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1.
Chem Commun (Camb) ; 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34651621

RESUMO

We demonstrate an economical polytetrafluoroethylene-assisted fluorination method to synthesize three binary sodium-rich fluorides Na2MVF7 (M = Mn, Fe, and Co). The optimal Na2FeVF7 cathode delivers a high reversible capacity of 146.5 mA h g-1 based on active Fe2+/Fe3+ and V3+/V4+ redox reactions in sodium-ion batteries. A steady cycling performance with a high capacity retention of 95% over 200 cycles is achieved owing to the negligible structural change during Na+ insertion/extraction.

2.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(7): 704-710, 2021 Jul 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34382586

RESUMO

OBJECTIVES: To investigate the risk factors for serious infections among hospitalized systemic lupus erythematosus (SLE) patients, and to provide the advice for preventing serious infections in SLE patients. METHODS: Information of SLE patients hospitalized from March 2017 to February 2019 at the Department of Rheumatology and Immunology, Xiangya Hospital, Central South University was obtained. The patients were assigned into a serious infection group and a non-serious infection group. The risk factors for serious infections among SLE inpatients were identified by comparison between the 2 groups and multivariate logistic regression analysis. RESULTS: There were 463 SLE inpatients in total, and 144 were in the serious infection group and 319 in the non-serious infection group. Multivariate logistic regression analysis showed that age ≥54.50 years old (OR=4.958, P<0.001), cardiovascular involvement (OR=6.287, P<0.001), hematologic involvement (OR=2.643, P=0.003), serum albumin <20 g/L (OR=2.340, P=0.036), C-reaction protein (CRP)/erythrocyte sedimentation rate (ESR)≥0.12 (OR=2.430, P=0.002), glucocorticoid dose ≥8.75 mg/d prednisone-equivalent (OR=2.465, P=0.002), and the combined use of immunosuppressive agents (OR=2.847, P=0.037) were the risk factors for serious infections in SLE inpatients. CONCLUSIONS: SLE patients with older age, cardiovascular involvement, hematologic involvement, low serum albumin are prone to suffering serious infections. Increased CRP/ESR ratio indicates serious infections in SLE inpatients. High-dose glucocorticoid and the combined use of immunosuppressive agents can increase the risk of serious infections in SLE inpatients.


Assuntos
Pacientes Internados , Lúpus Eritematoso Sistêmico , Idoso , Glucocorticoides/efeitos adversos , Humanos , Lúpus Eritematoso Sistêmico/complicações , Pessoa de Meia-Idade , Prednisona , Fatores de Risco
3.
BMC Genomics ; 22(1): 534, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256697

RESUMO

BACKGROUND: Cystic echinococcosis (CE) is a life-threatening zoonosis caused by the larval form of Echinococcus granulosus tapeworm. Our previous study showed that an approved drug pyronaridine (PND) is highly effective against CE, both in vitro and in an animal model. To identify possible target genes, transcriptome analysis was performed with E. granulosus sensu stricto protoscoleces treated with PND. RESULTS: A total of 1,321 genes were differentially expressed in protoscoleces treated with PND, including 541 upregulated and 780 downregulated genes. Gene ontology and KEGG analyses revealed that the spliceosome, mitogen-activated protein kinase (MAPK) pathway and ATP-binding cassette (ABC) transporters were the top three enriched pathways. Western blot analysis showed that PND treatment resulted in a dose-dependent increase in protein expression levels of EgMKK1 (MKK3/6-like) and EgMKK2 (MEK1/2-like), two members of MAPK cascades. Interestingly, several heat shock protein (HSP) genes were greatly downregulated including stress-inducible HSPs and their constitutive cognates, and some of them belong to Echinococcus-specific expansion of HSP70. CONCLUSIONS: PND has a great impact on the spliceosome, MAPK pathway and ABC transporters, which may underline the mechanisms by which PND kills E. granulosus protoscoleces. In addition, PND downregulates HSPs expression, suggesting a close relationship between the drug and HSPs.


Assuntos
Equinococose , Echinococcus granulosus , Preparações Farmacêuticas , Animais , Equinococose/tratamento farmacológico , Equinococose/genética , Echinococcus granulosus/genética , Perfilação da Expressão Gênica , Naftiridinas
4.
J Pain Res ; 14: 2165-2177, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34295185

RESUMO

Background: General anaesthesia is the commonly provided for breast cancer surgery, but the effects of inhalational anaesthesia and propofol-based intravenous anaesthesia on short- and long-term outcomes after breast cancer surgery are not clear. In this study, we conduct a meta-analysis of randomized controlled trials (RCTs) to explore the superior anaesthetic for breast cancer surgery patients. Methods: We searched the Embase, Medline, Cochrane Library, Web of Science, CNKI, and Wanfang databases (up to January, 2021) for RCTs in which inhalational anaesthesia and propofol-based intravenous anaesthesia were compared and short- and long-term outcomes were assessed in breast cancer surgical patients. The meta-analysis was performed by Stata 12.0. Results: Twenty RCTs with a total of 2201 patients were included. Compared with inhalational anaesthesia, propofol-based intravenous anaesthesia was associated with more postoperative rescue analgesia (I2 =0%, RR: 1.18, 95% CI: 1.07-1.30, P=0.001) but a lower incidence of postoperative nausea and vomiting (PONV) (I2 =25.5%, RR: 0.71, 95% CI: 0.62-0.81, P<0.001) and postoperative rescue antiemetics (I2 =0%, RR: 0.69, 95% CI: 0.58-0.82, P<0.001). Propofol-based intravenous anaesthesia preserved nature killer cell cytotoxicity (I2 =86.2%, SMD: 0.76, 95% CI: 0.13-1.39, P=0.018), decreased IL-6 level (I2 =98.0%, SMD: -3.09, 95% CI: -5.70- -0.48, P=0.021) and neutrophil-to-lymphocyte ratio (I2 =0%, SMD: -0.28, 95% CI: -0.53- -0.03, P=0.030), and increased 2-year recurrence-free survival rate (I2 =0%, RR: 1.10, 95% CI: 1.00-1.20, P=0.043) but did not affect recurrence or the overall survival rate (P>0.05). Conclusion: Propofol-based intravenous anaesthesia increases postoperative rescue analgesia but reduces PONV compared with inhalational anaesthesia in breast cancer surgery. The benefit of propofol over inhalational anaesthetics in the preservation of anti-cancer immunity is obvious, but it is difficult to conclude that propofol can exert long-term benefits due to the small sample size.

5.
World J Surg Oncol ; 19(1): 191, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187485

RESUMO

BACKGROUND: Clinical evidence has proved that enhanced recovery after surgery (ERAS) can improve short-term clinical outcomes after various types of surgeries, but the long-term benefits have not yet been examined, especially with respect to cancer surgeries. Therefore, a systematic review of the current evidence was conducted. METHODS: The Pubmed, Cochrane Library, Embase, and Web of Science databases were searched using the following key words as search terms: "ERAS" or "enhanced recovery" or "fast track", "oncologic outcome", "recurrence", "metastasis", "long-term outcomes", "survival", and "cancer surgery". The articles were screened using the inclusion and exclusion criteria, and the data from the included studies were extracted and analyzed. RESULTS: A total of twenty-six articles were included in this review. Eighteen articles compared ERAS and conventional care, of which, 12 studies reported long-term overall survival (OS), and only 4 found the improvement by ERAS. Four studies reported disease-free survival (DFS), and only 1 found the improvement by ERAS. Five studies reported the outcomes of return to intended oncologic treatment after surgery (RIOT), and 4 found improvements in the ERAS group. Seven studies compared high adherence to ERAS with low adherence, of which, 6 reported the long-term OS, and 3 showed improvements by high adherence. One study reported high adherence could reduce the interval from surgery to RIOT. Four studies reported the effect of altering one single item within the ERAS protocol, but the results of 2 studies were controversial regarding the long-term OS between laparoscopic and open surgery, and 1 study showed improvements in OS with restrictive fluid therapy. CONCLUSIONS: The use of ERAS in cancer surgeries can improve the on-time initiation and completion of adjuvant chemotherapy after surgery, and the high adherence to ERAS can lead to better outcomes than low adherence. Based on the current evidence, it is difficult to determine whether the ERAS protocol is associated with long-term overall survival or cancer-specific survival.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Laparoscopia , Neoplasias , Humanos , Tempo de Internação , Neoplasias/cirurgia , Prognóstico , Recuperação de Função Fisiológica
6.
Chin Med J (Engl) ; 134(12): 1422-1430, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34091519

RESUMO

BACKGROUND: Functional dyspepsia (FD) has rarely been investigated in areas with a high prevalence of esophageal squamous cell carcinoma (ESCC). This study aims to reveal the epidemiological and clinical features of FD and organic dyspepsia (OD) in such a population. METHODS: A middle-aged and elderly population-based study was conducted in a region with a high incidence of ESCC. All participants completed the Gastroesophageal Reflux Disease Questionnaire and Functional Gastrointestinal Disease Rome III Diagnostic Questionnaire, and they underwent gastroscopy. After exclusion of gastroesophageal reflux disease, uninvestigated dyspepsia (UID) was divided into OD and FD for further analyses. RESULTS: A total of 2916 participants were enrolled from July 2013 to March 2014 in China. We detected 166 UID cases with questionnaires, in which 17 patients with OD and 149 with FD were diagnosed via gastroscopy. OD cases presented as reflux esophagitis (RE), ESCC, and duodenal ulcer. Heartburn (52.94%) and reflux (29.41%) were common in OD, but no symptomatic differences were found between FD and OD. Male sex, low education level, and liquid food were the risk factors for OD, while frequent fresh vegetable consumption was a protective factor. FD included 56 (37.58%) cases of postprandial distress syndrome (PDS), 52 (34.89%) of epigastric pain syndrome (EPS), nine (6.04%) of PDS + EPS, and 32 (21.48%) of FD + functional esophageal disorders. The Helicobacter pylori infection rate in FD patients was not higher than that in the control group (34.23% vs. 42.26%, P = 0.240). Frequent spicy food consumption was associated with PDS (odds ratio [OR]: 2.088, 95% confidence interval [CI]: 1.028-4.243), while consumption of deep well water was protective for PDS (OR: 0.431, 95% CI: 0.251-0.741). CONCLUSIONS: The prevalence of FD was 5.11% in the studied population. Gastroscopy should be prescribed for dyspepsia patients in case that ESCC and RE would be missed in UID cases diagnosed solely by the Rome III questionnaire. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01688908; https://clinicaltrials.gov/ct2/show/record/NCT01688908.


Assuntos
Dispepsia , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Infecções por Helicobacter , Helicobacter pylori , Idoso , China/epidemiologia , Dispepsia/epidemiologia , Neoplasias Esofágicas/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade
7.
Acta Trop ; 219: 105919, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33861972

RESUMO

Animal trypanosomiasis, caused by the members of subgenus Trypanozoon (Trypanosoma brucei brucei, T. evansi and T. equiperdum), has reduced animal productivity leading to significant negative economic impacts in endemic regions. Due to limited drug discovery and the emergence of drug-resistance over many recent decades, novel and effective compounds against animal trypanosomiasis are urgently required. This study was conducted to evaluate the antitrypanosomal potential of a batch of carbazole aminoalcohol derivatives. Among them, we found that the most effective compound was H1402, which exhibited potent trypanocidal efficacy against the bloodstream-form of T. b. brucei (EC50 = 0.73 ± 0.05 µM) and presented low cytotoxicity against two mammalian cell lines with CC50 > 30 µM. Using a murine model of acute infection, oral administration with H1402 demonstrated a complete clearance of T. b. brucei and all the infected mice were cured when they were treated twice daily for 5 days at a dose of 100 mg/kg. Furthermore, parasites were not detected in mice infected with T. evansi and T. equiperdum (the causative agents of surra and dourine, respectively, in animals) within 30 days following the same regimen with H1402. In addition, H1402 caused severe morphological and ultrastructural destruction to trypanosomes, as well as causing phosphatidylserine externalization, which are suggested to be the most likely cause of cell death. Overall, the present data demonstrated that H1402 could be promising as a rapid, safe and orally active lead compound for the development of new chemotherapeutics for animal trypanosomiasis.


Assuntos
Álcoois/química , Carbazóis/química , Carbazóis/farmacologia , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Tripanossomíase/tratamento farmacológico , Administração Oral , Animais , Carbazóis/administração & dosagem , Carbazóis/uso terapêutico , Camundongos , Tripanossomicidas/administração & dosagem , Tripanossomicidas/uso terapêutico , Trypanosoma brucei brucei/efeitos dos fármacos , Trypanosoma brucei brucei/fisiologia
8.
Ecotoxicol Environ Saf ; 214: 112116, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33706140

RESUMO

Environmental factors play an important role in the development of ulcerative colitis (UC). However, only few studies have examined the effects of air pollution on UC occurrence. We conducted a time-series analysis to explore the association between short-term exposure to fine particulate matter (PM2.5) and outpatient visits for UC in Beijing, China. In total, 84,000 outpatient visits for UC were retrieved from the Beijing Medical Claim Data for Employees between January 1, 2010 and June 30, 2012. Measurements of daily PM2.5 concentrations were obtained from the United States Embassy air-monitoring station. A generalized additive model with quasi-Poisson link was applied to examine the association between PM2.5 concentrations and outpatient visits for UC stratified by sex, age, and season. We found that short-term exposure to PM2.5 was significantly associated with increased daily outpatient visits for UC at lag 0 day. A 10 µg/m3 increase in PM2.5 concentration at lag 0 day corresponded to a 0.32% increase in outpatient visits for UC (95% confidence interval (CI), 0.05-0.58%; P = 0.019). There was a clear concentration-response association between daily outpatient visits for UC and PM2.5 concentrations. The PM2.5 effects were significant across all sex and season subgroups, without evidence of effect modification by sex (P = 0.942) or season (P = 0.399). The association was positive in patients younger than 65 years old but negative in those 65 years old or older, although the difference was not significant (P = 0.883). In conclusion, our study demonstrated that short-term exposure to ambient PM2.5 was significantly associated with an increased risk of daily outpatient visits for UC, especially in younger people. Additional studies are warranted to confirm our findings.


Assuntos
Poluentes Atmosféricos/análise , Colite Ulcerativa/epidemiologia , Material Particulado/análise , Idoso , Poluição do Ar/análise , Pequim/epidemiologia , Exposição Ambiental/análise , Feminino , Humanos , Masculino , Pacientes Ambulatoriais , Estações do Ano
9.
J Gastroenterol Hepatol ; 36(8): 2131-2140, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33586808

RESUMO

BACKGROUND AND AIM: Concerns regarding adverse events associated with proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) for gastrointestinal bleeding (GIB) prophylaxis in the intensive care unit have increased in recent years. Few studies have focused on acid suppressant use in the cardiac care unit (CCU) setting exclusively. We performed a cohort study to determine the efficacy and safety of acid suppressants for GIB prophylaxis in CCU patients. METHODS: This retrospective cohort study included adults who were admitted directly to the CCU for more than 2 days from January 1, 2014, to April 30, 2019. The Crusade score was calculated to evaluate the risk of GIB. The primary outcomes were clinically important gastrointestinal bleeding (CIGIB), hospital-acquired pneumonia (HAP), and in-hospital mortality. RESULTS: Of the 3318 patients enrolled, 2284 (68.8%) patients received PPIs, 515 (15.5%) received H2RAs, and 519 (15.7%) received no acid suppressants. After adjusting for potential confounders, utilization of PPIs (2.69, 95% confidence interval [0.62-11.73]) and H2RAs (1.41, 95% confidence interval [0.19-10.36]) were not associated with a lower risk of CIGIB than the control. Sensitivity analyses revealed that PPI use was an independent risk factor for in-hospital mortality in patients over 75 years old, with an adjusted odds ratio of 4.08 (1.14-14.63). PPIs increased the risk of HAP in patients over 75 years old and in those with heart failure, with adjusted odds ratios of 2.38 (1.06-5.34) and 2.88 (1.34-7.28), respectively. CONCLUSIONS: Proton pump inhibitors and H2RAs for GIB prophylaxis in CCU patients were not associated with a lower risk of CIGIB than the controls. PPI therapy is associated with increased risks of HAP and in-hospital mortality in patients over 75 years old. PPIs may increase the risk of HAP in patients with heart failure.

10.
Acta Pharmacol Sin ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33558654

RESUMO

Accumulating evidence shows that agents targeting gut dysbiosis are effective for improving symptoms of irritable bowel syndrome (IBS). However, the potential mechanisms remain unclear. In this study we investigated the effects of berberine on the microbiota-gut-brain axis in two rat models of visceral hypersensitivity, i.e., specific pathogen-free SD rats subjected to chronic water avoidance stress (WAS) and treated with berberine (200 mg· kg-1 ·d-1, ig, for 10 days) as well as germ-free (GF) rats subjected to fecal microbiota transplantation (FMT) from a patient with IBS (designated IBS-FMT) and treated with berberine (200 mg· kg-1 ·d-1, ig, for 2 weeks). Before the rats were sacrificed, visceral sensation and depressive behaviors were evaluated. Then colonic tryptase was measured and microglial activation in the dorsal lumbar spinal cord was assessed. The fecal microbiota was profiled using 16S rRNA sequencing, and short chain fatty acids (SCFAs) were measured. We showed that berberine treatment significantly alleviated chronic WAS-induced visceral hypersensitivity and activation of colonic mast cells and microglia in the dorsal lumbar spinal cord. Transfer of fecal samples from berberine-treated stressed donors to GF rats protected against acute WAS. FMT from a patient with IBS induced visceral hypersensitivity and pro-inflammatory phenotype in microglia, while berberine treatment reversed the microglial activation and altered microbial composition and function and SCFA profiles in stools of IBS-FMT rats. We demonstrated that berberine did not directly influence LPS-induced microglial activation in vitro. In both models, several SCFA-producing genera were enriched by berberine treatment, and positively correlated to the morphological parameters of microglia. In conclusion, activation of microglia in the dorsal lumbar spinal cord was involved in the pathogenesis of IBS caused by dysregulation of the microbiota-gut-brain axis, and the berberine-altered gut microbiome mediated the modulatory effects of the agent on microglial activation and visceral hypersensitivity, providing a potential option for the treatment of IBS.

11.
Pharmacol Res ; 165: 105439, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33493658

RESUMO

The gut microbiota is recognized as a promising therapeutic target for anxiety. Berberine (BBR) has shown efficacy in the treatment of diseases such as postmenopausal osteoporosis, obesity, and type 2 diabetes through regulating the gut microbiota. However, the effects of BBR on postmenopausal anxiety are still unclear. The purpose of the study is to test whether BBR ameliorates anxiety by modulating intestinal microbiota under estrogen-deficient conditions. Experimental anxiety was established in specific pathogen-free (SPF) ovariectomized (OVX) rats, which were then treated with BBR for 4 weeks before undergoing behavioral tests. Open field and elevated plus maze tests demonstrated that BBR treatment significantly ameliorated anxiety-like behaviors of OVX rats compared with vehicle-treated counterparts. Moreover, as demonstrated by 16S rRNA sequencing and liquid chromatography/mass spectrometry (LC/MS) analysis, BBR-treated OVX rats harbored a higher abundance of beneficial gut microbes, such as Bacteroides, Bifidobacterium, Lactobacillus, and Akkermansia, and exhibited increased equol generation. Notably, gavage feeding of BBR had no significant anti-anxiety effects on germ-free (GF) rats that underwent ovariectomy, whereas GF rats transplanted with fecal microbiota from SPF rats substantially phenocopied the donor rats in terms of anxiety-like symptoms and isoflavone levels. This study indicates that the gut microbiota is critical in the treatment of ovariectomy-aggravated anxiety, and that BBR modulation of the gut microbiota is a promising therapeutic strategy for treating postmenopausal symptoms of anxiety.

12.
Gastrointest Endosc ; 93(5): 1065-1073.e3, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32950597

RESUMO

BACKGROUND AND AIMS: At present, the surveillance strategy for premalignant esophageal lesions in China is based solely on the pathologic diagnosis in Lugol's chromoendoscopy (LCE). In this study, we sought to determine the degree to which various unstained features under LCE may lead to improved ability to predict the risk of progression in esophageal lesions. METHODS: We re-examined and followed up on 1058 subjects who had Lugol-unstained lesions (LULs) together with a pathologic diagnosis that was lower than severe dysplasia at baseline screening based on a population-based randomized controlled trial over a median time of 5.8 years. We established a logistic regression model and calculated the adjusted cumulative incidence of severe dysplasia or malignancy. RESULTS: LUL size was predictive of progression to malignant lesions in individuals with a nondysplastic diagnosis (adjusted odd ratio6-10 mm vs ≤5 mm, 6.7; 95% confidence interval, 1.7-25.7; adjusted odds ratio>10 mm vs ≤5 mm, 27.9; 95% confidence interval, 7.3-105.7), and the corresponding adjusted cumulative incidence of malignant lesions was 3.6 and 13.2 per 100 persons. This is higher than that of small (≤5 mm) lesions, which showed mild dysplasia (2.7 per 100 persons), a condition for which surveillance every 3 years is recommended. Under the current approach, 65.3% of interval cancers missed at surveillance would be detected if individuals with medium (6-10 mm) and large (>10 mm) nondysplastic LULs were additionally monitored. CONCLUSIONS: We propose a modified surveillance strategy that combines findings under LCE examination and the pathologic analysis, where follow-up endoscopy is recommended for individuals with relatively large nondysplastic lesions.


Assuntos
Neoplasias Esofágicas , Lesões Pré-Cancerosas , China/epidemiologia , Corantes , Neoplasias Esofágicas/epidemiologia , Esofagoscopia , Humanos , Iodetos , Lesões Pré-Cancerosas/epidemiologia
13.
Mol Genet Genomic Med ; 9(1): e1568, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33280276

RESUMO

BACKGROUND: Glycogen storage disease (GSD) type Ib is an autosomal recessive disease caused by defects of glucose-6-phosphate transporter (G6PT), encoded by the SLC37A4 gene. To date, over 100 mutations have been revealed in the SLC37A4 gene. GSD-Ib patients manifest a metabolic phenotype of impaired blood glucose homeostasis and also carry the additional complications of neutropenia and myeloid dysfunction. METHODS: Here, we present two daughters with an initial diagnosis of gout in a Chinese consanguineous family. Whole-exome sequencing was performed to identify the mutations. The mechanism of leukocytopenia was investigated. RESULTS: Whole-exome sequencing analysis of the proband identified a novel homozygous p.P119L mutation in SLC37A4, leading to a diagnosis of GSD-Ib. We found that the potential pathogenic p.P119L mutation leads to an unusual phenotype characterized by gout at onset, and GSD-Ib arising from this variant also manifests multiple metabolic abnormalities, leukocytopenia, and anemia, but no hepatomegaly. The leukocytes from the proband showed increased mRNA levels of sXBP-1, BIP, and CHOP genes in the unfolded protein response pathway, and enhanced Bax mRNA and caspase-3 activity, which might contribute to leukocytopenia. CONCLUSION: Our findings broaden the variation spectrum of SLC37A4 and suggest no strict genotype-phenotype correlations in GSD-Ib patients.

14.
Dig Liver Dis ; 53(2): 253-254, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33229274
15.
Perit Dial Int ; : 896860820962901, 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33249994

RESUMO

OBJECTIVES: The primary objective of the Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study is to explore potential predictors and their effects on patient survival, technique survival, and the occurrence of infectious and noninfectious complications. DESIGN: The PDTAP study is a national-level cohort study in China. A newly developed PD telemedicine application provided a unique and convenient way to collect multicenter, structured data across units. SETTING: The PDTAP study was underway in 27 hospitals from 14 provinces located at 7 geographical regions (northwest, northeast, north, central, southwest, southeast, and south) in China. PARTICIPANTS: Our study aims to enroll at least 7000 adult patients with end-stage renal disease receiving PD. METHODS: Approval has been obtained through the ethics committees of all hospitals. All participants signed the informed consent form after the center had received ethics board approval in accordance with the Declaration of Helsinki. MAIN OUTCOME MEASURES: Patient survival, technique survival, hospitalization, and the occurrence of infectious and noninfectious complications. CONCLUSIONS: The PDTAP study aims to explore potential predictors and their effects on patient survival, technique survival, and infectious and noninfectious complications using a newly developed PD telemedicine system to collect multicenter, structured data in real-world practice. Substantial and transformable findings in relation to PD practices were expected. This study also developed a national-level infrastructure for further collaboration and ancillary investigation.

16.
Front Cell Infect Microbiol ; 10: 580980, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194817

RESUMO

Background and Aims: Irritable bowel syndrome (IBS) and depression have high tendencies of comorbidity. In particular, diarrhea-predominant IBS (IBS-D) and depression exhibit similar fecal microbiota signatures, yet little is known about their pathogenic mechanism. Here, we propose that the differences in structure and composition of IBS-D and depression gut microbiota give rise to different downstream functions, which lead to distinct clinical phenotypes via host metabolism and further influence the interaction of brain-gut axis. Methods: We performed multiomics study, including fecal metagenome-wide sequencing and serum metabolomics profiling in 65 individuals with IBS-D (n=22), depression (n=15), comorbid patients (n=13), and healthy controls (n=15). We analyzed functional genes contributed by the primary genus and evaluated their correlations with clinical indices and host metabolites. Results: Metagenomic analysis revealed 26 clusters of orthologous groups of protein (COG) categories consisting of a total of 4,631 functional genes. Trehalose and maltose hydrolase (COG1554) and fucose permease (COG0738) were the most relevant and enriched functional genes in the IBS-D patients; urease accessory proteins UreE (COG2371) was that in the depression patients. Context based genome annotation suggest that an alteration of Escherichia coli and Enterobacter cloacae in IBS-D and depression respectively may be responsible for the enrichment described above. Correlation with host metabolites, such as maltotriose and isomaltose in carbohydrate metabolism and anandamide in neuroactive metabolism, drew further connections between these findings. Conclusions: These changes led us to propose a connection between genomic signatures and clinical differences observed in IBS-D and depression. Our findings provide further insights into the involvement of gut microbiota in diseases related to brain-gut disorder.


Assuntos
Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Bactérias/genética , Depressão , Fezes , Humanos
17.
Br J Pharmacol ; 177(24): 5569-5579, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32959888

RESUMO

BACKGROUND AND PURPOSE: Malaria is one of the deadliest diseases in the world. Novel chemotherapeutic agents are urgently required to combat the widespread Plasmodium resistance to frontline drugs. Here, we report the discovery of a novel benzonaphthyridine antimalarial, methnaridine, which was identified using a structural optimization strategy. EXPERIMENTAL APPROACH: An integrated pharmacological approach was used to evaluate the antimalarial profile of methnaridine. The pharmacokinetic properties of methnaridine were investigated along with the associated safety profile. Host immune response patterns were also analysed. KEY RESULTS: Methnaridine exhibited potent antimalarial activity against P. falciparum (3D7: IC50 = 0.0066 µM; Dd2: IC50 = 0.0056 µM). In P. berghei-infected mice, oral administration effectively suppressed parasitemia (ED50 = 0.52 mg·kg-1 ·day-1 ) and cured the established infection (CD50 = 10.13 mg·kg-1 ·day-1 ). These results are equivalent to or better than those of other antimalarial agents in clinical use. Notably, a four-dose oral regimen at a dosage of 25 mg·kg-1 achieved a complete cure of P. berghei infection in mice. Methnaridine exhibited a rapid parasiticidal profile (PCT99 = 36.0 h) and showed no cross-resistance to chloroquine. Pharmacokinetic studies revealed that methnaridine is readily absorbed, long-lasting and slowly cleared. The safety profile of methnaridine is also satisfactory (maximum tolerated dose = 1,125 mg·kg-1 ). In addition, following methnaridine treatment, infection-induced Th1 immune response was almost fully alleviated in mice. CONCLUSION AND IMPLICATIONS: Methnaridine is an orally bioavailable, fast-acting and long-lasting agent with excellent antimalarial properties. Our study highlights the potential of methnaridine for clinical development as a promising antimalarial candidate.


Assuntos
Antimaláricos , Malária , Animais , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Homicídio , Malária/tratamento farmacológico , Camundongos , Plasmodium berghei , Plasmodium falciparum
18.
Spectrochim Acta A Mol Biomol Spectrosc ; 241: 118685, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-32653821

RESUMO

Two fluorescent probes were designed by connecting indomethacin to coumarin through different linkers. The introduction of indomethacin quenched the fluorescence of coumarin-based probes with apparent red-shifts in the absorption and emission maxima, probably due to the photoinduced electron transfer (PET) from the indomethacin to the fluorophore and the formation of folding conformation. The addition of human serum albumin (HSA) triggered about 40-fold fluorescence enhancements of ADC-IMC-2 and ADC-IMC-6 with 85 nm blue-shifts. The probe with longer spacer ADC-IMC-6 exhibited ratiometric fluorescent response toward HSA, and that with shorter linker showed "off-on" fluorescence response to HSA. However, insignificant spectral changes of the reference compounds (ADC-6 and ADC-2) initiated by HSA implied that indomethacin played critical role in the identification of HSA. The competitive assays and molecular docking results reveal that the indomethacin in ADC-IMC-6 could tightly combine at drug site I of HSA. Fluorescence bio-imaging experiments show that both probes could distinguish cancer cells from normal cells.


Assuntos
Corantes Fluorescentes , Neoplasias , Humanos , Indometacina , Simulação de Acoplamento Molecular , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Ligação Proteica , Albumina Sérica Humana , Espectrometria de Fluorescência
19.
Adv Parasitol ; 110: 1-62, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32563322

RESUMO

Being a zoonotic parasitic disease, schistosomiasis was widely spread in 12 provinces of Southern China in the 1950s, severly harming human health and hindering economic development. The National Institute of Parasitic Diseases at the Chinese Center for Diseases Control and Prevention, and Chinese Center for Tropical Diseases Research (NIPD-CTDR), as the only professional institution focussing on parasitic diseases at the national level, has played an important role in schistosomiasis control in the country. In this article, we look back at the changes of schistosomiasis endemicity and the contribution of NIPD-CTDR to the national schistosomiasis control programme. We review NIPD-CTDR's activities, including field investigations, design of control strategies and measures, development of diagnostics and drugs, surveillance-response of endemic situation, and monitoring & evaluation of the programme. The NIPD-CTDR has mastered the transmission status of schistosomiasis, mapped the snail distribution, and explored strategies and measures suitable for different types of endemic areas in China. With a good understanding of the life cycle of Schistosoma japonicum and transmission patterns of the disease, advanced research carried out in the NIPD-CTDR based on genomics and modern technology has made it possible to explore highly efficient and soft therapeutic drugs and molluscicides, making it possible to develop new diagnostic tools and produce vaccine candidates. In the field, epidemiological studies, updated strategies and targeted intervention measures developed by scientists from the NIPD-CTDR have contributed significantly to the national schistosomiasis control programme. This all adds up to a strong foundation for eliminating schistosomiasis in China in the near future, and recommendations have been put forward how to reach this goal.


Assuntos
Academias e Institutos , Doenças Endêmicas/prevenção & controle , Programas Governamentais , Programas Nacionais de Saúde , Esquistossomose Japônica , Animais , Bovinos , China/epidemiologia , Erradicação de Doenças , Desenvolvimento de Medicamentos , Humanos , Moluscocidas , Esquistossomose Japônica/tratamento farmacológico , Esquistossomose Japônica/epidemiologia , Esquistossomose Japônica/transmissão , Vacinação
20.
Sheng Li Xue Bao ; 72(3): 361-370, 2020 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-32572433

RESUMO

Stress is the non-specific systemic response that occurs when the body is stimulated by various factors, and it can affect multiple systems of the body. Recent studies have shown that gut microbiota is an essential part of human microecology, and plays a pivotal role in keeping the body healthy. Stress can result in gut dysbiosis by affecting the function of intestinal mucosal barrier, intestinal immune and gastrointestinal motility. This article reviewed the alteration of gut microbiota caused by stress and the possible mechanisms involved.


Assuntos
Microbioma Gastrointestinal , Disbiose , Motilidade Gastrointestinal , Humanos , Mucosa Intestinal
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