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4.
Zhonghua Xue Ye Xue Za Zhi ; 45(6): 561-565, 2024 Jun 14.
Artículo en Chino | MEDLINE | ID: mdl-39134487

RESUMEN

Objective: To compare the consistency of lymphoma multigene detection panels based on next-generation sequencing (NGS) with FISH detection of B-cell lymphoma gene rearrangement. Methods: From January 2019 to May 2023, fusion genes detected by lymphoma-related 413 genes that targeted capture sequencing of 489 B-cell lymphoma tissues embedded in paraffin were collected from Henan Cancer Hospital, and the results were compared with simultaneous FISH detection of four break/fusion genes: BCL2, BCL6, MYC, and CCND1. Consistency was defined as both methods yielding positive or negative results for the same sample. The relationship between fusion mutation abundance in NGS and the positivity rate of cells in FISH was also analyzed. Results: Kappa consistency analysis revealed high consistency between NGS and FISH in detecting the four B-cell lymphoma-related gene rearrangement (P<0.001 for all) ; however, the detection rates of positive individuals differed for the four genes. Compared with FISH, NGS demonstrated a higher detection rate for BCL2 rearrangement, a lower detection rate for BCL6 and MYC rearrangement, and a similar detection rate for CCND1 rearrangement. No correlation was found between fusion mutation abundance in NGS and the positivity rate of cells in FISH. Conclusions: NGS and FISH detection of B-cell lymphoma gene rearrangement demonstrate overall good consistency. NGS is superior to FISH in detecting BCL2 rearrangement, inferior in detecting MYC rearrangement, and comparable in detecting CCND1 rearrangement.


Asunto(s)
Reordenamiento Génico , Secuenciación de Nucleótidos de Alto Rendimiento , Hibridación Fluorescente in Situ , Linfoma de Células B , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Linfoma de Células B/genética , Linfoma de Células B/diagnóstico , Hibridación Fluorescente in Situ/métodos , Proteínas Proto-Oncogénicas c-bcl-2/genética , Ciclina D1/genética , Proteínas Proto-Oncogénicas c-bcl-6/genética , Mutación , Proteínas Proto-Oncogénicas c-myc/genética
6.
Zhonghua Zhong Liu Za Zhi ; 46(8): 755-763, 2024 Aug 23.
Artículo en Chino | MEDLINE | ID: mdl-39143798

RESUMEN

Objective: To explore the gene mutation characteristics and the relationship between gene mutations and long-term prognosis in clinical stage ⅠA lung adenocarcinoma patients. Methods: A retrospective analysis was conducted on 63 clinical stage ⅠA lung adenocarcinoma patients who underwent surgical resection at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2007 to October 2012, with documented postoperative recurrence or metastasis, as well as those who had a follow-up duration of 10 years or more without recurrence or metastasis. Whole exome sequencing (WES) technology was used to analyze the gene mutation profiles in tumor tissues and univariate and multivariate Cox regression analysis were used to clarify the influencing factors for patient prognosis. Results: After long term follow-up, 13 out of the 63 patients (21%) experienced recurrence or metastasis. WES technology analysis revealed that the most common tumor related gene mutations occurred in epidermal growth factor receptor (EGFR), with a mutation rate of 65.1% (41/63), followed by tumor protein p53 (TP53), fatatypical cadherin 1 (FAT1), low density lipoprotein receptor-related protein 1B (LRP1B), mechanistic target of rapamycin (MTOR), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG), and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), with mutation rates of 30.2% (19/63), 20.6% (13/63), 15.9% (10/63), 15.9% (10/63), 15.9% (10/63), and 15.9% (10/63), respectively. Multivariate Cox regression analysis showed that PIK3CG mutations (HR=21.52, 95% CI: 3.19-145.01),smoothened (SMO) mutations (HR=35.28, 95% CI: 3.12-398.39), catenin beta 1 (CTNNB1) mutations (HR=332.86, 95% CI: 15.76-7 029.05), colony stimulating factor 1 receptor (CSF1R) mutations (HR=8 109.60, 95% CI: 114.19-575 955.17), and v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutations (HR=23.65, 95% CI: 1.86-300.43) were independent risk factors affecting the prognosis of clinical stage ⅠA lung adenocarcinoma patients. Conclusions: PIK3CG, SMO, CTNNB1, CSF1R, BRAF gene mutations are closely related to long-term recurrence or metastasis in clinical stage ⅠA lung adenocarcinoma. Patients with these gene mutations should be given closer clinical attention.


Asunto(s)
Adenocarcinoma del Pulmón , Receptores ErbB , Neoplasias Pulmonares , Mutación , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Proteína p53 Supresora de Tumor , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Estudios Retrospectivos , Pronóstico , Receptores ErbB/genética , Proteína p53 Supresora de Tumor/genética , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Cadherinas/genética , Cadherinas/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Secuenciación del Exoma , Estudios de Seguimiento , Masculino , Femenino , Persona de Mediana Edad , Proteínas de Unión al ADN , Receptores de LDL , Factores de Transcripción
7.
Nat Commun ; 15(1): 6782, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39117648

RESUMEN

Intermetallic alloys have traditionally been characterized by their inherent brittleness due to their lack of sufficient slip systems and absence of strain hardening. However, here we developed a single-phase B2 high-entropy intermetallic alloy that is both strong and plastic. Unlike conventional intermetallics, this high-entropy alloy features a highly distorted crystalline lattice with complex chemical order, leading to multiple slip systems and high flow stress. In addition, the alloy exhibits a dynamic hardening mechanism triggered by dislocation gliding that preserves its strength across a wide range of temperatures. As a result, this high-entropy intermetallic circumvents precipitous thermal softening, with extensive plastic flows even at high homologous temperatures, outperforming a variety of both body-centered cubic and B2 alloys. These findings reveal a promising direction for the development of intermetallic alloys with broad engineering applications.

9.
Zhonghua Er Ke Za Zhi ; 62(7): 669-675, 2024 Jul 02.
Artículo en Chino | MEDLINE | ID: mdl-38955686

RESUMEN

Objective: To investigate and summarize pediatric patients with severe Mycoplasma pneumoniae pneumonia (MPP) presenting with varied clinical and chest imaging features in order to guide the individualized treatment. Methods: This was a retrospective cohort study. Medical records of clinical, imaging and laboratory data of 505 patients with MPP who were admitted to the Department Ⅱ of Respirology Center, Beijing Children's Hospital, Capital Medical University from January 2016 to October 2023 and met the enrollment criteria were included. They were divided into severe group and non-severe group according to whether lower airway obliterans was developed. The clinical and chest imaging features of the two groups were analyzed. Those severe cases with single lobe ≥2/3 consolidation (lobar consolidation) were further divided into subtype lung-necrosis and subtype non-lung-necrosis based on whether lung necrosis was developed. Comparison on the clinical manifestations, bronchoscopic findings, whole blood C-reactive protein (CRP) and other inflammatory indicators between the two subtypes was performed. Comparisons between two groups were achieved using independent-sample t-test, nonparametric test or chi-square test. Univariate receiver operating characteristic (ROC) curve analyses were performed on the indicators such as CRP of the two subtypes. Results: Of the 505 cases, 254 were male and 251 were female. The age of the onset was (8.2±2.9) years. There were 233 severe cases, among whom 206 were with lobar consolidation and 27 with diffuse bronchiolitis. The other 272 belonged to non-severe cases, with patchy, cloudy infiltrations or single lobe <2/3 uneven consolidation or localized bronchiolitis. Of the 206 cases (88.4%) severe cases with lobar consolidation, 88 harbored subtype lung-necrosis and 118 harbored subtype non-lung-necrosis. All 206 cases (100.0%) presented with persistent high fever, among whom 203 cases (98.5%) presented with inflammatory secretion obstruction and plastic bronchitis under bronchoscopy. Of those 88 cases with subtype lung-necrosis, there were 42 cases (47.7%) with dyspnea and 39 cases (44.3%) with moderate to massive amount of pleural effusion. There were 35 cases (39.8%) diagnosed with lung embolism during the disease course, of which other 34 cases (38.6%) were highly suspected. Extensive airway mucosal necrosis was observed in 46 cases (52.3%), and the level of their whole blood CRP was significantly higher than that of subtype non-lung-necrosis (131.5 (91.0, 180.0) vs. 25.5 (12.0, 43.1) mg/L, U=334.00, P<0.001). They were regarded as subtype "lung consolidation-atelectasis-necrosis". Of those 118 cases with subtype non-lung-necrosis, 27 cases (22.9%) presented with dyspnea and none were with moderate to massive amount of pleural effusion. Sixty-five cases (55.1%) presented with plastic bronchitis and localized airway mucosal necrosis was observed in 32 cases (27.1%). They were deemed as subtype "lung consolidation-atelectasis". ROC curve analyses revealed that whole blood CRP of 67.5 mg/L on the 6-10 th day of disease course exhibited a sensitivity of 0.96, a specificity of 0.89, and an area under the curve of 0.97 for distinguishing between these two subtypes among those with lobar consolidation. Conclusions: Pediatric patients with severe MPP present with lobar consolidation or diffuse bronchiolitis on chest imaging. Those with lobar consolidation harbor 2 subtypes as "lung consolidation-atelectasis-necrosis" and "lung consolidation-atelectasis". Whole blood CRP of 67.5 mg/L can be applied as an early discriminating indicator to discriminate between these two subtypes.


Asunto(s)
Proteína C-Reactiva , Pulmón , Mycoplasma pneumoniae , Fenotipo , Neumonía por Mycoplasma , Humanos , Femenino , Masculino , Neumonía por Mycoplasma/diagnóstico , Estudios Retrospectivos , Niño , Pulmón/patología , Pulmón/diagnóstico por imagen , Proteína C-Reactiva/análisis , Broncoscopía/métodos , Índice de Severidad de la Enfermedad , Preescolar , Necrosis , Bronquiolitis/diagnóstico , Bronquiolitis/patología
10.
Zhonghua Xue Ye Xue Za Zhi ; 45(4): 345-350, 2024 Apr 14.
Artículo en Chino | MEDLINE | ID: mdl-38951061

RESUMEN

Objective: This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma. Methods: The clinical data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) . Results: Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group [20% (6/30) vs 13% (4/32), P=0.028]. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration (P<0.001). After 1 month of antiresorptive (AR) drug application, the decrease in the serum ß-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group (68% vs 59% vs 27%, P<0.001). The increase in serum procollagen type Ⅰ N-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group (34% vs 20% vs 11%, P<0.05). The level of intact parathyroid hormone in each group increased after AR drug treatment. None of the patients developed osteonecrosis of the jaw and renal adverse events, and no statistically significant differences in the overall response rate, complete remission and stringent complete remission rates were found among the groups (P>0.05), and the median PFS and OS time were not reached (P>0.05) . Conclusions: In the treatment of MBD, DENOS minimizes nephrotoxicity and has strong AR effect. Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.


Asunto(s)
Conservadores de la Densidad Ósea , Enfermedades Óseas , Denosumab , Hipocalcemia , Mieloma Múltiple , Ácido Zoledrónico , Humanos , Ácido Zoledrónico/administración & dosificación , Denosumab/efectos adversos , Denosumab/administración & dosificación , Mieloma Múltiple/tratamiento farmacológico , Estudios Retrospectivos , Enfermedades Óseas/etiología , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/efectos adversos , Hipocalcemia/inducido químicamente , Hipocalcemia/etiología , Masculino , Femenino , Resultado del Tratamiento , Persona de Mediana Edad , Anciano
11.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 36(3): 299-303, 2024 Apr 29.
Artículo en Chino | MEDLINE | ID: mdl-38952317

RESUMEN

OBJECTIVE: To evaluate the potential risk of transmission of angiostrongyliasis by common freshwater snails in Dali Bai Autonomous Prefecture, Yunnan Province, so as to provide insights into local surveillance of angiostrongyliasis. METHODS: Common freshwater snails were collected from Dali Bai Autonomous Prefecture, Yunnan Province from March to April, 2020, and identified and bred in laboratory. SD rats were infected with third-stage larvae of Angiostrongylus cantonensis that were isolated from commercially available Pomacea canaliculata snails in Dali Bai Autonomous Prefecture, and freshwater snails were infected with the first-stage larvae of A. cantonensis that were isolated from the feces of SD rats 39 days post-infection at room temperature. The developmental process and morphological characteristics of worms in hosts were observed, and the percentages of A. cantonensis infections in different species of freshwater snails were calculated. Then, SD rats were infected with the third-stage larvae of A. cantonensis that were isolated from A. cantonensis-infected freshwater snails, and the larval development and reproduction was observed. RESULTS: More than 3 000 freshwater snail samples were collected from farmlands, ditches and wetlands around Erhai Lake in Dali Bai Autonomous Prefecture, and Cipangopaludina chinensis, P. canaliculata, Parafossarulus striatulus, Oncomelania hupensis robertsoni, Galba pervia, Physa acuta, Radix swinhoei, Assiminea spp., Tricula spp. and Bellamya spp. were morphologically identified. A total of 105 commercially available P. canaliculata snails were tested for A. cantonensis infections, and 2 P. canaliculata snails were found to be infected with A. cantonensis, in which the third-stage larvae of A. cantonensis were isolated. Ten species of freshwater snails were artificially infected with the third-stage larvae of A. cantonensis, and all 10 species of freshwater snails were found to be infected with A. cantonensis, with the highest positive rate of A. cantonensis infections in Bellamya spp. (62.3%, 137/204), and the lowest in C. chinensis (35.5%, 11/31). After SD rats were infected with the third-stage larvae of A. cantonensis isolated from different species of freshwater snails, mature adult worms of A. cantonensis were yielded. CONCLUSIONS: Multiple species of freshwater snails may serve as intermediate hosts of A. cantonensis under laboratory conditions in Dali Bai Autonomous Prefecture of Yunnan Province. Further investigations on natural infection of A. cantonensis in wild snails in Dali Bai Autonomous Prefecture seem justified.


Asunto(s)
Angiostrongylus cantonensis , Agua Dulce , Ratas Sprague-Dawley , Caracoles , Animales , Caracoles/parasitología , China , Angiostrongylus cantonensis/fisiología , Angiostrongylus cantonensis/aislamiento & purificación , Ratas , Agua Dulce/parasitología , Larva/fisiología , Larva/crecimiento & desarrollo , Infecciones por Strongylida/parasitología , Infecciones por Strongylida/veterinaria , Infecciones por Strongylida/transmisión
13.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(6): 1048-1058, 2024 Jun 20.
Artículo en Chino | MEDLINE | ID: mdl-38977334

RESUMEN

OBJECTIVE: To explore the mechanism by which soybean isoflavone (SI) reduces calcium overload induced by cerebral ischemia-reperfusion (I/R). METHODS: Forty-eight SD rats were randomized into 4 groups to receive sham operation, cerebral middle artery occlusion for 2 h followed by 24 h of reperfusion (I/R model group), or injection of adeno-associated virus carrying Frizzled-2 siRNA or empty viral vector into the lateral cerebral ventricle after modeling.Western blotting was used to examine Frizzled-2 knockdown efficiency and changes in protein expressions in the Wnt/Ca2+ signaling pathway.Calcium levels and pathological changes in the ischemic penumbra (IP) were measured using calcium chromogenic assay and HE staining, respectively.Another 72 SD randomly allocated for sham operation, I/R modeling, or soy isoflavones pretreatment before modeling were examined for regional cerebral blood flow using a Doppler flowmeter, and the cerebral infarct volume was assessed using TTC staining.Pathologies in the IP area were evaluated using HE and Nissl staining, and ROS level, Ca2+ level, cell apoptosis, and intracellular calcium concentration were analyzed using immunofluorescence assay or flow cytometry; the protein expressions of Wnt5a, Frizzled-2, and P-CaMK Ⅱ in the IP were detected with Western blotting and immunohistochemistry. RESULTS: In rats with cerebral I/R, Frizzled-2 knockdown significantly lowered calcium concentration (P < 0.001) and the expression levels of Wnt5a, Frizzled-2, and P-CaMK Ⅱ in the IP area.In soy isoflavones-pretreated rats, calcium concentration, ROS and MDA levels, cell apoptosis rate, cerebral infarct volume, and expression levels of Wnt/Ca2+ signaling pathway-related proteins were all significantly lower while SOD level was higher than those in rats in I/R model group. CONCLUSION: Soy isoflavones can mitigate calcium overload in rats with cerebral I/R by inhibiting the Wnt/Ca2+ signaling pathway.


Asunto(s)
Isquemia Encefálica , Calcio , Glycine max , Isoflavonas , Ratas Sprague-Dawley , Daño por Reperfusión , Vía de Señalización Wnt , Animales , Isoflavonas/farmacología , Isoflavonas/uso terapéutico , Ratas , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Vía de Señalización Wnt/efectos de los fármacos , Isquemia Encefálica/metabolismo , Calcio/metabolismo , Glycine max/química , Apoptosis/efectos de los fármacos , Masculino , Proteína Wnt-5a/metabolismo , ARN Interferente Pequeño/genética
14.
Zhonghua Yu Fang Yi Xue Za Zhi ; 58(7): 998-1003, 2024 Jul 06.
Artículo en Chino | MEDLINE | ID: mdl-39034783

RESUMEN

Objective: To establish an absolute quantitative method for high ethanol-producing klebsiella pneumoniae in a viable non-culturable (VBNC) state. Methods: High ethanol-producing Klebsiella pneumonia was induced to enter the VBNC state and then the ethanol production was evaluated. A PMA-ddPCR method was established to count the copies of live cell genes in the VBNC state of high ethanol-producing Klebsiella pneumoniae using single-copy genes. Further, the sensitivity and adaptability of ddPCR for detecting low-concentration samples were evaluated in VBNC fecal simulation. Results: The lower detection limit of ddPCR for quantitative analysis of high ethanol-producing Klebsiella pneumoniae gradient diluent was 10 times that of qPCR. At low temperature and low nutritional state, high ethanol-producing Klebsiella pneumoniae entered the VBNC state on the 45th day. The quantitative results of PMA-ddPCR on VBNC state cells were (5.46±0.05) log10 DNA copies/ml. The ethanol production in the VBNC state was<2.2 mmol/L and the ability to produce ethanol was restored after recovery. The minimum detection limit for ddPCR in fecal simulated samples with VBNC state was 3.2 log10 DNA copies/ml. Conclusion: The ddPCR detection method for high ethanol-producing Klebsiella pneumoniae with VBNC state has good sensitivity and adaptability, and can be used for the detection of VBNC state cells in clinical samples.


Asunto(s)
Etanol , Klebsiella pneumoniae , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/aislamiento & purificación , Etanol/metabolismo , Reacción en Cadena de la Polimerasa/métodos
15.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(5): 904-912, 2024 May 20.
Artículo en Chino | MEDLINE | ID: mdl-38862448

RESUMEN

OBJECTIVE: To explore the effect of pristimerin combined with cisplatin on proliferation and apoptosis of nasopharyngeal carcinoma cells. METHODS: CCK-8 assay was used to examine the survival rate of HNE-1 and CNE-2Z cells following treatment for 24 h with different concentrations of pristimerin, cisplatin or their combination. The changes in colony formation ability, apoptosis, and intracellular reactive oxygen species (ROS) levels of the treated cells were analyzed using colony formation assay and flow cytometry. Western blotting was performed to detect the changes in protein expressions in the cells. The effects of pre-treatment with NAC on proliferation, apoptosis, and PI3K/AKT signaling pathway were observed in pristimerin- and/or cisplatin-treated cells. RESULTS: Both pristimerin and cisplatin significantly lowered the survival rate of HNE-1 and CNE-2Z cells (P < 0.05). Compared with pristimerin or cisplatin alone, their combination more strongly inhibited survival and colony formation ability of the cells, increased cell apoptosis rate and intracellular ROS levels, upregulated the protein expressions of Bax, cleaved caspase-3, and cleaved PARP, and downregulated the protein expressions of Bcl-2, Mcl-1, PARP and p-PI3K and p-AKT (P < 0.05). NAC pretreatment significantly attenuated proliferation inhibition and apoptosis-promoting effects of pristimerin combined with cisplatin, and partially restored the downregulated protein expressions of p-PI3K and p-AKT in HNE-1 and CNE-2Z cells with the combined treatment (P < 0.05). CONCLUSION: Pristimerin can enhance cisplatin-induced proliferation inhibition and apoptosis in nasopharyngeal carcinoma cells, the mechanism of which may involve ROS-mediated deactivation of the PI3K/AKT signaling pathway.


Asunto(s)
Apoptosis , Proliferación Celular , Cisplatino , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Especies Reactivas de Oxígeno , Transducción de Señal , Humanos , Cisplatino/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Proliferación Celular/efectos de los fármacos , Triterpenos Pentacíclicos/farmacología , Triterpenos/farmacología
16.
Zhonghua Bing Li Xue Za Zhi ; 53(6): 535-540, 2024 Jun 08.
Artículo en Chino | MEDLINE | ID: mdl-38825896

RESUMEN

The 5th edition of the World Health Organization (WHO) classification of haematolymphoid tumours used the hierarchical system to classify T-cell and NK-cell lymphoid proliferations and lymphomas (T/NK-LPD/LYM) based on research advances and clinicopathological characteristics of the diseases. In this edition of classification, tumour-like lesions were included, some tumors were added/deleted, the names or terms of certain diseases were refined, and the diagnostic criteria or subtypes of some diseases were revised. This group of diseases was reintegrated from non-clonal hyperplasia to highly aggressive lymphoma, which would further reflect the nature of T/NK-LPD/LYM and benefit to clinical application.


Asunto(s)
Células Asesinas Naturales , Linfoma , Linfocitos T , Organización Mundial de la Salud , Humanos , Células Asesinas Naturales/patología , Células Asesinas Naturales/inmunología , Linfocitos T/patología , Linfocitos T/inmunología , Linfoma/patología , Linfoma/clasificación , Linfoma/inmunología , Linfoma de Células T/patología , Linfoma de Células T/clasificación , Linfoma de Células T/inmunología , Trastornos Linfoproliferativos/patología , Trastornos Linfoproliferativos/clasificación , Trastornos Linfoproliferativos/inmunología
17.
J Cannabis Res ; 6(1): 26, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38822413

RESUMEN

BACKGROUND: Cannabis has been shown to impact driving due to changes produced by delta-9-tetrahydrocannabinol (THC), the psychoactive component of cannabis. Current legal thresholds for blood THC while driving are based predominantly on evidence utilizing smoked cannabis. It is known that levels of THC in blood are lower after eating cannabis as compared to smoking yet the impact of edibles on driving and associated blood THC has never been studied. METHODS: Participants drove a driving simulator before and after ingesting their preferred legally purchased cannabis edible. In a counterbalanced control session, participants did not consume any THC or cannabidiol (CBD). Blood was collected for measurement of THC and metabolites as well as CBD. Subjective experience was also assessed. RESULTS: Participants consumed edibles with, on average, 7.3 mg of THC, which is less than the maximum amount available in a single retail package in Ontario, providing an ecologically valid test of cannabis edibles. Compared to control, cannabis edibles produced a decrease in mean speed 2 h after consumption but not at 4 and 6 h. Under dual task conditions in which participants completed a secondary task while driving, changes in speed were not significant after the correction for multiple comparison. No changes in standard deviation of lateral position (SDLP; 'weaving'), maximum speed, standard deviation of speed or reaction time were found at any time point or under either standard or dual task conditions. Mean THC levels were significantly increased, relative to control, after consuming the edible but remained relatively low at approximately 2.8 ng/mL 2 h after consumption. Driving impairment was not correlated with blood THC. Subjective experience was altered for 7 h and participants were less willing/able to drive for up to 6 h, suggesting that the edible was intoxicating. INTERPRETATION: This is the first study of the impact of cannabis edibles on simulated driving. Edibles were intoxicating as revealed by the results of subjective assessments (VAS), and there was some impact on driving. Detection of driving impairment after the use of cannabis edibles may be difficult.

18.
J Endocrinol Invest ; 47(10): 2521-2537, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38907823

RESUMEN

BACKGROUND AND PURPOSE: Subclinical hypothyroidism (SCH) has been identified to be associated with implantation failure, in which the dysfunction of trophoblast cells is involved. In this study, the transcriptomics of aborted placenta from SCH rats were analyzed. Jupiter microtubule-associated homolog 2 (JPT2) was downregulated in the aborted placenta. This study aims to investigate its role in SCH-associated miscarriage. METHODS: Spontaneous abortion was observed in SCH rats generated by thyroidectomy combined with levothyroxine administration. The transcriptomics analysis was performed using aborted placenta. Afterward, the effects of JPT2 on trophoblast cells were explored using gain-and loss-of-function experiments. RESULTS: Transcriptomics analysis showed 1286 downregulated genes and 2300 upregulated genes in the aborted placenta, and JPT2 was significantly downregulated in the aborted placenta from SCH rats. Afterward, gain-and loss-of-function experiments exhibited that overexpression of JPT2 promoted the proliferation, migration, invasion, spheroid formation of HTR-8/SVneo trophoblast cells and their attachment to endometrial stromal cells, while these biological behaviors were suppressed by JPT2 knockdown. Furthermore, JPT2 accelerated the transcription of leptin receptor (LEPR), and activated signal transducer and activator of transcription 3 (STAT3) signal in a transcription factor AP-2γ-dependent manner. In addition, silencing of LEPR abolished the role of JPT2. CONCLUSION: Our results revealed that JPT2, which was downregulated in the aborted placenta from SCH rats, promoted proliferation, migration, invasion, spheroid formation, and attachment of trophoblast cells via regulating LEPR/STAT3 axis as a transcription co-factor. It is indicated that low expression of JPT2 may contribute to the abortion in individuals with SCH.


Asunto(s)
Aborto Espontáneo , Hipotiroidismo , Factor de Transcripción STAT3 , Femenino , Animales , Hipotiroidismo/metabolismo , Hipotiroidismo/genética , Hipotiroidismo/patología , Ratas , Embarazo , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Aborto Espontáneo/metabolismo , Aborto Espontáneo/genética , Aborto Espontáneo/etiología , Receptores de Leptina/genética , Receptores de Leptina/metabolismo , Trofoblastos/metabolismo , Trofoblastos/patología , Placenta/metabolismo , Ratas Sprague-Dawley , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Asociadas a Microtúbulos/genética , Humanos , Proliferación Celular , Transducción de Señal
19.
Zhonghua Er Ke Za Zhi ; 62(6): 542-547, 2024 Jun 02.
Artículo en Chino | MEDLINE | ID: mdl-38763876

RESUMEN

Objective: To observe the expression of Galectin-7 in the serum and sputum of asthmatic children and to explore its significance in asthmatic children. Methods: The study prospectively case-control selected 183 children diagnosed with bronchial asthma at Department Ⅱ of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital of Capital Medical University. The control group consisted of 41 children with other bronchial diseases and 43 healthy children. Children in the asthma group were divided into acute and non-acute exacerbation groups. Acute exacerbation group was divided as mild acute, moderate acute and severe acute groups; non-acute exacerbation group was divided as mild persistent, moderate persistent and severe persistent groups. Children without acute exacerbation asthma in the asthma group were divided into high and low Galectin-7 groups based on median serum Galectin-7 levels. Serum and sputum were collected, Galectin-7 levels were measured using enzyme-linked immunosorbent assay. The study compared and analyzed the differences in Galectin-7 levels between children with asthma and the control groups using Mann-Whitney U test or the Kruskal-Wallis or the Chi-square test for inter-group comparisons. Results: Among 183 children, 61 cases had acute asthma exacerbation, and 122 cases had persistent asthma without acute exacerbation. The asthma group comprised 110 males and 73 females. The control group consisted of 41 children with other bronchial diseases, including 24 cases of bronchiectasis and 17 cases of obliterans bronchitis. The control group comprised 26 males and 15 females. Forty-three healthy children who underwent physical examination, including 22 males and 21 females. The levels of Galectin-7 in serum were significantly higher in children with an acute asthma exacerbation than that of healthy children (0.1 (0, 0.7) vs. 0 (0, 0.2) µg/L, Z=2.09, P=0.001). Galectin-7 levels in sputum were higher in children with an acute asthma exacerbation than that in children with other bronchial diseases (1.2 (0.1,3.7) vs. 0.4 (0.1, 1.5) µg/L, Z=2.20, P<0.001). Serum Galectin-7 levels were significantly higher in children with persistent asthma compared to children with other bronchial diseases and healthy children (0.6 (0.3, 1.2) vs. 0.1 (0, 0.5) and 0 (0, 0.2) µg/L, Z=-6.12,-7.63, both P<0.001), and the levels were significantly and positively correlated with asthma severity (r=0.77, P<0.001), disease duration (r=0.34, P=0.001), and number of previous attacks (r=0.51, P<0.001). There were 61 children in the high-Galectin-7 group and 61 children in the low-Galectin-7 group. Children with high Galectin-7 had more asthma triggers, a greater proportion with a positive family history, more previous asthma attacks, longer duration of asthma, and higher serum total IgE levels compared to those with low Galectin-7 (χ2=9.30, 22.46, Z=5.06, 3.57, 2.31, all P<0.05). Conclusion: The expression of Galectin-7 is found to be elevated in the serum and sputum of asthmatic children and correlated with asthma conditions.


Asunto(s)
Asma , Galectinas , Esputo , Humanos , Galectinas/sangre , Galectinas/metabolismo , Asma/metabolismo , Asma/sangre , Asma/diagnóstico , Esputo/metabolismo , Niño , Estudios de Casos y Controles , Estudios Prospectivos , Masculino , Femenino , Adolescente , Biomarcadores/sangre , Preescolar
20.
Zhonghua Bing Li Xue Za Zhi ; 53(5): 452-457, 2024 May 08.
Artículo en Chino | MEDLINE | ID: mdl-38678325

RESUMEN

Objective: To investigate the role of RNA m6A methylation in mediating cerebellar dysplasia through analyzing the phenotypes of the mouse cerebella and the expression of several key m6A regulators upon hypobaric hypoxia treatment. Methods: Five-day old C57/BL6 mice were exposed to hypobaric hypoxia for 9 days. The status of mouse cerebellar development was analyzed by comparing the body weights, brain weights and histological features. Immunostaining of cell-type-specific markers was performed to analyze the cerebellar morphology. Real-time PCR, Western blot and immunohistochemical staining were performed to detect the expression of key m6A regulators in the mouse cerebella. Results: Compared with the control, the body weights, brain weights and cerebellar volumes of hypobaric hypoxic mice were significantly reduced (P<0.01). The expression of specific markers in different cells, including NeuN (mature neuron), Calbindin-D28K (Purkinje cell) and GFAP (astrocyte), was decreased in hypobaric hypoxic mouse cerebella (P<0.01), accompanied with disorganized cellular structure. The expression of methyltransferase METTL3 was significantly down-regulated in the cerebella of hypobaric hypoxic mice (P<0.05). Conclusions: Hypobaric hypoxia stimulation causes mouse cerebellar dysplasia, with structural abnormalities in mature granular neurons, Purkinje cells and astrocytes. Expression of METTL3 is decreased in hypobaric hypoxic mice cerebellum compared with that of normobaric normoxic mice, suggesting that its mediated RNA m6A methylation may play an important role in hypobaric hypoxia-induced mouse cerebellar dysplasia.


Asunto(s)
Calbindinas , Cerebelo , Proteínas de Unión al ADN , Hipoxia , Metiltransferasas , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso , Células de Purkinje , Animales , Ratones , Cerebelo/metabolismo , Hipoxia/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Células de Purkinje/metabolismo , Células de Purkinje/patología , Calbindinas/metabolismo , Calbindinas/genética , Metiltransferasas/metabolismo , Metiltransferasas/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Proteína Ácida Fibrilar de la Glía/genética , Astrocitos/metabolismo , Regulación hacia Abajo , Metilación , Adenosina/metabolismo , Adenosina/análogos & derivados , Malformaciones del Sistema Nervioso/metabolismo , Malformaciones del Sistema Nervioso/genética
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