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1.
Br J Haematol ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39295138

RESUMO

Covalent Bruton's tyrosine kinase-inhibitors (cBTK-i) are highly active in MYD88-mutated (MYD88Mut) Waldenstrom's macroglobulinaemia and suppress nuclear factor kappa-light-chain-enhancer of activated B cells and extracellular signal-regulated kinases-1/2 (ERK1/2)-related signalling. BTKCys481 mutations are associated with cBTK-i acquired resistance and are accompanied by reactivation of ERK1/2 that promotes inflammatory cytokine secretion and paracrine-mediated resistance of BTK wild-type (BTKWT) tumour cells. Pirtobrutinib is a non-covalent BTK-inhibitor that binds at non-BTKCys481 sites. We show that pirtobrutinib blocked p-ERK1/2, ERK1/2-driven inflammatory cytokines, and overcame paracrine-mediated resistance in MYD88Mut lymphoma cells expressing mutated BTKCys481. Our results provide important mechanistic insights for the activity of pirtobrutinib in MYD88Mut lymphomas carrying BTKCys481 mutations.

3.
Br Poult Sci ; : 1-7, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39250000

RESUMO

1. This study calculated descriptive statistics for the production traits of two broiler populations: 1) the Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF white broilers), including fat and lean lines; and 2) the Guangxi yellow broilers. Their genetic parameters were estimated, including (co)variance components, heritability (h2) and genetic correlations (rg), using the REML method.2. Heritability estimates (h2) for NEAUHLF white broilers ranged from 0.07 to 0.61. Traits with high heritability (h2 >0.3) included body weight at 3, 5 and 7 weeks of age (BW3, BW5, BW7), carcass weight (CW), metatarsal circumference (MeC), liver weight (LW), gizzard weight (GW), spleen weight (SW) and testis weight (TeW), while in Guangxi yellow broilers, heritability estimates ranged from 0.18 to 0.76, with every trait exhibiting high heritability, except for SW (0.18).3. Positive genetic correlations for NEAUHLF were found (rg >0.3, ranging from 0.31 to 0.84) between BW7 and metatarsal length (MeL), MeC, body oblique length (BoL), chest angle (ChA), LW, GW, heart weight (HW) and SW. Genetic correlations between abdominal fat weight (AFW) and BW1, BW3, BW5, CW, MeL, keel length (KeL), BoL and LW were positive (rg >0.3, ranging from 0.31 to 0.58).4. Among the Guangxi population, BW (125 d of age) showed strong positive genetic correlations with all other traits (rg >0.3, ranging from 0.30 to 0.99), while AFW displayed strong positive genetic correlations with leg muscle weight (LeW), CW, BW and thigh diameter (TD) (rg >0.3, ranging from 0.44 to 0.51).5. It was concluded that the characteristics of the two populations were different, which means there is a need to use different strategies when performing the breeding work to improve productivity and efficiency in both broiler populations.

4.
Zhonghua Fu Chan Ke Za Zhi ; 59(9): 675-681, 2024 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-39313419

RESUMO

Objective: To investigate the effect of prenatal dexamethasone on short-term outcomes and long-term neurological development in late preterm infants with twin pregnancy. Methods: A total of 315 pregnant women with twin pregnancy and their preterm infants who delivered in Peking University Third Hospital from January 2019 to December 2022 were retrospectively analyzed. The clinical data of pregnant women and preterm infants were collected. They were divided into non-medication group (93 pregnant women and 186 preterm infants), medication after 34 weeks group (123 pregnant women and 246 preterm infants), and medication before 34 weeks group (99 pregnant women and 198 preterm infants). Short-term outcomes of preterm infants were analyzed, including the incidence of neonatal respiratory distress syndrome (NRDS), wet lung, hypoglycemia, neonatal septicemia, intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD) and neonatal necrotizing enterocolitis (NEC). "Ages and Stages Questionnaire-Third Edition (ASQ-3) scale" was used to follow up the late neurological development of preterm infants at the corrected age of 6-54 months, and the level of neurological development was compared. Results: (1) General conditions: the gestational age at delivery in the non-medication group [36.1 weeks (35.6, 36.6 weeks)] was later than that in the medication after 34 weeks group [36.1 weeks (35.2, 36.4 weeks)] and medication before 34 weeks group [35.2 weeks (34.2, 36.2 weeks)] groups, and the differences were statistically significant (all P<0.05). After correcting for gestational age, there was no significant difference in birth weight among the three groups (H=3.808, P=0.149). There were no significant differences in gender and the proportion of small for gestational age among the three groups (all P>0.05). (2) Short-term outcome: the incidence of wet lung was 7.0% (13/186), 11.0% (27/246) and 16.2% (32/198) in the non-medication group, medication after 34 weeks group and medication before 34 weeks group, respectively, and the difference was statistically significant (P=0.018). There were no significant differences in the incidence rates of NRDS, hypoglycemia, sepsis, IVH, BPD, and NEC among the three groups (all P>0.05). Logistic regression analysis with gestational age and newborn birth weight as confounding factors showed that early gestational age (OR=0.884, 95%CI: 0.837-0.933, P<0.001) and increased incidence of selective intrauterine growth restriction type I (OR=2.967, 95%CI: 1.153-7.639, P=0.024) could both lead to an increased incidence of wet lung. (3) Long-term outcomes: a total of 109 pregnant women completed the follow-up, and 218 preterm infants with a corrected age of 6-54 months at the end of follow-up were enrolled, including 86 cases in the non-medication group, 66 cases in the medication after 34 weeks group, and 66 cases in the medication before 34 weeks group. There were no significant differences in the scores of communication, gross motor, fine motor, problem solving and personal-social among the three groups (all P>0.05). Conclusion: Prenatal administration of a single course of dexamethasone does not affect the neonatal birth weight and short-term outcomes of twin late preterm infants, and has no adverse effect on the neurological development of twin late preterm infants with a corrected age of 6-54 months.


Assuntos
Dexametasona , Recém-Nascido Prematuro , Gravidez de Gêmeos , Humanos , Feminino , Gravidez , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Recém-Nascido , Estudos Retrospectivos , Adulto , Idade Gestacional , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Síndrome do Desconforto Respiratório do Recém-Nascido/prevenção & controle , Resultado da Gravidez
5.
Clin Radiol ; 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39271306

RESUMO

AIM: In this study, we investigated the feasibility of the Alberta Stroke Program Early CT Score (ASPECTS) and multiphase computed tomography angiography (mCTA) lateral branch circulation grading combined with clinical and laboratory indicators to predict the clinical prognosis of patients with acute ischemic stroke after 90 days. MATERIALS AND METHODS: The clinical data of 80 patients with acute anterior circulation ischemic stroke were retrospectively analyzed and divided into the good prognosis (37 cases) and poor prognosis groups (43 cases) according to their clinical function score at 90 days after discharge. Various factors, including basic imaging parameters (ASPECTS), occluded vessel location, affected side location and clinical indicators (time from onset to computed tomography examination, height, weight, body mass index, previous hypertension, and degree of hypertension and diabetes mellitus), laboratory blood rutine, and biochemical tests (white blood count, neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio, hematocrit test, platelet count, international normalized ratio, blood glucose, triglycerides, uric acid, and D-dimer) were considered in the analysis. RESULTS: Logistic regression analysis showed that the mCTA score, hypertension, and neutrophil count were significant independent predictors. CONCLUSION: A nomogram of the mCTA score, hypertension, and neutrophil count may predict functional recovery after 90 days in patients with acute ischemic stroke.

6.
Zhonghua Liu Xing Bing Xue Za Zhi ; 45(9): 1283-1290, 2024 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-39307703

RESUMO

Objective: To develop a prediction model for the risk of diabetic retinopathy (DR) in patients with newly diagnosed type 2 diabetes mellitus (T2DM). Methods: Patients with new diagnosis of T2DM recorded in Yinzhou Regional Health Information Platform between January 1, 2015 and December 31, 2022 were included in the study. The predictor variables were selected by using Lasso-Cox proportional hazards regression model. Cox proportional hazards regression models were used to establish the prediction model for the risk of DR. Bootstrap method (500 resamples) was used for internal validation, and the performance of the model was assessed by C-index, the receiver operating characteristic curve and area under the curve (AUC), and calibration curve. Results: The predictor variables included in the final model were age of T2DM onset, education level, fasting plasma glucose, glycated hemoglobin A1c, urinary albumin, estimated glomerular filtration rate, and history of lipid-lowering agent and angiotensin converting enzyme inhibitor uses. The C-index of the final model was 0.622, and the mean corrected C-index was 0.623 (95%CI: 0.607-0.634). The AUC values for predicting the risk of DR after 3, 5, and 7 years were 0.631, 0.620, and 0.624, respectively, with a high degree of overlap of the calibration curves with the ideal curves. Conclusion: In this study, a simple and practical risk prediction model for DR risk prediction was developed, which could be used as a reference for individualized DR screening and intervention in newly diagnosed T2DM patients.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Modelos de Riscos Proporcionais , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/diagnóstico , Incidência , Fatores de Risco , Curva ROC , Hemoglobinas Glicadas/análise , Glicemia/análise , Feminino , China/epidemiologia , Masculino , Pessoa de Meia-Idade
7.
Zhonghua Liu Xing Bing Xue Za Zhi ; 45(9): 1321-1326, 2024 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-39307708

RESUMO

Population based health data collection and analysis are important in epidemiological research. In recent years, with the rapid development of big data, Internet and cloud computing, artificial intelligence has gradually attracted attention of epidemiological researchers. More and more researchers are trying to use artificial intelligence algorithms for genome sequencing and medical image data mining, and for disease diagnosis, risk prediction and others. In recent years, machine learning, a branch of artificial intelligence, has been widely used in epidemiological research. This paper summarizes the key fields and progress in the application of machine learning in epidemiology, reviews the development history of machine learning, analyzes the classic cases and current challenges in its application in epidemiological research, and introduces the current application scenarios and future development trends of machine learning and artificial intelligence algorithms for the better exploration of the epidemiological research value of massive medical health data in China.


Assuntos
Aprendizado de Máquina , Humanos , China/epidemiologia , Inteligência Artificial , Mineração de Dados/métodos , Algoritmos , Big Data , Epidemiologia
8.
Zhonghua Xue Ye Xue Za Zhi ; 45(8): 738-747, 2024 Aug 14.
Artigo em Chinês | MEDLINE | ID: mdl-39307720

RESUMO

Objective: To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) . Methods: A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results: Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype (P=0.02, OR=0.39, 95%CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation (P=0.02, OR=0.22, 95%CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95%CI 21.14-30.19) months. HMA response (P=0.036, HR=0.47, 95%CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype (P=0.024, HR=2.14, 95%CI 1.10-4.15) , leukemia transformation (P<0.001, HR=2.839, 95%CI 1.64-4.92) , and TP53 mutation (P=0.012, HR=2.19, 95%CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion: Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.


Assuntos
Síndromes Mielodisplásicas , Humanos , Síndromes Mielodisplásicas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Idoso , Adulto , Idoso de 80 Anos ou mais , Adulto Jovem , Adolescente , Resultado do Tratamento , Azacitidina/uso terapêutico
9.
Artigo em Chinês | MEDLINE | ID: mdl-39223051

RESUMO

Objective: To establish a method for the determination of eight N-nitrosamines (N-nitrosodimethylamine, N-nitrosodimethylamine, N-nitrosomethylmethylamine, N-nitrosodibutylamine, N-nitrosopropylamine, N-nitrosomorpholine, N-nitrosodianiline and N-nitrosopiperidine) in the air of workplace by gas chromatography-tandem mass spectrometry (GC-MS/MS) . Methods: From January to August 2023, eight N-nitrosamines in the air of workplace were collected by ThermoSorb/N column, eluted with 4 ml methanol-dichloromethane (1∶1 volume ratio), separated by VF-624 ms capillary column, detected by multiple reaction monitoring mode and quantified by external standard method. The detection limit and precision of the method were also analyzed. Results: The linear range of the method for the determination of eight N-nitrosamines was 1.0-20.0 µg/L, the correlation coefficient was 0.9993-0.9999, the detection limit was 0.051-0.132 µg/L, and the minimum quantitative concentration was 0.030-0.078 µg/m(3) (calculated by collecting 22.5 L of air sample and eluting with 4.0 ml stripping liquid). The within-run precisions were 2.05%-6.89% and the between-run precisions were 2.41%-8.26%. The desorption rates were 67.20%-102.60%. The sample can be kept at least 7 days at 4 ℃. Conclusion: GC-MS/MS method for the determination of eight N-nitrosamines in workplace air has high sensitivity and good precision, and can accurately determine the content of eight N-nitrosamines in workplace air.


Assuntos
Poluentes Ocupacionais do Ar , Cromatografia Gasosa-Espectrometria de Massas , Nitrosaminas , Espectrometria de Massas em Tandem , Local de Trabalho , Nitrosaminas/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Massas em Tandem/métodos , Poluentes Ocupacionais do Ar/análise , Exposição Ocupacional/análise , Dimetilnitrosamina/análise , Monitoramento Ambiental/métodos
10.
Artigo em Chinês | MEDLINE | ID: mdl-39223053

RESUMO

This paper analyzes the pathogenesis, clinical characteristics, treatment measures and prognosis of a case of methemoglobin and hemolytic anemia caused by acute nitrogen trifluoride poisoning. The patient with occupational exposure to nitrogen trifluoride was treated immediately after the onset of illness, methemoglobin was monitored and a comprehensive examination was conducted. After comprehensive analysis, it was considered that acute nitrogen trifluoride poisoning could cause methemoglobinemia, hemolytic anemia and liver injury. The patient was disengaged and given symptomatic treatment such as oxygen therapy, methylene blue, low-dose methylpredrone, vitamin C and reduced glutathione. The prognosis of the patient is good, which provides a reference for the clinical treatment and occupational health examination of nitrogen trifluoride poisoning.


Assuntos
Anemia Hemolítica , Metemoglobinemia , Humanos , Metemoglobinemia/induzido quimicamente , Masculino , Anemia Hemolítica/induzido quimicamente , Anemia Hemolítica/terapia , Adulto , Exposição Ocupacional/efeitos adversos , Pessoa de Meia-Idade
11.
Balkan J Med Genet ; 27(1): 69-74, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39263646

RESUMO

Congenital diarrheal disorders (CDD) are a group of rare inherited intestinal disorders, among which CDD7 was recently identified to be associated with only 24 mutations in gene coding for diacylglycerol-acyltransferase 1 (DGAT1). We report on a female patient who presented with diarrhea, vomiting, hypoalbuminemia, and failure to thrive after birth. Two novel variants of c.1215_1216delAG and c.838C>T were found in the DGAT1 gene by whole exome sequencing, which was confirmed to be compound heterozygous by Sanger sequencing. Her symptoms and nutritional status improved significantly after 1 year of a fat-restricted enteral diet. Weight for age and weight for length increased from -5.0 SDS and -4.0 SDS at 3 months to +0.08 SDS and +1.75 SDS at 15 months, respectively. This report expanded the mutation spectrum of DGAT1-related CDD7 and enriched our knowledge of the clinical features. Moreover, early fat-restricted enteral diet intervention was suggested for the treatment of such patients.

12.
Nat Commun ; 15(1): 7610, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39218971

RESUMO

Single-cell transcriptomics has emerged as a powerful tool for understanding how different cells contribute to disease progression by identifying cell types that change across diseases or conditions. However, detecting changing cell types is challenging due to individual-to-individual and cohort-to-cohort variability and naive approaches based on current computational tools lead to false positive findings. To address this, we propose a computational tool, scDist, based on a mixed-effects model that provides a statistically rigorous and computationally efficient approach for detecting transcriptomic differences. By accurately recapitulating known immune cell relationships and mitigating false positives induced by individual and cohort variation, we demonstrate that scDist outperforms current methods in both simulated and real datasets, even with limited sample sizes. Through the analysis of COVID-19 and immunotherapy datasets, scDist uncovers transcriptomic perturbations in dendritic cells, plasmacytoid dendritic cells, and FCER1G+NK cells, that provide new insights into disease mechanisms and treatment responses. As single-cell datasets continue to expand, our faster and statistically rigorous method offers a robust and versatile tool for a wide range of research and clinical applications, enabling the investigation of cellular perturbations with implications for human health and disease.


Assuntos
COVID-19 , Células Dendríticas , RNA-Seq , SARS-CoV-2 , Análise de Célula Única , Transcriptoma , Análise de Célula Única/métodos , Humanos , COVID-19/virologia , COVID-19/genética , RNA-Seq/métodos , Células Dendríticas/metabolismo , SARS-CoV-2/genética , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Células Matadoras Naturais/metabolismo , Imunoterapia/métodos , Análise de Sequência de RNA/métodos , Análise da Expressão Gênica de Célula Única
14.
Sci Rep ; 14(1): 20565, 2024 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-39232000

RESUMO

Studies on MECP2 function and its implications in Rett Syndrome (RTT) have traditionally centered on neurons. Here, using human embryonic stem cell (hESC) lines, we modeled MECP2 loss-of-function to explore its effects on astrocyte (AST) development and dysfunction in the brain. Ultrastructural analysis of RTT hESC-derived cerebral organoids revealed significantly smaller mitochondria compared to controls (CTRs), particularly pronounced in glia versus neurons. Employing a multiomics approach, we observed increased gene expression and accessibility of a subset of nuclear-encoded mitochondrial genes upon mutation of MECP2 in ASTs compared to neurons. Analysis of hESC-derived ASTs showed reduced mitochondrial respiration and altered key proteins in the tricarboxylic acid cycle and electron transport chain in RTT versus CTRs. Additionally, RTT ASTs exhibited increased cytosolic amino acids under basal conditions, which were depleted upon increased energy demands. Notably, mitochondria isolated from RTT ASTs exhibited increased reactive oxygen species and influenced neuronal activity when transferred to cortical neurons. These findings underscore MECP2 mutation's differential impact on mitochondrial and metabolic pathways in ASTs versus neurons, suggesting that dysfunctional AST mitochondria may contribute to RTT pathophysiology by affecting neuronal health.


Assuntos
Astrócitos , Proteína 2 de Ligação a Metil-CpG , Mitocôndrias , Mutação , Neurônios , Espécies Reativas de Oxigênio , Síndrome de Rett , Proteína 2 de Ligação a Metil-CpG/metabolismo , Proteína 2 de Ligação a Metil-CpG/genética , Mitocôndrias/metabolismo , Astrócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Humanos , Neurônios/metabolismo , Síndrome de Rett/genética , Síndrome de Rett/metabolismo , Síndrome de Rett/patologia , Células-Tronco Embrionárias Humanas/metabolismo , Linhagem Celular
15.
Zhonghua Yi Xue Za Zhi ; 104(35): 3328-3333, 2024 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-39266497

RESUMO

Objective: To investigate the efficacy of Da Vinci robotic transanal minimally invasive surgery (R-TAMIS) for rectal neoplasms. Methods: The patients of rectal neoplasms who underwent R-TAMIS and were regularly followed up at the First Medical Center of Chinese PLA General Hospital from January 2021 to January 2024 were retropectively selected. Follow-up visits were conducted at 1, 2, and 4 weeks postoperatively, and then every 3 months until January 20, 2024. The perioperative situation, postoperative histopathological results, and follow-up status of the patients were observed. Results: A total of 17 patients were included, including 10 males and 7 females, aged 35-80 (59±13) years. Eleven patients underwent surgery using the da Vinci® Si robot, while 6 patients underwent surgery using the da Vinci® Xi robot. The height of the resected tumor from the anal verge [M (Q1, Q3)] was 3.5 (3.0, 3.8) cm. The total operative time was 55.0 (50.0, 55.0) minutes, the platform installation time was 32.5 (30.0, 35.0) minutes. The actual surgical operation time was 22.5 (20.0, 27.5) minutes. Intraoperative blood loss was 9.2 (5.0, 10.0) ml. The postoperative hospital stay was 3.2 (3.0, 3.8) days. The total treatment cost was (29 447±4 765) yuan. Two patients who achieved clinical complete remission after neoadjuvant chemoradiotherapy experienced incision dehiscence one week postoperatively, which was resolved after four weeks of rectal irrigation therapy. All surgical specimens were intact, and all resection margins were negative. A total of 44(31,73) weeks were followed up, without local recurrence or distant metastasis. Conclusion: Da Vinci robotic transanal minimally invasive local resection may be a safe and feasible treatment option for rectal neoplasms.


Assuntos
Procedimentos Cirúrgicos Minimamente Invasivos , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Humanos , Neoplasias Retais/cirurgia , Masculino , Pessoa de Meia-Idade , Feminino , Procedimentos Cirúrgicos Robóticos/métodos , Idoso , Adulto , Idoso de 80 Anos ou mais , Canal Anal/cirurgia , Duração da Cirurgia , Cirurgia Endoscópica Transanal/métodos , Resultado do Tratamento , Tempo de Internação
16.
Zhonghua Yan Ke Za Zhi ; 60(9): 773-775, 2024 Sep 11.
Artigo em Chinês | MEDLINE | ID: mdl-39267556

RESUMO

The patient is a 28-year-old male who presented with hemifield slide for 10 months following surgery for a large pituitary adenoma. A comprehensive ophthalmological examination and visual function tests were conducted, including best corrected visual acuity, visual field, stereopsis, accommodative convergence, Worth four-dot test, and prism cover test for quantifying strabismus, along with assessments using a depression scale and a visual function questionnaire. Rehabilitation plans included applying press-on prisms to correct vertical strabismus, binocular vision training, and saccadic training. After rehabilitation, the patient was able to maintain binocular single vision at near and intermediate distances, experienced improved visual comfort, and showed significant improvements in scores on the depression scale and visual function questionnaire.


Assuntos
Neoplasias Hipofisárias , Humanos , Masculino , Adulto , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/reabilitação , Acuidade Visual , Visão Binocular , Estrabismo/cirurgia , Adenoma/cirurgia , Adenoma/reabilitação , Campos Visuais
17.
Zhonghua Gan Zang Bing Za Zhi ; 32(8): 753-760, 2024 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-39267570

RESUMO

Objective: To analyze the blood differential metabolites of patients with intrahepatic cholestasis (IHC) by liquid chromatography-mass spectrometry metabolomics technology so as to find potential metabolic target. Method: Serum samples were collected from thirty patients with intrahepatic cholestasis and thirty healthy individuals after metabolomics analysis. The differential metabolites were initially screened based on the multiple differences and significance. KEGG enrichment analysis was performed on the differential metabolites to determine the candidate targets. The potential clinical application value of these characteristic metabolites was analyzed using the receiver operating characteristic curve. Result: A total of thirty patients with intrahepatic cholestasis and thirty healthy adults were included. The age difference between the two groups was not statistically significant (P>0.05). The clinical condition was consistent with the statistically significant differences in liver biochemical indicators, blood routine, coagulation, and inflammatory indicators between the two groups (P<0.05). Furthermore, a blood metabolomics screening analysis revealed 99 differentially expressed metabolites associated with intrahepatic cholestasis. Of these, 15 showed statistically significant differences. Glucose, lipid, and energy metabolisms were the various primary types of differential metabolites involved. The receiver operating characteristic curve>0.9 included the following twelve kinds of metabolites: 1H-indole-3-carboxaldehyde, 6-hydroxy-1H-indole-3-acetamide, phenylalanyl tryptophan, 1-methylguanosine, 2-ethoxy-5-methylpyrazine, p-hydroxybenzaldehyde, 5-(2-chlorophenyl)-3,4-dihydro-2H-pyrrole, methylthioadenosine, alanylisoleucine, anabsinthin, N-acetyl-DL-histidine monohydrate, N-methylnicotinamide, and others. The fifteen metabolites that were previously identified and calculated according to the differential quantitative value of the metabolite corresponding ratio exhibited fold-changes in the upregulated and downregulated potential biomarkers (phenylalanine tryptophan, phenylalanine, 5'-methylthioadenosine, anabsinthin, and N-methylnicotinamide) in combination with the area under the receiver operating characteristic curve>0.9. Conclusion: Phenylalanyl tryptophan, phenylalanylalanine, 5'-methylthioadenosine, anabsinthin, and N-methylnicotinamide may serve as potential metabolic markers to distinguish patients with cholestasis from healthy controls. N-methylnicotinamide, among them, is of great importance as a potential marker.


Assuntos
Biomarcadores , Colestase Intra-Hepática , Metabolômica , Humanos , Metabolômica/métodos , Biomarcadores/sangue , Colestase Intra-Hepática/sangue , Colestase Intra-Hepática/diagnóstico , Colestase Intra-Hepática/metabolismo , Cromatografia Líquida/métodos , Estudos de Casos e Controles , Espectrometria de Massas/métodos , Feminino , Masculino , Espectrometria de Massa com Cromatografia Líquida
19.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(8): 1476-1484, 2024 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-39276043

RESUMO

OBJECTIVE: To investigate the effects of kuwanon G (KG) on proliferation, apoptosis, migration and invasion of gastric cancer cells and the molecular mechanisms. METHODS: The effects of KG on proliferation and growth of gastric cancer cells were assessed with CCK-8 assay and cell clone formation assay, by observing tumor formation on the back of nude mice and using immunohistochemical analysis of Ki-67. The effect of KG on cell apoptosis was analyzed using Annexin V-FITC/PI apoptosis detection kit, Western blotting and TUNEL staining. The effects of KG on cell migration and invasion were detected using Transwell migration and invasion assay and Western blotting for matrix metalloproteinase (MMP). The role of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in KG-mediated regulation of gastric cancer cell proliferation, migration, and invasion was verified by Western blotting and rescue assay. RESULTS: KG significantly inhibited proliferation and reduced clone formation ability of gastric cancer cells in a concentration-dependent manner (P < 0.05). KG treatment also increased apoptosis, enhanced the expressions of cleaved caspase-3 and Bax, down-regulated Bcl-2, lowered migration and invasion capacities and inhibited the expression of MMP2 and MMP9 in gastric cancer cells (P < 0.05). Mechanistic validation showed that KG inhibited the activation of the PI3K/AKT/mTOR pathway, and IGF-1, an activator of the PI3K/AKT/mTOR pathway, reversed the effects of KG on proliferation, migration and invasion of gastric cancer cells (P < 0.05). CONCLUSION: KG inhibits proliferation, migration and invasion and promotes apoptosis of gastric cancer cells at least in part by inhibiting the activation of the PI3K/AKT/mTOR pathway.


Assuntos
Apoptose , Movimento Celular , Proliferação de Células , Camundongos Nus , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Neoplasias Gástricas , Serina-Treonina Quinases TOR , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos , Apoptose/efeitos dos fármacos , Animais , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Invasividade Neoplásica , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Caspase 3/metabolismo
20.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(8): 1571-1581, 2024 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-39276053

RESUMO

OBJECTIVE: To explore the mechanism underlying the protective effect of Lonicerae japonicae flos (LJF) extract against doxorubicin (DOX) -induced liver injury in mice. METHODS: Network pharmacology methods were used to obtain the intersection genes between LJF targets and disease targets, based on which the protein-protein interaction (PPI) network was constructed using STRING database for screening the core targets using Cytoscape software. DAVID database was used for bioinformatics analysis, and the core components and core targets were verified using molecular docking study. In a mouse model of DOX-induced liver injury, the effect of LJF extract on liver pathologies, serum levels of ALT and AST, and hepatic expressions of HYP, ROS, TNF-α, IL-6, COL-Ⅳ and P53 proteins were evaluated using HE and Masson staining, ELISA, and Western blotting. RESULTS: We identified 12 core targets from 43 intersection genes involving cancer pathway, IL-17 signaling pathway, and TNF signaling pathways. Molecular docking study suggested that 10 core components of LJF could bind to different core targets. The mice with DOX-induced liver injury showed elevated serum AST and ALT levels with obvious liver injury and fibrosis, increased ROS content, and enhanced expressions of TNF-α, IL-6, HYP, COL-Ⅳ and P53 proteins in the liver tissue. All these changes in the mouse models were significantly alleviated by treatment with LJF extract, suggesting obviously lowered levels of oxidative stress, inflammation and fibrosis in the liver tissues. CONCLUSION: LJF extract is capable of alleviating DOX-induced liver injury in mice by downregulating Trp53, TNF and IL-6 to reduce liver oxidative stress, inflammation and fibrosis.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Doxorrubicina , Interleucina-6 , Lonicera , Simulação de Acoplamento Molecular , Fator de Necrose Tumoral alfa , Animais , Doxorrubicina/efeitos adversos , Camundongos , Lonicera/química , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Extratos Vegetais/farmacologia , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Proteína Supressora de Tumor p53/metabolismo , Substâncias Protetoras/farmacologia , Mapas de Interação de Proteínas , Transdução de Sinais/efeitos dos fármacos , Farmacologia em Rede
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