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1.
J Anat ; 244(3): 527-536, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38009263

RESUMO

Corticotropin-releasing hormone (CRH) neurons are densely distributed in the medial prefrontal cortex (mPFC), which plays a crucial role in integrating and processing emotional and cognitive inputs from other brain regions. Therefore, it is important to know the neural afferent patterns of mPFCCRH neurons, which are still unclear. Here, we utilized a rabies virus-based monosynaptic retrograde tracing system to map the presynaptic afferents of the mPFCCRH neurons throughout the entire brain. The results show that the mPFCCRH neurons receive inputs from three main groups of brain regions: (1) the cortex, primarily the orbital cortex, somatomotor areas, and anterior cingulate cortex; (2) the thalamus, primarily the anteromedial nucleus, mediodorsal thalamic nucleus, and central medial thalamic nucleus; and (3) other brain regions, primarily the basolateral amygdala, hippocampus, and dorsal raphe nucleus. Taken together, our results are valuable for further investigations into the roles of the mPFCCRH neurons in normal and neurological disease states. These investigations can shed light on various aspects such as cognitive processing, emotional modulation, motivation, sociability, and pain.


Assuntos
Encéfalo , Hormônio Liberador da Corticotropina , Camundongos , Animais , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Mapeamento Encefálico , Vias Neurais/fisiologia
2.
Mol Psychiatry ; 28(9): 3982-3993, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37735502

RESUMO

Tau protein is implicated in the pathogenesis of Alzheimer's disease (AD) and other tauopathies, but its physiological function is in debate. Mostly explored in the brain, tau is also expressed in the pancreas. We further explored the mechanism of tau's involvement in the regulation of glucose-stimulated insulin secretion (GSIS) in islet ß-cells, and established a potential relationship between type 2 diabetes mellitus (T2DM) and AD. We demonstrate that pancreatic tau is crucial for insulin secretion regulation and glucose homeostasis. Tau levels were found to be elevated in ß-islet cells of patients with T2DM, and loss of tau enhanced insulin secretion in cell lines, drosophila, and mice. Pharmacological or genetic suppression of tau in the db/db diabetic mouse model normalized glucose levels by promoting insulin secretion and was recapitulated by pharmacological inhibition of microtubule assembly. Clinical studies further showed that serum tau protein was positively correlated with blood glucose levels in healthy controls, which was lost in AD. These findings present tau as a common therapeutic target between AD and T2DM.


Assuntos
Doença de Alzheimer , Diabetes Mellitus Tipo 2 , Humanos , Camundongos , Animais , Insulina/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Secreção de Insulina , Proteínas tau/metabolismo , Pâncreas/metabolismo , Pâncreas/patologia , Glucose/metabolismo , Doença de Alzheimer/metabolismo
3.
Ann Hematol ; 103(4): 1345-1351, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38316642

RESUMO

Myelodysplastic syndrome (MDS) is a rare clonal hematopoietic disorder in children. The risk stratification system and treatment strategy for adults are unfit for children. The role of hypomethylating agents (HMAs) in higher-risk childhood MDS has not been identified. This study aimed to investigate the outcomes of hematopoietic stem cell transplantation (HSCT) in children with higher-risk MDS at one single center. A retrospective study was conducted in children with higher-risk MDS undergoing HSCT between September 2019 and March 2023 at Blood Diseases Hospital CAMS. The clinical characteristics and transplantation information were reviewed and analyzed. A total of 27 patients were analyzed, including 11 with MDS with excess blasts (MDS-EB), 14 with MDS-EB in transformation (MDS-EBt) or acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), and 2 with therapy-related MDS/AML (t-MDS/AML). Eight patients harbored monosomy 7. Before transplantation, induction therapy was administered to 25 patients, and 19 of them achieved bone marrow blasts <5% before HSCT. The stem cell source was unmanipulated-related bone marrow or peripheral blood stem cells for nineteen patients and unrelated cord blood for eight. All patients received decitabine-containing and Bu/Cy-based myeloablative conditioning; 26 patients achieved initial engraftment. The cumulative incidences of grade II-IV and grade III-IV acute graft-versus-host disease (GvHD) at 100 days were 65.4% and 42.3%, respectively. The incidence of cGvHD was 38.5%. The median follow-up was 26 (range 4-49) months after transplantation. By the end of follow-up, two patients died of complications and two died of disease progression. The probability of 3-year overall survival (OS) was 84.8% (95%CI, 71.1 to 98.5%). In summary, decitabine-containing myeloablative conditioning resulted in excellent outcomes for children with higher-risk MDS undergoing allogeneic HSCT.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Adulto , Criança , Humanos , Decitabina/uso terapêutico , Estudos Retrospectivos , Transplante Homólogo , Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes Mielodisplásicas/tratamento farmacológico , Condicionamento Pré-Transplante/métodos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle
4.
Pharmacol Res ; 200: 107070, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38218353

RESUMO

Fibrotic hypersensitivity pneumonitis (FHP) is a fatal interstitial pulmonary disease with limited treatment options. Lung macrophages are a heterogeneous cell population that exhibit distinct subsets with divergent functions, playing pivotal roles in the progression of pulmonary fibrosis. However, the specific macrophage subpopulations and underlying mechanisms involved in the disease remain largely unexplored. In this study, a decision tree model showed that matrix metalloproteinase-14 (MMP14) had higher scores for important features in the up-regulated genes in macrophages from mice exposed to the Saccharopolyspora rectivirgula antigen (SR-Ag). Using single-cell RNA sequencing (scRNA-seq) analysis of hypersensitivity pneumonitis (HP) mice profiles, we identified MMP14high macrophage subcluster with a predominant M2 phenotype that exhibited higher activity in promoting fibroblast-to myofibroblast transition (FMT). We demonstrated that suppressing toll-like receptor 2 (TLR2) and nuclear factor kappa-B (NF-κB) could attenuate MMP14 expression and exosome secretion in macrophages stimulation with SR-Ag. The exosomes derived from MMP14-overexpressing macrophages were found to be more effective in regulating the transition of fibroblasts through exosomal MMP14. Importantly, it was observed that the transfer of MMP14-overexpressing macrophages into mice promoted lung inflammation and fibrosis induced by SR-Ag. NSC-405020 binding to the hemopexin domain (PEX) of MMP-14 ameliorated lung inflammation and fibrosis induced by SR-Ag in mice. Thus, MMP14-overexpressing macrophages may be an important mechanism contributing to the exacerbation of allergic reactions. Our results indicated that MMP14 in macrophages has the potential to be a therapeutic target for HP.


Assuntos
Alveolite Alérgica Extrínseca , Pneumonia , Fibrose Pulmonar , Camundongos , Animais , Fibrose Pulmonar/metabolismo , Metaloproteinase 14 da Matriz/genética , Metaloproteinase 14 da Matriz/metabolismo , Alveolite Alérgica Extrínseca/metabolismo , Alveolite Alérgica Extrínseca/patologia , Macrófagos/metabolismo , Pneumonia/metabolismo , Camundongos Endogâmicos C57BL
5.
Anal Bioanal Chem ; 416(2): 583-595, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38062195

RESUMO

Arnebiae Radix, commonly known as "Zicao," can be easily confused with other compounding species, posing challenges for its clinical use. Here, we developed a comprehensive strategy to systematically characterize the diverse components across Arnebiae Radix and its three confusing species. First, an offline two-dimensional liquid chromatography (2D-LC) system integrating hydrophilic interaction chromatography (HILIC) and reverse phase (RP) separations was established, enabling effective separation and detection of more trace constituents. Second, a polygonal mass defect filtering (MDF) workflow was implemented to screen target ions and generate a precursor ion list (PIL) to guide multistage mass (MSn) data acquisition. Third, a three-step characterization strategy utilizing diagnostic ions and neutral losses was developed for rapid determination of molecular formulas, structure classes, and compound identification. This approach enabled systematic characterization of Arnebiae Radix and its three confusing species, with 437 components characterized including 112 shikonins, 22 shikonfurans, 144 phenolic acids, 131 glycosides, 18 flavonoids, and 10 other compounds. Additionally, 361, 230, 340, and 328 components were identified from RZC, YZC, DZC, and ZZC, respectively, with 142 common components and 30 characteristic components that may serve as potential markers for distinguishing the four species. In summary, this is the first comprehensive characterization and comparison of the phytochemical profiles of Arnebiae Radix and its three confusing species, advancing our understanding of this herbal medicine for quality control.


Assuntos
Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Espectrometria de Massa com Cromatografia Líquida , Flavonoides/análise , Íons
6.
Ecotoxicol Environ Saf ; 277: 116314, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38642409

RESUMO

Fine particulate matter (PM2.5) has been extensively implicated in the pathogenesis of neurodevelopmental disorders, but the underlying mechanism remains unclear. Recent studies have revealed that PM2.5 plays a role in regulating iron metabolism and redox homeostasis in the brain, which is closely associated with ferroptosis. In this study, the role and underlying mechanism of ferroptosis in PM2.5-induced neurotoxicity were investigated in mice, primary hippocampal neurons, and HT22 cells. Our findings demonstrated that exposure to PM2.5 could induce abnormal behaviors, neuroinflammation, and neuronal loss in the hippocampus of mice. These effects may be attributed to ferroptosis induced by PM2.5 exposure in hippocampal neurons. RNA-seq analysis revealed that the upregulation of iron metabolism-related protein Heme Oxygenase 1 (HO-1) and the activation of mitophagy might play key roles in PM2.5-induced ferroptosis in HT22 cells. Subsequent in vitro experiments showed that PM2.5 exposure significantly upregulated HO-1 in primary hippocampal neurons and HT22 cells. Moreover, PM2.5 exposure activated mitophagy in HT22 cells, leading to the loss of mitochondrial membrane potential, alterations in the expression of autophagy-related proteins LC3, P62, and mTOR, as well as an increase in mitophagy-related protein PINK1 and PARKIN. As a heme-degradation enzyme, the upregulation of HO-1 promotes the release of excess iron, genetically inhibiting the upregulation of HO-1 in HT22 cells could prevent both PM2.5-induced mitophagy and ferroptosis. Furthermore, pharmacological inhibition of mitophagy in HT22 cells reduced levels of ferrous ions and lipid peroxides, thereby preventing ferroptosis. Collectively, this study demonstrates that HO-1 mediates PM2.5-induced mitophagy-dependent ferroptosis in hippocampal neurons, and inhibiting mitophagy or ferroptosis may be a key therapeutic target to ameliorate neurotoxicity following PM2.5 exposure.


Assuntos
Ferroptose , Heme Oxigenase-1 , Hipocampo , Mitofagia , Neurônios , Material Particulado , Regulação para Cima , Animais , Material Particulado/toxicidade , Ferroptose/efeitos dos fármacos , Mitofagia/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Camundongos , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/genética , Regulação para Cima/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Poluentes Atmosféricos/toxicidade , Proteínas de Membrana
7.
Genomics ; 115(5): 110682, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37454939

RESUMO

Photoaging is unique to the skin and is accompanied by an increased risk of tumors. To explore the transcriptomic regulatory mechanism of skin photoaging, the epidermis, and dermis of 16 healthy donors (eight exposed and eight non-exposed) were surgically excised and detected using total RNA-Seq. Weighted gene co-expression network analysis (WGCNA) identified the most relevant modules with exposure. The hub genes were identified using correlation, p-value, and enrichment analysis. The critical genes were identified using Support Vector Machine-Recursive Feature Elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO) regression, then enriched using single-gene GSEA. A competitive endogenous RNA (ceRNA) network was constructed and validated using qRT-PCR. Compared with non-exposed sites, 430 mRNAs, 168 lncRNAs, and 136 miRNAs were differentially expressed in the exposed skin. WGCNA identified the module MEthistle and 12 intersecting genes from the 71 genes in this module. The enriched pathways were related to muscle. The critical genes were KLHL41, MYBPC2, and ERAP2. Single-gene GSEA identified the Hippo signaling pathway, basal cell carcinoma, cell adhesion molecules, and other pathways. Six miRNAs and 18 lncRNAs related to the critical genes constituted the ceRNA network and were verified using qPCR. The differential expression of KLHL41, MYBPC2, and ERAP2 at the protein level was verified using immunohistochemistry. KLHL41, MYBPC2, and ERAP2 genes are related to skin photoaging. The prediction model based on the three critical genes can indicate photoaging. These critical genes may have a role in skin photoaging by regulating cell growth, intercellular adhesion, and substance metabolism pathways.


Assuntos
MicroRNAs , RNA Longo não Codificante , Humanos , Pele , MicroRNAs/genética , Perfilação da Expressão Gênica , Transcriptoma , Redes Reguladoras de Genes , Aminopeptidases
8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(3): 257-265, 2024 Mar 10.
Artigo em Zh | MEDLINE | ID: mdl-38448011

RESUMO

OBJECTIVE: To assess the value of optical genome mapping (OGM) for the detection of chromosomal structural abnormalities including ring chromosomes, balanced translocations, and insertional translocations. METHODS: Clinical data of four patients who underwent pre-implantation genetic testing concurrently with OGM and chromosomal microarray analysis at the Center of Reproductive Medicine of the Sixth Affiliated Hospital of Sun Yat-sen University from January to October 2022 due to chromosomal structural abnormalities were selected as the study subjects. Some of the results were verified by multi-color fluorescence in situ hybridization. RESULTS: The OGM has successfully detected a balanced translocation and fine mapped the breakpoints in a patient. Among two patients with insertional translocations, OGM has provided more refined breakpoint locations than karyotyping analysis in a patient who had chromosome 3 inserted into chromosome 6 and determined the direction of the inserted fragment. However, OGM has failed to detect the chromosomal abnormality in a patient with chromosome 8 inserted into the Y chromosome. It has also failed to detect circular signals in a patient with ring chromosome mosaicism. CONCLUSION: OGM has successfully detected chromosomal structural variations in the four patients and provided assistance for their diagnosis.


Assuntos
Cromossomos Humanos Par 3 , Cromossomos em Anel , Humanos , Hibridização in Situ Fluorescente , Cromossomos Humanos Par 6 , Translocação Genética , Mapeamento Cromossômico
9.
Neurobiol Dis ; 188: 106344, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37926169

RESUMO

Epilepsy, a common complication of diffuse low-grade gliomas (DLGGs; diffuse oligodendroglioma and astrocytoma collectively), severely compromises the quality of life of patients. DLGG epileptogenicity may primarily be generated by interactions between the tumor and the neocortex. Neuronal uptake of dysfunctional mitochondria from the extracellular environment can lead to abnormal neuronal discharge. Mitochondrial dysfunction is frequently observed in gliomas that can transmigrate across the plasma membranes. Here, we examined the role of the Rho GTPase-activating protein 44 (RICH2) in mitochondrial dynamics and DLGG-related epilepsy. We investigated the association between mitochondrial and RICH2 expression in human DLGG tissues using immunohistochemistry. We examined the association between RICH2 and epilepsy in nude mouse glioma models by electrophysiology. The effect of RICH2 on mitochondrial morphology and calcium motility were assessed by single cell fluorescence microscopy. Quantitative RT-PCR (qRT-PCR) and Western blot analysis were performed to characterize RICH2 induced expression changes in the genes related to mitochondrial dynamics, mitogenesis and mitochondrial function. We found that RICH2 expression was higher in oligodendroglioma than in astrocytoma and was correlated with better prognosis and higher epilepsy rate in patients. The expression of mitochondria may be associated with clinical DLGG-related epilepsy and reduced by RICH2 overexpression. And RICH2 could promote DLGG-related epilepsy in tumorigenic nude mice. RICH2 overexpression decreased calcium flow and the mitochondria released from glioma cells (SW1088 and U251) into the extracellular environment, potentially via downregulation of MFN-1/MFN-2 levels which suggests reduced mitochondrial fusion. In addition, we observed decreased mitochondrial trafficking into neurons (released from glioma cells and trafficked into neurons), which could explain the higher incidence of DLGG-related epilepsy due to reduced neuroprotection. Furthermore, RICH2 downregulated MAPK/ERK/HIF-1 pathway. In conclusion, these results suggest that RICH2 could promote epilepsy by (i) inhibiting mitochondrial fusion via MFN downregulation and Drp-1 upregulation; (ii) altering the MAPK/ERK/Hif-1 signaling axis. RICH2 may be a potential target in the treatment of DLGG-related epilepsy.


Assuntos
Astrocitoma , Glioma , Oligodendroglioma , Animais , Camundongos , Humanos , Cálcio , Camundongos Nus , Qualidade de Vida , Mitocôndrias
10.
Vascular ; 31(6): 1209-1213, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35786111

RESUMO

INTRODUCTION: The stent revascularization for severely calcified renal artery lesions can be challenging, due to a deficiency in back-up force provided by the guide catheter. The aim of this report is to describe the use of the balloon anchoring technique to increase device maneuverability and deliverability after the failure of conventional renal artery revascularization. TECHNICAL NOTE: This technique was adopted in a patient with subtotal occlusive and severely calcified lesion in the proximal portion of the right main renal artery. Two guidewires were separately introduced into the proximal side branch (SB) and main branch (MB) of the renal artery. Anchor balloon inflated at low pressure in SB, anchoring the MB-wire and the guide catheter, thus giving us the ability to cross the tight calcified proximal cap of the MB lesion with a non-compliant balloon. After performing pre-dilatations and retrieving the anchor balloon, we implanted a balloon-expandable stent and achieved optimal final angiographic results. CONCLUSIONS: The balloon anchoring technique can improve device maneuverability and deliverability during various catheterization procedures. Our report firstly demonstrates how to perform the balloon anchoring technique in renal angioplasty treatment and then explains its effectiveness in revascularization of the renal artery with challenging anatomies.


Assuntos
Aterosclerose , Obstrução da Artéria Renal , Humanos , Artéria Renal/diagnóstico por imagem , Obstrução da Artéria Renal/diagnóstico por imagem , Obstrução da Artéria Renal/terapia , Procedimentos Cirúrgicos Vasculares , Stents
11.
BMC Med Educ ; 23(1): 44, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658530

RESUMO

BACKGROUND: In recent years, flipped classes have emerged and become popular in college medical education. However, due to the huge medical learning system and the limited pre-class study time of students, it is difficult to implement in all courses. And then we adopted the semi-flipped classes (SFCs) to evaluate its teaching effect. This study analysed three educational methods that can be used in oral medicine courses: online education, offline education, and semi-flipped classes. METHODS: We used two surveys to evaluate the three educational methods. In the first survey 46 teachers and 238 undergraduates shared their experience of the live-streaming and traditional offline courses offered in the different oral medicine curricula; we used anonymous questionnaires to evaluate their class experience. In the second survey 94 students shared their experience of the semi-flipped and traditional classrooms. Students who attended the SFCs in the experimental group learned about the oral mucosa disease by themselves using an online video course and then participated in offline interaction with teachers. The evaluation of the above educational methods was conducted using the anonymous questionnaires and final exam assessment. RESULTS: According to the first survey, teachers and students both agreed that the overall teaching experience and learning effectiveness in offline education are superior to those in online education. According to the second survey, students who participated in the SFCs performed better in the final exam than those who participated in the simple offline classes. Additionally, the survey showed that the new teaching method helped students gain more knowledge and positively influenced their clinical practice. CONCLUSIONS: Compared with the online and offline educational methods, the SFC showed better results in both the questionnaire and final exam assessment. Hence, the effectiveness of medical education can be improved by adopting a teaching mode that combines online and offline teaching methods. Scientific and logical SFCs designs, along with their effective implementation, would eventually make SFCs an important tool for medical education.


Assuntos
Medicina Bucal , Humanos , Currículo , Aprendizagem , Estudantes , Escolaridade , Aprendizagem Baseada em Problemas , Ensino
12.
Eur J Dent Educ ; 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38148502

RESUMO

INTRODUCTION: Virtual reality (VR) and haptic simulation technology have been increasingly implemented in dental training. Since the first haptic VR dental simulator (Simodont) was introduced 10 years ago, it has been applied in more than 40 universities in mainland China. This scoping review aimed to review literature, showcasing the teaching reform of dental virtual simulation in mainland China to global dental education peers. METHODS: This scoping review was conducted using the PRISMA extension for scoping review guidelines. Seven electronic databases were searched, and two reviewers independently performed the selection and characterization of the studies. RESULTS: The final scoping review included 12 studies. Four studies focused on the G. V. Black class II cavity, three on manual dexterity skills training, two on full metal crown preparation, one on pulpal access and coronal cavity preparation, one on flipped classroom teaching, and one on 'doctor-patient communication' skills. DISCUSSION: The most critical scenarios, self-assessment, working posture, curriculum setting, training and cost are analysed and discussed. CONCLUSION: Haptic simulation technology is a valuable complementary tool to the phantom head in dental education. The combined utilization of these two training devices has been superior to either in isolation. However, there is a lack of research on the sequencing of the two systems, as well as the appropriate distribution of curriculum between them. It is necessary for educators to organize or engage in experience sharing, collaboration and knowledge dissemination. These actions are essential for promoting effective teaching within dental educational institutions.

13.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(4): 374-380, 2023 Apr 15.
Artigo em Zh | MEDLINE | ID: mdl-37073842

RESUMO

OBJECTIVES: To study the safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia (R/R-ALL). METHODS: Six children with R/R-ALL who received blinatumomab treatment from August 2021 to August 2022 were included as subjects, and a retrospective analysis was performed for their clinical data. RESULTS: Among the six children, there were three boys and three girls, with a median age of 10.5 (5.0-13.0) years at the time of inclusion. Of all six children, one had refractory ALL and did not achieve remission after several times of chemotherapy, and 5 relapsed for the first time, with a median time of 30 (9-60) months from diagnosis to relapse. Minimal residual disease (MRD) before treatment was 15.50% (0.08%-78.30%). Three children achieved complete remission after treatment, among whom two had negative conversion of MRD. Five children had cytokine release syndrome (CRS), among whom 3 had grade 1 CRS and 2 had grade 2 CRS. Four children were bridged to allogeneic hematopoietic stem cell transplantation, with a median interval of 50 (40-70) days from blinatumomab treatment to transplantation. The six children were followed up for a median time of 170 days, and the results showed an overall survival rate of 41.7% (95%CI: 5.6%-76.7%) and a median survival time of 126 (95%CI: 53-199) days. CONCLUSIONS: Blinatumomab has good short-term safety and effectiveness in the treatment of childhood R/R-ALL, and its long-term effectiveness needs to be confirmed by studies with a larger sample size.


Assuntos
Anticorpos Biespecíficos , Antineoplásicos , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Masculino , Criança , Feminino , Humanos , Adolescente , Estudos Retrospectivos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Anticorpos Biespecíficos/efeitos adversos
14.
Reprod Biomed Online ; 45(6): 1176-1181, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36207251

RESUMO

RESEARCH QUESTION: Is there any difference in clinical outcomes between a human chorionic gonadotrophin (HCG)-only trigger and a dual trigger combining gonadotrophin-releasing hormone agonist (GnRHa) and HCG in a progestin-primed ovarian stimulation (PPOS) protocol? DESIGN: This retrospective cohort study included women younger than 40 years old with a normal ovarian reserve who underwent IVF/intracytoplasmic sperm injection treatment with a PPOS protocol. Participants were allocated to two groups according to the triggering medicines. The clinical outcomes were compared, with cumulative live birth rate (CLBR) being the primary outcome. RESULTS: In total, 1066 women were included, 565 in the HCG-only group and 501 in the dual trigger group. Demographic parameters were comparable between the groups. Fewer oocytes were retrieved in the HCG-only trigger group (dual trigger 12.56 ± 7.12 versus HCG-only trigger 11.62 ± 6.02, P = 0.020). No significant difference was observed in the numbers of two-pronuclear embryos (7.12 ± 4.90 versus 6.76 ± 4.45, P = 0.208) and high-quality embryos (4.01 ± 3.70 versus 3.96 ± 3.32, P = 0.815). The CLBR after one complete cycle was also similar (40.72% versus 43.72%, P = 0.354). Multivariate logistic analysis confirmed that the trigger method had no association with CLBR (odds ratio [OR] 0.763, 95% confidence interval [CI] 0.578-1.005, P = 0.055) in the PPOS-treated patients. CONCLUSIONS: Compared with the HCG-only trigger group, comparable embryological and clinical outcomes were achieved, although more oocytes were retrieved in the dual trigger group. This suggests that there may be no extra benefit from dual triggering, and that it should not be recommended for routine use in the general population undergoing PPOS protocols.


Assuntos
Fertilização in vitro , Progestinas , Adulto , Feminino , Humanos , Gravidez , Gonadotropina Coriônica/farmacologia , Gonadotropina Coriônica/uso terapêutico , Fertilização in vitro/métodos , Hormônio Liberador de Gonadotropina , Oócitos , Indução da Ovulação/métodos , Taxa de Gravidez , Progestinas/farmacologia , Estudos Retrospectivos
15.
Cell Biol Toxicol ; 38(3): 409-426, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34023961

RESUMO

Bisphenol F (BPF) is a replacement to bisphenol A, which has been extensively used in industrial manufacturing. Its wide detection in various human samples raises increasing concern on its safety. Currently, whether a low dose of BPF compromises cardiac function is still unknown. This study provides the first evidence that low-dose BPF can induce cardiac hypertrophy by using cardiomyocytes derived from human embryonic stem cells (hES). Non-cytotoxic BPF increased cytosolic Ca 2+ influx ([Ca2+ ]c), which was most remarkable at low dose (7 ng/ml) rather than at higher doses. Significant changes in the morphological parameters of mitochondria and significant decreases in ATP production were induced by 7 ng/ml BPF, representing a classic hypertrophic cardiomyocyte. After eliminating the direct effects on mitochondrial fission-related DRP1 by administration of the DRP1 inhibitor Mdivi-1, we examined the changes in [Ca 2+ ]c levels induced by BPF, which enhanced the calcineurin (Cn) activity and induced the abnormal mitochondrial fission via the CnAß-DRP1 signaling pathway. BPF triggered excessive Ca 2+ influx by disrupting the L-type Ca 2+channel in cardiomyocytes. The interaction between ERß and CnAß cooperatively involved in the BPF-induced Ca 2+ influx, which resulted in the abnormal mitochondrial fission and compromised the cardiac function. Our findings provide a feasible molecular mechanism for explaining low-dose BPF-induced cardiac hypertrophy in vitro, preliminarily suggesting that BPF may not be as safe as assumed in humans.


Assuntos
Células-Tronco Embrionárias Humanas , Dinâmica Mitocondrial , Compostos Benzidrílicos , Calcineurina/metabolismo , Calcineurina/farmacologia , Cardiomegalia/induzido quimicamente , Cardiomegalia/metabolismo , Dinaminas/metabolismo , Receptor beta de Estrogênio/metabolismo , Humanos , Miócitos Cardíacos , Fenóis , Transdução de Sinais
16.
Cell Mol Biol (Noisy-le-grand) ; 67(4): 189-194, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-35809288

RESUMO

Stress ulcer refers to a specific type of irritation of the inner wall of the gastrointestinal tract that occurs rapidly due to acute physiological stress such as severe disease, infection, or trauma. This study investigated the serum Hs-CRP level and clinical significance of patients with stress ulcers caused by massive blood loss after trauma. For this purpose, we studied 113 patients with enormous blood loss after trauma. During the study, 26 patients developed stress ulcers. Therefore, patients with massive blood loss after trauma were divided into two groups with and without stress ulcers. In addition to clinical and demographical evaluations, serum Hs-CRP levels were measured by ELISA test method in all patients at baseline, 6, and 12 days after starting the study. Results showed that 24 patients were excluded from the study due to termination of cooperation or death. Finally, 89 patients participated in the final analysis. Of these 89 patients, 26 developed stress ulcers. There was a significant difference between the two groups with stress and non-stress ulcers in terms of mean age (P=0.001) and gender (P=0.041). Also, there was a significant difference between the two groups regarding re-bleeding (P=0.012), the number of hospitalization days (P=0.001), and a decrease in hemoglobin (P=0.035). But there was no difference between the two groups regarding the need for re-surgery (P=0.276). The results of this study showed that increased serum hs-CRP levels are directly related to stress ulcers. Patients with higher serum Hs-CRP levels were more likely to develop stress ulcers than patients without stress ulcers during six days (P=0.04) and twelve days after starting the study (P=0.001). Current research results also show that the prevalence of stress ulcers occurs in men more than women. The risk of stress ulcers increases among older patients. People with stress ulcers also lose more hemoglobin, and finally, patients with more trauma and more extended hospital stays have a higher chance of developing stress ulcers.


Assuntos
Proteína C-Reativa , Úlcera Gástrica , Doença Aguda , Proteína C-Reativa/análise , Feminino , Hemorragia , Humanos , Masculino , Úlcera
17.
Appl Opt ; 61(29): 8657-8663, 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36255998

RESUMO

Sensors based on irregularly shaped bent optical fiber devices have attracted considerable interest in many applications. However, the effective interference length and bent radius of the irregular shape fiber have not been given accurately. Here an equivalent arc model is proposed to define the effective interference length and bent radius of the U-shaped fiber device: the U-shaped optical fiber is equivalent to a regular arc. We found that the effective interference length of devices varies greatly with the structure's height changes in some special structure sizes, which is highly useful for micro-displacement measurement. In terms of this model, an ultra-sensitive micro-displacement sensor of -1.2838nm/µm in a measurement range of 0-60 µm has been realized. The sensitivity of this device is one order of magnitude higher than that in any previously reported bent optical fiber work. More importantly, the analysis strategy of the equivalent arc model can be generalized to various irregular bent fiber micro-displacement sensors and other sensing fields.

18.
BMC Med Educ ; 22(1): 610, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35945563

RESUMO

BACKGROUND: Complete denture, as an important restoration method for edentulism, is difficult to study for beginners, especially in linking the theory with clinical practice. OBJECTIVE: This study was aimed to compare the teaching effects between case-based learning combined with Rain Classroom teaching and traditional lecture method in the clinical course of complete denture prosthesis for undergraduate interns. METHODS: In a course called "Problems and treatment strategies of complete denture after wearing", interns were divided into two groups: one for traditional lecture-based teaching with PowerPoint slideshow (the control group, n = 28); and the other for case-based learning combined with Rain Classroom teaching, which published information before class, discussed specific clinic cases in class and got real-time interns' feedback via WeChat (the test group, n = 22). Both groups received the same exam and questionnaire survey after class. The Q&A participation of interns in class, theoretical test scores and questionnaire survey responses were used to evaluate the teaching effects. An independent sample t-test and the chi-square test or Fisher's exact test were used for statistical analysis in this study. RESULTS: The Q&A participation of interns in the test group was much better than that of the control group. The average score on the theoretical test after class in the test group (72.14 ± 12.24) was significantly higher than that in the control group (61.29 ± 20.12) (P < 0.05). In the test group, 94.54% (21/22) of the interns preferred the new teaching mode. CONCLUSION: Case-based learning combined with Rain Classroom teaching is helpful to enliven the classroom atmosphere, inspire studying enthusiasm, and achieve a good learning effect in both theory and clinical practice related to complete denture prosthesis.


Assuntos
Aprendizagem , Estudantes , Prótese Total , Humanos , Chuva , Inquéritos e Questionários , Ensino
19.
J Environ Sci (China) ; 113: 300-310, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34963539

RESUMO

Visibility observed at different altitudes is favorable to understand the causes of air pollution. We conducted 4-years of observations of visibility at 2.8 and 60 m and particulate matter (PM) concentrations from 2015 to 2018 in Shenyang, a provincial city in Northeast China. The results indicated that visibility increased with the increasing height in winter (especially at night), and decreased with height in summer (especially at the daytime). PM concentration exhibited opposite vertical variation to visibility, reflecting that visibility degrades with the increase of aerosol concentration in the air. The radiosonde meteorological data showed that weak turbulence in the planetary boundary layer (PBL) in winter favored aerosols' accumulation near the surface. Whereas in summer, unstable atmospheric conditions, upper-level moister environment, and regional transport of air pollutants resulted in the deterioration of upper-level visibility. Inter-annual variation in the two-level visibility indicated that the upper-level visibility improved more significantly than low-level visibility, much likely due to the reduction in emission of elevated point sources in Shenyang. Our study suggested that strengthening the control of surface non-point emissions is a promising control strategy to improve Shenyang air quality.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Monitoramento Ambiental , Material Particulado/análise , Estações do Ano
20.
BMC Cancer ; 21(1): 1190, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34749705

RESUMO

BACKGROUND: Children with acute lymphoblastic leukemia (ALL) undergoing chemotherapy experience a relatively high risk of infection. And the disturbance of gut microbiota is generally believed to impair intestinal barrier function and may induce bacterial infections and inflammation. The study aimed to investigate the alterations in the gut microbiota and assess its relationship with chemotherapy-induced pneumonia in pediatric ALL patients. METHODS: We conducted a case-control study with 14 cases affected by pneumonia and 44 unaffected subjects and characterized the physiological parameters and gut microbiota by microarray-based technique. RESULTS: There were significant differences in α- and ß-diversity in the affected group compared with the control group. At species level, the LEfSe analysis revealed that Enterococcus malodoratus, Ochrobactrum anthropi and Actinomyces cardiffensis were significantly abundant in the affected subjects. A receiver operating characteristic (ROC) curve yielded the area under the curve (AUC) of 0.773 for classification between the two groups. In addition, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in the bacterial secretion system were more enriched in the affected group than in the control group. CONCLUSIONS: Gut microbiota alteration was associated with chemotherapy-induced pneumonia in pediatric ALL patients, which provided a new perspective on the personalized clinical care of pediatric ALL.


Assuntos
Antineoplásicos/efeitos adversos , Disbiose/induzido quimicamente , Microbioma Gastrointestinal/efeitos dos fármacos , Pneumonia/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Estudos de Casos e Controles , Criança , Disbiose/diagnóstico , Disbiose/imunologia , Disbiose/microbiologia , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/imunologia , Humanos , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/métodos , Masculino , Pneumonia/induzido quimicamente
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