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1.
World J Gastroenterol ; 26(19): 2403-2415, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32476801

RESUMO

BACKGROUND: Different types of periampullary diverticulum (PAD) may differentially affect the success of endoscopic retrograde cholangiopancreatography (ERCP) cannulation, but the clinical significance of the two current PAD classifications for cannulation is limited. AIM: To verify the clinical value of our newly proposed PAD classification. METHODS: A new PAD classification (Li-Tanaka classification) was proposed at our center. All PAD patients with native papillae who underwent ERCP from January 2012 to December 2017 were classified according to three classification systems, and the effects of various types of PAD on ERCP cannulation were compared. RESULTS: A total of 3564 patients with native papillae were enrolled, including 967 (27.13%) PAD patients and 2597 (72.87%) non-PAD patients. In the Li-Tanaka classification, type I PAD patients exhibited the highest difficult cannulation rate (23.1%, P = 0.01), and type II and IV patients had the highest cannulation success rates (99.4% in type II and 99.3% in type IV, P < 0.001). In a multivariable-adjusted logistic model, the overall successful cannulation rate in PAD patients was higher than that in non-PAD patients [odds ratio (OR) = 1.87, 95% confidence interval (CI): 1.04-3037, P = 0.037]. In addition, compared to the non-PAD group, the difficulty of cannulation in the type I PAD group according to the Li-Tanaka classification was greater (OR = 2.04, 95%CI: 1.13-3.68, P = 0.004), and the successful cannulation rate was lower (OR = 0.27, 95%CI: 0.11-0.66, P < 0.001), while it was higher in the type II PAD group (OR = 4.44, 95%CI: 1.61-12.29, P < 0.01). CONCLUSION: Among the three PAD classifications, the Li-Tanaka classification has an obvious clinical advantage for ERCP cannulation, and it is helpful for evaluating potentially difficult and successful cannulation cases among different types of PAD patients.

2.
ChemSusChem ; 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32369677

RESUMO

Capturing CO 2  from post-combustion gas streams is an energy-intensive process that is required prior to either converting or sequestering CO 2 . There are a few commercial offerings aqueous amine technologies, however the cost of capturing CO 2 with these technologies remains high. To decrease costs, researchers are designing efficient drop-in replacements using aqueous amine infrastructure. Water-lean solvents are a part of an approach that aims to increase efficiency by reducing the water content in solution. Water-lean solvents such as GE's GAP/TEG are promising technologies, with potential to halve the parasitic load to a coal-fired power plant, only if high solution viscosities and hydrolysis of the siloxane moieties could be mitigated. We present here, an integrated multidisciplinary approach to overhaul the GAP/TEG solvent at the molecular level to mitigate hydrolysis and reduce viscosity. Molecular-level insights into chemical speciation of CO 2 -containing ions, show that co-solvents and diluents have a negligible effect on reducing viscosity and are not needed. This finding allowed for the design of single-component siloxane-free diamines with site-specific chemical moieties for direct placement and orientation of hydrogen bonding to reduce viscosity. Ultimately, we present new single-component diamine formulations less susceptible to hydrolysis that exhibit up to a 98% reduction in viscosity compared to the initial GAP/TEG formulation.

3.
Eur J Neurol ; 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32441879

RESUMO

With great interest, we read the article by Costello M et al. entitled "Effect of non-vitamin-K oral anticoagulants on stroke severity compared to warfarin: a meta-analysis of randomized controlled trials." published in the March 2020 issue of European Journal of Neurology 1 . The study is of profound academic importance, and there are some points we would like to address. In the section "Statistical Analysis", the authors stated that I2 values were calculated for each analysis to examine study heterogeneity. Consequently, I2 regarding the pooled data of Fatal or Disabling Stroke in the section "Results", was 51% and P for heterogeneity was 0.06 (as shown in its forest plot).

4.
Br J Anaesth ; 124(6): 670-675, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32234250

RESUMO

BACKGROUND: The safety of performing spinal anaesthesia for both patients and anaesthetists alike in the presence of active infection with the novel coronavirus disease 2019 (COVID-19) is unclear. Here, we report the clinical characteristics and outcomes for both patients with COVID-19 and the anaesthetists who provided their spinal anaesthesia. METHODS: Forty-nine patients with radiologically confirmed COVID-19 for Caesarean section or lower-limb surgery undergoing spinal anaesthesia in Zhongnan Hospital, Wuhan, China participated in this retrospective study. Clinical characteristics and perioperative outcomes were recorded. For anaesthesiologists exposed to patients with COVID-19 by providing spinal anaesthesia, the level of personal protective equipment (PPE) used, clinical outcomes (pulmonary CT scans), and confirmed COVID-19 transmission rates (polymerase chain reaction [PCR]) were reviewed. RESULTS: Forty-nine patients with COVID-19 requiring supplementary oxygen before surgery had spinal anaesthesia (ropivacaine 0.75%), chiefly for Caesarean section (45/49 [91%]). Spinal anaesthesia was not associated with cardiorespiratory compromise intraoperatively. No patients subsequently developed severe pneumonia. Of 44 anaesthetists, 37 (84.1%) provided spinal anaesthesia using Level 3 PPE. Coronavirus disease 2019 infection was subsequently confirmed by PCR in 5/44 (11.4%) anaesthetists. One (2.7%) of 37 anaesthetists who wore Level 3 PPE developed PCR-confirmed COVID-19 compared with 4/7 (57.1%) anaesthetists who had Level 1 protection in the operating theatre (relative risk reduction: 95.3% [95% confidence intervals: 63.7-99.4]; P<0.01). CONCLUSIONS: Spinal anaesthesia was delivered safely in patients with active COVID-19 infection, the majority of whom had Caesarean sections. Level 3 PPE appears to reduce the risk of transmission to anaesthetists who are exposed to mildly symptomatic surgical patients.


Assuntos
Raquianestesia/efeitos adversos , Raquianestesia/métodos , Anestesistas , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/transmissão , Pneumonia Viral/transmissão , Adulto , Anestesiologistas , China , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/etiologia , Feminino , Humanos , Masculino , Pandemias , Equipamento de Proteção Individual , Pneumonia Viral/diagnóstico , Pneumonia Viral/etiologia , Estudos Retrospectivos , Risco
5.
Life Sci ; 252: 117642, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32259600

RESUMO

AIMS: To determine whether ginsenoside Rg1 is involved in scratch wound healing through altered expression of related molecules in astrocytes and improved functional recovery after spinal cord injury (SCI). MATERIALS AND METHODS: Astrocytes were isolated from rats, followed by Rg1 treatment. The wound healing test was performed to observe the scratch wound healing in different groups. The expression of nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), basic fibroblast growth factor (bFGF), and components of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway were detected by western blot. Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the altered expression of laminin (LN) and fibronectin (FN). A revised Allen's method for the SCI model was performed, followed by Rg1 treatment. Then, functional scoring was conducted to evaluate the functional recovery. Hematoxylin-eosin (HE) staining showed changes in the void area. Finally, western blot assessed the expression of glial fibrillary acidic protein (GFAP) and chondroitin sulfate proteoglycans (CSPGs). KEY FINDINGS: Rg1 mediated scratch wound healing through inducing an increased release of LN, FN, NGF, GDNF, and bFGF in vitro. Additionally, Rg1 activated the PI3K/Akt signaling pathway and promoted the functional recovery of hindlimb movement in rats. Furthermore, Rg1 significantly reduced the void area and downregulated the expression of GFAP and CSPGs. SIGNIFICANCE: Rg1 not only enhanced the scratch wound repair in vitro through the release of astroglial neurotrophic factors, adhesion factors, and inhibitory factors, but it also improved the functional recovery in vivo following SCI.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32297118

RESUMO

To examine the status and risk of heavy metal pollution in an urban wetland in China, the distribution and speciation of chromium (Cr) and other metals (Cd, Cu, Pb, and Zn) were examined. We investigated the impact of three major land uses (residential and industrial (RI), orange plantation (OP), and mixed OP and RI (OPRI)) on the heavy metal characteristics using sediment cores (0-60 cm below water/sediment interface) collected in Sanyang Wetland, China. It was found that all the metals (Cr, Cd, Cu, Pb, and Zn) had lower concentrations in the top layers but higher contents in the bottom layers of sediments. Species of metals in sediments were dominated by their secondary phase (i.e., exchangeable and carbonate bound, Fe-Mn bound and organic bound) with relatively low contents of primary phase (i.e., residual form), except for Cr in RI affected river sediments that had a relatively high content of primary phase (20.97-36.07%). The ratio of secondary phase to primary phase (RSP) and risk assessment code (RAC) methods were applied to assess environmental risk. The results implied that the metal mobility and bioavailability could significantly cause urban wetland environmental quality decline, and thus enhanced strategies should be required to target the capture and removal of metals.

7.
Oxid Med Cell Longev ; 2020: 1645249, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32256945

RESUMO

Oxidative stress and subsequent cardiac myocyte apoptosis play central roles in the initiation and progression of myocardial ischemia-reperfusion (I/R) injury. Homeobox transcript antisense intergenic RNA (Hotair) was previously implicated in various heart diseases, yet its role in myocardial I/R injury has not been clearly demonstrated. Mice with cardiac-restricted knockdown or overexpression of Hotair were exposed to I/R surgery. H9c2 cells were cultured and subjected to hypoxia/reoxygenation (H/R) stimulation to further verify the role and underlying mechanisms of Hotair in vitro. Histological examination, molecular detection, and functional parameters were determined in vivo and in vitro. In response to I/R or H/R treatment, Hotair expression was increased in a bromodomain-containing protein 4-dependent manner. Cardiac-restricted knockdown of Hotair exacerbated, whereas Hotair overexpression prevented I/R-induced oxidative stress, cardiac myocyte apoptosis, and cardiac dysfunction. Mechanistically, we observed that Hotair exerted its beneficial effects via activating AMP-activated protein kinase alpha (AMPKα). Further detection revealed that Hotair activated AMPKα through regulating the enhancer of zeste homolog 2/microRNA-451/calcium-binding protein 39 (EZH2/miR-451/Cab39) axis. We provide the evidence that endogenous lncRNA Hotair is an essential negative regulator for oxidative stress and cardiac myocyte apoptosis in myocardial I/R injury, which is dependent on AMPKα activation via the EZH2/miR-451/Cab39 axis.

8.
Int J Infect Dis ; 95: 38-43, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32251792

RESUMO

OBJECTIVE: To compare the efficacy and safety of standard-dose (SD) daptomycin with those of high-dose (HD) daptomycin in complicated skin and soft tissue infections (cSSTIs) in an Asian population. MATERIALS AND METHODS: Patients from three medical centers diagnosed with cSSTIs were screened in the clinical information system. Patients included in the analysis were divided into two groups: those who received daptomycin at doses ≥ 6 mg/kg (HD group) and those receiving 4 mg/kg (SD group). The demographics and clinical treatment information were analyzed. RESULTS: Overall, 155 patients were recruited, including 108 patients in the SD group and 47 patients in the HD group. The rate of healthcare-associated infections was higher in the HD group (61.70% vs. 37.04%), demonstrating a statistically significant difference (P = 0.005). Compared with the SD group, the HD group had statistically significant early clinical stabilization (72.34% vs 52.78%, P = 0.023). The results of the multivariate analysis indicated that HD daptomycin was an independent effector for early clinical stabilization (HR=0.394, P < 0.001). The rate of drug-related adverse events was equally distributed in the HD and SD groups (36.17% vs. 26.85%, P = 0.243). CONCLUSION: Compared with SD daptomycin, HD daptomycin increased the rate of early clinical stabilization in Asian patients with cSSTIs, whereas the incidence of adverse events did not increase.

9.
Clinics (Sao Paulo) ; 75: e1486, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32187280

RESUMO

OBJECTIVES: Previous studies have not shown any correlation between bile acid metabolism and bone mineral density (BMD) in women with postmenopausal osteoporosis. Thus, the current study evaluated the association between bile acid levels as well as BMD and bone turnover marker levels in this group of women. METHODS: This single-center cross-sectional study included 150 postmenopausal Chinese women. According to BMD, the participants were divided into three groups: osteoporosis group, osteopenia group, and healthy control group. Serum bile acid, fibroblast growth factor 19 (FGF19), and bone turnover biomarker levels were assessed. Moreover, the concentrations of parathyroid hormone, 25-hydroxy vitamin D [25(OH)D], procollagen type I N-peptide (P1NP), and beta-CrossLaps of type I collagen containing cross-linked C-terminal telopeptide (ß-CTX) were evaluated. The BMD of the lumbar spine and proximal femur were examined via dual-energy X-ray absorptiometry. RESULTS: The serum total bile acid levels in the osteoporosis and osteopenia groups (5.28±1.56 and 5.31±1.56 umol/L, respectively) were significantly lower than that in the healthy control group (6.33±2.04 umol/L; p=0.002 and 0.018, respectively). Serum bile acid level was positively associated with the BMD of the lumbar spine, femoral neck, and total hip. However, it negatively correlated with ß-CTX concentration. Moreover, no correlation was observed between bile acid and P1NP levels, and the levels of the other biomarkers that were measured did not differ between the groups. CONCLUSION: Serum bile acid was positively correlated with BMD and negatively correlated with bone turnover biomarkers reflecting bone absorption in postmenopausal women. Thus, bile acid may play an important role in bone metabolism.

10.
Analyst ; 145(8): 3049-3055, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32140698

RESUMO

Surface modification of gold nanoparticles (AuNPs) has significant and complicated effects on their interactions with cell membranes. In this study, we used a lipid/polyacetylene (PDA) vesicle sensor as the lipid membrane model to evaluate AuNP-lipid membrane interactions. Based on the colorimetric response (CR) of PDA vesicles before and after incubation with AuNPs, it was found that the interaction was highly dependent on the surface charge of AuNPs. As compared to the positively charged NPs, neutral and zwitterionic NPs adsorbed much less on the lipid membrane. Negatively charged NPs did not induce any noticeable color changes even at high concentrations. A class of cationic AuNPs with different degrees of surface hydrophobicity was further selected to investigate the role of hydrophobicity in interacting with lipid/PDA vesicles, and log(EC50) was employed as the evaluation index. According to the log(EC50)-NP concentration curve, the hydrophobicity of NPs enhanced the lipid membrane affinity, but electrostatic interactions weakened this effect. Finally, different concentrations of bovine serum albumin (BSA) were used to study the effect of the protein corona on NP-lipid membrane interactions. The formation of a NP-protein corona was found to mask the electrostatic interactions, leading to the decrease of the CR values of cationic NPs, and highly hydrophobic NPs were less affected by a low concentration of BSA due to the strong hydrophobic interactions. Although the effect of NP surface properties on their interactions with cells is far more complicated, our study provides a rapid and effective method for the evaluation of the interactions between surface modified AuNPs and lipid membranes.

11.
Cancer Commun (Lond) ; 40(2-3): 93-104, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32175698

RESUMO

BACKGROUND: Human leukocyte antigen-identical sibling donor (ISD)-hematopoietic stem cell transplantation (SCT) is a potentially curative treatment for high-risk pediatric acute myeloid leukemia (AML). A haploidentical donor (HID) is readily available to almost all children. Previous studies have demonstrated that patients with HID-SCT had similar outcomes compared to ISD-SCT for pediatric and adult AML. However, the role of HID-SCT in high-risk pediatric AML is unclear. METHODS: To compare the overall survival of high-risk AML children who underwent either HID-SCT or ISD-SCT, we analyzed 179 cases of high-risk AML patients under 18 years of age treated with either ISD-SCT (n = 23) or HID-SCT (n = 156). Granulocyte colony-stimulating factor plus anti-thymocyte globulin-based regimens were used for HID-SCT. We also analyzed the subgroup data of AML patients at first complete remission (CR1) before SCT with known cytogenetic risk. RESULTS: The numbers of adverse cytogenetic risk recipients were 8 (34.8%) and 13 (18.8%) in the ISD-SCT group and the HID-SCT group, and the number of patients with disease status beyond CR1 were 6 (26.1%) and 14 (20.3%) in the two groups. The cumulative rates of grades II-IV acute graft-versus-host disease (GVHD) were 13.0% in the ISD-SCT group and 34.8% in the HID-SCT group (P = 0.062), with a three-year cumulative rates of chronic GVHD at 14.1% and 34.9%, respectively (P = 0.091). The relapse rate in the ISD-SCT group was significantly higher than that in the HID-SCT group (39.1% vs. 16.4%, P = 0.027); with non-relapse mortality at 0.0% and 10.6% (P = 0.113), respectively. The three-year overall survival rates were 73.0% for the ISD-SCT group and 74.6% for the HID-SCT group (P = 0.689). In subgroup analysis, the three-year relapse rate in the ISD-SCT group was higher than that in the HID-SCT group (50.0% vs. 9.2%, P = 0.001) and the three-year DFS in the ISD-SCT group (50.0%) was lower than that in the HID-SCT group (81.2%) (P = 0.021). CONCLUSIONS: Unmanipulated HID-SCT achieved DFS and OS outcomes comparable to those of ISD-SCT for high-risk pediatric AML patients with potentially higher rate but manageable GVHD.

12.
J Environ Manage ; 261: 110197, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32148270

RESUMO

One of the major advances of this research is to produce porous glass ceramics (PGCs) via a feasible and cost-effective powder forming chemistry to convert solid wastes, extracted titanium tailing (ETT) and waste glass (WG) into the value-added PGCs. The maximum handling amount of ETT (30%) is determined from systematic experiments, based on the end use of these PGCs, which are manifested as controlled-crystalline porous structures of hybrid matrices. These multiscale porous networks are composed of a tunable pore size, high surface area and accessibility. The synthetic PGCs are found to display enhanced physical properties, as a result, the stewardship of their intrinsic chemical behaviors can be secured. To elucidate, the PGC shows an apparent density of 0.60 ± 0.01 g cm-3, a porosity of 76.0 ± 0.4%, a high compressive strength of 3.8 ± 0.2 MPa, an available water adsorption ratio of 4.4 ± 0.1%, a heat conductivity of 0.103 ± 0.003 W m-1 °C-1 and an applicable coefficient of thermal expansion ((5.43 ± 0.05) × 10-6 m m-1 °C -1). This study indicates that indeed the powder forming chemistry provide a simple method to advance the conversion of industry and municipal solid waste (ETT & WG) into value-added PGCs with improved physical and chemical properties.


Assuntos
Cerâmica , Titânio , Vidro , Porosidade
14.
Mol Brain ; 13(1): 20, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-32059688

RESUMO

Toll-like receptor 4 (TLR4) is a crucial receptor in neuroinflammation and apoptotic neuronal death, and increasing evidences indicated that ß2-microglobulin (B2M) is thought to be a major contributor to age-related cognitive decline. In present study, we designed to investigate the effects of TLR4 on B2M-induced age-related cognitive decline. Wild-type (WT) C57BL/6, TLR4 knockout (TLR4 -KO) mice and hippocampal neurons from the two type mice were respectively divided into two groups: (1) Veh group; (2) B2M-treated group. The behavioral responses of mice were measured using Morris Water Maze. Hippocampal neurogenesis and neuronal damage, inflammatory response, apoptosis, synaptic proteins and neurotrophic factors, and TLR4/MyD88/NF-κB signaling pathway proteins were examined using molecular biological or histopathological methods. The results showed that WT mice received B2M in the DG exhibited age-related cognitive declines, increased TLR4 mRNA expression and high levels of interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α) and apoptotic neuronal death in the hippocampus, which were partially attenuated in TLR4-KO mice. Moreover, in absence of TLR4, B2M treatment improved hippocampus neurogenesis and increased synaptic related proteins. Our cell experiments further demonstrated that deletion of TLR4 could significantly increase synaptic related protein, decrease neuroinflammatory fators, inhibited apoptotic neuronal death, and regulated MyD88/NF-κB signal pathway after B2M treatment. In summary, our results support the TLR4 contributes to B2M-induced age-related cognitive decline due to neuroinflammation and apoptosis through TLR4/MyD88/NF-κB signaling pathway via a modulation of hippocampal neurogenesis and synaptic function. This may provide an important neuroprotective mechanism for improving age-related cognitive decline.

16.
Neurochem Res ; 45(4): 956-963, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32008150

RESUMO

Exposure to sevoflurane and other inhalational anesthetics can induce cognitive impairment in elderly patients. Studies have indicated that methylene blue (MB) has beneficial effects on multiple neurodegenerative diseases and the mechanism involves mitochondrial function preservation. However, whether MB can attenuate the cognitive decline induced by sevoflurane in aged mice requires further investigation. Forty-five 18-month-old C57/BL mice were used to establish a model of sevoflurane-induced cognitive impairment in which the mice were exposed to 3% sevoflurane for 2 h. Mice in the MB group were intraperitoneally injected with MB at a dose of 5 mg/kg before sevoflurane inhalation. The Morris water maze test was used to evaluate the learning and memory performances. We also examined changes in mitochondrial morphology as well as the expression and interaction of related proteins in the aged hippocampus. Parkin, BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), mitochondrial dynamin-related protein 1 (Drp1), small ubiquitin-like modifier (SUMO2/3), SUMO-specific proteases 3 (SENP3), and ubiquitin-like conjugating enzyme 9 expression in the mouse hippocampus was detected by western blotting, and SUMO2/3-Drp1 was examined by coimmunoprecipitation. Exposure to sevoflurane increased SENP3 expression and Drp1 deSUMOylation in the aged hippocampus and resulted in cognitive deficiency. MB attenuated sevoflurane-induced memory loss and mitochondrial fragmentation and decreased Drp1 deSUMOylation in the aged hippocampus. This neuroprotective effect provides a mechanistic explanation for how the SUMOylation status of Drp1 acts as a key switch in the cognitive dysfunction induced by sevoflurane.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32078223

RESUMO

In hunting for safe and cost-effective materials for post-Li-ion energy storage, the design and synthesis of high-performance solid electrolytes (SEs) for all-solid-state batteries are bottlenecks. Many issues associated with chemical stability during processing and storage and use of the SEs in ambient conditions need to be addressed. Now, the effect of water as well as oxyhdryl group (. OH) on NaBi3 O4 Cl2 are investigated by evaluating ionic conductivity. The presence of water and . OH results in an increase in ionic conductivity of NaBi3 O4 Cl2 owing to diffusion of H2 O into NaBi3 O4 Cl2 , partially forming binding . OH through oxygen vacancy repairing. Ab initio calculations reveal that the electrons significantly accumulate around . OH and induce a more negative charge center, which can promote Na+ hopping. This finding is fundamental for understanding the essential role of H2 O in halide-based SEs and provides possible roles in designing water-insensitive SEs through control of defects.

18.
Biomed Pharmacother ; 122: 109700, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31918273

RESUMO

Hypoxia induces cardiomyocytes injury, which further triggers the occurrence and development of cardiovascular diseases. There is a paucity of specific treatment options available with proven efficacy. Chinese patented pharmaceutical product Salidroside (Sal) has potent efficacy on treating hypoxic injury. However, the molecular mechanism remains obscure. In the present study, a UPLC-QTOFMS-based metabolomic method combined with cell viability and apoptosis assays were established to explore the therapeutic mechanisms of Sal against hypoxic injury. Significant protective effects of Sal against inhibited cell viability and apoptosis induced by hypoxic injury were observed in the pharmacodynamic evaluation. Moreover, 40 significantly changed metabolites related to hypoxic injury were identified, of which, 26 can be significantly regulated by Sal. Metabolic pathway enrichment analysis revealed that the mechanisms of Sal against hypoxic injury may be attributed to modulating the disordered homeostasis of energy and lipid metabolism. The present study provides new experimental information on the pathogenesis of hypoxia, unravels the potential targeted metabolic pathways of Sal against hypoxia on the whole metabolic network and highlights the importance of metabolomics as a potential tool for deciphering drug-targeted metabolic pathways.

19.
Dig Dis Sci ; 65(1): 329-335, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31332625

RESUMO

BACKGROUND: Endoscopic variceal sequential ligation (EVSL) is currently endorsed in our hospital, as the preferred endoscopic treatment for prevention of variceal rebleeding and achieving adequate hemostasis. There is currently a lack of consensus surrounding EVSL-induced changes in esophageal motor function and abnormal reflux. AIMS: To explore alterations in esophageal motor function and risk of abnormal gastroesophageal reflux in liver cirrhosis patients with esophageal varices, after EVSL. METHODS: Twenty-one liver cirrhosis patients with esophageal varices were studied using manometry and 24-h pH monitoring 1 day prior to and 1 month following EVSL. The EVSL consisted of performing esophageal variceal ligation using a multi-band ligator, which was repeated every 4 weeks until the varices were eradicated. RESULTS: The amplitude and duration of peristaltic contraction waves and the percentage of abnormal esophageal contraction waveforms were unaltered in both the proximal (P > 0.05) and the distal (P > 0.05) esophagus after EVSL. However, the lower esophageal sphincter pressure was decreased following EVSL (16.1 ± 7.9 mmHg vs 21.1 ± 6.3 mmHg (P < 0.05)). Various quantitative parameters including percentage of total monitoring time with pH < 4.0, total number of reflux episodes, number of reflux episodes > 5 min, and DeMeester scores were not increased in post-EVSL patients. Abnormal reflux monitored by 24-h pH monitoring occurred in ten (47.6%) pre-EVSL patients and 11 (52.4%) post-EVSL patients. CONCLUSIONS: Although EVSL affects esophageal motility by relatively decreasing LES pressure, it does not induce substantial motor abnormalities nor increase risk of abnormal gastroesophageal reflux disease in cirrhosis patients.

20.
Exp Anim ; 69(1): 45-53, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31391379

RESUMO

Ip3r1 encodes an inositol 1,4,5-trisphosphate-responsive calcium channel. Mutations in the IP3R1 gene in humans may cause Gillespie syndrome (GS) typically presents as fixed dilated pupils in affected infants, which was referred to as iris hypoplasia. However, there is no report of mice with Ip3r1 heterozygous mutations showing dilated pupils. Here, we report a new Ip3r1 allele with short-term dilated pupil phenotype derived from an N-ethyl-N-nitrosourea (ENU) mutagenesis screen. This allele carries a G5927A transition mutation in Ip3r1 gene (NM_010585), which is predicted to result in a C1976Y amino acid change in the open reading frame of IP3R1 (NP_034715). We named this novel Ip3r1 allele Ip3r1C1976Y. Histology and pharmacological tests show that the dilated pupil phenotype is a mydriasis caused by the functional defect in the iris constrictor muscles in Ip3r1C1976Y. The dilated pupil phenotype in Ip3r1C1976Y was referred to as mydriasis and excluding iris hypoplasia. IHC analysis revealed increased expression of BIP protein, the master regulator of unfolded protein response (UPR) signaling, in Ip3r1C1976Y mice that did not recover. This study is the first report of an Ip3r1 mutation being associated with the mydriasis phenotype. Ip3r1C1976Y mice represent a self-healing model that may be used to study the therapeutic approach for Ip3r1-related diseases.

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