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2.
Environ Int ; 158: 106913, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34624590

RESUMO

BACKGROUND: Epidemiological studies on the associations of legacy per- and polyfluoroalkyl substances (PFASs) and glucose homeostasis remain discordant. Understanding of PFAS alternatives is limited, and few studies have reported joint associations of PFASs and PFAS alternatives. OBJECTIVES: To investigate associations of novel PFAS alternatives (chlorinated perfluoroalkyl ether sulfonic acids, Cl-PFESAs and perfluorobutanoic acid, PFBA) and two legacy PFASs (Perfluorooctanoic acid, PFOA and perfluorooctane sulfonate, PFOS) with glucose-homeostasis markers and explore joint associations of 13 legacy and alternative PFASs with the selected outcomes. METHODS: We used cross-sectional data of 1,038 adults from the Isomers of C8 Health Project in China. Associations of PFASs and PFAS alternatives with glucose-homeostasis were explored in single-pollutant models using generalized linear models with natural cubic splines for PFASs. Bayesian Kernel Machine Regression (BKMR) models were applied to assess joint associations of exposures and outcomes. Sex-specific analyses were also conducted to evaluate effect modification. RESULTS: After adjusting for confounders, both legacy (PFOA, PFOS) and alternative (Cl-PFESAs and PFBA) PFASs were positively associated with glucose-homeostasis markers in single-pollutant models. For example, in the total study population, estimated changes with 95% confidence intervals (CI) of fasting glucose at the 95th percentile of 6:2Cl-PFESA and PFOS against the thresholds were 0.90 (95% CI: 0.59, 1.21) and 0.44 (95% CI: 0.26, 0.62). Positive joint associations were found in BKMR models with 6:2Cl-PFESA contributing most. Sex-specific associations existed in both single- and multi-pollutant models. CONCLUSIONS: Legacy and alternative PFASs were positively associated with glucose-homeostasis markers. 6:2Cl-PFESA was the primary contributor. Sex-specific associations were also identified. These results indicate that joint associations and effect modification should be considered in risk assessment. However, further studies are recommended to strengthen our findings and to elucidate the mechanisms of action of legacy and alternative PFASs.

3.
Lett Appl Microbiol ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34586632

RESUMO

Tellurium is a scarce and valuable metalloid, which can be found in some mine tailings. In this work, an indigenous Acidithiobacillus ferrooxidans strain was used to leach Te from mine tailings collected in the Shimian Te mine region, China. Under the optimized conditions of initial pH of 2.0, pulp density of 4%, and temperature of 30℃, 47.77% of Te can be dissolved after 24 days of bioleaching. The leaching of Te by different systems such as bioleaching, Ferric ion (Fe(III)) leaching and acid leaching was compared. The results showed that the leaching behavior of Te is similar to that of sulfur in sulfide minerals, that is Fe(III) firstly oxidizes telluride (Te(-II)) in minerals to elemental Te, and then elemental Te can be oxidized by bacteria to Te(IV) and Te(VI). Besides, it was also showed by SEM observation and FTIR analysis of the ore sample before and after bioleaching that some bedded structure covered on the surface of the ore after bioleaching, acting as a reaction compartment, and the changing of active groups indicated a possible attachment between bacteria and ore. There is an indirect mechanism involved in bioleaching of Te.

4.
BMC Neurosci ; 22(1): 56, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34525970

RESUMO

BACKGROUND: NRXN1 deletions are identified as one of major rare risk factors for autism spectrum disorder (ASD) and other neurodevelopmental disorders. ASD has 30% co-morbidity with epilepsy, and the latter is associated with excessive neuronal firing. NRXN1 encodes hundreds of presynaptic neuro-adhesion proteins categorized as NRXN1α/ß/γ. Previous studies on cultured cells show that the short NRXN1ß primarily exerts excitation effect, whereas the long NRXN1α which is more commonly deleted in patients involves in both excitation and inhibition. However, patient-derived models are essential for understanding functional consequences of NRXN1α deletions in human neurons. We recently derived induced pluripotent stem cells (iPSCs) from five controls and three ASD patients carrying NRXN1α+/- and showed increased calcium transients in patient neurons. METHODS: In this study we investigated the electrophysiological properties of iPSC-derived cortical neurons in control and ASD patients carrying NRXN1α+/- using patch clamping. Whole genome RNA sequencing was carried out to further understand the potential underlying molecular mechanism. RESULTS: NRXN1α+/- cortical neurons were shown to display larger sodium currents, higher AP amplitude and accelerated depolarization time. RNASeq analyses revealed transcriptomic changes with significant upregulation glutamatergic synapse and ion channels/transporter activity including voltage-gated potassium channels (GRIN1, GRIN3B, SLC17A6, CACNG3, CACNA1A, SHANK1), which are likely to couple with the increased excitability in NRXN1α+/- cortical neurons. CONCLUSIONS: Together with recent evidence of increased calcium transients, our results showed that human NRXN1α+/- isoform deletions altered neuronal excitability and non-synaptic function, and NRXN1α+/- patient iPSCs may be used as an ASD model for therapeutic development with calcium transients and excitability as readouts.

5.
J Cosmet Dermatol ; 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34536054

RESUMO

INTRODUCTION: Stem cell-derived exosomes are cell-free vesicles secreted by stem cells. Exosomes play a pivotal role in cell-to cell communication due to the functional proteins and genetic information which they carry. In addition, studies on cell migration, tumor invasion, tissue regeneration, myocardial repair after injury, and fracture healing have been widely reported. OBJECTIVES: The purpose of this review is to sum up the current state of research on multiple stem cell-derived exosomes in cosmetic dermatology and to discuss the current challenges and future directions. METHODS: We searched "skin" and "exosome" from PubMed to find the application of stem cell exosomes in cosmetic dermatology. RESULTS: We found that stem cell-derived exosomes have an important place in skin cosmetology such as wound healing, skin aging, and scar formation. CONCLUSION: Stem cell derived exosomes supply a potential tool to cosmetic dermatology. The performance of stem cell derived exosomes in regulating skin physiological and pathobiological functions suggests that stem cell derived exosomes have potential in cosmetic dermatology.

6.
Clin Chim Acta ; 523: 196-200, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34592307

RESUMO

BACKGROUND: Serofast status is challenging to interpret in clinical work, and distinguishing active syphilis in serofast patients can provide a reference for clinical diagnosis and treatment. However, effective serologic markers for active syphilis are still lacking. OBJECTIVES: We aimed to explore the possibility of nontreponemal IgM antibodies in distinguishing active syphilis in serofast patients. METHODS: A total of 1501 clinical serum samples were collected from 301 serofast patients, and nontreponemal IgM antibodies were detected by chemiluminescence immunoassay. RESULTS: The results showed that a total of 29 samples (9.63%) of 301 serofast patients were positive for nontreponemal IgM antibodies, and our limited follow-up data showed that 66.67% (2/3) of the serofast patients progressed to neurosyphilis and cardiovascular syphilis. CONCLUSION: These findings demonstrate that most serofast patients with positive nontreponemal IgM antibodies have evidence of progressive syphilis, and nontreponemal IgM antibodies can be used as a new serologic marker for the activity of syphilis. Nontreponemal IgM antibodies may play a role in the management of serofast patients.

7.
J Clin Anesth ; 75: 110467, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34343737

RESUMO

STUDY OBJECTIVE: Previous studies reported that controlled low central venous pressure (CVP) can reduce blood loss during liver resection. This systematic review and meta-analysis sought to explore the efficacy and safety of low CVP in patients undergoing hepatectomy. DESIGN: A systematic review and meta-analysis of randomized controlled trials (RCTs). REVIEW METHODS: RCTs were searched in PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese BioMedical database, Chinese Scientific Journals Database, and Wanfang database from inception to April 30, 2021. Subgroup analyses were performed based on different surgical methods (open hepatectomy vs laparoscopic hepatectomy) and published countries (China vs other countries). The quality of evidence was assessed by Grading of Recommendations, Assessment, Development, and Evaluation. MAIN RESULTS: Eighteen RCTs containing 1285 participants (626 patients in the low CVP group and 659 patients in the control group) were included in this study. The forest plot showed that low CVP effectively reduced blood loss during liver resection compared with the control group (MD = -311.92 mL, 95% CI [-429.03, -194.81]; P < 0.001, I2 = 96%). Furthermore, blood transfusion volume (MD = -158.85 mL, 95% CI [-218.30, -99.40]; P < 0.001, I2 = 55%) and the number of patients requiring transfusion (RR 0.41, 95% CI 0.27-0.65, P < 0.001, I2 = 0%) were decreased in the low CVP group. Subgroup analyses showed similar results. Notably, the alanine transaminase level was significantly lower in the low CVP group during the first five postoperative days. However, no significant differences were observed for other postoperative liver function indicators (aspartate aminotransferase, total bilirubin, serum albumin, and prothrombin time), renal function indicators (blood urea nitrogen and serum creatinine) and perfusion parameters (heart rate, mean arterial pressure, and urine volume). The incidence of complications was similar between the two groups. CONCLUSION: The findings of this study showed that low CVP is effective and safe during hepatectomy. Therefore, this technique is recommended to reduce blood loss during hepatectomy. PROSPERO registration number: CRD42021232829.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34454169

RESUMO

BACKGROUND & AIMS: The ligand-activated transcription factor, aryl hydrocarbon receptor (AHR) can sense xenobiotics, dietary, microbial, and metabolic cues. Roles of Ahr in intestinal epithelial cells (IECs) have been much less elucidated compared with those in intestinal innate immune cells. Here, we explored whether the IEC intrinsic Ahr could modulate the development of alcohol-related liver disease (ALD) via the gut-liver axis. METHODS: Mice with IEC specific Ahr deficiency (AhrΔIEC) were generated and fed with a control or ethanol diet. Alterations of intestinal microbiota and metabolites were investigated by 16S ribosomal RNA sequencing, metagenomics, and untargeted metabolomics. AHR agonists were used to evaluate the therapeutic potentials of intestinal Ahr activation for ALD treatment. RESULTS: AhrΔIEC mice showed more severe liver injury after ethanol feeding than control mice. Ahr deficiency in IECs altered the intestinal metabolite composition, creating an environment that promoted the overgrowth of Helicobacter hepaticus and Helicobacter ganmani in the gut, enhancing their translocation to mesenteric lymph nodes and liver. Among the altered metabolites, isobutyric acid was increased in the cecum of ethanol-fed AhrΔIEC mice relative to control mice. Furthermore, both H hepaticus and isobutyric acid administration aggravated ethanol-induced liver injury in vivo and in vitro. Supplementation with AHR agonists, 6-formylindolo[3,2-b]carbazole and indole-3-carbinol, protected mice from ALD development by specifically activating intestinal Ahr without affecting liver Ahr function. Alcoholic patients showed lower intestinal AHR expression and higher H hepaticus levels compared with healthy individuals. CONCLUSIONS: Our results indicate that targeted restoration of IEC intrinsic Ahr function may present as a novel approach for ALD treatment.

9.
BMC Plant Biol ; 21(1): 376, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34399701

RESUMO

BACKGROUND: Glycolytic pathway is common in all plant organs, especially in oxygen-deficient tissues. Phosphofructokinase (PFK) is a rate-limiting enzyme in the glycolytic pathway and catalyses the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate. Cassava (M. esculenta) root is a huge storage organ with low amount of oxygen. However, less is known about the functions of PFK from M. esculenta (MePFK). We conducted a systematic analysis of MePFK genes to explore the function of the MePFK gene family under hypoxic stress. RESULTS: We identified 13 MePFK genes and characterised their sequence structure. The phylogenetic tree divided the 13 genes into two groups: nine were MePFKs and four were pyrophosphate-fructose-6-phosphate phosphotransferase (MePFPs). We confirmed by green fluorescent protein fusion protein expression that MePFK03 and MePFPA1 were localised in the chloroplast and cytoplasm, respectively. The expression profiles of the 13 MePFKs detected by quantitative reverse transcription polymerase chain reaction revealed that MePFK02, MePFK03, MePFPA1, MePFPB1 displayed higher expression in leaves, root and flower. The expression of MePFK03, MePFPA1 and MePFPB1 in tuber root increased gradually with plant growth. We confirmed that hypoxia occurred in the cassava root, and the concentration of oxygen was sharply decreasing from the outside to the inside root. The expression of MePFK03, MePFPA1 and MePFPB1 decreased with the decrease in the oxygen concentration in cassava root. Waterlogging stress treatment showed that the transcript level of PPi-dependent MePFP and MeSuSy were up-regulated remarkably and PPi-dependent glycolysis bypass was promoted. CONCLUSION: A systematic survey of phylogenetic relation, molecular characterisation, chromosomal and subcellular localisation and cis-element prediction of MePFKs were performed in cassava. The expression profiles of MePFKs in different development stages, organs and under waterlogging stress showed that MePFPA1 plays an important role during the growth and development of cassava. Combined with the transcriptional level of MeSuSy, we found that pyrophosphate (PPi)-dependent glycolysis bypass was promoted when cassava was under waterlogging stress. The results would provide insights for further studying the function of MePFKs under hypoxic stress.


Assuntos
Genoma de Planta , Manihot/enzimologia , Manihot/genética , Fosfofrutoquinases/genética , Fosfofrutoquinases/metabolismo , Cloroplastos/enzimologia , Mapeamento Cromossômico , Cromossomos de Plantas , Sequência Conservada , Citoplasma/enzimologia , Éxons , Flores/enzimologia , Íntrons , Família Multigênica , Oxigênio/metabolismo , Filogenia , Folhas de Planta/enzimologia , Raízes de Plantas/enzimologia , Regiões Promotoras Genéticas , Estresse Fisiológico/genética , Transcriptoma
10.
Acta Pharmacol Sin ; 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294887

RESUMO

Lack of efficiency has been a major problem shared by all currently developed anti-SARS-CoV-2 therapies. Our previous study shows that SARS-CoV-2 structural envelope (2-E) protein forms a type of cation channel, and heterogeneously expression of 2-E channels causes host cell death. In this study we developed a cell-based high throughput screening (HTS) assay and used it to discover inhibitors against 2-E channels. Among 4376 compounds tested, 34 hits with cell protection activity were found. Followed by an anti-viral analysis, 15 compounds which could inhibit SARS-CoV-2 replication were identified. In electrophysiological experiments, three representatives showing inhibitory effect on 2-E channels were chosen for further characterization. Among them, proanthocyanidins directly bound to 2-E channel with binding affinity (KD) of 22.14 µM in surface plasmon resonance assay. Molecular modeling and docking analysis revealed that proanthocyanidins inserted into the pore of 2-E N-terminal vestibule acting as a channel blocker. Consistently, mutations of Glu 8 and Asn 15, two residues lining the proposed binding pocket, abolished the inhibitory effects of proanthocyanidins. The natural product proanthocyanidins are widely used as cosmetic, suggesting a potential of proanthocyanidins as disinfectant for external use. This study further demonstrates that 2-E channel is an effective antiviral drug target and provides a potential antiviral candidate against SARS-CoV-2.

11.
Orthop Surg ; 13(5): 1618-1627, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34142446

RESUMO

OBJECTIVES: The aim of this study was to evaluate the clinical outcomes of the Wiltse approach and percutaneous pedicle screw placement under O-arm navigation for the treatment of thoracolumbar fracture. METHODS: We enrolled a total of 54 patients with neurologically intact thoracolumbar fracture who received minimally invasive treatments between October 2014 and October 2018 in this retrospective study. Among these, 28 patients (22 males and six females, with a mean age of 48.6 ± 9.6 years) were treated with pedicle screw fixation through the Wiltse approach (WPSF), and another 26 (15 males and 11 females, with a mean age of 45.7 ± 10.6 years) received percutaneous pedicle screw fixation under O-arm navigation (OPSF). Statistical methods were used to perform a detailed comparison of clinical outcomes, radiologic findings, and complications between the two groups obtained preoperatively, postoperatively, and at last follow-up. RESULTS: All patients underwent surgery successfully and finished a follow-up of more than 12 months. No serious complications, such as infection, blood vessel injury, or spinal cord or nerve root injury occurred. Visual analog scale (VAS) scores, Oswestry disability index (ODI) scores, local Cobb angle (LCA), vertebral wedge angle (VWA), and R value were notably improved after surgery, though there was no clear discrepancy between the groups at each time point (P > 0.05). During the follow-up period, no patients developed neurological impairment or implant-related complications, and no patients underwent revision surgery. The WPSF group had a significantly shorter operation time than the OPSF group (68.1 ± 9.8 vs 76.1 ± 9.0 minutes, P = 0.005). Moreover, the WPSF group showed less cost of surgery than the WPSF group (48142.1 ± 1430.1 vs 59035.4 ± 1152.7 CNY, P < 0.001). There were no significant differences between the two groups in terms of the intraoperative bleeding, length of incision, or postoperative hospitalization time (P > 0.05). The accuracy of pedicle screw placement was 95.2% (160/168) in the WPSF group and 96.8% (151/156) in the OPSF group, with no significant difference between the groups (P = 0.432). CONCLUSION: Both WPSF and OPSF were safe and effective for the treatment of thoracolumbar fracture. Although the two groups showed favorable clinical and radiologic outcomes through to final follow-up, we recommended the minimally invasive WPSF given its shorter operation time and lower cost of surgery.

12.
BMC Surg ; 21(1): 250, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34011342

RESUMO

BACKGROUND: Venous thromboembolism remains a common but preventable complication for cancerous lung surgical patients. Current guidelines recommend thromboprophylaxis for lung patients at high risk of thrombosis, while a consensus about specific administration time is not reached. This study was designed to investigate the safety profile of preoperative administration of low-molecular-weight-heparin (LMWH) for lung cancer patients. METHODS: From July 2017 to June 2018, patients prepared to undergo lung cancer surgery were randomly divided into the preoperative LMWH-administration group (PRL) for 4000 IU per day and the postoperative LMWH-administration group (POL) with same dosage, all the patients received thromboprophylaxis until discharge. Baseline characteristics including demographics and preoperative coagulation parameters were analyzed, while the endpoints included postoperative coagulation parameters, postoperative drainage data, hematologic data, intraoperative bleeding volume and reoperation rate. RESULTS: A total of 246 patients were collected in this RCT, 34 patients were excluded according to exclusion criterion, 101 patients were assigned to PRL group and 111 patients belonged to POL group for analysis finally. The baseline characteristic and preoperative coagulation parameters were all comparable except the PRL group cost more operation time (p = 0.008) and preoperative administration duration was significantly longer (p < 0.001). The endpoints including postoperative day 1 coagulation parameters, mean and total drainage volume, drainage duration, intraoperative bleeding volume and reoperation rate were all similar between the two groups. Moreover, coagulation parameters for postoperative day 3 between the two groups demonstrated no difference. CONCLUSION: Preoperative administration of low-molecular-weight-heparin demonstrated safety and feasibility for lung cancer patients intended to receive minimally invasive surgery. TRIAL REGISTRATION: ChiCTR2000040547 ( www.chictr.org.cn ), 2020/12/1, retrospectively registered.


Assuntos
Neoplasias Pulmonares , Tromboembolia Venosa , Anticoagulantes/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Neoplasias Pulmonares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
13.
Poult Sci ; 100(7): 101129, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34058564

RESUMO

Polysaccharide Of Atractylodes Macrocephala Koidz (PAMK) has been proved to have anti-cancer, antitumor, anti-inflammation function and improve the immune level of the organism. The miRNA plays a very important role in regulating the immune function by negatively regulate the expression of target genes. To explore the molecular mechanism of PAMK active the lymphocytes, thirty 61-d-old geese were randomly divided into 4 groups (C, CTX, PAMK, PAMK+CTX). The thymus morphology, the level of serum granulocyte-macrophage colony-stimulating factor (GMC-SF), IL-1ß, IL-3, IL-5, the relative mRNA expression of CD25, novel_mir2, CTLA4 and CD28 signal pathway were measured. Further more, the lymphocytes was extracted from thymus to measure the relative mRNA expression of CD28 signal pathway. The results showed that PAMK could significantly maintain normal cell morphology of thymus, alleviate the decrease level of GMC-SF, IL-1ß, IL-5, IL-6, TGF-ß, the increase level of IL-4, IL-10, and the decrease relative mRNA expression of novel_mir2, CD25 and CD28 signal pathway in thymus and lymphocytes induced by cyclophosphamide (CTX). In conclusion, PAMK alleviated the decreased T lymphocytes activation levels induced by CTX through novel_mir2/CTLA4/CD28/AP-1 signal pathway.


Assuntos
Atractylodes , Animais , Antígenos CD28 , Galinhas , Ciclofosfamida , Gansos , Imunossupressão/veterinária , Polissacarídeos , Transdução de Sinais , Linfócitos T , Fator de Transcrição AP-1
14.
Sci Rep ; 11(1): 7573, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33828187

RESUMO

In quantitative PCR research, appropriate reference genes are key to determining accurate mRNA expression levels. In order to screen the reference genes suitable for detecting gene expression in tissues of the reproductive axis, a total of 420 (males and females = 1:5) 3-year-old Magang geese were selected and subjected to light treatment. The hypothalamus, pituitary and testicular tissues were subsequently collected at different stages. Ten genes including HPRT1, GAPDH, ACTB, LDHA, SDHA, B2M, TUBB4, TFRC, RPS2 and RPL4 were selected as candidate reference genes. The expression of these genes in goose reproductive axis tissues was detected by real-time fluorescent quantitative PCR. The ΔCT, geNorm, NormFinder and BestKeeper algorithms were applied to sort gene expression according to stability. The results showed that ACTB and TUBB4 were the most suitable reference genes for the hypothalamic tissue of Magang goose in the three breeding stages; HPRT1 and RPL4 for pituitary tissue; and HPRT1 and LDHA for testicular tissue. For all three reproductive axis tissues, ACTB was the most suitable reference gene, whereas the least stable reference gene was GAPDH. Altogether, these results can provide references for tissue expression studies in geese under light treatment.

15.
Emerg Microbes Infect ; 10(1): 905-912, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33870851

RESUMO

Without an effective vaccine against SARS-CoV-2, the build-up of herd immunity through natural infection has been suggested as a means to control COVID-19. Although population immunity is typically estimated by the serological investigation of recovered patients, humoral immunity in asymptomatic subjects has not been well studied, although they represent a large proportion of all SARS-CoV-2 infection cases. In this study, we conducted a serosurvey of asymptomatic infections among food workers and performed serological and cellular response analyses of asymptomatic subjects in Wuhan, the original epicenter of the COVID-19 outbreak. Our data showed that up to 5.91% of the food workers carried SARS-CoV-2 IgG antibodies asymptomatically; however, in 90.4% of them, the antibody level declined over a 2-week period. IgM and IgG antibodies, including neutralizing antibodies, were significantly lower in asymptomatic subjects than in recovered symptomatic patients with similar disease courses. Furthermore, the asymptomatic subjects showed lymphopenia and a prominent decrease in the B-cell population, as well as a low frequency of antibody-secreting cells and a low cytokine response. These factors probably contributed to the low and unsustained antibody levels in asymptomatic subjects. Our results show that asymptomatic subjects are likely to be vulnerable to SARS-CoV-2 reinfection, and neither the proportion of population immunity nor the breadth of immune responses is sufficient for herd immunity.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Infecções Assintomáticas , Teste Sorológico para COVID-19 , COVID-19/imunologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Pandemias , SARS-CoV-2/imunologia , Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/biossíntese , Linfócitos B , COVID-19/epidemiologia , Teste de Ácido Nucleico para COVID-19 , China/epidemiologia , Convalescença , Citocinas/sangue , Suscetibilidade a Doenças , Ensaio de Imunoadsorção Enzimática , Seguimentos , Manipulação de Alimentos , Genoma Viral , Humanos , Imunidade Coletiva , Imunoglobulina G/biossíntese , Imunoglobulina M/biossíntese , Contagem de Linfócitos , Linfopenia/etiologia , Filogenia , RNA Viral/sangue , Reação em Cadeia da Polimerase em Tempo Real , SARS-CoV-2/genética , Estudos Soroepidemiológicos , Escarro/virologia
17.
Ann Palliat Med ; 10(4): 4232-4241, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33894727

RESUMO

BACKGROUND: Malnutrition dramatically increases the risk of postoperative complications and delays patient recovery. Therefore, a feeding jejunostomy tube (FJT) is routinely placed during esophagectomy to maintain the postoperative nutrition supply. However, recently published studies have questioned the need of a FJT in every esophageal cancer patient. Because most patients can resume oral intake shortly after surgery, the nutrition-providing function of a FJT becomes much less critical. In contrast, FJT-related complications could be severe. METHODS: Relevant publications were found out by systemic searching of four medical databases (PubMed, EMBASE, Medline, and Cochrane Center Register of Controlled Trials). By reading the titles and the abstracts, potentially relevant studies were screened from the search results. The incidence of postoperative complications and FJT-related complications were calculated and compared to evaluate the efficacy of a FJT. RESULTS: Eighteen studies were included in the meta-analysis. The no-FJT group had a similar or even lower incidence of postoperative complications [anastomotic leakage (AL), pulmonary complications, and wound infections] compared with the FJT group. Ileus and FJT site infections were the most common FJT-related complications. The incidence of ileus was approximately 6% (95% CI: 3-12%), and over 63% of the patients with an ileus required re-operation to relieve the obstruction. The pooled mean rate of FJT site infections was 7% (95% CI: 6-9%). Approximately 7% of patients had dysfunction (obstruction or dislocation) of the jejunostomy tube (95% CI: 3-14%). CONCLUSIONS: The non-selective placement of a FJT during esophagectomy provides few benefits to the patients and may even increase the risk of postoperative complications. Therefore, an intraoperative FJT should be selectively prescribed, but not routinely in the surgical treatment of esophageal cancer.


Assuntos
Neoplasias Esofágicas , Esofagectomia , Nutrição Enteral , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Humanos , Intubação Gastrointestinal , Jejunostomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
18.
Pain Ther ; 10(1): 333-347, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33826110

RESUMO

Lumbar spine surgery is one of the most widespread types of surgery for treating back and leg pain. However, the postoperative period always presents with severe pain due to the removal of skin, subcutaneous tissues, bones, and ligaments. Patients usually require high doses of opioids to relieve pain during the initial three days after operation, as well as experience drug-related complications and prolonged length of stay in hospital. We found that Erector spinae plane block significantly reduced postoperative opioid consumption and pain scores. The present systematic review revealed that ESPB was effective and safe for postoperative analgesia.

19.
Metabolism ; 119: 154771, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33831422

RESUMO

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a chronic disease with hallmarks of hyperglycemia and hyperlipidemia. Long-term hyperglycemia damages the functions of multiple tissues and organs leading to a series of complications and disability or even death. Nuclear receptor farnesoid X receptor (FXR) antagonism has been recently discovered to exhibit beneficial effect on glucose metabolism in T2DM mice, although the underlying mechanisms remain unclear. Here, we performed the study on the discovery of new FXR antagonist and investigated the mechanism underlying the amelioration of FXR antagonism on glucose homeostasis in T2DM mice by using the determined FXR antagonist as a probe. METHODS: FXR antagonist Mebhydrolin was discovered by screening against the lab in-house FDA approved drug library through surface plasmon resonance (SPR), microscale thermophoresis (MST), AlphaScreen, mammalian one-hybrid and transactivation assays. Activity of Mebhydrolin in improving glucose homeostasis was evaluated in db/db and HFD/STZ-induced T2DM mice, and the mechanisms governing the regulation of Mebhydrolin were investigated by assays of immunostaining, Western blot, ELISA, RT-PCR against liver tissues of both T2DM mice and the T2DM mice with liver-specific FXR knockdown injected via adeno-associated-virus AAV-FXR-RNAi and mouse primary hepatocytes. Finally, molecular docking and molecular dynamics (MD) technology-based study was performed to investigate the structural basis for the antagonistic regulation of Mebhydrolin against FXR at an atomic level. FINDINGS: Mebhydrolin ameliorated blood glucose homeostasis in T2DM mice by both suppressing hepatic gluconeogenesis via FXR/miR-22-3p/PI3K/AKT/FoxO1 pathway and promoting glycogen synthesis through FXR/miR-22-3p/PI3K/AKT/GSK3ß pathway. Structurally, residues L291, M332 and Y373 of FXR were required for Mebhydrolin binding to FXR-LBD, and Mebhydrolin induced H2 and H6 shifting of FXR potently affecting the regulation of the downstream target genes. CONCLUSIONS: Our work has revealed a novel mode for the regulation of FXR against glucose metabolism in T2DM mice and highlighted the potential of Mebhydrolin in the treatment of T2DM.


Assuntos
Carbolinas/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose/metabolismo , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Carbolinas/química , Carbolinas/farmacocinética , Células Cultivadas , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/metabolismo , Gluconeogênese/efeitos dos fármacos , Gluconeogênese/genética , Células HEK293 , Homeostase/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Simulação de Acoplamento Molecular , Domínios e Motivos de Interação entre Proteínas , Receptores Citoplasmáticos e Nucleares/química , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Estreptozocina
20.
Virol Sin ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33835391

RESUMO

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused more than 96 million infections and over 2 million deaths worldwide so far. However, there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the disease causative agent. Vaccine is the most effective approach to eradicate a pathogen. The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations. Here we evaluated the safety, immunogenicity, and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates. Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates, and subsequently provided partial (in low dose) or full (in high dose) protection of challenge in the tested animals. In addition, passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice. These results warranted positive outcomes in future clinical trials in humans.

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