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1.
Biomed Chromatogr ; : e5265, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34648212

RESUMO

Poloxamer (PL)188 is a commonly used pharmaceutical excipient with unique physicochemical properties. In this study, a MSALL quantitative method for the determination of PL188 in rat plasma by UHPLC-Q-TOF/MS was developed and validated. PL188 was analyzed on PLRP-S Reversed-Phase column (50 × 4.6 mm, 8 µm, 1000 Å) with mobile phase 0.1% formic acid-water and 0.1% formic acid-acetonitrile: isopropanol (2:3, v/v). The liner range was 0.1~10.0 µg/mL. Pharmacokinetic study was experimented on rats at a dose of 5 mg/kg by intravenous injection. The pharmacokinetic parameters of intravenous injection were as follows: t1/2 was 2.0 ± 1.1 h, Vd was 5.1± 3.2 L/kg, AUC(0-t) was 3.0 ± 0.6 µg/L*h, CL was 1.7 ± 0.3 L/h/kg. The results indicated that PL188 could be rapidly distributed to tissues with a high clearance rate. This study can provide a good reference for the further study of PL188.

2.
Bioorg Chem ; 116: 105384, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34601294

RESUMO

The Src homology-2 domain containing-protein tyrosine phosphatase-2 (SHP2) is a convergent node for oncogenic cell-signaling cascades including the PD-L1/PD-1 pathway. As an oncoprotein as well as a potential immunomodulator, SHP2 has now emerged as an attractive target for novel anti-cancer agents. Although significant progress has been made in identifying chemotypes of SHP2 inhibitors, these specific compounds might not be clinically useful to inhibit frequently encountered mutated SHP2 variants. Consequently, it is highly desirable to develop chemically different SHP2 inhibitors sensitive to SHP2 mutants. This work developed a new type of SHP2 inhibitors with 2,5-diaryl-1,3,4-oxadiazole scaffold. The representative compound 6l exhibited SHP2 inhibitory activity with IC50 of 2.73 ± 0.20 µM, showed about 1.56-fold, 5.26-fold, and 7.36-fold selectivity for SHP2 over SHP1, PTP1B and TCPTP respectively. Further investigations confirmed that 6l behaved as mixed-type inhibitor sensitive to leukemia cell TF-1 and inhibited SHP2 mediated cell signaling and proliferation. Molecular dynamics simulation provided more detailed information on the binding modes of compounds and SHP2 protein. These preliminary results could provide a possible opportunity for the development of novel SHP2 inhibitors sensitive to SHP2 mutants with optimal potency and improved pharmacological properties.

3.
JAMA Surg ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34613330

RESUMO

Importance: Preventing anastomotic leakage (AL) is crucial for colorectal surgery. Some studies have suggested a positive role of transanal drainage tubes (TDTs) in AL prevention after low anterior resection, but this finding is controversial. Objective: To assess the effect of TDTs in AL prevention after laparoscopic low anterior resection for rectal cancer. Design, Setting, and Participants: This multicenter randomized clinical trial with parallel groups (TDT vs non-TDT) was performed from February 26, 2016, to September 30, 2020. Participants included patients from 7 different hospitals in China who were undergoing laparoscopic low anterior resection with the double-stapling technique for mid-low rectal cancer; 576 patients were initially enrolled in this study, and 16 were later excluded. Ultimately, 560 patients were randomly divided between the TDT and non-TDT groups. Interventions: A silicone tube was inserted through the anus, and the tip of the tube was placed approximately 5 cm above the anastomosis under laparoscopy at the conclusion of surgery. The tube was fixed with a skin suture and connected to a drainage bag. The TDT was scheduled for removal 3 to 7 days after surgery. Main Outcomes and Measures: The primary end point was the postoperative AL rate within 30 days. Results: In total, 576 patients were initially enrolled in this study; 16 of these patients were excluded. Ultimately, 560 patients were randomly divided between the TDT group (n = 280; median age, 61.5 years [IQR, 54.0-68.8 years]; 177 men [63.2%]) and the non-TDT group (n = 280; median age, 62.0 years [IQR, 52.0-69.0 years]; 169 men [60.4%]). Intention-to-treat analysis showed no significant difference between the TDT and non-TDT groups in AL rates (18 [6.4%] vs 19 [6.8%]; relative risk, 0.947; 95% CI, 0.508-1.766; P = .87) or AL grades (grade B, 14 [5.0%] and grade C, 4 [1.4%] vs grade B, 11 [3.9%] and grade C, 8 [2.9%]; P = .43). In the stratified analysis based on diverting stomas, there was no significant difference in the AL rate between the groups, regardless of whether a diverting stoma was present (without stoma, 12 [5.8%] vs 15 [7.9%], P = .41; and with stoma, 6 [8.3%] vs 4 [4.5%], P = .50). Anal pain was the most common complaint from patients in the TDT group (130 of 280, 46.4%). Accidental early TDT removal occurred in 20 patients (7.1%), and no bleeding or iatrogenic colonic perforations were detected. Conclusions and Relevance: The results from this randomized clinical trial indicated that TDTs may not confer any benefit for AL prevention in patients who undergo laparoscopic low anterior resection for mid-low rectal cancer without preoperative radiotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02686567.

4.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(4): 590-594, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34494531

RESUMO

Objective To investigate the oral health status and awareness of urban children in Lhasa,aiming to provide a data basis for the prevention and treatment of children's caries and the promotion of oral health education. Methods A total of 504 Tibetan students were selected by cluster sampling from 2 primary schools in Chengguan District of Lhasa.All the participants were required to take oral health examination and complete a questionnaire about oral health awareness and behavior. Results The caries prevalence rate and mean decayed-missing-filled tooth(DMFT)of permanent teeth were 75.00% and 2.18±1.91,respectively.The rates of pit and fissure sealant and filling of permanent teeth were 3.77% and 6.81%,respectively.The caries prevalence rate of first permanent molars was 47.62%.The mean DMFT of permanent teeth and caries prevalence rate of first permanent molar were significantly higher in female group(P=0.001 and P=0.007,respectively).The prevalence rate of dental fluorosis was 61.51%,and the detection rate of dental calculus was 71.83%.Multivariate logistic regression analysis showed that prevalence of caries was influenced by many independent factors including gender,oral health awareness,intention of dental intervention,and dental experience. Conclusion High caries prevalence rate,low filling rate,and poor oral hygiene and health awareness were found among the primary school students in Lhasa,which require continuous dentistry investment and oral health education for the local students and their parents.


Assuntos
Cárie Dentária , Saúde Bucal , Criança , Índice CPO , Cárie Dentária/epidemiologia , Feminino , Humanos , Higiene Bucal , Prevalência , Instituições Acadêmicas , Estudantes , Inquéritos e Questionários
5.
Biomed Phys Eng Express ; 7(6)2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34500439

RESUMO

Melanoma is one of the most aggressive skin cancers. However, there remain many limitations in the current clinical treatments of it. Zinc oxide nanoparticles (ZnO NPs) have been considered to be a promising antitumor drug due to their excellent biocompatibility, biodegradability and biofunctionality. In this study, we prepared spherical ZnO NPs with an average diameter of less than 10 nm by a simple chemical method. According to thein vitrocytotoxicity assay, ZnO NPs in a certain concentration range (20-35µg ml-1) showed significant cytotoxicity to B16F10 melanoma cells, while having little effect on the viability of 3T3L1 fibroblasts. When cultured with B16F10 melanoma cells, ZnO NPs induced the generation of reactive oxygen and mitochondrial superoxide through the release of Zn2+, leading to oxidative stress in the cells, further reducing the mitochondrial membrane potential and decreasing the number of mitochondrial cristae. Furthermore, damaged mitochondria induced the release of apoptosis factors to promote cell apoptosis. FITC-Annexin V/propidium iodide double staining assay was used to analyze different apoptosis stages of B16F10 cells induced by ZnO NPs. A polymer hydrogel (Gel-F127-ZnO NPs) with Pluronic F127 as the carrier of ZnO NPs was fabricated for evaluating the antitumor effect of ZnO NPsin vivo. Thein vivoexperiment indicated that the tumor recurrence was significantly inhibited in tumor-bearing mice after treated with Gel-F127-ZnO NPs. Conclusively, ZnO NPs showed a strong antitumor effect bothin vitroandin vivo.

6.
J Immunol ; 207(8): 2179-2191, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34497150

RESUMO

Gut microbes play an important role in the development of host B cells. It has been controversial whether GALT is the development site of B cells in pigs. By investigating the relationship between gut microbes and the development of B cells in the GALT of piglets, we found, to our knowledge for the first time, that early B cells exist in the gut lamina propria (LP) in pigs at different ages. We further used Lactobacillus rhamnosus GG (LGG) to treat piglets. The results showed that LGG promotes the development of the early B lineage, affects the composition of the Ig CDR3 repertoires of B cells, and promotes the production of IgA in the intestinal LP. Additionally, we found that the p40 protein derived from LGG can activate the EGFR/AKT and NF-κB signaling pathways, inducing porcine intestinal epithelial cells (IPEC-J2) to secrete a proliferation-inducing ligand (APRIL), which promotes IgA production in B cells. Finally, we identified ARF4 and DIF3 as candidates for p40 receptors on IPEC-J2 by GST pull-down, liquid chromatography-mass spectrometry/mass spectrometry analysis, and coimmunoprecipitation. In conclusion, LGG could promote early B cell differentiation and development in the intestinal LP in piglets and might contribute to promoting IgA production via secretion of p40, which interacts with the membrane receptors on IPEC-J2 and induces them to secrete APRIL. Our study will provide insight to aid in better utilization of probiotics to increase human health.

7.
Ecotoxicol Environ Saf ; 225: 112791, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34555721

RESUMO

Mercury (Hg) brings adverse effects to the environment and human beings and inorganic mercury (IHg) is a typical hepatic toxin. This work studied the impacts of IHg on gut microbes and metabolome together with its damage to liver and gut in rats through gut microbiome, metabolomics and metallomics. Sprague Dawley (SD) rats were orally exposed to 0.4 µg/mL IHg and sacrificed after 24 h. It was found that IHg perturbed greatly on the gut microbiota, such as increased pathogenic bacteria like G. bacillus. In addition, IHg also changed gut-liver axis related metabolites, which was confirmed by the secretion of a large number of inflammatory factors in both the gut and the liver. The changed gut-liver axis related metabolites correlated well to the changes of gut microbiome. In all, besides the direct deposition in liver of Hg, the perturbance to gut microbiome and alteration of gut-liver axis related metabolites by IHg also contributed to its hepatoxicity, which provides new insights about the hepatoxicity of chemicals. The strategy applied in this work may also be used to understand the hepatoxicity of other chemicals.


Assuntos
Microbioma Gastrointestinal , Mercúrio , Animais , Fígado , Mercúrio/toxicidade , Metabolômica , Ratos , Ratos Sprague-Dawley
8.
Molecules ; 26(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34577115

RESUMO

Poloxamer188 (PL188), as one of the most commonly used pharmaceutical excipients, has unique physicochemical properties and good biocompatibility, and so is playing an increasingly extensive role in the field of medicine. Currently, there are few studies on the tissue distribution of PL188 in vivo. In this study, the LC-MS method based on MSALL technique of quadrupole time of flight mass spectrometry for absolute quantitative analysis of poloxamer 188 in biological substrates was established for the first time. The tissue distribution of poloxamer188 in SD rats were studied using the established quantitative analysis method. To explore the distribution of PL188 in organs and tissues, PL188 was administered via rat tail vein at a dose of 5 mg/kg. Eight kinds of tissues including heart, liver, spleen, lung, kidney, stomach, muscle and brain of rats were collected at 0.25 h, 1 h and 4 h after administration. Tissue distributions showed the highest level was observed in kidney, then in stomach, which indicated PL188 mainly bioaccumulated in the kidney. This study can provide references for the further study of PL188.

9.
Blood Adv ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34500454

RESUMO

Homing and engraftment of hematopoietic stem/progenitor cells (HSPCs) into the bone marrow (BM) microenvironment are tightly regulated by the chemokine SDF-1 and its G-protein-coupled receptor CXCR4, which on engagement with G-protein subunits, trigger downstream migratory signals. Regulators of G-protein signaling (RGS) are GTPase-accelerating protein of the Gα subunit and R4 subfamily members have been implicated in SDF-1-directed trafficking of mature hematopoietic cells, yet their expression and influence on HSPCs remain mostly unknown. Here, we demonstrated that human CD34+ cells expressed multiple R4 RGS genes, of which RGS1, RGS2, RGS13,and RGS16 were significantly upregulated by SDF-1 in a CXCR4-dependent fashion. Forced overexpression of RGS1, RGS13, or RGS16 in CD34+ cellsnot only inhibited SDF-1-directed migration, calcium mobilization, and phosphorylation of AKT, ERK, and STAT3 in vitro, but also markedly reduced BM engraftment in transplanted NOD/SCID mice. Genome-wide microarray analysis of RGS-overexpressing CD34+ cells detected downregulation of multiple effectors with established roles in stem cell trafficking/maintenance. Convincingly, gain-of-function of selected effectors or ex vivo priming with their ligands significantly enhanced HSPC engraftment. We also constructed an evidence-based network illustrating the overlapping mechanisms of RGS1, RGS13 and RGS16 downstream of SDF-1/CXCR4 and Gαi. This model shows that these RGS members mediate compromised kinase signaling and negative regulation of stem cell functions, complement activation, proteolysis and cell migration. Collectively, this study uncovers an essential inhibitory role of specific R4 RGS proteins in stem cell engraftment, which could potentially be exploited to develop improved clinical HSPC transplantation protocols.

10.
J Agric Food Chem ; 69(38): 11171-11184, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34529412

RESUMO

Purple wheat is thought to have beneficial effects on humans owing to its high anthocyanin content. However, a systematic understanding of the anthocyanin biosynthesis process in developing wheat grain is lacking. Here, the dynamic changes in anthocyanin components and transcripts in the grain of purple wheat ZNM168 at five developmental stages (10, 15, 20, 25, and 30 DAF) were characterized. Compared with other anthocyanins, four components, cyanidin 3-O-rutinoside, cyanidin 3-O-glucoside, cyanidin 3,5-O-diglucoside, and malvidin 3-O-glucoside, were significantly accumulated with grain development. In particular, the considerable accumulation of cyanidin 3-O-rutinoside indicated that it was the pivotal pigment for the purple grain. Transcriptome analysis revealed that the nine differentially expressed genes related to anthocyanin biosynthesis belonged to the BZ1 group, the homologous enzyme encoded by the maize Bronze-1 locus, which may primarily serve to glucosylate anthocyanidins. By constructing a gene coexpression network based on weighted gene coexpression network analysis, the TaBZ1 UniGene (TraesCS1D02G019200) was predicted as a core gene in anthocyanin biosynthesis. In addition, correlation analysis between the metabolites and transcripts suggested that TraesCS2A01G527700 (TaCHS) and TraesCS6B01G006200 (TaANS) were considered critical structural genes in the anthocyanin biosynthesis pathway. This study provides insights to exploit genes pinpointed as genetic engineering targets, thereby breeding anthocyanin-enriched wheat.


Assuntos
Antocianinas , Triticum , Regulação da Expressão Gênica de Plantas , Humanos , Metabolômica , Melhoramento Vegetal , Transcriptoma , Triticum/genética
11.
J Sep Sci ; 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34435744

RESUMO

Poloxamer is a commonly used pharmaceutical excipient. It is a high molecular polymer formed using polypropylene oxide and polyethylene oxide units. Specifically, poloxamer 124 is one of the smaller molecular weight in the poloxamer series; however, its pharmacokinetic behaviors in vivo are still unclear. In this study, a method for quantifying poloxamer 124 in rat plasma through ultra-high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry was developed. The intravenous dosage of PL124 was 10 mg/kg. Plasma was collected at different times. The calibration curve was linear in the range of 0.1-5 µg/mL for the poloxamer 124 (r ≥ 0.9956) with the lower limit of quantitation of 0.1 µg/ml. The relative standard deviation of the intraday and interday precisions was below 8.0%, and the relative error of the accuracy was within ±12.0%. The extraction recovery, matrix effect, and stability were satisfactory in rat plasma. The validated method was successfully applied to a pharmacokinetic study of poloxamer 124 in rats. Results indicated that poloxamer 124 could be rapidly absorbed and eliminated through caudal vein injection. This study is helpful for the further study of poloxamer 124.

12.
Mikrochim Acta ; 188(9): 308, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34453216

RESUMO

The ternary NiCoAl hydrotalcite (NiCoAl-LDH) was combined with carboxylic multi-walled carbon nanotube (MWCNT) to fabricate a novel electrochemical sensor for simultaneously determining the co-existing trace phenolic substances. The morphology, structure, and electrochemical behavior of the as-prepared materials were characterized by various techniques. Benefitting from the great conductivity of MWCNT and high electrocatalytic activity of NiCoAl-LDH for phenolic substances, the advanced MWCNT/NiCoAl-LDH sensor presented a fast response, high sensitivity, excellent stability, and satisfactory replicability. The sensor offered good linear responses in the ranges1.50~600 µM to hydroquinone (HQ), 5.00~1.03 × 103 µM to catechol (CC), and 6.00 × 10-2~250 µM to bisphenol A (BPA). The detection limits of HQ, CC, and BPA were 0.4, 0.8, and 6. × 10-3 µM (S/N = 3), respectively. In environmental water, the sensor achieved satisfactory recoveries for the simultaneous detection of HQ (98.6~101%), CC (98.0~101%), and BPA (97.5~101%), with relative standard deviations less than 4.4%.

13.
Contrast Media Mol Imaging ; 2021: 9668836, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34377105

RESUMO

This study focused on the application value of MRI images processed by a Support Vector Machine (SVM) algorithm-based model in diagnosis of benign and malignant solitary pulmonary nodule (SPN). The SVM algorithm was constrained by a self-paced regularization item and gradient value to establish the MRI image segmentation model (SVM-L) for lung. Its performance was compared factoring into the Dice index (DI), sensitivity (SE), specificity (SP), and Mean Square Error (MSE). 28 SPN patients who underwent the parallel MRI examination were selected as research subjects and were divided into the benign group (11 patients) and malignant group (17 patients) according to different plans for diagnosis and treatment. The apparent diffusion coefficient (ADC) at different b values was analyzed, and the steepest slope (SS) and washout ratio (WR) values in the two groups were calculated. The result showed that the MSE, DI, SE, SP values, and operation time of the SVM-L model were (0.41 ± 0.02), (0.84 ± 0.13), (0.89 ± 0.04), (0.993 ± 0.004), and (30.69 ± 2.60)s, respectively, apparently superior to those of the other algorithms, but there were no statistic differences (P > 0.05) in the WR value between the two groups of patients. The SS values of the time-signal curve in the benign and malignant groups were (2.52 ± 0.69) %/s and (3.34 ± 00.41) %/s, respectively. Obviously, the SS value of the benign group was significantly lower than that of the malignant group (P < 0.01). The ADC value with different b values in the benign group was significantly lower than that of the malignant group (P < 0.01). It suggested that the SVM-L model significantly improved the quality of lung MRI images and increased the accuracy to differentiate benign and malignant SPN, providing reference for the diagnosis and treatment of SPN patients.

14.
Sci Adv ; 7(34)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34407949

RESUMO

The signaling pathway directly controlling the maintenance of adult glutamatergic synapses has not been well understood. Planar cell polarity (PCP) signaling components were recently shown to play essential roles in the formation of glutamatergic synapses. Here, we show that they are localized in the adult synapses and are essential for their maintenance. Synapse loss at early stages of Alzheimer's disease is thought to be induced by ß-amyloid (Aß) pathology. We found that oligomeric Aß binds to Celsr3 and assists Vangl2 in disassembling synapses. Moreover, a Wnt receptor and regulator of PCP signaling, Ryk, is also required for Aß-induced synapse loss. In the 5XFAD mouse model of Alzheimer's disease, Ryk conditional knockout or a function-blocking monoclonal Ryk antibody protected synapses and preserved cognitive function. We propose that tipping of the fine balance of Wnt/PCP signaling components in glutamatergic synapses may cause synapse degeneration in neurodegenerative disorders with Aß pathology.

15.
Obes Facts ; 14(5): 450-455, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34428761

RESUMO

INTRODUCTION: This study aimed to investigate whether neck circumference (NC) was associated with the incidence of type 2 diabetes in Chinese elderly individuals. METHODS: A community-based cohort study was conducted on elderly inhabitants in Shanghai with a mean age of 71.0 ± 5.8 years (n = 2,646). Binary logistic regression analysis was performed to evaluate the association between NC and the prevalence of type 2 diabetes, while a Cox regression model was used to determine the association between NC and the incidence of type 2 diabetes after a follow-up of 2 years. RESULTS: Logistic regression analysis showed that a larger NC was significantly associated with an increased risk for type 2 diabetes in men (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.07-1.31; p = 0.001) and women (OR 1.25, 95% CI 1.13-1.38; p < 0.001). Cox regression analysis revealed that NC was independently associated with the incidence of type 2 diabetes in both men (hazard ratio [HR] 1.14, 95% CI 1.05-1.23; p = 0.002) and women (HR 1.18, 95% CI 1.10-1.27; p < 0.001). CONCLUSIONS: A larger NC was associated with a higher risk of developing type 2 diabetes in Chinese elderly individuals. However, studies with larger sample sizes and longer follow-up durations are needed to definitively determine the relationship between NC and the risk of developing type 2 diabetes.

16.
mSphere ; 6(4): e0028321, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34346706

RESUMO

Dystonia is a complex neurological movement disorder characterized by involuntary muscle contractions. Increasing studies implicate the microbiome as a possible key susceptibility factor for neurological disorders, but the relationship between the gut microbiota and dystonia remains poorly explored. Here, the gut microbiota of 57 patients with isolated dystonia and 27 age- and environment-matched healthy controls was analyzed by 16S rRNA gene amplicon sequencing. Further, integrative analysis of the gut microbiome and serum metabolome measured by high-performance liquid chromatography-mass spectrometry was performed. No difference in α-diversity was found, while ß-diversity was significantly different, with a more heterogeneous community structure among dystonia patients than among controls. The most significant changes in dystonia highlighted an increase in Clostridiales, including Blautia obeum, Dorea longicatena, and Eubacterium hallii, and a reduction in Bacteroides vulgatus and Bacteroides plebeius. The functional analysis revealed that genes related to tryptophan and purine biosynthesis were more abundant in gut microbiota from patients with dystonia, while genes linked to citrate cycle, vitamin B6, and glycan metabolism were less abundant. The evaluation of serum metabolites revealed altered levels of l-glutamic acid, taurine, and d-tyrosine, suggesting changes in neurotransmitter metabolism. The most modified metabolites strongly inversely correlated with the abundance of members belonging to the Clostridiales, revealing the effect of the gut microbiota on neurometabolic activity. This study is the first to reveal gut microbial dysbiosis in patients with isolated dystonia and identified potential links between gut microbiota and serum neurotransmitters, providing new insight into the pathogenesis of isolated dystonia. IMPORTANCE Dystonia is the third most common movement disorder after essential tremor and Parkinson's disease. However, the cause for the majority of cases is not known. This is the first study so far that reveals significant alterations of gut microbiome and correlates the alteration of serum metabolites with gut dysbiosis in patients with isolated dystonia. We demonstrated a general overrepresentation of Clostridiales and underrepresentation of Bacteroidetes in patients with dystonia in comparison with healthy controls. The functional analysis found that genes related to the biosynthesis of tryptophan, which is the precursor of the neurotransmitter serotonin, were more active in isolated dystonia patients. Altered levels of several serum metabolites were found to be associated with microbial changes, such as d-tyrosine, taurine, and glutamate, indicating differences in neurotransmitter metabolism in isolated dystonia. Integrative analysis suggests that neurotransmitter system dysfunction may be a possible pathway by which the gut microbiome participates in the development of dystonia. The gut microbiome changes provide new insight into the pathogenesis of dystonia, suggesting new potential therapeutic directions.

17.
Ann Palliat Med ; 10(7): 7919-7932, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34353079

RESUMO

BACKGROUND: This study sought to systematically evaluate the distribution characteristics and high-risk factors of pulmonary mycosis pathogens, and provide evidence for the clinical treatment and prognosis of patients with pulmonary mycosis. METHODS: The Embase, Ovid, PubMed, Medline, and Springer databases were searched to find publications on the distribution characteristics and high-risk factors of pulmonary mycosis pathogens that had been published between the establishment of the databases and April 1, 2021. The Cochrane Handbook 5.0.2 was used to evaluate the risk of bias of the articles included in this study, and Review Manager 5.3 was used to conduct a meta-analysis of the included articles. RESULTS: Eleven articles were included in this study, comprising 6,415 subjects. The meta-analysis results showed that pathogen infection significantly increased the mortality of patients [MD =2.67; 95% confidence interval (CI): (1.52, 4.68); Z=3.43; P=0.0006]. Patient age was significantly correlated with the incidence of pulmonary mycosis [MD =1.21; 95% CI: (0.78, 1.86); Z=0.84; P=0.40]. The use of antibiotics was significantly correlated to the incidence of pulmonary mycosis [MD =1.41; 95% CI: (1.15, 1.72); Z=3.30; P=0.001]. Glucocorticoid use was significantly correlated to the incidence of pulmonary mycosis [MD =1.81; 95% CI: (1.13, 2.91); Z=2.45; P=0.01]. However, gender had no obvious correlation with the incidence of pulmonary mycosis [MD =1.21; 95% CI: (0.78, 1.86); Z=0.84; P=0.40]. Further, no correlation was found between smoking history and the incidence of pulmonary mycosis [MD =0.86; 95% CI: (0.51, 1.45); Z=0.57; P=0.57]. DISCUSSION: The main types of bacterial infections in patients with pulmonary mycosis were Pseudomonas aeruginosa, Haemophilus influenzae, Streptococcus pneumoniae, Candida albicans, and Helicobacter pylori. In addition to the lungs, pathogens were found to be distributed in the intestines, urinary tract, and digestive tract. Additionally, patient age, antibiotic use, and glucocorticoid use increased the incidence of pulmonary mycosis. Thus, these factors should be paid attention to in the clinical treatment of patients with pulmonary mycosis.


Assuntos
Prognóstico , Humanos
18.
J Gastroenterol ; 56(9): 856-867, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34292372

RESUMO

BACKGROUND: Nucleos(t)ide analogues (NAs) cessation is not widely practiced and remains a controversial, but highly relevant subject in patients infected with hepatitis B virus (HBV). We aimed to explore the related factors for safe NAs cessation. METHODS: This is a multicenter prospective cohort study. Overall, 139 initially HBV e antigen (HBeAg)-positive patients meeting the stopping criteria were included in 12 hospitals in China. Enrolled patients ceased NAs and were followed up every 3 months for 24 months or until clinical relapse (CR). RESULTS: The 24 month cumulative rates of virological relapse (VR), CR, HBeAg reversion and HBV surface antigen (HBsAg) loss were 50.4, 24.5, 11.5 and 9.4%, respectively. Patients with end of treatment (EOT) HBsAg < 100 IU/mL plus negative HBV RNA had the lowest 24 month cumulative VR rate (5 vs 58%, p < 0.001). EOT HBsAg ≥ 2 log10 IU/mL [odds ratio (OR) = 6.686, p = 0.006], EOT positive HBV RNA (OR = 3.453, p = 0.008) and EOT hepatitis B core-related antigen (HBcrAg) ≥ 4log U/mL (OR = 3.702, p = 0.002) were found to independently predict the risk of VR. To predict VR, the area under the receiver-operating characteristic (AUROC) value of the EOT HBsAg < 100 IU/mL plus EOT HBV RNA negative was 0.698 (p < 0.001), which was higher than other parameters alone or combinations. CONCLUSIONS: NAs cessation is suitable only for a small and selected patients. An EOT HBsAg < 100 IU/mL and EOT negative HBV RNA identified a patient with low risk of off-treatment VR.

19.
Dis Colon Rectum ; 64(10): 1286-1296, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34310517

RESUMO

BACKGROUND: Opinions vary on the medial border of D3 lymphadenectomy for right colon cancer. Most surgeons place the medial border along the left side of the superior mesenteric vein, but some consider the left side of the superior mesenteric artery as the medial border. OBJECTIVES: This study investigated the clinical outcomes of laparoscopic D3 lymphadenectomy for right colon cancer with the medial border along the left side of superior mesenteric artery. DESIGN: This was a retrospective study. SETTINGS: The study was conducted in specialized colorectal cancer department of 5 tertiary hospitals. PATIENTS: Patients receiving laparoscopic D3 lymphadenectomy for right colon cancer from January 2013 to December 2018 were included. MAIN OUTCOME MEASURES: After propensity score matching, 307 patients receiving laparoscopic D3 lymphadenectomy along the left side of the superior mesenteric artery were assigned to the superior mesenteric artery group and 614 patients were assigned to the superior mesenteric vein group. Univariate, multivariate, and Kaplan-Meier analyses were performed to assess the clinical data. RESULTS: The short-term outcomes were similar between the 2 groups; however, the superior mesenteric artery group had a higher rate of chylous leakage (p < 0.001). More lymph nodes were harvested from the superior mesenteric artery group than from the superior mesenteric vein group (p = 0.001). The number (p = 0.005) of metastatic lymph nodes and the lymph node ratio (p = 0.041) in main nodes were both higher in the superior mesenteric artery group. The 2 groups had similar long-term survival, but the superior mesenteric artery group tended to show better disease-free survival in patients with stage disease III (p = 0.056). LIMITATIONS: This was a retrospective, nonrandomized study. CONCLUSION: Laparoscopic D3 lymphadenectomy along the left side of the superior mesenteric artery, except for a higher rate of chylous leakage, had short-term outcomes comparable to the superior mesenteric vein group. The superior mesenteric artery group tended to achieve better disease-free survival in patients with stage III disease, but further study is required to better elucidate differences in these approaches because risks/benefits do exist.

20.
Artigo em Chinês | MEDLINE | ID: mdl-34304539

RESUMO

Oncocytic carcinoma of tongue is extremely rare. This paper reports a case of malignant transformation from oncocytic adenoma to oncocytic carcinoma. A 29-year-old man complained of pharyngeal bleeding and swallowing obstruction. The tumor at the base of the tongue was surgically removed and the pathological diagnosis was oncocytic adenoma. After 5 years, the patient found a tumor of the right neck and felt pharyngeal bleeding and swallowing obstruction again. The next year, he was treated with surgery, chemotherapy and radiotherapy, and was diagnosed as oncocytic carcinoma with cervical lymph node metastasis. The patient showed no sign of recurrence until 30 months after the second operation, when tumor of tongue was detected by electronic laryngoscope. Surgery, chemotherapy and radioactive seed implantation were adopted again. Up to now, the follow-up data showed no evidence of recurrence.


Assuntos
Adenocarcinoma , Neoplasias da Língua , Adulto , Humanos , Linfonodos , Metástase Linfática , Masculino , Esvaziamento Cervical , Recidiva Local de Neoplasia , Língua , Neoplasias da Língua/cirurgia
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