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1.
Exp Eye Res ; 244: 109919, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38729254

RESUMO

Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly, which is primarily attributed to oxidative stress-induced damage to the retinal pigment epithelium (RPE). Human amniotic mesenchymal stem cells (hAMSC) were considered to be one of the most promising stem cells for clinical application due to their low immunogenicity, tissue repair ability, pluripotent potential and potent paracrine effects. The conditional medium (hAMSC-CM) and exosomes (hAMSC-exo) derived from hAMSC, as mediators of intercellular communication, play an important role in the treatment of retinal diseases, but their effect and mechanism on oxidative stress-induced retinal degeneration are not explored. Here, we reported that hAMSC-CM alleviated H2O2-induced ARPE-19 cell death through inhibiting mitochondrial-mediated apoptosis pathway in vitro. The overproduction of reactive oxygen species (ROS), alteration in mitochondrial morphology, loss of mitochondrial membrane potential and elevation of Bax/Bcl2 ratio in ARPE-19 cells under oxidative stress were efficiently reversed by hAMSC-CM. Moreover, it was found that hAMSC-CM protected cells against oxidative injury via PI3K/Akt/FoxO3 signaling. Intriguingly, exosome inhibitor GW4869 alleviated the inhibitory effect of hAMSC-CM on H2O2-induced decrease in cell viability of ARPE-19 cells. We further demonstrated that hAMSC-exo exerted the similar protective effect on ARPE-19 cells against oxidative damage as hAMSC-CM. Additionally, both hAMSC-CM and hAMSC-exo ameliorated sodium iodate-induced deterioration of RPE and retinal damage in vivo. These results first indicate that hAMSC-CM and hAMSC-exo protect RPE cells from oxidative damage by regulating PI3K/Akt/FoxO3 pathway, suggesting hAMSC-CM and hAMSC-exo will be a promising cell-free therapy for the treatment of AMD in the future.


Assuntos
Âmnio , Exossomos , Proteína Forkhead Box O3 , Células-Tronco Mesenquimais , Estresse Oxidativo , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Degeneração Retiniana , Epitélio Pigmentado da Retina , Transdução de Sinais , Humanos , Células-Tronco Mesenquimais/metabolismo , Exossomos/metabolismo , Âmnio/citologia , Meios de Cultivo Condicionados/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia , Degeneração Retiniana/etiologia , Proteína Forkhead Box O3/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Apoptose , Células Cultivadas , Espécies Reativas de Oxigênio/metabolismo , Potencial da Membrana Mitocondrial , Western Blotting , Animais , Sobrevivência Celular , Peróxido de Hidrogênio/toxicidade
2.
Pediatr Res ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438553

RESUMO

BACKGROUND: To facilitate the identification of less common clinical phenotypes of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in children. METHODS: We retrospectively reviewed medical records of 236 patients with MOGAD. The following phenotypes were considered to be typical for MOGAD: ADEM, ON, TM, and NMOSD. Less common onset clinical phenotypes were screened out; their clinical and magnetic resonance imaging (MRI), diagnosis, treatment, and prognosis were summarized and analyzed. RESULTS: 16 cases (6.8%) presented as cortical encephalitis, with convulsions, headache, and fever as the main symptoms. 15 cases were misdiagnosed in the early period. 13 cases (5.5%) showed the overlapping syndrome of MOGAD and anti-N-methyl-D aspartate receptor encephalitis (MNOS), with seizures (92.3%) being the most common clinical symptom. 11 cases (84.6%) showed relapses. The cerebral leukodystrophy-like phenotype was present in seven cases (3.0%), with a recurrence rate of 50%. Isolated seizures without any findings on MRI phenotype was present in three cases (1.3%), with the only clinical symptom being seizures of focal origin. Three cases (1.3%) of aseptic meningitis phenotype presented with prolonged fever. CONCLUSION: 40/236 (16.9%) of children with MOGAD had less common phenotypes. Less common clinical phenotypes of pediatric MOGAD are susceptible to misdiagnosis and deserve more attention. IMPACT: This is the first comprehensive analysis and summary of all less commonl clinical phenotypes of MOGAD in children, while previous studies have only focused on a specific phenotype or case reports. We analyzed the characteristics of MOGAD in children and further revealed the reasons why these less common clinical phenotypes are prone to misdiagnosis and deserve more attention. Our research on treatment has shown that early detection of MOG antibodies and early treatment are of great significance for improving the prognosis of these patients.

3.
J Immunol ; 209(6): 1059-1070, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-36002233

RESUMO

The BCR-associated protein 31 (BAP31), a transmembrane protein in the endoplasmic reticulum, participates in the regulation of immune cells, such as microglia and T cells, and has potential functions in macrophages that remain to be unexplored. In this study, we designed and bred macrophage-specific BAP31 knockdown mice to detect the polarization and functions of macrophages. The results revealed that M2 macrophage-associated genes were suppressed in mouse bone marrow-derived macrophages of Lyz2 Cre-BAP31flox/flox mice. Multiple macrophage-associated transcription factors were demonstrated to be able to be regulated by BAP31. Among these factors, C/EBPß was the most significantly decreased and was regulated by early growth response 2. BAP31 could also affect C/EBPß via modulating IL-4Rα ubiquitination and proteasome degradation in IL-4-stimulated macrophages. Furthermore, we found that BAP31 affects macrophages functions, including angiogenesis and skin fibrosis, during the wound healing process through IL-4Rα, as confirmed by infection with adeno-associated virus-short hairpin (sh)-IL-4Rα in Lyz2 Cre-BAP31flox/flox mice. Our findings indicate a novel mechanism of BAP31 in regulating macrophages and provide potential solutions for the prevention and treatment of chronic wounds.


Assuntos
Macrófagos , Proteínas de Membrana , Complexo de Endopeptidases do Proteassoma , Cicatrização , Animais , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Proteína 2 de Resposta de Crescimento Precoce/metabolismo , Macrófagos/citologia , Proteínas de Membrana/metabolismo , Camundongos , Complexo de Endopeptidases do Proteassoma/metabolismo , Receptores de Superfície Celular/metabolismo
4.
Lipids Health Dis ; 23(1): 164, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831466

RESUMO

OBJECTIVE: Although blood urea nitrogen (BUN) has a crucial impact on many diseases, its effect on outcomes in patients with hyperlipidemia remains unknown. The study aimed to investigate the relationships between BUN levels and all-cause and cardiovascular disease (CVD) mortality in individuals with hyperlipidemia. METHODS: This analysis comprised 28,122 subjects with hyperlipidemia from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. The risk of BUN on mortality was evaluated using weighted Cox regression models. Additionally, to illustrate the dose-response association, the restricted cubic spline (RCS) was used. RESULTS: During the observation period, 4276 participant deaths were recorded, of which 1206 were due to CVD. Compared to patients with hyperlipidemia in the third BUN quintile, the hazard ratios (HRs) for all-cause mortality were 1.26 (95% CIs: 1.09, 1.45) and 1.22 (95% CIs: 1.09, 1.37) for patients in the first and fifth quintiles of BUN, respectively. The HRs for CVD mortality among patients in the fifth quintile of BUN were 1.48 (95% CIs: 1.14, 1.93). BUN levels were found to have a U-shaped association with all-cause mortality and a linear association with CVD mortality using restricted triple spline analysis. CONCLUSIONS: This study revealed that both low and high BUN levels in patients with hyperlipidemia are associated with heightened all-cause mortality. Furthermore, elevated BUN levels are also associated with increased CVD mortality. The findings indicate that patients with hyperlipidemia may face an elevated risk of death if they have abnormal BUN levels.


Assuntos
Nitrogênio da Ureia Sanguínea , Doenças Cardiovasculares , Hiperlipidemias , Inquéritos Nutricionais , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/sangue , Modelos de Riscos Proporcionais , Idoso , Adulto , Fatores de Risco
5.
Int J Mol Sci ; 25(8)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38673941

RESUMO

Abdominal aortic aneurysm (AAA) is a serious vascular disease which is associated with vascular remodeling. CD38 is a main NAD+-consuming enzyme in mammals, and our previous results showed that CD38 plays the important roles in many cardiovascular diseases. However, the role of CD38 in AAA has not been explored. Here, we report that smooth-muscle-cell-specific deletion of CD38 (CD38SKO) significantly reduced the morbidity of AngII-induced AAA in CD38SKOApoe-/- mice, which was accompanied with a increases in the aortic diameter, medial thickness, collagen deposition, and elastin degradation of aortas. In addition, CD38SKO significantly suppressed the AngII-induced decreases in α-SMA, SM22α, and MYH11 expression; the increase in Vimentin expression in VSMCs; and the increase in VCAM-1 expression in smooth muscle cells and macrophage infiltration. Furthermore, we demonstrated that the role of CD38SKO in attenuating AAA was associated with the activation of sirtuin signaling pathways. Therefore, we concluded that CD38 plays a pivotal role in AngII-induced AAA through promoting vascular remodeling, suggesting that CD38 may serve as a potential therapeutic target for the prevention of AAA.


Assuntos
ADP-Ribosil Ciclase 1 , Angiotensina II , Aneurisma da Aorta Abdominal , Camundongos Knockout , Miócitos de Músculo Liso , Remodelação Vascular , Animais , Masculino , Camundongos , ADP-Ribosil Ciclase 1/metabolismo , ADP-Ribosil Ciclase 1/genética , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/patologia , Modelos Animais de Doenças , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Cadeias Pesadas de Miosina/metabolismo , Cadeias Pesadas de Miosina/genética , Transdução de Sinais , Remodelação Vascular/genética
6.
Angew Chem Int Ed Engl ; 63(2): e202314304, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38009446

RESUMO

Bridged benzazepine scaffolds, possessing unique structural and physicochemical activities, are widespread in various natural products and drugs. The construction of these skeletons often requires elaborate synthetic effort with low efficiency. Herein, we develop a simple and divergent approach for constructing various bridged benzazepines by a photocatalytic intermolecular dearomatization of naphthalene derivatives with readily available α-amino acids. The bridged motif is created via a cascade sequence involving photocatalytic 1,4-hydroaminoalkylation, alkene isomerization and cyclization. Interestingly, the diastereoselectivity can be regulated through different reaction modes in the cyclization step. Moreover, aminohydroxylation and its further bromination have also been demonstrated to access highly functionalized bridged benzazepines. Preliminary mechanistic studies have been performed to get insights into the mechanism. This method provides a divergent synthetic approach for construction of highly functionalized bridged benzazepines, which have been otherwise difficult to access.

7.
Biomed Chromatogr ; 37(1): e5509, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36097410

RESUMO

Hyperlipidemia has been highlighted as one of the most prominent and global chronic conditions nowadays. Bidens bipinnata L. (BBL), a folk medicine in contemporary China, has efficacy in the treatment of hyperlipidemia (HLP) in China. Although some physiological and pathological function parameters of hyperlipidemia have been investigated, little information about the changes in small metabolites in biofluids has been reported. In the present study, global metabolic profiling with high-performance liquid chromatography-linear ion trap/Orbitrap high-resolution mass spectrometry (HPLC-LTQ/Orbitrap MS) combined with a pattern recognition method was performed to discover the underlying lipid-regulating mechanisms of BBL on hyperlipidemic rats induced by high-fat diet (HFD). The total of four metabolites, up- or down-regulated (p < 0.05 or 0.01), were identified and contributed to the progression of hyperlipidemia. These promising identified biomarkers underpin the metabolic pathway, including glyoxylate and dicarboxylate metabolism, the TCA cycle, sphingolipid metabolism and purine metabolism. They are disturbed in hyperlipidemic rats, and are identified using pathway analysis with MetPA. The altered metabolite indices could be regulated closer to normal levels after BBL intervention. The results demonstrated that urinary metabolomics is a powerful tool in the clinical diagnosis and treatment of hyperlipidemia to provide information on changes in metabolite pathways.


Assuntos
Bidens , Hiperlipidemias , Ratos , Animais , Ratos Sprague-Dawley , Metabolômica/métodos , Redes e Vias Metabólicas , Hiperlipidemias/metabolismo , Cromatografia Líquida de Alta Pressão
8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(1): 108-113, 2023 Jan.
Artigo em Zh | MEDLINE | ID: mdl-36647652

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an ongoing global pandemic of coronavirus disease 2019 (COVID-19). Proper nutritional support helps boost the immunity of the human body, strengthen the high-risk populations' defense against SARS-CoV-2, reduce the prevalence of COVID-19, prevent mild cases from developing into severe cases, and reduce the occurrence of adverse symptoms during recovery. Nutritional support is an important guarantee to provide protection against virus infection, promote patient recovery, and improve patient prognosis. Whole nutritional food formulas designed according to the characteristic clinical symptoms of COVID-19 provide patients with comprehensive nutritional support of appropriate nutritional content, which effectively improves the nutritional status of patients and provides strong technical support to improve their quality of survival. During the critical period of COVID-19 prevention and control, more emphasis should be placed on the essential role of nutritional support and the clinical efficacy of nutritional support should be given full play.


Assuntos
COVID-19 , Humanos , COVID-19/prevenção & controle , Estado Nutricional , Fatores de Risco , SARS-CoV-2 , Resultado do Tratamento
9.
Angew Chem Int Ed Engl ; 62(17): e202300036, 2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-36826223

RESUMO

The catalytic bis-allylation of alkynes is an important but challenging protocol to construct all-carbon tetra-substituted alkenes. Particularly, the catalytic unsymmetrical bis-allylation of alkynes remains as an underexplored task to date. We herein report an unprecedented unsymmetrical bis-allylation by simultaneously utilizing electrophilic trifluoromethyl alkene and nucleophilic allylboronate as the allylic reagents. With the aid of robust Ni0 /NHC catalysis, valuable skipped trienes can be obtained in high regio- and stereo-selectivities under mild conditions. Mechanistic studies indicate that the reaction may proceed through a ß-fluorine elimination of a nickelacycle followed by a transmetalation step with allylboronate. The present method exhibits a good tolerance of various functional groups. Besides, the skipped triene products can undergo an array of elaborate transformations, which highlights the potential applications of this strategy.

10.
Angew Chem Int Ed Engl ; 62(22): e202303656, 2023 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-37016511

RESUMO

Stable isotope chemical labeling methods have been widely used for high-throughput mass spectrometry (MS)-based quantitative proteomics in biological and clinical applications. However, the existing methods are far from meeting the requirements for high sensitivity detection. In the present study, a novel isobaric stable isotope N-phosphorylation labeling (iSIPL) strategy was developed for quantitative proteome analysis. The tryptic peptides were selectively labeled with iSIPL tag to generate the novel reporter ions containing phosphoramidate P-N bond with high intensities under lower collision energies. iSIPL strategy are suitable for peptide sequencing and quantitative analysis with high sensitivity and accuracy even for samples of limited quantity. Furthermore, iSIPL coupled with affinity purification and mass spectrometry was applied to measure the dynamics of cyclin dependent kinase 9 (CDK9) interactomes during transactivation of the HIV-1 provirus. The interaction of CDK9 with PARP13 was found to significantly decrease during Tat-induced activation of HIV-1 gene transcription, suggesting the effectiveness of iSIPL strategy in dynamic analysis of protein-protein interaction in vivo. More than that, the proposed iSIPL strategy would facilitate large-scale accurate quantitative proteomics by increasing multiplexing capability.


Assuntos
Proteoma , Espectrometria de Massas em Tandem , Proteoma/análise , Espectrometria de Massas em Tandem/métodos , Fosforilação , Peptídeos/química , Marcação por Isótopo/métodos , Isótopos
11.
Glia ; 70(1): 106-122, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34498776

RESUMO

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized primarily by impaired social communication and rigid, repetitive, and stereotyped behaviors. Many studies implicate abnormal synapse development and the resultant abnormalities in synaptic excitatory-inhibitory (E/I) balance may underlie many features of the disease, suggesting aberrant neuronal connections and networks are prone to occur in the developing autistic brain. Astrocytes are crucial for synaptic formation and function, and defects in astrocytic activation and function during a critical developmental period may also contribute to the pathogenesis of ASD. Here, we report that increasing hippocampal astrogenesis during development induces autistic-like behavior in mice and a concurrent decreased E/I ratio in the hippocampus that results from enhanced GABAergic transmission in CA1 pyramidal neurons. Suppressing the aberrantly elevated GABAergic synaptic transmission in hippocampal CA1 area rescues autistic-like behavior and restores the E/I balance. Thus, we provide direct evidence for a developmental role of astrocytes in driving the behavioral phenotypes of ASD, and our results support that targeting the altered GABAergic neurotransmission may represent a promising therapeutic strategy for ASD.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Animais , Transtorno do Espectro Autista/genética , Hipocampo/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Células Piramidais/fisiologia , Transmissão Sináptica
12.
Future Oncol ; 18(2): 149-161, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34643088

RESUMO

Background: Chemoresistance usually occurs in ovarian cancer. We aimed to explore the mechanisms of chemoresistance. Methods: Western blotting assay was used to detect the expression of GALNT14. Further cell function experiments were performed to investigate the effect of GALNT14 in ovarian cancer. Results: GALNT14 is significantly upregulated in ovarian cancer. Downregulation of GALNT14 significantly inhibits both apoptosis and ferroptosis of ovarian cancer cells. A further mechanism assay illustrated that downregulation of GALNT14 suppresses the activity of the mTOR pathway through modifying O-glycosylation of EGFR. Finally, an additive effect promoting cell death occurs with a combination of an mTOR inhibitor and cisplatin. Conclusion: Our study might provide a promising method to overcome cisplatin resistance for patients with ovarian cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , N-Acetilgalactosaminiltransferases/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptores ErbB/metabolismo , Feminino , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Regulação Neoplásica da Expressão Gênica , Glicosilação/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Ovário/patologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Sirolimo/análogos & derivados , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Regulação para Cima
13.
J Nanobiotechnology ; 20(1): 54, 2022 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-35093074

RESUMO

BACKGROUND: Harnessing the immune system to fight cancer has led to prominent clinical successes. Strategies to stimulate innate immune effectors are attracting considerable interest in cancer therapy. Here, through conjugating multivalent Fc fragments onto the surface of mesoporous silica nanoparticles (MSN), we developed a nanoparticle-based innate immune system activator (NISA) for breast cancer immunotherapy. METHODS: NISA was prepared through conjugating mouse IgG3 Fc to MSN surface. Then, long-chain PEG5000, which was used to shield Fc to confer nanoparticle colloidal stability, was linked to the MSN surface via matrix metalloprotease-2 (MMP-2)-cleavable peptide (GPLGIAGQC). The activation of multiple components of innate immune system, including complement and the innate cells (macrophages and dendritic cells) and the associated anticancer effect were investigated. RESULTS: Fc fragments of NISA can be exposed through hydrolysis of long-chain PEG5000 by highly expressed MMP-2 in tumor microenvironment. Then, effective stimulation and activation of multiple components of innate immune system, including complement, macrophages, and dendritic cells were obtained, leading to efficient antitumor effect in 4T1 breast cancer cells and orthotopic breast tumor model in mice. CONCLUSIONS: The antitumor potency conferred by NISA highlights the significance of stimulating multiple innate immune elements in cancer immunotherapy.


Assuntos
Nanopartículas , Neoplasias , Animais , Linhagem Celular Tumoral , Imunoterapia , Macrófagos , Camundongos , Nanopartículas/uso terapêutico , Microambiente Tumoral
14.
Neurol Sci ; 43(4): 2449-2460, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34694512

RESUMO

BACKGROUND AND PURPOSE: We aimed to build a nomogram, based on patients with spontaneous intracerebral hemorrhage (SICH), to predict the probability of mortality and morbidity at 7 days and 90 days, respectively. METHODS: We performed a retrospective study, with patients at less than 6 h from ictus admitted to the department of neurosurgery in a single institute, from January 2011 to December 2018. A total of 1036 patients with SICH were included, 486 patients (46.9%) were 47-66 years old at diagnosis, and 711 patients (68.6%) were male. The least absolute shrinkage and section operator method was performed to identify the key adverse factors predicting the outcomes in patients with SICH, and multivariate logistic regression analysis was built on these variables, and then the results were visualized by a nomogram. The discrimination of the prognostic models was measured and compared by means of Harrell's concordance index (C-index), calibration curve, area under the curve (AUC), and decision curve analysis (DCA). RESULTS: Multivariate logistic regression analysis revealed that factors affecting 7-day mortality, including the following: age, therapy, Glasgow Coma Scale (GCS) admission, location, ventricle involved, hematoma volume, white blood cell (WBC), uric acid (UA), and L-lactic dehydrogenase (LDH); and factors affecting 90-day mortality, including temperature, therapy, GCS admission, ventricle involved, WBC, international normalized ratio, UA, LDH, and systolic blood pressure. The C-index for the 7-day mortality and 90-day mortality prediction nomogram was 0.9239 (95% CI = 0.9061-0.9416) and 0.9241 (95% CI = 0.9064-0.9418), respectively. The AUC of 7-day mortality was 92.4, as is true of 90-day mortality. The calibration curve and DCA indicated that nomograms in our study had a good prediction ability. For 90-day morbidity, age, marital status, and GCS at 7-day remained statistically significant in multivariate analysis. The C-index for the prediction nomogram was 0.6898 (95% CI = 0.6511-0.7285), and the calibration curve, AUC as well as DCA curve indicated that the nomogram for the prediction of good outcome demonstrated good agreement in this cohort. CONCLUSIONS: Nomograms in this study revealed many novel prognostic demographic and laboratory factors, and the individualized quantitative risk estimation by this model would be more practical for treatment management and patient counseling.


Assuntos
Hemorragias Intracranianas , Nomogramas , Adulto , Idoso , China/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos
15.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(3): 511-516, 2022 May.
Artigo em Zh | MEDLINE | ID: mdl-35642163

RESUMO

Objective: To establish a brain hematoma CT image segmentation method based on watershed and region-growing algorithm so as to measure hematoma volume quickly and accurately, to explore the consistency between the results of this segmentation method and those of manual segmentation, the clinical gold standard, and to compare the results of this method with the calculation of the two Tada formulas commonly used in clinical practice. Methods: The preoperative CT images of 152 patients who were treated for spontaneous cerebral hemorrhage at the Department of Neurosurgery, West China Hospital, Sichuan University between January 2018 and June 2019 were retrospectively collected. The CT images were randomly assigned, by using a random number table, to the training set, the test set and the validation set, which contained 100 patients, 22 patients and 30 patients, respectively. The labeling results of the training set and the test set were used in algorithm training and testing. Four methods, namely, manual segmentation, algorithm segmentation, i.e., segmentation calculation based on watershed and regional growth algorithm, Tada formula, i.e., the traditional Tada formula calculation, and accurate Tada formula, i.e., accurate Tada formula calculation based on 3D-Slicer, were applied on the validation set to measure the hematoma volume. The Digital Imaging and Communications in Medicine (DICOM) data of subjects meeting the selection criteria of the study were manually segmented by two experienced neurosurgeons. The hematoma segmentation model was built based on watershed algorithm and regional growth algorithm. Seed point selected by neurosurgeons was taken as the starting point of growth. Regional grayscale difference criterion combined with manual segmentation validation were adopted to determine the regional growth threshold that met the segmentation precision requirements for intracranial hematoma. Using manual segmentation as the gold standard, Bland-Altman consistency analysis was used to verify the consistency of the three other methods for measuring hematoma volume. Results: With manual segmentation as the gold standard, among the three methods of measuring hematoma volume, algorithm segmentation had the smallest percentage error, the narrowest range of difference, the highest intra-group correlation coefficient (0.987), good consistency, and the narrowest 95% limits of agreement ( LoA). The percentage error of its segmentation was not statistically significant for hematomas of different volumes. Conclusion: The segmentation method of spontaneous intracerebral hemorrhage based on watershed and regional growth algorithm shows stable measurement performance and good consistency with the clinical gold standard, which has considerable clinical significance, but it still needs further validation with more clinical samples.


Assuntos
Hematoma , Tomografia Computadorizada por Raios X , Algoritmos , Hemorragia Cerebral/diagnóstico por imagem , Hematoma/diagnóstico por imagem , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
16.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(1): 114-120, 2022 Jan.
Artigo em Zh | MEDLINE | ID: mdl-35048610

RESUMO

OBJECTIVE: To examine the performance and application value of improved Unet network technology in the recognition and segmentation of hemorrhage regions in brain CT images. METHODS: A total of 476 brain CT images of patients with spontaneous intracerebral hemorrhage (SICH) were retrospectively included. The improved Unet network was used to identify and segment the hemorrhage regions in the patients' brain CT images. The CT imaging data of the hemorrhage regions were manually labelled by clinicians. After randomized sorting, 430 data sets from 106 patients were selected for inclusion in the training set and 46 data sets from 11 patients were included in the test set. After data enhancement, the experimental data set underwent network training and model testing in order to assess the segmentation performance. The segmentation results were compared with the those of the Unet network (Base), FCN-8s network and Unet++ network. RESULTS: In the segmentation of brain CT image hemorrhage region with the improved Unet network, the three evaluation indicators of Dice similarity coefficient, positive predictive value (PPV), and sensitivity coefficient (SC) reached 0.8738, 0.9011 and 0.8648, respectively, increasing by 8.80%, 7.14% and 8.96%, respectively, compared with those of FCN-8s, and increasing by 4.56%, 4.44% and 4.15%, respectively, compared with those of Unet network (Base). The improved Unet network also showed better segmentation performance than that of Unet++ network. CONCLUSION: The improved method based on Unet network proposed in this report displayed good performance in the recognition and segmentation of hemorrhage regions in brain CT images, and is an appropriate method for the recognition and segmentation of hemorrhage regions in brain CT images, showing potential application value for assisting clinical decision-making and preventing early hematoma expansion.


Assuntos
Processamento de Imagem Assistida por Computador , Tomografia Computadorizada por Raios X , Encéfalo/diagnóstico por imagem , Hemorragia , Humanos , Estudos Retrospectivos
17.
Zhongguo Zhong Yao Za Zhi ; 47(11): 2955-2963, 2022 Jun.
Artigo em Zh | MEDLINE | ID: mdl-35718517

RESUMO

In this paper, a flavonoid extract powder properties-process parameters-granule forming rate prediction model was constructed based on design space and radial basis function neural network(RBFNN) to predict the formability of flavonoid extract gra-nules. Box-Behnken experimental design was employed to explore the mathematical relationships between critical process parameters and quality attributes. The design space of critical process parameters was developed, and the accuracy of the design space was verified by Monte Carlo method(MC). Design Expert 10 was used for Box-Behnken design and mixture design. Scutellariae Radix mixed powder was prepared and its powder properties were measured. The mixed powder was then subjected to dry granulation and the granule forming rate was determined. The correlations between powder properties were analyzed by variance influence factor(VIF), and principal component analysis(PCA) was performed for the factors with strong collinearity. In this way, a prediction model of powder properties-process parameters-granule forming rate was established based on RBFNN, the accuracy of which was evaluated with examples. The results showed that the model had a good predictive effect on the granule forming rate, with the average relative error of 1.04%. The predicted value and the measured value had a high degree of fitting, which indicated that model presented a good prediction ability. The prediction model established in this study can provide reference for the establishment of quality control methods for Chinese medicinal preparations with similar physical properties.


Assuntos
Medicamentos de Ervas Chinesas , Flavonoides , Tamanho da Partícula , Pós , Controle de Qualidade , Comprimidos
18.
Zhongguo Zhong Yao Za Zhi ; 47(4): 1103-1113, 2022 Feb.
Artigo em Zh | MEDLINE | ID: mdl-35285211

RESUMO

At present, there have been many clinical trials and systematic reviews/Meta-analysis proving the good clinical efficacy of Shufeng Jiedu Capsules in the treatment of respiratory diseases, while comprehensive discussion is still required. This article overviews and analyzes the systematic reviews/Meta-analysis of Shufeng Jiedu Capsules to provide evidence support for clinical practice. The systematic reviews/Meta-analysis of Shufeng Jiedu Capsules were searched from CBM, Wanfang, CNKI, VIP, PubMed, EMbase and Cochrane Library. The AMSTAR 2 scale and GRADE system were respectively employed for the evaluation of methodological quality and the grading of evidence quality. Finally, 8 systematic reviews/Meta-analysis published during 2018-2021 were included for analysis. The diseases involved include acute exacerbation of chronic obstructive pulmonary disease, community-acquired pneumonia, acute tonsillitis, acute exacerbation of chronic bronchitis and acute upper respiratory tract infection. The number of included RCTs studies ranged from 8 to 25. The results showed that Shufeng Jiedu Capsules combined with western medicine routine had better therapeutic effect than the latter alone in the treatment of the above five diseases. The reported adverse reactions caused by Shufeng Jiedu Capsules were mainly gastrointestinal discomforts such as mild nausea, diarrhoea and vomiting, with low incidence and mild symptoms, which can be relieved by drug withdrawal. The methodological quality of the included studies was extremely low, and the outcome indicators were mainly of low and very low grades. The efficacy and safety of Shufeng Jiedu Capsules in the clinical treatment of diseases still need to be verified based on more high-quality studies. The relevant clinical research and systematic review/Meta-analysis should pay more attention to methodological quality and reporting standards and strengthen the scientificity of research.


Assuntos
Medicamentos de Ervas Chinesas , Cápsulas , Medicamentos de Ervas Chinesas/uso terapêutico , Revisões Sistemáticas como Assunto , Resultado do Tratamento
19.
Zhongguo Yi Liao Qi Xie Za Zhi ; 46(3): 323-325, 2022 May 30.
Artigo em Zh | MEDLINE | ID: mdl-35678445

RESUMO

OBJECTIVE: 10 instructions of infusion pumps were contrasted and analyzed in order to explore the problems of instructions, furthermore improve the product safety. METHODS: Analyzed the scopes of application, requirements of infusion apparatus, maintenance methods and cycles, battery maintenance, and service life, etc. RESULTS: There were 5 products in 10 which did not indicate contraindications. One product only provided the thickness range of the tube wall of the infusion apparatus instead of specific brands. The cleaning cycles of 9 products varied from 2 to 12 months. One product did not clarify the service life. CONCLUSIONS: It is recommended that manufactures should improve the product instructions to ensure the safety of infusion pumps.


Assuntos
Fontes de Energia Elétrica , Bombas de Infusão , Medição de Risco
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(9): 1061-1067, 2022.
Artigo em Zh | MEDLINE | ID: mdl-36111727

RESUMO

OBJECTIVES: To establish a system for regulating the gene expression of embryonic mouse cerebral cortex neural stem cells (NSCs) using in utero electroporation (IUE). METHODS: At embryonic day 14.5, the mouse cerebral cortex NSCs were electro-transfected with the pCIG plasmid injected into the ventricle of the mouse embryo. At embryonic day 16.5 or day 17.5, embryonic mouse brain tissues were collected to prepare frozen sections. Immunofluorescence staining was used to observe the proliferation, apoptosis, division, directional differentiation, migration, and maturation of NSCs. RESULTS: The differentiation of NSCs into intermediate progenitors, the proliferation and apoptosis of NSCs, and the morphological development of radial axis of radial glial cells were observed at embryonic day 16.5. The differentiation of NSCs into neurons in layers V-VI of the cerebral cortex, the migration of NSCs to the lateral cerebral cortex, the development of dendrites of migrating neurons, and the maturation of neurons were observed at embryonic day 17.5. CONCLUSIONS: The system for regulating the gene expression of embryonic mouse cerebral cortex NSCs can be established using IUE, which is useful for the study of neural development related to the proliferation, apoptosis, division, directional differentiation, migration and maturation of NSCs in the cerebral cortex.


Assuntos
Células-Tronco Neurais , Animais , Córtex Cerebral/metabolismo , Eletroporação , Expressão Gênica , Camundongos , Neurônios/metabolismo
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