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Dimethyl oxalate is one of the occupational toxic chemicals and causes strong renal toxicity. On May 16, 2023, a patient with acute dimethyl oxalate poisoning was admitted to Dingxi People's Hospital. The patient presented with nausea, vomiting, lumbar distension, weakness, poor appetite, anuria, and rapidly progressing acute kidney injury. Renal biopsy confirmed acute oxalate nephropathy. After symptomatic supportive treatments such as blood purification, anti-oxidative stress, glucocorticoid, fluid supplementation, alkalized urine, anti-infection, controlling blood pressure, calcium supplementation and anemia correction, the patient's symptoms disappeared, and the kidney function basically returned to normal. This case suggested that the etiology of patients with acute kidney injury must be clearly identified, and renal biopsy was an important examination method. For patients suffering from acute dimethyl oxalate poisoning, comprehensive treatment based on blood purification should be performed as soon as possible, aiming to improve the prognosis.
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Lesión Renal Aguda , Humanos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/terapia , Masculino , Adulto , Riñón/patología , Oxalatos/envenenamientoRESUMEN
Objective: To study the expressions of C-C class chemokine 17 (CCL17), C-C class chemokine 22 (CCL22), and C-C chemokine receptor 4 (CCR4) in newly diagnosed multiple myeloma (NDMM) for analyzing their correlations with clinical features and to preliminarily explore their roles in the development of NDMM. Methods: The study included 40 patients with NDMM and 20 healthy volunteers from the Department of Hematology of the Affiliated Hospital of Zunyi Medical University from July 2020 to December 2022. Peripheral blood, bone marrow, and bone marrow biopsy tissue samples were collected from the two groups. The expression levels of CCL17, CCL22, and CCR4 in patients with NDMM were analyzed using real-time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry. The mRNA expression levels of CCL17, CCL22, and CCR4 in the bone marrow mononuclear cell (BMMNC) of patients with NDMM were analyzed to assess their correlations with clinical indicators. Results: The mRNA expression levels of CCL17, CCL22, and CCR4 in BMMNC were higher in patients with NDMM than in controls (all P<0.05). The protein expression levels of CCL17 and CCL22 in peripheral blood supernatants and bone marrow supernatants were higher in patients with NDMM than in controls (all P<0.05). The expression levels of CCL17, CCL22, and CCR4 in bone marrow biopsy tissues were higher in patients with NDMM than in controls (all P<0.05). The mRNA expression level of CCL17 was increased in NDMM patients with combined anemia, bone damage, renal damage, and M protein level ≥30 g/L (all P<0.05). The mRNA expression level of CCL22 was increased in NDMM patients with combined anemia, bone damage, and renal damage (all P<0.05). The mRNA expression level of CCR4 was increased in NDMM patients with combined anemia and renal damage (all P<0.05) . Conclusion: CCL17, CCL22, and CCR4 were highly expressed in clinical samples from patients with NDMM compared to those from controls, and they may be involved in the occurrence and development of NDMM.
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Quimiocina CCL17 , Quimiocina CCL22 , Mieloma Múltiple , Receptores CCR4 , Humanos , Receptores CCR4/metabolismo , Quimiocina CCL17/metabolismo , Quimiocina CCL17/genética , Quimiocina CCL22/metabolismo , Quimiocina CCL22/genética , Mieloma Múltiple/metabolismo , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/genética , Médula Ósea/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Relevancia ClínicaRESUMEN
OBJECTIVES: This study aims to evaluate the age- and sex-specific associations of comorbidities with stroke and MI and further calculate the population-attributable fractions (PAFs) of five comorbid diseases for stroke and myocardial infarction (MI) by age and sex. STUDY DESIGN: This is a prospective cohort study. METHODS: This study leveraged data from a sub-cohort of the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project. Participants aged 35-75 years without a prevalent stroke and MI were enrolled from January 2016 to December 2020, with follow-up through December 2021. Five common comorbidities were collected at baseline, and the study outcome was hospitalization for stroke and MI identified from the Inpatients Registry. RESULTS: Of 100,873 participants, the mean age was 54.2 (±10.2) years, 34.2% were ≥60 years old, and 60.8% were women. After a median follow-up of 3.52 years, 4156 participants had stroke/MI. The strengths of the associations between hypertension, diabetes, and obesity with stroke/MI were higher in younger individuals than in seniors, and obesity had a more hazardous impact on stroke/MI in men than in women. The five comorbidities collectively explained a higher population attributable fraction (PAF) for stroke/MI in the young group (51.5[46.9, 55.7] %) than in the senior group (41.3[37.0, 45.4] %), in men (45.6[40.9, 49.9] %) than in women (41.1[36.1, 45.7] %). CONCLUSIONS: Most of the common comorbidities were significantly associated with stroke and MI. Several age and sex differences in the impacts of comorbidities on stroke/MI were observed, highlighting the importance of age- and sex-specific preventive strategies to reduce premature stroke and MI.
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Comorbilidad , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Persona de Mediana Edad , Femenino , Masculino , Infarto del Miocardio/epidemiología , Accidente Cerebrovascular/epidemiología , Anciano , Adulto , China/epidemiología , Estudios Prospectivos , Factores Sexuales , Factores de Edad , Factores de Riesgo , Hipertensión/epidemiología , Diabetes Mellitus/epidemiología , Obesidad/epidemiologíaRESUMEN
On 9 October 2022, the Large High Altitude Air Shower Observatory (LHAASO) reported the observation of the very early TeV afterglow of the brightest-of-all-time gamma-ray burst 221009A, recording the highest photon statistics in the TeV band ever obtained from a gamma-ray burst. We use this unique observation to place stringent constraints on the energy dependence of the speed of light in vacuum, a manifestation of Lorentz invariance violation (LIV) predicted by some quantum gravity (QG) theories. Our results show that the 95% confidence level lower limits on the QG energy scales are E_{QG,1}>10 times the Planck energy E_{Pl} for the linear LIV effect, and E_{QG,2}>6×10^{-8}E_{Pl} for the quadratic LIV effect. Our limits on the quadratic LIV case improve previous best bounds by factors of 5-7.
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In this Letter we try to search for signals generated by ultraheavy dark matter at the Large High Altitude Air Shower Observatory (LHAASO) data. We look for possible γ rays by dark matter annihilation or decay from 16 dwarf spheroidal galaxies in the field of view of the LHAASO. Dwarf spheroidal galaxies are among the most promising targets for indirect detection of dark matter that have low fluxes of astrophysical γ-ray background while having large amount of dark matter. By analyzing more than 700 days of observational data at LHAASO, no significant dark matter signal from 1 TeV to 1 EeV is detected. Accordingly we derive the most stringent constraints on the ultraheavy dark matter annihilation cross section up to EeV. The constraints on the lifetime of dark matter in decay mode are also derived.
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Objective: To investigate the influence of circ_BACH2 on the malignant biological behavior of papillary thyroid cancer and its molecular mechanism. Methods: Cancer tissues and paracancer tissues of 51 patients with papillary thyroid carcinoma from the Fourth Central Hospital of Tianjin between 2017 and 2019 were collected. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of circ_BACH2, miR-370-3p and G protein coupled receptor kinase interacting factor 1 (GIT1) mRNA in tissues and cells; flow cytometry to detect cell apoptosis and cell cycle; plate clone formation experiment to detect the number of cell clones; cell counting kit 8 (CCK-8) to detect cell proliferation; Transwell array to detect cell migration and invasion; western blot to detect protein expressions; dual luciferase report experiment to detect the targeting relationship between circ_BACH2, miR-370-3p and GIT1; the nude mouse tumor formation experiment to detect the effect of circ_BACH2 on tumors in mice. Results: Compared with adjacent tissues, the expressions of circ_BACH2 and GIT1 in papillary thyroid cancer tissues was increased, while the expression of miR-370-3p was decreased. Compared with Nthy-ori3-1 cells, the expressions of circ_BACH2 in papillary thyroid cancer cells TPC-1 and SW579 were increased, the mRNA and protein levels of GIT1 were increased, miR-370-3p expression was decreased. The expression level of GIT1 mRNA was negatively correlated with that of miR-370-3p (r=-0.634), and the expression level of circ_BACH2 was positively correlated with that of GIT1 (r=0.635). The expression level of circ_BACH2 was negatively correlated with that of miR-370-3p (r=-0.394, Pï¼0.05). Circ_BACH2 and miR-370-3p has a binding site at the 3' UTR of GIT1. After knocking down circ_BACH2, the proportion of G0/G1 cells in papillary thyroid cancer cells TPC-1 and SW579 was increased, the proportion of S-phase cells was decreased and the proportion of G2/M-phase cells did not change significantly. The cell absorbance value was lower than that in si-NC group. The number of cell clone formation was decreased (43±5 vs 100±6, 54±8 vs 100±9); the cell apoptosis rate was increased [(19.60±2.40)% vs (4.30±0.20)%, (18.10±2.10)% vs (5.10±0.23)%]; cell migration number was decreased (61±7 vs 134±15, 58±6 vs 112±11), the invasion number was also decreased (45±6 vs 113±11, 47±4 vs 92±9); the expressions of Snail and Twist1 were decreased, and the expression of E-cadherin was increased (Pï¼0.000). Inhibition of miR-370-3p expression reversed the effect of circ_BACH2 knockdown on proliferation, migration, invasion and apoptosis of thyroid papillary cancer cells. Overexpression of GIT1 reversed the effects of overexpression of miR-370-3p on proliferation, migration, invasion and apoptosis of thyroid papillary cancer cells. Mice injected with TPC-1 cells stably transfected with sh-circ_BACH2 showed a reduction in tumor volume [(535±91) mm3 vs (857±114) mm3] after 35 days of culture; tumor weight was decreased [(0.62±0.13) mg vs (1.06±0.15) mg, Pï¼0.05]; the expressions of circ_BACH2 and GIT1 were decreased, and the expression of miR-370-3p was increased in nude mouse tumor tissue. Conclusion: Silencing circ_BACH2 may inhibit the proliferation, migration and invasion of papillary thyroid cancer cells in vitro, promote cell apoptosis, and inhibit tumor growth in vivo through targeted regulation of miR-370-3p/GIT1.
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Proliferación Celular , Ratones Desnudos , MicroARNs , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , MicroARNs/metabolismo , MicroARNs/genética , Humanos , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/metabolismo , Cáncer Papilar Tiroideo/patología , Animales , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Ratones , Línea Celular Tumoral , Apoptosis , ARN Circular/metabolismo , ARN Circular/genética , Movimiento Celular , Regulación Neoplásica de la Expresión Génica , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Ciclo Celular , ARN Mensajero/metabolismo , ARN Mensajero/genéticaRESUMEN
This study was to investigate the relationship between spring pollen distribution concentration, species and the detection results of air-borne pollen allergens in Taiyuan City, Shanxi Province during March to May 2022 and March to May 2023.A retrospective study was conducted in the Otorhinolaryngology Head and Neck Surgery Clinic of the First Hospital of Shanxi Medical University.Pollen particles will be monitored by gravity sedimentation method on the roof of the outpatient department of the First Hospital of Shanxi Medical University in downtown Taiyuan from March to May 2022-2023, and pollen species and quantity will be observed and recorded under an optical microscope.The air-borne pollen allergen detection results of all allergic rhinitis patients in the otolaryngology Head and Neck surgery Department of the First Hospital of Shanxi Medical University were extracted from the relevant outpatient system. SPSS software and Pearson correlation analysis were used to compare the correlation between the allergens and the dominant air-borne pollen monitoring results. Results are as follows: (1)A total of 18 species of spring pollen in Taiyuan City were monitored in 2022-2023, with 101 177.5 grains, and the dominant airborne pollen was poplar (16.69%) and pine (29.06%) pollen. The pollen of poplar (11.96%), elm (7.89%) and cypress (8.68%) were dominant in early spring; Pine (25.16%) pollen predominated in late spring. The two peaks of pollen dispersal in Taiyuan were in late March (15 479 grains) and early and mid May (15 094/15 343 grains).(2) The positive rates of allergens in serum specific IgE detection were: wormwood (46%, 248/541 cases), tree combination (26%, 143/541 cases), ragweed (19%, 101/541 cases), humulus scandens (9%, 49/541 cases).(3)There was a linear positive correlation between the positive rate of air-borne pollen allergens in allergic rhinitis patients in the Department of Otolaryngology Head and Neck Surgery in the First Hospital of Shanxi Medical University and the dominant air-borne pollen concentration in the same period (P<0.05, r=0.999). In conclusion, two spring pollen dispersal peaks were formed in late March and early to mid May in Taiyuan City, and the dominant air-borne pollens were poplar and pine pollens. The positive rate of air borne pollen allergen sIgE showed that wormwood allergy was the highest.There was a positive correlation between the concentration of air-borne pollen and the positive rate of air-borne pollen allergens in patients with allergic rhinitis in the Department of otorhinolaryngology and head and neck surgery in Taiyuan in 2022 and 2023.The monitoring of pollen distribution in spring can provide an important scientific basis for clinical workers to formulate prevention and treatment plans for patients with allergic rhinitis in the season, and provide data reference for the epidemiological investigation of allergic diseases in Taiyuan in the future.
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Alérgenos , Polen , Humanos , China , Estudios Retrospectivos , Inmunoglobulina E/sangre , Estaciones del Año , Rinitis Alérgica , Rinitis Alérgica EstacionalRESUMEN
Bronchopulmonary dysplasia (BPD) is a common serious complication of premature babies. No effective means control it. Hyperoxia damage is one of the important mechanisms of BPD. The reaserach confirmed pyroptosis existed in BPD. Dexmedetomidine is a new, high-specific α2 receptor agonist. Previous research foundation found that dexmedetomidine has a protective effect on BPD. To investigate how dexmedetomidine improves hyperoxic lung injury in neonatal mice by regulating pyroptosis. Neonatal rats were randomly divided into four groups: normal control group, hyperoxic injury group, air plus dexmedetomidine group, and hyperoxia plus dexmedetomidine group. After seven days the lungs of rats in each group were extracted, and the wet-to-dry weight ratio of the lung was measured. The lung injury in rats was observed using hematoxylin-eosin staining. Additionally, the expression and localization of nucleotide-binding oligomerization domain-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and gasdermin D (GSDMD) proteins were examined in the lungs of rats using immunofluorescence staining. The mRNA levels of NLRP3, ASC, caspase-1, and interleukin 18 (IL-18) in the lungs of rats were determined using real-time PCR. Moreover, the protein levels of NLRP3, ASC, caspase-1/cleaved caspase-1, interleukin 1beta (IL-1ß), IL-18, and tunor necrosis factor alpha (TNF-α) were detected in lungs of rats using Western blot. The extent of mitochondrial damage in lung tissues of each group was observed by transmission electron microscopy. The lung tissue injury of the neonatal rats was significantly improved in the hyperoxia plus dexmedetomidine group compared to the hyperoxic injury group. Furthermore, the expressions of pyroptosis-related proteins such as NLRP3, ASC, cleaved-caspase-1, and GSDMD were significantly decreased, along with the expressions of inflammatory factors in lung tissues. By inhibiting the NLRP3/caspase-1/GSDMD pyroptosis pathway, dexmedetomidine reduces the activation and release of inflammatory factors and provides a protective effect against hyperoxic lung injury in neonatal mice.
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Animales Recién Nacidos , Dexmedetomidina , Hiperoxia , Lesión Pulmonar , Pulmón , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Ratas Sprague-Dawley , Animales , Dexmedetomidina/farmacología , Dexmedetomidina/uso terapéutico , Hiperoxia/metabolismo , Hiperoxia/complicaciones , Hiperoxia/tratamiento farmacológico , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Piroptosis/efectos de los fármacos , Lesión Pulmonar/metabolismo , Lesión Pulmonar/prevención & control , Lesión Pulmonar/patología , Lesión Pulmonar/tratamiento farmacológico , Ratas , Proteínas de Unión a Fosfato/metabolismo , Proteínas Adaptadoras de Señalización CARD/metabolismo , Caspasa 1/metabolismo , Interleucina-18/metabolismo , Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Agonistas de Receptores Adrenérgicos alfa 2/uso terapéutico , Masculino , GasderminasAsunto(s)
Atrofia Muscular Espinal , Humanos , Masculino , Femenino , Lactante , Preescolar , Atrofia Muscular Espinal/terapia , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/tratamiento farmacológico , Atrofias Musculares Espinales de la Infancia/terapia , Atrofias Musculares Espinales de la Infancia/genética , Atrofias Musculares Espinales de la Infancia/diagnóstico , Atrofias Musculares Espinales de la Infancia/tratamiento farmacológico , Proteína 2 para la Supervivencia de la Neurona Motora/genética , Niño , Exones , OligonucleótidosRESUMEN
Total mesorectal excision is the standard procedure for the treatment of low and medium rectal cancer. Anastomotic leakage has always been one of the serious complications in these patients. Blood supply, tension and intestinal condition are important factors affecting anastomotic quality. How to optimize the surgical technique and reduce the occurrence of anastomotic leakage is the goal of surgeons. Based on traditional total mesorectal excision, we integrated several surgical techniques, including (1) Preserving the left colic artery; (2) High ligation of the inferior mesenteric vein; (3) Patterned mobilization of the spleen flexure and left transverse colon; (4) Multi-plane mesocolic tailoring; (5) Selective anastomosis suturing, and proposed the concept of multi-technique integrated total mesorectal resection (MTI-TME). The application of MTI-TME in clinical practice and significance was discussed.
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Anastomosis Quirúrgica , Neoplasias del Recto , Humanos , Neoplasias del Recto/cirugía , Anastomosis Quirúrgica/métodos , Fuga Anastomótica/prevención & control , Recto/cirugíaRESUMEN
AIMS: The objective of our study was to establish and verify a novel combined model based on multiparameter magnetic resonance imaging (MRI) radiomics and clinical features to distinguish intraspinal schwannomas from meningiomas. MATERIALS AND METHODS: This research analyzed the preoperative magnetic resonance (MR) images and clinical characteristics of 209 patients with intraspinal tumors who received tumor resection at three institutions. 159 individuals from institutions 1 and 2 were randomly assigned into a training group (n=111) and a test group (n=48) in a 7-3 ratio. A nomogram was constructed using the training cohort and was internally and externally verified in the test cohort and an independent validation cohort (n=50). Model performance was assessed utilizing the area under the curve (AUC) of receiver operating characteristics (ROC), decision curve analysis (DCA), and calibration curves. RESULTS: The nomogram exhibited superior predictive efficacy in distinguishing between spinal schwannomas and meningiomas when compared to both the radiomics model and the clinical model. The nomogram yielded AUCs of 0.994, 0.962, and 0.949 in the training, test, and external validation cohorts, respectively, indicating its exceptional differentiating ability. The DCAs demonstrated that the nomogram yielded the best net benefit. The calibration curves indicated that the nomogram got good agreement between the predicted and the actual observation. CONCLUSION: This research suggests that the nomogram incorporating clinical and radiomic features may be an effective auxiliary tool for distinguishing between intraspinal schwannomas and meningiomas, and has important clinical significance for clinical decision-making and prognosis prediction.
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Aprendizaje Automático , Imagen por Resonancia Magnética , Meningioma , Neurilemoma , Nomogramas , Humanos , Meningioma/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Neurilemoma/diagnóstico por imagen , Neurilemoma/cirugía , Imagen por Resonancia Magnética/métodos , Adulto , Diagnóstico Diferencial , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/cirugía , Anciano , Estudios Retrospectivos , RadiómicaRESUMEN
PURPOSE: The lack of reliable biomarkers for the prognosis and radiotherapy efficacy in esophageal cancer (EC) necessitates further research. The aim of our study was to investigate the predictive utility of plasma cell-free DNA (cfDNA) kinetics in patients with EC. MATERIALS AND METHODS: We retrospectively analyzed the clinical data and cfDNA levels (pre-radiotherapy [pre-RT] and post-radiotherapy [post-RT]) and the cfDNA kinetics (cfDNA ratio: post-RT cfDNA/pre-RT cfDNA) of 88 patients. We employed Kaplan-Meier curves to examine the relationship between cfDNA and overall survival (OS) as well as progression-free survival (PFS). Univariate and multivariate Cox regression analyses were executed to ascertain the independent risk factors in EC. RESULTS: The pre-RT cfDNA levels were positively correlated with clinical stage (P=0.001). The pre-RT cfDNA levels (cutoff value=16.915ng/mL), but not the post-RT cfDNA levels, were linked to a diminished OS (P<0.001) and PFS (P=0.0137). CfDNA kinetics (cutoff value=0.883) were positively associated with OS (P=0.0326) and PFS (P=0.0020). Notably, we identified independent risk factors for OS in EC treated with RT, including cfDNA ratio (high/low) (HR=0.447 [0.221-0.914] P=0.025), ECOG (0/1/2) (HR=0.501 [0.285-0.880] p=0.016), and histological type (esophagal squamous cell carcinoma [ESCC]/non-ESCC) (HR=3.973 [1.074-14.692] P=0.039). CONCLUSION: Plasma cfDNA kinetics is associated with prognosis and radiotherapy effect in EC undergoing RT, suggesting potential clinical application of a cheap and simple blood-based test.
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Biomarcadores de Tumor , Ácidos Nucleicos Libres de Células , Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Anciano , Biomarcadores de Tumor/sangre , Ácidos Nucleicos Libres de Células/sangre , Estimación de Kaplan-Meier , Supervivencia sin Progresión , Carcinoma de Células Escamosas de Esófago/radioterapia , Carcinoma de Células Escamosas de Esófago/sangre , Adulto , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/mortalidad , Anciano de 80 o más Años , CinéticaRESUMEN
1. The accumulation of excessive fat plays a role in the development of non-alcoholic fatty liver disease (NAFLD) and phytogenic feed additives have the potential to ameliorate this. This study involved the isolation and culture of primary hepatocytes from chicken embryos to establish a model of hepatic steatosis induced by oleic acid/dexamethasone (OA/DEX). Lipid accumulation and cell viability were assessed using Nile Red staining, Oil Red O staining and cell count Kit -8 (CCK8) following treatment with varying concentrations of quercetin (Que). The potential mechanism by which Que exerts its effects was preliminarily investigated.2. The results indicated that OA effectively treated lipid accumulation in hepatocytes. There was no notable variance in cell proliferation between the normal and OA/DEX groups when subjected to Que treatment at concentrations of 1000 ng/ml and 10 000 ng/ml. Triglycerides and cholesterol (low and high density) decreased with Que treatment, with the most substantial reduction observed at 10 000 ng/ml.3. Gene expression levels decreased to levels similar to those in the control groups. Western blot data demonstrated that sterol regulatory element-binding protein 1 (SREBP-1) protein expression correlated with its mRNA expression level. Que mitigated lipid accumulation through the alpha serine/threonine protein kinase (AKT) and extracellular signal-regulated kinase (ERK) pathways. Expression levels of lipid-related genes (APOB, PPARα, CYP3A5 and SREBP-1) decreased to levels similar to the control groups. Western blot data demonstrated that the SREBP-1 protein expression correlated with its mRNA expression level.4. Supplementation with Que ameliorated lipid accumulation through AKT and ERK signalling pathway in OA/DEX-induced high-fat hepatocytes.
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Hepatocitos , Metabolismo de los Lípidos , Quercetina , Animales , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Quercetina/farmacología , Quercetina/administración & dosificación , Embrión de Pollo , Metabolismo de los Lípidos/efectos de los fármacos , Ácido Oléico/farmacología , Dexametasona/farmacología , Pollos , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Células CultivadasRESUMEN
We present the measurements of all-particle energy spectrum and mean logarithmic mass of cosmic rays in the energy range of 0.3-30 PeV using data collected from LHAASO-KM2A between September 2021 and December 2022, which is based on a nearly composition-independent energy reconstruction method, achieving unprecedented accuracy. Our analysis reveals the position of the knee at 3.67±0.05±0.15 PeV. Below the knee, the spectral index is found to be -2.7413±0.0004±0.0050, while above the knee, it is -3.128±0.005±0.027, with the sharpness of the transition measured with a statistical error of 2%. The mean logarithmic mass of cosmic rays is almost heavier than helium in the whole measured energy range. It decreases from 1.7 at 0.3 PeV to 1.3 at 3 PeV, representing a 24% decline following a power law with an index of -0.1200±0.0003±0.0341. This is equivalent to an increase in abundance of light components. Above the knee, the mean logarithmic mass exhibits a power law trend towards heavier components, which is reversal to the behavior observed in the all-particle energy spectrum. Additionally, the knee position and the change in power-law index are approximately the same. These findings suggest that the knee observed in the all-particle spectrum corresponds to the knee of the light component, rather than the medium-heavy components.
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Objective: To explore the mechanism of cross-linked hyaluronic acid-dexamethasone hydrogel (cHA-Dex) in inhibiting chondrocyte apoptosis and alleviating early post-traumatic osteoarthritis (PTOA). Methods: To generate PTOA model, anterior cruciate ligament transection (ACLT)was performed on SD rats (n=70), and the sham surgery group (n=70) was set as control. The changes in inflammatory indicators such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-13 (MMP-13) in the joint lavage fluid were measured at different time points (1-14 days, 5 rats at each time point) after surgery. The cHA-Dex (0.5 mg/ml) hydrogel (experimental group, n=70) and ordinary low-molecular-weight hyaluronic acid (HA) hydrogel premixed with Dex, that was, HA-Dex (0.5 mg/ml) hydrogel (control group, n=70) were injected into the joint cavity of PTOA rats, and the release amount and cumulative release amount of Dex in the joint fluid of rats at each time point(1-14 days, 5 rats at each time point) were detected to reveal the release mechanism of cHA-Dex hydrogel. The cartilage of knee joint of patients with osteoarthritis (OA) who underwent knee arthroplasty in the Second Hospital of Shanxi Medical University from January 2020 to December 2022 was taken for in vitro tissue block culture (Outbridge score=1 or 2,n=18). After the cartilage tissue block was treated with cHA-Dex hydrogel premixed with 0.1, 0.2, and 0.5 mg/ml Dex, the mRNA expression levels of IL-1ß, IL-6, TNF-α, MMP-3, and MMP-13 in the articular cartilage tissue block were detected. OA chondrocytes were isolated from cartilage samples using enzymatic hydrolysis and cultured in vitro (n=18). Chondrocytes were divided into 4 groups: saline, cHA hydrogel, Dex (0.5 mg/ml), and cHA-Dex (0.5 mg/ml) hydrogel group. The effects of different interventions on chondrocyte proliferation and apoptosis were tested. Results: The Osteoarthritis Research Society International (OARSI) score of safranine O-solid green staining in PTOA group was 3.34±0.35, and it was 1.17±0.21 in Sham group(P=0.010). The Meachim score of knee joint osteophytes in PTOA rats was significantly higher than that in the Sham group (2.66±0.41 vs 0.22±0.17, P=0.010), indicating PTOA model in rat was established successfully. The cHA-Dex hydrogel, which corresponded to the peak changes of inflammatory factors in the joints of PTOA rats in the early stage, was also released in the early stage and sustained-released in the late stage. After the OA articular cartilage tissue block was treated with cHA-Dex hydrogel premixed with 0.1, 0.2, and 0.5 mg/ml Dex, the mRNA expression levels of IL-1 ß, IL-6, TNF-α, MMP-3, and MMP-13 in the tissue block were reduced significantly (all P<0.05) and in a dose-dependent manner. Compared with Dex (0.5 mg/ml) alone group, the apoptosis rate of cHA-Dex (0.5 mg/ml) hydrogel group was significantly reduced (0.60±0.07 vs 6.63±0.98, P=0.010).Compared with the normal saline or the cHA hydrogel alone group, the cHA-Dex (0.5 mg/ml) hydrogel group had significant cell proliferation, and the difference at each time point were all significant statistically (all P<0.05). Conclusion: For the early inflammation of PTOA, cHA-Dex hydrogel can not only inhibit cartilage inflammation, but also reverse the increased apoptosis and decreased proliferation rate of chondrocytes caused by Dex, and finally alleviate the progress of PTOA by releasing Dex.
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Cartílago Articular , Osteoartritis , Humanos , Ratas , Animales , Ácido Hialurónico/farmacología , Metaloproteinasa 3 de la Matriz/farmacología , Metaloproteinasa 13 de la Matriz/metabolismo , Metaloproteinasa 13 de la Matriz/farmacología , Interleucina-6 , Factor de Necrosis Tumoral alfa/metabolismo , Ratas Sprague-Dawley , Osteoartritis/metabolismo , Cartílago Articular/metabolismo , Cartílago Articular/patología , Inflamación , Condrocitos , Dexametasona/farmacología , Hidrogeles/farmacología , ARN MensajeroRESUMEN
OBJECTIVE: To evaluate the effectiveness of the central government-funded echinococcosis control programme in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, so as to provide insights into echinococcosis control. METHODS: Administrative villages were sampled using a multi-stage cluster random sampling method from Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, and all residents at ages of 12 years and older in the sampled villages were screened for echinococcosis, and schools were sampled using a cluster sampling method, and all children at ages of 12 years and older in the sampled schools were screened for echinococcosis. Domestic dogs were sampled using a systematic random sampling method, and one domestic dog stool sample was collected from each household. Stray dog stool samples were collected outside the villages, and Echinococcus coproantigens were detected using enzyme-linked immunosorbent assay in domestic and stray dogs. In addition, echinococcosis was screened in sheep and cattle in designated slaughterhouses in Tianzhu Tibetan Autonomous County. The trends in the prevalence of echinococcosis in humans and livestock and the positive rate of Echinococcus coproantigens in dogs were examined with the Cochran-Armitage trend test. In addition, individuals screened for echinococcosis were randomly sampled from 2007 to 2022 for survey on the awareness of echinococcosis control knowledge. RESULTS: A total of 290 356 person-times were screened for echinococcosis among residents at ages of 12 years and older in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 1 094 residents detected with cystic echinococcosis, and the detection of echinococcosis appeared a tendency towards a gradual decline over years (χ2 = 358.602, P < 0.001). A total of 32 931 person-times were screened for echinococcosis among children at ages of 12 years and older in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 296 children detected with echinococcosis, and the detection of echinococcosis appeared a tendency towards a gradual decline over years (χ2 = 267.673, P < 0.001). A total of 33 230 domestic dog stool samples were tested for Echinococcus coproantigens in Tianzhu Tibetan Autonomous County, Gansu Province from 2007 to 2022, with 1 777 Echinococcus coproantigens-positive samples tested, and the positive rate of Echinococcus coproantigens appeared a tendency towards a decline in domestic dogs over years (χ2 = 2 210.428, P < 0.001), while the positive rate of Echinococcus coproantigens showed a tendency towards a rise in domestic animals from 2016 to 2022 (χ2 = 37.745, P < 0.001). The positive rate of Echinococcus coproantigens remained relatively stable in stray dogs in Tianzhu Tibetan Autonomous County, Gansu Province from 2019 to 2022 (χ2 = 0.315, P = 0.575). A total of 10 973 sheep were screened for echinococcosis in Tianzhu Tibetan Autonomous County from 2007 to 2022, with 334 sheep detected with echinococcosis, and the detection of echinococcosis appeared a tendency towards a decline in sheep over years (χ2 = 53.579, P < 0.001); however, there was no significant change in the detection of echinococcosis during the period from 2015 through 2022 (χ2 = 1.520, P = 0.218). A total of 2 400 cattle were screened for echinococcosis in Tianzhu Tibetan Autonomous County from 2017 to 2022, with 231 cattle detected with echinococcosis, and the detection of echinococcosis showed a tendency towards a decline over years (χ2 = 5.579, P < 0.05). The awareness of echinococcosis control knowledge increased from 44.37% in 2007 to 94.00% in 2022 among residents at ages of 12 years and older and from 52.50% in 2007 to 92.50% in 2022 among children at ages of 12 years and older in Tianzhu Tibetan Autonomous County, respectively. CONCLUSIONS: There has been a reduction in the detection of echinococcosis in humans and domestic animals and the positive rate of Echinococcus coproantigens in dogs and a rise in the awareness of the echinococcosis control knowledge following the implementation of the central government-funded echinococcosis control programme in Tianzhu Tibetan Autonomous County, Gansu Province; however, integrated echinococcosis control measures are still required for further control of the prevalence of echinococcosis.
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Enfermedades de los Perros , Equinococosis , Echinococcus , Niño , Humanos , Animales , Perros , Bovinos , Ovinos , Tibet/epidemiología , Equinococosis/epidemiología , Equinococosis/prevención & control , Equinococosis/veterinaria , Animales Domésticos , Prevalencia , Gobierno , China/epidemiología , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/prevención & controlRESUMEN
By conducting retrospective analysis, this study aim to investigate the resistance mechanism of quinolones in non-typhoidal Salmonella (NTS). A total of 105 strains of NTS isolated from clinical specimens from the Fifth Affiliated Hospital of Southern Medical University from May 2020 to February 2021 were used as research objects. VITEK2 Compact automatic identification drug sensitivity analysis system and serological test were used to identify the strains. The sensitivity of the strains to ciprofloxacin, levofloxacin and nalidixic acid was detected by AGAR dilution method. The whole genome of 105 strains of NTS was sequenced. Abricate and other softwares were used to analyze drug-resistant genes, including plasmid-mediated quinolone resistance gene (PMQR) and Quinolone resistance determination region (QRDR). Serotypes and ST types were analyzed using SISTR and MLST, and phylogenetic trees were constructed. The results showed that the NTS isolated in this region were mainly ST34 Salmonella typhimurium (53.3%). The drug sensitivity results showed that the drug resistance rates of NTS to ciprofloxacin, levofloxacin and nalidixic acid were 30.4%, 1.9% and 22.0%, respectively, and the intermediate rates of ciprofloxacin and levofloxacin were 27.6% and 54.2%.A total of 46 (74.2%) of the 62 quinolone non-susceptible strains carried the PMQR gene, mainly qnrS1 (80.4%), followed by aac(6')-Ib-cr(15.2%); there were 14 NTS and 8 NTS had gyrA and parC gene mutations, respectively. The gyrA was mutations at the amino acid position 87, Asp87Tyr, Asp87Asn, Asp87Gly, and Thr57Ser mutations were detected in parC. In conclusion, this study found that NTS had relatively high resistance to quinolones, carrying qnrS1 gene mainly resulted in decreased sensitivity of NTS to ciprofloxacin and levofloxacin, and gyrA:87 mutation mainly resulted in NTS resistance to Nalidixic acid; Salmonella typhimurium in clinical isolates showed clonal transmission and required further epidemiological surveillance.
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Quinolonas , Humanos , Quinolonas/farmacología , Ácido Nalidíxico/farmacología , Levofloxacino/farmacología , Filogenia , Tipificación de Secuencias Multilocus , Estudios Retrospectivos , Girasa de ADN/genética , Salmonella , Ciprofloxacina , Plásmidos , Mutación , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genéticaRESUMEN
AIMS: The PCAR study aimed to assess the efficacy and safety of preoperative transcatheter rectal arterial chemoembolisation (TRACE) in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS: This was a single-centre, prospective, phase II trial conducted in China. Eligible patients were adults aged 18 years and older with histologically confirmed stage II or III rectal carcinoma and an Eastern Cooperative Oncology Group performance status of 0-1. Patients received TRACE with oxaliplatin, followed by radiotherapy with a cumulative dose of 45 Gy (1.8 Gy/time/day, five times a week for 5 weeks) and received oral S1 capsules twice daily (7 days a week for 4 weeks). Patients underwent total mesorectal excision 4-8 weeks after the completion of chemoradiotherapy, followed by mFOLFOX6 or CAPOX regimens for 4-6 months. The hypothesis of this study was that adding TRACE to preoperative neoadjuvant chemoradiotherapy would improve tumour regression and prognosis. The primary end point was the pathological complete response rate; secondary end points included the major pathological response rate, anal preservation rate, 5-year disease-free survival (DFS), 5-year overall survival and treatment-related adverse events. RESULTS: In total, 111 LARC patients received TRACE and subsequent scheduled treatment plans. The pathological complete response and major pathological response rates were 20.72% and 48.65%, respectively. The 5-year DFS and 5-year overall survival were 61.89% (95% confidence interval 51.45-74.45) and 74.80% (95% confidence interval 65.05-86.01), respectively. Grade 3-4 toxicities were reported in 29 patients (26.13%). The postoperative complication rate was 21.62%, without serious surgical complications. Multivariate Cox regression analysis showed that ypN stage (hazard ratio = 4.242, 95% confidence interval 2.101-8.564, P = 0.00017) and perineural invasion (hazard ratio = 2.319, 95% confidence interval 1.058-5.084, P = 0.0487) were independent risk factors associated with DFS, whereas ypN stage (hazard ratio = 3.164, 95% confidence interval 1.347-7.432, P = 0.0101), perineural invasion (hazard ratio = 4.118, 95% confidence interval 1.664-10.188, P = 0.0134) and serum carbohydrate antigen 199 (CA199; hazard ratio = 4.142, 95% confidence interval 1.290-13.306, P = 0.0344) were independent predictors for overall survival. CONCLUSION: The current study provides evidence that adding TRACE to neoadjuvant chemoradiotherapy can improve the pathological remission rate in LARC patients with acceptable toxicity. Given its promising effectiveness and safe profile, incorporating TRACE into the standard treatment strategy for patients with LARC should be considered.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias del Recto , Adulto , Humanos , Resultado del Tratamiento , Estudios Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía , Supervivencia sin Enfermedad , Quimioradioterapia/efectos adversos , Terapia Neoadyuvante/efectos adversos , Terapia Neoadyuvante/métodos , Estadificación de Neoplasias , Respuesta Patológica Completa , FluorouraciloRESUMEN
OBJECTIVES: To assess the prevalence, all-cause mortality and determinants of advanced HIV disease (AHD) or severe immunosuppression (SIS) in the rural-urban communities of Southwestern China. STUDY DESIGN: Retrospective cohort study. METHOD: Data on HIV/AIDS cases reported in 2005-20 were collected from Case Report System. A binary logistic regression model assessed the risk factors of AHD/SIS prevalence. Survival curves across rural-urban regions were compared using Kaplan-Meier estimates and log-rank tests. Determinants of all-cause mortality were identified using the Cox proportional hazard model. RESULTS: Among 14,533 newly diagnosed HIV/AIDS patients, 7497 (51.6%) presented with AHD and 2564 (17.6%) with SIS. Compared with urban patients, rural patients had a higher prevalence of AHD (56.7% vs 40.7%) and SIS (20.1% vs 12.4%), all-cause mortality (AHD 12.3 vs 5.6, SIS 16.3 vs 5.5, per 100 person-years). Their 5-year survival probability (AHD 59.5% vs 77.1%; SIS 54.4% vs 76.3%) and mean survival time (AHD 106.5 vs 140.6 months, SIS 95.3 vs 144.2 months, p < 0.0001) were lower. Rural patients had an increased risk of SIS prevalence (adjusted odds ratios 1.45, 95% confidence interval [CI] 1.28-1.64; p < 0.0001) and mortality of the total cohort (adjusted hazard ratios 1.41, 95% CI 1.29-1.55; p < 0.0001), AHD cohort (1.38, 1.24-1.54; p < 0.0001), and SIS cohort (1.49, 1.23-1.81; p < 0.0001). CONCLUSIONS: A high prevalence of AHD/SIS was a severe phenomenon that caused high mortality in rural areas. A regional point-of-care strategy targeting AHD/SIS detection and management is essential for reducing the mortality risk.