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Objective: The aim of this study was to explore the development of enteric glial cells (EGCs) in different segments of Hirschsprung's disease (HSCR).Methods: Colonic specimens from 35 children with HSCR were selected to analyze the relative expression of glial fibrillary acidic protein and S100 calcium-binding protein B using Western blotting and real-time fluorescence quantitative PCR. Immunofluorescence and immunohistochemical staining were performed to determine the distribution of myenteric EGCs and neuronal cells in different segments of HSCR.Results: There was a trend of diminished protein and mRNA expression of glial fibrillary acidic protein and S100 calcium-binding protein B from the proximal, dilated, and transitional segments to the aganglionic segment (p < 0.05). Immunofluorescence and immunohistochemistry showed that the EGCs in the aganglionic, transitional, and dilated colonic muscles were morphologically abnormal, which was consistent with the dysplasia of myenteric neurons.Conclusion: Aberrant development of myenteric EGCs was observed in the colon of HSCR, which may affect the survival of enteric neurons.

OBJECTIVE This study aimed to evaluate and discuss whether the transareola endoscopic surgery has similar outcome outcomes to open surgery in the treatment of papillary thyroid carcinoma (PTC). METHOD A total of 102 patients with PTC were enrolled in this study. Among them, 53 patients were treated by transareola endoscopic surgery (endoscopic group) and 49 patients were treated by open surgery (open group). Some specific factors, including thyroglobulin (Tg), radioactive iodine uptake (RAIU), postoperative nuclide imaging in thyroid area, postoperative nuclide imaging of lymph nodes suspicious for metastasis (PNILNSM), etc. were analyzed and compared between the 2 groups. RESULTS There were no significant differences between the 2 groups regarding body mass index (22.9±3.4 vs. 24.0±3.3, P=0.103), operation time (173.3±43.2 vs. 158.8±47.9 min, P=0.110), intraoperative blood loss (41.8±19.4 vs. 35.8±31.0 mL, P=0.251, P=0.251), tumor diameter (19.0±6.8 vs. 20.2±7.2 mm, P=0.400), and overall complications (11.3% vs. 10.2%, P=0.868). No significant difference was found in the specific factors between the 2 groups concerning RAIU-2h/24h (2.44±1.34 vs. 2.58±1.65%/2.83±3.75 vs. 2.35±3.44%, P=0.646/ P=0.506), number of dissected lymph nodes (4.4±1.4 vs. 4.6±1.5, P=0.595), Tg before radioiodine therapy (4.46±5.50 vs. 5.60±8.36; P=0.495), Tg after radioiodine therapy (1.03±1.93 vs. 1.11±1.61, P=0.812, P=0.812), postoperative nuclide imaging in thyroid area (1.76±1.50 vs. 2.19±1.85 cm, P=0.195), PNILNSM before radioiodine (none: 79.2% vs. 83.7%, P=0.566; central: 17.0% vs. 12.2%, P=0.653; lateral: 1.9% vs. 4.1%, P=0.450; central+lateral: 1.9% vs. 0%, P=1.000), and PNILNSM after radioiodine (none: 94.3% vs. 95.9%, P=0.111; central: 3.8% vs. 2.0%, P=1.000; lateral: 0 vs. 2.0%, P=0.480; central+lateral: 1.9% vs. 0%, P=1.000). CONCLUSIONS Transareola endoscopic total thyroidectomy and central lymph nodes dissection are safe and effective. According to the evaluated postoperative specific factors, this technique achieves similar outcomes to open surgery in selected patients with PTC.

Background Regulatory T cells (Tregs) suppress excessive immune responses and play a crucial protective role in acute kidney injury (AKI). The aim of this study was to examine the therapeutic potential of transforming growth factor (TGF)-β1-overexpressing mesenchymal stromal cells (MSCs) in inducing local generation of Tregs in the kidney after ischemia/reperfusion (I/R) injury. Methods MSCs were transduced with a lentiviral vector expressing the TGF-β1 gene; TGF-β1-overexpressing MSCs (designated TGF-β1/MSCs) were then transfused into the I/R-injured kidney via the renal artery. Results MSCs genetically modified with TGF-β1 achieved overexpression of TGF-β1. Compared with green fluorescent protein (GFP)/MSCs, TGF-β1/MSCs markedly improved renal function after I/R injury and reduced epithelial apoptosis and subsequent inflammation. The enhanced immunosuppressive and therapeutic abilities of TGF-β1/MSCs were associated with increased generation of induced Tregs and improved intrarenal migration of the injected cells. Futhermore, the mechanism of TGF-β1/MSCs in attenuating renal I/R injury was not through a direct canonical TGF-β1/Smad pathway. Conclusion TGF-β1/MSCs can induce a local immunosuppressive effect in the I/R-injured kidney. The immunomodulatory activity of TGF-β1–modified MSCs appears to be a gateway to new therapeutic approaches to prevent renal I/R injury.

Background: Peritoneal dialysis (PD) is a kind of replacement therapies for end-stage renal disease (ESRD) patients. In the first 4-8 weeks of PD therapy, the patients were given an empirical dialysis prescription due to unknown peritoneal transport characteristics.Methods: Proteomic analysis was used to identify serum biomarkers which can predict the baseline peritoneal transport characteristics. Results: A discovery set of serum samples from ESRD patients were collected. After 4-8 weeks of PD therapy, these patients were divided into three groups according to the peritoneal equilibration test (PET) results: high (H), high average (HA), low average and low (LA&L) transporters. A total of 1051 differential proteins were screened by nano High Performance Liquid Chromatography - Mass Spectrometry / Mass Spectrometry (Nano HPLC-MS/MS). The top two proteins among different peritoneal transport characteristics were Orosomucoid 2 (ORM2) and C-reactive protein (CRP). To verify the above biomarkers, a larger population of PD patients were enrolled. Immunoturbidimetric assay showed that CRP was significantly elevated in H group than LA&L group, consistent with the result of proteomic analysis. Western blot validated that ORM2 in serum was increased in LA&L group compared with H and HA group. The expression of ORM2 in peritoneum also altered progressively in three groups. At last, supplying exogenous ORM could actually change peritoneal substances transport by reducing peritoneal proteins loss, without causing an excessive pro-inflammatory response in mice.Conclusions: Serum ORM2 and CRP could be used as biomarkers to predict the baseline peritoneal transport characteristics, so as to guide the early PD treatment. ORM also raised the possibility of decreasing peritoneal proteins loss in PD patients.

Objective. To identify the risk factors for cervical lymph node metastasis (CLNM) and the feasibility of prophylactic central lymph node dissection. Methods. The characteristics of 1107 patients were extracted and analyzed. Univariate and multivariate analyses were used to identify risk factors associated with lymph node metastasis. The relationship between the central lymph node dissection (CLND) and lateral lymph node metastasis (LLNM) was analyzed using the correlation analysis. Results. The probability of CLNM was closely related to the male gender, age

Aims Cisplatin is an anticancer agent marred by nephrotoxicity. Limiting this adverse effect may allow the use of higher doses to improve its efficacy. The Wnt/β-catenin signaling pathway plays a critical role in nephrogenesis and repair of renal diseases. BIO, a small molecule agonist of this pathway, exerted a protective effect in adriamycin nephropathy and promoted nephrogenesis. The aim of this study, therefore, was to investigate whether Wnt/β-catenin agonist BIO could protect against cisplatin-induced nephrotoxicity in vivo and in vitro, as well as its possible mechanism. Main methods Male mice and human renal proximal tubular cells (HK-2) were subjected to cisplatin to study reno-protective effect of BIO. Renal function, cell viability, tubular apoptosis, production of reactive oxygen species (ROS) and proliferative level were analyzed respectively. Additionally, xenograft model was induced to investigate if BIO would impair the antitumor effect of cisplatin. Key findings Cisplatin increased serum creatinine levels and promoted histological renal injury as well as oxidative stress levels. Besides, renal apoptotic level and the expression of pro-apoptotic proteins, Bax/bcl-2 and cleaved-caspase3 included, in the kidney were increased. All these features were decreased by BIO, which also activated Wnt/β-catenin pathway in cisplatin-induced nephrotoxicity. Similarly, accompanied by the motivation of Wnt/β-catenin pathway, BIO exerted a positively protective effect on HK-2 challenged cisplatin. Last, the chemotherapeutic effects of cisplatin in xenograft mice of ovary tumor models and in lung cancer cells weren't compromised by BIO. Significance Wnt/β-catenin agonist BIO has the potential to prevent cisplatin nephrotoxicity without compromising its anti-proliferation efficacy.

Background: A few studies have shown that urinary kidney injury molecule-1 (uKIM-1) levels are increased in acute kidney injury (AKI); however, the correlation between uKIM-1 and histological tubular injury, which is considered to be the gold standard for evaluating renal damage and predicting prognosis, is still unclear. We performed this study to determine whether the predicted value of uKIM-1 is correlated with renal KIM-1 (tKIM-1) expression and tissue damage in AKI patients. Methods: This retrospective study recruited 14 healthy individuals and 27 biopsy-proven acute tubular injury (ATI) patients. uKIM-1 and plasma KIM-1 (sKIM-1) levels were measured by ELISA, and tKIM-1 expression was evaluated by immunohistochemistry. Results: Elevated levels of urinary, plasma, and renal KIM-1 were found in ATI patients. The uKIM-1 concentration was positively correlated with tKIM-1 expression and reflected the severity of renal histological injury. The outcome of ATI was associated with uKIM-1 expression: the ATI patients with higher uKIM-1 levels had an increased potential for an incomplete recovery of renal function during follow-up. Additionally, the level of KIM-1, regardless of source, was negatively related to the eGFR, and ROC curve analysis revealed that the ROC-AUC was 0.923 (p = 0.000) for the diagnosis of ATI based on a combination of high uKIM-1 and sKIM-1 levels. Conclusion: The uKIM-1 level corresponds with the severity of renal histological damage and can be a potential reliable predictor of adverse renal outcomes in ATI patients. Moreover, combining uKIM-1 and sKIM-1 can increase the sensitivity and specificity of the diagnosis of severe ATI.

Background/Aims: To compare the serum concentration of Indoxyl sulfate (IS) in patients on continuous ambulatory peritoneal dialysis (CAPD) and low-flux hemodialysis (HD), and analyze the risk factors associated with IS. Methods: We performed a single-center, cross-sectional observational study including 169 patients on CAPD and 115 patients on low-flux HD. Patients were divided into the anuric HD group, anuric peritoneal dialysis (PD) group, and non-anuric PD group on the basis of dialysis modality and residual urinary output. Serum concentration of IS was determined by high-performance liquid chromatography electrospray tandem mass spectrometry. Results: After matching the urinary volume and dialysis vintage, 58 anuric patients on PD and 58 anuric patients on HD were enrolled. The serum level of IS was significantly lower in patients on PD than that in those on HD (28.05 ± 13.98 vs. 39.64 ± 18.25 μg/mL; p < 0.001). This result persisted even after adjustment for confounding risk factors including nutritional status (β = 0.338, p < 0.001). In addition, the serum level of IS was significantly lower in non-anuric PD patients than that anuric PD patients (18.70 ± 11.21 vs. 28.05 ± 13.98 μg/mL; p < 0.001). After the adjustment for risk factors such as dialysis vintage, IS serum concentration in patients on PD was still significantly correlated with residual renal function (RRF; β = –0.355, p < 0.001). Conclusions: Dialysis modality is the independent risk factor of IS serum concentration and it is substantially lower in patients on CAPD than that in those on low-flux HD. Additionally, RRF was independently associated with IS serum concentration in CAPD patients, and the better the RRF is, the lower IS serum concentration.

Euglycemic diabetic ketoacidosis (EDKA) was considered a rare condition with its specific definition and precipitating factors. However, with the wide use of sodium glucose cotransporter 2 (SGLT-2) inhibitors, the newest class of antidiabetic agents, EDKA has come back into the spotlight. Relevant cases are increasingly being reported along with insights into the mechanism of EDKA. It seems increasingly clear that EDKA is more common than we used to believe. The SGLT-2 inhibitor-associated EDKA also indicates a necessary review of our previous understanding of “diabetic” ketoacidosis, since the SGLT-2 inhibitor predisposes patients to DKA in a “starvation” way. Actually, there are growing reports about starvation-induced ketoacidosis as well. The previously “exclusive” nomenclature and cognition of these entities need to be reexamined. That the hormonal interactions in DKA may differ from the severity of insulin deficiency also may have served in the scenario of EDKA. The SGLT-2 inhibitors are newly approved in China. The main purpose of this work is to have a better understanding of the situation and update our knowledge with a focus on the pathogenesis of EDKA.

Background/Aims: Even though delayed ischemic preconditioning (DIPC) has been reported to produce renal protection, the underlying mechanism remains poorly understood. We reported that a 15-minute renal ischemic preconditioning (IPC) 4 days before subsequent ischemia-reperfusion attenuated renal injury Kidney dendritic cells (DCs) are abundant in the renal tubulointerstitium and, depending on their status, can induce immune activation or tolerance. The aim of the present study was to investigate the role of DCs in IPC of the kidney. Methods: Mouse kidneys were challenged by transient brief episodes of sublethal ischemia followed by subsequent prolonged ischemia. DC abundance and maturation in the spleen and kidney were measured by flow cytometry and immunohistochemical staining. To confirm the function of mature DCs in the renoprotective effect of IPC on renal ischemia-reperfusion injury the A2 adenosine receptor (A2AR) antagonist SCH58261 was administered to stimulate DC maturation prior to assessment of renal functional and histological injury and the inflammatory reaction. Results: Compared with sham-operated animals, preconditioned mice had a reduced injury with less CD11c+ cells, lower levels of the pro-inflammatory cytokine IL-17 and reduced expression of the mature DC marker CCR7. Preconditioned mice also produced more of the anti-inflammatory cytokine IL-10. Both renal cells and splenocytes from these mice had more DCs (CD45+/CD11c+/F4/80-), but fewer of these DCs were mature (CD45+/CD11c+/ F4/80-/MHC-II+/CD80+) compared with those from sham-treated animals, suggesting that the immunomodulatory effect of renal ischemic preconditioning is both local and systemic. Additionally, injection of the A2AR antagonist SCH58261 reversed IPC-induced inhibition of DC maturation and mitigated the protective effect of preconditioning, suggesting that DC maturation contributes to immune cell-mediated ischemic preconditioning. Conclusion: Our results show that DIPC of the kidney provides local and systemic immunosuppression by inhibiting DC maturation and hence mediates a renal protective effect.

Acute respiratory distress syndrome (ARDS) is a disease that seriously threatens human life and health. The aim of the study was to investigate the effects of ulinastatin combined with mechanical ventilation on oxygen metabolism, inflammation and stress response, as well as the antioxidant capacity of ARDS. Eighty patients with ARDS treated in Yiwu Central Hospital from January, 2015 to December, 2016 were enrolled in the present study and divided into the observation (n=40) and control (n=40) groups, using a random number table. The control group was treated with mechanical ventilation, while the observation group, based on treatment of the control group, was treated with ulinastatin for 14 consecutive days as one course of treatment. The changes in the relevant indexes of oxygen metabolism, lung function, time of ventilator treatment, total hospital stay, and St. George's Respiratory Questionnaire (SGRQ) score of the two groups after intervention were compared, and the changes in inflammatory cytokine levels, dopamine receptor-related hormone levels, superoxide dismutase (SOD), malondialdehyde (MDA) and total antioxidant capacity of the two groups before intervention and at 1 and 4 weeks after intervention were compared. After intervention, the arterial blood lactate in the observation group was significantly lower than that in the control group (P0.05). At 1 and 4 weeks after intervention, the SGRQ scores of the observation group were significantly increased to those of the control group (P

Objects To look into the discharge pharmacotherapy for type 2 diabetics admitted to two general hospitals of different ranks and inspect current real-world management of discharge pharmacology and its related factors. Methods Type 2 diabetics admitted to a tertiary general hospital (Ningbo Medical Treatment Centre Lihuili Hospital, LHLH) or a secondary general hospital (Simen Hospital, SMH) for intensification of their anti-diabetics were included for retrospective analysis. Patients' demographics, clinical characteristics, admission diabetes therapy and discharge diabetes pharmacology were analyzed and compared among patients in each hospital as well as between two hospitals. Results 391 patients from LHLH and 164 patients from SMH were included for analyzing. Compared with patients from LHLH, patients from SMH were older, more illiterate and had higher HbA1c concentrations. While there was a nearly equal split of oral anti-diabetes drugs (OADs)-only and Insulin treatment in LHLH's discharge pharmacotherapy, insulin treatment dominated SMH's. Basal-and-bolus insulin assumed the majority of SMH's insulin regimens but only accounted for less than 20% of LHLH's. The principal discrepancy in OADs-only treatment existed in the utilization of newer classes of OADs. Cost and body mass index (BMI) were the main differentiating factors among OADs-only treatments while duration, BMI and HbA1c differ among insulin treatments at LHLH. Clinical characteristics didn't significantly differ among OADs-only treatments and HbA1c was the only differentiating factor among insulin treatments at SMH. Overall, hospital, duration, HbA1c, and vascular diseases were main factors that affect discharge pharmacology. Conclusions Great disparities exist in the discharge pharmacotherapy at two hospitals. Diabetes management is mostly glucose-oriented at SMH while multifactorial considerations were reflected in LHLH's discharge pharmacotherapy. Besides differences in patients' demographics, medication availability and diagnosis of early-stage vascular complications, lack of practical algorithm for discharge management in T2DM may be the underlying deficiency and a key part for future improvement.

As an effective way to obtain solar energy and separate the soluble contaminants from water, solar-driven interfacial evaporation is used in desalination, wastewater treatment, electricity generation, and domestic water heating system. Herein, we demonstrate a monolithic sponge with three-dimensional porous structure as the solar-energy evaporator, which is composed of hydrophilic polymer (Konjac Glucomannan, KGM) and solar absorbent (reduced graphene oxide, rGO). Under one sun irradiation, the sponge achieves a rapid evaporation rate (1.60 kg m−2 h−1) and high interfacial water evaporation efficiency (92 %) due to its good absorption, photothermal, thermal insulation, and fast water transport properties. Meanwhile, the concentrations of radioactive elements (strontium, cesium, and uranium) in wastewater dropped from grams to micrograms after purification, even under radiation and acidic conditions. Additionally, the durability and repeatability of the sponge also have been verified. The results showed that solar-driven interfacial evaporation can effectively treat radioactive wastewater and enrich various radionuclides in a more energy-saving manner.

Increasing crop yields while reducing environmental impacts are a great challenge to ensuring food security and environmental quality for the world agriculture. Increasing planting density appropriately is one of the most effective strategies for increasing maize (Zea mays L.) yield. In China, overuse of nitrogen (N) fertilization on maize has resulted in excessive N surplus in the soil and environmental impacts. To address this challenge we conducted 212 site-year field experiments at two planting densities of 60000 and 75000 plants per ha with the same inputs of N. Results showed that maize yield could be increased 5.59% across China and 10.5%, 2.7%, 5.2% and 10.3% respectively in Southwest (SW), Huanghuaihai (HM), North (NM) and Northwest (NW) maize regions without extra inputs of N. The Life-cycle assessment showed that reactive N loss intensity and GHG intensity decreased by 2.2% to 10.2% across different regions of China, indicating that yield increase could be achieved without extra N inputs and further negative environmental impacts if planting density was increased by 15000 plants per ha under the current condition of excessive N surplus in China. If farmers in China increase maize planting density by 15000 per ha across the whole country the total maize production from the same planting area of 2017 would be 290 Mt which will be close to the expected demand of 315 Mt by 2030 while reducing the environmental impacts of intensive agriculture.

Emerging evidence indicates that retinoid-related orphan receptor (ROR)α, a member of the ROR nuclear receptor subfamily, mediates key cellular adaptions to hypoxia and contributes to the pathophysiology of many disease states. However, the effects of RORα in renal ischemia/reperfusion (I/R) injury remain unclear. Wild-type (WT) C57 black 6 (C57BL/6) mice and RORα-deficient stagger [ROR(sg/sg)] mice and their WT littermates were used for in vivo studies. The renal I/R injury model was induced by bilateral renal pedicle clamping for 35 min. Human proximal tubule cell line cells were treated with hypoxia (1% oxygen) to establish the cell hypoxia/reoxygenation (H/R) model. We investigated the renal expression and biologic function of RORα, and we found that RORα was significantly down-regulated after renal I/R injury. ROR(sg/sg) mice displayed dramatically augmented renal dysfunction and morphologic damage compared with WT mice at 24 h post-I/R. Further study revealed that the detrimental effects of RORα deficiency were attributable to tubular epithelial cell apoptosis and, consequently, renal inflammation and oxidative stress. The proapoptotic effect of RORα deficiency was associated with aggravated mitochondrial dysfunction in renal tubular cells after I/R. However, pretreatment of C57BL/6 mice with the RORα agonist SR1078 ameliorated I/R-induced renal dysfunction and damage and elicited a concomitant decrease in tubular epithelial cell apoptosis. In summary, our study provides experimental evidence showing that RORα is a novel endogenous protector against renal I/R injury and that ROR-α activation is a promising therapeutic strategy for the prevention of acute kidney injury.-Cai, J., Jiao, X., Fang, Y., Yu, X., Ding, X. The orphan nuclear receptor RORα is a potential endogenous protector in renal ischemia/reperfusion injury.

Liver metastases develop in more than half of the patients with colorectal cancer (CRC) and are associated with a poor prognosis. The factors influencing liver metastasis of CRC are poorly characterized, but this information is urgently needed. We have now discovered that small extracellular vesicles (sEVs; exosomes) derived from CRC can be specifically targeted to liver tissue and induce liver macrophage polarization toward an interleukin-6 (IL-6)-secreting proinflammatory phenotype. More importantly, we found that microRNA-21-5p (miR-21) was highly enriched in CRC-derived sEVs and was essential for creating a liver proinflammatory phenotype and liver metastasis of CRC. Silencing either miR-21 in CRC-sEVs or Toll-like receptor 7 (TLR7) in macrophages, to which miR-21 binds, abolished CRC-sEVs' induction of proinflammatory macrophages. Furthermore, miR-21 expression in plasma-derived sEVs was positively correlated with liver metastasis in CRC patients. Collectively, our data demonstrate a pivotal role of CRC-sEVs in promoting liver metastasis by inducing an inflammatory premetastatic niche through the miR-21-TLR7-IL-6 axis. Thus, sEVs-miR-21 represents a potential prognostic marker and therapeutic target for CRC patients with liver metastasis.

Autologous fat transplantation is increasingly applied in plastic and reconstructive surgery. Stromal vascular fraction cells (SVFs) combined with angiogenic factors, such as VEGF (vascular endothelial growth factor A) and Ang-1 (angiogenin-1), can improve angiogenesis, which is a critical factor for graft survival. However, direct transplant with such a mixture is insufficient owing to the short half-life of angiogenic factors. In this study, we evaluated whether a double sustained release system of VEGF/ANG-1-PLGA (poly (lactic-co-glycolic acid)) microspheres plus SVFs can improve angiogenesis and graft survival after autologous fat transplantation. VEGF/ANG-1-PLGA-sustained release microspheres were fabricated by a modified double emulsion-solvent evaporation technique. Human aspirated fat was mixed with SVF suspension plus VEGF/ANG-1 sustained release microspheres (Group C), SVF suspension (Group B) alone, or Dulbecco's modified Eagle's medium as the control (Group A). Eighteen immunocompromised nude mice were injected with these three mixtures subcutaneously at random positions. After 8 weeks, the mean volume of grafts was greater in the SVFs plus VEGF/ANG-1-PLGA group than in the control and SVFs groups (1.08 ± 0.069 ml vs. 0.62 ± 0.036 ml, and 0.83 ± 0.059 ml, respectively). Histological assessments showed that lower fibrosis, but greater microvascular density in the SVFs plus VEGF/ANG-1-PLGA group than in the other groups, though the SVFs group also had an appropriate capillary density and reduced fibrosis. Our findings indicate that SVFs plus VEGF/ANG-1-PLGA-sustained release microspheres can improve angiogenesis and graft survival after autologous fat transplantation.

Background: Currently, there is an urgent need to find ways of identifying primary membranous nephropathy (PMN) patients who are likely to benefit from calcineurin inhibitors (CNI) or who are resistant to them. In this study, we employed nano-HPLC-MS/MS analysis to identify serum biomarkers that predict the clinical response to CNI therapy in PMN patients. Methods: The endpoint was complete remission (CR) after CNI treatment. PMN patients were grouped into no-remission (NR) or CR groups to screen predictive candidates using the nano-HPLC-MS/MS analysis. Results: Compared with NR patients, 3 upregulated proteins and 5 downregulated proteins were found to present a twofold change in CR patients’ serum. Serum amyloid A1 protein (SAA1) was further validated by ELISA; it was decreased in patients in the NR group compared with patients in the CR group, but SAA1 in patients in these groups was lower than in healthy controls and minimal change disease patients. The area under the receiver operating characteristic (ROC) curve of SAA1 was used to distinguish PMN NR patients from those in remission and was 0.901, with a sensitivity of 78.3% and specificity of 86.8%, similar to that of the phospholipase A2 receptor (PLA2R) antibody. Combining SAA1 with the PLA2R antibody, the area under the ROC curve was 0.956, which was higher than that of SAA1 or the PLA2R antibody alone. Conclusions: Serum SAA1 may be a candidate PMN biomarker that can be used to discriminate CNI NR cases from remission patients. The combination of SAA1 and the PLA2R antibody increases the accuracy of diagnosis.

Mesenchymal stem cell (MSC) transplantation is a promising therapy for acute kidney injury; however, the efficacy is limited due to poor survival after transplantation. In this study, we investigated how MSC transplantation timing affected the survival and therapeutic potential of MSCs in the kidney ischemia-reperfusion (I/R) injury model. After kidney I/R injury, the inflammatory process and tissue damage were characterized over 1 week post-I/R, we found that inflammation peaked at 12-24 h post-I/R (h.p.i.), and urine neutrophil gelatinase-associated lipocalin (NGAL) measurements correlated highly with measures of inflammation. We cultured MSCs with supernatants from I/R injured kidney tissue homogenates collected at different time points and found that kidney homogenates from 12 and 24 h.p.i. were most toxic to MSCs, whereas homogenates from 1 h.p.i. were not as cytotoxic as those from 12 and 24 h.p.i. Compared with MSCs administered at 12, or 24 h.p.i., cells administered immediately after ischemia or 1 h.p.i. yielded the highest renoprotective and anti-inflammatory effects. Our findings indicate that MSC treatment for acute kidney injury is most effective when applied prior to the development of a potent inflammatory microenvironment, and urine NGAL may be helpful for detecting inflammation and selecting MSC transplantation timing in I/R kidney injury.

Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling plays a dominant role in the pathogenesis of liver ischemia-reperfusion (IR) injury. Dexmedetomidine (Dex) protects the liver against IR injury via α2-adrenoceptor activation, but the contribution of TLR4 signaling remains unknown. The authors aimed to examine whether pretreatment with Dex produces hepatic protection and investigate the influence of Dex on TLR4/NF-κB signaling. Dex was given via intraperitoneal injection 30 min prior to orthotopic autologous liver transplantation (OALT) in rats, and three α2-adrenoceptor antagonists including atipamezole (a nonselective α2 receptor blocker), ARC-239 (a specific α2B/C blocker) and BRL-44408 (a specific α2A blocker) were injected intraperitoneally 10 min before Dex administration. Histopathologic evaluation of the liver and the measurement of serum alanine aminotransferase activity, TLR4/NF-κB expression in the liver, and pro-inflammatory factors (serum tumor necrosis factor-α, interleukin-1β and hepatic myeloperoxidase) concentrations were performed 8 h after OALT. Dex ameliorated liver injury after OALT probably by suppressing the TLR4/NF-κB pathway and decreasing inflammatory mediator levels. The protective effects of Dex were reversed by atipamezole and BRL-44408, but not by ARC-239, suggesting that these effects were mediated in part by the α2A subtype. In conclusion, Dex attenuates liver injury partly via the α2A-adrenoceptor subtype, and the mechanism is due to the suppression of the TLR4/NF-κB pathway.

Preeclampsia (PE) is known to represent an exaggerated maternal inflammatory response to pregnancy. Lipoxin A(4) (LXA(4)), considered as an endogenous stop signal in inflammation, has been extensively studied pre clinically for its inflammatory pro-resolving effects. Thus, in the current study, we tested the effect of BML-111 (synthetic analogue of LXA(4)) on experimental PE rats induced by low-dose endotoxin (LPS) and of LXA(4) on human extravillous trophoblast cell line (TEV-1). In vivo experiment results showed that systolic blood pressure, 24 h-urinary albumin excretion, serum TNF-α and IL-8 levels and morphologic damage of placenta and kidney caused by LPS were all effectively alleviated by BML-111. LXA(4) also inhibited LPS-triggered apoptosis, activation of NF-κB, TNF-α and IL-8 mRNA and protein expression in TEV-1 cells. At the same time, BML-111 protected the cells from LPS-reduced proliferation. The current study demonstrated for the first time that LXA(4) could alleviate the symptoms of PE in endotoxin exposed rats.

Alpha-lipoic acid (ALA) is a powerful antioxidant, and its effect in ameliorating complications of diabetes mellitus has been widely documented. The aim of this study was to investigate the role of ALA in the disease progression of remnant kidneys (RK). Systolic blood pressure (SBp), hemoglobin, renal function, kidney malondialdehyde (MDA), glutathione (GSH), vitamin E (Vit E) concentrations, p65 nuclear factor (NF)-κB activity, and macrophage infiltration were analyzed in sham and RK rats supplemented with ALA (100 mg/kg body weight, i.p., every other day) or vehicle for 12 weeks. RK rats exhibited increases in SBp, kidney MDA concentration, p65 NF-κB activity, and macrophage infiltration, which were prominent in weeks 4 and 8 and decreased at week 12. RK rats also showed anemia, microalbuminuria, and decreased renal function and kidney GSH and Vit E concentrations. These changes were all attenuated by 8 weeks of ALA treatment compared to RK vehicle group. But the continued ALA treatment after week 8 reversed the beneficial effect on SBp, kidney MDA concentration, p65 NF-κB activity, macrophage infiltration, anemia, microalbuminuria, and renal function, while the beneficial effect was maintained if the treatment was discontinued after week 8. Furthermore, ALA increased albuminuria and kidney MDA concentration in sham animals. In conclusion, ALA administration attenuates oxidative stress, inflammation, and hypertension and delayed the deterioration of kidney function in RK rats with enhanced oxidative stress, while in healthy animals or RK rats with a well-balanced redox state, ALA may act as a pro-oxidant, contributing to renal dysfunction.

Aim: Hypoxia-inducible factor (HIF) activity during the course of chronic kidney disease (CKD) development is poorly defined, and the effect of HIF activation on CKD is still controversial. The purpose of the present study was to characterize HIF expression during the course of CKD development, and to investigate the effect of HIF activation on CKD by using prolyl hydroxylase (PHD) inhibitor L-mimosine. Methods: Rats with remnant kidneys (RK) were killed at week 1, 2, 4, 6, 8, 12 after subtotal nephrectomy. An additional group of RK rats was treated with L-mimosine to study the effect of HIF-α activation. Results: Tubulointerstitial hypoxia in the remnant kidney began at week 1 and continued, albeit attenuated, until week 12, the last time point examined. The nuclear expression of HIF-1α and HIF-2α, as well as typical HIF target genes VEGF (vascular endothelial growth factor), HO-1 (heme oxygenase-1), GLUT-1 (glucose transporter-1) and EPO (erythropoietin), were all upregulated in the early stage of RK when renal function was stable, and returned to the basal level later, accompanied by impaired renal function and interstitial fibrosis. L-mimosine administered from week 5 to week 12 led to accumulation of HIF-1α and HIF-2α proteins, increased expression of VEGF, HO-1 and GLUT-1, and improved renal function. Furthermore, fibrosis markers α-smooth muscle actin (α-SMA) and Collagen III, as well as peritubular capillary rarefaction index, were all significantly decreased after L-mimosine treatment. Conclusion: There was a transient HIF-α activation in the remnant kidney of rats at the early stage following subtotal nephrectomy. L-mimosine administered in later stages re-activated HIF-α and reduced tubulointerstitial fibrosis.

Peripheral primitive neuroectodermal tumors (peripheral PNETs) are rare in the abdomen. We report the imaging findings of four peripheral PNETs arising in the abdomen. Three were ill-demarcated tumors and one was a well-demarcated tumor, with extensive local invasion and lymph node metastasis in two cases, respectively. The tumors are of inhomogeneous attenuation and heterogeneous enhancement after intravenous administration of contrast materials. Although their imaging manifestations cannot distinguish them from other sarcomas, recognition of these imaging features may be helpful in suggesting the possibility of peripheral PNETs in some cases.

Bryophyte is a very important category in the plant community. By using the field survey and literature review method, the paper focuses on the investigation of bryophyte landscape status. The main research results are as follows: (1) putting forward three principles of bryophytes in landscape design, the scientific principle, cultural principle and artistic principle. (2)illustrating the analysis and composition of bryophytes in landscape design, and applying the expression idea and methods of dot, line, plane and bulk of bryophytes in different plant landscape creations. (3)presenting the match method and recommendation modes of bryophytes with other landscape elements. The match mode of native bryophytes includes thuidium cymbifolium zoysia japonica ficus virens, or liverworts sweet-scented osmanthus trees – rhododendrons, or polytrichum commune funaria hygrometrica leucobryum neilgherrense etc. Keywords—bryophytes; landscape design; principle; landscape elements

This paper aims to explore whether pretreatment with dexmedetomidine (Dex) has antioxidative and renal protective effects during orthotopic autologous liver transplantation (OALT) and its impact on nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Sprague-Dawley rats were randomized into groups that include sham-operated (group S), model (group M), low dose Dex (group D1), high dose Dex (group D2), atipamezole (a nonspecificα2receptor blocker) + high dose Dex (group B1), ARC239 (a specificα2B/creceptor blocker) + high dose Dex (group B2), and BRL-44408 (a specificα2Areceptor blocker) + high dose Dex (group B3). Then histopathologic examination of the kidneys and measurement of renal function, the renal Nrf2 protein expression, and oxidants and antioxidants were performed 8 hours after OALT. We found that pretreatment with Dex activated Nrf2 in glomerular cells and upregulated antioxidants but reduced oxidants (allP<0.01, group D2 versus group M). Atipamezole and BRL-44408, but not ARC239, reversed these protective effects. In conclusion, pretreatment with Dex activates Nrf2 throughα2Areceptor, increases the antioxidant levels, and attenuates renal injury during OALT.

CXC chemokines and their cognate receptors have been implicated wildly in cancer pathogenesis. In the present study, we report a critical cause relationship between CXCR4 expression and tumorigenesis in the setting of human esophageal squamous cell carcinoma (ESCC). In ESCC cells, CXCR4 expression was significantly higher than in human esophageal epithelial cells (HEEC). Reduction of CXCR4 in ESCC cells reduced cell proliferation and invasion in vitro and tumor growth in vivo. Among the potential downstream targets of CXCR4-CXCL12 are RhoA, Rac-1, and Cdc42, which are likely to contribute to the invasiveness of ESCC cells. Finally, we found that CXCR4-CXCL12/AKT axis regulates RhoA, Rac-1, and Cdc42 to modulate cell invasion and tumor metastasis. Together, these results demonstrate a role for CXCR4 in ESCC metastasis and progression and suggest potential targets for therapeutic intervention.

Objectives Esophageal squamous cell carcinoma is one of the most frequent malignant tumors. Cancer stem cells are considered to be responsible for tumor growth, metastasis, and recurrence. Cluster of differentiation 133 (CD133) and C-X-C chemokine receptor type 4 (CXCR4) are frequently applied markers for the identification and isolation of cancer stem cells. However, few studies have investigated the coexpression of CD133 and CXCR4 in esophageal squamous cell carcinoma. This study aims to explore the clinical and biological role of stem-like CD133 + CXCR4 + cells in esophageal squamous cell carcinoma. Methods Immunohistochemical staining was performed to detect the expression of CD133 and CXCR4 in esophageal squamous cell carcinoma tissues of patients. Flow cytometry and fluorescence-activated cell sorting were applied to analyze and isolate each subgroup in esophageal squamous cell carcinoma cell line TE-1. The characteristic differences between each subgroup were assayed in vitro. The association between CD133/CXCR4 expression and patients' prognosis was analyzed by Kaplan–Meier and Cox regression. Results Among 154 patient tissues, concomitant high CD133-CXCR4 expression accounts for 20.78% (32/154). In vitro, CXCR4 + cells (CD133 + CXCR4 + and CD133 − CXCR4 + ) showed high invasive potential and CD133 + CXCR4 + cells showed high proliferative capacity. Clinically, patients with concomitant high CD133-CXCR4 expression had decreased disease-free survival and overall survival ( P Conclusions Esophageal squamous cell carcinoma cells coexpressing CD133 and CXCR4 possess the characteristics of cancer stem cells. The concomitant high CD133-CXCR4 expression might be a novel marker for predicting the poor prognosis of patients with esophageal squamous cell carcinoma, and CD133 and CXCR4 may serve as potential therapeutic targets.

Contrast-induced acute kidney injury (CI-AKI) is a serious complication in patients after administration of iodinated contrast media. Proper animal models of CI-AKI can help understand the mechanisms involved and prevent the disorder. We used the 5/6-nephrectomized (NE) rat to develop a CI-AKI model and to evaluate differences in the toxic effects on the kidney between iohexol and iodixanol. We found that six weeks after ablative surgery was the preferred time to induce CI-AKI. We compared multiple pretreatment plans and found that dehydration for 48 hours before iodixanol (320, 10 mL/kg) administration was optimal to induce CI-AKI in the 5/6 NE rats. Compared with iodixanol, iohexol induced a significantly greater reduction in renal function, severe renal tissue damage, intrarenal hypoxia, and apoptotic tubular cells. Iohexol and iodixanol resulted in similarly marked increases in levels of inflammation and oxidative stress. In summary, the 5/6 NE rat combined with dehydration for 48 hours is a useful pretreatment to establish a novel and reliable CI-AKI model. Iohexol induced more severe CI-AKI than iodixanol in this model.

Contrast-induced acute kidney injury (CI-AKI) resulting from the use of intravascular iodinated contrast media for diagnostic and interventional cardiovascular procedures is associated with substantial morbidity and mortality. Despite preventative measures intended to mitigate the risk of CI-AKI, there remains a need for a novel and effective therapeutic approach. Limb ischemic preconditioning (LIPC), where short-term ischemia/reperfusion is applied to an arm prior to administration of the contrast agent, has been shown in several trials to preserve renal function in patients at high risk for CI-AKI. However, the underlying mechanism by which this procedure provides renoprotection against contrast media insults is not known. Here, we explored the molecular mechanism(s) of LIPC-induced protection of the kidneys from CI-AKI, particularly the role of phosphorylated glycogen synthase kinase-3β (GSK-3β). We used a novel CI-AKI model consisting of 5/6 nephrectomized (NE) rats at 6 weeks after the ablative surgery. LIPC- or sham-treated rats were administered iohexol (10 ml/kg, 3.5 gI) via the tail vein. The results showed that LIPC protected the kidneys against iohexol-induced injury. This protective effect was accompanied by the attenuation of renal dysfunction, tubular damage, apoptosis, mitochondrial swelling, oxidative stress, and inflammation. Furthermore, LIPC-induced renoprotection was blocked via treatment with inhibitors of PI3K (wortmannin or LY294002), but not ERK (U0126 or PD98059). LIPC also increased the protein expression levels of phospho-Akt, phospho-GSK-3β, and nuclear Nrf2, and decreased the levels of nuclear NF-κB. A specific GSK-3β inhibitor (SB216763) mimicked this effect of LIPC, by inhibiting the opening of the mitochondrial permeability transition pore and reducing the levels of oxidative stress and inflammation via activation of Nrf2 and suppression of NF-κB. The above results demonstrate that LIPC induces protection against CI-AKI, making this procedure a promising strategy for preventing CI-AKI. In particular, this renoprotective effect involves the phosphorylation of GSK-3β.

In patients with chronic renal failure, whether they have had hemodialysis or not, the specificity of some of the serum tumor markers for the diagnosis of the corresponding tumors is decreased while others remain as valuable as they are in patients with normal kidney function. The detection of tumor markers is extensively used for the diagnosis of corresponding tumors. It has been recently shown that some tumor markers are higher in patients with chronic kidney disease (CKD) than in the normal population. The effects of renal function and hemodialysis were examined on serum levels of some of the tumor markers including CEA, CA199, CA125, AFP, CA153, CA724, CYFRA21-1, NSE, SCC-Ag, PSA, and fPSA. The 232 non-dialysis patients with CKD and 37 chronic uremic patients treated with maintenance hemodialysis were enrolled in this study. The 232 non-dialysis patients were divided into three groups according to their Ccr. In group 1, Ccr was [Symbol: see text] 25 mL/min. In group 2, Ccr was between 25 and 50 mL/min. In group 3, Ccr was [Symbol: see text] 50 mL/min. The male patients were also divided into three groups to compare the serum levels of PSA and fPSA among the three groups. Nine tumor markers in 37 uremic patients were tested. For comparison, 37 non-dialysis patients with similar Ccr of the same age and gender served as controls. There existed significant differences in serum levels of CEA, CA199, CYFRA21-1, NSE, and SCC-Ag among different Ccr groups and the markers bore a negative correlation with Ccr. There were no significant differences among the three groups in the serum concentrations of CA125, AFP, CA153, CA724, PSA and fPSA. The serum levels of CA125 and NSE were significantly higher (P0.01) in hemodialysis patients than in the nondialysis control patients. In patients with chronic renal failure, who were or were not on hemodialysis, the specificity of serum CEA, CA199, CYFRA21-1, NSE, CA125 and SCC-Ag for the diagnosis of the corresponding tumors was decreased while serum AFP, CA153, CA724, PSA and fPSA were as valuable as they were in patients with normal kidney function. Hemodialysis further increased the serum level of CA125 and NSE.

Primary peritoneal malignant mixed mullerian tumors are very rare. We report the case of a patient presenting with pain in the right upper quadrant of the abdomen and in whom the physical examination demonstrated a peritoneal mass. Computed tomography (CT) confirmed the presence of a mass, with invasion of adjacent organs.

Backgrounds Despite the potential therapeutic benefits, cell therapy in renal ischemia-reperfusion (I/R) injury is currently limited by low rates of cell engraftment after systemic delivery. In this study, we investigate whether locally administration through renal artery can enhance the migration and therapeutic potential of mesenchymal stem cells (MSCs) in ischemic kidney. Methods The model of renal I/R injury was induced by 45 min occlusion of the left renal pedicle and right nephrectomy in rat. Followed by reperfusion, graded doses of CM-Dil labeled MSCs were implanted via three routes: tail vein (TV), carotid artery (CA), and renal artery (RA). Renal blood flow was evaluated by color and spectral Doppler ultrasound at 1 h and 24 h post-I/R. All the samples were collected for analysis at 24 h post-I/R. Results After injection of 1×106 MSCs, RA group showed obviously increased renal retention of grafted MSCs compared with TV and CA group; however, the renal function was even further deteriorated. When graded doses of MSCs, the maximal therapeutic efficiency was achieved with renal artery injection of 1×105 MSCs, which was significantly better than TV and CA group of 1×106 MSCs. In addition, further fluorescent microscopic and ultrasonic examination confirmed that the aggravated renal dysfunction in RA group was due to renal hypoperfusion caused by cell occlusion. Conclusion Administration route and dosage are two critical factors determining the efficiency of cell therapy and 1×105 MSCs injected through renal artery produces the most dramatic improvement in renal function and morphology in rat model of renal I/R injury.

Aims: To investigate the impacts of combinatorial atorvastatin (Ator) perioperative administration and mesenchymal stem cell (MSC) implantation on therapeutic effects in the rat experimental acute kidney injury. Methods: The model of renal ischemia-reperfusion (I/R) injury was induced by the release of bilateral renal pedicle clamps following 45 min of occlusion. Immediately after reperfusion, CM-Dil-labeled MSCs (1 × 106 cells) or vehicles only were administered through the carotid artery of the animals pretreated with or without Ator. Results: The combined treatment with Ator and MSCs (Ator+MSCs) markedly reduced the elevated levels of serum creatinine and blood urea nitrogen, as well as the severity of renal damage 24 h after I/R injury. In addition, we also observed inhibition of renal tubular cell apoptosis and promotion of proliferation in the Ator+MSCs group compared with the other groups. Consistent with the improvement in renal function and morphology, Ator pretreatment significantly ameliorated oxidative stress, inhibited inflammation response, and increased the viability of implanted MSCs. With regard to the further mechanism, we found that the expression of Toll-like receptor 4 (TLR4) and high-mobility group box 1, potential mediators of innate immunity, was significantly decreased in the Ator-treated groups. Conclusion: Ator treatment may protect the kidney undergoing I/R injury through suppression of TLR4 signaling, creating a better environment for the survival of grafted MSCs. The extra benefit of the Ator+MSCs combined therapy may result from the Ator-mediated inhibition of oxidative stress and inflammation in the ischemic kidney.

Aminoglycoside antibiotics, especially gentamicin, are widely used to treat Gram-negative infections due to their efficacy and low cost. Nevertheless the use of gentamicin is limited by its major side effect, nephrotoxicity. Xenon (Xe) provided substantial organoprotective effects in acute injury of the brain and the heart and protected against renal ischemic-reperfusion injury. In this study, we investigated whether xenon could protect against gentamicin-induced nephrotoxicity. Male Wistar rats were intermittently exposed to either 70% xenon or 70% nitrogen (N2) balanced with 30% oxygen before and during gentamicin administration at a dose of 100 mg/kg for 7 days to model gentamicin-induced kidney injury. We observed that intermittent exposure to Xe provided morphological and functional renoprotection, which was characterized by attenuation of renal tubular damage, apoptosis, and oxidative stress, but not a reduction in inflammation. We also found that Xe pretreatment upregulated hypoxia-inducible factor 2α (HIF-2α) and its downstream effector vascular endothelial growth factor, but not HIF-1α. With regard to the three HIF prolyl hydroxylases, Xe pretreatment upregulated prolyl hydroxylase domain-containing protein-2 (PHD2), suppressed PHD1, and had no influence on PHD3 in the rat kidneys. Pretreatment with Xe also increased the expression of miR-21, a microRNA known to have anti-apoptotic effects. These results support Xe renoprotection against gentamicin-induced nephrotoxicity.

Mesenchymal stem cell (MSC) administration is known to enhance the recovery of the kidney following injury. Here we tested the potential of hypoxic-preconditioned-MSC transplantation to enhance the efficacy of cell therapy on acute kidney injury (AKI) by improving MSC migration to the injured kidney. Cobalt was used as hypoxia mimetic preconditioning (HMP). MSC were subjected to HMP through 24 h culture in 200 µmol/L cobalt. Compared to normoxia cultured MSC (NP-MSC), HMP significantly increased the expression of HIF-1α and CXCR4 in MSC and enhanced the migration of MSC in vitro. This effect was lost when MSC were treated with siRNA targeting HIF-1α or CXCR4 antagonist. SPIO labeled MSC were administered to rats with I/R injury followed immediately by magnetic resonance imaging. Imaging clearly showed that HMP-MSC exhibited greater migration and a longer retention time in the ischemic kidney than NP-MSC. Histological evaluation showed more HMP-MSC in the glomerular capillaries of ischemic kidneys than in the kidneys receiving NP-MSC. Occasional tubules showed iron labeling in the HMP group, while no tubules had iron labeling in NP group, indicating the possibility of tubular transdifferentiation after HMP. These results were also confirmed by fluorescence microscopy study using CM-DiI labeling. The increased recruitment of HMP-MSC was associated with reduced kidney injury and enhanced functional recovery. This effect was also related to the increased paracrine action by HMP-MSC. Thus we suggest that by enhancing MSC migration and prolonging kidney retention, hypoxic preconditioning of MSC may be a useful approach for developing AKI cell therapy.

Background. Chronic hypoxia in the kidney has been suggested as a final common pathway in the progression of chronic kidney disease (CKD) leading to eventual kidney failure. Hypoxia-inducible factor (HIF) activation might offer a promising approach to the protection of hypoxic tissues, but the effect of HIF activation on CKD is still controversial. In this study, we investigated whether HIF activation had a beneficial or deleterious effect on CKD in the rat remnant kidney (RK) model. Methods. One week after as ubtotal nephrectomy, rats were randomized and each received special administration of prolyl hydroxylases (PHD) inhibitor L-mimosine (L-Mim) as follows: in the early long-time L-Mim treatment group they were administered L-Mim at Weeks 2–12; in the advanced medium-term L-Mim treatment group they were administered L-Mim at Weeks 4–12 and in the end-stage L-Mim treatment group they were administered L-Mim at Weeks 8–12. Results. Compared with the control group, renal dysfunction and increased collagen III deposition, a-smooth muscle actin expression and ED-1-positive macrophage infiltration in tubulointerstitium were exacerbated by early long-term L-Mim treatment and improved by advanced medium-term L-Mim treatment. End-stage L-Mim treatment had no effect on RK rats. Furthermore, early long-term L-Mim treatment activated HIF-1a, connective tissue growth factor (CTGF) and phospho-Smad3 prominently throughout the time course and activated HIF-2a, vascular endothelial growth factor (VEGF) and erythropoietin (EPO) slightly at the end stage, while advanced medium-term L-Mim treatment activated HIF-2a, VEGF and EPO significantly and had no effect on HIF-1a, CTGF and phospho-Smad3. Conclusion. HIF-a activation by PHD inhibitor L-Mim has dual roles in the development of CKD in the rat RK model depending on the timing of the administration and possibly the activated isoform of HIF-a.

Our study was designed to explore the applied characteristics of the back propagation artificial neural network (BPANN) on studying the genetic variants in adipnectin ADIPOQ, peroxisome proliferator-activated receptor (PPAR)-γ, and retinoid X receptor-α (RXR-α) genes and type 2 diabetes mellitus (T2DM) risks in a Chinese Han population.We used BPANN as the fitting model based on data gathered from T2DM patients (n=913) and normal controls (n=1,001). The mean impact value (MIV) for each input variables were calculated, and the sequence of the factors according to their absolute MIVs was sorted.The results from BPANN were compared with multiple logistic regression analysis, and the generalized multifactor dimensionality reduction (GMDR) method was used to calculate the joint effects of ADIPOQ, PPAR-γ, and RXR-α genes. By BPANN analysis, the sequence according to the importance of the T2DM risk factors was in the order of serum adiponectin level, rs3856806, rs7649121, hypertension, rs3821799, rs17827276, rs12495941, rs4240711, age, rs16861194, waist circumference, rs2241767, rs2920502, rs1063539, alcohol drinking, smoking, hyperlipoproteinemia, gender, rs3132291, T2DM family history, rs4842194, rs822394, rs1801282, rs1045570, rs16861205, rs6537944, body mass index, rs266729, and rs1801282. However, compared with multiple logistic regression analysis, only 11 factors were statistically significant. After overweight and obesity were taken as environment adjustment factors into the analysis, model A2 B4 C5 C6 C8 (rs3856806, rs4240711, rs7649121, rs3821799, rs12495941) was the best model (coefficient of variation consistency=10/10, P=0.0107) in the GMDR method.These results suggested the interactions of ADIPOQ, PPAR-γ, and RXR-α genes might play a role in susceptibility to T2DM. BPANN could be used to analyze the risk factors of diseases and provide more complicated relationships between inputs and outputs.

The serum levels of adiponectin are paradoxically decreased in obesity and may play important roles in the development of type 2 diabetes mellitus (T2DM). Potentially functional polymorphisms in the peroxisome proliferator-activated receptor-γ (PPAR-γ) and retinoid X receptor-α (RXR-α) genes may alter T2DM risks by increasing the human adiponectin promoter activity in cells. Therefore, we hypothesized that single nucleotide polymorphisms (SNPs) in PPAR-γ and RXR-α were associated with risk of T2DM. To test this hypothesis, three potentially functional SNPs of PPAR-γ and four of RXR-α with a minor allele frequency of ≥ 0.05 in the Chinese Han population were identified from the National Center for Biotechnology Information dbSNPs database to evaluate their association with T2DM.Polymerase chain reaction-restriction fragment length polymorphism was performed to test the genotypes in T2DM patients (n = 540) and normal controls (n = 604).The variant genotypes rs2920502CC, rs3856806CT, rs3856806CT/TT, and rs4240711AG/GG were associated with T2DM. Furthermore, the prevalences of haplotype GTC and CTG in PPAR-γ and GTAC in RXR-α were less frequent in cases (17.1%, 2.6%, and 2.4%, respectively) than in controls (22.3%, 3.8%, and 6.6%, respectively), whereas GTGT in RXR-α was more frequent in cases (6.9%) than in controls (4.4%) (P 0.05 for both two-sided χ(2) test and thousand times permutation tests). Patients with genotype CT/TT of rs3856806 and genotype AG/GG of rs4240711 had higher levels of serum adiponectin than those with the genotype CC and genotype AA (P = 0.026 and 0.021, respectively). Model X2 X5 X6 X7 (rs3856806, rs3132291, rs4240711, and rs4842194) was the best model with the highest test balanced accuracy (0.5764) (cross-validation consistency = 10/10) in the multifactor dimensionality reduction method.The PPAR-γ and RXR-α gene variants associated with the development of T2DM in this study must be investigated in a larger population to reveal any potential effects on metabolism.

Gastrointestinal stromal tumors (GISTs) are the most common gastrointestinal mesenchymal tumors. Computed tomography (CT) often shows exophytic gastrointestinal masses with cystic changes, necrosis or fistula formation, and heterogeneous enhancement. After Gleevec therapy, the primary tumor, its metastases, and its recurrences can develop cystic changes and decrease in size, these findings can be satisfactorily monitored by CT. We report on 42 patients with proven GISTs, five presenting with metastases and nine patients with recurrence or development of metastases after surgery and chemotherapy.

This study was aimed to explore the associations between the combined effects of several polymorphisms in the PPAR-γ and RXR-α gene and environmental factors with the risk of metabolic syndrome by back-error propagation artificial neural network (BPANN). We established the model based on data gathered from metabolic syndrome patients (n = 1012) and normal controls (n = 1069) by BPANN. Mean impact value (MIV) for each input variable was calculated and the sequence of factors was sorted according to their absolute MIVs. Generalized multifactor dimensionality reduction (GMDR) confirmed a joint effect of PPAR-γ and RXR-α based on the results from BPANN. By BPANN analysis, the sequences according to the importance of metabolic syndrome risk factors were in the order of body mass index (BMI), serum adiponectin, rs4240711, gender, rs4842194, family history of type 2 diabetes, rs2920502, physical activity, alcohol drinking, rs3856806, family history of hypertension, rs1045570, rs6537944, age, rs17817276, family history of hyperlipidemia, smoking, rs1801282 and rs3132291. However, no polymorphism was statistically significant in multiple logistic regression analysis. After controlling for environmental factors, A1, A2, B1 and B2 (rs4240711, rs4842194, rs2920502 and rs3856806) models were the best models (cross-validation consistency 10/10, P = 0.0107) with the GMDR method. In conclusion, the interaction of the PPAR-γ and RXR-α gene could play a role in susceptibility to metabolic syndrome. A more realistic model is obtained by using BPANN to screen out determinants of diseases of multiple etiologies like metabolic syndrome.

ObjectiveAcute kidney injury is a common clinical complication of cardiac surgery. Volatile anesthetics have been shown to protect against it in animal experiments. Clinically, however, the effect of volatile anesthetics has been unclear. We conducted a systematic review and meta-analysis of randomized, controlled trials to explore whether volatile anesthetics could provide renal protection to patients undergoing cardiac surgery.MethodsRandomized, controlled trials were identified in PubMed, Ovid, Excerpta Medica Database, Cochrane Library, Current Controlled Trials Register, reviews, and reference lists of relevant articles. Ten trials with 1600 total participants were eligible. Data were analyzed with both fixed- and random-effects models.ResultsRelative to control data, volatile anesthetics significantly reduced acute kidney injury incidence (relative risk [RR], 0.65; 95% confidence interval [CI], 0.43-0.97; P = .04). Although there was no significant difference between groups in absolute postoperative serum creatinine level and mortality, patients receiving volatile anesthetics had significantly (or borderline) lower increase in serum creatinine level from baseline on the first (weighted mean difference, −0.04 mg/dL; 95% CI, −0.07 to −0.01 mg/dL; P = .002) and second (weighted mean difference, −0.07 mg/dL, 95% CI, −0.14 to −0.00 mg/dL; P = .05) postoperative days and reduced incidences of prolonged intensive care unit stay (RR, 0.46; 95% CI, 0.34-0.64; P