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1.
Biomaterials ; 313: 122816, 2025 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39250864

RESUMO

Pro-fibrotic M2-like macrophages are widely implicated in the pathogenesis and progression of lung fibrosis due to their production of pro-fibrotic growth factors and cytokines. Yeast beta-glucan (YBG) microparticles have shown potential as immunomodulators that can convert macrophage polarization from a pro-fibrotic phenotype to an anti-fibrotic phenotype through the engagement of the Dectin-1 receptor. However, the processing conditions used to fabricate YBG microparticles can lead to unpredictable immunomodulatory effects. Herein, we report the use of Pressurized Gas eXpanded liquids (PGX) Technology® to fabricate YBG (PGX-YBG) microparticles with higher surface areas, lower densities, and smaller and more uniform size distributions compared to commercially available spray-dried YBGs. PGX-YBG is shown to activate Dectin-1 more efficiently in vitro while avoiding significant TLR 2/4 activation. Furthermore, PGX-YBG microparticles effectively modulate M2-like fibrosis-inducing murine and human macrophages into fibrosis-suppressing macrophages both in vitro as well as in ex vivo precision-cut murine lung slices, suggesting their potential utility as a therapeutic for addressing a broad spectrum of fibrotic end-point lung diseases.


Assuntos
Macrófagos , beta-Glucanas , Animais , beta-Glucanas/química , beta-Glucanas/farmacologia , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Humanos , Camundongos Endogâmicos C57BL , Lectinas Tipo C/metabolismo , Células RAW 264.7 , Fibrose Pulmonar/patologia , Fibrose Pulmonar/tratamento farmacológico , Saccharomyces cerevisiae , Tamanho da Partícula
3.
Artigo em Inglês | MEDLINE | ID: mdl-39289903

RESUMO

OBJECTIVE: Performing obstetric ultrasound scans is challenging for inexperienced operators; therefore, the prenatal screening artificial intelligence system (PSAIS) software was developed to provide real-time feedback and guidance for trainees during their scanning procedures. The aim of this study was to investigate the potential benefits of utilizing such an artificial intelligence system to enhance the efficiency of obstetric ultrasound training in acquiring and interpreting standard basic views. METHODS: A prospective, single-center randomized controlled study was conducted at The First Affiliated Hospital of Sun Yat-sen University. From September 2022 to April 2023, residents with no prior obstetric ultrasound experience were recruited and assigned randomly to either a PSAIS-assisted training group or a conventional training group. Each trainee underwent a four-cycle practical scan training program, performing 20 scans in each cycle on pregnant volunteers at 18-32 gestational weeks, focusing on acquiring and interpreting standard basic views. At the end of each cycle, a test scan evaluated trainees' ability to obtain standard ultrasound views without PSAIS assistance, and image quality was rated by both the trainees themselves and an expert (in a blinded manner). The primary outcome was the number of training cycles required for each trainee to meet a certain standard of proficiency (i.e. end-of-cycle test scored by the expert at ≥ 80%). Secondary outcomes included the expert ratings of the image quality in each trainee's end-of-cycle test and the discordance between ratings by trainees and the expert. RESULTS: In total, 32 residents and 1809 pregnant women (2720 scans) were recruited for the study. The PSAIS-assisted trainee group required significantly fewer training cycles compared with the non-PSAIS-assisted group to meet quality requirements (P = 0.037). Based on the expert ratings of image quality, the PSAIS-assisted training group exhibited superior ability in acquiring standard imaging views compared with the conventional training group in the third (P = 0.012) and fourth (P < 0.001) cycles. In both groups, the discordance between trainees' ratings of the quality of their own images and the expert's ratings decreased with increasing training time. A statistically significant difference in overall trainee-expert rating discordance between the two groups emerged at the end of the first training cycle and remained at every cycle thereafter (P < 0.013). CONCLUSION: By assisting inexperienced trainees in obtaining and interpreting standard basic obstetric scanning views, the use of artificial intelligence-assisted systems has the potential to improve training effectiveness. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

5.
Zhonghua Bing Li Xue Za Zhi ; 53(8): 789-796, 2024 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-39103259

RESUMO

Objective: To analyze the clinicopathological features of prostate cancers with BRCA2 pathogenic mutations, and the association between BRCA2 pathogenic mutation and clinicopathological characteristics. Patient survivals were also examined. Methods: Clinicopathological data of 249 prostate cancer patients who underwent genetic testing in West China Hospital of Sichuan University, Chengdu, China from June 2014 to August 2021 were collected. A retrospective analysis of histopathological morphology, clinicopathological characteristics, and patient survivals was conducted. Results: The genetic testing in the 249 prostate cancer patients showed a pathogenic mutation of DNA damage repair gene (DRG) in 73 cases (73/249, 29.3%), including 22 cases (8.8%) with BRCA2 pathogenic mutation and 51 cases with pathogenic mutations of other DRG. Among the 22 patients with BRCA2 pathogenic mutation, 14 patients (5.6%) harbored germline mutations and 8 patients (3.2%) somatic mutations. Their ages ranged from 48 to 91 years, with a median of 67 years. Seventeen patients (77.3%) had distant metastasis, including 16 cases with bone metastasis and 1 case with multiple metastases. Thirteen patients (59.1%) were castration-resistant prostate cancer. The histological type was mainly classical prostatic acinar adenocarcinoma, including 16 cases (72.7%) with intraductal carcinoma of the prostate (IDC-P). Six cases (27.3%) showed focal neuroendocrine differentiation. Perineural/vascular invasion and extraprostatic extension were seen in 11 cases (50.0%) and 8 cases (36.4%), respectively. The Gleason scores of 19 patients (86.4%) were≥8. IDC-P was more commonly found in patients with BRCA2 germline pathogenic mutation than those with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.002). With a total follow-up time of 189 months, the median overall survival (OS) was 132.3 months. Patients with DRG pathogenic mutation had shorter OS than those with no-DRG pathogenic mutation (P=0.040). The OS of patients with BRCA2 germline pathogenic mutation did not significantly differ from that of patients with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.216). Conclusions: The presence of BRCA2 gene pathogenic mutation is common in the prostate cancers with high Gleason grade, advanced clinical stage, and castration resistance. IDC-P is more commonly noted in cases with BRCA2 germline pathogenic mutation than those without. Patients with DRG pathogenic mutation have shorter OS than those with no-DRG pathogenic mutation, but there is no significant association between BRCA2 pathogenic mutations and OS.


Assuntos
Proteína BRCA2 , Mutação , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteína BRCA2/genética , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Idoso de 80 Anos ou mais , Neoplasias Ósseas/genética , Neoplasias Ósseas/secundário , Neoplasias Ósseas/patologia
6.
Biomed Pharmacother ; 178: 117145, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39038374

RESUMO

Vitamin D is a critical fat-soluble vitamin for the nervous system. Research suggests a potential link between vitamin D deficiency and attention-deficit hyperactivity disorder (ADHD), particularly in children and adolescents. The core symptoms of ADHD are associated with deficits in striatal functions, and maintaining sufficient levels of vitamin D may help prevent or alleviate ADHD symptoms. However, the molecular changes in the striatum caused by vitamin D supplementation that may contribute to the brain processes linked to ADHD symptoms remain unclear. In this study, we established a mouse model fed diets with three different dose gradients of vitamin D3 (0, 500, and 2000 IU/kg·day) from postnatal day 21 (P21) to 14 weeks of age. Striatal tissues from mice with gradient vitamin D3 intake were subjected to reduced representation bisulfite sequencing (RRBS), RNA-sequencing, and neurotransmitter profiling by liquid chromatography-mass spectrometry (LC-MS). Our findings indicate that vitamin D supplementation since childhood influenced the overall landscape of DNA methylations and the expression of many genes involved in critical neurological functions in a dose-dependent manner. Additionally, our data demonstrate how vitamin D modulated neuropeptide signaling pathways, as well as cholinergic and dopaminergic synapses in the striatum, through an orchestrated mechanism involving epigenetic and transcriptional regulations. Furthermore, we observed a synergistic effect of vitamin D on dopamine release following acute methylphenidate injection into our mouse model. In summary, this study provides mechanistic insights into how dietary vitamin D supplementation since childhood can modulate specific signal transductions among striatal cells, underscoring the importance of vitamin D supplementation for ADHD management.


Assuntos
Corpo Estriado , Suplementos Nutricionais , Camundongos Endogâmicos C57BL , Transdução de Sinais , Vitamina D , Animais , Transdução de Sinais/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/efeitos dos fármacos , Camundongos , Masculino , Vitamina D/farmacologia , Metilação de DNA/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Colecalciferol/farmacologia , Colecalciferol/administração & dosagem , Multiômica
8.
Zhonghua Bing Li Xue Za Zhi ; 53(6): 521-527, 2024 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-38825894

RESUMO

Pathological diagnosis is vital in medicine. Developing and implementing high-quality pathology guidelines and consensus can enhance disease diagnosis accuracy and reduce unnecessary misdiagnosis and missed diagnoses. This article will cover the current status of pathology guidelines and consensus, methods for high-quality development, and the distinctions between them. Additionally, it will provide thoughts and suggestions for promoting their development in China.


Assuntos
Consenso , Humanos , Guias de Prática Clínica como Assunto , China , Patologia/normas
9.
Clin Radiol ; 79(9): e1108-e1116, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38849236

RESUMO

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.


Assuntos
Aprendizado de Máquina , Imageamento por Ressonância Magnética , Meningioma , Neurilemoma , Nomogramas , Humanos , Meningioma/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Neurilemoma/diagnóstico por imagem , Neurilemoma/cirurgia , Imageamento por Ressonância Magnética/métodos , Adulto , Diagnóstico Diferencial , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Idoso , Estudos Retrospectivos , Radiômica
11.
Eur Rev Med Pharmacol Sci ; 28(6): 2186-2191, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38567581

RESUMO

OBJECTIVE: To investigate the efficacy and safety of tirofiban and low molecular weight heparin (LMWH) in the treatment of patients undergoing acute progressive pontine infarction. PATIENTS AND METHODS: Patients with acute progressive pontine infarction who were hospitalized in the Neurology Department from June 2021 to June 2023 were included in the study and randomly divided into two groups, namely the experimental group (tirofiban group) and the control group (LMWH group). All patients in both groups were required to receive conventional comprehensive treatment and dual antiplatelet therapy with aspirin + clopidogrel at the beginning of admission. The National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index (BI) were used to evaluate the neurological deficits on the first day of admission, the next day with stroke progression, and at discharge after treatment with tirofiban and LMWH, respectively in the two groups. The modified Rankin Scale was employed to assess prognosis on the 90th day after treatment. Clinical adverse events were followed up for 90 days, comparing the clinical efficacy and safety of the two treatment methods. RESULTS: There was no statistical significance in NIHSS score and Barthel Index between the tirofiban group and the LMWH group on the first day of admission and the next day with stroke progression (p > 0.05). After stroke progression, tirofiban and LMWH were separately used for treatment in the two groups. We found that the NIHSS score of the tirofiban group was lower than that of the LMWH group, and the Barthel Index score was higher than that of the LMWH group at discharge (p < 0.05). After three months of follow-up, the mRS score of the tirofiban group was dramatically higher than that of the LMWH group (p < 0.05). No significant harmful or adverse reactions, such as bleeding events, were found in the two groups (p > 0.05). CONCLUSIONS: Tirofiban may be more effective and safer than LMWH in controlling the progression of acute pontine infarction, but further and large-sample studies are still needed to confirm this finding.


Assuntos
Heparina de Baixo Peso Molecular , Acidente Vascular Cerebral , Humanos , Fibrinolíticos , Heparina de Baixo Peso Molecular/uso terapêutico , Infarto/induzido quimicamente , Infarto/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Tirofibana/uso terapêutico , Resultado do Tratamento
13.
Eur Rev Med Pharmacol Sci ; 28(4): 1610-1613, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38436193

RESUMO

BACKGROUND: Clinical pharmacists identified contraindications in two cases concerning the co-administration of cefoperazone and ambroxol hydrochloride injection, prompting a thorough investigation. CASE PRESENTATION: Clinically, two cases of contraindications for the co-administration of cefoperazone and ambroxol hydrochloride injection were discovered. After the intervention and analysis by clinical pharmacists, the possible reason could be the precipitation of free alkali due to the immediate administration of ambroxol after the infusion of cefoperazone. Clinical pharmacists suggested avoiding the co-administration of the two and recommended flushing the intravenous lines with 5% glucose injection or 0.9% sodium chloride injection during intravenous infusion to prevent direct drug interaction causing precipitation, thereby reducing the occurrence of adverse events. No adverse events occurred after the intervention, and no harm was caused to the patients. CONCLUSIONS: The co-administration of cefoperazone and ambroxol hydrochloride injection can lead to the precipitation of free alkali, posing a risk of adverse events. Clinical pharmacists' intervention could prevent this interaction. This practice has been shown to be effective, with no subsequent adverse events reported.


Assuntos
Ambroxol , Farmacêuticos , Humanos , Cefoperazona/uso terapêutico , Contraindicações , Álcalis
15.
Zhonghua Liu Xing Bing Xue Za Zhi ; 45(1): 139-147, 2024 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-38228537

RESUMO

Objective: To compare the prevalence of frailty and related factors in middle-aged and elderly people aged ≥45 years in island and mountainous areas of Taizhou, Zhejiang Province. Methods: Based on cross-sectional design, stratified cluster sampling and quota sampling methods were adopted. One administrative district was randomly selected from each of six coastal and three inland administrative districts in Taizhou during July to August, representing two different geographical terrains. In the island area (Jiaojiang District), all residents aged ≥45 years were included by cluster sampling. In the mountainous area (Xianju County), participants were selected through quota sampling, with same gender and age distributions. Data about their demographic characteristics, lifestyle and health-related factors were collected through questionnaire surveys and laboratory examinations. The prevalence of frailty was assessed using the Fried frailty phenotype scale. Hierarchical analysis and multivariate logistic regression analysis were used to compare the influencing factors of frailty. Results: A total of 1 011 local residents were studied, in whom island and mountainous residents accounted for 48.1% (486/1 011) and 51.9% (525/1 011) respectively; men and women accounted for 45.9% (464/1 011) and 54.1% (547/1 011) respectively. Middle-aged (45-49 years), younger elderly (60-74 years), and older elderly (≥75 years) residents accounted for 38.6% (390/1 011), 44.6% (451/1 011), and 16.8% (170/1 011) respectively. The overall prevalence rate of frailty was 3.6% (36/1 011), the prevalence rate was 3.7% (17/464) in men and 3.5% (19/547) in women. The prevalence rates in age groups 45-59,60-74 years and ≥75 years were 0.3% (1/390), 2.2% (10/451), and 14.7% (25/170), respectively. The prevalence rates of frailty and pre-frailty in island area were 6.0% (29/486) and 39.1% (190/486), respectively, which was higher than those in mountainous area (1.3%, 7/525) and (30.9%, 162/525). After adjusting for potential confounding factors, the risk for frailty in island residents was significantly higher than that in mountainous residents (aOR=1.55,95%CI: 1.07-2.25,P=0.019). In island area, older age (60-74 years:aOR=2.52,95%CI: 1.56-4.13; ≥75 years:aOR=11.65,95%CI:5.38-26.70), being women (aOR=1.94,95%CI: 1.20-3.17), suffering from depression (aOR=1.09,95%CI:1.02-1.17) were associated with frailty symptoms. In mountainous area, older age was also associated with an increased risk of frailty symptoms, but the OR value was lower than those in island area (60-74 years: aOR=1.74,95%CI:1.04-2.94;≥75 years: aOR=4.78,95%CI:2.45-9.50). Polydrug use (aOR=2.08,95%CI: 1.14-3.80) and suffering from depression (aOR=1.10,95%CI: 1.02-1.18) had significant positive association with frailty symptoms. Higher education level had significant negative association with frailty symptoms (junior high school: aOR=0.40,95%CI: 0.21-0.75; senior high school and technical secondary school: aOR=0.29,95%CI: 0.15-0.53; college or above:aOR=0.22,95%CI: 0.11-0.42). Conclusions: The prevalence of frailty in middle-aged and elderly community residents was significantly higher in island area than in mountainous area in Taizhou. The frailty-related factors varied with area. The elderly people (≥75 years) and women in island area had higher risk for frailty. Older age and suffering from depression were the independent risk factors for frailty. It is necessary to pay attention to the health risk factors and special environment in island area, and take comprehensive intervention measures to delay the process of debilitation and improve the quality of life of middle-aged and elderly people.


Assuntos
Fragilidade , Idoso , Masculino , Pessoa de Meia-Idade , Humanos , Feminino , Fragilidade/epidemiologia , Qualidade de Vida , Prevalência , Estudos Transversais , Fatores de Risco , Idoso Fragilizado
16.
Zhonghua Zhong Liu Za Zhi ; 46(1): 19-39, 2024 Jan 23.
Artigo em Chinês | MEDLINE | ID: mdl-38246778

RESUMO

Lung cancer (LC) is the leading cause of death among patients with cancer both in worldwide and China. China accounts for 11.4% of the total number of cancer cases and 18.0% of the total number of cancer deaths in the world. Standardizing the diagnosis and treatment of LC is a key measure to improve the survival rate of LC patients and reduce the mortality rate. However, county hospitals generally face the problem of inaccessibility to advanced diagnostic and treatment technologies. Therefore, when developing quality control standards and clinical diagnosis and treatment specifications, it is necessary to combine the actual situation of county hospitals and formulate specific recommendations. The recommendations of treatment measures also need to consider the approval status of indications and whether it is included in the National Reimbursement Drug List (NRDL), to ensure the access to medicines. In order to solve the above problems, based on existing guidelines at home and abroad and the clinical work characteristics of county hospitals, the first clinical pathway in Chinese county for LC diagnosis and treatment (2023 edition) was compiled. This pathway elaborated on the imaging diagnosis, pathological diagnosis, molecular testing, and precision medicine based on histological-pathological types, tumor-node-metastasis (TNM) classification, and molecular classification, developed different diagnosis and treatment processes for different types of LC patients. Simultaneously, according to the actual work situation of county hospitals, the diagnosis and treatment recommendations in clinical scenarios are divided into basic strategies and optional strategies for elaboration. The basic strategies are the standards that county hospitals must meet, while the optional strategies provide more choices for hospitals, which are convenient for county doctors to put into clinical practice. All the recommended diagnostic and treatment plans strictly refer to existing guidelines and consensus, ensuring the scientificity.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Procedimentos Clínicos , Medicina de Precisão , Diagnóstico Diferencial , China
17.
Animal ; 18(1): 101052, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38181459

RESUMO

Low-tannin sorghum is an excellent energy source in pig diets. However, sorghum contains several anti-nutritional factors that may have negative effects on nutrient digestibility. The impacts of proteases on growth performance, nutrient digestibility, blood parameters, and gut microbiota of growing pigs fed sorghum-based diets were studied in this study. Ninety-six pigs (20.66 ± 0.65 kg BW) were allocated into three groups (eight pens/group, four pigs/pen): (1) CON (control diet, sorghum-based diet included 66.98% sorghum), (2) PRO1 (CON + 200 mg/kg proteases), (3) PRO2 (CON + 400 mg/kg proteases) for 28 d. No differences were observed in growth performance and apparent total tract digestibility (ATTD) of nutrients between CON and PRO1 groups. Pigs fed PRO2 diet had increased (P < 0.05) BW on d 21 and 28, and increased (P < 0.05) average daily gain during d 14-21 and the overall period compared with pigs fed CON diet. In addition, pigs fed PRO2 diet had improved (P < 0.05) ATTD of gross energy, CP, and DM compared with pigs fed CON and PRO1 diets. Pigs fed PRO2 diet had lower (P < 0.05) plasma globulin (GLB) level and higher (P < 0.05) plasma glucose, albumin (ALB) and immunoglobulin G levels, and ALB/GLB ratio than pigs fed CON and PRO1 diets. Furthermore, pigs fed PRO2 diet had decreased (P < 0.05) the relative abundance of Acidobacteriota at the phylum level and increased (P < 0.05) the relative abundance of Prevotella_9 at the genus level. The linear discriminant analysis effect size analysis also showed that pigs fed PRO2 diet had significantly enriched short-chain fatty acid-producing bacteria, such as Subdoligranulum and Parabacteroides. In conclusion, protease supplementation at 400 mg/kg improved the growth performance of growing pigs fed sorghum-based diets, which may be attributed to the improvement of nutrient digestibility, host metabolism, immune status and associated with the altered gut microbiota profiles.


Assuntos
Microbioma Gastrointestinal , Sorghum , Animais , Suínos , Peptídeo Hidrolases , Digestão , Ração Animal/análise , Dieta/veterinária , Nutrientes , Suplementos Nutricionais/análise , Fenômenos Fisiológicos da Nutrição Animal
18.
Zhonghua Xin Xue Guan Bing Za Zhi ; 52(1): 42-48, 2024 Jan 24.
Artigo em Chinês | MEDLINE | ID: mdl-38220454

RESUMO

Objective: To assess the association between body mass index (BMI) and major adverse cardiovascular and cerebrovascular events (MACCE) among patients with acute coronary syndrome (ACS). Methods: This was a multicenter prospective cohort study, which was based on the Improving Care for Cardiovascular Disease in China (CCC) project. The hospitalized patients with ACS aged between 18 and 80 years, registered in CCC project from November 1, 2014 to December 31, 2019 were included. The included patients were categorized into four groups based on their BMI at the time of admission: underweight (BMI<18.5 kg/m2), normal weight (BMI between 18.5 and 24.9 kg/m2), overweight (BMI between 25.0 and 29.9 kg/m2), and obese (BMI≥30.0 kg/m2). Multivariate logistic regression models was used to analyze the relationship between BMI and the risk of in-hospital MACCE. Results: A total of 71 681 ACS inpatients were included in the study. The age was (63.4±14.7) years, and 26.5% (18 979/71 681) were female. And the incidence of MACCE for the underweight, normal weight, overweight, and obese groups were 14.9% (322/2 154), 9.5% (3 997/41 960), 7.9% (1 908/24 140) and 7.0% (240/3 427), respectively (P<0.001). Multivariate logistic regression analysis showed a higher incidence of MACCE in the underweight group compared to the normal weight group (OR=1.30, 95%CI 1.13-1.49, P<0.001), while the overweight and obese groups exhibited no statistically significant difference in the incidence of MACCE compared to the normal weight group (both P>0.05). Conclusion: ACS patients with BMI below normal have a higher risk of in-hospital MACCE, suggesting that BMI may be an indicator for evaluating short-term prognosis in ACS patients.


Assuntos
Síndrome Coronariana Aguda , Sobrepeso , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Índice de Massa Corporal , Sobrepeso/complicações , Magreza/epidemiologia , Estudos Prospectivos , Fatores de Risco , Obesidade/complicações , Hospitais
19.
Proc Natl Acad Sci U S A ; 121(4): e2317283121, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38227666

RESUMO

Despite many clinical trials, CAR-T cells are not yet approved for human solid tumor therapy. One popular target is mesothelin (MSLN) which is highly expressed on the surface of about 30% of cancers including mesothelioma and cancers of the ovary, pancreas, and lung. MSLN is shed by proteases that cleave near the C terminus, leaving a short peptide attached to the cell. Most anti-MSLN antibodies bind to shed MSLN, which can prevent their binding to target cells. To overcome this limitation, we developed an antibody (15B6) that binds next to the membrane at the protease-sensitive region, does not bind to shed MSLN, and makes CAR-T cells that have much higher anti-tumor activity than a CAR-T that binds to shed MSLN. We have now humanized the Fv (h15B6), so the CAR-T can be used to treat patients and show that h15B6 CAR-T produces complete regressions in a hard-to-treat pancreatic cancer patient derived xenograft model, whereas CAR-T targeting a shed epitope (SS1) have no anti-tumor activity. In these pancreatic cancers, the h15B6 CAR-T replicates and replaces the cancer cells, whereas there are no CAR-T cells in the tumors receiving SS1 CAR-T. To determine the mechanism accounting for high activity, we used an OVCAR-8 intraperitoneal model to show that poorly active SS1-CAR-T cells are bound to shed MSLN, whereas highly active h15B6 CAR-T do not contain bound MSLN enabling them to bind to and kill cancer cells.


Assuntos
Neoplasias Pancreáticas , Receptores de Antígenos Quiméricos , Feminino , Humanos , Linhagem Celular Tumoral , Proteínas Ligadas por GPI/metabolismo , Mesotelina , Neoplasias Pancreáticas/tratamento farmacológico , Linfócitos T/metabolismo
20.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(1): 108-118, 2024 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-38293982

RESUMO

OBJECTIVE: To investigate the mechanism that mediates the inhibitory effect of Xinfeng Capsule (XFC) on interleukin (IL)-1ß-induced impairment of chondrocytes. METHODS: XFC-medicated serum was collected from SD rats with XFC gavage, and its optimal concentration for chondrocyte treatment was determined using Cell Counting Kit-8 assay and flow cytometry. Dual luciferase reporter analysis was performed to analyze the targeting relationship between miR-502-5p and TRAF2. In cultured human chondrocytes induced with IL-1ß, the effects of transfection with miR-502-5p inhibitor and XFC-medicated serum, alone or in combination, on expression levels of IL-1ß, tumor necrosis factor-α (TNF-α), IL-4, and IL-10 were examined with ELISA, and the changes in the expressions of collagen type Ⅱ alpha 1 (COL2A1), matrix metalloproteinase 13 (MMP13), adisintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), and miR-502-5p/TRAF2/NF-κB axis gene expression were detected using RT-qPCR, Western blotting, and immunofluorescence assay. RESULTS: In cultured human chondrocytes, treatment with IL-1ß significantly decreased the cell viability, increased cell apoptosis rate, lowered miR-502-5p, IL-4, IL-10, and COL2A1 expressions, and enhanced IL-1ß, TNF-α, ADAMTS5, MMP13, TRAF2, and NF-κB p65 expressions (P < 0.05), and these changes were significantly improved by treatment with XFC-medicated serum at the optimal concentration of 20% (P < 0.05). Transfection of the chondrocytes with miR-502-5p inhibitor resulted in elevated expressions of IL-1ß, TNF-α, ADAMTS5, MMP13, TRAF2, and NF-κB p65 and lowered expressions of miR-502-5p, IL-4, IL-10, and COL2A1, and XFC-medicated serum obviously reversed the effects of miR-502-5p inhibitor. CONCLUSION: XFC can inhibit IL-1ß-induced inflammatory response and ECM degradation in cultured human chondrocytes possibly by regulating the miR-502-5p/TRAF2/NF-κB axis.


Assuntos
Medicamentos de Ervas Chinesas , MicroRNAs , NF-kappa B , Humanos , Animais , Ratos , NF-kappa B/metabolismo , Interleucina-10 , Fator 2 Associado a Receptor de TNF/metabolismo , Fator 2 Associado a Receptor de TNF/farmacologia , Condrócitos/metabolismo , Interleucina-1beta/farmacologia , Interleucina-1beta/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , MicroRNAs/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-4/metabolismo , Ratos Sprague-Dawley , Inflamação/metabolismo , Matriz Extracelular/metabolismo
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