Mechanism of miRNA-141-3p in Calcium Oxalate-Induced Renal Tubular Epithelial Cell Injury via NLRP3-Mediated Pyroptosis.

BACKGROUND/AIMS: Renal calculi represent a prevalent disorder associated with mineral deposition in renal calyces and the pelvis. Aberrant microRNA (miRNA) expression is implicated in renal injury. This study investigated the mechanism of miR-141-3p in calcium oxalate (CaOx) crystal-induced renal tubular epithelial cell (RTEC) injury. METHODS: Human RTECs HK-2 cells were treated with CaOx crystals to induce RTEC injury. Cell viability was evaluated using Cell Counting Kit-8 assay, and apoptosis was measured using flow cytometry. The contents of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), interleukin (IL)-1ß, and IL-18 were measured using enzyme-linked immunosorbent assay kits. The expressions of NLRP3, cleaved caspase-1, and GSDMD-N were detected using Western blot. miR-141-3p and NLRP3 expressions were determined using reverse transcription quantitative polymerase chain reaction. The binding of miR-141-3p and NLRP3 was validated using a dual-luciferase assay. The role of NLRP3 in the protection of miR-141-3p on RTEC injury was verified using functional rescue experiments. RESULTS: CaOx crystals induced RTEC injury, manifested as attenuated cell viability, enhanced apoptosis, elevated intracellular LDH and MDA levels, and decreased SOD level. Pyroptosis of RTECs was enhanced by CaOx crystal induction, evidenced by elevated expressions of cleaved caspase-1, GSDMD-N, IL-1ß, and IL-18. miR-141-3p expression was reduced in CaOx crystal-induced RTECs. miR-141-3p overexpression alleviated CaOx crystal-induced RTEC injury and suppressed pyroptosis of RTECs. miR-141-3p bound to NLRP3 and thereby repressed NLRP3 expression. NLRP3 overexpression reversed the protective effect of miR-141-3p overexpression on RTECs. CONCLUSION: miR-141-3p repressed NLRP3-mediated pyroptosis by suppressing NLRP3 expression, thus protecting CaOx crystal-induced RTEC injury.

Induction of cell-cycle arrest and apoptosis in human cholangiocarcinoma cells by pristimerin.

Pristimerin, a triterpenoid isolated from Celastraceae and Hippocrateaceae, is known to induce cytotoxicity in several cancer cell lines. However, whether pristimerin can induce apoptosis in cholangiocarcinoma cells and the underlying mechanism remain unexplored. We assessed the function of human cholangiocarcinoma QBC and RBE cell lines using various experimental methods such as the cell viability assay to elucidate the viability of cells, flow cytometry to detect the death rate of cells, and Western blot analysis to evaluate the expression of cell cycle-related proteins and autophagy-related proteins. Human cholangiocarcinoma QBC cells were transplanted to nude mice to establish an animal model, and the effect of pristimerin on tumor growth in this model was observed. QBC and RBE cell lines treated with pristimerin (0, 5, 10, and 20 µmol/L) demonstrated the induction of apoptosis in a dose-dependent manner. The cell viability assay revealed a reduction in the cell viability with an increase in the pristimerin concentration. Similarly, flow cytometry revealed a gradual increase in the cell death rate with an increase in the pristimerin concentration. In addition, pristimerin significantly lowered the expression of apoptosis-related proteins (Bcl-2, Bcl-xL, and procaspase-3), but increased the Bax expression. Furthermore, pristimerin resulted in the G0/G1 cell-cycle arrest, reducing the expression of cell cycle-related proteins (cyclin E, CDK2, and CDK4), and increased the expression of autophagy-related proteins (LC3) in QBC cell line. Treatment with pristimerin could inhibit tumor growth in the nude mouse model. Overall, this study suggests the potential effect of pristimerin on the cell-cycle arrest and apoptosis in human cholangiocarcinoma cells.

Tunable optical forces enhanced by plasmonic modes hybridization in optical trapping of gold nanorods with plasmonic nanocavity.

The optomechanical interaction between a plasmonic nanocavity and a gold nanorod through optical forces is demonstrated. It is revealed that strong localized plasmon resonance mode hybridization induced by a gold nanorod results in the resonance mode of the nanocavity splitting into two different plasmon resonance modes (bonding plasmon resonance mode and antibonding plasmon resonance mode). When the whole system (gold nanorod and gold nanocavity) is excited at the antibonding plasmon mode, the gold nanorod can receive an optical pushing force and be pushed away from the gold nanocavity. On the other hand, an optical pulling force acts on the gold nanorod and the gold nanorod can be trapped by the gold nanocavity when the plasmonic tweezers work at the bonding mode. The optical pulling force acting on the gold nanorod can be enhanced by two orders of magnitude larger than that of the same sized dielectric nanorod, which benefits from the strong resonant nearfield interaction between the gold nanorod and the gold nanocavity. More importantly, the shape and the position of the optical potential can be tuned by tailoring the wavelength of the laser used in the optical trapping, which can be used to manipulate the gold nanorod within a nanoscale region. Our findings have important implications for optical trapping, manipulation, sorting, and sieving of plasmonic nanoparticles with plasmonic tweezers.

Advantages of Pure Platelet-Rich Plasma Compared with Leukocyte- and Platelet-Rich Plasma in Treating Rabbit Knee Osteoarthritis.

BACKGROUND Concentrated leukocytes in leukocyte- and platelet-rich plasma (L-PRP) may deliver increased levels of pro-inflammatory cytokines to activate the NF-κB signaling pathway, to counter the beneficial effects of growth factors on osteoarthritic cartilage. However, to date no relevant studies have substantiated that in vivo. MATERIAL AND METHODS Autologous L-PRP and pure platelet-rich plasma (P-PRP) were prepared, measured for componential composition, and injected intra-articularly after 4, 5, and 6 weeks post-anterior cruciate ligament transection. Caffeic acid phenethyl ester (CAPE) was injected intraperitoneally to inhibit NF-κB activation. All rabbits were sacrificed after 8 weeks postoperative. Enzyme-linked immunosorbent assays were performed to determine interleukin 1ß (IL-1ß) and prostaglandin E2 (PGE2) concentrations in the synovial fluid, Indian ink staining was performed for gross morphological assessment, and hematoxylin and eosin staining and toluidine blue staining were performed for histological assessment. RESULTS Compared with L-PRP, P-PRP injections achieved better outcomes regarding the prevention of cartilage destruction, preservation of cartilaginous matrix, and reduction of IL-1ß and PGE2 concentrations. CAPE injections reversed the increased IL-1ß and PGE2 concentrations in the synovial fluid after L-PRP injections and improved the outcome of L-PRP injections to a level similar to P-PRP injections, while they had no influence on the therapeutic efficacy of P-PRP injections. CONCLUSIONS Concentrated leukocytes in L-PRP may release increased levels of pro-inflammatory cytokines to activate the NF-κB signaling pathway, to counter the beneficial effects of growth factors on osteoarthritic cartilage, and finally, result in a inferior efficacy of L-PRP to P-PRP for the treatment of osteoarthritis.

Nobiletin inhibited hypoxia-induced epithelial-mesenchymal transition of lung cancer cells by inactivating of Notch-1 signaling and switching on miR-200b.

Epithelial-mesenchymal transition (EMT) is an early step in the process of tumor metastasis. It is well known that tumor microenvironment affects malignancy in various carcinomas; in particular, that hypoxia induces EMT. Deregulated notch signaling also contributes a lot to the development of EMT in lung cancer. In this study, we investigated the use of Notch-1-inhibiting compound as novel therapeutic candidates to regulate hypoxia-induced EMT in lung cancer cells. According to previous screening, nobiletin was selected as a Notch-1 inhibitor. Hypoxia-induced EMT was characteristic of increased N-cadherin & vimentin expressions and decreased E-cadherin expressions. Treatment with nobiletin notably attenuated hypoxia-induced EMT, invasion and migration in H1299 cells, accompanied with reduced Notch-1, Jagged1/2 expressions and its downstream genes Hey-1 and Hes-1. Nobiletin treatment also promoted tumorsuppressive miR-200b level. Moreover, notch-1 siRNA prevented hypoxia-mediated cell migration and decreased Twist1, Snail1, and ZEB1/2 expressions, which are key EMT markers. Re-expression of miR-200b blocked hypoxia-induced EMT and cell invasion. Our findings suggest that downregulation of Notch-1 and reexpression of miR-200b by nobiletin might be a novel remedy for the therapy of lung cancer.

Photodynamic therapy mediated by 5-aminolevulinic acid suppresses gliomas growth by decreasing the microvessels.

Although 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) has been demonstrated to be a novel and effective therapeutic modality for some human malignancies, its effect and mechanism on glioma are still controversial. Previous studies have reported that 5-ALA-PDT induced necrosis of C6 rat glioma cells in vitro. The aim of this study was to further investigate the effect and mechanism of 5-ALA-PDT on C6 gliomas implanted in rats in vivo. Twenty-four rats bearing similar size of subcutaneously implanted C6 rat glioma were randomly divided into 3 groups: receiving 5-ALA-PDT (group A), laser irradiation (group B), and mock procedures but without any treatment (group C), respectively. The growth, histology, microvessel density (MVD), and apoptosis of the grafts in each group were determined after the treatments. As compared with groups B and C, the volume of tumor grafts was significantly reduced (P<0.05), MVD was significantly decreased (P<0.001), and the cellular necrosis was obviously increased in group A. There was no significant difference in apoptosis among the three groups. The in vivo studies confirmed that 5-ALA-PDT may be an effective treatment for gliomas by inhibiting the tumor growth. The mechanism underlying may involve increasing the cellular necrosis but not inducing the cellular apoptosis, which may result from the destruction of the tumor microvessels.

Prognostic significance of lymph node status in patients with metastatic colorectal carcinoma treated with lymphadenectomy.

BACKGROUND AND OBJECTIVES: To test prognostic significance of lymph node status in patients with metastatic colorectal carcinoma (mCRC). METHODS: Four hundred ninety six patients diagnosed with synchronous mCRC and treated with lymphadenectomy between 1995 and 2008 were identified and divided into groups pN0, pN1, and pN2 (140 (28.2%) in pN0, 223 (45.0%) in pN1, and 133 (26.8%) in pN2 group) according to their lymph node status. The Kaplan-Meier and Cox regression analyses were used to test associations and independent predictor status of lymph node involvement. RESULTS: The Cox proportional hazards regression showed pN as significantly associated with disease-specific survival (DSS) both in univariate (HR = 1.609, 95% CI 1.411 to 1.835, P < 0.001) and multivariate (HR = 1.630, 95% CI 1.422 to 1.868, P < 0.001) analyses. The Kaplan-Meier analysis demonstrated that patients with pN2 and pN1 had a significantly worse DSS compared with patients with pN0 tumors (respectively, 17.273 ± 1.020 and 27.145 ± 1.715 vs. 34.992 ± 2.143 months; P < 0.001). In accuracy analyses based on AUC values, nodal status demonstrated the highest accuracy (65.1%) out of all the variables. CONCLUSIONS: Our findings indicate that optimal TNM staging for mCRC should incorporate lymph node status to provide a more effective and predictive model.

A simple and effective method to enrich endogenous DNA from mammalian faeces.

Utilization of faeces has long been a popular approach for genetic and ecological studies of wildlife. However, the success of molecular marker genotyping and genome resequencing is often unpredictable due to insufficient enrichment of endogenous DNA in the total faecal DNA that is dominated by bacterial DNA. Here, we report a simple and cheap method named PEERS to predominantly lyse animal cells over bacteria by using sodium dodecyl sulphate so as to discharge endogenous DNA into liquid phase before bacterial DNA. By brief centrifugation, total DNA with enriched endogenous fraction can be extracted from the supernatant using routine methods. Our assessments showed that the endogenous DNA extracted by PEERS was significantly enriched for various types of faeces from different species, preservation time and conditions. It significantly improves the genotyping correctness and efficiency of genome resequencing with the total additional cost of $ 0.1 and a short incubation step to treat a faecal sample. We also provide methods to assess the enrichment efficiency of mitochondrial and nuclear DNA and models to predict the usability of faecal DNA for genotyping of short tandem repeat, single-nucleotide polymorphism and whole-genome resequencing.

Fungal corneal ulcer after repair of an overhanging filtering bleb: A case report.

BACKGROUND: Overhanging filtering bleb is a common complication after trabeculectomy and surgical repair is an effective treatment when the patient presents with apparent symptoms. Filtering bleb relevant infection including in the filtering bleb itself and even endophthalmitis in some severe cases has been reported. However, corneal fungal infection after filtering bleb repair is rarely reported. CASE SUMMARY: A 57-year-old Chinese man who had sensations of redness and foreign body sensations in the left eye 3 wk after repair of overhanging filtering bleb. 3 wk ago, due to sensations of a foreign body in the left eye for 3 years with worsening for 3 mo. The patient was diagnosed as overhanging filtering bleb and underwent a repair of overhanging filtering bleb. Postoperative, the filtering bleb formed well and the intraocular pressure is normal. But the patient gradually develop redness, pain and a grey infiltrate of the cornea in the eye. Finally it developed into fungal corneal ulcer. Through asking the medical history, we found the patient had irregularly self-medicated for years with glucocorticoid eye drops for years to relieve the foreign body sensation in the eye caused by filtering bleb overhanging. Because the glucocorticoid eye drops he used years ago had provide normal sensation to the eye. After 3 mo of anti-fungal treatment, the inflammation was controlled. CONCLUSION: In addition to avoiding the development of overhanging filtering bleb after trabeculectomy, the present case report also suggests that clinicians should pay more attention to the patient's ocular self-medication history. Particularly in patients with a history of glaucoma or eye surgery. Because these patients may be exposed to more types of eye drops than other individuals, they may select the wrong medications for long-term use, based on their previous experience.

Autologous transplantation of peripheral blood-derived circulating endothelial progenitor cells attenuates endotoxin-induced acute lung injury in rabbits by direct endothelial repair and indirect immunomodulation.

BACKGROUND: Studies have demonstrated the role of circulating endothelial progenitor cells (EPCs) in maintaining normal endothelial function and in endothelial repairing. This study was aimed to observe the protective effects of autologous transplantation of circulating EPCs against endotoxin-induced acute lung injury in rabbits and to investigate the underlying mechanisms. METHODS: One-hundred-and-fifty rabbits were enrolled. After acute lung injury was induced by endotoxin, autologous circulating EPCs, endothelial cell, or normal saline were transfused intravenously, respectively. Pao(2)/FiO(2) ratios, concentrations of plasma nitric oxide, malonyldialdehyde, and activity of superoxide dismutase were examined. The lung wet-to-dry weight ratios were counted; polymorphonuclear cell ratios and areas of hyaline membrane formation and hemorrhage were measured. The levels of interleukin-1ß, E-selectin, intercellular adhesion molecule-1, interleukin-10, vascular endothelial growth factor protein, and inducible nitric oxide synthase protein were analyzed. RESULTS: Pao(2)/FiO(2) ratios were significantly increased with EPC transfusion. Infiltration of polymorphonuclear cells, lung wet-to-dry weight ratios, and area of hyaline membrane and hemorrhage in lung tissue were significantly decreased after EPC transplantation. Plasma level of nitric oxide and malondialdehyde were significantly inhibited, and the activity of superoxide dismutase was enhanced in the EPC-treated animals. EPC transplantation significantly increased level of interleukin-10 and vascular endothelial growth factor protein and reduced levels of interleukin-1ß, E-selectin, intercellular adhesion molecule-1, and inducible nitric oxide synthase in injury lung tissues. CONCLUSIONS: Autologous transplantation of circulating EPCs can partly restore the pulmonary endothelial function and effectively attenuate endotoxin-induced acute lung injury by direct endothelial repair and indirect immunomodulation of antioxidation and antiinflammation.

Chemical profiles and identification of key compound caffeine in marine-derived traditional Chinese medicine Ostreae concha.

To compare the chemical differences between the medicinal and cultured oyster shells, their chemical profiles were investigated. Using the ultra performance liquid chromatography-electron spraying ionization-mass spectrometry (UPLC-ESI-MS), combined with principal component analysis (PCA) and orthogonal projection to latent structures discriminant analysis (OPLS-DA), the discrimination of the chemical characteristics among the medicinal and cultured oyster shells was established. Moreover, the chemometric analysis revealed some potential key compounds. After a large-scale extraction and isolation, one target key compound was unambiguously identified as caffeine based on extensive spectroscopic data analysis (1D and 2D NMR, MS, and UV) and comparison with literature data.

Postreperfusion syndrome during orthotopic liver transplantation: a single-center experience.

BACKGROUND: Marked hemodynamic alteration, commonly referred to as postreperfusion syndrome (PRS), often occurs after revascularization of the donor organ during orthotopic liver transplantation (OLT) and is associated with poor outcomes. This study aimed to investigate the incidence, predictive factors and clinical outcomes of PRS in Chinese patients following OLT at a liver transplantation center in China. METHODS: Over a 5-year period, 330 consecutive patients who had undergone OLT for hepatocellular carcinoma or cirrhosis were included in this retrospective study. PRS was defined as a >30% decrease in the mean arterial pressure compared with that before revascularization for more than 1 minute during the first 5 minutes of graft reperfusion. The patients were divided into 2 groups according to the development of PRS: group 1 (patients with PRS, n=56) and group 2 (patients without PRS, n=274). The demographic characteristics, operative and postoperative courses, and outcomes of the patients were analyzed using SPSS version 18.0. RESULTS: Multivariate regression analysis showed that left ventricular diastolic dysfunction determined by echocardiography and prolonged cold ischemia time were the independent risk factors for PRS. More patients in group 1 showed postoperative renal dysfunction than those in group 2 (19.23% vs 8.4%). Moreover, patients in group 1 also had higher intraoperative (7.14% vs 0%) and postoperative mortalities (26.92% vs 12.04%). CONCLUSION: Left ventricular diastolic dysfunction and prolonged cold ischemia time contribute to a high incidence of PRS, which is associated with adverse outcomes in Chinese patients following OLT.

[Empirical research of measuring elderly health utility in the outskirts of Beijing by using European quality of life 5-dimensions].

OBJECTIVE: To evaluate health utility values of the elderly in the outskirts of Beijing by European quality of life 5-dimensions (EQ-5D) from the EuroQol Group, and to compare the health utility values by using different translation models. METHODS: In the cross-sectional study, EQ-5D was used to measure the quality of life for 65 to 79 year-old usual residents in the town of Qinglonghu and Zhoukoudian in Fangshan District of Beijing. The health index which represented the health utility was calculated by using the Japan, the United Kingdom (UK), the United States (US) population-based time trade-off (TTO) models. Kruskal-Wallis H test was adopted to compare the health indexes calculated by the different models, and intraclass correlations coefficients (ICCs) and Bland-Altman plot were used to evaluate the consistency of the utility calculated by the three models. Mann-Whitney U test was used to compare the impacts of Cardio-vascular diseasel (CVD) on the 3 kinds of health index. The Spearman rho correlation coefficients between the 3 kinds of health index, EQ-VAS (visual analogue scales) score and age, gender, health status were also calculated. RESULTS: There were 2 406 participants in this analysis, with a mean age of 70.3 years, of whom 34.3% were male. The median and quantile range of Japan weights, US weights and UK weights health indexes were 1 (0.28), 1 (0.24) and 1 (0.29), respectively. The minimum and maximum of the three indexes were -0.06/1, -0.43/1 and -0.03/1, respectively. The US weights yielded the highest scores and the UK weights the lowest scores. The Japan, US and UK weight scores differed from each other (P<0.005). The Japan and US scores had the highest ICCs (0.987, 95%CI 0.986-0.988), followed by the US and UK scores (0.941, 95%CI 0.937- 0.946) and then the Japan and UK scores (0.921, 95%CI 0.915-0.927). The difference scores of 96.9%, 95.1% and 95.0% were found between the limits of agreement in Bland-Altmand plot. Negative correlations existed between the US/UK score and the number of CVDs, but not existed between the Japan score and the number of CVDs. CONCLUSION: The health indexes calculated by using the different EQ-5D TTO transform models were different for the elderly people in the Beijing suburban district, TTO model based on Chinese health preference should be developed.

Phosphatidylserine eversion regulated by phospholipid scramblase activated by TGF-ß1/Smad signaling in the early stage of kidney stone formation.

The mechanism underlying phosphatidylserine eversion in renal tubule cells following calcium oxalate-mediated damage remains unclear; therefore, we investigated the effects of TGF-ß1/Smad signaling on phosphatidylserine eversion in the renal tubule cell membrane during the early stage of kidney stone development. In a rat model of early stage of calcium oxalate stone formation, phosphatidylserine eversion on the renal tubular cell membrane was detected by flow cytometry, and the expression of TGF-ß1 (transforming growth factor-ß1), Smad7, and phospholipid scramblase in the renal tubular cell membrane was measured by western blotting. We observed that the TGF-ß1/Smad signaling pathway increased phosphatidylserine eversion at the organism level. The results of in vitro studies demonstrated that oxalate exposure to renal tubule cells induced TGF-ß1 expression, increasing phospholipid scramblase activity and phosphatidylserine eversion in the renal tubule cell membrane. These results indicate that TGF-ß1 stimulates phosphatidylserine eversion by increasing the phospholipid scramblase activity in the renal tubule cell membrane during the early stage of kidney stone development. The results of this study form a basis for further detailed research on the development of therapeutic agents that specifically treat urolithiasis and exert fewer adverse effects.

Hydroxyethyl starch for cardiovascular surgery: a systematic review of randomized controlled trials.

PURPOSE: The objective of this study was to appraise the safety profiles of HES preparations and to find out which HES preparation was the most acceptable in cardiovascular surgery through a comparison with control solutions. METHODS: Pertinent randomized controlled trials were selected through a search of Pubmed, Embase, and Cochrane Controlled Trials Register. Quantitative and qualitative analysis was carried out to evaluate blood loss, blood transfusion, renal function, complications, reoperation, and mortality. RESULTS: A total of 3,234 patients from 52 randomized controlled trials were included. HES preparations versus control solutions in blood loss: HES 130 kD vs. albumin (SMD -0.61, 95% CI -0.82, -0.40), HES 200 kD vs. albumin (SMD -0.01, 95% CI -0.29, 0.28), HES 450 kD vs. albumin (SMD 0.47, 95% CI 0.26, 0.68). When comparing control solutions with HES preparations, 50% (HES 450 kD), 40.9% (HES 200 kD), and 18.2% (HES 130 kD) of the comparisons showed more blood/blood products infusion with HES than with control solutions. A numerically lower mortality rate seemed to be related to HES preparations (2.68 vs 4.23%). No difference was found in terms of complications, renal failure, or reoperation. CONCLUSIONS: Perioperative administration of HES preparations is comparatively safe. The data appraising safety profiles of HES preparations are insufficient to make direct comparisons among themselves. As the third generation of HES preparations, HES 130 kD showed a trend toward lower blood loss and transfusion rates and is a suitable choice for cardiovascular surgery.

[Gender-specific differences in relative effects of cardiovascular risk factors among rural population].

OBJECTIVE: To investigate the prevalence and association of cardiovascular disease and its risk factors in Fangshan District, Beijing. METHODS: A total of 7 577 rural residents aged over 40 years were surveyed to estimate the prevalence of cardiovascular disease and its risk factors by questionnaire survey, physical examination and biochemical measures. The prevalence odds ratio (POR) was calculated for the association of stroke / coronary heart disease (CHD) with its risk factors in multiple logistic regression models. RESULTS: Prevalence of CHD, stroke, diabetes, hypertension, dyslipidemia, overweight and obesity was presented as 6.5%, 4.1%, 10.7%, 39.5%, 56.7%, 44.0% and 13.6%, respectively. In the adjusted multiple logistic regression models, hypertension showed stronger association with stroke (POR=2.780, 95%CI: 2.146-3.602), while diabetes had a higher correlation with CHD (POR=2.671, 95%CI: 2.121-3.363). After stratification by gender, significant risk factors for stroke were overweight / obesity (POR=1.652, 95%CI: 1.122-2.433), body mass index (POR=1.048, 95%CI: 1.002- 1.096), systolic blood pressure (POR=1.017, 95%CI: 1.005-1.030) and serum glucose (POR=1.093, 95%CI: 1.048-1.140) in females, whereas dyslipidemia (POR=1.615, 95%CI: 1.124-2.319), total cholesterol (POR=3.932, 95%CI: 1.533-10.086) and high-density lipoprotein cholesterol (POR=0.072, 95%CI: 0.022-0.236) were associated with stroke in males. CONCLUSION: Highly prevalent cardiovascular risk factors aggravated the burden brought by stroke and CHD in the rural population, and the various risk factors for stroke and CHD exhibited heterogeneous contributions among the population with different gender.

The Spatiotemporal Evolution Analysis of Ecosystem Pattern in Wenchuan (Magnitude 8.0) Earthquake Disaster Area, China.

The ecological system is the basis of human survival and global environmental protection. In the process of development, countries will pay close attention to the changing state of the ecosystem. Taking the ecosystem pattern as the research object, a three-layer analysis method was proposed. The transfer matrix and landscape index were used as the first layer to analyze the basic changes. Grey correlation, range-coupling coordination and relative priority were used as the second layer to analyze the reasons of the change. The interval-entropy weight, TOPSIS (Technique for Order Preference by Similarity to an Ideal Solution), was used as the third layer to evaluate the quality of the change. The ten counties in the worst-hit areas of the Wenchuan earthquake were analyzed from different angles, with county region, intensity zone and ecosystem as the objects, and the following results were obtained: (1) Taking Mianzhu City as an example, from 2000 to 2010 and 2018, the conversion ratio of forest, grassland and farmland is 54.24, 59.19, 17.21, 20.06, 37.39 and 52.86%, which were distributed in the north, central and southern parts, respectively. (2) Taking the ninth intensity zone as an example, the forest landscape fragmentation increased, disturbance decreased, and species diversity increased. There is a high influence and restriction relationship between ecosystem and landscape pattern in the total landscape area change. Additionally, the relationship between them tends to develop in a benign way. As of 2018, it is in the change state of moderate imbalance-ecosystem lag. (3) Taking the county ecosystem change as an example, urban type is the best in the counties of ecosystem change, of which Shifang is the best and Pingwu is the worst. The results show that this method can effectively compare and analyze the changes in the multi-regional ecosystem pattern, which has the characteristics of universality and can also be applied to the research of ecosystem pattern change in special regions.

Vitamin a supplements alleviate inflammatory responses in reproductive tracts of male mice infected with pseudorabies virus.

Vitamin A is largely thought to have immune potential for mammal health; however, no conclusive mechanisms exist regarding its role in the pathogen-initiated innate immune response, or in the linkage between the innate and adaptive immune system during sperm formation in the male reproductive tract. Therefore, this study was conducted to evaluate the nutritional protective effect of vitamin A supplementation on reproductive performance and immune function of the male mouse challenged with pseudorabies virus (PRV). Sperm quality, testis toll-like receptors (TLRs) mRNA expression levels, and serum concentration of cytokines and immunoglobulins at 7 or 14 days post-injection were compared between control mice and PRV-challenged mice fed the same diet supplemented with vitamin A at 0, 4000, 10,000, 25,000 and 50,000 IU/kg, respectively. PRV- and phosphate buffered saline (PBS)-injection were performed when the mice in the unsupplemented group were marginally deficient in vitamin A. Sperm quality (sperm density and deformity ratio) of PRV-injected mice was significantly harmed by PRV, but this effect was attenuated by increased vitamin A consumption. Vitamin A supplements also attenuated PRV-challenge-induced increase in testis TLR3, TLR7, and TLR9 mRNA expression and serum pro-inflammatory cytokine (gamma interferon, IFN-gamma; and interleukin 1-beta,IL-1beta) concentration, and decrease in serum anti-inflammatory cytokine (IL-10) concentration. Higher than normal vitamin A consumption was recommended to counteract the deleterious effects of viral invasion, possibly through the downregulated expression of TLRs, and thus to improve immunity and reproductivity of male mice challenged with an invading pathogen.

EP4 activation ameliorates liver ischemia/reperfusion injury via ERK1/2­GSK3ß­dependent MPTP inhibition.

Prostaglandin E receptor subtype 4 (EP4) is widely distributed in the heart, but its role in hepatic ischemia/reperfusion (I/R), particularly in mitochondrial permeability transition pore (MPTP) modulation, is yet to be elucidated. In the present study, an EP4 agonist (CAY10598) was used in a rat model to evaluate the effects of EP4 activation on liver I/R and the mechanisms underlying this. I/R insult upregulated hepatic EP4 expression during early reperfusion. In addition, subcutaneous CAY10598 injection prior to the onset of reperfusion significantly increased hepatocyte cAMP concentrations and decreased serum ALT and AST levels and necrotic and apoptotic cell percentages, after 6 h of reperfusion. Moreover, CAY10598 protected mitochondrial morphology, markedly inhibited mitochondrial permeability transition pore (MPTP) opening and decreased liver reactive oxygen species levels. This occurred via activation of the ERK1/2­GSK3ß pathway rather than the janus kinase (JAK)2­signal transducers and activators of transcription (STAT)3 pathway, and resulted in prevention of mitochondria­associated cell injury. The MPTP opener carboxyatractyloside (CATR) and the ERK1/2 inhibitor PD98059 also partially reversed the protective effects of CAY10598 on the liver and mitochondria. The current findings indicate that EP4 activation induces ERK1/2­GSK3ß signaling and subsequent MPTP inhibition to provide hepatoprotection, and these observations are informative for developing new molecular targets and preventative therapies for I/R in a clinical setting.

[Exploration on the modification of macroscopic classification of colorectal cancer].

OBJECTIVE: To explore the feasibility and clinical significance of a modified macroscopic classification of colorectal cancer. METHODS: The data of 1379 patients with colorectal cancer surgically treated between 1975 and 2003 were retrospectively analyzed. The patients were divided into four groups according to the primary macroscopic appearance: protruding type (group 1), local ulcerative type (group 2), invasive type (group 3) and non-invasive ulcerative type (group 4). The new classification system was simplified into two types: non-invasive type (group A, including group 1 and 2) and invasive type (group B, including group 3 and 4). The histo-differentiation, invasive depth into the intestinal wall, distance and number of lymph node metastasis and 5-year survival rate were analyzed and compared among the groups. RESULTS: There was no significant difference between group 1 and 2, and between group 3 and 4 in histodifferentiation, invasive depth into the intestinal wall, distance and number of lymph node metastasis and 5-year survival rate (P>0.05). However, after modification of the primary macroscopic classification, a significant difference was observed in all the above mentioned parameters between group A and group B (P<0.05). CONCLUSION: Our results demonstrate that the clinicopathological characteristics of the group 1 and 2, and of the group 3 and 4 are similar to each other. So it is reasonable to merge the protruding type and local ulcerative type into non-invasive type, while invasive type and non-invasive ulcerative type into invasive type. This simplified macroscopic classification should be practical and instructive in diagnosis, treatment and prognosis of colorectal cancer.