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DNA damage is a key factor affecting gametogenesis and embryo development. The integrity and stability of DNA are fundamental to a woman's successful conception, embryonic development, pregnancy and the production of healthy offspring. Aging, reactive oxygen species, radiation therapy, and chemotherapy often induce oocyte DNA damage, diminished ovarian reserve, and infertility in women. With the increase of infertility population, there is an increasing need to study the relationship between infertility related diseases and DNA damage and repair. Researchers have tried various methods to reduce DNA damage in oocytes and enhance their DNA repair capabilities in an attempt to protect oocytes. In this review, we summarize recent advances in the DNA damage response mechanisms in infertility diseases such as PCOS, endometriosis, diminished ovarian reserve and hydrosalpinx, which has important implications for fertility preservation.
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Daño del ADN , Reparación del ADN , Infertilidad Femenina , Femenino , Humanos , Infertilidad Femenina/genética , Infertilidad Femenina/terapia , Oocitos , Síndrome del Ovario Poliquístico/genética , Endometriosis/genética , Reserva Ovárica/fisiología , Preservación de la Fertilidad/métodosRESUMEN
Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.
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OBJECTIVES: This study explored the association between the Frailty Index (FI) and low back pain (LBP) in middle-aged and older Chinese adults. We hypothesised that a higher FI correlates with increased LBP prevalence. DESIGN: Cross-sectional analysis. SETTING: The study used data from the China Health and Retirement Longitudinal Study (CHARLS) across various regions of China. PARTICIPANTS: The analysis included 6375 participants aged 45 and above with complete LBP and FI data from the CHARLS for 2011, 2013 and 2015. We excluded individuals under 45, those with incomplete LBP data, participants with fewer than 30 health deficit items and those missing covariate data. OUTCOME MEASURES: We constructed an FI consisting of 35 health deficits. Logistic multivariable regression examined the relationship between FI and LBP, using threshold analysis to identify inflection points. Sensitivity analyses were performed to ensure the robustness of the findings. RESULTS: Of the participants, 27.2% reported LBP. A U-shaped association was observed between FI and LBP, with the highest quartile (Q4, FI ≥0.23) showing more than a twofold increased risk of LBP (OR=2.90, 95% CI: 2.45-3.42, p<0.001). Stratified analysis showed a significant association in participants under 60, particularly in the lowest FI quartile (OR=1.43, 95% CI: 1.14 to 1.79). Sensitivity analysis upheld the robustness of the primary results. CONCLUSIONS: The findings suggest a complex relationship between frailty and LBP, highlighting the need for early screening and tailored interventions to manage LBP in this demographic. Further research is necessary to understand the mechanisms of this association and to validate the findings through longitudinal studies.
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Fragilidad , Dolor de la Región Lumbar , Humanos , Dolor de la Región Lumbar/epidemiología , Masculino , China/epidemiología , Femenino , Estudios Transversales , Persona de Mediana Edad , Anciano , Estudios Longitudinales , Fragilidad/epidemiología , Fragilidad/diagnóstico , Prevalencia , Modelos Logísticos , Factores de Riesgo , Anciano de 80 o más Años , Pueblos del Este de AsiaRESUMEN
BACKGROUND: Droplet digital PCR (ddPCR) is increasingly used in diagnosing clinical pathogens, but its effectiveness in cirrhosis patients with suspected ascites infection remains uncertain. METHODS: The diagnostic performance of ddPCR was assessed in 305 ascites samples, utilizing culture and clinical composite standards. The quantitative value and potential clinical impact of ddPCR were further analyzed in patients with spontaneous bacterial peritonitis. RESULTS: With culture standards, ddPCR demonstrated a sensitivity of 86.5% and specificity of 83.2% for bacterial or fungal detection. After adjustment of clinical composite criteria, specificity increased to 96.4%. Better diagnostic performance for all types of targeted pathogens, particularly fungi, was observed with ddPCR compared to culture, and more polymicrobial infections were detected (30.4% versus 5.7%, p < 0.001). Pathogen loads detected by ddPCR correlated with white blood cell count in ascites and blood, as well as polymorphonuclear cell (PMN) count in ascites, reflecting infection status rapidly. A positive clinical impact of 55.8% (43/77) was observed for ddPCR, which was more significant among patients with PMN count ≤ 250/mm3 in terms of medication adjustment and new diagnosis. ddPCR results for fungal detection were confirmed by clinical symptoms and other microbiological tests, which could guide antifungal therapy and reduce the risk of short-term mortality. CONCLUSIONS: ddPCR, with appropriate panel design, has advantages in pathogen detection and clinical management of ascites infection, especially for patients with fungal and polymicrobial infections. Patients with atypical spontaneous bacterial peritonitis benefited more from ddPCR.
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Ascitis , Infecciones Bacterianas , Cirrosis Hepática , Peritonitis , Reacción en Cadena de la Polimerasa , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/microbiología , Cirrosis Hepática/diagnóstico , Femenino , Masculino , Reacción en Cadena de la Polimerasa/métodos , Persona de Mediana Edad , Peritonitis/diagnóstico , Peritonitis/microbiología , Ascitis/microbiología , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/microbiología , Sensibilidad y Especificidad , Anciano , Micosis/diagnóstico , Micosis/microbiologíaRESUMEN
BACKGROUND: The genus Triplostegia contains two recognized species, T. glandulifera and T. grandiflora, but its phylogenetic position and species delimitation remain controversial. In this study, we assembled plastid genomes and nuclear ribosomal DNA (nrDNA) cistrons sampled from 22 wild Triplostegia individuals, each from a separate population, and examined these with 11 recently published Triplostegia plastomes. Morphological traits were measured from herbarium specimens and wild material, and ecological niche models were constructed. RESULTS: Triplostegia is a monophyletic genus within the subfamily Dipsacoideae comprising three monophyletic species, T. glandulifera, T. grandiflora, and an unrecognized species Triplostegia sp. A, which occupies much higher altitude than the other two. The new species had previously been misidentified as T. glandulifera, but differs in taproot, leaf, and other characters. Triplotegia is an old genus, with stem age 39.96 Ma, and within it T. glandulifera diverged 7.94 Ma. Triplostegia grandiflora and sp. A diverged 1.05 Ma, perhaps in response to Quaternary climate fluctuations. Niche overlap between Triplostegia species was positively correlated with their phylogenetic relatedness. CONCLUSIONS: Our results provide new insights into the species delimitation of Triplostegia, and indicate that a taxonomic revision of Triplostegia is needed. We also identified that either rpoB-trnC or ycf1 could serve as a DNA barcode for Triplostegia.
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Caprifoliaceae , Genoma de Plastidios , Humanos , Adulto , Filogenia , Caprifoliaceae/genética , Genoma de Plastidios/genética , Fenotipo , ADN RibosómicoRESUMEN
OBJECTIVES: Most Asian countries have employed Chinese medicine (CM) and Western medicine to treat lumbar spinal stenosis (LSS). Evidence synthesis and comparison of effectiveness are difficult since outcomes examined and presented through trials possess heterogeneity. This study aimed to solve the outcome problems for CM clinical trials in LSS by building a core outcome set (COS). METHODS: To achieve an agreement on a set of core outcome domains, a four-phase study was carried out. First, we identified candidate outcome domains by systematically reviewing trials. In addition, we identified outcome domains associated with patients by conducting semistructured interviews with patients. Next, outcome domains were processed through a national two-round Delphi survey, in which 18 patients and 21 experts were recruited. Finally, the above domains were converted as a core outcome domain set based on a consensus meeting, in which 24 stakeholders were recruited. RESULTS: Seventeen outcome subdomains were identified by the systematic review and interviews. The Delphi survey assigned a priority to four outcome domains in the first round and four outcomes additionally in the second round. The core outcome domains were determined through discussion and redefinition of outcomes in the consensus meeting: pain and discomfort, health-related quality of life, lumbar function, activities of daily living, measures of walking, patient global assessment, adverse events and CM-specific outcomes. CONCLUSION: COS-CM-LSS is likely to enhance the consistency of outcomes reported in clinical trials. In-depth research should be conducted for the exploration of the best methods to examine the above outcomes.
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Medicina Tradicional China , Estenosis Espinal , Humanos , Calidad de Vida , Actividades Cotidianas , Técnica Delphi , Proyectos de Investigación , Evaluación de Resultado en la Atención de Salud/métodos , Resultado del TratamientoRESUMEN
OBJECTIVE: The global aim to lower preterm birth rates has been hampered by the insufficient and incomplete understanding of its etiology, classification, and diagnosis. This study was designed to evaluate the association of phenotypically classified preterm syndromes with neonatal outcomes; to what extent would these outcomes be modified after the obstetric interventions, including use of glucocorticoid, magnesium sulfate, and progesterone. METHODS: This was a retrospective cohort study conducted at Tongji Hospital (composed of Main Branch, Optical Valley Branch and Sino-French New City Branch) in Wuhan. A total of 900 pregnant women and 1064 neonates were retrospectively enrolled. The outcomes were the distribution of different phenotypes among parturition signs and pathway to delivery, the association of phenotypically classified clusters with short-term unfavorable neonatal outcomes, and to what extent these outcomes could be modified by obstetric interventions. RESULTS: Eight clusters were identified using two-step cluster analysis, including premature rupture of fetal membranes (PPROM) phenotype, abnormal amniotic fluid (AF) phenotype, placenta previa phenotype, mixed condition phenotype, fetal distress phenotype, preeclampsia-eclampsia & hemolysis, elevated liver enzymes, and low platelets syndrome (PE-E&HELLP) phenotype, multiple fetus phenotype, and no main condition phenotype. Except for no main condition phenotype, the other phenotypes were associated with one or more complications, which conforms to the clinical practice. Compared with no main condition phenotype, some phenotypes were significantly associated with short-term adverse neonatal outcomes. Abnormal AF phenotype, mixed condition phenotype, PE-E&HELLP phenotype, and multiple fetus phenotype were risk factors for neonatal small-for gestation age (SGA); placenta previa phenotype was not associated with adverse outcomes except low APGAR score being 0-7 at one min; mixed condition phenotype was associated with low APGAR scores, SGA, mechanical ventilation, and grade HI-W intraventricular hemorrhage (IVH); fetal distress phenotype was frequently associated with neonatal SGA and mechanical ventilation; PE-E&HELLP phenotype was correlated with low APGAR score being 0-7 at one min, SGA and neonatal intensive care unit (NICU) admission; multiple fetus phenotype was not a risk factor for the outcomes included except for SGA. Not all neonates benefited from obstetric interventions included in this study. CONCLUSION: Our research disclosed the independent risk of different preterm phenotypes for adverse pregnancy outcomes. This study is devoted to putting forward the paradigm of classifying preterm birth phenotypically, with the ultimate purpose of defining preterm phenotypes based on multi-center studies and diving into the underlying mechanisms.
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Síndrome HELLP , Placenta Previa , Complicaciones del Embarazo , Nacimiento Prematuro , Recién Nacido , Embarazo , Femenino , Humanos , Estudios Retrospectivos , Sufrimiento FetalRESUMEN
The impact of COVID-19 is global, and uncertain information will affect product quality and worker efficiency in the complex supply chain network, thus bringing risks. Aiming at individual heterogeneity, a partial mapping double-layer hypernetwork model is constructed to study the supply chain risk diffusion under uncertain information. Here, we explore the risk diffusion dynamics, drawing on epidemiology, and establish an SPIR (Susceptible-Potential-Infected-Recovered) model to simulate the risk diffusion process. The node represents the enterprise, and hyperedge represents the cooperation among enterprises. The microscopic Markov chain approach (MMCA) is used to prove the theory. Network dynamic evolution includes two removal strategies: (i) removing aging nodes; (ii) removing key nodes. Using Matlab to simulate the model, we found that it is more conducive to market stability to eliminate outdated enterprises than to control key enterprises during risk diffusion. The risk diffusion scale is related to interlayer mapping. Increasing the upper layer mapping rate to strengthen the efforts of official media to issue authoritative information will reduce the infected enterprise number. Reducing the lower layer mapping rate will reduce the misled enterprise number, thereby weakening the efficiency of risk infection. The model is helpful for understanding the risk diffusion characteristics and the importance of online information, and it has guiding significance for supply chain management.
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BACKGROUND: MiRNAs can affect the radiosensitization of head and neck squamous cell carcinoma (HNSCC). We aimed to analyze the function of miR-125 family members in HNSCC using The Cancer Genome Atlas (TCGA) and determine their effect on radiation in laryngeal squamous cell cancer (LSCC). METHODS: First, we systematically analyzed the role of the miR-125 family in HNSCC using the TCGA database and found that miR-125a-5p is associated with radiotherapy. We then performed comprehensive enrichment analysis of miR-125a-5p and predicted target genes. Then, we performed transfection, cell proliferation assays, reverse transcription polymerase chain reaction, apoptosis assays, micronucleus tests, and western blotting on hep-2 cells selected with puromycin. RESULTS: MiR-125 family members exhibited significantly different expression in HNSCC. They were significantly associated with tumor-node-metastasis staging, clinical stages, and histological grades. Radiation therapy had a statistically effect on miR-125 family members, except miR-125a-3p. Moreover, miR-125a-5p was related to overall survival in LSCC. Thus, we predicted 110 target genes and seven hub genes of miR-125a-5p. The proliferation rate of cells transfected with lentivirus vector expressing miR-125a-5p was significantly reduced compared to the other groups. The radiation effect was enhanced in cells transfected with miR-125a-5p. The ratio of apoptotic cells transfected and exposed to X-rays (10 Gy) was distinctly higher than that of the Ad-control group. Western blotting analysis revealed that miR-125a-5p upregulated the apoptotic regulators P53 and rH2AX. Thus, miR-125a-5p may increase radiosensitivity in LSCC via upregulation of pro-apoptotic genes. CONCLUSIONS: MiR-125 family members could be prognostic biomarkers of HNSCC and improve HNSCC sensitivity to radiotherapy by activating P53. Upregulating miR-125a-5p via lentivirus vectors may be a novel strategy to strengthen the effect of radiotherapy on LSCC.
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Neoplasias de Cabeza y Cuello , MicroARNs , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Proteína p53 Supresora de Tumor/genética , Línea Celular Tumoral , MicroARNs/genética , Tolerancia a Radiación/genética , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/radioterapia , Regulación Neoplásica de la Expresión Génica , Proliferación Celular/genéticaRESUMEN
Sarcopenia, a decrease in skeletal muscle mass and function caused by aging, impairs mobility, raises the risk of fractures, diabetes, and other illnesses, and severely affects a senior's quality of life. Nobiletin (Nob), polymethoxyl flavonoid, has various biological effects, such as anti-diabetic, anti-atherogenic, anti-inflammatory, anti-oxidative, and anti-tumor properties. In this investigation, we hypothesized that Nob potentially regulates protein homeostasis to prevent and treat sarcopenia. To investigate whether Nob could block skeletal muscle atrophy and elucidate its underlying molecular mechanism, we used the D-galactose-induced (D-gal-induced) C57BL/6J mice for 10 weeks to establish a skeletal muscle atrophy model. The findings demonstrated that Nob increased body weight, hindlimb muscle mass, lean mass and improved the function of skeletal muscle in D-gal-induced aging mice. Nob improved myofiber sizes and increased skeletal muscle main proteins composition in D-gal-induced aging mice. Notably, Nob activated mTOR/Akt signaling to increase protein synthesis and inhibited FOXO3a-MAFbx/MuRF1 pathway and inflammatory cytokines, thereby reducing protein degradation in D-gal-induced aging mice. In conclusion, Nob attenuated D-gal-induced skeletal muscle atrophy. It is a promising candidate for preventing and treating age-associated atrophy of skeletal muscles.
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Galactosa , Sarcopenia , Ratones , Animales , Galactosa/metabolismo , Sarcopenia/metabolismo , Proteostasis , Calidad de Vida , Ratones Endogámicos C57BL , Atrofia Muscular/inducido químicamente , Atrofia Muscular/tratamiento farmacológico , Atrofia Muscular/metabolismo , Músculo Esquelético/metabolismo , EnvejecimientoRESUMEN
OBJECTIVE: The objective of the study was to assess the effectiveness of utilizing Non-Pharmaceutical Chinese Medical (NPCM) therapy singularly or in combination for the treatment of Degenerative Lumbar Spinal Stenosis (DLSS). METHODS: The comprehensive search for all randomized controlled trials regarding NPCM therapies for the treatment of DLSS was performed through online databases searches, commencing from their inception to January 1st, 2023. The relevant literature underwent a thorough screening process, and the data was meticulously extracted and subjected to analysis through the implementation of RevMan 5.3 software. The Cochrane Risk of Bias tool was employed to assess the potential risk of bias. The synthesis of evidence was performed Grading of Recommendations Assessment, Development, and Evaluation. RESULTS: The extensive search procedure produced 5674 records, including data from 37 studies of 38 comparisons (2965 participants). Moderate evidence was obtained demonstrating that the application of acupuncture for a duration of 6-8 weeks was significantly superior to sham acupuncture in terms of intermediate-term (6 months) alleviation of back pain (2 trials, n = 128; MD, -1.08; 95% CI, -1.81â¼-0.34) and improvement in lumbar function (2 trials, n = 128; MD, -1.40; 95% CI, -2.93â¼-0.13). The available low evidence suggested that, as compared to sham acupuncture, acupuncture was effective in reducing short-term (3 months) back pain and enhancing lumbar function but had no impact on leg pain. A trial with low risk of bias found that acupuncture was more effective than sham acupuncture in enhancing disability and walking capabilities. The other studies presented inconsistent evidence with regards to the efficacy of the various interventions employed. CONCLUSIONS: Evidence of low-to-moderate quality suggests that for DLSS patients, the implementation of acupuncture in comparison to sham acupuncture presents favorable outcomes in terms of short- and intermediate-term alleviation of back pain, improvement in lumbar function, enhancement of disability and walking capacity. The conclusion regarding the efficacy of other NPCM therapies was not obtained due to the insufficient quality of the available evidence. REGISTRATION: PROSPERO CRD42022307631.
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Terapia por Acupuntura , Estenosis Espinal , Humanos , Terapia por Acupuntura/métodos , Dolor de Espalda , Ensayos Clínicos Controlados Aleatorios como Asunto , Estenosis Espinal/terapia , Medicina Tradicional ChinaRESUMEN
BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.
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Asma , Productos Biológicos , Pólipos Nasales , Rinitis , Sinusitis , Humanos , Asma/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Enfermedad Crónica , Consenso , Pólipos Nasales/complicaciones , Pólipos Nasales/tratamiento farmacológico , Omalizumab/uso terapéutico , Calidad de Vida , Rinitis/complicaciones , Rinitis/tratamiento farmacológico , Sinusitis/complicaciones , Sinusitis/tratamiento farmacológico , Esteroides/uso terapéuticoRESUMEN
OBJECTIVE: This study is to explore the efficacy of contrast-enhanced ultrasound (CEUS) / Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) fusion imaging-guidedï¼fusion groupï¼radiofrequency ablation (RFA) versus conventional ultrasound imaging-guided (conventional group) RFA for colorectal cancer liver metastases (CRLM) in a short-term. METHODS: From December 2020 to December 2021, patients who underwent imaging-guided RFA of CRLM at our hospital with available CT/MRI images were enrolled consecutively. 22 patients with 46 lesions had undergone conventional group RFA whereas 29 patients with 63 lesions had undergone fusion group RFA. The lesion detection rate, technical success, local tumor progression (LTP) and complications were calculated. RESULT: In this retrospective study, 51 patients with 130 lesions were diagnosed with CRLM. However, there were 12 lesions and 9 lesions invisible in the conventional group and fusion group, respectively. The lesion detection rate on the fusion imaging was significantly higher than on the US or CEUS in the fusion group (Pï¼0.05). There were no significant differences of the detection rate between the conventional group and the fusion group (P=0.207). In both groups, the technical success rate was 100%. For local tumor progression (LTP), there were no significant differences between the two groups (Pï¼0.05). The complications after ablation had no significant differences between the two groups (P=0.97). CONCLUSION: CEUS/ Gd-EOB-DTPA-enhanced MRI fusion imaging is a safe and effective method for RFA in the management of CRLM patients, and it may improve the therapeutic effect by detecting small lesions early.
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INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. It can progress from simple steatosis to nonalcoholic steatohepatitis and may even develop into liver fibrosis, hepatocirrhosis, or hepatocellular carcinoma, but there is no effective treatment. MATERIAL AND METHODS: Wild-type (wt) and diabetic (db/db) mouse NAFLD-induced models were used to investigate the hepatoprotective effects and potential mechanisms of dapagliflozin (a new oral hypoglycaemic drug) on type 2 diabetes mellitus (T2DM) complicated with NAFLD, and to establish wt and db/db mouse NAFLD-induced and dapagliflozin treatment models. RESULTS: Dapagliflozin reduces blood glucose, glycosylated haemoglobin, blood lipids, and serum transaminase levels in db/db mice and improves T2DM-related liver injury accompanied by NAFLD; the mechanism may be related to the decrease in dipeptidyl-peptidase-4 (DPP4) protein expression and improvement in liver enzymes. Further mechanism-related studies by our team revealed that dapagliflozin can also downregulate the expression of DPP4 proteins in the liver and reduce serum soluble DPP4 enzyme levels, thereby improving the hepatic steatosis and insulin resistance of NAFLD. CONCLUSION: Dapagliflozin may be an effective drug for the treatment of T2DM-induced NAFLD and NAFLD, providing a reliable laboratory basis and new treatment methods for the clinical treatment of NAFLD.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Enfermedad del Hígado Graso no Alcohólico , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Dipeptidil Peptidasa 4/metabolismo , Dipeptidil Peptidasa 4/farmacología , Dipeptidil Peptidasa 4/uso terapéutico , HígadoRESUMEN
Aim: Lumbar spinal stenosis (LSS) is a long-term degenerative disease. Considering the risks and advantages of the patient's age range and the characteristics of the condition, non-surgical treatment is recommended. To determine the best first-line non-surgical therapy for LSS, few studies have examined different non-surgical therapies. Therefore, the main objective of this study is to determine whether the selection of comprehensive Chinese medicine (CM) treatment for LSS is more successful than non-surgical conservative treatment. Patients and Methods: In this two-armed, parallel, single-centered, pragmatic randomized controlled study, 94 LSS participants will be randomized to receive 24 sessions of comprehensive CM therapy or conservative treatment for 3 months, with follow-up assessments at 6, 9, 12, and 15 months. The primary outcome will be based on the success rate of the Zurich Claudication Questionnaire (ZCQ) for the most clinical important difference (MCID) at 3 and 15 months. Secondary outcomes include Numerical Rating Scale (NRS) scores for back and leg pain, ZCQ scores, Oswestry Disability Index scores for lumbar dysfunction, and Short-Form 12 scores for health-related quality of life at 3, 6, 9, 12, and 15 months. Adverse events and incidences of surgery will be reported anytime during the trial and follow-up. Conclusion: This protocol examines the comparative efficacy of comprehensive CM therapy compared with conventional care through a pragmatic randomized controlled trial to present data to facilitate clinical or policy decision-making. The outcomes will make it easier to decide which patient-centered treatments to prioritize for LSS.
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Age-associated loss of skeletal muscle mass and function is one of the main causes of the loss of independence and physical incapacitation in the geriatric population. This study used the D-galactose-induced C2C12 myoblast aging model to explore whether nobiletin (Nob) could delay skeletal muscle aging and determine the associated mechanism. The results showed that Nob intervention improved mitochondrial function, increased ATP production, reduced reactive oxygen species (ROS) production, inhibited inflammation, and prevented apoptosis as well as aging. In addition, Nob improved autophagy function, removed misfolded proteins and damaged organelles, cleared ROS, reduced mitochondrial damage, and improved skeletal muscle atrophy. Moreover, our results illustrated that Nob can not only enhance mitochondrial function, but can also enhance autophagy function and the protein synthesis pathway to inhibit skeletal muscle atrophy. Therefore, Nob may be a potential candidate for the prevention and treatment of age-related muscle decline.
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Galactosa , Mitocondrias , Adenosina Trifosfato/metabolismo , Anciano , Envejecimiento/metabolismo , Senescencia Celular , Flavonas , Galactosa/efectos adversos , Galactosa/metabolismo , Humanos , Mitocondrias/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/inducido químicamente , Atrofia Muscular/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Breaking through the traditional 1,7,3,5-aryl substituted aza-BODIPY structure, asymmetric aza-BODIPYs, tBu-azaBDPs, containing non-aryl group at 3-site were prepared for the first time. tBu-azaBDP exhibited a severely twisted configuration. tBu-azaBDPs had a near-infrared fluorescence emission and high molar extinction coefficients. Although the barrier-free rotation of the distal -tBu group in tBu-azaBDP resulted in low fluorescence quantum yield, the photothermal conversion efficiency was markedly enhanced. tBu-azaBDP nanoparticles with laser irradiation were revealed to induce cell apoptosis in photothermal therapy. We consider that development of aza-BODIPYs with the barrier-free rotation of the -tBu group at 3-site provides a strong platform for design of phototherapy agents for cancer treatment in photothermal therapy by apoptosis.
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Neoplasias , Terapia Fototérmica , Apoptosis , Compuestos de Boro/química , Neoplasias/tratamiento farmacológicoRESUMEN
Anacardic acid (AA) is a phenolic acid extract found in a number of plants, crops, and fruits. It exhibits a wide range of biological activities. This study displayed that AA effectively alleviated EAE, a classical mouse model of multiple sclerosis. AA administered to the EAE greatly decreased inflammatory cell infiltration to the CNS and protected the myelin integrity in the white matter of the spinal cord. AA could block lipopolysaccharide-induced DC activation. inhibited the polarization of 2D2 mice-derived T cells by inhibiting the DCs activity. Immunoblot results indicated that the phosphorylation of NF-κB is significantly suppressed in AA-treated DCs. This work displayed that AA possessed a potential anti-inflammatory therapeutic effect for the treatment of autoimmune disease.
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Encefalomielitis Autoinmune Experimental , Ácidos Anacárdicos , Animales , Células Dendríticas , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Ratones , Ratones Endogámicos C57BL , Enfermedades Neuroinflamatorias , Médula EspinalRESUMEN
PURPOSE: Radiation-induced lung injury limits the implementation of radiotherapy plans and severely impairs the quality of life. Crocetin has the capability to protect against radiation. This study is aimed at estimate the preventive effect and mechanism of crocetin on acute radiation induced lung injury. METHODS AND MATERIALS: In this study, we offer a strategy for radiation-induced lung injury by using crocetin, an extract of gardenia fruit. Histopathology, transcriptomics, flow cytometry, and other methods have served to examine the effect and mechanism of crocetin on acute radiation-induced lung injury. RESULTS: Crocetin effectively alleviates radiation-induced alveolar wall thickening and alveolar destruction. The number of normal alveoli and lung structure of mice is well protected by the prevention of crocetin. It is found that crocetin inhibits necroptosis to achieve effective radioprotection by down regulating the Tnfrsf10b gene in vitro. CONCLUSION: Crocetin inhibits necroptosis through transcriptional regulation of the Tnfrsf10b gene, thereby preventing radiation-induced lung injury. This work may provide a new strategy for the prevention of lung radiation injury by the extract from Chinese herbal medicine.