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1.
Stem Cells Int ; 2021: 5660927, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34876908

RESUMO

Radiation-induced bone injury (RIBI) is one of the complications after radiotherapy for malignant tumors. However, there are no effective measures for the treatment of RIBI in clinical practice, and the mechanism of RIBI is unclear. We use a single high-dose ionizing radiation (6Gy) to analyze the effect of radiotherapy on osteoblast function. Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) were cocultured with irradiated osteoblasts to examine their therapeutic effects and mechanisms on osteoblast injury. The hUCB-MSC transplantation mouse model is used to confirm the in vivo role of hUCB-MSC treatment in radiation bone injury. Western blot analysis, qRT-PCR, immunohistochemistry, and immunofluorescence staining were used to analyze gene expression and angiogenesis. The apoptosis and migration of osteoblasts were measured by Hoechst staining, scratch test, and transwell. The differentiation of osteoblasts was measured by ALP and Alizarin red staining and transmission electron microscopy. The bone-related parameters of mice were evaluated by micro-CT analysis. We found that radiation can damage the DNA of osteoblasts; induce apoptosis; reduce the differentiation, migration, and adhesion of osteoblasts, leading to lipogenesis of bone marrow mesenchymal stem cells (BMSCs) and reducing the source of osteoblasts; and increase the number of osteoclasts in bone tissue, while MSC treatment prevents these changes. Our results reveal the inhibitory effect of radiation on osteoblast function. hUCB-MSCs can be used as a therapeutic target for the development of new therapeutic strategies for radiotherapy of bone injury diseases.

2.
Int J Gen Med ; 14: 8919-8927, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34866933

RESUMO

Purpose: Chronic kidney disease (CKD) is common in patients admitted with acute coronary syndrome (ACS), and it is associated with poor outcomes. However, data are limited. Hence, we examined the long-term prognostic significance of estimated glomerular filtration rate (eGFR) among Chinese patients hospitalized with ACS. Patients and Methods: This is a multicenter, observational study that included 1860 ACS patients enrolled between March 2014 and June 2019 from 11 hospitals in Chengdu. CKD-EPI equation was used to calculate the baseline eGFR. Patients were divided into three groups: eGFR ≥ 90 mL/min (normal renal function), eGFR 60 to <90 mL/min (mild impaired renal function), and eGFR < 60 mL/min (moderate or severe renal dysfunction). The endpoint was all-cause death during follow-up. Results: At baseline, 714 patients had normal renal function, while 746 patients had mild impaired renal function, and 400 patients had moderate or severe renal dysfunction. In the follow-up of 15 months (10 months, 22 months), 261 (14.0%) patients died;, 139 (34.8%) in the moderate or severe renal dysfunction group, 94 (12.6%) in the mild impaired renal function group, and 28 (3.9%) in the normal renal function group (log-rank p-value from Kaplan-Meier analysis <0.001). In multivariable Cox Proportional hazard analysis, age, systolic blood pressure (SBP), heart rate, eGFR, ST-elevation myocardial infarction (STEMI), and percutaneous coronary intervention (PCI) were independent predictors of all-cause death. Conclusion: In this study, among Chinese patients with ACS, renal insufficiency was associated with unfavorable long-term prognosis. Age, SBP, heart rate, eGFR, STEMI, and PCI could identify those at risk.

3.
Front Immunol ; 12: 772511, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868035

RESUMO

Recent exposure to seasonal coronaviruses (sCoVs) may stimulate cross-reactive antibody responses against severe acute respiratory syndrome CoV 2 (SARS-CoV-2). However, previous studies have produced divergent results regarding protective or damaging immunity induced by prior sCoV exposure. It remains unknown whether pre-existing humoral immunity plays a role in vaccine-induced neutralization and antibody responses. In this study, we collected 36 paired sera samples from 36 healthy volunteers before and after immunization with inactivated whole-virion SARS-CoV-2 vaccines for COVID-19, and analyzed the distribution and intensity of pre-existing antibody responses at the epitope level pre-vaccination as well as the relationship between pre-existing sCoV immunity and vaccine-induced neutralization. We observed large amounts of pre-existing cross-reactive antibodies in the conserved regions among sCoVs, especially the S2 subunit. Excep t for a few peptides, the IgG and IgM fluorescence intensities against S, M and N peptides did not differ significantly between pre-vaccination and post-vaccination sera of vaccinees who developed a neutralization inhibition rate (%inhibition) <40 and %inhibition ≥40 after two doses of the COVID-19 vaccine. Participants with strong and weak pre-existing cross-reactive antibodies (strong pre-CRA; weak pre-CRA) had similar %inhibition pre-vaccination (10.9% ± 2.9% vs. 12.0% ± 2.2%, P=0.990) and post-vaccination (43.8% ± 25.1% vs. 44.6% ± 21.5%, P=0.997). Overall, the strong pre-CRA group did not show a significantly greater increase in antibody responses to the S protein linear peptides post-vaccination compared with the weak pre-CRA group. Therefore, we found no evidence for a significant impact of pre-existing antibody responses on inactivated vaccine-induced neutralization and antibody responses. Our research provides an important basis for inactivated SARS-CoV-2 vaccine use in the context of high sCoV seroprevalence.

4.
J Med Genet ; 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34916234

RESUMO

BACKGROUND: Von Hippel-Lindau (VHL) disease is an autosomal dominant genetic tumour syndrome with poor prognosis. The clinical manifestation was found to be more serious in affected offspring of patients with VHL disease, but the risk factors and survival for them have never been reported before. We aimed to explore how these patients were influenced by genetic and clinical factors. METHODS: In this retrospective study, we collected 372 affected offspring of VHL patients from 118 unrelated VHL families. Patients were stratified into different groups based on sets of variables. The age-related risk, overall survival and central nervous systemhaemangioblastoma (CHB)-specific survival were analysed between different groups using Kaplan-Meier survival analysis and Cox regression analysis. RESULTS: The estimated median life expectancy and median age of onset for affected offspring of VHL patients were 66 years and 28 years, respectively. The later generation and patients with mutations in exon 3 had an earlier onset age. The first presenting symptom was the only independent risk factor influencing overall survival and CHB-specific survival. Patients that the first presenting symptom is central nervous system (CNS) significantly had a lower life expectancy both in overall survival and CHB-specific survival analysis than abdominal lesions group. CONCLUSION: This study indicated that affected offspring of VHL patients with CNS as the first presenting symptom was an independent risk factor for overall survival and CHB-specific survival. Generation and mutation region only had an effect on the onset age, which is helpful to clinical decision-making and generate a more precise surveillance protocol.

5.
Autophagy ; : 1-17, 2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-34964701

RESUMO

Deficient bone regeneration causes bone defects or nonunion in a substantial proportion of trauma patients that urges for novel therapies. To develop a reliable therapy, we investigated the effect of negative pressure wound therapy (NPWT) on bone regeneration in vivo in a rat calvarial defect model. Negative pressure (NP) treatment in vitro was mimicked to test its effect on osteoblast differentiation in rat mesenchymal stem cells (MSCs) and MC3T3-E1 cells. Transcriptomic analyses, pharmaceutical interventions, and shRNA knockdowns were conducted to explore the underlying mechanism and their clinical relevance was investigated in samples from patients with nonunion. The potential application of a combined therapy of MSCs in hydrogels with negative pressure was tested in the rat critical-size calvarial defect model. We found that NPWT promoted bone regeneration in vivo and NP treatment induced osteoblast differentiation in vitro. NP induced osteogenesis via activating macroautophagy/autophagy by AMPK-ULK1 signaling that was impaired in clinical samples from patients with nonunion. More importantly, the combined therapy involving MSCs in hydrogels with negative pressure significantly improved bone regeneration in rat critical-size calvarial defect model. Thus, our study identifies a novel AMPK-ULK1-autophagy axis by which negative pressure promotes osteoblast differentiation of MSCs and bone regeneration. NPWT treatment can potentially be adopted for therapy of bone defects.Abbreviations: ADP, adenosine diphosphate; AICAR/Aic, acadesine; ALP, alkaline phosphatase; ALPL, alkaline phosphatase, biomineralization associated; AMP, adenosine monophosphate; AMPK, AMP-activated protein kinase; ARS, alizarin red S staining; ATG7, autophagy related 7; ATP, adenosine triphosphate; BA1, bafilomycin A1; BGLAP/OCN, bone gamma-carboxyglutamate protein; BL, BL-918; BS, bone surface; BS/TV, bone surface per tissue volume; BV/TV, bone volume per tissue volume; C.C, compound C; CCN1, cellular communication network factor 1; COL1A1, collagen type I alpha 1 chain; COL4A3, collagen type IV alpha 3 chain; COL4A4, collagen type IV alpha 4 chain; COL18A1, collagen type XVIII alpha 1 chain; CQ, chloroquine; GelMA, gelatin methacryloyl hydrogel; GO, Gene Ontology; GSEA, gene set enrichment analysis; HIF1A, hypoxia inducible factor 1 subunit alpha; HPLC, high-performance liquid chromatography; ITGAM/CD11B, integrin subunit alpha M; ITGAX/CD11C, integrin subunit alpha X; ITGB1/CdD9, integrin subunit beta 1; KEGG, Kyoto Encyclopedia of Genes and Genomes; MAP1LC3B/LC3B, microtubule associated protein 1 light chain 3 beta; micro-CT, microcomputed tomography; MSCs, mesenchymal stem cells; MTOR, mechanistic target of rapamycin kinase; NP, negative pressure; NPWT, negative pressure wound therapy; PRKAA1/AMPKα1, protein kinase AMP-activated catalytic subunit alpha 1; PRKAA2, protein kinase AMP-activated catalytic subunit alpha 2; PTPRC/CD45, protein tyrosine phosphatase receptor type C; ROS, reactive oxygen species; RUNX2, RUNX family transcription factor 2; SBI, SBI-0206965; SPP1/OPN, secreted phosphoprotein 1; THY1/CD90, Thy-1 cell surface antigen; SQSTM1, sequestosome 1; TGFB3, transforming growth factor beta 3; ULK1/Atg1, unc-51 like autophagy activating kinase 1.

6.
J Glob Health ; 11: 05023, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34912549

RESUMO

Background: In response to the COVID-19 pandemic, two new temporary hospitals were constructed in record time in Wuhan, China, to help combat the fast-spreading virus in February 2020. Using the experience of one of the hospitals as a case study, we discuss the health and economic implications of this response strategy and its potential application in other countries. Methods: This retrospective observational study analyzed health resource utilization and clinical outcomes data for 2011 inpatients diagnosed with COVID-19 and admitted to Leishenshan Hospital during its 67 days of operation from February 8th to April 14th, 2020. We used a top-down costing approach to estimate the total cost of treating patients at the Leishenshan Hospital, including capital cost for hospital construction, health personnel costs, and direct health care costs. We used a multivariate generalized linear model to examine risk factors associated with in-hospital deaths. Results: During the 67 days of hospital operation, 19 medical teams comprising of 933 doctors and 2312 nurses were gradually transferred to Leishenshan Hospital from across China. Of the 2011 admissions, 4.5% used intensive care and 2.0% used ventilators. Overall median length of stay was 19 days, and 21 days for patients in the intensive care unit (ICU). The case fatality rate (CFR) was 2.3% overall, 41.8% in the ICU, and 0.4% in general ward (GW). CFRs were 55% and 50% among patients using non-invasive and invasive ventilators, respectively. The mean total cost and direct health care cost were CNY806 997 (US$114 793) and CNY16 087 (US$2288), respectively. Patients admitted to the ICU had much higher direct health care costs, on average, compared to those in the GW (CNY150 415 vs CNY9720, or US$21 396 vs US$1383). The mean direct health care cost per patient with severe or critical diseases was more than five times higher than those with mild or moderate diseases (CNY45 191 vs CNY8838, or US$6428 vs US$1257). Older age, having comorbidities, and critical disease were associated with higher risks of death from COVID-19. Lower health worker to patient ratio (<2.6) was not associated with in-hospital death. Conclusion: An adequate health workforce were mobilized and deployed to a new temporary hospital. The Leishenshan Hospital increased access to care during the surge in COVID-19 infections, facilitated timely treatment, and transferred COVID-19 patients between GWs and ICUs within the hospital, all of which are potential contributors to lowering the CFR. Patients in the ICU experienced a much higher CFR and a greater burden of health care cost than those in GW. Our results have important implications for other countries interested in constructing temporary emergency hospitals, such as the need for adequate infrastructure capacities and financial support, centralized strategies to mobilize health workforce and to provide respiratory protective devices, and improvement in access to health care.


Assuntos
COVID-19 , Idoso , Mortalidade Hospitalar , Hospitais , Humanos , Unidades Móveis de Saúde , Pandemias , SARS-CoV-2
7.
Front Pharmacol ; 12: 775680, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34970146

RESUMO

Brusatol (Bru), a Chinese herbal extract, has a variety of anti-tumor effects. However, little is known regarding its role and underlying mechanism in glioblastoma cells. Here, we found that Bru could inhibit the proliferation of glioblastoma cells in vivo and in vitro. Besides, it also had an inhibitory effect on human primary glioblastoma cells. RNA-seq analysis indicated that Bru possibly achieved these effects through inhibiting the expression of extracellular matrix protein 1 (ECM1). Down-regulating the expression of ECM1 via transfecting siRNA could weaken the proliferation and invasion of glioblastoma cells and promote the inhibitory effect of Bru treatment. Lentivirus-mediated overexpression of ECM1 could effectively reverse this weakening effect. Our findings indicated that Bru could inhibit the proliferation and invasion of glioblastoma cells by suppressing the expression of ECM1, and Bru might be a novel effective anticancer drug for glioblastoma cells.

8.
Oxid Med Cell Longev ; 2021: 2896674, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34820053

RESUMO

Bone resorption diseases, including osteoporosis, are usually caused by excessive osteoclastogenesis. Unc-51-like autophagy activating kinase 1 (ULK1), a mammalian serine/threonine kinase, may participate in the regulation of bone homeostasis and osteolytic metastasis. In this study, ULK1 expression during osteoclastogenesis was detected with RT-PCR. We knocked down or overexpressed ULK1 through siRNA or lentiviral transduction in bone marrow macrophage (BMM). TRAP and phalloidin staining were performed to detect the osteoclastogenesis activity. Ovariectomized (OVX) mouse model of osteoporosis and a mouse of model osteoclast-induced bone resorption were applied to explore the role of ULK1 in bone resorption in vivo. The results showed that ULK1 expression was downregulated during osteoclast differentiation and was clinically associated with osteoporosis. ULK1 inhibited osteoclast differentiation in vitro. Knockdown of ULK1 expression activated phosphorylation of c-Jun N-terminal kinase (JNK) and spleen tyrosine kinase (Syk). Docking protein 3 (DOK3) was coexpressed with ULK1 during osteoclastogenesis. Downregulation of DOK3 offsets the effect of ULK1 on osteoclastogenesis and induced phosphorylation of JNK and Syk. Activation of ULK1 impeded bone loss in OVX mice with osteoporosis. Additionally, upregulation of ULK1 inhibited osteoclast-induced bone resorption in vivo. Therefore, our study reveals a novel ULK1/DOK3/Syk axis that regulates osteoclast differentiation and bone resorption, and targeting ULK1 is a potential therapeutic strategy for osteoporosis.

10.
Adv Ther ; 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34816373

RESUMO

INTRODUCTION: Adalimumab has been used successfully in the treatment of psoriasis. The objective of the study is to compare the efficacy, safety, and immunogenicity between HLX03, an adalimumab biosimilar, and adalimumab in Chinese patients with moderate-to-severe plaque psoriasis. METHODS: In this double-blind, active-controlled, parallel-group study, 262 patients with moderate-to-severe plaque psoriasis were randomized (1:1) to receive HLX03 or adalimumab (80 mg at week 1, 40 mg at week 2, and then 40 mg every 2 weeks) for 48 weeks. The primary endpoint was improvement in Psoriasis Area and Severity Index (PASI) score at week 16 comparing to baseline. Equivalence was demonstrated if 95% confidence interval (CI) of the between group difference fell within the equivalence margins of ± 15%. Other efficacy endpoints, safety and immunogenicity were also evaluated. RESULTS: In the full analysis set, PASI improvements at week 16 was 83.5% (n = 131) in the HLX03 group and 82.0% (n = 130) in the adalimumab group, with a least-square-mean difference of 1.5% (95% CI - 3.9% to 6.8%). There were no significant between-group differences in all secondary efficacy analyses including proportion of patients achieving ≥ 75% improvement from baseline PASI (PASI 75), physician global assessment (PGA) 0/1 (clear or almost clear) and change in dermatology life quality index (DLQI) score. The incidences of adverse events and the proportion of patients with antidrug antibodies were also comparable between the two treatment groups. CONCLUSION: HLX03 demonstrated equivalent efficacy, similar safety and immunogenicity to reference adalimumab, supporting its development as an alternative treatment for patients with plaque psoriasis in China. CLINICAL TRIAL REGISTRATION: Chinadrugtrials.org.cn, CTR20171123 (November 27, 2017); ClinicalTrials.gov, NCT03316781 (October 20, 2017).

12.
J Coll Physicians Surg Pak ; 31(12): 1394-1398, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34794276

RESUMO

OBJECTIVE: To investigate standard modifiable cardiovascular risk factors (SMuRFs) and prognosis of patients with acute coronary syndrome (ACS) aged 50 years or younger. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Eleven general hospitals in Chengdu, Sichuan Province, China, from January 2017 to June 2019. METHODOLOGY: Patients with ACS were stratified into younger group (≤50 years) and older group (>50 years). The baseline characteristics and prognosis were compared for two groups. Survival analysis was used to assess the long-term prognosis. RESULTS: Among a total of 1982 ACS patients, 322 (16.2%) were of ≤50 years. Compared with older patients, younger patients were more likely to have at least one SMuRFs (90.0% vs. 84.3%, p=0.013). The younger group had a higher prevalence of smoking (62.8% vs. 34.1%, p <0.001) and hypercholesterolemia (36.2% vs. 23.4%, p <0.001) compared with the older group. Younger male patients were more likely to have at least one SMuRFs than younger female patients (91.6% vs. 74.1%, p = 0.011). After the follow-up of 15 (10, 22) months, the cumulative rates of major adverse cardiovascular and cerebrovascular events (MACCE) of the younger patients were significantly lower than those in the older patients [hazard ratio (HR): 0.2661, 95% confidence interval (CI): 0.1932 - 0.3665, p <0.001]. CONCLUSION: Younger patients with ACS were more likely to have at least one SMuRFs; and were likely to have a better prognosis than older patients. Key Words: Coronary artery disease, Acute coronary syndrome, Middle aged, Risk factors, Prognosis.


Assuntos
Síndrome Coronariana Aguda , Doenças Cardiovasculares , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/epidemiologia , Doenças Cardiovasculares/epidemiologia , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco
13.
Int J Med Robot ; : e2352, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34773371

RESUMO

BACKGROUND: To present our experiences with partial nephrectomy (PN) through retroperitoneal approach (RP) with the Kangduo robotic system. METHODS: From December 2020 to February 2021, the perioperative data of 11 patients underwent PN through RP with the Kangduo robotic system were collected prospectively. RESULTS: For the R.E.N.A.L. nephrometry score, 72.7% of patients had a low score (4-6) and 27.3% of patients had a medium score (7-9). Seven tumours were posterior (P), four tumours were on the midline (X). All procedures were completed successfully. The median warm ischemia time was 18.5 (IQR, 13.7-21.0) min. None of the patients had positive surgical margins at definitive histology (all pT1a). No high-grade perioperative complications or device-related adverse events occurred. At a mean follow-up of 8 ± 0.8 months, no complications occurred in all patients. CONCLUSIONS: RPPN using the novel Kangduo robotic system is a safe and effective option for managing posterior and lateral renal tumours with R.E.N.A.L. nephrometry scores ≤9.

14.
J Am Heart Assoc ; 10(20): e022453, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34622672

RESUMO

Irisin, a novel hormone like polypeptide, is cleaved and secreted by an unknown protease from a membrane-spanning protein, FNDC5 (fibronectin type III domain-containing protein 5). The current knowledge on the biological functions of irisin includes browning white adipose tissue, regulating insulin use, and anti-inflammatory and antioxidative properties. Dysfunction of irisin has shown to be involved in cardiovascular diseases such as hypertension, coronary artery disease, myocardial infarction, and myocardial ischemia-reperfusion injury. Moreover, irisin gene variants are also associated with cardiovascular diseases. In this review, we discuss the current knowledge on irisin-mediated regulatory mechanisms and their roles in the pathogenesis of cardiovascular diseases.

15.
Clin Oral Investig ; 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34628546

RESUMO

OBJECTIVE: This study aimed to investigate the potential relationship between oral hygiene and the risk of oral cancer and its subtypes after controlling the effects of several confounding factors. MATERIALS AND METHODS: A large-scale case-control study was conducted from January 2010 to August 2019, recruiting a total of 1,288 oral cancer cases with newly diagnosed and 4,234 healthy controls. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were utilized to minimize confounding effects. Conditional logistic regression was used to evaluate the effects of oral hygiene indicators on oral cancer. RESULTS: A composite oral hygiene score was developed based on five indicators selected based on PSM and IPTW analysis (including tooth loss, dentures wearing, the frequency of tooth brushing, regular dental visits, and recurrent dental ulcer). Participants with a higher score, compared with their lower counterparts, showed a 49% increased risk (the odds ratio (OR) was 1.49 (95% confidence interval (CI): 1.26-1.75). A similar association pattern was found following IPTW analyses (OR = 1.32; 95% CI: 1.22-1.42). Of note, the adverse effects of poor oral hygiene were more evident among the sites of gingival and buccal (PSM analysis: 2.03-fold and 2.68-fold increased risk; IPTW analysis: 1.57-fold and 2.07-fold increased risk, respectively). Additionally, a greater positive association was observed between poor oral hygiene and oral squamous cell carcinoma, compared with other pathological types. CONCLUSION: This study establishes a composite oral hygiene score and provides supportive evidence of poor oral hygiene associated with a higher risk of oral cancer, particularly in the gingival and buccal mucosa sites and in the squamous cell carcinoma. CLINICAL RELEVANCE: The data highlights the importance of improving poor oral hygiene habits, which has public health implications for the prevention of oral cancer.

16.
Mol Cancer Res ; 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34654722

RESUMO

Lymphatic metastasis is a common clinical symptom in nasopharyngeal carcinoma (NPC), the most common Epstein-Barr virus (EBV)-associated head and neck malignancy. However, the effect of EBV on NPC lymph node (LN) metastasis is still unclear. In this study, we demonstrated that EBV infection is strongly associated with advanced clinical N stage and lymphangiogenesis of NPC. We found that NPC cells infected with EBV promote LN metastasis by inducing cancer-associated lymphangiogenesis, whereas these changes were abolished upon clearance of EBV genomes. Mechanistically, EBV-induced VEGF-C contributed to lymphangiogenesis and LN metastasis, and PHLPP1, a target of miR-BART15, partially contributed to AKT/HIF1a hyperactivity and subsequent VEGF-C transcriptional activation. In addition, administration of anti-VEGF-C antibody or HIF1α inhibitors attenuated the lymphangiogenesis and LN metastasis induced by EBV. Finally, we verified the clinical significance of this prometastatic EBV/VEGF-C axis by determining the expression of PHLPP1, AKT, HIF1a, and VEGF-C in NPC specimens with and without EBV. These results uncover a reasonable mechanism for the EBV-modulated LN metastasis microenvironment in NPC, indicating that EBV is a potential therapeutic target for NPC with lymphatic metastasis. IMPLICATIONS: This research demonstrates that EBV induces lymphangiogenesis in NPC by regulating PHLPP1/p-AKT/HIF1a/VEGF-C, providing a new therapeutic target for NPC with lymphatic metastasis.

17.
BMC Gastroenterol ; 21(1): 389, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34670510

RESUMO

BACKGROUND: The sensitivity of regular arrangement of collecting venules (RAC)-positive pattern for predicting Helicobacter pylori (H. pylori)-negative status greatly altered from 93.8 to 48.0% in recent two decades of various studies, while the reason behind it remained obscure. The aim of this study was to investigate the value of RAC as an endoscopic feature for judging H. pylori status in routine endoscopy and reviewed the underlying mechanism. METHODS: A prospective study with high-definition non-magnifying endoscopy was performed. RAC-positive and RAC-negative patients were classified according to the collecting venules morphology of the lesser curvature in gastric corpus. Gastric biopsy specimens were obtained from the lesser and greater curvature of corpus with normal RAC-positive or abnormal RAC-negative mucosal patterns. Helicobacter pylori status was established by hematoxylin and eosin staining and immunohistochemistry. RESULTS: 41 RAC-positive and 124 RAC-negative patients were enrolled from June 2020 to September 2020. The prevalence of H. pylori infection in patients with RAC-positive pattern and RAC-negative pattern was 7.3% (3/41) and 71.0% (88/124), respectively. Among all 124 RAC-negative patients, 36 (29.0%) patients were H. pylori-negative status. Ten patients (32.3%) demonstrated RAC-positive pattern in 31 H. pylori-eradicated cases. The sensitivity, specificity, positive predictive value, and negative predictive value of RAC-positive pattern for predicting H. pylori-negative status were 51.4% (95% CI, 0.395-0.630), 96.7% (95% CI, 0.900-0.991), 92.7% (95% CI, 0.790-0.981), and 71.0% (95% CI, 0.620-0.786), respectively. CONCLUSIONS: RAC presence can accurately rule out H. pylori infection of gastric corpus, and H. pylori-positive status cannot be predicted only by RAC absence in routine endoscopy. Trial registration The present study is a non-interventional trial.


Assuntos
Gastrite , Helicobacter pylori , Mucosa Gástrica , Gastroscopia , Humanos , Estudos Prospectivos , Vênulas
18.
Front Psychol ; 12: 711489, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671295

RESUMO

This study aims to evaluate the practical application value of the teaching method under the guidance of educational psychology and artificial intelligence (AI) design, taking the deep learning theory as the basis of teaching design. The research objects of this study involve all the teachers, students, and students' parents of Ningbo Middle School. The questionnaires are developed to survey the changes in the performance of students before and after the implementation of the teaching design and the satisfaction of all teachers, students, and parents to different teaching methods by comparing the two results and the satisfaction ratings. All objects in this study volunteer to participate in the questionnaire survey. The results suggest the following: (1) the effective return rates of the questionnaires to teachers, students, and parents are 97, 99, and 95%, respectively, before implementation; whereas those after implementation are 98, 99, and 99%, respectively. Comparison of the two return results suggests that there was no significant difference statistically (P > 0.05). (2) Proportion of scoring results before and after implementation is given as follows: the proportions of levels A, B, C, and D are 35, 40, 15, and 10% before implementation, respectively; while those after implementation are 47, 36, 12, and 5%, respectively. After the implementation, the proportion of level A is obviously higher than that before the implementation, and the proportions of other levels decreased in contrast to those before the implementation, showing statistically obvious differences (P < 0.05). (3) The change in the performance of each subject after 1 year implementation is significantly higher than that before the implementation, and the change in the average performance of each subject shows an upward trend. In summary, (1) the comparison on the effective return rate of the satisfaction survey questionnaire proves the feasibility of its scoring results. (2) The comparison of the survey scoring results shows that people are more satisfied with the new educational design teaching method. (3) The comparison of the change in the performance of each subject before and after the implementation indirectly reflects the drawbacks of partial subject education, indicating that the school should pay the same equal attention to every subject. (4) Due to various objective and subjective factors, the results of this study may be different from the actual situation slightly, and its accuracy has to be further explored in the future.

19.
Int J Endocrinol ; 2021: 9930059, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504526

RESUMO

Objective: Dopamine agonists (DAs) are recommended as the first-line treatment for prolactinomas; however, tumour recurrence after drug withdrawal remains a clinical problem. Recent studies have reported high remission rates via surgery in microprolactinomas. The aim of this systematic review and meta-analysis was to compare the clinical result of DA treatment with surgery as initial therapy in patients with treatment-naive microprolactinoma. Methods: A comprehensive literature search for studies and reports regarding microprolactinoma patients treated with DAs and/or surgery published between January 1970 and November 2020 was conducted using four electronic databases (PubMed, Embase, Google Scholar, and the Cochrane Library). Clinical treatment outcome was evaluated by the biochemical remission of serum prolactin level to normal after treatment. The I 2 statistic was used to quantify heterogeneity. Pooled data were analysed according to a random effect model. Results: Eighteen studies with 661 patients were included for analysis. The DA treatment group achieved a higher remission rate at ≥12 months follow-up (96% vs. 86%; P=0.019). Surgery showed a higher remission rate than the DA treatment group after the treatment withdrawal (78% vs. 44%; P=0.003). Patients with preoperative prolactin level of ≤200 ng/mL had a higher remission rate than patients with preoperative prolactin level of >200 ng/mL (92% vs. 40%; P=0.029). Conclusion: Surgery showed a high remission rate in treatment-naive microprolactinoma patients after treatment withdrawal and may be an alternative first-line treatment strategy in addition to DAs, particularly in patients with a preoperative prolactin level of ≤200 ng/mL.

20.
Oxid Med Cell Longev ; 2021: 6324912, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504641

RESUMO

In the skeletal system, inflammation is closely associated with many skeletal disorders, including periprosthetic osteolysis (bone loss around orthopedic implants), osteoporosis, and rheumatoid arthritis. These diseases, referred to as inflammatory bone diseases, are caused by various oxidative stress factors in the body, resulting in long-term chronic inflammatory processes and eventually causing disturbances in bone metabolism, increased osteoclast activity, and decreased osteoblast activity, thereby leading to osteolysis. Inflammatory bone diseases caused by nonbacterial factors include inflammation- and bone resorption-related processes. A growing number of studies show that exosomes play an essential role in developing and progressing inflammatory bone diseases. Mechanistically, exosomes are involved in the onset and progression of inflammatory bone disease and promote inflammatory osteolysis, but specific types of exosomes are also involved in inhibiting this process. Exosomal regulation of the NF-κB signaling pathway affects macrophage polarization and regulates inflammatory responses. The inflammatory response further causes alterations in cytokine and exosome secretion. These signals regulate osteoclast differentiation through the receptor activator of the nuclear factor-kappaB ligand pathway and affect osteoblast activity through the Wnt pathway and the transcription factor Runx2, thereby influencing bone metabolism. Overall, enhanced bone resorption dominates the overall mechanism, and over time, this imbalance leads to chronic osteolysis. Understanding the role of exosomes may provide new perspectives on their influence on bone metabolism in inflammatory bone diseases. At the same time, exosomes have a promising future in diagnosing and treating inflammatory bone disease due to their unique properties.

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