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1.
BMC Med Educ ; 24(1): 203, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413943

RESUMO

PURPOSE: Point-of-care ultrasound (POCUS) instruction is prevalent in medical schools but not in pediatric residency programs, even though the majority of pediatric residents desire POCUS instruction. Virtual ultrasound instruction with affordable handheld ultrasound devices may help remedy this deficiency by allowing qualified instructors to circumvent geographic and financial limitations to reach this population. This study sought to determine if virtual ultrasound instruction is an effective alternative to traditional in-person instruction in a cohort of pediatric residents for the extended Focused Assessment with Sonography in Trauma (eFAST) exam. METHODS: Pediatric residents were randomized to receive either in-person or virtual instruction to learn the eFAST exam using a Sonosite Edge (Sonosite, Inc., Bothell, WA) or Butterfly iQ (Butterfly Network, Inc., Guilford, CT), respectively. After the instructional session, the participants completed a timed assessment in which all required images for the eFAST exam were obtained on the same anatomic model. The content and quality of the images were then scored by expert faculty. RESULTS: There were no significant differences in assessment scores (65.8% and 61.8%, p = 0.349) and assessment duration (482.6 s and 432.6 s, p = 0.346) between pediatric residents who received in-person instruction and those who received virtual instruction. CONCLUSION: Virtual ultrasound instruction appears to be an effective alternative to traditional in-person instruction.


Assuntos
Medicina de Emergência , Internato e Residência , Humanos , Criança , Ultrassonografia/métodos , Aprendizagem , Medicina de Emergência/educação , Docentes
2.
J Inflamm Res ; 17: 1057-1082, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38375021

RESUMO

As the body's largest organ, the skin harbors a highly diverse microbiota, playing a crucial role in resisting foreign pathogens, nurturing the immune system, and metabolizing natural products. The dysregulation of human skin microbiota is implicated in immune dysregulation and inflammatory responses. This review delineates the microbial alterations and immune dysregulation features in common Inflammatory Skin Diseases (ISDs) such as psoriasis, rosacea, atopic dermatitis(AD), seborrheic dermatitis(SD), diaper dermatitis(DD), and Malassezia folliculitis(MF).The skin microbiota, a complex and evolving community, undergoes changes in composition and function that can compromise the skin microbial barrier. These alterations induce water loss and abnormal lipid metabolism, contributing to the onset of ISDs. Additionally, microorganisms release toxins, like Staphylococcus aureus secreted α toxins and proteases, which may dissolve the stratum corneum, impairing skin barrier function and allowing entry into the bloodstream. Microbes entering the bloodstream activate molecular signals, leading to immune disorders and subsequent skin inflammatory responses. For instance, Malassezia stimulates dendritic cells(DCs) to release IL-12 and IL-23, differentiating into a Th17 cell population and producing proinflammatory mediators such as IL-17, IL-22, TNF-α, and IFN-α.This review offers new insights into the role of the human skin microbiota in ISDs, paving the way for future skin microbiome-specific targeted therapies.

3.
J Agric Food Chem ; 72(7): 3606-3621, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38324392

RESUMO

Ulcerative colitis is closely associated with the dysregulation of gut microbiota. There is growing evidence that natural products may improve ulcerative colitis by regulating the gut microbiota. In this research, we demonstrated that bergenin, a naturally occurring isocoumarin, significantly ameliorates colitis symptoms in dextran sulfate sodium (DSS)-induced mice. Transcriptomic analysis and Caco-2 cell assays revealed that bergenin could ameliorate ulcerative colitis by inhibiting TLR4 and regulating NF-κB and mTOR phosphorylation. 16S rRNA sequencing and metabolomics analyses revealed that bergenin could improve gut microbiota dysbiosis by decreasing branched-chain amino acid (BCAA) levels. BCAA intervention mediated the mTOR/p70S6K signaling pathway to exacerbate the symptoms of ulcerative colitis in mice. Notably, bergenin greatly decreased the symbiotic bacteria Bacteroides vulgatus (B. vulgatus), and the gavage of B. vulgatus increased BCAA concentrations and aggravated the symptoms of ulcerative colitis in mice. Our findings suggest that gut microbiota-mediated BCAA metabolism plays a vital role in the protective effect of bergenin on ulcerative colitis, providing novel insights for ulcerative colitis prevention through manipulation of the gut microbiota.


Assuntos
Bacteroides , Benzopiranos , Colite Ulcerativa , Colite , Animais , Camundongos , Humanos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Células CACO-2 , RNA Ribossômico 16S , Colite/induzido quimicamente , Colite/tratamento farmacológico , Aminoácidos de Cadeia Ramificada , Serina-Treonina Quinases TOR/genética , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Colo
4.
Br Poult Sci ; 65(2): 179-190, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38372614

RESUMO

1. A study used gene synthesis to obtain the functional domains of chicken epidermal growth factor (cEGF) and examined their impact on broiler growth performance, small intestinal morphology, digestive enzyme activities in the intestinal contents and the structure of duodenal microflora.2. The pET-32a-cEGF recombinant expression vector was constructed. The specific band at 26 KDa was shown by SDS-PAGE analysis and WB results. The purified protein content was shown to be 1687 µg/ml by assay.3. A total of 180 healthy, one-day-old Arbor Acres male, white-feathered broilers were randomly divided into three dietary treatment groups (six replicate pens, 10 birds per replicate): A control diet (ND); cEGF diet (cEGF), control supplemented with 250 mg/kg cEGF and the control diet (CD) supplemented with 250 mg/kg chlortetracycline.4. The results showed that feeding the cEGF and CD diet reduced FCR of broilers aged 1-21 d, average daily feed intake (ADFI) at 22-42 d, and the FCR in the whole period (1-42 d; p < 0.05). Compared with the ND group, the cEGF diet increased duodenal α-amylase and alkaline phosphatase activities in the 1-21 d, duodenal lipase, alkaline phosphatase, and ileal alkaline phosphatase activities in the post-period and increased villus height in the duodenum and ileum (p < 0.05). In addition, the ACE and Chao1 index for the birds fed cEGF were higher than the ND group (p < 0.05). At the phyla level, Firmicutes and Proteobacteria were dominant in all groups. At the genus level, the dominant genus was Lactobacillus. The LEfSe analysis showed that the cEGF group was enriched by 11 species including Brevibacillus, Eisenbergiella, Cloacibacterium, Butyricoccus spp.5. The addition of 250 mg/kg cEGF to the diet can increase growth performance by improving intestinal development and digestive enzyme activity, which may be related to the duodenal intestinal microflora. Therefore, cEGF is an effective alternative to antibiotics in broiler farming.


Assuntos
Galinhas , Intestinos , Animais , Masculino , Intestinos/anatomia & histologia , Galinhas/fisiologia , Escherichia coli/genética , Fator de Crescimento Epidérmico , Fosfatase Alcalina , Suplementos Nutricionais/análise , Dieta/veterinária , Duodeno , Morfogênese , Ração Animal/análise
6.
Zhonghua Bing Li Xue Za Zhi ; 53(2): 136-142, 2024 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-38281780

RESUMO

Objective: To investigate the clinicopathological characteristics and genetic mutations of SMARCA4-deficient lung adenocarcinoma. Methods: From January 2021 to April 2023 in the First Affiliated Hospital of Zhengzhou University, 42 cases of SMARCA4-deficienct lung adenocarcinoma were diagnosed and now analyzed. All cases were retrospectively studied using hematoxylin-eosin staining and immunohistochemistry. The clinicopathological features were reviewed. Next-generation sequencing (NGS) was performed to investigate the mutations of related genes. Results: Among the 42 cases, there were 35 biopsy and 7 surgical specimens. There were 38 males and 4 females. The male to female ratio was 9.5∶1.0, with an age range from 42 to 78 years. Thirty-three patients were smokers. Overall, 4 cases (9.5%), 2 cases (4.7%), 18 cases (42.9%) and 18 cases (42.9%) were at stages Ⅰ, Ⅱ, Ⅲ, and Ⅳ, respectively. Microscopically, all the cases were non-mucinous adenocarcinoma, without lepidic pattern. The morphology was diverse. Rhabdomyoid cells, tumor giant cells and tumor necrosis were present. Most of the tumor cells had eosinophilic cytoplasm and occasionally clear cytoplasm. Defined cell borders and variable cytoplasmic hyaline secretory globules could be found. Inflammatory cells infiltrated the tumor stroma. Immunohistochemistry showed 29 cases (69.0%, 29/42) expressed TTF1, 10 cases (40.0%, 10/25) expressed Napsin A, and 20 cases (100.0%, 20/20) expressed INI1. Forty cases (95.2%, 40/42) showed BRG1 loss in all tumor cells, while 2 cases (4.8%, 2/42) had partial BRG1 loss. PD-L1 (22C3) was positive in 59.2% of the cases (16/27). NGS revealed mutations in EGFR, ROS1, MET, RET and KRAS. Six cases (6/8) showed SMARCA4 mutation, while some cases were accompanied by mutations of TP53 (7/15), STK11 (4/8), and KEAP1 (1/8). Driver gene mutations were more common in women (P<0.05). Patients were followed up for 1-25 months. Four patients died and 20 patients' diseases progressed. Conclusions: SMARCA4-deficient lung adenocarcinoma lacks characteristic morphology. Most of them express TTF1 and harbor driver gene mutations. It is necessary to identify this subset of lung adenocarcinoma by carrying out BRG1 stain routinely on lung adenocarcinoma. These patients can then be identified and benefit from targeted therapies.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteínas Tirosina Quinases/genética , Estudos Retrospectivos , Proteínas Proto-Oncogênicas/genética , Fator 2 Relacionado a NF-E2/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Mutação , Biomarcadores Tumorais/genética , DNA Helicases/genética , Proteínas Nucleares/genética , Fatores de Transcrição/genética
7.
Arch Osteoporos ; 18(1): 144, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-38015253

RESUMO

Fracture probabilities derived from the original FRAX model for Brazil were compared to those from an updated model based on more recent regional estimates of the incidence of hip fracture. Fracture probabilities were consistently lower in the updated FRAX model. Despite large differences between models, differences in the rank order of fracture probabilities were minimal. OBJECTIVE: Recent epidemiological data indicate that the risk of hip fracture in Brazil is lower than that used to create the original FRAX model. This paper describes the epidemiology of hip fracture in Brazil and the synthesis of an updated FRAX model with the aim of comparing this new model with the original model. METHODS: Hip fracture rates from three cities in three regions were combined, weighted by the population of each region. For other major fractures, incidence rates for Brazil were estimated using Swedish ratios for hip to other major osteoporotic fracture (humerus, forearm or clinical vertebral fractures). Mortality estimates were taken from the UN. RESULTS: Compared to the original FRAX model, the updated model gave lower 10-year fracture probabilities in men and women at all ages. Notwithstanding, there was a very close correlation in fracture probabilities between the original and updated models (r > 0.99) so that the revisions had little impact on the rank order of risk. CONCLUSION: The disparities between the original and updated FRAX models indicate the importance of updating country-specific FRAX models with the advent of significant changes in fracture epidemiology.


Assuntos
Fraturas do Quadril , Fraturas da Coluna Vertebral , Masculino , Humanos , Feminino , Brasil/epidemiologia , Fraturas do Quadril/epidemiologia , Fraturas da Coluna Vertebral/epidemiologia , Cidades , Antebraço
8.
Heliyon ; 9(11): e20922, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37920517

RESUMO

Objective: To evaluate the relationship between periodontitis and postmenopausal osteoporosis. Methods: This research was carried out according to the principles laid down by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline statement. We searched the Web of Science, Embase, PubMed, The Cochrane Library, CNKI, VIP, and WanFang databases from inception to July 1, 2023 to collect all relevant publications, with no restrictions on publication date or Languages. Cochrane's tool for assessing RoB was used to evaluate the RoB for RCTs. The Newcastle-Ottawa Scale was used to assess the RoB for cohort studies and case-control studies. Mean differences (MD) with 95 % confidence intervals (CI) were used for analysis of continuous data. Heterogeneity was measured using the I2 statistic. Revman 5.4 software was used for the meta-analysis. Results: 28 observational studies with 19611 patients, including 5813 cases in the postmenopausal osteoporosis group and 13798 cases in the non-osteoporosis group. The studies showed that the degrees of clinical attachment loss (CAL), probing depth (PD), gingival recession (GR), simplified oral hygiene index (OHIS), and percentage of sites with bleeding on probing (BOP) in the postmenopausal osteoporosis group were higher than those in the non-osteoporosis group[CAL(MD = 0.89(mm), 95 % CI [0.48,1.30], p < 0.00001), PD (MD = 0.27(mm), 95 % CI [0.13, 0.41], p = 0.0001), GR (MD = 0.28(mm), 95 % CI [0.20, 0.35], p < 0.00001), OHIS (MD = 1.32,95 % CI [1.12,1.51], p < 0.00001), BOP(MD = 12.71(%), 95 % CI [3.24,22.18], p = 0.009)]. Eleven studies found that bone mineral density (BMD) in the postmenopausal osteoporosis group was lower than that in non-osteoporosis group (MD = -0.41(U/cm2), 95 % CI [-0.77,-0.05], p = 0.03). The combined analysis results of the studies in the two groups showed that there were no significant differences in the loss of alveolar crestal height (ACH)[(MD = -1.76(%),95%CI [-3.64,0.12], p = 0.07)]. Conclusion: Postmenopausal osteoporosis patients are more likely to suffer from periodontitis, and the condition is easily aggravated.

9.
Zhonghua Bing Li Xue Za Zhi ; 52(9): 918-923, 2023 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-37670621

RESUMO

Objective: To investigate the clinicopathological features and molecular genetics of diffuse large B-cell lymphomas (DLBCL) with concurrent or secondary to nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFHL-AI). Methods: The clinicopathological features and molecular genetics of DLBCL associated with nTFHL-AI diagnosed between January 2015 and October 2022 at the First Affiliated Hospital of Zhengzhou University were analyzed using histology, immunohistochemistry, PCR, EBV-encoded RNA in situ hybridization and fluorescence in situ hybridization (FISH). Clinical information was collected and analyzed. Results: A total of 6 cases including 3 nTFHL-AI with secondary DLBCL and 3 composite lymphomas were reviewed. There were 4 male and 2 female patients, whose ages ranged from 40 to 74 years (median 57 years). All patients presented with nodal lesions at an advanced Ann Arbor stage Ⅲ/Ⅳ (6/6). Bone marrow involvement was detected in 4 patients. All cases showed typical histologic and immunophenotypic characteristics of nTFHL-AI. Among them, 5 cases of DLBCL with concurrent nTFHL-AI exhibited numerous large atypical lymphoid cells and the tumor cells were CD20 and CD79α positive. The only case of DLBCL secondary to nTFHL-AI showed plasma cell differentiation and reduced expression of CD20. All of cases were activated B-cell (ABC)/non-germinal center B-cell (non-GCB) subtype. Three of the 6 cases were EBV positive with>100 positive cells/high power field, meeting the diagnostic criteria of EBV+DLBCL. The expression of MYC and CD30 protein in the DLBCL region was higher than that in the nTFHL-AI region (n=5). C-MYC, bcl-6 and bcl-2 translocations were not detected in the 4 cases that were subject to FISH. Four of the 6 patients received chemotherapy after diagnosis. For the DLBCL cases of nTFHL-AI with secondary DLBCL, the interval was between 2-20 months. During the follow-up period ranging from 3-29 months, 3 of the 6 patients died of the disease. Conclusions: DLBCL associated with nTFHL-AI is very rare. The expansion of EBV-infected B cells in nTFHL-AI may progress to secondary EBV+DLBCL. However, EBV-negative cases have also been reported, suggesting possible other mechanisms. The up-regulation of MYC expression in these cases suggests a possible role in B-cell lymphomagenesis. Clinicians should be aware that another biopsy is still necessary to rule out concurrent or secondary DLBCL when nodal and extranodal lesions are noted after nTFHL-AI treatment.


Assuntos
Linfoma Difuso de Grandes Células B , Feminino , Masculino , Humanos , Hibridização in Situ Fluorescente , Linfócitos B , Biópsia , Linfócitos T Auxiliares-Indutores
11.
Zhonghua Er Ke Za Zhi ; 61(8): 695-699, 2023 Aug 02.
Artigo em Chinês | MEDLINE | ID: mdl-37528009

RESUMO

Objective: To investigate the relationship between amino acid variations of respiratory syncytial virus (RSV) nonstructural protein (NS) 1 and the clinical characteristics. Method: A retrospective case review was conducted. From December 2018 to January 2020, a total of 81 cases of hospitalized children who were tested only positive for RSV by RT-PCR or PCR at the Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University were included in the study. The NS1 genes of RSV subtype A and subtype B were amplified by PCR and sequenced. The amino acid sequences were analyzed. The Chi-square test and Mann-Whitney rank sum test were used to compare the clinical characteristics and type Ⅰ interferon levels of children with or without NS1 variation in the variation and non-variation groups. Results: Among 81 cases, there were 58 males and 23 females. There were 11 cases in the variation group, the age of onset was 2.0 (1.0, 11.0) months, included 4 cases of subtype A (variant sites were: 2 cases for Lys33Gln, one case for Gly2Asp, Pro67Ser, Leu137Phe, respectively) and 7 cases of subtype B (variant sites were: two cases for Val121Ile, one case for Tyr30Cys, Val65Met, Asn85Ser, Ser118Asn, Asp124Asn, respectively). These variant sites all appeared at a very low frequency 0.08 (0.04, 0.29) % in the NCBI PROTEIN database. There were 70 cases in non-variation group, the onset age was 3.5 (1.0, 7.0) months. The proportion of dyspnea in the variation group was higher than that in the non-variation group (10/11 vs. 47% (33/70), χ2=7.31, P<0.01). Conclusions: There are some variant sites in nonstructural protein NS1 of RSV. Children may be prone to have dyspnea with NS1 variations.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Criança , Masculino , Feminino , Humanos , Lactente , Aminoácidos , Estudos Retrospectivos , Vírus Sincicial Respiratório Humano/genética , Reação em Cadeia da Polimerase
12.
Zhonghua Er Ke Za Zhi ; 61(8): 719-725, 2023 Aug 02.
Artigo em Chinês | MEDLINE | ID: mdl-37528013

RESUMO

Objective: To investigate the risk factors for airway mucus hypersecretion in childhood pneumonia infected by different pathogens. Method: A retrospective cohort included 968 children who were hospitalized for Mycoplasma pneumoniae pneumonia (MPP), respiratory syncytial virus (RSV) pneumonia, adenovirus pneumonia and underwent bronchoscopy in Respiratory Department of Children's Hospital of Chongqing Medical University from January 2019 to December 2021 was conducted. The children were divided into two groups distinguished by airway mucus secretion according to the airway mucus hypersecretion score which were scored according to the mucus secretion under the bronchoscope. The demographic characteristics, clinical characteristics, laboratory tests and disease severity of the two groups were compared. And the risk factors for the development of airway mucus hypersecretion in two groups were analyzed. Chi square test, Mann-Whithey U test and Fisher exact test were used to analyze the differences between the two groups, and multivariate Logistic regression was used to analyze the influencing factors. Result: There were 559 males and 409 females in the 968 children, with an age of 4.0 (1.4, 6.0) years. Among the 642 children with MPP, 185 cases were in the hypersecretion group and 457 cases were in the non-hypersecretion group. There were 41 cases in the hypersecretion group and 160 cases in the non-hypersecretion group of 201 children with RSV pneumonia. In the 125 children with adenovirus pneumonia, there were 39 cases in the hypersecretion group and 86 cases in the non-hypersecretion group. In these children, the age of children in the hypersecretion group was older than that in the non-hypersecretion group (6.0 (4.0, 7.0) vs. 5.0 (3.0, 7.0) years old, 1.5 (0.5, 3.6) vs. 0.8 (0.4, 1.6) years old, 2.0 (1.2, 4.5) vs. 1.3 (0.8, 2.0) years old, U=35 295.00, 2 492.00, 1 101.00, all P<0.05). Through multivariate Logistic regression analysis it found that increased risk of airway mucus hypersecretion was present in childhood MPP with increase in peripheral blood white blood cell count (OR=3.30, 95%CI 1.51-7.93, P=0.004) or increase in neutrophil ratio (OR=2.24, 95%CI 1.16-4.33, P=0.016) or decrease in lymphocyte count (OR=3.22, 95%CI 1.66-6.31, P<0.001) or decrease in serum albumin (OR=2.00, 95%CI 1.01-3.98, P=0.047). The risk of airway mucus hypersecretion was increased in children with RSV pneumonia combined with elevated peripheral blood eosinophils (OR=3.04, 95%CI 1.02-8.93, P=0.043). Meanwhile, airway mucus hypersecretion was associated with severe pneumonia (OR=2.46, 95%CI 1.03-6.15, P=0.047) in children with RSV pneumonia. Older age was associated with increased risk of airway mucus hypersecretion in children with adenovirus pneumonia (OR=1.02, 95%CI 1.00-1.04, P=0.026). In these children with occurrence of pulmonary rales, wheezes or sputum sounds (OR=3.65, 95%CI 1.22-12.64, P=0.028) had an increased risk of airway mucus hypersecretion. Neutrophils in bronchoalveolar lavage fluid (BALF) demonstrated higher ratio in hypersecretion group from children with MPP (0.65 (0.43, 0.81) vs. 0.59 (0.34, 0.76), U=24 507.00, P<0.01), while the proportion of macrophages in BALF was lower (0.10 (0.05, 0.20) vs. 0.12 (0.06, 0.24), U=33 043.00, P<0.05). Nucleated cell count and neutrophil ratio in BALF were higher in hypersecretion group of children with RSV pneumonia (1 210 (442, 2 100)×106 vs. 490 (210, 1 510)×106/L, 0.43 (0.26, 0.62) vs. 0.30 (0.13, 0.52), U=2 043.00, 2 064.00, all P<0.05). Conclusions: The increase in peripheral blood white blood cell count, neutrophil ratio and decrease in lymphocyte count, serum albumin in children with MPP is related to the development of airway mucus hypersecretion. In children with RSV pneumonia, the abnormal increase of eosinophils in peripheral blood has relationship with hypersecretion. The appearance of lung rale, wheezing, and sputum rale are associated with airway mucus hypersecretion in children with adenovirus pneumonia. In addition, local neutrophil infiltration in the respiratory tract is closely related to the occurrence of airway mucus hypersecretion caused by Mycoplasma pneumoniae and RSV infection.


Assuntos
Pneumonia por Mycoplasma , Pneumonia Viral , Infecções por Vírus Respiratório Sincicial , Criança , Masculino , Feminino , Humanos , Lactente , Pré-Escolar , Estudos Retrospectivos , Sons Respiratórios , Pulmão , Muco , Fatores de Risco
13.
Mol Psychiatry ; 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37604975

RESUMO

The brain circuit projecting from the ventral tegmental area (VTA) to the nucleus accumbens lateral shell (NAcLat) has a key role in methamphetamine (MA) addiction. As different dopamine (DA) neuron subpopulations in the VTA participate in different neuronal circuits, it is a challenge to isolate these DA neuron subtypes. Using retrograde tracing and Patch-seq, we isolated DA neurons in the VTA-NAcLat circuit in MA-treated mice and performed gene expression profiling. Among the differentially expressed genes, KCNQ genes were dramatically downregulated. KCNQ genes encode Kv7 channel proteins, which modulate neuronal excitability. Injection of both the Kv7.2/3 agonist ICA069673 and the Kv7.4 agonist fasudil into the VTA attenuated MA-induced conditioned place preference and locomotor sensitization and decreased neuronal excitability. Increasing Kv7.2/3 activity decreased neural oscillations, synaptic plasticity and DA release in the VTA-NacLat circuit in MA-treated mice. Furthermore, overexpression of only Kv7.3 channels in the VTA-NacLat circuit was sufficient to attenuate MA-induced reward behavior and decrease VTA neuron excitability. Activation of Kv7 channels in the VTA may become a novel treatment strategy for MA abuse.

14.
Osteoporos Int ; 34(12): 2027-2045, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37566158

RESUMO

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX. INTRODUCTION: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD). METHODS: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted ß-coefficients. RESULTS: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination. CONCLUSION: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.


Assuntos
Fraturas do Quadril , Osteoporose , Fraturas por Osteoporose , Masculino , Humanos , Feminino , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/complicações , Osteoporose/complicações , Fraturas do Quadril/etiologia , Fraturas do Quadril/complicações , Densidade Óssea , Fatores de Risco , Medição de Risco
16.
Sci Bull (Beijing) ; 68(14): 1540-1555, 2023 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-37422372

RESUMO

Gut microbiota dysbiosis is associated with the development of rheumatoid arthritis (RA). Sinomenine (SIN) is an effective immunosuppressive and anti-inflammatory drug used for treating RA, but how SIN regulates gut microbiota to alleviate RA remains underexplored. To identify the critical gut microbial species and microbial metabolites associated with the RA-protective effects of SIN, the microbiota-dependent anti-RA effects of SIN were assessed by 16S rRNA gene sequencing, antibiotic treatment, and fecal microbiota transplantation. Metabolomics analysis, transcriptional analysis, and targeted bacteria/metabolites gavage were conducted to explore how SIN regulates gut microbiota to reduce the severity of RA. SIN could restore intestinal microbial balance by mainly modulating the abundance of Lactobacillus, and significantly relieve collagen-induced arthritis (CIA) symptoms in a gut microbiota-dependent manner. SIN significantly elevated microbial tryptophan metabolites indole-3-acrylic acid (IA), indole-3-propionic acid (IPA), and indole-3-acetic acid (IAA). Tryptophan metabolites supplementation could activate aryl hydrocarbon receptor (AhR) and regulate Th17/Treg balance in CIA rats. Intriguingly, SIN relieved the arthritis symptoms involving the enrichment of two beneficial anti-CIA Lactobacillus species, L. paracasei and L. casei by mono-colonization. The promising therapeutic function of SIN was mostly attributed to the activation of AhR by explicitly targeting the Lactobacillus and microbial tryptophan metabolites. The intestinal bacterium L. paracasei and L. casei may be used to reduce the severity of CIA.

17.
Biochem Biophys Res Commun ; 671: 96-104, 2023 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-37300946

RESUMO

The orbitofrontal cortex (OFC)-dorsal striatum (DS) is an important neural circuit that contributes to addictive behavior, including compulsive reinforcement, yet the specific types of neurons that play a major role still need to be further elucidated. Here, we used a place conditioning paradigm to measure the conditioned responses to methamphetamine (MA). The results demonstrated that MA increases the expression of c-Fos, synaptic plasticity in OFC and DS. Patch-clamp recording showed that MA activated projection neurons from the OFC to the DS, and chemogenetic manipulation of neuronal activity in OFC-DS projection neurons affects conditioned place preference (CPP) scores. And the combined patch-electrochemical technique was used to detect the DA release in OFC, the data indicated that the DA release was increased in MA group. Additionally, SCH23390, a D1R antagonist, was used to verify the function of D1R projection neurons, showing that SCH23390 reversed MA addiction-like behavior. Collectively, these findings provide evidence for the D1R neuron is sufficient to regulate MA addiction in the OFC-DS pathway, and the study provides new insight into the underlying mechanism of pathological changes in MA addiction.


Assuntos
Corpo Estriado , Metanfetamina , Corpo Estriado/metabolismo , Córtex Pré-Frontal/metabolismo , Metanfetamina/farmacologia , Neurônios/metabolismo , Receptores de Dopamina D1/metabolismo
18.
Aust Dent J ; 68(3): 179-185, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37337920

RESUMO

BACKGROUND: Rotary nickel-titanium (NiTi) instruments are made to exacting standards and are costly to manufacture, and quality control is paramount. Consequently, unauthorized factories make counterfeit instruments that are less expensive and may therefore be attractive to dentists. Little information exists about the metallurgy and manufacturing quality of such instruments. There is the potential for counterfeit instruments to be at higher risk of fracture during treatment, thereby compromising clinical outcomes. The aim of this study was to evaluate physical and manufacturing properties of genuine and counterfeit ProTaper Next™ and Mtwo® rotary NiTi instruments. METHODS: This study investigated the metallurgical properties, manufacturing quality, microhardness and number of cycles to failure of two commonly used rotary NiTi systems and compared them with counterfeit products purporting to be genuine articles. RESULTS: Counterfeit instruments were found to be inferior in manufacturing standards and were less resistant to cyclic fatigue when compared to genuine instruments. CONCLUSIONS: Counterfeit rotary NiTi instruments may be less efficient at preparing root canals and may be at higher risk of fracture during endodontic treatment. Dentists must be aware that, although less expensive, counterfeit instruments may be of dubious manufacturing quality and at higher risk of fracture if used in patients. © 2023 Australian Dental Association.


Assuntos
Ligas Dentárias , Níquel , Humanos , Titânio , Falha de Equipamento , Preparo de Canal Radicular , Austrália , Instrumentos Odontológicos , Teste de Materiais , Desenho de Equipamento
19.
J Agric Food Chem ; 71(19): 7312-7323, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37139957

RESUMO

Disturbance of the gut microbiota plays a critical role in the development of nonalcoholic fatty liver disease (NAFLD). Increasing evidence supports that natural products may serve as prebiotics to regulate the gut microbiota in the treatment of NAFLD. In the present study, the effect of nobiletin, a naturally occurring polymethoxyflavone, on NAFLD was evaluated, and metabolomics, 16S rRNA gene sequencing, and transcriptomics analysis were performed to determine the underlying mechanism of nobiletin, and the key bacteria and metabolites screened were confirmed by in vivo experiment. Nobiletin treatment could significantly reduce lipid accumulation in high-fat/high-sucrose diet-fed mice. 16S rRNA analysis demonstrated that nobiletin could reverse the dysbiosis of gut microbiota in NAFLD mice and nobiletin could regulate myristoleic acid metabolism, as revealed by untargeted metabolomics analysis. Treatment with the bacteria Allobaculum stercoricanis, Lactobacillus casei, or the metabolite myristoleic acid displayed a protective effect on liver lipid accumulation under metabolic stress. These results indicated that nobiletin might target gut microbiota and myristoleic acid metabolism to ameliorate NAFLD.


Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , RNA Ribossômico 16S , Ácidos Graxos Monoinsaturados/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fígado/metabolismo , Camundongos Endogâmicos C57BL
20.
J AOAC Int ; 106(5): 1295-1304, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37243686

RESUMO

BACKGROUND: Platycladus orientalis leaves (POL), as the source of the traditional Chinese medicine (TCM) Platycladi Cacumen, has frequently been found to be misused with five adulterants including Chamaecyparis obtusa leaves (COL), Cupressus funebris leaves (CFL), Juniperus virginiana leaves (JVL), Sabina chinensis leaves (SCL), and Juniperus formosana leaves (JFL). OBJECTIVE: The purpose of this study was to distinguish POL (fresh leaves) from its five adulterants (fresh leaves). METHODS: The micromorphological features in terms of transection and microscopic characteristics of POL and adulterants were captured and compared using the an microscope. Both HPLC and TLC methods for the simultaneous determination of six bioactive flavonoids (myricitrin, isoquercitrin, quercitrin, amentoflavone, afzelin, and hinokiflavone) have been developed. RESULTS: There were significant differences in microscopic features of transverse section and powders. The TLC results suggested that the spots of myricitrin in POL were more obvious than those in the five adulterants. The contents of myricitrin and quercitrin, or the total content of flavonoids in POL, determined by HPLC, were significantly higher than those in the adulterants. CONCLUSION: POL was successfully distinguished from its five adulterants by the comparison of morphology, microscopic characteristics, and chemical profiles. HIGHLIGHTS: This research provides a comprehensive morphology, microscopic identification, TLC, and HPLC analysis for authenticating POL and its five adulterants.


Assuntos
Cupressaceae , Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão/métodos , Flavonoides/análise , Cupressaceae/química , Medicamentos de Ervas Chinesas/análise , Medicina Tradicional Chinesa
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