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BACKGROUND: Circular RNAs (circRNAs) have been implicated in the development and progression of gastric cancer (GC). However, it remains unclear whether dysregulated circRNA affects immune escape and the efficacy of immunotherapy in GC. Our aim is to investigate the molecular mechanism of circRNA affecting GC immunotherapy and identify effective molecular therapeutic targets. METHODS: The differential expression profile of circRNAs was established through circRNA sequencing, comparing three paired GC tissues with their adjacent non-cancerous gastric tissues. The expression level of circRHBDD1 in GC tissues was then assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The biological characteristics of circRHBDD1 were verified through a series of experiments, including agarose gel electrophoresis assays, RNase R treatment, and actinomycin D experiments. The prognostic value of circRHBDD1 in GC was evaluated by conducting both univariate and multivariate survival analyses. Furthermore, loss- and gain-of-function approaches were utilized to investigate the impact of circRHBDD1 on GC immune escape. RNA-sequencing, immunoprecipitation, flow cytometry, and methylated RNA immunoprecipitation (meRIP) analysis were performed to elucidate the underlying molecular mechanisms. RESULTS: We discovered that circRHBDD1 exhibited remarkably high expression levels in GC tissues and cell lines. Notably, the high expression of circRHBDD1 was significantly correlated with poor overall survival and disease-free survival among GC patients. Both in vitro and in vivo experiments revealed that circRHBDD1 upregulated the expression of PD-L1 and impeded the infiltration of CD8+ T cells. Further, we found that circRHBDD1 binds to IGF2BP2, disrupting the interaction between E3 ligase TRIM25 and IGF2BP2, and ultimately inhibiting IGF2BP2 ubiquitination and degradation. Intriguingly, IGF2BP2 enhances PD-L1 mRNA stability through m6A modification. Additionally, we developed Poly (lactide-co-glycolic acid) (PLGA)-Polyethylene glycol (PEG)-based nanoparticles loaded with circRHBDD1 siRNA. In vivo experiments validated that the combination of PLGA-PEG(si-circRHBDD1) and anti-PD-1 offers a safe and efficacious nano-drug regimen for cancer immunotherapy. CONCLUSION: Our results demonstrated that circRHBDD1 promoted GC immune escape by upregulating the expression of PD-L1 and reprogramming T cell-mediated immune response. Inhibition of circRHBDD1 expression could potentially enhance the response of GC patients to immunotherapy, thus improving treatment outcomes. Additionally, the development of a nanodrug delivery system provides a feasible approach for future clinical applications.
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Antígeno B7-H1 , ARN Circular , Proteínas de Unión al ARN , Transducción de Señal , Neoplasias Gástricas , Escape del Tumor , Neoplasias Gástricas/genética , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/patología , Humanos , ARN Circular/genética , ARN Circular/metabolismo , Línea Celular Tumoral , Antígeno B7-H1/metabolismo , Masculino , Femenino , Animales , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Persona de Mediana Edad , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , Ratones , PronósticoRESUMEN
The corpus callosum, historically considered primarily for homotopic connections, supports many heterotopic connections, indicating complex interhemispheric connectivity. Understanding this complexity is crucial yet challenging due to diverse cell-specific wiring patterns. Here, we utilized public AAV bulk tracing and single-neuron tracing data to delineate the anatomical connection patterns of mouse brains and conducted wide-field calcium imaging to assess functional connectivity across various brain states in male mice. The single-neuron data uncovered complex and dense interconnected patterns, particularly for interhemispheric-heterotopic connections. We proposed a metric "heterogeneity" to quantify the complexity of the connection patterns. Computational modeling of these patterns suggested that the heterogeneity of upstream projections impacted downstream homotopic functional connectivity. Furthermore, higher heterogeneity observed in interhemispheric-heterotopic projections would cause lower strength but higher stability in functional connectivity than their intrahemispheric counterparts. These findings were corroborated by our wide-field functional imaging data, underscoring the important role of heterotopic-projection heterogeneity in interhemispheric communication.
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Cuerpo Calloso , Neuronas , Animales , Cuerpo Calloso/fisiología , Masculino , Ratones , Neuronas/fisiología , Vías Nerviosas/fisiología , Conectoma , Encéfalo/fisiología , Simulación por Computador , Modelos Neurológicos , Red Nerviosa/fisiología , Calcio/metabolismoRESUMEN
BACKGROUND: Cuproptosis, as a unique modality of regulated cell death, requires the involvement of ubiquitin-binding enzyme UBE2D2. However, the prognostic and immunotherapeutic values of UBE2D2 in pan-cancer remain largely unknown. METHODS: Using UCSC Xena, TIMER, Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) databases, we aimed to explore the differential expression pattern of UBE2D2 across multiple cancer types and to evaluate its association with patient prognosis, clinical features, and genetic variations. The association between UBE2D2 and immunotherapy response was assessed by gene set enrichment analysis, tumor microenvironment, immune gene co-expression and drug half maximal inhibitory concentration (IC50) analysis. RESULTS: The mRNA and protein levels of UBE2D2 were markedly elevated in most cancer types, and UBE2D2 exhibited prognostic significance in liver hepatocellular carcinoma (LIHC), kidney chromophobe (KICH), uveal melanomas (UVM), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and kidney renal papillary cell carcinoma (KIRP). UBE2D2 expression was correlated with clinical features, tumor mutation burden, microsatellite instability, and anti-tumor drug resistance in several tumor types. Gene enrichment analysis showed that UBE2D2 was significantly associated with immune-related pathways. The expression level of UBE2D2 was correlated with immune cell infiltration, including CD4 + T cellsãMacrophages M2ãCD8 + T cells in pan-cancer. PDCD1, CD274 and CTLA4 expression levels were positively correlated with UBE2D2 level in multiple cancers. CONCLUSIONS: We comprehensively investigated the potential value of UBE2D2 as a prognostic and immunotherapeutic predictor for pan-cancer, providing a novel insight for cancer immunotherapy.
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Primary liver cancer is the sixth most common cancer and the third leading cause of cancer-related death worldwide. The role of the 'Other' subfamily of HECT E3 ligases (E3s) in hepatocellular carcinoma (HCC) remains unknown. The expression of the 'Other' HECT E3s was performed using The Cancer Genome Atlas (TCGA) data, and the authors found that the 'Other' HECT E3s were differentially expressed in HCC. Prognostic values were assessed using the Kaplan-Meier method and indicated that the high expressions of HECTD2, HECTD3, and HACE1 were associated with a worse clinical prognosis of HCC patients. The expression of HECTD2 was significantly correlated with the infiltration of CD4+ T cells and neutrophils. The levels of HECTD3 and HACE1 were notably related to the dendritic cells and memory B cells infiltrated in HCC. In addition, the three previously mentioned genes have shown to be associated with immune checkpoint genes, such as FOXP3, CCR8, STAT5B, TGFB1 and TIM-3. Moreover, HECTD2 could promote the proliferative activity, cell migration and invasive ability of HCC cells. Collectively, the authors' study demonstrated that HECTD2 was a novel immune-related prognostic biomarker for HCC, providing new insight into the treatment and prognosis of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Ubiquitina-Proteína Ligasas/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Biomarcadores de Tumor , Microambiente TumoralRESUMEN
BACKGROUND: Cholangiocarcinoma (CCA) is a fatal cancer of the bile duct with a poor prognosis owing to limited therapeutic options. The incidence of intrahepatic CCA (iCCA) is increasing worldwide, and its molecular basis is emerging. Environmental factors may contribute to regional differences in the mutation spectrum of European patients with iCCA, which are underrepresented in systematic genomic and transcriptomic studies of the disease. METHODS: We describe an integrated whole-exome sequencing and transcriptomic study of 37 iCCAs patients in Germany. RESULTS: We observed as most frequently mutated genes ARID1A (14%), IDH1, BAP1, TP53, KRAS, and ATM in 8% of patients. We identified FGFR2::BICC1 fusions in two tumours, and FGFR2::KCTD1 and TMEM106B::ROS1 as novel fusions with potential therapeutic implications in iCCA and confirmed oncogenic properties of TMEM106B::ROS1 in vitro. Using a data integration framework, we identified PBX1 as a novel central regulatory gene in iCCA. We performed extended screening by targeted sequencing of an additional 40 CCAs. In the joint analysis, IDH1 (13%), BAP1 (10%), TP53 (9%), KRAS (7%), ARID1A (7%), NF1 (5%), and ATM (5%) were the most frequently mutated genes, and we found PBX1 to show copy gain in 20% of the tumours. According to other studies, amplifications of PBX1 tend to occur in European iCCAs in contrast to liver fluke-associated Asian iCCAs. CONCLUSIONS: By analyzing an additional European cohort of iCCA patients, we found that PBX1 protein expression was a marker of poor prognosis. Overall, our findings provide insight into key molecular alterations in iCCA, reveal new targetable fusion genes, and suggest that PBX1 is a novel modulator of this disease.
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Colangiocarcinoma , Factor de Transcripción 1 de la Leucemia de Células Pre-B , Proteínas Proto-Oncogénicas , Humanos , Colangiocarcinoma/genética , Factor de Transcripción 1 de la Leucemia de Células Pre-B/genética , Masculino , Proteínas Proto-Oncogénicas/genética , Femenino , Pronóstico , Persona de Mediana Edad , Anciano , Neoplasias de los Conductos Biliares/genética , Alemania/epidemiología , Biomarcadores de Tumor/genética , Adulto , Genómica/métodos , Proteínas Tirosina QuinasasRESUMEN
This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.
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Animales , Ratones , Ácido Clorogénico , Medicamentos Herbarios Chinos/farmacología , Ácido gamma-Aminobutírico , Interleucina-6 , Medicina Tradicional China , Simulación del Acoplamiento Molecular , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Excessive application of chemical fertilizer has caused many problems in Angelica dahurica var. formosana planting, such as yield decline and quality degradation. In order to promote the green cultivation mode of A. dahurica var. formosana and explore rhizosphere fungus resources, the rhizosphere fungi with nitrogen fixation, phosphorus solubilization, potassium solubilization, iron-producing carrier, and IAA-producing properties were isolated and screened in the rhizosphere of A. dahurica var. formosana from the genuine and non-genuine areas, respectively. The strains were identified comprehensively in light of the morphological characteristics and ITS rDNA sequences, and the growth-promoting effect of the screened strains was verified by pot experiment. The results showed that 37 strains of growth-promoting fungi were isolated and screened from the rhizosphere of A. dahurica var. formosana, mostly belonging to Fusarium. The cultured rhizosphere growth-promoting fungi of A. dahurica var. formosana were more abundant and diverse in the genuine producing areas than in the non-genuine producing areas. Among all strains, Aspergillus niger ZJ-17 had the strongest growth promotion potential. Under the condition of no fertilization outdoors, ZJ-17 inoculation significantly promoted the growth, yield, and accumulation of effective components of A. dahurica var. formosana planted in the soil of genuine and non-genuine producing areas, with yield increases of 73.59% and 37.84%, respectively. To a certain extent, it alleviated the restriction without additional fertilization on the growth of A. dahurica var. formosana. Therefore, A. niger ZJ-17 has great application prospects in increasing yield and quality of A. dahurica var. formosana and reducing fertilizer application and can be actually applied in promoting the growth of A. dahurica var. formosana and producing biofertilizer.
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Fertilizantes , Rizosfera , Angelica/química , Hongos/genética , FósforoRESUMEN
@#Objective Toinvestigatetheregulatoryeffect of microRNA-33a-3p(miR-33a-3p)on chemoresistances of colorectal cancer(CRC). Methods Theexpression of miR-33a-3pin CRC parentalcells(HCT8)and drug-resistantcelllines(HCT8/5-Fu and HCT8/DDP) was detected by quantitative real-time PCR. The miR-33a-3p mimics and negative control mimics were constructed andtransfectedinto CRCdrug-resistantcells. Cell proliferation,apoptosis,cellcycledistributionandchemosensitivity weretested. Thetarget genes of miR-33a-3p were predicted via bioinformatics methods,andtheeffect of overexpressed miR- 33a-3p onthe downstreamtarget gene EphA2 was detected by quantitative real-time PCR and Western blot. Results The expression of miR-33a-3pin HCT8/5-Fu and HCT8/DDP cells was significantlylowerthanthat ofthe parentalcells(P <0.01) .Compared with the negative control group,overexpression of miR-33a-3p could suppress HCT8/5-Fu and HCT8/DDP cells proliferation and promotecell apoptosis,and block cells cyclein G2/M phase as well as enhancecell chemosensitivity(P <0.05) .Bioinformatics predictionresults showedthat EphA2 might bea downstreamtarget gene of miR-33a-3p,andits expression was significantlyreducedin HCT8/5-Fu and HCT8/DDP cells transfected with miR-33a-3p mimics. Conclusion The miR-33a-3p mayreversethechemoresistance of CRC byregulatingthe expressionlevel of downstreamtarget gene EphA2.
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Colorectal cancer (CRC) is a common malignant tumor of the digestive tract, which seriously threatens human health. In recent years, many studies have found that Fusobacterium nucleatum (Fn) is positively related to the occurrence of CRC. In the process of CRC carcinogenesis, Fn can play an important role by inducing the expression of pro-inflammatory cytokines and triggering chronic inflammation, inhibiting the function of immune cells, inducing chemotherapy resistance, promoting the expressions of tumor genes and microRNAs and regulating glycolysis.
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ObjectiveTo explore the mechanism of Didangtang (DDT) against the inflammatory cascade triggered by foam cell pyroptosis in high-glucose environment. MethodOxidized low density lipoprotein (ox-LDL, 100 mg·L-1) was used to induce pyroptosis of foam cells. The control group (5.5 mmol·L-1 glucose), foam cell group (100 mg·L-1 ox-LDL), high-glucose group (33.3 mmol·L-1 glucose), DDT group (10% DDT-containing serum), and NOD-like receptor family pyrin domain-containing 3 (NLRP3) inhibitor group (MCC950, 10 nmmol·L-1) were designed. The cell membrane damage was observed by lactate dehydrogenase (LDH) release assay. The expression of cysteinyl aspartate-specific proteinase-1 (Caspase-1) was detected by immunofluorescence method, and expression of key proteins NLRP3, Caspase-1, gastermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in the pyroptosis pathway was determined by Western blot. The release of IL-18 and IL-1β, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor α (TNF-α) in cell supernatant was measured by enzyme-linked immunosorbent assay (ELISA). ResultThe expression of NLRP3, Caspase-1, and GSDMD was up-regulated (P<0.01) and the release of IL-1β, IL-18, MCP-1, IL-1α, and TNF-α was increased (P<0.01) in foam cell group compared with those in the control group. The expression of NLRP3, Caspase-1, and GSDMD was higher (P<0.01) and the release of inflammatory factors was more (P<0.01) in the high-glucose group than in the foam cell group. DDT and MCC950 can inhibit expression of NLRP3, Caspase-1, GSDMD and reduce the release of IL-1β, IL-18, MCP-1, IL-1α, and TNF-α. ConclusionDDT can suppress the pyroptosis of foam cells induced by NLRP3/Caspase-1 pathway in high-glucose environment and thereby alleviate the inflammatory cascade.
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@#Objective ( ) To investigate the association between urinary polycyclic aromatic hydrocarbons PAHs metabolites - Methods and high normal blood pressure in coke oven workers. A total of 433 coke oven workers were selected as the study - subjects using convenient sampling method. They were divided into normal blood pressure group and high normal blood pressure group according to their blood pressure level. The levels of ten kinds of urinary hydroxylated PAHs metabolites were measured by - Results - high performance liquid chromatography mass spectrometry. Among the subjects,57.5% had high normal blood - , - , - pressure. The levels of 1 hydroxynathalene 2 hydroxyphenanthrene 1 hydroxyphenanthrene and the metabolite of total PAHs - ( P ) in the high normal blood pressure group were higher than those in the normal blood pressure group all <0.05 . The results of - , - , - , the multivariate logistic regression analysis showed that urinary 1 hydroxynathalene 2 hydroxyfluorene 3 hydroxychrysene - ( P ), and metabolite of total PAHs were all risk factors for high normal blood pressure in coke oven workers all <0.05 after , , , , , adjusting for confounding factors such as gender length of service body mass index smoking index alcohol consumption tea , , , Conclusion consumption night shift exercise frequency and other PAHs metabolites. Exposure to PAHs in coke oven plants may increase the risk of elevated blood pressure within the normal range among coke oven workers.
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In recent years, the MYB-related gene family has been found pivotal in plant growth and development. MYB-related gene family in Angelica dahurica var. formosana was systematically investigated based on "Chuanzhi No. 2" through transcriptome database search and bioinformatics and the temporal and spatial expression patterns were analyzed through real-time fluorescence-based quantitative polymerase chain reaction(PCR). The results showed that 122 MYB-related proteins family were identified, mainly including the unstable hydrophilic proteins with good thermal stability. Most of the proteins were located in nuclei. The majority of the proteins had the structures of random coil and α-helix. Five MYB-related proteins family of A. dahurica var. formosana had membrane-binding domains. The conserved domain analysis of MYB-related proteins family of A. dahurica var. formosana showed that the MYB domains of genes in five subgroups, similar to 2 R-, 3 R-, and 4 R-MYB proteins, contained three evenly distributed Trp(W) residues in the MYB repeat sequence. The phylogenetic analysis of MYB-related proteins family in A. dahurica var. formosana and Arabidopsis thaliana showed that the MYB-related members were unevenly distributed in five subgroups, and A. thaliana and A. dahurica var. formosana had almost the same number of genes in the CCA1-like subgroup. There were differences in the number, type, and distribution of motifs contained in 122 encoded proteins. Transcription factors with similar branches had similar domains and motifs. The expression pattern analysis showed that the transcription factors AdMYB53, AdMYB83, and AdMYB89 responded to hormones to varying degrees, and they were highly expressed in leaves and responded quickly in roots. This study lays a foundation for further investigating the function of MYB-related transcription factors of A. dahurica var. formosana and solving the corresponding biological problems such as bolting early.
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Animales , Angelica/química , Biología Computacional , Gastrópodos , Filogenia , Hojas de la Planta , Proteínas de Plantas/genética , Factores de Transcripción/genéticaRESUMEN
Chronic pain of knee osteoarthritis (KOA) greatly affects the quality of life and functional activities of patients. It is important to clarify the underlying mechanisms of KOA pain and the analgesic effect of different therapies. Neuroimaging technology has been widely used in the basic and clinical research of pain. In the recent years, neuroimaging technology has played an important role in the basic and clinical research of KOA pain. Increasing evidence demonstrates that chronic pain in KOA includes both nociceptive and neuropathic pain. The neuropathic mechanism involved in KOA pain is complex, which may be caused by peripheral or central sensitization. In this paper, we review the regional changes of brain pathophysiology caused by KOA pain based on magnetic resonance imaging (MRI), electroencephalogram (EEG), magnetoencephalogram (MEG), near-infrared spectroscopy (NIRS) and other neuroimaging techniques. We also discuss the central analgesic mechanism of different KOA therapies, with a focus on the latest achievements in the evaluation and prediction of pain. We hope to provide new thoughts for the treatment of KOA pain, especially in the early and middle stages of KOA.
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Humanos , Dolor Crónico/diagnóstico por imagen , Neuroimagen , Osteoartritis de la Rodilla/diagnóstico por imagen , Calidad de Vida , TecnologíaRESUMEN
Objective:To explore the different design of readiness assurance process (RAP) and application in TBL teaching of rehabilitation medicine, and to compare the teaching effects.Methods:A total of 40 students who had clinical rotation in our department were chose as research subjects, and they were taught with TBL teaching. Two chapters of "Stroke Rehabilitation" and "Spinal Cord Injury Rehabilitation" were chosen for the two lectures. During the course of "Stroke Rehabilitation", the RAP adopted open-ended questions, and the application part simulated Teamwork meetings. In the course of "Spinal Cord Injury Rehabilitation", the RAP used close-ended multiple-choice questions, and the application part simulated making rehabilitation plan. At the end of the two lectures, questionnaires were send to students.Results:For the RAP part, more students preferred open-ended questions. In the application part, students preferred to make rehabilitation plan.Conclusion:The process of clinical diagnosis and treatment and the formulation of rehabilitation plan in clinical practice of rehabilitation medicine has been applied to different parts of TBL teachings, and students are favor of this teaching method, which provides a reference for the future TBL teaching design of rehabilitation medicine.
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Objective: To evaluate the effectiveness of therapeutic massage (tuina) for treating knee osteoarthritis (KOA). Methods: Six English and Chinese databases, including Chinese National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full-text Database (Wanfang), Chongqing VIP Database (CQVIP), China Biology Medicine Disc (CBM), Cochrane Library and PubMed databases, were independently searched to identify appropriate randomized controlled trials (RCTs) studying therapeutic massage for KOA compared to oral non-steroidal anti-inflammatory drugs (NSAIDs) alone. The main outcome measures were total effectiveness and the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) score. Results: A total of 8 RCTs were included and they were of average quality. The results showed that therapeutic massage was more effective than NSAIDs comparing total effectiveness [risk ratio (RR)=1.14, 95% confidence interval (CI) (1.07, 1.21), P<0.0001]; compared with NSAIDs, therapeutic massage produced more significant improvements in pain [mean difference (MD)=-2.06, 95%CI (-2.75, -1.36), P<0.00001], stiffness intensity [MD=-0.90, 95%CI (-1.05, -0.75), P<0.00001] and joint function [MD=-12.48, 95%CI (-13.91, -11.05), P<0.00001]. Conclusion: Therapeutic massage was more effective than oral NSAIDs in treating KOA. In relieving pain and stiffness and improving the function of knee joint, therapeutic massage was superior to NSAIDs.
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NAC(NAM/ATAF/CUC) protein plays an important role in plant growth and development, secondary cell wall formation and stress response. In this study, based on the sequencing data of Angelica dahurica, the NAC family was systematically analyzed using bioinformatics methods and its expression pattern was analyzed. Studies showed that 75 candidate genes had been selected from the NAC transcription factor family of A. dahurica, with the protein size of 148-641, all of which were unstable hydrophilic proteins. Most NAC proteins were localized in the nucleus, and had complete NAC domain. Phylogenetic analysis of NAC family proteins of A.dahurica and Arabidopsis thaliana showed that among the 17 subfamilies, NAC members were unevenly distributed in each subfamily, indicating that the evolution of species is developing in multiple directions. Among them, ANAC063 subfamily contained no NAC sequence of A. dahurica, which might be due to the functional evolution of the species. Analysis of protein transmembrane structure and signal peptide showed that NAC transcription factor could carry out transmembrane transportation, but its signal peptide function had not been found. Expression analysis showed that most transcription factors responded to abiotic stress and hormones to varying degrees, and the effects of hormones were obvious, especially ABA and IAA. In different organs of A. dahurica, most members of the NAC family had higher expression in root phloem, followed by root xylem. This study lays a foundation for further research on the function of A. dahurica NAC transcription factor and for solving the biological problems of A. dahurica.
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Angelica , Biología Computacional , Regulación de la Expresión Génica de las Plantas , Filogenia , Proteínas de Plantas/metabolismo , Estrés Fisiológico , Factores de Transcripción/metabolismoRESUMEN
Macroangiopathy is a complication of Type II Diabetes Mellitus (T2DM), which is mainly caused by fibrosis of blood vessels. Using T2DM rat models, we investigated whether the traditional Chinese medicine, Di-Dang Decoction (DDD), exhibited anti-fibrotic actions on great vessels. T2DM rats were randomly divided into non-intervention group, early-, middle-, late-stage DDD intervention groups and control groups, including pioglitazone group and aminoguanidine group. After administration of DDD to T2DM rats at different times, we detected the amount of extracellular matrix (ECM) deposition in the thoracic aorta. The results showed that early-stage intervention with DDD could effectively protect great vessels from ECM deposition. Considering that TGF-β1 is the master regulator of fibrosis, we further validated at the molecular level that, compared to middle- and late-stage intervention with DDD, early-stage intervention with DDD could significantly decrease the expression levels of factors related to the activated TGF-β1/Smad signalling pathway, as well as the expression levels of downstream effectors including CTGF, MMP and TIMP family proteins, which were directly involved in ECM remodelling. Therefore, early-stage intervention with DDD can reduce macrovascular fibrosis and prevent diabetic macroangiopathy.
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The proportion of mycobiome is less than 1% of human microbiome. However, fungal community plays a key role in human health and diseases. With high-throughput sequencing applications, the structure and composition of mycobiome in the mouth, lung, gut, vagina, and skin have been analyzed, and the role of microbiome in diseases has been investigated. Mycobiome also influences the composition of bacteriome and includes key species that maintain the structure and function of microbial communities. Fungi also influence host immune responses. In this review, we summarized the mycobiome com-position at various sites and different diseases and the interactions between fungi-bacteria and fungi-host.
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Femenino , Humanos , Bacterias , Enfermedad , Hongos , Microbiota , Boca , MicobiomaRESUMEN
Objective To evaluate the effect of three different doses of oxycodone hydrochloride injection on uterine cramping pain and emotion in patients of artificial abortion.Methods Four hundred female patients, aged 17-38 years, BMI 18.5-23.9 kg/m2, falling into ASA physical statusⅠ orⅡ, undergoing elective artificial abortion were randomized into four groups using a random number table:group O1 (oxycodone 0.06 mg/kg), group O2 (oxycodone 0.08 mg/kg), group O3 (oxycodone 0.1 mg/kg), and group F, 100 cases in each.In group O1, group O2 and group O3, oxycodone 0.06, 0.08, 0.1 mg/kg were intravenously injected respectively, while in group F fentanyl1μg/kg was intravenously injected.Then, propofol 2.5 mg/kg was intravenously injected as induced dose.The operation was started when eyelash reflexes disappeared, propofol 0.4 mg/kg was intravenously injected when body movement appeared during the operation.The propofol doses, operation time and recovery time were recorded.HR, MAP, RR before anesthesia (T0), when loss of eyelash reflex (T1), operation (T2) and recovery (T3) were recorded.The uterine cramping pain was assessed with numerical rating scale (NRS) at recovery, 10, 30, 60 min after operation.Patients'satisfaction was recorded after operation.Patients'emotion was assessed with positive and negative affect scale (PANAS) both before and after operation in one hour.Rescue analgesia, nausea and vomiting, dizziness, respiratory depression, pruritus, uroschesis, cognitive dysfunction, sweatiness were recorded.Results The propofol doses and recovery time in groups O2, O3 and F were significantly lower than those in group O1 (P<0.05).The NRS score of uterine cramping pain in groups O1, O2 and O3 were significantly lower than that in group F (P<0.05).Patients'satisfaction in groups O1, O2 and O3 were significantly higher than that in group F (P<0.05).The positive affective score after operation in one hour among the four groups were significantly higher than that before operation (P<0.05), and the negative affective score after operation in one hour among the four groups were significantly lower than that before operation (P<0.05).The positive affective score after operation in one hour in groups O1, O2 and O3 were significantly higher than that in group F (P<0.05), and the rescue analgesia in groups O1, O2 and O3 were significantly lower than that in group F (P<0.05).There were no significant differences among the four groups as to the dizziness, nausea and vomiting.No respiratory depression, pruritus, emergence agitation, cognitive dysfunction, uroschesis and sweatiness were reported.Conclusion Oxycodone 0.08 mg/kg combined with propofol in patients undergoing artificial abortion is effective in preventing uterine cramping pain.Furthermore, the patients'satisfaction and positive affective score can also be improved.
RESUMEN
Acute closed Achilles tendon rupture is a common sport injury.Rupture of the Achilles tendon may limit the ability of physical exercises and activities of daily life.Conservative treatment has long recovery time and high risk of re-rupture of Achilles tendon.In recent years,with the early functional rehabilitation exercise,including early weight bearing and ankle joint flexion and extension exercise under the protection of orthopaedic braces,re-rupture risk of Achilles tendon has been significantly reduced,thus conservative treatment is becoming more and more popular.The surgical treatment mainly includes traditional open surgery and minimally invasive surgery.Minimally invasive treatment has less trauma,low re-rupture rate like open surgery,low risk of wound infection and is helpful for early rehabilitation.However,the risk of the sural nerve injury is higher.Open surgery has clear operating field and low re-rupture rate and low risk of the sural nerve injury.However,it still has some problems such as superficial and deep infection of the incision,suture reaction,tissue adhesion and so on.Both of them can achieve satisfactory results in the treatment of acute closed Achilles tendon rupture.Although the mechanism of injury of acute closed rupture of the Achilles tendon and epidemic characteristics have a deeper understanding,including degenerative tendon rupture and mechanical rupture of Achilles tendon,the incidence rate showed a rising trend,and affected by the geographical,gender,age and other factors,due to the existence of a variety of patient groups,there is still controversy over the optimal treatment modalities resulting from the diversity of the patient population.According to the individual differences of different groups of patients,the combination of early rehabilitation exercise can achieve satisfactory clinical effects as long as the treatment methods are appropriate.At present,the effect of biological therapy on the healing of Achilles tendon and the prevention of deep vein thrombosis are still controversial.There is no definitive evidence for the effectiveness of biological therapy and the need for prophylactic anticoagulation.The purpose of this study is to summarize the treatment of acute closed Achilles tendon rupture,and to discuss the importance of early functional exercise for acute closed Achilles tendon rupture and its effect on prognosis.