Mendelian randomization analysis reveals the impact of physical and occupational activities on the risk of gastroesophageal reflux disease and Barrett's esophagus.

BACKGROUND: Recent studies have indicated that participating in physical activity may provide a safeguard against gastroesophageal reflux disease (GERD). Nevertheless, the precise links between physical and occupational activity and the occurrence of GERD and Barrett's esophagus (BE) are still uncertain. METHODS: Conducting univariate and multivariate Mendelian randomization investigations to examine the causal relationship between exposures and outcomes. Genetic variation simulation was used in randomized experiments. Data on physical and occupational activity were obtained from the UK Biobank and GWAS catalog. In the meantime, data on GERD and BE were extracted from a high quality meta-analysis. RESULTS: The results of univariate Mendelian randomization analysis using multiple methods suggest a causal relationship between strenuous sports or other forms of exercise (as a protective factor) and GERD/BE. At the same time, three types of occupational related physical activities, including heavy manual or physical work, shift work and walking or standing work, are risk factors for GERD/BE and have a causal relationship with them. These results were reconfirmed through multivariate Mendelian randomization analysis, which excluding the influence of other potential confounding factors. CONCLUSIONS: The findings indicated that strenuous sports or other forms of exercise could lower the likelihood of GERD/BE, while excessive physical strain in the workplace, prolonged periods of standing or walking, and shift work could raise the risk of GERD/BE. Acknowledging this risk and implementing suitable measures can contribute to the prevention of GERD and BE, thus mitigating the associated health burden.

Nurse-led sequential multiple assignment randomized trial of nudging intervention for early antiretroviral therapy initiation among patients with HIV/AIDS: Implementation study protocol.

AIMS: In China, more than 30% of patients have not initiated treatment within 30 days of HIV diagnosis. Delayed initiation has a detrimental influence on disease outcomes and increases HIV transmission. The study aims to evaluate the effectiveness of a nurse-led antiretroviral therapy initiation nudging intervention for people newly diagnosed with HIV in China to find the optimal intervention implementation strategy. METHODS: A Hybrid Type II sequential multiple assignment randomized trial will be conducted at four Centers for Disease Control and Prevention in Hunan, China. This study will recruit 447 people newly diagnosed with HIV aged ≥18 years and randomly assign them into two intervention groups and one control group. On top of the regular counselling services and referrals, intervention groups will receive a 4-week, 2-phase intervention based on the dual-system theory and the nudge theory. The control group will follow the currently recommended referral procedures. The primary outcomes are whether treatment is initiated, as well as the length of time it takes. The study outcomes will be measured at the baseline, day 15, day 30, week 12, week 24 and week 48. Generalized estimating equations and survival analysis will be used to compare effectiveness and explore factors associated with antiretroviral therapy initiation. Both qualitative and quantitative information will be collected to assess implementation outcomes. DISCUSSION: Existing strategies mostly target institutional-level factors, with little consideration given to patients' decision-making. To close this gap, we aim to develop an effective theory-driven nudging strategy to improve early ART initiation. IMPACT: This nurse-led study will help to prevent delayed initiation by employing implementation science strategies for people newly diagnosed with HIV. This study contributes to the United Nations' objective of ending the AIDS pandemic by 2030. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300070140. The trial was prospectively registered before the first participant was recruited. PATIENT AND PUBLIC INVOLVEMENT: The nudging intervention was finalized through the Nominal Group Technique where we invited five experts in the related field and five people living with HIV to participate.

Effects of comprehensive nursing interventions on wound pain in patients undergoing catheter insertion for peritoneal dialysis.

This study investigates the effects of comprehensive nursing interventions on wound pain in patients undergoing catheter insertion for peritoneal dialysis. Sixty patients who underwent catheter insertion for peritoneal dialysis from January 2021 to January 2023 at our hospital were selected as subjects and randomly divided into an experimental group and a control group using a random number table method. The control group received routine nursing care, while the experimental group was subjected to comprehensive nursing interventions. The study compared the impact of nursing measures on visual analogue scale (VAS), self-rating anxiety scale (SAS), self-rating depression scale (SDS) and nursing satisfaction between the two groups. The analysis revealed that on the third, fifth and seventh days post-intervention, the experimental group's wound VAS scores were significantly lower than those of the control group (p < 0.001). Furthermore, levels of anxiety and depression were markedly lower in the experimental group compared with the control group (p < 0.001). In addition, the nursing satisfaction rate was significantly higher in the experimental group than in the control group (96.67% vs. 73.33%, p = 0.011). This study indicates that the application of comprehensive nursing interventions in patients undergoing catheter insertion for peritoneal dialysis is highly effective. It can alleviate wound pain and negative emotions to a certain extent, while also achieving high patient satisfaction, thus demonstrating significant clinical value.

Narirutin exerts anti-inflammatory activity by inhibiting NLRP3 inflammasome activation in macrophages.

Citrus peel has long been used in traditional medicine in Asia to treat common cold, dyspepsia, cough, and phlegm. Narirutin-a flavanone-7-O-glycoside-is the major flavonoid in citrus peel, and has anti-oxidative, anti-allergic, and anti-inflammatory activities. However, the anti-inflammatory mechanism of narirutin has not been fully elucidated. This study is aimed to investigate the effects of narirutin on the Nod-like receptor protein 3 (NLRP3)-mediated inflammatory response in vitro and in vivo, and determine the underlying mechanism. THP-1 differentiated macrophages and bone marrow-derived macrophages (BMDMs) were used for in vitro experiments, while dextran sulfate sodium (DSS)-induced colitis and alum-induced peritonitis mouse models were constructed to test inflammation in vivo. Narirutin suppressed secretion of interleukin (IL)-1ß and pyroptosis in lipopolysaccharide (LPS)/ATP-stimulated macrophages. Narirutin decreased the expression of NLRP3 and IL-1ß in the LPS-priming step through inhibition of NF-κB, MAPK and PI3K /AKT signaling pathways. Narirutin inhibited NLRP3-ASC interaction to suppress NLRP3 inflammasome assembly. Furthermore, oral administration of narirutin (300 mg/kg) alleviated inflammation symptoms in mice with peritonitis and colitis. These results suggest that narirutin exerts its anti-inflammatory activity by suppressing NLRP3 inflammasome activation via inhibition of the NLRP3 inflammasome priming processes and NLRP3-ASC interaction in macrophages.

A preoperative prediction model based on Lymphocyte-C-reactive protein ratio predicts postoperative anastomotic leakage in patients with colorectal carcinoma: a retrospective study.

BACKGROUND & AIMS: Lymphocyte-C-reactive Protein Ratio (LCR) has been demonstrated as a promising new marker for predicting surgical and oncological outcomes in colorectal carcinoma (CRC). However, anastomotic leakage (AL) is also likely related to this inflammatory marker. Herein, we aimed to identify preoperative predictors of AL and build and develop a novel model able to identify patients at risk of developing AL. METHODS: We collected 858 patients with CRC undergoing elective radical operation between 2007 and 2018 at a single center were retrospectively reviewed. We performed univariable and multivariable analyses and built a multivariable model that predicts AL based on preoperative factors. Propensity adjustment was used to correct the bias introduced by non-random matching of the LCR. The model's performance was evaluated by using the area under the receiver operator characteristic curves (AUROCs), decision curve analysis (DCA), Brier scores, D statistics, and R2 values. RESULTS: Age, nutrition risk screening 2002 (NRS2002) score, tumor location and LCR, together with hemoglobin < 90 g/l, were independent predictors of AL. The models built on these variables showed good performance (internal validation: c-statistic = 0.851 (95%CI 0.803-0.965), Brier score = 0.049; temporal validation: c-statistic = 0.777 (95%CI 0.823-0.979), Brier score = 0.096). A regression equation to predict the AL was also established by multiple linear regression analysis: [Age(≥ 60 year) × 1.281] + [NRS2002(≥ 3) × 1.341] + [Tumor location(pt.) × 1.348]-[LCR(≤ 6000) × 1.593]-[Hemoglobin(< 90 g/L) × 1.589]-6.12. CONCLUSION: Preoperative LCR is an independent predictive factor for AL. A novel model combining LCR values, age, tumor location, and NRS2002 provided an excellent preoperative prediction of AL in patients with CRC. The nomogram can help clinical decision-making and support future research.

Usnic acid suppresses cervical cancer cell proliferation by inhibiting PD-L1 expression and enhancing T-lymphocyte tumor-killing activity.

The programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway is abnormally expressed in cervical cancer cells. Moreover, PD-1/PD-L1 blockade reduces the apoptosis and exhaustion of T cells and inhibits the development of malignant tumors. Usnic acid is a dibenzofuran compound originating from Usnea diffracta Vain and has anti-inflammatory, antifungal, and anticancer activities. However, the molecular mechanism of its antitumor effects has not been fully elucidated. In this work, we first observed that usnic acid decreased the expression of PD-L1 in HeLa cells and enhanced the cytotoxicity of co-cultured T cells toward tumor cells. Usnic acid inhibited PD-L1 protein synthesis by reducing STAT3 and RAS pathways cooperatively. It was subsequently shown that usnic acid induced MiT/TFE nuclear translocation through the suppression of mTOR signaling pathways, and promoted the biogenesis of lysosomes and the translocation of PD-L1 to the lysosomes for proteolysis. Furthermore, usnic acid inhibited cell proliferation, angiogenesis, migration, and invasion, respectively, by downregulating PD-L1, thereby inhibiting tumor growth. Taken together, our results show that usnic acid is an effective inhibitor of PD-L1 and our study provide novel insights into the mechanism of its anticancer targeted therapy.

Panaxadiol inhibits programmed cell death-ligand 1 expression and tumour proliferation via hypoxia-inducible factor (HIF)-1α and STAT3 in human colon cancer cells.

Panaxadiol is a triterpenoid sapogenin monomeric compound found in the roots of Panax ginseng and has a variety of biological activities such as neuroprotective and anti-tumour functions. However, the mechanisms how panaxadiol exerts the anticancer effects remain unknown. The current study aimed to investigate the potential activity of panaxadiol on programmed cell death-ligand 1 (PD-L1) expression and tumour proliferation in human colon cancer cells and to identify the underlying mechanism. Results showed that panaxadiol showed little cytotoxicity as assessed by a cytotoxicity assay and significantly inhibited PD-L1 expression at the protein and mRNA level in a dose-dependent manner. Furthermore, panaxadiol supressed the hypoxia-induced synthesis of hypoxia-inducible factor (HIF)-1α via the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways without affecting HIF-1α degradation. Simultaneously, panaxadiol inhibited STAT3 activation through the JAK1, JAK2, and Src pathways. Moreover, pre-treatment with panaxadiol enhanced the activity of cytotoxic T lymphocytes (CTL) and regained their capacity of tumour cell killing in a T cell and tumour cell co-culture system. Immunoprecipitation showed that panaxadiol inhibited PD-L1 expression by blocking the interaction between HIF-1α and STAT3. The inhibitory effect of panaxadiol on tumour proliferation was further demonstrated by colony formation and EdU labelling assays. The anti-proliferative effect of panaxadiol was also proved by a xenograft assay in vivo. Taken together, the current work highlights the anti-tumour effect of panaxadiol, providing insights into development of cancer therapeutic through PD-L1 inhibition.

Comparative study of micro-transplantation from HLA fully mismatched unrelated and partly matched related donors in acute myeloid leukemia.

Micro-transplantation (MST) by chemotherapy, combined with granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (GPBSC) infusion, from an HLA partial matched related donor has shown some encouraging effective therapy for acute myeloid leukemia (AML). However, the outcome of human leukocyte antigen (HLA) fully mismatched unrelated donor-derived MST in such patients is still unknown. In the present study, we compared the efficacy of HLA fully mismatched unrelated donor-derived MST, and partly matched related donor-derived MST, in AML of 126 patients from two centers in China, These patients, aged 16 to 65 years, were given three or four courses of MST, which consisted of a high dosage cytarabine followed by GPBSC from unrelated donor or related donor. There was a statistically significant difference in 3-year leukemia-free survival (LFS) and 3-year overall survival (OS) between the unrelated and the related group. The non-treatment-related mortality (NRM) rates of patients, and other adverse complications, were no different in the two groups. In conclusion, unrelated donor-derived MST is believed to be a safe treatment, with efficacy similar to or higher than related donor-derived MST. This result provides support for the potential of MST for expanding the donor selection. However, the specific mechanism of action needs further study.

Reassessing water slippage in hydrophobic nanostructures.

Reported data of measured slip lengths in nanostructures span several orders of magnitude, from a few nanometers to tens of micrometers. Small roughness on surfaces caused by structural defects or thermal fluctuations dramatically reduces slippage. Tiny bubbles entrapped on rough surfaces can also affect slippage. We used an asymptotic solution and a high density-ratio pseudopotential lattice Boltzmann model to systematically study the drag resistance of a rough surface with attached bubbles. As bubbles nucleate and grow, drag resistance is slightly reduced until the tri-phase contact line reaches the edges of roughness, where bubbles with small angles substantially reduce drag resistance. As bubbles grow to become a continuous gas layer on the surface, the drag resistance greatly decreases. However, the interface deformation from flat to curved shape greatly hinders liquid flow, and the vortex structures cause a wave-like fluctuation in the effective slip length. This finding sheds light on the controversies of reported large variations in the slip length of super-hydrophobic surfaces in nanostructures, e.g., carbon nanotubes.

Inulin-type fructans supplementation improves glycemic control for the prediabetes and type 2 diabetes populations: results from a GRADE-assessed systematic review and dose-response meta-analysis of 33 randomized controlled trials.

BACKGROUND: Currently, many clinical trials have shown that inulin-type fructans (ITF) supplementation is associated with glycemic control; nevertheless, the results are inconclusive. The aim of this meta-analysis of randomized controlled trials was to assess the effects of ITF supplementation on glycemic control. METHODS: PubMed, EMBASE and the Cochrane Library were searched for eligible articles up to March 6, 2019. A random-effects model was used to analyze the pooled results, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was applied to assess the quality of evidence. The dose-response model was used to recommend the daily dose and duration for ITF supplementation. RESULTS: Thirty-three trials involving 1346 participants were included. Overall, ITF supplementation could significantly reduce concentrations of fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS) and homeostasis model assessment-insulin resistance (HOMA-IR). In the prediabetes and type 2 diabetes (T2DM) population, a more significant reduction in FBG [weighted mean difference (WMD): - 0.60 mmol/l; 95% CI - 0.71, - 0.48 mmol/l; high rate], HbA1c (WMD: - 0.58%; 95% CI - 0.83, - 0.32%; high rate), FINS (WMD: - 1.75 µU/ml; 95% CI - 2.87, - 0.63 µU/ml; low rate), and HOMA-IR (WMD: - 0.69; 95% CI - 1.10, - 0.28; low rate) were observed, and ITF supplementation with a daily dose of 10 g for a duration of 6 weeks and longer was recommended. Moreover, subgroup analyses suggested that the effects of glycemic control were significantly influenced by the sex of the subjects and the type and the method of intake of ITF. CONCLUSIONS: Our analyses confirmed that these four main glycemic indicators were significantly reduced by ITF supplementation, particularly in the prediabetes and T2DM population. Evidence supports that reasonable administration of ITF supplementation may have potential clinical value as an adjuvant therapy for prediabetes and T2DM management. Trial registration The trial was registered at PROSPERO as CRD42018115875 on November 23, 2018.

Convallatoxin protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB signaling through activation of PPARγ.

Convallatoxin (CNT) is a cardiac glycoside isolated from Adonis amurensis Regel et Radde and has both anti-inflammatory and anti-proliferative properties. In the present study, the anti-inflammatory mechanisms of action of CNT was investigated in vitro and in vivo. Stimulation of mouse macrophages with lipopolysaccharide induced secretion of proinflammatory cytokines via suppression of peroxisome proliferator-activated receptor gamma (PPARγ) and activation of nuclear factor-κB (NF-κB), two transcription factors implicated in many inflammatory diseases. Notably, the effects of lipopolysaccharide were reversed by concomitant treatment of macrophages with CNT. Knockdown of PPARγ by siRNA inhibited the effect of convallatoxin on NF-κB activation. Because these transcription factors play a role in the development of ulcerative colitis in humans, the mice with experimental colitis induced by dextran sodium sulfate (DSS) was employed. Indeed, concomitant treatment with CNT ameliorated DSS-induced colitis symptoms, tissue damage, inflammatory cell infiltration, and proinflammatory cytokine production in the colon, and also reversed the activation of NF-κB and suppression of PPARγ. Collectively, these data indicate that CNT ameliorates colitic inflammation via activation of PPARγ and suppression of NF-κB, and suggest that CNT may be a promising treatment for inflammatory bowel disease (IBD).

Association of insulin, C-peptide and blood lipid patterns in patients with impaired glucose regulation.

BACKGROUND: To investigate any associations between blood glucose (BG) and lipid levels in patients with different glucose tolerance statuses, including type 2 diabetes (T2DM) and impaired glucose regulation (IGR) cases as well as normal glucose tolerance (NGT) individuals. METHODS: A total of 354 participants were recruited to this study including 174 in the T2DM group, 112 in the IGR group and 68 in the NGT group. We compared BG, insulin and C-peptide (CP), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) serum levels during a 3 h oral glucose tolerance test (OGTT) in the 3 groups. RESULTS: Basic overall HbA1c serum concentration percentages were 5.52, 6.33 and 9.76% for the NTG, IGR and T2DM cases. During the OGTT, insulin secretion in the IGR group was almost double that of the T2DM group. CP levels were highest in the IGR patients and OGTT related BG concentrations were highest in the T2DM group followed by IGR, but in the IGR group hyperglycemia was less pronounced than in T2DM patients (P <  0.001). Compared to the NGT group, TC, TG and LDL-C serum concentrations were significantly higher (P ≤ 0.001) and HDL-C concentrations were significantly lower (P ≤ 0.001) in IGR and T2DM cases compared to the NTG group. CONCLUSIONS: IGR led to similar unfavorable blood lipid patterns compared with T2DM patients and an imbalance of insulin and CP serum concentrations during an OGTT.

Fraxinellone has anticancer activity in vivo by inhibiting programmed cell death-ligand 1 expression by reducing hypoxia-inducible factor-1α and STAT3.

Dictamnus dasycarpus is a traditional Chinese medicine thathas been commonly used in the treatment of cancer. Fraxinellone is a natural product isolated from the D. dasycarpus plant, which has been shown to exhibit neuroprotective and anti-inflammatory activities. However, whether fraxinellone exerts anticancer effects and the mechanisms by which it may inhibit tumor growth remain unknown. Here, we found that fraxinellone, in a dose-dependented manner, inhibited the expression of programmed cell death ligand-1 (PD-L1), which plays a pivotal role in tumorigenesis. It was subsequently shown that fraxinellone reduced HIF-1α protein synthesis via the mTOR/p70S6K/eIF4E and MAPK pathways. It also inhibited activation of STAT3 via the JAK1, JAK2, and Src pathways. Immunoprecipitation and western blotting assays showed that fraxinellone inhibited PD-L1 expression by reducing STAT3 and HIF-1α cooperatively. Flow cytometry, colony formation, and EdU incorporation assays demonstrated that fraxinellone inhibited cell proliferation through suppression of PD-L1. Tube formation, migration, and invasion assays showed that fraxinellone inhibits angiogenesis by suppressing PD-L1. In vivo studies further supported anticancer role for fraxinellone, demonstrating that fraxinellone treatment inhibited the growth of tumor xenografts. We concluded that fraxinellone inhibits PD-L1 expression by downregulating the STAT3 and HIF-1α signaling pathways, subsequently inhibiting proliferation and angiogenesis in cancer cells. These studies reveal previously unknown characteristics of fraxinellone and provide new perspectives into the mechanism of cancer inhibition of the compound.

Traditional manual acupuncture combined with rehabilitation therapy for shoulder hand syndrome after stroke within the Chinese healthcare system: a systematic review and meta-analysis.

OBJECTIVE: To investigate the effectiveness of traditional manual acupuncture combined with rehabilitation therapy versus rehabilitation therapy alone for shoulder hand syndrome after stroke. DATA SOURCES: PubMed, EMBASE, the Cochrane Library, Chinese Biomedicine Database, China National Knowledge Infrastructure, VIP Information Database, Wan Fang Database and reference lists of the eligible studies were searched up to July 2017 for relevant studies. METHODS: Randomized controlled trials that compared the combined effects of traditional manual acupuncture and rehabilitation therapy to rehabilitation therapy alone for shoulder hand syndrome after stroke were included. Two reviewers independently screened the searched records, extracted the data and assessed risk of bias of the included studies. The treatment effect sizes were pooled in a meta-analysis using RevMan 5.3 software. RESULTS: A total of 20 studies involving 1918 participants were included in this study. Compared to rehabilitation therapy alone, the combined therapy significantly reduced pain on the visual analogue scale and improved limb movement on the Fugl-Meyer Assessment scale and the performance of activities of daily living (ADL) on the Barthel Index scale or Modified Barthel Index scale. Of these, the visual analogue scale score changes were significantly higher (mean difference = 1.49, 95% confidence interval = 1.15-1.82, P < 0.00001) favoring the combined therapy after treatment, with severe heterogeneity ( I2 = 71%, P = 0.0005). CONCLUSION: Current evidence suggests that traditional manual acupuncture integrated with rehabilitation therapy is more effective in alleviating pain, improving limb movement and ADL. However, considering the relatively low quality of available evidence, further rigorously designed and large-scale randomized controlled trials are needed to confirm the results.

Chelidonine inhibits TNF-α-induced inflammation by suppressing the NF-κB pathways in HCT116 cells.

Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a complex that regulates several hundreds of genes, including those involved in immunity and inflammation, survival, proliferation, and the negative feedback of NF-κB signaling. Chelidonine, a major bioactive, isoquinoline alkaloid ingredient in Chelidonium majus, exhibits antiinflammatory pharmacological properties. However, its antiinflammatory molecular mechanisms remain unclear. In this work, we explored the effect of chelidonine on TNF-induced NF-κB activation in HCT116 cells. We found chelidonine inhibited the phosphorylation and degradation of the inhibitor of NF-κB alpha and nuclear translocation of RELA. Furthermore, by inhibiting the activation of NF-κB, chelidonine downregulated target genes involved in inflammation, proliferation, and apoptosis. Chelidonine also inhibited mitogen-activated protein kinase pathway activation by blocking c-Jun N-terminal kinase and p38 phosphorylation. These results suggest that chelidonine may be a potential therapeutic agent against inflammatory diseases in which inhibition of NF-κB activity plays an important role.

The long-term outcome of reduced-intensity allogeneic stem cell transplantation from a matched related or unrelated donor, or haploidentical family donor in patients with leukemia: a retrospective analysis of data from the China RIC Cooperative Group.

This study compared 6-year follow-up data from patients undergoing reduced-intensity conditioning (RIC) transplantation with an HLA-matched related donor (MRD), an HLA-matched unrelated donor (MUD), or an HLA-haploidentical donor (HID) for leukemia. Four hundred and twenty-seven patients from the China RIC Cooperative Group were enrolled, including 301 in the MRD, 79 in the HID, and 47 in the MUD groups. The conditioning regimen involved fludarabine combined with anti-lymphocyte globulin and cyclophosphamide. Graft-versus-host disease (GVHD) prophylaxis was administered using cyclosporin A (CsA) and mycophenolate mofetil (MMF). Four hundred and nineteen patients achieved stable donor chimerism. The incidence of stage II-IV acute GVHD in the HID group was 44.3 %, significantly higher than that in the MRD (23.6 %) and MUD (19.1 %) groups. The 1-year transplantation-related mortality (TRM) rates were 44.3, 17.6, and 21.3, respectively. Event-free survival (EFS) at 6 years in the HID group was 36.7 %, significantly lower than that of the MRD and MUD groups (59.1 and 66.0 %, P < 0.001 and P = 0.001, respectively). For advanced leukemia, the relapse rate of the HID group was 18.5 %, lower than that of the MRD group (37.5 %, P = 0.05), but the EFS at 6 years was 31.7 and 30.4 % (P > 0.05), respectively. RIC transplantation with MRD and MUD had similar outcome in leukemia which is better than that with HID. RIC transplantation with HID had lower relapsed with higher TRM and GVHD rate, particularly in advanced leukemias. RIC transplantation with MRD and MUD had similar outcomes in leukemia and they were better than those with HID. RIC transplantation with HID had a lower relapse rate but higher TRM and GVHD rates, particularly in cases of advanced leukemia.

Determination of the Main Nucleosides and Nucleobases in Natural and Cultured Ophiocordyceps xuefengensis.

Ophiocordyceps xuefengensis, a recently described species of Ophiocordycepsthat is associated with the larvae of Phassusnodus (Hepialidae) in the living root or trunk of the medicinal plant Clerodendrumcyrtophyllum, isthe largest known Cordycepsspecies and is recognized as a desirable alternative for natural Ophiocordycepssinensis. This study investigated the main nucleosides and nucleobases in natural and cultured Ophiocordycepsxuefengensis. The contents of the nucleosides and nucleobases in the natural and cultured samples were determined by reverse phase HPLC. The highest concentration of adenosine was found in the natural fruit body and the cultured stroma, with almost no adenosine in the cadaver of Phassusnodus. The contents of adenine, guanosine, uridine and uracil in the cultured mycelium were significantly higher than those in the natural sample. Inosine was only detected in the natural samples. Thymidine and 2-deoxyadenosine were only found in the cadaver of Phassusnodus. Cordycepin was not detected in the five samples examined. These results suggested that the cultured mycelium and cultured stroma of Ophiocordycepsxuefengensis might be a promising substitute for natural O. xuefengensis.

Microwave exposure impairs synaptic plasticity in the rat hippocampus and PC12 cells through over-activation of the NMDA receptor signaling pathway.

OBJECTIVE: The aim of this study is to investigate whether microwave exposure would affect the N-methyl-D-aspartate receptor (NMDAR) signaling pathway to establish whether this plays a role in synaptic plasticity impairment. METHODS: 48 male Wistar rats were exposed to 30 mW/cm2 microwave for 10 min every other day for three times. Hippocampal structure was observed through H&E staining and transmission electron microscope. PC12 cells were exposed to 30 mW/cm2 microwave for 5 min and the synapse morphology was visualized with scanning electron microscope and atomic force microscope. The release of amino acid neurotransmitters and calcium influx were detected. The expressions of several key NMDAR signaling molecules were evaluated. RESULTS: Microwave exposure caused injury in rat hippocampal structure and PC12 cells, especially the structure and quantity of synapses. The ratio of glutamic acid and gamma-aminobutyric acid neurotransmitters was increased and the intracellular calcium level was elevated in PC12 cells. A significant change in NMDAR subunits (NR1, NR2A, and NR2B) and related signaling molecules (Ca2+/calmodulin-dependent kinase II gamma and phosphorylated cAMP-response element binding protein) were examined. CONCLUSION: 30 mW/cm2 microwave exposure resulted in alterations of synaptic structure, amino acid neurotransmitter release and calcium influx. NMDAR signaling molecules were closely associated with impaired synaptic plasticity.

Associations between endothelial nitric oxide synthase polymorphisms and risk of diabetic nephropathy: an updated meta-analysis.

BACKGROUND: Genetic polymorphism of endothelial nitric oxide synthase (eNOS) has been implicated in the risk of diabetic nephropathy (DN), but the published findings were inconsistent. We performed a comprehensive meta-analysis to derive a more precise estimation of the association between genetic polymorphisms of eNOS and the risk of DN. METHODS: Six online database were researched on the associations between polymorphisms of eNOS (T786C, G894T, 4b/4a) and DN risk. PRISMA statement and Hardy-Weinberg equilibrium assessment were used in this report. Odds ratio and 95% confidence interval were estimated based on the following genetic contrast/models: allelic model, dominant model, recessive model and co-dominant model. The publication bias and sensitivity analysis were also performed to guarantee the statistical power. RESULTS: A total of 49 case-control studies with 11,990/9754/5131 participants for DN/DM/HC group were eligible for meta-analysis (7/25/31 studies for T786C/G984T/4b/a). For the eNOS-T786C, C allele showed a weak association between C allele and DN risk in DN/T2DM group. For eNOS-G894T, there was an association between T allele and DN risk in the global, Asian and African population in DN/T2DM group. For the eNOS-4b/4a, 4a allele was found contributing significantly to increased DN risk in the global population. CONCLUSION: Our comprehensive meta-analysis suggests that three polymorphisms of eNOS may be the increased risk factors of DN development, especially in Asian population and T2DM group.