown etiology. In 14.8% of the families, we detected promising variants of uncertain significance in candidate genes associated with renal development or renal disease. Furthermore, we reported the secondary findings of oncogenes in 4.4% of the patients and known single-nucleotide polymorphisms associated with pharmacokinetics in our cohort to predict the drug levels of tacrolimus and mycophenolate. The diagnostic utility of the genetic findings has provided new clinical insight in most families that help with preplanned renal transplantation.

Background: Significant advances have been made in recent years to utilize natural enzymes with antioxidant properties for the treatment of acute kidney injury (AKI). However, these enzymes have limited clinical utility due to their limited cellular uptake, poor pharmacokinetic properties, and suboptimal stability. We prepared a novel biomimetic mineralization approach to overcome these limitations.Results: Catalase (CAT) and superoxide dismutase (SOD) were encapsulated in a zeolitic imidazolate framework-8 (ZIF-8), then this SOD@CAT@ZIF-8 complex was anchored with MPEG2000-COOH to yield an MPEG2000-SOD@CAT@ZIF-8 (PSCZ) composite. This composite was then utilized as a stable tool with antioxidant properties for the integrated cascade-based treatment of AKI, remarkably improved intracellular enzyme delivery. The PSCZ composite showed a significantly relieve ability of H2O2 induced ROS and prevented apoptosis in HEK293 cells. In vivo, this composite showed a protective effect in the cisplatin-induced AKI mouse model. In addition, PSCZ treatment mitigated renal dysfunction and histological injury, like tubulointerstitial infiltration. RNA sequencing results further confirmed the protective effect of PSCZ and the potential molecular mechanism was revealed. PSCZ treatment reduced renal inflammation and inflammatory gene expression and ameliorated increased apoptosis and inflammatory infiltration of renal tubules. Moreover, PSCZ administration regulated renal injury via the p53 signaling pathway. These renoprotective effects of PSCZ treatment were more potent in CP-AKI mice than those of SOD or CAT alone. This dual-enzyme-embedded metal-organic framework was able to scavenge reactive oxygen species synergistically and effectively. Conclusion: PSCZ can remarkably improve intracellular enzyme delivery, and it can be used as a stable tool with antioxidant properties for the integrated cascade-based treatment of AKI. The ZIF-8-based “armor plating” represents an effective means of shielding enzymes with improved therapeutic utility to guide the precision medicine-based treatment of AKI.

Iron deficiency is the most common micronutrient deficiency worldwide. While iron deficiency is known to suppress embryonic organogenesis, its effect on the adult organ in the context of clinically relevant damage has not been considered. Here we report that iron deficiency is a risk factor for nephrotoxic intrinsic acute kidney injury of the nephron (iAKI). Iron deficiency exacerbated cisplatin-induced iAKI by markedly increasing non-heme catalytic iron and Nox4 protein which together catalyze production of hydroxyl radicals followed by protein and DNA oxidation, apoptosis and ferroptosis. Crosstalk between non-heme catalytic iron/Nox4 and downstream oxidative damage generated a mutual amplification cycle that facilitated rapid progression of cisplatin-induced iAKI. Iron deficiency also exacerbated a second model of iAKI, rhabdomyolysis, via increasing catalytic heme-iron. Heme-iron induced lipid peroxidation and DNA oxidation by interacting with Nox4-independent mechanisms, promoting p53/p21 activity and cellular senescence. Our data suggests that correcting iron deficiency and/or targeting specific catalytic iron species are strategies to mitigate iAKI in a wide range of patients with diverse forms of kidney injury.

A new type of polyhalite potassium ore (NTPPO) was found in the Lower Triassic Jialingjiang Formation, NE Sichuan Basin, SW China. It is water soluble, therefore can be exploited using the water-solution method, and is of great potential of economic value and research significance. Based on cores, thin sections, energy spectrum and SEM analyses, its microfeatures, macrofeatures and origin are discussed, and a genetic model is established to provide a scientific basis for future evaluation, prediction and exploration of potassium ore in the Sichuan Basin. It is proposed that the NTPPO was caused by storm activities: (1) the storm broke the original sedimentary polyhalite–gypsum beds, whose fragments were transported into the salt basin with high content of K+ and Mg2+; (2) in the basin, the polyhalite continued to be formed from gypsum by metasomatism with K- and Mg-rich brine; (3) during diagenesis, under high temperature and high pressure, K–Mg-rich brine from halite continued to replace anhydrite (or gypsum) to form polyhalite.

BackgroundAntibody-mediated rejection (AMR) occupies a major position for chronic rejection after kidney transplantation. Regulatory B cell (Breg) has been reported to have an inhibitory immune function, which contributes to the resistance for AMR.MethodsA nested case–control study for nine healthy donors, 25 stable (ST) patients, and 18 AMR patients was performed to determine the type of Breg in maintaining immune tolerance and preventing AMR.ResultsCompared to the ST group, circulating interleukin (IL)-10+ Bregs, but not Bregs, significantly decreased. The receiver operating characteristic (ROC) curve analysis revealed that rather than the circulating Bregs, decreased circulating IL-10+ Breg levels were positively associated with AMR. However, kidney B cell and IL-10 infiltration was significantly increased in the AMR group with high expression of C-X-C motif chemokine 13 (CXCL13). In addition, circulating IL-10+ Bregs, rather than Bregs, remained higher than those at pre-operation, during the 90-day post-operation in immune homeostasis.ConclusionThe circulating IL-10+ Breg levels are more appropriate measures for assessing the resistance of AMR after kidney transplantation.

Background Access to kidney transplantation by uremic children is very limited due to the lack of donors in many countries. We sought to explore small pediatric kidney donors as a strategy to provide transplant opportunities for uremic children. Methods A total of 56 cases of single pediatric kidney transplantation and 26 cases of en bloc kidney transplantation from pediatric donors with body weight (BW) less than 10 kg were performed in two transplant centers in China and the transplant outcomes were retrospectively analyzed. Results The 1-year and 2-year death-censored graft survival in the en bloc kidney transplantation (KTx) group was inferior to that in the single KTx group. Subgroup analysis of the single KTx group found that the 1-year and 2-year death-censored graft survival in the group where the donor BW was between 5 and 10 kg was 97.7 and 90.0%, respectively. However, graft survival was significantly decreased when donor BW was ≤5 kg (p

The International Pediatric Nephrology Association (IPNA) Global Kidney Replacement Therapy (KRT) Registry was established to evaluate the incidence and outcomes of kidney replacement therapy (dialysis and transplantation) provided to children worldwide. Analysis of registry data for separate regions is feasible.Three centers located in Shanghai, Guangzhou, and Zhengzhou, which have the greatest number of pediatric kidney transplantation cases in China, participated in this analysis of transplant data. Data were registered by each center for patients under the age of 19 years who received a single-organ kidney transplant for the first time between 2011 and 2018.In total, 415 patients (59.8% male) aged 1.4-18.7 (median 12.1) years were followed for 0.3-97.1 (median 27.7) months. The number of kidney transplants increased from a total of 129 during 2011-2014 to 286 cases during 2015-2018. 85.8% of patients received the transplanted kidney from a pediatric (age 19 years) donor, and deceased donors accounted for 94% of all donors. 8.0% of grafts were lost. One and 5-year patient survival rates were 97.6% and 95.5%, respectively. The major cause of death was infection (7/14). Similar graft and patient survival rates were observed for organs from pediatric and adult donors in 6-11 and 12-18 year recipient age groups, whereas recipients 6 years showed inferior patient and graft survival.Pediatric kidney transplantation shows favorable short-term and medium-term outcomes in China. Our experience supports use of pediatric donors in pediatric kidney transplantation, but attention directed to the outcome of recipients aged under 6 is necessary. Graphical abstract.

Additional file 1: Table S1. Clinical characteristics of donor and recipients in single and en bloc kidney transplantation group.

Renal iron recycling preserves filtered iron from urinary excretion. However, it remains debated whether ferroportin (FPN), the only known iron exporter, is functionally involved in renal iron recycling and whether renal iron recycling is required for systemic iron homeostasis. We deleted FPN in whole nephrons by use of a Nestin-Cre and in the distal nephrons and collecting ducts, using a Ksp-Cre, and investigated its impacts on renal iron recycling and systemic iron homeostasis. FPN deletion by Nestin-Cre, but not by Ksp-Cre, caused excess iron retention and increased ferritin heavy chain (FTH1) specifically in the proximal tubules and resulted in the reduction of serum and hepatic iron. The systemic iron redistribution was aggravated, resulting in anemia and the marked downregulation of hepatic hepcidin in elderly FPN knockout (KO)/Nestin-Cre mice. Similarly, in iron-deficient FPN KO/Nestin-Cre mice, the renal iron retention worsened anemia with the activation of the erythropoietin-erythroferrone-hepcidin pathway and the downregulation of hepatic hepcidin. Hence, FPN likely located at the basolateral membrane of the proximal tubules to export iron into the circulation and was required for renal iron recycling and systemic iron homeostasis particularly in elderly and iron-deficient mice. Moreover, FPN deletion in the proximal tubules alleviated ischemic acute kidney injury, possibly by upregulating FTH1 to limit catalytic iron and by priming antioxidant mechanisms, indicating that FPN could be deleterious in the pathophysiology of ischemic acute kidney injury (AKI) and thus may be a potential target for the prevention and mitigation of ischemic AKI.

// Jinfeng Li 1 , Jiajia Sun 1 , Ruiming Rong 2 , Long Li 2 , Wenjun Shang 1 , Dongkui Song 3 , Guiwen Feng 1 and Feifei Luo 4 1 Kidney Transplantation Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China 2 Department of Urology, Zhongshan Hospital and School of Basic Medical Sciences, Fudan University, Shanghai, China 3 Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China 4 Department of Digestive Diseases, Huashan Hospital and Biotherapy Research Center, Fudan University, Shanghai, China Correspondence to: Guiwen Feng, email: fengguiwen123@126.com Feifei Luo, email: feifeiluo@fudan.edu.cn Keywords: high-mobility group box-1, myeloid-derived suppressor cells, renal cell carcinoma Received: July 11, 2016 Accepted: June 02, 2017 Published: June 28, 2017 ABSTRACT Despite high immunogenicity and marked presence of immune cells in the RCC(renal cell carcinoma), immunotherapy fails to develop effective anti-tumor immune responses. This is due to the negative regulatory factors in the tumor microenvironment. As the main contributor of immunosuppression, myeloid-derived suppressor cells (MDSCs) inhibited anti-tumor immunity and promoted tumor progression. Meanwhile, it is confirmed that high mobility group box-1 protein (HMGB1) shows a high expression in many solid tumors and HMGB1 with high expression is involved in tumor immune escape. However, the mechanisms linking HMGB1 with tumor immune escape are unclear. The present study aimed to explore whether HMGB1 can promote RCC immune escape by inducing the generation of MDSCs. In this study, Renca mouse model was established and the influence of HMGB1 on MDSCs was investigated by using HMGB1 antibody to downregulate the expression of HMGB1 in tumor-bearing mice. The result showed that with the down-regulation of HMGB1, the tumor growth was inhibited significantly and the mice survival was prolonged greatly. Furthermore, the differentiation and proliferation of MDSCs were inhibited both in vitro and in vivo , and the inhibition rate showed a positive correlation with the degree of down-regulation of HMGB1. When MDSCs were eliminated with Gr-1 antibody in vivo , the ability of the HMGB1 to promote tumor growth was severely impaired. Thus, our findings indicated that HMGB1 might mediate tumor immune escape by promoting MDSCs cell proliferation, which provided a novel theoretical basis for preventing RCC using HMGB1 as the target.

Liver injury is one of the most common complications in patients after kidney transplantation. Bicyclol tablets possess obvious anti-inflammatory and liver-protective functions. This study aimed to explore the clinical effect of preventive application of Bicyclol on drug induced liver injuries at an early stage after kidney transplantation. A total of 1600 patients who accepted kidney transplantations at our hospital from January 2009 to May 2015 were enrolled in this study, and divided into the prevention group (Bicyclol) and the control group (no hepatic protectors) based on whether or not hepatic protectors were regularly administered after the operation. The occurrence of liver injuries at an early stage after the operation and their influencing factors were analyzed. Total of 745 cases were included in the final analysis of which 82 developed liver injuries post-operation, with 22 in the prevention group (4.82%) as compared to 60 in the control group (20.76%) (P= 0.001). As compared to the control group, OR (95% CI) of the prevention group was 0.197 (0.116, 0.334) after revising HBsAg status, age and maintenance immunosuppression. Prophylactic application of Bicyclol as liver-protective treatment was a protective factor against drug induced liver injuries at an early stage after kidney transplantation.

microRNA-342-3p plays an important role in tumor occurrence and development. However, the expression pattern and roles of microRNA-342-3p in nonsmall cell lung cancer remain poorly understood. In the current study, we explored the roles and underlying mechanisms of microRNA-342-3p in nonsmall cell lung cancer via gain- and loss-of-function analyses. We used quantitative reverse-transcription-polymerase chain reaction and western blotting assays to measure the expression levels of microRNA-342-3p in nonsmall-cell lung cancer and B-cell lymphoma-2. Furthermore, we used small interfering RNA and RNA mimics to analyze the functions and underlying mechanisms of microRNA-342-3p in nonsmall cell lung cancer cells. A luciferase reporter assay was performed to evaluate the direct binding site of the 5′-untranslated region of B-cell lymphoma-2 targeted by microRNA-342-3p. We found that the expression of microRNA-342-3p was significantly lower in nonsmall cell lung cancer cells and tissues than in normal cells and tissues. The upregulation of microRNA-342-3p suppressed cell proliferation while promoting apoptosis in H1975, H460, and H226 cells. The overexpression of microRNA-342-3p in nonsmall cell lung cancer cells led to the downregulation of mRNA and protein levels in B-cell lymphoma-2 cells. Thus, B-cell lymphoma-2 was identified as a direct target of microRNA-342-3p. These findings indicate that microRNA-342-3p inhibits the growth of nonsmall cell lung cancer by repressing the expression of B-cell lymphoma-2, which suggests that microRNA-342-3p could be a potential target for the treatment of nonsmall cell lung cancer.

Salt mounds are commonly distributed along playa margins and typically comprise alternating layers of loose fine sand and slightly hard halite-rich sediments as a result of long-term underground spring activity. A model of salt mound development was constructed for this study. It suggests that wind-blown sand supply and upward recharge of underground springs are two important factors in salt mound construction. Furthermore, it proposes that salt mound height is mainly controlled by the vertical transport range of underground springs and the thickness of the capillary fringe. A 1.5 m representative profile dug from the center of salt mound LP1 in the Lop Nor playa revealed a fairly complicated mineral assemblage including halite, gypsum, anhydrite, glauberite, epsomite, anhydrite, calcite, bischofite, polyhalite, schoenite, kieserite and carnallite. This matches closely with the assemblage predicted by the EQL/EVP model. The groundwater in the area is highly concentrated brine rich in Cl − and Na + and poor in Ca 2+ , displaying low alkalinity, and containing considerable amounts of SO 4 2− , Mg 2+ and K + . Chemical analysis of groundwater revealed considerable variation in the salinity and chemical composition of groundwater over time. The Cs-137 technique was used to measure the accumulated ages of the salt mounds. This method may prove useful in the research of relatively young playa environments where carbon dating techniques are unworkable because of an absence of carbon-rich materials in recent saline sediments.

Early damage to transplanted organs initiates excess inflammation that deteriorates existing injury, which is a leading cause of graft loss. Long noncoding RNAs (lncRNAs) are recently thought to play a significant role in cellular homeostasis during pathological process of kidney diseases. The aim of this study was to assess the function and mechanism of lncRNA, maternally expressed gene 3 (MEG3), on early renal allografts pathogenesis. Real-time polymerase chain reaction (RT-PCR) analysis found that the levels of MEG3 and miR-181b-5p were increased and decreased respectively in grafted kidney. The Western blot assay showed that TNF-alpha was upregulated in the kidney and in HK-2 cells. Administering MEG3-specific small interfering RNA (siRNA) in mice silenced MEG3 expression and protected kidney renal allograft from injury. Bioinformatical analysis and luciferase assay indicated that MEG3 is a target of miR-181b-5p. MEG3 inhibition and overexpression promoted and suppressed miR-181b-5p levels respectively. In addition, Western blot and immunohistochemical staining suggested that decreased TNF-alpha expression was observed in the kidney. In contrary to MEG3, miR181b overexpression attenuated hypoxia-induced HK-2 cell apoptosis, as well as suppressed hypoxia-induced TNF-alpha upregulation. In luciferase reporter assay, we confirmed that miR-181b directly bound to the 3'-untranslated region (3'-UTR) of TNF-alpha, thereby negatively regulating the TNF-alpha expression. Our data suggested that MEG3 functions as a competing endogenous RNA for miR-181b to regulate the TNF-alpha expression in hypoxia-induced kidney injury in acute renal allografts.

Background MicroRNAs (miRNAs) contribute to the progression of chronic kidney disease (CKD) by regulating renal homeostasis. This study explored the effects of miR-181a on CKD through the Toll-like receptor (TLR)/nuclear factor-kappa B (NF-κB) pathway by binding to CRY1. Methods Seventy male rats were selected and assigned into specific groups: miR-181a mimic, miR-181a inhibitor, and siRNA against CRY1, with each group undergoing different treatments to investigate many different outcomes. First, 24-h urinary protein was measured. ELISA was used to determine the serum levels of SOD, ROS, MDA, IL-1β, IL-6, and TNF-α. Biochemical tests for renal function were performed to measure albumin, uric acid, and urea in urine and urea nitrogen and creatinine in serum. The glomerulosclerosis index (GSI) and renal tubular epithelial (RTE) cell apoptosis were detected using PASM staining and TUNEL staining, respectively. Finally, RT-qPCR and western blot were done to determine miR-181a, CRY1, TLR2, TLR4, and NF-κB expression. Results CRY1 is the target gene of miR-181a, according to a target prediction program and luciferase assay. Rats diagnosed with CKD presented increases in 24-h urinary protein; GSI; RTE cell apoptosis rate; serum ROS, MDA, IL-1β, IL-6, and TNF-α; and CRY1, TLR2, TLR4, and NF-κB expression, as well as decreases in SOD level and miR-181a expression. Following transfection with either the miR-181a mimic or si-CRY1, 24-h urinary protein, renal damage, GSI, and cell apoptosis rate were all decreased. In addition, the overexpression of miR-181a or inhibition of CRY1 alleviated the degree of kidney injury through suppression of the TLR/NF-κB pathway. Conclusion miR-181a alleviates both GS and RTE injury in CKD via the down-regulation of the CRY1 gene and the TLR/NF-κB pathway.

To report clinical outcomes of kidney transplantation from pediatric brain and cardiac death donors (DBCD) in a single Chinese center and to investigate its feasibility to expand organ donor pool. 18 recipients, transplanted between August 2011 and October 2013 in the First Affiliated Hospital of Zhengzhou University, receive a single graft from DBCD donors age ranged from 1.5 to 13 years old. Renal function expressed as serum creatinine, blood urea nitrogen as well as eGFR values at 1, 2 weeks as well as 1-, 3-, 6-, and 12-months post-transplantation was evaluated. Graft size was also monitored at the same time by ultrasonography. In addition, delayed graft function, acute rejection, surgical complication as well as patient and graft survival were also assessed. The primary causes of DBCD donors included six cases of severe brain trauma and three cases of cerebral hemorrhage. The mean age of DBCD donors was (7.2 ± 3.4) years (range 1.5-13). The mean weight of DBCD donors was (29.8 ± 15.3) kilogram (range 13-67). The mean height of DBCD donors was (118.3 ± 27.8) centimeter (range 70-173). ECMO was applied to DBCD donors to avoid warm ischemia time and the applicating time was (79.8 ± 44.5) (range 32-180) minutes.There were seven males and 11 females recipients. Among which, 16 recipients were pediatrics and two recipients were adults. The mean age of the recipients was (14.6 ± 9.7) years (range 4-47). The mean weight of recipients was (31.9 ± 12.4) kilogram (range 11-54). The mean height of recipients was (138.0 ± 23.7) centimeter (range 84-172). Renal function recovered to normal within the first-week post-operation except one recipient which occurred acute rejection. Two cases of renal artery stenosis were found 2-week and 3-month post-transplantation, respectively. They subsequently underwent ballon angioplasty and followed up for 8 and 12 months, respectively, and no recurrence was found. One recipient developed ureteral leak. Five weeks later, the ureter leak healed after adequate drainage and prolongation of indwelling catheter. Graft size significantly and continuously increased during the first year, especially in the first 3-month post-transplantation. All the 18 recipients are alive at the last follow-up. Among which, 16 recipients are followed up for 12 months and 1-year recipient/graft survival rate is 100 %. The use of single kidney graft from pediatric DBCD could yield good short-term results.

Rabbit antithymocyte globulin (ATG-F) is an extensively used induction agent. To our knowledge, no study to date has assessed reduced ATG-F dosage in children undergoing renal transplantation. This was a retrospective analysis of pediatric renal recipients in the Department of Kidney Transplantation, The First Affiliated Hospital of Zhengzhou University, from May 2007 to February 2013. Thirty-nine children underwent renal transplantation including 25 living related and 14 cardiac deceased donor transplantation. Each recipient received ATG-F 1.5 mg/kg/d once daily for 4 days. Of the 39 recipients, five (12.8%) showed delayed graft function, including one of 25 recipients (4%) of living donor and four of 14 recipients (28.6%) of deceased donor transplantation (p0.05). Six of the 39 recipients (15.4%) showed acute rejection on renal biopsy. Follow-up in these children ranged from 6 to 87 months. The one-, three-, and five-yr recipients and grafts survival rates postoperation were each 94.9% and 97.3%, 97.3%, and 94.6%, respectively. The incidence of postoperative infection was 35.9% (14/39), and did not differ significantly in the living related and deceased donor groups (p0.05). Low-dose ATG-F can be safely used as an immune induction agent in pediatric renal transplantation.

Objective To determine whether a new desensitization protocol (mycophenolate mofetil [MMF], plasmapheresis and antithymocyte globulin [ATG], complemented with human leucocyte antigen [HLA] amino acid residue matching) could reduce panel-reactive antibody (PRA) levels in sensitized patients, to facilitate successful renal transplantation. Methods Patients awaiting transplantation with PRA levels >10% received treatment with MMF; those with PRA levels >30% were also treated with plasmapheresis. Patients whose PRA level was Results Thirty-two sensitized patients were enrolled. Desensitization produced a significant decrease in PRA levels; 27 patients (84.4%) became eligible for transplantation and 26 (81.2%) subsequently underwent successful transplantation. Residue matching improved the proportion with a mismatch number of 0–1 from 7.7% to 65.4%, compared with traditional HLA matching. Postoperatively, all patients showed immediate graft function. Acute rejection occurred in three patients (11.5%) and infections in seven patients (25.9%); all were treated successfully. Conclusion The combination of a desensitization protocol (MMF, plasmapheresis and ATG) and residue matching appears to be an effective strategy for sensitized patients awaiting renal transplantation.

Over-expression of the proto-oncogene pleomorphic adenoma gene 1 (PLAG1) plays a crucial role in the formation of pleomorphic adenoma, which is the most common type of salivary gland tumor. To understand the molecular mechanisms governing PLAG1-mediated tumorigenesis, we used a microarray-based approach to identify PLAG1 target genes. We validated the expression of several genes, including Bax, Fas, p53, p21, p16, Cyclin D1, Egfr, Trail-R/DR5, c-Fos, c-myc and Igf2, by real-time RT-PCR or western blotting. Using luciferase reporter gene assays, we determined that the promoters of Bax, Fas, p53, TRAIL-R/DR5, and c-Fos were transactivated by PLAG1. PLAG1 not only activates genes that promote cell proliferation and tumor formation but also genes that inhibit these cellular processes. Therefore, we conclude that PLAG1 may play a dual role in tumor formation.

Acute kidney injury (AKI) is one of the most common complications of various serious conditions, and early diagnosis is therefore critical for the treatment of AKI. Increase of the classic AKI biochemical markers such as serum creatinine is not evident until renal function is irreversibly damaged, which adds to the difficulties of early identification of AKI and results in an increase of the mortality rate. In order to improve the prevention, diagnosis, treatment, and prognosis prediction of AKI, novel early markers of AKI are required. Recent evidence demonstrates that neutrophil gelatinase- associated lipocalin (NGAL) is closely associated with AKI. Several experimental and clinical studies have shown that the expression of urine and serum NGAL increases significantly in AKI. In particular, the urine NGAL level is closely associated with the severity of kidney injury, and could be detected earlier than other AKI markers. Therefore, NGAL shows potential to be a new effective early biochemical marker of AKI. Further studies are needed to confirm the significant advantages of NGAL in the diagnosis of early AKI and its value in clinical applications.

Chronic kidney disease is becoming a global public health problem, which will usually cause uremia at the end stage of chronic kidney failure. So far, kidney transplant is the most effective and proper therapy for uremia, however, the short supply of matched donor kidney has been a persistent bottleneck for transplantation. HLA matching of HLA-A, -B and -DRB1 loci is very important for the allocation of kidney transplants. In this study, we investigated genotypes of HLA-A, -B and -DRB1 loci based on 1,464 uremia patients and 10,000 unrelated healthy individuals in Henan province of China, and compared the frequency distribution of these HLA alleles and corresponding haplotypes between patient and healthy groups. We detected 23 HLA-A, 49 HLA-B and 17 HLA-DRB1 alleles in total. The predominant alleles of HLA-A, -B and -DRB1 loci in patients are the same as those in healthy group. The seven most frequent alleles account for about 87%, 50%, and 77% at HLA-A, -B and -DRB1 loci, respectively. The haplotypes (combinations of HLA-A, -B, and -DRB1) with significantly different frequency between patients and controls mostly account for less than 1%. Overall, this suggests that HLA matching is not a potential difficulty for kidney transplant of uremia patients. However, three of the top seven frequent HLA-DRB1 alleles have a significantly different distribution in patients and controls, while only one alleles for HLA-B and zero for HLA-A loci. These HLA-DRB1 alleles may be closely associated with uremia. This study sheds new lights on the composition and difference of HLA genotypes in uremia patients and healthy populations in Central China that can serve as a guide to HLA matching for kidney transplants and a resource for HLA typing-related studies.

SUMMARY What is known and Objective: Invasive fungal infections are a major threat to renal transplant recipients. Micafungin and voriconazole are two useful antifungal agents for treating such infections. Our objective is to evaluate the comparative efficacy and safety of micafungin and voriconazole in the initial treatment of such infections. Methods: In this prospective, multicentre, open-labelled, randomized, controlled trial, renal transplant recipients with invasive fungal infections were assigned to receive either micafungin or voriconazole. The enrolled subjects received a kidney transplant between March 2008 and March 2010 at one of the two transplant centres in Henan Province, China. The efficacy and adverse effects of the two treatments were compared. Results and Discussion: The clinical trial enrolled 65 patients, of whom 31 were treated with micafungin, and 34 with voriconazole. The rates of microbiological evidence of infection in the micafungin and voriconazole groups were 64AE5% and 70AE5%, respectively, whereas the rates of Candida as the major cultured fungus were 80AE0% and 75AE0%, respectively. Complicated bacterial infection rates in the two treatment groups were 38AE7% and 32AE4%, respectively, whereas complicated CMV viral infection occurred at a rate of 19AE2% and 23AE5%, respectively. Fungal infection within one to 3 months after transplant was 83AE6% (26/31) and 85AE3% (29/34) in the micafungin and voriconazole groups, respectively. There was no significant difference between the two groups in terms of efficacy, survival beyond 10 days and discontinuation of treatment because of lack of efficacy (P >0 AE05). Mortality rates in the micafungin and voriconazole groups were 9AE7% (3/31) and 12AE1% (4/33), respectively. Rates of adverse effects in the two groups were 41AE9% and 51AE6% (P >0 AE05), respectively. What is new and Conclusions: This is the first comparison of micafungin and voriconazole in renal transplant patients. Our study shows that the effectiveness of micafungin was similar to that of voriconazole in such patients.