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1.
Neural Regen Res ; 17(3): 608-617, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34380901

RESUMO

Glial cells play an important role in signal transduction, energy metabolism, extracellular ion homeostasis and neuroprotection of the central nervous system. However, few studies have explained the potential effects of exosomes from glial cells on central nervous system health and disease. In this study, the genes expressed in exosomes from astrocytes and microglia were identified by deep RNA sequencing. Kyoto Encyclopedia of Genes and Genomes analysis indicated that several pathways in these exosomes are responsible for promoting neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Huntington's disease. Gene ontology analysis showed that extracellular exosome, mitochondrion and growth factor activity were enriched in exosomes from the unique astrocyte group, while extracellular exosome and mitochondrion were enriched in exosomes from the unique microglia group. Next, combined with the screening of hub genes, the protein-protein interaction network analysis showed that exosomes from astrocytes influence neurodegenerative diseases through metabolic balance and ubiquitin-dependent protein balance, whereas exosomes from microglia influence neurodegenerative diseases through immune inflammation and oxidative stress. Although there were differences in RNA expression between exosomes from astrocytes and microglia, the groups were related by the hub genes, ubiquitin B and heat shock protein family A (Hsp70) member 8. Ubiquitin B appeared to be involved in pleiotropic regulatory functions, including immune regulation, inflammation inhibition, protein catabolism, intracellular protein transport, exosomes and oxidative stress. The results revealed the clinical significance of exosomes from glia in neurodegenerative diseases. This study was approved by the Animal Ethics Committee of Nantong University, China (approval No. S20180102-152) on January 2, 2018.

2.
J Ethnopharmacol ; 283: 114747, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34656667

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The Plant Xanthoceras sorbifolium Bunge (X. sorbifolia) has a long history of medicinal use as a traditional Chinese herbal medicine to deal with sterilizing, killing sperm, stabilizing capillary, hemostasis, lowering cholesterol, rheumatism, and pediatric enuresis. Additionally, X. sorbifolia is an oil crop for the production of edible oil due to the health-promotion effect. In recent years, X. sorbifolia has attracted worldwide attention as an important economic crop with low investment and high-income potential. AIM OF THE REVIEW: This review aims to provide a comprehensive appraisal of X. sorbifolia, including the traditional uses, nutrients, phytochemical data, biological activities, and current applications. The natural compounds of X. sorbifolia and potential utilization in pharmacology are highlighted. The aim of this review is to inspire the research enthusiasm to X. sorbifolia and promote the comprehensive utilization of X. sorbifolia. MATERIALS AND METHODS: The research information of X. sorbifolia was collected via Elsevier, American Chemical Society (ACS), PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Baidu scholar, and Google scholar. Additionally, some information was collected from Ph.D. and Master's dissertations, as well as local books. RESULTS: The identification of approximately 195 major phytochemical compounds from different parts of X. sorbifolia is presented in this review, including triterpenoids, flavonoids, phenolic acids, coumarins, lignans, meroterpenoids, monoterpene, alkaloids, and sterol. Among them, triterpenoids, flavonoids, and phenolic acids are the major compounds. Extracts from X. sorbifolia exhibited a wide range of biological activities, such as antioxidant, antibacterial, anti-tumor, anti-neuroinflammatory, anti-adipogenesis, anti-obesity, anti-HIV, gastroprotective, immunoregulatory, and anti-inflammatory activities. CONCLUSIONS: Modern pharmacological studies have been well supported and clarified the traditional medicinal uses of X. sorbifolia, which brought a promising prospect for the pharmaceutical value of this plant. However, the related mechanisms between the structure and pharmacological effects were seldom reported. Also, at present, effective and in-depth research on X. sorbifolia is still relatively lacking. Moreover, there is little research on toxicological experiments. Further clinical trials should also be performed to accelerate the drug research and development.

3.
BMJ Open ; 11(11): e048992, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34728444

RESUMO

INTRODUCTION: Plaque control plays a critical role in the prevention and treatment of periodontitis. Antibacterial mouthwash is one of the most important tools for plaque control. Pudilan, including extracts of Scutellaria baicalensis root, Taraxacum mongolicum, Bunge corydalis herb and Isatis indigotica, was reported playing the role of anti-inflammatory and anti-bacterial. However, its effect on dental plaque and periodontal inflammation remains unknown. We aimed to assess the efficacy of Pudilan Keyanning antibacterial mouthwash which contains the active essence of Pudilan and 0.03%-0.06% cetylpyridinium chloride, as well as Pudilan active essence for plaque control and gingival anti-inflammation in patients during periodontal maintenance phase. METHODS AND ANALYSIS: In this double-blind, randomised, placebo-controlled clinical trial, a total of 120 participants during periodontal maintenance phase will be enrolled. After supragingival scaling, they will be randomly assigned into three groups in a 1:1:1 ratio: the Pudilan Keyanning antibacterial mouthwash group, a chlorhexidine acetate mouthwash (0.12%) group or a placebo group with mouthwash containing the same components as the Pudilan Keyanning mouthwash except for Pudilan active ingredients. They will rinse with mouthwash, respectively, two times per day for 6 weeks. Clinical parameters (such as plaque index, bleeding index) and the level of volatile sulfide in the breath will be measured and analysed. The subgingival plaque will be collected and analysed microbiologically. Questionnaire feedback will be analysed. ETHICS AND DISSEMINATION: The study protocol (V.4) was reviewed and approved by the Medical Ethical Committee of Peking University School and Hospital of Stomatology (Ethics Approval No. PKUSSIRB-201950153b). All participants signed a written consent form. TRIAL REGISTRATION NUMBER: ChiCTR2000041253.

4.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(11): 1141-1148, 2021 Nov 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34753546

RESUMO

OBJECTIVES: To investigate the epidemic situation of hand-foot-mouth disease (HFMD) in Hunan Province, China, from 2008 to 2019, as well as its spatial autocorrelation characteristics and spatial-temporal clustering, and to provide a reference for the prevention and control of HFMD in Hunan Province. METHODS: Spatial autocorrelation and spatial-temporal clustering analyses were used to analyze the monitoring data of HFMD in Hunan Province from 2008 to 2019. RESULTS: The epidemic situation of HFMD in Hunan Province from 2008 to 2019 showed obvious seasonal distribution, with a low incidence rate in January to March and a high incidence rate in April to July. As for population distribution, children aged 0-5 years had the highest number of HFMD cases and accounted for 95.89% (1 460 391/1 522 910) of all cases, with a mean annual incidence rate of 2 197.784/100 000, and scattered children had the highest number of cases and accounted for 82.59% (1 257 739/1 522 910) of all cases. The global spatial autocorrelation analysis showed that the onset of HFMD in Hunan Province showed a significant clustering distribution, and the local spatial autocorrelation analysis showed that the high clustering areas of HFMD were mainly the districts and counties of Changsha, Zhuzhou, and Yueyang cities. Time-space scanning showed that clustering time was mainly April to July; the cases were clustered in the northeast of Hunan Province from 2008 to 2010 and in the central part of Hunan Province from 2011 to 2019. CONCLUSIONS: The high incidence rate of HFMD is observed in April to July in Hunan Province. Children under 5 years of age are at a high risk of this disease. Spatial-temporal clustering is observed for the epidemic of HFMD, mainly clustered in the northeastern and central areas of Hunan Province. It is suggested that the results may be used as guidance to determine the key areas for HFMD prevention and control in Hunan Province and optimize the allocation of health resources.


Assuntos
Doença de Mão, Pé e Boca , Criança , Pré-Escolar , China/epidemiologia , Análise por Conglomerados , Doença de Mão, Pé e Boca/epidemiologia , Humanos , Incidência , Lactente , Análise Espaço-Temporal
6.
Br J Radiol ; : 20210897, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34797694

RESUMO

OBJECTIVES: This study aimed to compare diagnostic efficiency for axillary sentinel lymph node (SLN) metastasis between lymphatic contrast-enhanced ultrasound (LCEUS) and intravenous contrast-enhanced ultrasound (ICEUS) in patients with breast cancer. We also examined whether adding ICEUS to LCEUS could improve the diagnostic accuracy of LCEUS. METHODS: Sixty-nine patients with breast cancer were recruited preoperatively. All patients underwent LCEUS followed by ICEUS, and the enhancement pattern of one SLN was analysed for each patient. The targeted SLN was marked with wire and excised during surgery. The imaging diagnosis was compared with the histopathological result. Diagnostic efficiency was compared among LCEUS, ICEUS, and the combination of LCEUS and ICEUS. RESULTS: The sensitivity values for LCEUS, ICEUS, and the combination of LCEUS and ICEUS were 86.2%, 82.6% and 93.1%, respectively. Specificity values for the three methods were 95.0%, 92.5% and 87.5%, respectively. Accuracy values for the three methods were 91.3%, 88.4% and 89.9%, respectively. The area under the receiver operating characteristic (ROC) curve for LCEUS was 0.906, and there was no significant difference among LCEUS, ICEUS, and the combination of LCEUS and ICEUS (p = 0.752). CONCLUSIONS: LCEUS may represent an accurate method for predicting SLN metastasis preoperatively. Our findings suggest that adding ICEUS to LCEUS for SLN evaluation in patients with breast cancer is unnecessary. ADVANCES IN KNOWLEDGE: This is the first study in which both LCEUS and ICEUS were performed for the same lymph node and the first to compare the diagnostic efficiency of LCEUS, ICEUS, and the combination of LCEUS + ICEUS.

7.
J Mater Chem B ; 9(46): 9514-9523, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34755742

RESUMO

Accurate, in situ and long-term electrically monitoring of cell development plays an important role in cell study, which brings in challenges in terms of biocompatibility, processability, and sensing capability of electrochemical sensors. Based on biocompatible conductive polyaniline (PAni) hydrogels, we constructed a flexible sensor with flexible carbon cloth for electrical analysis of living cells. The carbon fiber substrate modified with conductive PAni hydrogels was selected as the electrode to promote the current collection of the sensor. The three dimensional nanostructured mesoporous matrix of PAni hydrogels is favorable for in situ generation of catalytic Pt nanoparticles and cell growth. With these hierarchically nanostructured features, the hydrogel electrochemical sensor was endowed with high sensitivity and selectivity in the detection of H2O2 (with a low detection limit of 1.6 µM in 0.01 M PBS and a wide linear range from 10 µM to 10 mM), and good biocompatibility for cell growth as long as 5 days. The accurate detection of H2O2 released from cells enabled us to differentiate the physiological states of cells and imitate the different stimuli-responsive behavior, which can provide real-time information on cell biological events. With outstanding biocompatibility, operability and repeatability, this strategy can be expanded to the fields of other biosensor fabrication and cell-related biomarker monitoring, which exhibits a broad application potential in bioanalysis catering to new generation sensors.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34842181

RESUMO

OBJECTIVE: To investigate the association between ultrasound appearances and pathological features in small breast cancer. MATERIALS AND METHODS: A total of 186 small breast cancers in 186 patients were analyzed in this retrospective study from January 2015 to December 2019 according to pathological results. Forty-seven cases of axillary lymph node metastasis were found. All patients underwent radical axillary surgery following conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) examinations. The association between ultrasound appearances and pathological features was analyzed using univariate distributions and multivariate analysis. Then, a logistic regression model was established using the pathological diagnosis of lymph node metastasis and biochemical indicators as the dependent variable and the ultrasound appearances as independent variables. RESULTS: In small breast cancer, risk factors of axillary lymph node metastasis were crab claw-like enhancement on CEUS and abnormal axillary lymph nodes on US. The logistic regression model was established as follows: (axillary lymph node metastasis) = 1.100×(crab claw-like enhancement of CEUS) + 2.749×(abnormal axillary lymph nodes of US) -5.790. In addition, irregular shape on CEUS and posterior echo attenuation on US were risk factors for both positive estrogen receptor and progesterone receptor expression, whereas calcification on US was a risk factor for positive Her-2 expression. A specific relationship could be found using the following logistic models: (positive ER expression) = 1.367×(irregular shape of CEUS) + 1.441×(posterior echo attenuation of US) -5.668; (positive PR expression) = 1.265×(irregular shape of CEUS) + 1.136×(posterior echo attenuation of US) -4.320; (positive Her-2 expression) = 1.658×(calcification of US) -0.896. CONCLUSION: Logistic models were established to provide significant value for the prediction of pre-operative lymph node metastasis and positive biochemical indicators, which may guide clinical treatment.

9.
Front Neurosci ; 15: 738022, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34819832

RESUMO

Retinal pigment epithelium (RPE) serves critical functions in maintaining retinal homeostasis. An important function of RPE is to degrade the photoreceptor outer segment fragments daily to maintain photoreceptor function and longevity throughout life. An impairment of RPE functions such as metabolic regulation leads to the development of age-related macular degeneration (AMD) and inherited retinal degenerative diseases. As substrate recognition subunit of a ubiquitin ligase complex, suppressor of cytokine signaling 2 (SOCS2) specifically binds to the substrates for ubiquitination and negatively regulates growth hormone signaling. Herein, we explore the role of SOCS2 in the metabolic regulation of autophagy in the RPE cells. SOCS2 knockout mice exhibited the irregular morphological deposits between the RPE and Bruch's membrane. Both in vivo and in vitro experiments showed that RPE cells lacking SOCS2 displayed impaired autophagy, which could be recovered by re-expressing SOCS2. SOCS2 recognizes the ubiquitylated proteins and participates in the formation of autolysosome by binding with autophagy receptors and lysosome-associated membrane protein2 (LAMP-2), thereby regulating the phosphorylation of glycogen synthase kinase 3ß (GSK3ß) and mammalian target of rapamycin (mTOR) during the autophagy process. Our results imply that SOCS2 participates in ubiquitin-autophagy-lysosomal pathway and enhances autophagy by regulating GSK3ß and mTOR. This study provides a potential therapeutic target for AMD.

10.
Pharm Biol ; 59(1): 1594-1606, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34808067

RESUMO

CONTEXT: Xiaoyaosan decoction (XYS), a classical Traditional Chinese Medicine (TCM) formula is used to treat liver fibrosis in clinics. OBJECTIVE: This study explores defined compound combinations from XYS decoction to treat liver fibrosis. MATERIALS AND METHODS: Network pharmacology combined with transcriptomics analysis was used to analyze the XYS decoction and liver depression and spleen deficiency syndrome liver fibrosis. From the constructed XYS-Syndrome-liver fibrosis network, the top 10 active formulas were developed by topological analysis according to network stability. The most active formula was determined by in vitro study. The anti-fibrosis effect was evaluated by in vitro and in vivo studies. RESULTS: According to the network XYS-Syndrome-liver fibrosis network, 8 key compounds and 255 combinations were predicted from in XYS. Luteolin, licochalcone A, aloe-emodin and acacetin formula (LLAAF) had a synergistic effect on the proliferation inhibition of hepatic stellate cells compared to individual compounds alone. The treatment of XYS and LLAAF showed a similar anti-liver fibrotic effect that reduced histopathological changes of liver fibrosis, Hyp content and levels of α-SMA and collagen I in CCl4-induced liver fibrosis in rats. Transcriptomics analysis revealed LLAAF regulated PI3K-Akt, AMPK, FoxO, Jak-STAT3, P53, cell cycle, focal adhesion, and PPAR signalling. Furthermore, LLAAF was confirmed to regulate Jak-STAT and PI3K-Akt-FoxO signalling in vitro and in vivo. CONCLUSIONS: This study developed a novel anti-liver formula LLAAF from XYS, and demonstrated its anti-liver fibrotic activity which may be involved in the regulation of Jak-STAT and PI3K-Akt-FoxO signalling.

11.
Materials (Basel) ; 14(22)2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34832404

RESUMO

In this research, a high-boron-content composite material with both neutron and γ rays shielding properties was developed by an optimized design and manufacture. It consists of 304 stainless steel as the matrix and spherical boron carbide (B4C) particles as the functional particles. The content of B4C is 24.68 wt%, and the particles' radius is 1.53 mm. The density of the newly designed material is 5.17 g·cm-3, about 68.02% of that of traditional borated stainless steel containing 1.7 wt% boron, while its neutrons shielding performance is much better. Firstly, focusing on shielding properties and material density, the content and the size of B4C were optimized by the Genetic Algorithm (GA) program combined with the MCNP program. Then, some samples of the material were manufactured by the infiltration casting technique according to the optimized results. The actual density of the samples was 5.21 g cm-3. In addition, the neutron and γ rays shielding performance of the samples and borated stainless steel containing 1.7 wt% boron was tested by using an 241Am-Be neutron source and 60Co and 137Cs γ rays sources, respectively, and the results were compared. It can be concluded that the new designed material could be used as a material for nuclear power plants or spent-fuel storage and transportation containers with high requirements for mobility.

12.
EClinicalMedicine ; 42: 101187, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34841235

RESUMO

Background: We compared the efficacy, safety, and immunogenicity of MIL60 with reference bevacizumab as first-line treatment in patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) in this phase 3, randomized, double-blind study. Methods: Patients with untreated advanced or recurrent NSCLC were randomized (1:1 ratio) to receive either MIL60 or bevacizumab in combination with paclitaxel/carboplatin. Patients with non-progressive disease continued maintenance single-agent MIL60 until disease progression, or intolerable toxicity. The primary endpoint was the 12-week objective response rates (ORR12) by independent review committee (IRC) using RECIST 1.1. Bioequivalence was established if the ORR ratio located between 0.75 and 1/0.75. The trial was registered with clinicaltrials.gov (NCT03196986). Findings: Between Aug 23, 2017, and May 8, 2019, 517 patients were randomly assigned to MIL60 group (n=257) and bevacizumab group (n=260). In the full analysis set (FAS) population including all randomized and evaluable patients who received at least one dose of MIL60 or bevacizumab, the ORR12 in MIL60 group and bevacizumab group were 48.6% and 43.1%, respectively. The ORR ratio of these two groups were 1.14 (90% CI 0.97-1.33), which fell within the pre-specified equivalence boundaries (0.75-1/0.75). The median DOR was 5.7 months (95% CI 4.5-6.2) for MIL60 and 5.6 months (95% CI 4.3-6.4) for bevacizumab. No significant difference was noted in median PFS (7.2 vs. 8.1 months; HR 1.01, 95% CI 0.78-1.30, p=0.9606) and OS (19.3 vs. 16.3 months; HR 0.81, 95% CI 0.64-1.02, p=0.0755). Safety and tolerability profiles were similar between the two groups. No patient detected positive for Anti-drug antibody (ADA). Interpretation: The efficacy, safety and immunogenicity of MIL60 were similar with bevacizumab, providing an alternative treatment option for advanced or recurrent non-squamous NSCLC. Funding: This study was sponsored by Betta Pharmaceutical Co., Ltd.

13.
Pediatr Dermatol ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34647352

RESUMO

BACKGROUND/OBJECTIVES: Up to 30% of pediatric primary care visits include a cutaneous complaint, yet the pediatric dermatology workforce has historically been too small to provide adequate specialized care. This study assesses the geographic distribution of pediatric dermatologists to determine physician-to-patient ratios, analyzes urban-rural disparities, and determines post-fellowship migration patterns. METHODS: Board-certified pediatric dermatologists were identified using the Society for Pediatric Dermatology's public database, and their demographics and credentials were subsequently verified by an online search. Analysis included physician density per 100 000 children for each state and region, along with geographic distribution for rural and urban areas, based on the United States Census Bureau's definitions. The distances between practice locations and the American Board of Dermatology-approved Pediatric Dermatology fellowship training sites were reviewed. RESULTS: An estimated 336 board-certified pediatric dermatologists currently work in the United States with 76.8% being women and 71.1% practicing within 50 miles of the nearest fellowship program. 96.4% are located in urban areas and 3.6% in rural areas with an average ratio of 0.54 and 0.09 per 100 000 children, respectively. The average ratio of pediatric dermatologists in the United States was 0.46 per 100 000 children. On average (standard deviation), there are 6.6 (8.8) pediatric dermatologists per state but with 7 states having zero. CONCLUSIONS: The demand for pediatric dermatologists continues to outpace the current physician availability with a disparity between urban and rural areas. Further awareness and emphasis on training and recruitment of additional pediatric dermatologists are essential to addressing this important issue.

14.
Am J Transl Res ; 13(9): 10056-10074, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650681

RESUMO

The gut microbiota can affect human metabolism, immunity, and other biologic pathways through the complex gut-kidney axis (GKA), and in turn participate in the occurrence and development of kidney disease. In this study, 39 patients with stage 4-5 chronic kidney disease (CKD) and 40 healthy individuals were recruited and 16S rDNA sequencing was performed to analyze the V3-V4 conserved regions of their microbiota. A total of 795 operational taxonomic units (OTUs) shared between groups or specific to each group were obtained, among which 255 OTUs with significant differences between the two groups were identified (P<0.05). Adonis differential analysis showed that the diversity of gut microbiota was highly correlated with CKD stages 4-5. Additionally, 61 genera with differences in the two groups were identified (P<0.05) and 111 species with significant differences in the phyla, classes, orders, families, and genera between the two groups were identified (P<0.05). The differential bacterial genera with the greatest contribution were, in descending order: c_Bacteroidia, o_Bacteroidales, p_Bacteroidetes, c_Clostridia, o_Clostridiales, etc. Those with the greatest contribution in stages 4-5 CKD were, in descending order: p_Proteobacteria, f_Enterobacteriaceae, o_Enterobacteriales, c_Gammaproteobacteria, c_Bacilli, etc. The results suggest that the diversity of the microbiota may affect the occurrence, development, and outcome of the terminal stages of CKD.

15.
Med Sci Monit ; 27: e932093, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34475371

RESUMO

BACKGROUND Reports of human papillomavirus (HPV) infection and genotype distribution in Chinese men are limited, and HPV vaccination has not yet been recommended for men in China. MATERIAL AND METHODS We retrospectively reviewed the prevalence and genotyping of male genital HPV. A total of 1227 male patients (aged 17 to 81 years) attending the dermatology and sexually transmitted disease clinics at Putuo District Center Hospital in Shanghai from 2015 to 2019 were included. Genital exfoliated specimens were obtained for detection and genotyping of 27 HPV types by Luminex-based multiplex assay. RESULTS The prevalence of any HPV was 65.5% (804/1227). The rate of multiple infection was 25.8% (317/1227). The 5 main HPV types were 6 (32.0%), 11 (23.2%), 16 (5.6%), 43 (4.3%), and 59 (4.0%). Among all detected HPV genotypes, 65.5% (875/1336) were 9-valent HPV genotypes. No significant differences were observed in the detection rate of HPV infection over 5 years (P>0.05). Age groups ≤24 years (70.7%) and ≥55 years (72.9%) showed higher infection rates, and significant differences were detected in rates of low-risk HPV infection in different age-stratified groups (P<0.05). Prevalence of HPV infection among patients with warts (74.4%) was significantly higher than that of patients with other clinical characteristics (40.4%) and physical examination (63.6%). CONCLUSIONS Our study suggested that more than half of Chinese male patients have detectable HPV infections, and penis-genital and anogenital warts were the most common clinical manifestations. Moreover, the available 9-valent HPV vaccine covers the most frequently observed HPV types among men.

16.
Cell Rep ; 36(12): 109743, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34551285

RESUMO

Paroxysmal kinesigenic dyskinesia (PKD) is the most common paroxysmal dyskinesia, characterized by recurrent episodes of involuntary movements provoked by sudden changes in movement. Proline-rich transmembrane protein 2 (PRRT2) has been identified as the major causative gene for PKD. Here, we report that PRRT2 deficiency facilitates the induction of cerebellar spreading depolarization (SD) and inhibition of cerebellar SD prevents the occurrence of dyskinetic movements. Using Ca2+ imaging, we show that cerebellar SD depolarizes a large population of cerebellar granule cells and Purkinje cells in Prrt2-deficient mice. Electrophysiological recordings further reveal that cerebellar SD blocks Purkinje cell spiking and disturbs neuronal firing of the deep cerebellar nuclei (DCN). The resultant aberrant firing patterns in DCN are tightly, temporally coupled to dyskinetic episodes in Prrt2-deficient mice. Cumulatively, our findings uncover a pivotal role of cerebellar SD in paroxysmal dyskinesia, providing a potent target for treating PRRT2-related paroxysmal disorders.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34581999

RESUMO

BACKGROUND: With recent COVID-19 vaccination rates relatively high in the USA, the USA still maintains the most documented cases globally,[1] even though COVID-19 cases, hospitalization, and mortality have been declining. However, the health burden has been largely felt in communities involving racial and ethnic minorities. Thus, in order to provide a clearer picture of what is happening in Black, Indigenous, and people of color communities, we examined the racial/ethnic differences of monthly COVID-19 deaths in Connecticut. METHODS: This is an epidemiological study analyzing mortality data from March 1, 2020, to February 28, 2021, obtained from the Connecticut State Department of Public Health. The data include cause of death (COVID-19 death identified by ICD-10 code U071), race/ethnicity (non-Hispanic White (White), non-Hispanic Black (Black), and Hispanic), sex, and age. Both crude and age-adjusted rates were reported by racial/ethnic groups. To compare age-adjusted rates between racial groups, with estimated age-adjusted death counts as outcomes, between-racial group rate ratios, 95% confidence intervals, and p values significant at < 0.05 were derived from the Poisson regression model. RESULTS: From March 2020 to May 2020 (wave 1) of COVID-19 cases, the COVID-19-related mortality rates were the highest for all three race groups (Whites, Blacks, and Hispanics) with statistical group differences (p < 0.05). Blacks had the highest rates of deaths followed by Hispanics and then Whites. Further, more Whites died in a nursing home when compared to Blacks and Hispanics. From June 2010 to October 2020 (wave 2), COVID-19 mortality declined significantly for all three race groups with no statistical differences between groups. COVID-19 deaths in nursing homes declined for all three racial/ethnic groups. From November 2020 to February 2021 (wave 3), COVID-19 mortality rates were significantly higher compared to wave 2 but lower than wave 1 for all three race groups. The mortality rates for Blacks and Hispanics were higher than Whites. Hispanics had the highest rates of deaths, followed by Blacks, and then Whites (p < 0.05). Whites showed the lowest mortality rates among all three racial/ethnic groups. CONCLUSIONS: In summary, COVID-19 health disparities among Black and Hispanic populations were evident in this study. Blacks and Hispanics had significantly higher mortality rates when compared to Whites. Blacks had the highest mortality rates during wave 1, and in wave 3, Hispanics has the highest mortality rates. Our data are important because they show monthly COVID-19 deaths data by race. Data reported this way gives a better and more accurate understanding of what is really happening in Black, Indigenous, and people of color populations.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34501952

RESUMO

Attention-deficit/hyperactivity disorder (ADHD) is the most common neuropsychiatric disorder in children. Several scales are available to evaluate ADHD therapeutic effects, including the Swanson, Nolan, and Pelham (SNAP) questionnaire, the Vanderbilt ADHD Diagnostic Rating Scale, and the visual analog scale. However, these scales are subjective. In the present study, we proposed an objective and automatic approach for evaluating the therapeutic effects of medication in patients with (ADHD). The approach involved using movement quantification of patients' skeletons detected automatically with OpenPose in outpatient videos. Eleven skeleton parameter series were calculated from the detected skeleton sequence, and the corresponding 33 features were extracted using autocorrelation and variance analysis. This study enrolled 25 patients with ADHD. The outpatient videos were recorded before and after medication treatment. Statistical analysis indicated that four features corresponding to the first autocorrelation coefficients of the original series of four skeleton parameters and 11 features each corresponding to the first autocorrelation coefficients of the differenced series and the averaged variances of the original series of 11 skeleton parameters significantly decreased after the use of methylphenidate, an ADHD medication. The results revealed that the proposed approach can support physicians as an objective and automatic tool for evaluating the therapeutic effects of medication on patients with ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Criança , Humanos , Escalas de Graduação Psiquiátrica , Esqueleto , Resultado do Tratamento
20.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(4): 407-414, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34374262

RESUMO

Objective: To retrospectively analyze the clinical characters and prognosis of the patients with Esophageal Squamous Cell Carcinomas as First Primary Malignancy (ESCCFPM), which will help us better understand the relationship between Esophageal Squamous Cell Carcinoma (ESCC) and other cancers, and to provide appropriate research evidence for the clinical diagnosis and treatment. Methods: The clinicopathological and follow-up data of 540 Patients with ESCCFPM between January 1, 2004 and December 31, 2016 were collected from the Surveillance, Epidemiology and End Results (SEER) database of National Cancer Institute. The Kaplan-Meier method was used to determine Overall Survival (OS) curves of ESCC patients, and the Log-Rank test was used to estimate differences in survival. The Cox proportional hazards models were adopted for the prognosis analyses. Results: Regarding the number of multiple primary malignancies (MPMs), 491 had two malignancies, 42 had three malignancies and 7 had four malignancies. ESCCFPM is more common among males. The high incidence age is between 61 and 80 years old. Tumors of the respiratory system (36.9%), were the most common MPMs followed by digestive system (35.2%) and reproductive system (8.9%). The 1-year, 3-year, 5-year OS rates for patients with ESCCFPM were 76.9%, 50.4% and 38.9%, respectively. The age of the ESCC diagnosed, T stage, time of occurrence, carcinoma number, lymph node dissection, surgery, radiotherapy and chemotherapy were the prognostic factor of overall survival for ESCCFPM patients. Age, race, T stage, time of occurrence surgery and radiotherapy were independent prognostic factors for the whole cohort by multivariate survival analysis. Conclusion: ESCCFPM,mainly two-lesion cancer, is most commonly found in respiratory system and digestive systems. Enhanced follow-up of respiratory and digestive tumors in ESCCFPM patients aged 61-80 may help identify multiple primary malignancies. Surgery, radiotherapy and chemotherapy may improve overall survival for ESCCFPM patients.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
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