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BACKGROUND: The aim of this study was to explore application value of iodine concentration from dual-energy spectral computed tomography (DESCT) in preoperative prediction of lymphovascular tumor thrombus in patients with colorectal cancer (CRC). METHODS: We finally retrospectively analyzed 50 patients with CRC who underwent abdominal DESCT before receiving any preoperative treatment and underwent surgery to obtain pathological specimens which were stained with hematoxylin-eosin (HE) staining. According to the presence of cancer cell nests in blood vessels and lymphatic vessels, the subjects were divided into the positive group and negative group of lymphovascular tumor thrombus. Two radiologists independently measured the normalized iodine concentration (NIC) values, effective atomic number (Zeff) and CT values of virtual monochromatic images (VMIs) at 40-90 keV of the primary tumors in the arterial phase (AP) and venous phase (VP). Used SPSS 17.0 to calculate the receiver operating characteristic (ROC) curve to evaluate diagnostic value. RESULTS: The patients were divided into lymphovascular tumor thrombus positive group(n = 16) and negative group(n = 34). The values of NIC-AP and NIC-VP in the positive group were 0.17 ± 0.09, 0.51 ± 0.13, respectively. And those in the negative group were 0.15 ± 0.06, 0.43 ± 0.12, respectively. There was significant difference in NIC-VP value between the two groups (p = 0.039), but there was no significant difference in NIC-AP value (p = 0.423). The optimal threshold value of NIC-VP value for diagnosis of lymphovascular tumor thrombus was 0.364. The sensitivity was 68.8% and the specificity was 67.6%. CONCLUSIONS: The NIC-VP value of DESCT can be used to predict the presence or absence of the lymphovascular tumor thrombus in CRC patients before operation, which is helpful to select the best treatment scheme and evaluate its prognosis.
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Neoplasias Colorrectales , Yodo , Trombosis , Humanos , Tomografía Computarizada por Rayos X/métodos , Estudios Retrospectivos , Trombosis/diagnóstico por imagen , Trombosis/cirugía , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/cirugíaRESUMEN
In this study, an ultra-performance liquid chromatography-quadrupole time-of-flight high resolution mass spectrometer(UPLC-Q-TOF-HRMS) was used to investigate the effects of the active ingredients in Periploca forrestii compound on spleen metabolism in rats with collagen-induced arthritis(CIA), and its potential anti-inflammatory mechanism was analyzed by network pharmacology. After the model of CIA was successfully established, the spleen tissues of rats were taken 28 days after administration. UPLC-Q-TOF-HRMS chromatograms were collected and analyzed by principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and MetPA. The results showed that as compared with the blank control group, 22 biomarkers in the spleen tissues such as inosine, citicoline, hypoxanthine, and taurine in the model group increased, while 9 biomarkers such as CDP-ethanolamine and phosphorylcholine decreased. As compared with the model group, 21 biomarkers such as inosine, citicoline, CDP-ethanolamine, and phosphorylcholine were reregulated by the active ingredients in P. forrestii. Seventeen metabolic pathways were significantly enriched, including purine metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism. Network pharmacology analysis found that purine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism played important roles in the pathological process of rheumatoid arthritis. This study suggests that active ingredients in P. forrestii compound can delay the occurrence and development of inflammatory reaction by improving the spleen metabolic disorder of rats with CIA. The P. forrestii compound has multi-target and multi-pathway anti-inflammatory mechanism. This study is expected to provide a new explanation for the mechanism of active ingredients in P. forrestii compound against rheumatoid arthritis.
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Artritis Reumatoide , Periploca , Ratas , Animales , Cisteína , Citidina Difosfato Colina , Farmacología en Red , Fosforilcolina , Metabolómica , Artritis Reumatoide/tratamiento farmacológico , Biomarcadores , Glicerofosfolípidos , Metionina , Purinas , Cromatografía Líquida de Alta PresiónRESUMEN
Objective To evaluate the safety and effectiveness of laparoscopic common bile duct exploration in the treatment of common bile duct stones. Methods A retrospective analysis was conducted for 158 patients with cholecystolithiasis and choledocholithiasis admitted to the Number One Hospital of Zhangjiakou from January 2015 to December 2019.The patients were assigned into three groups according to the diameters of cystic duct and common bile duct,degrees of abdominal infection and tissue edema,and operation method.Group A(16 cases):laparoscopic cholecystectomy,transcystic choledochoscopic exploration for stone removal;Group B(94 cases):laparoscopic cholecystectomy,common bile duct incision exploration combined with choledochoscopy for stone removal,T tube drainage;Group C(48 cases):laparoscopic cholecystectomy,common bile duct incision exploration combined with choledochoscopy for stone removal,primary closure of the common bile duct.The operation time,residual rate of stones,and complication(bleeding,bile leakage,and wound infection) rate were compared between groups. Results The operation time of groups A,B,and C was(95.1±14.7),(102.2±18.1),(110.1±16.4) minutes,respectively,which showed no statistical difference between each other(F=0.020,P=0.887).One case in group A had residual stones,while no residual stone appeared in groups B and C.The overall stone clearance rate was 99.4% and the overall complication rate was 1.9%.There was no perioperative death. Conclusion It is generally safe and effective to carry out laparoscopic cholecystectomy and common bile duct exploration for stone removal in suitable populations.
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Coledocolitiasis , Cálculos Biliares , Laparoscopía , Coledocolitiasis/cirugía , Conducto Colédoco/cirugía , Cálculos Biliares/cirugía , Humanos , Laparoscopía/métodos , Estudios RetrospectivosRESUMEN
BACKGROUND: Cholangiocarcinoma (CCA) is a relatively rare malignant biliary system tumor, and yet it represents the second most common primary hepatic neoplasm, following hepatocellular carcinoma. Regardless of the type, location, or etiology, the survival prognosis of these tumors remains poor. The only method of cure for CCA is complete surgical resection, but part of patients with complete resection are still subject to local recurrence or distant metastasis. SUMMARY: Over the last several decades, our understanding of the molecular biology of CCA has increased tremendously, diagnostic and evaluative techniques have evolved, and novel therapeutic approaches have been established. Key Messages: This review provides an overview of preoperative imaging evaluations of CCA. Furthermore, relevant information about artificial intelligence (AI) in medical imaging is discussed, as well as the development of AI in CCA treatment.
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Neoplasias de los Conductos Biliares/diagnóstico por imagen , Colangiocarcinoma/diagnóstico por imagen , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Inteligencia Artificial , Neoplasias de los Conductos Biliares/cirugía , Colangiocarcinoma/cirugía , Diagnóstico por Imagen , Humanos , Periodo Preoperatorio , PronósticoRESUMEN
BACKGROUND: Radiomics may provide more objective and accurate predictions for extrahepatic cholangiocarcinoma (ECC). In this study, we developed radiomics models based on magnetic resonance imaging (MRI) and machine learning to preoperatively predict differentiation degree (DD) and lymph node metastasis (LNM) of ECC. METHODS: A group of 100 patients diagnosed with ECC was included. The ECC status of all patients was confirmed by pathology. A total of 1200 radiomics features were extracted from axial T1 weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion weighted imaging (DWI), and apparent diffusion coefficient (ADC) images. A systematical framework considering combinations of five feature selection methods and ten machine learning classification algorithms (classifiers) was developed and investigated. The predictive capabilities for DD and LNM were evaluated in terms of area under precision recall curve (AUPRC), area under the receiver operating characteristic (ROC) curve (AUC), negative predictive value (NPV), accuracy (ACC), sensitivity, and specificity. The prediction performance among models was statistically compared using DeLong test. RESULTS: For DD prediction, the feature selection method joint mutual information (JMI) and Bagging Classifier achieved the best performance (AUPRC = 0.65, AUC = 0.90 (95% CI 0.75-1.00), ACC = 0.85 (95% CI 0.69-1.00), sensitivity = 0.75 (95% CI 0.30-0.95), and specificity = 0.88 (95% CI 0.64-0.97)), and the radiomics signature was composed of 5 selected features. For LNM prediction, the feature selection method minimum redundancy maximum relevance and classifier eXtreme Gradient Boosting achieved the best performance (AUPRC = 0.95, AUC = 0.98 (95% CI 0.94-1.00), ACC = 0.90 (95% CI 0.77-1.00), sensitivity = 0.75 (95% CI 0.30-0.95), and specificity = 0.94 (95% CI 0.72-0.99)), and the radiomics signature was composed of 30 selected features. However, these two chosen models were not significantly different to other models of higher AUC values in DeLong test, though they were significantly different to most of all models. CONCLUSION: MRI radiomics analysis based on machine learning demonstrated good predictive accuracies for DD and LNM of ECC. This shed new light on the noninvasive diagnosis of ECC.
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Adenocarcinoma/diagnóstico por imagen , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Colangiocarcinoma/diagnóstico por imagen , Metástasis Linfática/diagnóstico por imagen , Aprendizaje Automático , Imagen por Resonancia Magnética/métodos , Adenocarcinoma/patología , Adenocarcinoma/secundario , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Área Bajo la Curva , Neoplasias de los Conductos Biliares/patología , Colangiocarcinoma/patología , Colangiocarcinoma/secundario , Femenino , Humanos , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Valor Predictivo de las Pruebas , Curva ROC , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
While there is convincing evidence that excess body fatness in adulthood is positively associated with colorectal cancer risk, the association between body fatness at an early age (≤30 years) and the risk of colorectal cancer has been equivocal. The present meta-analysis was performed to clarify this association. PubMed and Web of Science databases were searched for relevant studies that investigated this association. The risk estimates from each study were transformed into a continuous variable for each 5 kg/m2 increase in body mass index (BMI). A random effects model was used to calculate the summary relative risks (RRs) with 95% confidence intervals (CIs). A total of 15 observational studies (13 cohort studies and two case-control studies) were included in this meta-analysis. Each 5 kg/m2 increase in BMI was significantly associated with a 13% (RR 1.13, 95% CI 1.08, 1.19), 17% (RR 1.17, 95% CI 1.09, 1.25) and 8% (RR 1.08, 95% CI 1.04, 1.11) higher risk of colorectal cancer overall, in men, and in women, respectively. Substantial heterogeneity was observed across studies. Based on the anatomic subsite, each 5 kg/m2 increase in BMI was significantly associated with a 14% (RR 1.14, 95% CI 1.07, 1.22) higher risk of colon cancer, whereas no association (RR 1.03, 95% CI 0.95, 1.13) was observed with rectal cancer. In summary, body fatness at an early age may affect colon cancer risk later in life. Prevention of overweight and obesity in young individuals should be emphasized to prevent early-onset colon cancer attributed to excess body fatness.
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Adiposidad , Neoplasias Colorrectales/epidemiología , Adolescente , Adulto , Factores de Edad , Distribución de la Grasa Corporal , Índice de Masa Corporal , Niño , Neoplasias Colorrectales/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Observacionales como Asunto , Adulto JovenRESUMEN
Although the treatment of adult T-cell acute lymphoblastic leukemia (T-ALL) has been significantly improved, the heterogeneous genetic landscape of the disease often causes relapse. Aberrant activation of mammalian target of rapamycin (mTOR) pathway in T-ALL is responsible for treatment failure and relapse, suggesting that mTOR inhibition may represents a new therapeutic strategy. In this study, we investigated whether the mTOR complex 1 (mTORC1) inhibitor everolimus could be used as a therapeutic agent against human T-ALL. We showed that rapamycin and its analog RAD001 (everolimus) exerted only mild inhibition on the viability of Jurkat, CEM and Molt-4 cell lines (for everolimus the maximum inhibition was <40% at 100 nM), but greatly enhanced the phosphorylation of eIF4E, a downstream substrate of MAPK-interacting kinase (MNK) that was involved in promoting cell survival. Furthermore, we demonstrated in Jurkat cells that mTOR inhibitor-induced eIF4E phosphorylation was independent of insulin-like growth factor-1/insulin-like growth factor-1 receptor axis, but was secondary to mTOR inhibition. Then we examined the antileukemia effects of CGP57380, a MNK1 inhibitor, and we found that CGP57380 (4-16 µM) dose-dependently suppressed the expression of both phosphor-MNK1 and phosphor-eIF4E, thereby inhibiting downstream targets such as c-Myc and survivin in T-ALL cells. Importantly, CGP57380 produced a synergistic growth inhibitory effect with everolimus in T-ALL cells, and treatment with this targeted therapy overcame everolimus-induced eIF4E phosphorylation. In conclusion, our results suggest that dual-targeting of mTOR and MNK1/eIF4E signaling pathways may represent a novel therapeutic strategy for the treatment of human T-ALL.
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Compuestos de Anilina/farmacología , Antineoplásicos/farmacología , Factor 4E Eucariótico de Iniciación/metabolismo , Péptidos y Proteínas de Señalización Intracelular/antagonistas & inhibidores , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamiento farmacológico , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Purinas/farmacología , Línea Celular Tumoral , Sinergismo Farmacológico , Everolimus/farmacología , Humanos , Diana Mecanicista del Complejo 1 de la Rapamicina/antagonistas & inhibidores , Fosforilación/efectos de los fármacos , Sirolimus/farmacologíaRESUMEN
Underwater operational turbine noise emitted by China's first offshore wind farm in the East China Sea Bridge of Shanghai was measured and analyzed in this study. Two sensors were used in the measurement: a hydrophone recording the underwater sound and an accelerometer placed in the turbine tower detecting the tower vibrations. Measurements were performed at two different types of wind turbines: a Sinovel 3 MW SL3000 turbine and a Shanghai Electric 3.6 MW W3600 turbine. The two turbines show similar tower vibration characteristics, characterized by a number of tonal components, mainly in the low-frequency domain (30-500 Hz). The peak vibration frequencies changed with the wind speed until the turbine approached its nominal power rating. Spectral analysis of the underwater acoustic data showed that the amplitude spectra had a strong correlation with the spectra of the turbine vibration intensity level, indicating that the measured underwater noise was generated by the tower mechanical vibration.
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Typhoon induced sediment warming has been proven important to coastal sound-field change in this study. It was observed that the temperature of the bottom waters off the coast of Qingdao increased by 5 °C after the passage of typhoon Damrey in 2012. Sediment warming due to bottom-water temperature increase was calculated and the change in sediment sound speed was estimated. Transmission loss (TL) was simulated both with and without consideration of the change in sediment sound speed induced by temperature variation and results showed TL change could be >10 dB within a distance of 16 km.
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The macrolide resistance gene erm(T) was identified for the first time in a porcine Erysipelothrix rhusiopathiae isolate from swine in China. The novel 3,749-bp small plasmid pER29, which carries erm(T), had a G+C content of 31% and four distinct open reading frames. The presence of pER29 increased by at least 128-fold the MICs of clindamycin and erythromycin for E. rhusiopathiae. The fitness cost of pER29 could be responsible for the low frequency of erm(T) in E. rhusiopathiae.
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Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Erysipelothrix/enzimología , Macrólidos/farmacología , Animales , Clindamicina/farmacología , Erysipelothrix/genética , Infecciones por Erysipelothrix/microbiología , Eritromicina/farmacología , Genes Bacterianos/genética , Pruebas de Sensibilidad Microbiana , Sistemas de Lectura Abierta/genética , Plásmidos/genética , PorcinosRESUMEN
This study was aimed to screen human papillomavirus (HPV) types associated with esophageal squamous cell carcinoma of Kazakh in Xinjiang using the gene chip technique and study the clinical significance of this application. The DNAs were collected from esophageal squamous cell carcinoma tissues and healthy esophageal mucosa of Kazakh adults in Xinjiang, and amplified firstly using HPV MY09/11 and then using HPV G5+/6+ to screen positive HPV specimens. These positive specimens were further detected by the gene chip technique to screen highly pathogenic HPV types. After determination with nested PCR amplification with HPV MY09/11 and G5+/6+, the infection rate of HPV was 66.67% in the esophageal squamous cell carcinoma group and 12.12% in the healthy control group. By testing the positive HPV specimens from the esophageal squamous cell carcinoma group, the infection rate of HPV16 was 97.72% and the co-infection rate of HPV16 and HPV18 was 2.27%. HPV16 infection may be involved in the development of esophageal squamous cell carcinoma in Xinjiang Hazakh adults.
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Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Papillomaviridae/genética , Infecciones por Papillomavirus/genética , Anciano , Pueblo Asiatico , Carcinoma de Células Escamosas/etnología , Carcinoma de Células Escamosas/virología , Estudios de Casos y Controles , China , ADN de Neoplasias/análisis , ADN de Neoplasias/genética , ADN Viral/análisis , ADN Viral/genética , Neoplasias Esofágicas/etnología , Neoplasias Esofágicas/virología , Femenino , Interacciones Huésped-Patógeno/genética , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Masculino , Persona de Mediana Edad , Tipificación Molecular/métodos , Tipificación Molecular/estadística & datos numéricos , Papillomaviridae/clasificación , Papillomaviridae/fisiología , Infecciones por Papillomavirus/etnología , Infecciones por Papillomavirus/virología , Reacción en Cadena de la PolimerasaRESUMEN
Wood-plastic composites are becoming increasingly recognized for their sustainability and their potential for use in various production processes. Nevertheless, enhancing their mechanical strength continues to be a difficult challenge. The objective of this research was to improve the mechanical strength of wood-plastic composite components manufactured through selective laser sintering (SLS). This was achieved by integrating a sustainable composite material, Prosopis chilensis (PCP), with polyethersulfone (PES) to form a composite referred to as PCPC. This study showcased the effect of various PCP particle sizes on mechanical strengths, dimensional accuracies (DAs), and surface roughness of PCPC parts manufactured using AFS-360 SLS. Single-layer sintering was employed to assess PCPC powder's formability with varying PCP particle sizes, and various tests were conducted to understand the materials' thermal properties and analyze particle dispersion and microstructure. The results demonstrated that PCP particle sizes ≤ 0.125 mm significantly enhanced the mechanical strength, forming quality, and DA compared to other particle sizes and pure PES. Key findings for PCPC parts with PCP ≤ 0.125 mm included a bending strength of 10.78 MPa, a tensile strength of 4.94 MPa, an impact strength of 0.91 kJ/m2, and a density of 1.003 g/cm3. Post-processing further improved these parameters, confirming that optimizing PCP particle size is crucial for enhancing the mechanical properties and overall quality of PCPC parts produced via SLS.
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Purpose: To investigate sleep problems in children with self-limited epilepsy with central temporal spiking (SeLECTS) and to assess the relationship between sleep problems and attention network dysfunction. Patients and methods: 107 children 6-14 years of age with SeLECTS and 90 age- and sex-matched healthy controls were recruited for this study. The sleep status of these participants was evaluated using the Children's Sleep Habits Questionnaire (CSHQ), while attentional network function was assessed with the attention network function test (ANT). Results: Together, these analyses revealed that children with SeLECTS exhibited higher total CSHQ scores and sleep disorder incidence relative to healthy controls (P< 0.001). Children with SeLECTS had higher scores in delayed sleep onset, sleep duration, night awakenings, parasomnias, daytime sleepiness and sleep anxiety (P<0.01). Total CSHQ scores were negatively correlated with average ANT correct rates (ρ= -0.253, P<0.01), while they were positively correlated with total reaction time (ρ=0.367, P<0.01) and negatively correlated with the efficiency of the alerting and executive control networks (ρ=-0.344 P<0.01; ρ=-0.418 P<0.01). Conclusion: Children with SeLECTS face a higher risk of experiencing sleep disorders relative to age-matched healthy children, while also demonstrating that the magnitude of the impairment of attentional network function in these children is positively correlated with sleep disorder severity. Thus, the prognosis and quality of life of children with SeLECTS can be improved by interventions addressing sleep disorders.
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As ubiquitous components among fruits, polyphenols, including flavonoids and phenolic acids, are somewhat embarrassed on their health benefits but low bioavailability, triggering a hotspot on their interaction with microbiota. Due to its structural characteristics similar to flavonoids and phenolic acids, dihydrochalcone phlorizin (PHZ) was selected as a reference, to illustrate its step-by-step metabolic fate associated with microbiota. The results confirmed that the metabolic flux of PHZ starts with its conversion to phloretin (PHT), sequentially followed by the formation of 3-(4-hydroxyphenyl) propionic acid (PHA), and 4-hydroxyphenylacetic acid (4-HPAA). Catabolic characteristics was comparatively elucidated by introducing apparent and potential kinetics. Besides, coupling catabolic processes with microbial changes suggested several potential bacteria involving in PHZ metabolism, as well as those regulated by PHZ and its metabolites. In particular, seven strains from Lactobacillus were selectively isolated and confirmed to be essential for deglycosylation of PHZ, implying a potential synergistic effect between PHZ and Lactobacillus.
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Microbioma Gastrointestinal , Hidroxibenzoatos , Florizina , Prebióticos , Polifenoles/metabolismo , Flavonoides/metabolismoRESUMEN
OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS: TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
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Dermatitis , Psoriasis , Enfermedades de la Piel , Masculino , Animales , Ratones , Tripterygium , Psoriasis/tratamiento farmacológico , Queratinocitos , Enfermedades de la Piel/metabolismo , Citocinas/metabolismo , Imiquimod/efectos adversos , Imiquimod/metabolismo , Dermatitis/metabolismo , Dermatitis/patología , Modelos Animales de Enfermedad , Ratones Endogámicos BALB C , Piel/metabolismoRESUMEN
OBJECTIVES: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that affects the quality of life (QoL) of patients. This study aimed to evaluate the differences in perceptions of PBC among physicians from different hospital departments and patients with PBC. METHODS: An online survey regarding the general knowledge, diagnosis, and management of PBC was completed by physicians and patients. RESULTS: A total of 239 patients with PBC and 239 physicians from eight hospital departments (gastroenterology, infectious diseases, rheumatology, hepatobiliary surgery, pathology, clinical laboratory, ultrasound, and radiology) completed the survey. The results showed that physicians from departments other than gastroenterologists and rheumatologists lacked knowledge of PBC, and that junior gastroenterologists were uncertain about the diagnostic and treatment pathways of PBC. Importantly, the lack of knowledge significantly impacted the QoL of patients, especially the emotional scores of PBC-40 (odds ratio -2.556, 95% confidence interval -3.852 to -1.260, P < 0.001). In addition, there was a perceived knowledge gap between patients and gastroenterologists. CONCLUSIONS: Physicians must improve their awareness of PBC. Patient education and patient-physician communication are important for improving the patient's QoL.
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Enfermedades Autoinmunes , Colangitis , Gastroenterólogos , Cirrosis Hepática Biliar , Humanos , Cirrosis Hepática Biliar/diagnóstico , Calidad de Vida , Encuestas y CuestionariosRESUMEN
AIM: To investigate the effects of BIIB021, an inhibitor of heat shock protein 90 (Hsp90) alone or in combination with triptolide (TPL) on T-cell acute lymphoblastic leukemia (T-ALL) and the mechanisms of action. METHODS: Human T-ALL cells line Molt-4 was examined. The cell viability was measured using MTT assay. Apoptotic cells were studied with Hoechst 33258 staining. Cell apoptosis and cell cycle were analyzed using flow cytometry with Annexin V/PI staining and PI staining, respectively. The levels of multiple proteins, including Akt, p65, CDK4/6, p18, Bcl-2 family proteins, MDM2, and p53, were examined with Western blotting. The level of MDM2 mRNA was determined using RT-PCR. RESULTS: Treatment of Molt-4 cells with BIIB021 (50-800 nmol/L) inhibited the cell growth in a dose-dependent manner (the IC50 value was 384.6 and 301.8 nmol/L, respectively, at 48 and 72 h). BIIB021 dose-dependently induced G0/G1 phase arrest, followed by apoptosis of Molt-4 cells. Furthermore, BIIB021 increased the expression of p18, decreased the expression of CDK4/6, and activated the caspase pathway in Molt-4 cells. Moreover, BIIB021 (50-400 nmol/L) dose-dependently decreased the phospho-MDM2 and total MDM2 protein levels, but slightly increased the phospho-p53 and total p53 protein levels, whereas TPL (5-40 nmol/L) dose-dependently enhanced p53 activation without affecting MDM2 levels. Co-treatment with BIIB021 and TPL showed synergic inhibition on Molt-4 cell growth. The co-treatment disrupted p53-MDM2 balance, thus markedly enhanced p53 activation. In addition, the co-treatment increased the expression of Bak and Bim, followed by increased activation of caspase-9. CONCLUSION: The combination of BIIB021 and TPL may provide a novel strategy for treating T-ALL by overcoming multiple mechanisms of apoptosis resistance.
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Adenina/análogos & derivados , Apoptosis/efectos de los fármacos , Diterpenos/farmacología , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Fenantrenos/farmacología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Piridinas/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Adenina/farmacología , Secuencia de Bases , Línea Celular Tumoral , Cartilla de ADN , Compuestos Epoxi/farmacología , Citometría de Flujo , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Global warming caused by carbon emissions is an environmental issue that is of great concern to all walks of life. Dynamic monitoring of the spatiotemporal evolution of urban carbon emissions is an important part of achieving the regional double-carbon goals. Taking the main urban area of Chongqing as an example, based on the data of land use and energy consumption, this study estimated the carbon emissions of 153 townships and streets in the main urban area of Chongqing from 2000 to 2020 by using the carbon emission coefficient method. Additionally, using the ESTDA framework to pass the LISA time path, spatiotemporal transition, and the standard deviation ellipse model from the perspective of spatiotemporal interaction, the spatiotemporal dynamic evolution of carbon emissions in the main urban area and the shift in the center of gravity over the past 20 years were analyzed. The results showed that: â in the past 20 years, the carbon emissions in the main urban and rural areas have had a significant positive spatial correlation, and the spatial convergence showed a trend of first decreasing and then increasing. â¡ In the past 20 years, there were 126 township streets with low and medium relative lengths (accounting for 82%), indicating that the local spatial structure of township carbon emissions in the main urban area had strong stability; the total number of township streets with low and medium curvatures was 138 (accounting for 90%), indicating that the volatility of the main urban and rural carbon emissions in the direction of spatial dependence was relatively stable; there were 113 township streets (accounting for 74%) of the synergistic growth type, indicating that the main urban and rural carbon emissions were relatively stable. The emission pattern had strong spatial integration. ⢠In the past 20 years, the spatiotemporal agglomeration index was greater than 70%, indicating that the local spatial correlation pattern and agglomeration characteristics of carbon emissions in the main urban and rural areas had strong stability. 4 In the past 20 years, the center of carbon emission in the main urban area had been distributed between 106°30'43â³-106°32'42â³E, 29°33'34â³-29°35'56â³N, and the center of gravity shifted to the northeast as a whole. The spatial distribution changed from the "northwest-southeast" pattern to the "northeast-southwest" pattern. These results can provide reference for the green and low-carbon sustainable development of Chongqing and the formulation of differentiated emission reduction policies, as well as provide reference for other similar mountain cities in western China.
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Carbono , Calentamiento Global , Carbono/análisis , Ciudades , Análisis Espacial , ChinaRESUMEN
This study intends to enhance the mechanical strength of wood-plastic composite selective laser sintering (SLS) parts by using a sustainable composite, peanut husk powder (PHP)/poly ether sulfone (PES) (PHPC). The study aims to address agricultural waste pollution by encouraging the eco-friendly utilization of such waste in SLS technology. To ensure the sintering quality and mechanical properties and prevent deformation and warping during sintering, the thermo-physical properties of PHP and PES powders were analyzed to determine a suitable preheating temperature for PHPC. Single-layer sintering tests were conducted to assess the formability of PHPC specimens with varying PHP particle sizes. The study showed the effects of different PHP particle sizes on the mechanical performance of PHPC parts. The evaluation covered various aspects of PHPC SLS parts, including mechanical strength, density, residual ash content, dimensional accuracy (DA), and surface roughness, with different PHP particle sizes. The mechanical analysis showed that PHPC parts made from PHP particles of ≤0.125 mm were the strongest. Specifically, the density bending strength, residual ash content, tensile, and impact strength were measured as 1.1825 g/cm3, 14.1 MPa, 1.2%, 6.076 MPa, and 2.12 kJ/cm2, respectively. Notably, these parameters showed significant improvement after the wax infiltration treatment. SEM was used to examine the PHP and PES powder particles, PHPC specimen microstructure, and PHPC SLS parts before and after the mechanical tests and waxing. Consequently, SEM analysis wholly confirmed the mechanical test results.
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OBJECTIVE: To analyze the clinical manifestations, therapeutic response and prognosis of patients with primary testicular diffuse large B-cell lymphoma (PT-DLBCL). METHODS: Thirty-eight patients with PT-DLBCL were enrolled, who hospitalized from January 2010 to April 2021, and their clinical characteristics, treatment regimen and efficacy were collected and analyzed retrospectively. RESULTS: The median age of the patients was 56 years old (ranged from 38 to 79 years). There were 4 cases (10.5%) with bilateral lesions, 13 cases (34.2%) with left lesions, and 21 cases (55.3%) right lesions. There were 2 cases(5.3%) with B symptoms, 6 cases (15.8%) of germinal center B-cell-like(GCB) subtype and 32 cases(84.2%) of non-GCB subtype. Efficacy was evaluated in 36 cases, including 10 cases with CHOP regimen, 21 cases with R-CHOP regimen (7 cases were treated with rituximab combined with high-dose methotrexate injection chemotherapy at intervals of R-CHOP regimen), and 5 cases with other regimens. In 36 patients, the efficacy evaluation of initial chemotherapy showed that the overall response rate (ORR) was 86.1%, 29 cases (80.6%) reached complete response (CR), and 2 cases (5.5%) reached partial response (PR). The R-CHOP group was superior to CHOP group in ORR (95.2% vs 60.0%, P=0.027) and CR (90.4% vs 50.0%, P=0.022). Of the 36 patients, 7 cases had central nervous system(CNS) recurrence and 4 cases had contralateral testicular recurrence. Compared with the CHOP group, the CNS recurrence rate in the R-CHOP group was significantly lower (4.8% vs 50.0%, P=0.007), and the testicular recurrence rate in the R-CHOP group was also lower than the CHOP group, but the difference was not statistically significant (4.8% vs 30.0%, P=0.087). The median follow-up time was 27(3-135) months, and the 5-year PFS and OS were 71% and 74%, respectively. Kaplan-Meier univariate analysis showed that the R-CHOP regimen significantly improved the patients' PFS (P=0.024) and OS (P=0.025) compared with the CHOP regimen. CONCLUSION: PT-DLBCL is mainly treated with comprehensive treatment. Compared with CHOP regimen, R-CHOP regimen can improve the CR rate and ORR, reduce CNS recurrence and contralateral testicular recurrence, and improve the patients' survival. Patients may benefit from high-dose methotrexate combined with rituximab interlaced with R-CHOP regimen.