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1.
Langmuir ; 38(13): 4111-4120, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35312331

RESUMO

Self-driven droplet transport along an open gradient surface is increasingly becoming popular for various microfluidics applications. In this work, a gradient copper oxide layer is formed on a copper sheet (as a bipolar electrode, BPE) in a KOH solution by bipolar electrochemistry. The deposits at different positions present a rich variety of colors, compositions, and microstructures along the longitudinal axis of the BPE. More than half the length of the anodic pole is covered by a Cu(OH)2/CuO composite layer of several micrometers thick, which is composed of dense micropillars with a decreasing spacing gradient to the anodic direction. The micropillar arrays are superhydrophilic, and after modified with 1-dodecanethiol, the tops of the dense micropillars constitute a hydrophobic and microscopically discontinuous surface with a wettability gradient. On such a gradient surface water droplets can move spontaneously to more hydrophilic direction at a velocity of about 16 mm s-1. The superhydrophobicity of the modified micropillar arrays is discussed through a comparison with the wax tubules on a lotus leaf. Theoretical analysis of the driving force reveals that the concave surface effect of water at the spacings between the micropillars is the critical factor for driving the rolling motion of the droplets along the gradient micropillar arrays.

2.
Front Med (Lausanne) ; 9: 737694, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911390

RESUMO

Purpose: This retrospective study aimed to compare the efficacy and safety of single-session OK-432 and multiple-session 99% ethanol sclerotherapy for symptomatic simple hepatic cysts. Methods: We reviewed patients who received aspiration sclerotherapy with OK-432 (group A) or 99% ethanol (group B) for symptomatic simple hepatic cysts at Guangdong Provincial People's Hospital from January 2013 to November 2019. Results: We included 42 patients in group A and 39 patients in group B. No significant difference was found in the mean volume of hepatic cysts between the two groups. The overall success rates were 92.9% (39 of 42 patients) in group A and 79.5% (31 of 39 patients) in group B (P = 0.08). The treatment success for cyst volumes <200 ml, 200-500 ml, and >500 ml was 100, 93.3, and 88.2% in group A, and 100, 84.6, and 57.1% in group B, respectively. The symptomatic relief rate in group A was higher than that in group B for cysts ≥500 ml (P = 0.049) and cysts <500 ml. For treatment-related complications, the incidence of pain at the injection site in group A was lower than that in group B. Conclusion: Single-session OK-432 sclerotherapy was safer and more effective than multiple-session 99% ethanol sclerotherapy for treating large cysts, although both treatments had similar effects on small cysts.

3.
Front Immunol ; 13: 896744, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911679

RESUMO

Toxoplasma gondii (T. gondii), one of the most important Apicomplexan protozoa, causes toxoplasmosis in human throughout the world. Galectin (Gal)-9 triggers a series of immune events via binding to its receptors, including T cell immunoglobulin and mucin-containing molecule 3, CD137, CD44, and protein disulfide isomerase. To examine the regulatory role of galectin-receptor interactions in anti-toxoplasmic activities, C57BL/6 mice were infected with T. gondii RH strain and intraperitoneally injected with alpha (α)-lactose to block the interactions of galectins and their receptors. Heatmaps showed upregulated values for Gal-9 and CD137 in the livers of T. gondii-infected mice and T. gondii-infected mice treated with α-lactose. Compared with T. gondii-infected mice, T. gondii-infected mice treated with α-lactose showed significantly increased survival rate, decreased tissue parasite burden, attenuated liver histopathology, increased mRNA expression levels of CD137, IFNγ, IL-4, and IL-10 in the liver, and increased Gal-9 mRNA expression level in the spleen. Correlation analysis showed that significant positive correlations existed between the mRNA expression levels of Gal-9 and CD137, Gal-9 and IFNγ, as well as between CD137 and IFNγ in the liver and spleen of T. gondii-infected mice; between CD137 and IFNγ in the liver of T. gondii-infected mice treated with α-lactose. In addition, blockage of galectin-receptor interactions showed enhanced M2 macrophage polarization in the liver of T. gondii-infected mice. Our data indicate that Gal-9-CD137 interaction may play an important role in T. gondii proliferation and liver inflammation in mice during acute T. gondii infection, through regulating T cell and macrophage immune responses.


Assuntos
Toxoplasma , Toxoplasmose , Animais , Galectinas/metabolismo , Humanos , Lactose/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/metabolismo
4.
Front Immunol ; 13: 922922, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911771

RESUMO

Objectives: Multiple sclerosis (MS) is a chronic inflammatory autoimmune and degenerative disorder of the central nervous system. Telomeres are protective structures located at the ends of linear chromosomes, and leukocyte telomere length (LTL) is closely connected with cell aging and senescence. However, the relationship between LTL and the risk of MS remains unknown. Methods: We performed a two-sample Mendelian randomization (MR) to evaluate whether LTL was causally associated with MS risk. Results: In our MR analysis, 12 LTL-related variants were selected as valid instrumental variables, and a causal relationship between LTL and MS was suggested. The risk of MS nearly doubled as the genetically predicted LTL shortened by one standard deviation (SD) under the inverse variance weighted (IVW) fixed effect model (odds ratio (OR) = 2.00, 95% confidence interval (CI): 1.52-2.62, p = 6.01e-07). Similar estimated causal effects were also observed under different MR models. The MR-Egger regression test did not reveal any evidence of directional pleiotropy (intercept = -0.005, stand error (SE) = 0.03, p = 0.87). The Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) analysis also indicated no directional pleiotropy or outliers for any LTL-related IVs (p-global test = 0.13). In addition, a leave-one-out sensitivity analysis showed similar findings, which further emphasized the validity and stability of the causal relationship. Conclusions: Our results suggest a potential causal effect of LTL on the risk of MS. Genetically predicted shorter LTL could increase the risk of MS in the European population. LTL should be noted and emphasized in the pathogenesis and treatment of MS.


Assuntos
Análise da Randomização Mendeliana , Esclerose Múltipla , Estudo de Associação Genômica Ampla , Humanos , Leucócitos , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único , Telômero/genética
5.
Curr Mol Med ; 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927807

RESUMO

BACKGROUND: Gliomas, the most common and malignant primary tumors, relate to the highest mortality rate of all central nervous system cancers. Previously, it has been demonstrated that Rap2A plays an essential role in tumor growth in human cancer cell lines. However, it remains largely unclear as to whether and how Rap2A is involved in the development of gliomas. In the current study, the role of Rap2A in glioma and its specific molecular mechanism are investigated by our group. METHODS: Expression of Rap2A was examined in glioma cell lines and human normal astrocyte cells using Western blot analysis. Using the CCK-8 cell proliferation assay, wound healing assay, and transwell migration assay, we elucidated the role of Rap2A in glioma cell proliferation and migration. Levels of E-cadherin, vimentin and phosphorylation of ERK1/2 were also determined using Western blot. RESULTS: The results suggested that Rap2A expression was remarkably decreased in glioma cells compared to the normal astrocyte cells. Overexpression of Rap2A prominently suppressed cell proliferation and migration as well as enhanced E-cadherin expression and reduced vimentin level in both U87 and U251 cells. In vivo assay proved that Rap2A overexpression slowed tumor growth of glioma. In particular, Rap2A overexpression remarkably inhibited ERK1/2 phosphorylation. CONCLUSIONS: Therefore, our findings demonstrated that Rap2A functioned as a tumor suppressor via modulating the ERK1/2 signaling pathway, which may be a potential therapeutic candidate for treating glioma.

6.
J Mater Chem B ; 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35930367

RESUMO

The issue of pervasively enhanced drug resistance of pancreatic cancer is fundamental to a better understanding of gemcitabine-based chemotherapy. Currently available treatment plans involving injectable therapeutics are mainly engineered to improve the performance and broaden their applications in the domain of biomedicine. Fixed-dose-rate infusion of free gemcitabine (Gem) has drawn appropriate attention for its potent anti-tumor efficacy against various solid tumors, whereas it remains a considerable challenge to extend its application and achieve better treatment. Here, we have prepared and demonstrated a long-acting delivery system using gemcitabine and injectable in situ hydrogel for the localized treatment of pancreatic cancer. The hydrogel was prepared using polysaccharide derivatives, oxidized-carboxymethylcellulose (OCMC) and carboxymethylchitosan (CMCS) at optimal ratios by a dopamine-functionalized method for the controlled release of Gem. In vitro drug release behaviors for up to a week indicated sustained drug release of the Gem delivery system. Moreover, desirable apoptosis promotion and apparent cellular proliferation inhibition associated with the drug depot have been found in vitro against BxPC-3 pancreatic cancer cells, bringing minimized side effects to systemic normal tissues. The current findings manifested that the release out of the localized delivery platform in a sustained pattern afforded a durable gemcitabine-based chemotherapy effect and inhibited tumor metastasis more persistently after intratumoral injection of the Gem@Gel system, thereby advancing the development of novel drug-loaded materials with properties not accessed previously.

7.
Int J Gen Med ; 15: 6365-6372, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935100

RESUMO

Purpose: Progression from latent tuberculosis infection (LTBI) to pulmonary TB (PTB) was associated with genetic polymorphisms, but there were limited genetic polymorphism data on LTBI and PTB. We aimed at examining the association of KEAP1 gene polymorphisms with PTB and LTBI. Patients and Methods: PTB patients and close contacts of PTB patients were recruited from West China Hospital of Sichuan University. After obtaining the patient's consent, we draw 2-5mL of blood from the patient's peripheral vein. Tag-SNPs of KEAP1 were chosen according to previous studies. The genotyping was done by improved multiplex ligase detection reaction (iMLDR). We used logistic regression to assess the association of SNPs with LTBI/PTB, with sex and age as covariates. Results: A total of 209 PTB patients, 201 LTBI, and 204 HCS were included in the present study. Three Tag-SNPs were included in this study. Significant association was found for KEAP1 rs1048290 between LTBI and HCS. Compared with the KEAP1 rs1048290 CC genotype, genotype GC had an 38% decreased risk for development LTBI (P = 0.043, OR = 0.62, 95% CI: 0.039-0.98). We also found that SNPs in KEAP1 were significantly related to PTB compared to LTBI. Compared with the rs11545829G allele, allele A had an 30% decreased risk for development PTB (P = 0.034, OR = 0.70, 95% CI: 0.51-0.97). We also found the rs11668429 polymorphism was related to PTB. Compared with TT, GT had a significantly increased risk of LTBI developing into PTB (P = 0.041, OR = 1.68, 95% CI: 1.02-2.77). Conclusion: Our study suggested that KEAP1 polymorphisms were significantly related to susceptibility to PTB and LTBI subjects.

8.
ESC Heart Fail ; 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35841124

RESUMO

AIMS: Orchestrating the transition from reversible medial hypertrophy to irreversible plexiform lesions is crucial for pulmonary arterial hypertension related to congenital heart disease (CHD-PAH). Transgelin is an actin-binding protein that modulates pulmonary arterial smooth muscle cell (PASMC) dysfunction. In this study, we aimed to probe the molecular mechanism and biological function of transgelin in the pathogenesis of CHD-PAH. METHODS AND RESULTS: Transgelin expression was detected in lung tissues from both CHD-PAH patients and monocrotaline (MCT)-plus aortocaval (AV)-induced PAH rats by immunohistochemistry. In vitro, the effects of transgelin on the proliferation, migration, and apoptosis of human PASMCs (HPASMCs) were evaluated by the cell count and EdU assays, transwell migration assay, and TUNEL assay, respectively. And the effect of transgelin on the expression of HPASMC phenotype markers was assessed by the immunoblotting assay. (i) Compared with the normal control group (n = 12), transgelin expression was significantly overexpressed in the pulmonary arterioles of the reversible (n = 15) and irreversible CHD-PAH group (n = 4) (reversible group vs. control group: 18.2 ± 5.1 vs. 13.6 ± 2.6%, P < 0.05; irreversible group vs. control group: 29.9 ± 4.7 vs. 13.6 ± 2.6%, P < 0.001; irreversible group vs. reversible group: 29.9 ± 4.7 vs. 18.2 ± 5.1, P < 0.001). This result was further confirmed in MCT-AV-induced PAH rats. Besides, the transgelin expression level was positively correlated with the pathological grading of pulmonary arteries in CHD-PAH patients (r = 0.48, P = 0.03, n = 19). (ii) Compared with the normal control group (n = 12), TGF-ß1 expression was notably overexpressed in the pulmonary arterioles of the reversible (n = 15) and irreversible CHD-PAH group (n = 4) (reversible group vs. control group: 14.8 ± 4.4 vs. 6.0 ± 2.5%, P < 0.001; irreversible group vs. control group: 20.1 ± 4.4 vs. 6.0 ± 2.5%, P < 0.001; irreversible group vs. reversible group: 20.1 ± 4.4 vs. 14.8 ± 4.4, P < 0.01). The progression-dependent correlation between TGF-ß1 and transgelin was demonstrated in CHD-PAH patients (r = 0.48, P = 0.04, n = 19) and MCT-AV-induced PAH rats, which was further confirmed at sub-cellular levels. (iii) Knockdown of transgelin diminished proliferation, migration, apoptosis resistance, and phenotypic transformation of HPASMCs through repressing the TGF-ß1 signalling pathway. On the contrary, transgelin overexpression resulted in the opposite effects. CONCLUSIONS: These results indicate that transgelin may be an indicator of CHD-PAH development via boosting HPASMC dysfunction through positive regulation of the TGF-ß1 signalling pathway, as well as a potential therapeutic target for the treatment of CHD-PAH.

9.
Regen Biomater ; 9: rbac037, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35784095

RESUMO

Central nervous system (CNS) injury, induced by ischemic/hemorrhagic or traumatic damage, is one of the most common causes of death and long-term disability worldwide. Reactive oxygen and nitrogen species (RONS) resulting in oxidative/nitrosative stress play a critical role in the pathological cascade of molecular events after CNS injury. Therefore, by targeting RONS, antioxidant therapies have been intensively explored in previous studies. However, traditional antioxidants have achieved limited success thus far, and the development of new antioxidants to achieve highly effective RONS modulation in CNS injury still remains a great challenge. With the rapid development of nanotechnology, novel nanomaterials provided promising opportunities to address this challenge. Within these, nanoceria has gained much attention due to its regenerative and excellent RONS elimination capability. To promote its practical application, it is important to know what has been done and what has yet to be done. This review aims to present the opportunities and challenges of nanoceria in treating CNS injury. The physicochemical properties of nanoceria and its interaction with RONS are described. The applications of nanoceria for stroke and neurotrauma treatment are summarized. The possible directions for future application of nanoceria in CNS injury treatment are proposed.

10.
BMC Gastroenterol ; 22(1): 330, 2022 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-35799116

RESUMO

BACKGROUND: Thyroid dysfunction has been reported in severe liver diseases. The aim of this study was to analyze the impact of serum thyroid-stimulation hormone (TSH) levels on the prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). METHODS: This retrospective cohort study included 1,862 patients with HBV-related ACLF. Risk factors associated with 30-day and 90-day survival, hazard ratios (HRs), and 95% confidence intervals (CIs) for TSH were estimated using Cox proportional hazards regression. The Area Under the ROC curve (AUROC) analysis was carried out, and the cut-off values were calculated. After grouping by the cut-off value, survival was compared between the groups using the log-rank test. This study data is from the "Survival Cohort Study (SCS)", which has been registered at ClinicalTrials.gov (NCT03992898). RESULTS: Multivariate analysis indicated that an elevated TSH level was a highly significant predictor for 30-day survival (HR = 0.743, 95% CI: 0.629-0.878, P < 0.001) and 90-day survival (HR = 0.807, 95% CI: 0.717-0.909, P < 0.001). The AUROC of TSH level for 30-day and 90-day mortality were 0.655 and 0.620, respectively, with the same best cut-off values of 0.261 µIU/mL. Log-rank test showed that the group with higher TSH level had higher 30-day (78.5%, 95% CI: 76.1%-80.9% vs. 56.9%, 95% CI: 53.4%-60.4%; P < 0.001) and 90-day survival rate (61.5%, 95% CI: 58.6%-64.4% vs. 42.8%, 95% CI: 39.3%-46.3%; P < 0.001). Similar findings were observed in subgroups analysis. After adjusting for age and other risk factors, the higher level of TSH remained associated with 30-day survival (HR = 0.602, 95% CI: 0.502-0.721, P < 0.001) and 90-day survival (HR = 0.704, 95% CI, 0.609-0.814, P < 0.001). CONCLUSIONS: Serum TSH level significantly correlate with HBV-related ACLF patients' survival and may be of value for predicting 30-day and 90-day survival of patients with HBV-related ACLF.


Assuntos
Insuficiência Hepática Crônica Agudizada , Hepatite B Crônica , Hepatite B , Estudos de Coortes , Hepatite B/complicações , Vírus da Hepatite B , Hormônios , Humanos , Prognóstico , Curva ROC , Estudos Retrospectivos , Glândula Tireoide , Tireotropina
11.
Front Cell Dev Biol ; 10: 880320, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35800890

RESUMO

Aortic dissection (AD) is mainly caused by hypertension and Marfan syndrome. However, it is unclear whether the cellular components and functions are different between the two causes. A total of 11 aortic samples were collected for single-cell RNA analysis and 20 clusters were disclosed, including VSMCs, fibroblasts, endothelial cells, T cells, B cells, monocytes, macrophages, mast cells, and neutrophils components. There were differences in cell subclusters and function between hypertension and Marfan patients. The cells also had different differentiations. Cellchat identified cell ligand-receptor interactions that were associated with hypertension and Marfan-induced AD involving SMC, fibroblast, mo-macrophages, and T-cell subsets. This study revealed the heterogeneity of cellular components and gene changes in hypertension and Marfan-induced AD. Through functional analysis and the changes in intercellular communication, the possible mechanisms of different causes of AD were explained from a new perspective, so we can better understand the occurrence and development of diseases.

12.
Cell Prolif ; : e13289, 2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35791492

RESUMO

OBJECTIVES: 3D-printing scaffold with specifically customized and biomimetic structures gained significant recent attention in tissue engineering for the regeneration of damaged bone tissues. However, constructed scaffolds that simultaneously promote bone regeneration and in situ inhibit bacterial proliferation remains a great challenge. This study aimed to design a bone repair scaffold with in situ antibacterial functions. MATERIALS AND METHODS: Herein, a general strategy is developed by using epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, firmly anchored in the nano-hydroxyapatite (HA) and coating the 3D printed polymerization of caprolactone and lactide (PCLA) scaffold. Then, we evaluated the stability, mechanical properties, water absorption, biocompatibility, and in vitro antibacterial and osteocyte inductive ability of the scaffolds. RESULTS: The coated scaffold exhibit excellent activity in simultaneously stimulating osteogenic differentiation and in situ resisting methicillin-resistant Staphylococcus aureus colonization in a bone repair environment without antibiotics. Meanwhile, the prepared 3D scaffold has certain mechanical properties (39.3 ± 3.2 MPa), and the applied coating provides the scaffold with remarkable cell adhesion and osteogenic conductivity. CONCLUSION: This study demonstrates that EGCG self-assembled HA coating on PCLA surface could effectively enhance the scaffold's water absorption, osteogenic induction, and antibacterial properties in situ. It provides a new strategy to construct superior performance 3D printed scaffold to promote bone tissue regeneration and combat postoperative infection in situ.

13.
Microbes Infect ; : 105020, 2022 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-35792202

RESUMO

BACKGROUND: The purpose of this research was to evaluate the effect of clofazimine on drug-resistant tuberculosis treatment outcomes. METHODS: A systematic search was conducted in the PubMed, Web of Science and EMBASE databases to identify eligible studies published up to July 10, 2021. The search terms were as follows: "clofazimine," "tuberculosis," "multidrug resistant tuberculosis" or "extensively drug resistant tuberculosis" and their synonyms or similar words. Two researchers independently screened the titles, abstracts, and full texts for inclusion. Meta-analysis was performed with Stata version 16.0 (Stata Corp., College Station, Texas, USA). Risk ratios (RRs) with 95% CIs were calculated to evaluate the treatment outcome. RESULTS: Eight studies including 3,219 participants were included in the meta-analysis. The meta-analysis found that the rates of treatment completion was higher in patients receiving clofazimine-containing regimens than in those not receiving clofazimine-containing regimens (RR: 1.185 (1.060-1.325), P = 0.003). Significant reduction in treatment failure (RR: 0.598 (0.473-0.756), P < 0.001) was found in the clofazimine treatment group. The subgroup analyses of randomized controlled trials (RCTs) found a higher rates of favorable outcomes, treatment completion and cure in the clofazimine group than in the control group (RR: 1.203 (1.029-1.407), P = 0.020; RR: 3.167 (2.043-4.908), P < 0.001; and RR: 1.251 (1.031-1.518), P = 0.023, respectively). Patients receiving clofazimine had a lower risk of treatment failure than those not receiving clofazimine (RR: 0.529 (0.454-0.616), P < 0.001). However, clofazimine treatment did not have a statistically significant effect on all-cause mortality in RCTs. CONCLUSIONS: This study demonstrated that compared with patients who do not receive clofazimine, this drug has the potential to achieve a higher favorable outcome, treatment completion and cure rates, and a lower treatment failure risk among drug-resistant tuberculosis cases.

14.
J Agric Food Chem ; 70(31): 9703-9710, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35856450

RESUMO

As a highly efficient 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor herbicide, topramezone is an ideal target for herbicide-resistant genetic engineering. In this study, two mutants, K-19 (N321Y) and K-63 (Q166R/E322V), with topramezone resistance increased by 205.3 and 58.5%, respectively, were screened from the random mutation library of SpHPPDm, a topramezone-resistant HPPD mutant that we previously obtained. Sites N321 and E322 were identified as key sites for increased topramezone resistance by single-site mutation analysis. A mutant KB-145 (N321Y/E322K) was further obtained by saturation mutation at sites N321 and E322. The topramezone resistance of KB-145 increased by 955.3% compared to mutant SpHPPDm. In conclusion, this study identifies two new sites that significantly affect the topramezone resistance of SpHPPDm, which provides new insights into the molecular mechanism of herbicide resistance of HPPD, and the acquired mutants have great application potential in the construction of herbicide-resistant crops.

15.
J Gastrointest Surg ; 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35776296

RESUMO

BACKGROUND: Anti-reflux mucosectomy (ARMS) is a choice for proton pump inhibitor (PPI)-dependent patients with gastroesophageal reflux disease (GERD). We present an extended anti-reflux mucosectomy, named ligation-assisted anti-reflux mucosectomy (L-ARMS). The aim of this study was to assess the feasibility of the procedure and short-term outcomes on PPI use and symptom resolution. METHODS: Institutional review board approval was obtained for retrospective review of a prospectively collected database including patients who underwent L-ARMS. L-ARMS includes mucosa ligation and endoscopic mucosectomy without submucosal injection around the squamocolumnar junction. The GERD symptoms, endoscopy, 24-h pH monitoring results, and manometry were collected by chart review. Voluntary validated surveys assessed symptomatic improvement over time. RESULTS: There were 69 patients available for review. The procedure was technically completed in all cases with no severe complications, and the average operation time was 33 min. At 6 months after L-ARMS, treatment with PPIs had been halted in 55.1% of the patients, 30.4% of the enrolled patients used PPIs occasionally, and the lower esophageal sphincter (LES) pressure, DeMeester scores, and GERD-health-related quality of life questionnaire (GERD-HRQL) scores showed a significant improvement compared with the baseline measurements (P < 0.001). Forty-five patients complained of mild dysphagia and were relieved in 4 weeks with no specific treatment. Compared to patients without dysphagia, patients complained of dysphagia after surgery had better clinical benefits indicated by GERD-HRQL and DeMeester score. CONCLUSIONS: As a modified ARMS, L-ARMS is an effective procedure for controlling GERD symptoms, esophageal acid exposure, and LES pressure, which can be safely performed endoscopically in a time-saving and simple manner.

16.
Front Mol Neurosci ; 15: 934167, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35898698

RESUMO

Methamphetamine is a highly addictive drug and its abuse leads to serious health and social problems. Until now, no effective medications are yet available for the treatment of methamphetamine addiction. Our study reveals that chloral hydrate, a clinical sedative drug, suppresses the seeking desire for methamphetamine. After 5 days of continuous administration (subanesthetic dose 50 mg/kg and 100 mg/kg), methamphetamine-seeking behavior of rats was inhibited in the condition place preference and intravenous self-administration tests. Furthermore, chloral hydrate treatment robustly suppressed cue-induced methamphetamine relapse. The whole brain c-fos immunostaining revealed that chloral hydrate treatment suppressed neuronal activity in the rhomboid thalamic nucleus (Rh), dorsal endopiriform nucleus (dEn), and claustrum (Cl) while enhanced zona incerta (ZI) activity during cue-induced methamphetamine relapse. Therefore, chloral hydrate could remodel neural network activity and serve as a potential medicine to treat methamphetamine addiction.

17.
Technol Cancer Res Treat ; 21: 15330338221112287, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35816375

RESUMO

Background: To evaluate the potential impact of radiation time on radiation-induced lymphopenia (RIL) and subsequently recovery after stereotactic body radiation therapy (SBRT) and to examine the associations between radiation time and with patient outcomes in early-stage non-small cell lung cancer (NSCLC). Methods: Clinical and laboratory records of subjects consisted of 115 patients who had received SBRT for early-stage NSCLC. Clinical and laboratory records were retrospective reviewed to assess the changes in total lymphocyte counts (TLCs) following SBRT. Associations of TLCs kinetics with the clinical and treatment features, and outcomes were analyzed. Results: Most patients (100/115, 86.96%) experienced significantly decreased median TLCs following SBRT (1700 vs 1100 cells/µL; P < .001), and 52 patients (45.21%) met the criteria for lymphopenia. Six months after SBRT, 44 patients (38.26%) had recovered. A negative correlation between TLCs reduction and radiation time was observed (r = -0.381, P < .001). According to the receiver-operating characteristic curve analysis, the optimal cut-off value for radiation time to was 3950 s to predict lymphocyte count recovery (LR) following RIL was 3950 s (P < .001). Multivariate analyses demonstrated that radiation time was significantly associated with LR (odds ratio [OR], 0.113; 95% confidence interval [CI], 0.029-0.432; P = .001) but not TLCs reduction (P = .575). LR within 6 months after SBRT was associated with improved progression-free survival in patients without non-lymphopenia (P = .034), but had little effect in patients with lymphopenia (P = .405). Conclusion: A longer radiation time was associated with a lower rate of LR within 6 months after SBRT in patients with early-stage NSCLC. Given the association of severe and persistent RIL with survival in NSCLC, further study of the effect of radiation time on immune status is warranted.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Linfopenia , Radiocirurgia , Carcinoma de Pequenas Células do Pulmão , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Linfopenia/diagnóstico , Linfopenia/etiologia , Estadiamento de Neoplasias , Radiocirurgia/efeitos adversos , Estudos Retrospectivos
18.
Immunity ; 2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35863346

RESUMO

Although many studies have addressed the regulatory circuits affecting neuronal activities, local non-synaptic mechanisms that determine neuronal excitability remain unclear. Here, we found that microglia prevented overactivation of pre-sympathetic neurons in the hypothalamic paraventricular nucleus (PVN) at steady state. Microglia constitutively released platelet-derived growth factor (PDGF) B, which signaled via PDGFRα on neuronal cells and promoted their expression of Kv4.3, a key subunit that conducts potassium currents. Ablation of microglia, conditional deletion of microglial PDGFB, or suppression of neuronal PDGFRα expression in the PVN elevated the excitability of pre-sympathetic neurons and sympathetic outflow, resulting in a profound autonomic dysfunction. Disruption of the PDGFBMG-Kv4.3Neuron pathway predisposed mice to develop hypertension, whereas central supplementation of exogenous PDGFB suppressed pressor response when mice were under hypertensive insult. Our results point to a non-immune action of resident microglia in maintaining the balance of sympathetic outflow, which is important in preventing cardiovascular diseases.

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