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1.
Front Immunol ; 12: 700995, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804005

RESUMO

The prevalence of inflammatory bowel disease (IBD) is increasing worldwide and correlates with dysregulated immune response because of gut microbiota dysbiosis. Some adverse early life events influence the establishment of the gut microbiota and act as risk factors for IBD. Prenatal maternal stress (PNMS) induces gut dysbiosis and perturbs the neuroimmune network of offspring. In this study, we aimed to investigate whether PNMS increases the susceptibility of offspring to colitis in adulthood. The related index was assessed during the weaning period and adulthood. We found that PNMS impaired the intestinal epithelial cell proliferation, goblet cell and Paneth cell differentiation, and mucosal barrier function in 3-week-old offspring. PNMS induced low-grade intestinal inflammation, but no signs of microscopic inflammatory changes were observed. Although there was no pronounced difference between the PNMS and control offspring in terms of their overall measures of alpha diversity for the gut microbiota, distinct microbial community changes characterized by increases in Desulfovibrio, Streptococcus, and Enterococcus and decreases in Bifidobacterium and Blautia were induced in the 3-week-old PNMS offspring. Notably, the overgrowth of Desulfovibrio persisted from the weaning period to adulthood, consistent with the results observed using fluorescence in situ hybridization in the colon mucosa. Mechanistically, the fecal microbiota transplantation experiment showed that the gut microbiota from the PNMS group impaired the intestinal barrier function and induced low-grade inflammation. The fecal bacterial solution from the PNMS group was more potent than that from the control group in inducing inflammation and gut barrier disruption in CaCo-2 cells. After treatment with a TNF-α inhibitor (adalimumab), no statistical difference in the indicators of inflammation and intestinal barrier function was observed between the two groups. Finally, exposure to PNMS remarkably increased the values of the histopathological parameters and the inflammatory cytokine production in a mouse model of experimental colitis in adulthood. These findings suggest that PNMS can inhibit intestinal development, impair the barrier function, and cause gut dysbiosis characterized by the persistent overgrowth of Desulfovibrio in the offspring, resulting in exacerbated experimental colitis in adulthood.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34723457

RESUMO

Despite great achievement that has been made in the synthesis of covalent organic frameworks (COFs), precise construction of COFs with well-defined nano/microstructures poses a rigorous challenge. Herein, we introduce a simple template-free strategy for controllable synthesis of hollow microtubular COFs. The obtained COFs show a spontaneous morphology transformation from a microfiber to a hollow microtubular structure when the concentrations of catalytic acid are regulated elaborately. Furthermore, the as-prepared COFs exhibit high crystallinity, well-defined hollow tubular morphology, and high surface areas (∼2600 m2/g). Taking the advantages of the unique morphological structure, the hollow microtubular COFs can serve as an ideal host material for enzymes. The resultant biocomposites show high catalytic performance and can be successfully applied to rapid and high-efficiency proteolysis of proteins. This work blazes a trail for controllable synthesis of the hollow microtubular COFs through a template-free process and expands the application of COFs as a promising platform for enzyme immobilization.

3.
Chin Med J (Engl) ; 134(21): 2535-2543, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34748524

RESUMO

BACKGROUND: It is crucial to differentiate accurately glioma recurrence and pseudoprogression which have entirely different prognosis and require different treatment strategies. This study aimed to assess the diagnostic accuracy of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as a tool for distinguishing glioma recurrence and pseudoprogression. METHODS: According to particular criteria of inclusion and exclusion, related studies up to May 1, 2019, were thoroughly searched from several databases including PubMed, Embase, Cochrane Library, and Chinese biomedical databases. The quality assessment of diagnostic accuracy studies was applied to evaluate the quality of the included studies. By using the "mada" package in R, the heterogeneity, overall sensitivity, specificity, and diagnostic odds ratio were calculated. Moreover, funnel plots were used to visualize and estimate the publication bias in this study. The area under the summary receiver operating characteristic (SROC) curve was computed to display the diagnostic efficiency of DCE-MRI. RESULTS: In the present meta-analysis, a total of 11 studies covering 616 patients were included. The results showed that the pooled sensitivity, specificity, and diagnostic odds ratio were 0.792 (95% confidence interval [CI] 0.707-0.857), 0.779 (95% CI 0.715-0.832), and 16.219 (97.5% CI 9.123-28.833), respectively. The value of the area under the SROC curve was 0.846. In addition, the SROC curve showed high sensitivities (>0.6) and low false positive rates (<0.5) from most of the included studies, which suggest that the results of our study were reliable. Furthermore, the funnel plot suggested the existence of publication bias. CONCLUSIONS: While the DCE-MRI is not the perfect diagnostic tool for distinguishing glioma recurrence and pseudoprogression, it was capable of improving diagnostic accuracy. Hence, further investigations combining DCE-MRI with other imaging modalities are required to establish an efficient diagnostic method for glioma patients.


Assuntos
Glioma , Recidiva Local de Neoplasia , Glioma/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/diagnóstico por imagem , Curva ROC , Sensibilidade e Especificidade
4.
Anal Chem ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34784186

RESUMO

Although matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has become a ubiquitous and effective tool for macromolecules, direct analysis of small molecules by MALDI-MS using conventional organic matrices poses a challenge. Herein, a large-area, uniform, and stable covalent organic framework (COF) nanofilm prepared directly on indium-tin oxide (ITO) glass was first introduced as a substrate for LDI-MS, which showed enhanced sensitivity, no background interference, and high reproducibility in the analysis of diverse small molecules. Taking into account all these merits, an attractive approach of COF nanofilm-based LDI-MS was developed to quantitatively evaluate the pharmacokinetics of 5-fluorouracil (5-FU) in mouse plasma. A good linear relationship (10-20,000 ng/mL) and a low limit of detection (LOD) for 5-FU (∼100 pg/mL) were achieved. In view of the fact that the COF nanofilm was uniform and without the requirement of additional matrix spraying, it was further extended for LDI-MS imaging (LDI-MSI) to visualize the spatial distribution of 5-FU in mouse liver at different interval times after intravenous and intragastric administrations. The results indicated that the decay of 5-FU in mouse liver obtained with the COF nanofilm-based LDI-MSI was consistent with the tendency of 5-FU pharmacokinetics. This work not only offers an alternative solution for LDI-MS/MSI analysis of small molecules but also extends the application fields of COF nanofilm in MS research.

5.
Diagn Interv Radiol ; 27(6): 716-724, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34792025

RESUMO

PURPOSE: We aimed to assess the diagnostic performance of radiomics using machine learning algorithms to predict the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter in glioma patients. METHODS: A comprehensive literature search of PubMed, EMBASE, and Web of Science until 27 July 2021 was performed to identify eligible studies. Stata SE 15.0 and Meta-Disc 1.4 were used for data analysis. RESULTS: A total of fifteen studies with 1663 patients were included: five studies with training and validation cohorts and ten with only training cohorts. The pooled sensitivity and specificity of machine learning for predicting MGMT promoter methylation in gliomas were 85% (95% CI 79%-90%) and 84% (95% CI 78%-88%) in the training cohort (n=15) and 84% (95% CI 70%-92%) and 78% (95% CI 63%-88%) in the validation cohort (n=5). The AUC was 0.91 (95% CI 0.88-0.93) in the training cohort and 0.88 (95% CI 0.85-0.91) in the validation cohort. The meta-regression demonstrated that magnetic resonance imaging sequences were related to heterogeneity. The sensitivity analysis showed that heterogeneity was reduced by excluding one study with the lowest diagnostic performance. CONCLUSION: This meta-analysis demonstrated that machine learning is a promising, reliable and repeatable candidate method for predicting MGMT promoter methylation status in glioma and showed a higher performance than non-machine learning methods.


Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Glioma/diagnóstico por imagem , Glioma/genética , Humanos , Aprendizado de Máquina , Metilação , Proteínas Supressoras de Tumor/genética
6.
Transl Oncol ; 15(1): 101284, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34839107

RESUMO

BACKGROUND: Ovarian cancer is one of the most common female cancers, with a high incidence worldwide. Aberrant expression of low-density lipoprotein (LDL) receptor-related protein 8 (LRP8) and microRNA (miR)-362-3p is involved in the pathogenesis of different cancers. METHODS: We aimed to elucidate the underlying mechanism of the miR-362-3p-LRP8 axis in ovarian cancer. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to examine miR-362-3p and LRP8 expression in ovarian cancer tissues and cells. The luciferase assay was used to determine the relationship between miR-362-3p and LRP8. The function of overexpression of miR-362-3p and LRP8 was determined by assessing the cell viability using the cell counting kit 8 (CCK-8) assay, proliferation using 5'­bromo-2'-deoxyuridine (BrdU) assay, migration using wound healing assay, invasion using transwell assay, and the protein expression levels of matrix metalloproteinase (MMP)-2, MMP9, and integrin α5 or ß1 using western blotting assays in ovarian cancer cells. RESULTS: miR-362-3p expression levels were decreased in ovarian cancer tissues and cells and negatively correlated with LRP8 levels. Overexpression of miR-362-3p dramatically repressed cell growth. Furthermore, overexpression of LRP8 significantly facilitated the proliferation, migration, and invasion of ovarian cancer cells, which counteracted the inhibitory effect of miR-362-3p on ovarian cancer cell growth. CONCLUSIONS: We reported that miR-362-3p hampered cell growth by repressing LRP8 expression in ovarian cancer cells. Our results provide new insights into ovarian cancer, involving both miR-362-3p and LRP8, which can be used as potential biomarkers for the treatment of ovarian cancer.

7.
J Int Med Res ; 49(10): 3000605211049074, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34633880

RESUMO

OBJECTIVE: The risk factors associated with iodine contrast extravasation immediately after endovascular thrombectomy (EVT) and subsequent hemorrhagic transformation within 24 hours remain unclear. METHODS: Mixed images, iodine overlay maps, and virtual non-contrast images were reconstructed from 106 consecutive acute ischemic stroke patients who underwent dual energy computed tomography immediately and 24 hours after EVT. Multivariate analyses of clinical and radiological data were performed to explore independent predictors of iodine contrast extravasation and hemorrhagic transformation. RESULTS: Sixty-eight (64.2%) patients exhibited pure iodine contrast extravasation after EVT; 30.9% developed hemorrhagic transformation within 24 hours after EVT. The number of stent retriever passes was independently associated with both iodine contrast extravasation (odds ratio 1.608; 95% confidence interval (CI) 1.047-2.469) and subsequent hemorrhagic transformation (odds ratio 1.477; 95% CI 1.003-2.175). Patients with more than two stent retriever passes were more likely to exhibit iodine contrast extravasation (sensitivity = 68.2%, specificity = 81.5%), while those with more than three stent retriever passes more often exhibited hemorrhage after iodine contrast extravasation (sensitivity = 64.6%, specificity = 87.2%). CONCLUSIONS: The number of stent retriever passes was an independent predictor for both iodine contrast extravasation and subsequent hemorrhagic transformation.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Animais , Hemorragia Cerebral , Cães , Humanos , Fatores de Risco , Trombectomia
8.
Exp Brain Res ; 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34687331

RESUMO

It is well known that hyperbaric oxygen (HBO) therapy achieves neuroprotective effects by modulating neuroinflammatory responses. However, its underlying therapeutic mechanisms are not yet fully elucidated. Based on our previous studies, we further investigated whether HBO therapy exerts neuroprotective effects in vivo by regulating the nuclear factor-kappa B (NF-κB)/ mitogen-activated protein kinases (MAPKs) chemokine (C-X-C motif) ligand (CXCL)1 inflammatory pathway. In our study, a rat model of traumatic brain injury (TBI) was established by controlled cortical impact (CCI) to verify that the expression of CXCL1 and chemokine (C-X-C motif) receptor (CXCR)2 increased after TBI, and CXCL1 was mainly expressed in astrocytes, while CXCR2 was mainly expressed in neurons. Increased apoptosis of cortical nerve cells in the injured cortex was also found after TBI. Reduced nerve cell apoptosis with improved neurological function was observed after application of a CXCR2 antagonist. The expression of phospho-extracellular signal-regulated kinase (p-ERK), phospho-c-Jun N-terminal kinase (p-JNK) and p-NF-κB increased after TBI, and application of ERK, JNK and NF-κB inhibitors decreased expression of CXCL1 and CXCR2 in rats. We further found that HBO therapy down-regulated the expression of p-ERK, p-JNK, p-NF-κB, CXCL1, and CXCR2, and reduced nerve cell apoptosis, improved the neurological function of TBI rats, and ultimately alleviated the secondary injury. In conclusion, HBO therapy may exert neuroprotective effect by regulating the NF-κB/MAPKs (JNK and ERK)-CXCL1 inflammatory pathways following TBI, which probably provide the theoretical and experimental basis for the clinical application of HBO therapy in the treatment of TBI.

9.
iScience ; 24(10): 103101, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34622156

RESUMO

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that would permanently damage the affected joints. Unfortunately, a large proportion of RA patients fail to respond adequately to current treatments. Here, repurposing hemin and its ultra-long-acting formulation were explored for the effective treatment of RA in animal models. We provided evidence that hemin prevented the onset and ameliorated the clinical course of RA. Notably, hemin treatment rescued the dysregulated gene expression in animal models of RA, resulting in attenuation of Th1/Th17 cell-mediated responses and proinflammatory cytokines. Moreover, we further formulated hemin into the in-situ forming implant, and a single injection of the ultra-long-acting hemin exerted potent disease-modifying effects for at least six weeks with a remarkable dose reduction. Taken together, given the potent anti-inflammatory and immunosuppressive effects, the once-monthly hemin injection holds promise for rapid clinical translation, and represents a potential strategy to treat RA and possibly other autoimmune diseases.

10.
Vet Sci ; 8(10)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34679047

RESUMO

To reduce the circulation path of the output current of traditional electroacupuncture (TEA) process in the body, a simple single-acupoint electroacupuncture (SEA) frame was designed and the acupuncture effect of SEA was evaluated through Hou-san-li (ST-36) and Qian-san-li (LI-10) acupoints. Forty-two healthy New Zealand rabbits were randomly divided into seven groups and underwent acupuncture for 20 min in an awake state. Blood samples aseptically collected from the ear vein 3 h before acupuncture and 0, 3, 6, 9, 12 and 24 h after acupuncture were used for the detection of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase MB (CK-MB) and motilin (MTL) in serum. The simple SEA frame was developed successfully, and the acupuncture results showed that the serum AST and ALT levels were significantly higher at 3 h after TEA with high frequency (p < 0.01) compared with the control group. Regarding serum CK-MB levels, no significant differences were found after SEA or TEA stimulation (p > 0.05). Serum MTL levels were significantly increased at 0 h after SEA and TEA (p < 0.05), but there were no significant differences at other time points after SEA and TEA treatment (p > 0.05). SEA not only maintains the effect of TEA but also shortens the circulation loop of the electroacupuncture (EA) current in the body, which effectively avoids body injury.

11.
ACS Appl Mater Interfaces ; 13(41): 49482-49489, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34636536

RESUMO

Although organic artificial enzymes have been reported as biomimetic oxidation catalysts and are widely used for colorimetric biosensors, developing organic artificial enzymes with high enzymatic activity is still a challenge. Two-dimensional (2D) covalent organic frameworks (COFs) have shown superior potential in biocatalysts because of their periodic π-π arrays, tunable pore size and structure, large surface area, and thermal stability. The interconnection of electron acceptor and donor building blocks in the 2D conjugated COF skeleton can lead to narrower band gaps and efficient charge separation and transportation and thus is helpful to improve catalytic activity. Herein, a donor-acceptor 2D COF was synthesized using tetrakis(4-aminophenyl)pyrene (Py) as an electron donor and thieno[3,2-b]thiophene-2,5-dicarbaldehyde (TT) as an electron acceptor. Under visible light irradiation, the donor-acceptor 2D COF exhibited superior enzymatic catalytic activity, which could catalyze the oxidation of chromogenic substrates such as 3,3',5,5'-tetramethylbenzidine (TMB) by the formation of superoxide radicals and holes. Based on the above property, the photoactivated donor-acceptor 2D COF with enzyme-like catalytic properties was designed as a robust colorimetric probe for cheap, highly sensitive, and rapid colorimetric detection of glutathione (GSH); the corresponding linear range of GSH was 0.4-60 µM, and the limit of detection was 0.225 µM. This study not only presents the construction of COF-based light-activated nanozymes for environmentally friendly colorimetric detection of GSH but also provides a smart strategy for improving nanozyme activity.

12.
J Int Med Res ; 49(9): 3000605211016208, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34510958

RESUMO

OBJECTIVE: This retrospective multicentre observational study was performed to assess the predictors of acute kidney injury (AKI) in patients with acute decompensated heart failure (ADHF) in emergency departments in China. METHODS: In total, 1743 consecutive patients with ADHF were recruited from August 2017 to January 2018. Clinical characteristics and outcomes were compared between patients with and without AKI. Predictors of AKI occurrence and underdiagnosis were assessed in multivariate regression analyses. RESULTS: Of the 1743 patients, 593 (34.0%) had AKI. AKI was partly associated with short-term all-cause mortality and cost. Cardiovascular comorbidities such as coronary heart disease, diabetes mellitus, and hypertension remained significant predictors of AKI in the univariate analysis. AKI was significantly more likely to occur in patients with a lower arterial pH, lower albumin concentration, higher creatinine concentration, and higher N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration. Patients treated with inotropic agents were significantly more likely to develop AKI during their hospital stay. CONCLUSION: This study suggests that cardiovascular comorbidities, arterial pH, the albumin concentration, the creatinine concentration, the NT-proBNP concentration, and use of inotropic agents are predictors of AKI in patients with ADHF.


Assuntos
Injúria Renal Aguda , Insuficiência Cardíaca , Doença Aguda , Injúria Renal Aguda/diagnóstico , Biomarcadores , Serviço Hospitalar de Emergência , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Humanos , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Prognóstico , Estudos Retrospectivos
13.
Sci Rep ; 11(1): 19044, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561515

RESUMO

Carcinoembryonic antigen (CEA) is not only used to aid the diagnosis of lung cancer, but also help monitor recurrence and determine the prognosis of lung cancer as well as evaluate the therapeutic efficacy for lung cancer. However, studies have also shown that CEA is present at low levels in the serum of patients with benign lung diseases (BLD), which will interfere with the accurate judgment of the disease. Due to difference in sample size, detection methods, cutoff values and sources of BLD, the positive rate of CEA in BLD is different with different literature. Therefore, it is necessary to define CEA levels in patients of different BLD in a large sample study. 4796 patients with BLD were included in this study. The results showed that the CEA levels of 3.1% (149/4796) patients with BLD were elevated, with three cases exceeds 20 ng/mL (0.06%, 3/4796). The results from the literature showed that BLD had a mean positive rate of 5.99% (53/885) and only two cases had CEA above 20 ng/mL. The CEA elevations mainly distributed in chronic obstructive pulmonary disease (COPD), pneumonitis and interstitial lung disease and significantly correlated with age of patients (OR 2.69, 95% CI 1.94-3.73, p < 0.001). Pulmonary tuberculosis (7/1311, 0.53%) had the lowest positive rate of CEA elevations while pulmonary alveolar proteinosis (6/27, 22.22%) had the highest positive rate. The majority of patients with abnormally elevated CEA levels had multiple underlying diseases, mainly diseases of the circulatory system (42.28% [63/149]), endocrine diseases (26.85% [40/149]), and respiratory or heart failure (24.16% [36/149]. In endocrine diseases, 87.5% (35/40) of patients had diabetes. In conclusion, CEA is present at a low positive rate in the serum of patients with BLD, but few exceed 20 ng/mL. For lung disease patients, if CEA levels rise, we should carry out comprehensive analysis of types of lung diseases, age of patients, and comorbid diseases.

15.
PLoS One ; 16(9): e0257475, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34543308

RESUMO

In daily life, some people are always seen dedicating available resources to support collective activities. In this paper, we call these people who care group goals more than individual goals dedicators. Inspired by this phenomenon, we studied the role of dedicators on the evolution of cooperation in public goods game (PGG) based on a Chinese Folk Spring Festival Gala. Three types of agents were introduced into our PGG model including cooperators, defectors and dedicators. Dedicators tried to donate when the Gala was short of funds. Cooperators and defectors imitated the strategy of the highest-payoff neighbor based on the rational mechanism. And their imitating probability was modified on account of the emotional mechanism for positive effect of the dedicator's donating behavior and negative effect of continuous poor performance. Through numerical simulations, we found that the existence of dedicators can indeed promote cooperation in PGG. It should be noted that dedicators' willingness to donate was more important than their donation quantity in facilitating cooperation. And the stronger the emotional effect intensity of dedicators' donating behavior was, the better. So, the selfless dedication of participants should be praised to promote cooperation by improving their emotional effect intensity. Last but not least, a reasonable activity budget was needed to sustain the highest level of cooperation.


Assuntos
Comportamento Cooperativo , Aniversários e Eventos Especiais , China , Teoria do Jogo , Humanos , Modelos Teóricos
16.
Mol Clin Oncol ; 15(4): 213, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34476097

RESUMO

Despite the success of anti-HER2 therapy in patients with breast cancer with HER2 amplification or HER2 overexpression, the results of clinical trials on anti-HER2 therapy for lung cancer have not been satisfactory. The aim of the present study was to report a case of a non-smoker, female patient diagnosed with stage IIIA lung adenocarcinoma harboring HER2 amplification. The disease progressed despite surgery and multiple lines of chemotherapy, plus trastuzumab or lapatinib. The pan-ErbB inhibitor pyrotinib (400 mg/day) was commenced as a fourth-line regimen, and the patient achieved complete response with a time to progression (TTP) of 6 months. After the lung adenocarcinoma progressed, pyrotinib was continued, along with anlotinib and nivolumab. The patient achieved stable disease (SD) status with another 6 months of TTP. The overall survival of the patient was 28 months. Therefore, the present case suggests that the development of novel drugs may provide new and effective therapeutic regimens for lung cancer with HER2 amplification.

17.
Bone ; 153: 116169, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34492360

RESUMO

OBJECTIVE: Skeletal dysplasia caused by genetic mutations places a heavy burden on families and society. This study was performed to precise diagnosis of variants of unknown significance and to expand the genotypic spectrum of lethal skeletal dysplasia. METHODS: According to the ultrasonic phenotype of the proband and whole-exome sequencing results, variation sites or genes that may be related to the disease were screened out. We verified the accuracy of the variation site through Sanger sequencing. Using bioinformatics, zebrafish models, and assisted reproduction technology (ART) combined with preimplantation genetic testing for monogenic diseases, the disease-causing mutation was verified. RESULTS: A missense mutation (c.3944G>A, p.Cys1315Tyr) was found in the coding region of COL2A1. Although the mutation is a variant of unknown significance, it is highly conserved and was predicted to be harmful by the SIFT and PolyPhen-2 software. In contrast to the control group, col2a1a mutation-expressing zebrafish larvae showed significant spinal curvature. Through preimplantation genetic testing for monogenic diseases excluding the missense mutation, a child conceived by ART was birthed with normal bone development. CONCLUSION: We identified a de novo mutation in human COL2A1 related to lethal skeletal dysplasia and expanded the mutation spectrum of type II collagenopathies. In addition, we provided a new strategy based on a zebrafish model and ART for patients who harbour variants of unknown significance to have a healthy baby without genetic disease similar to the proband.


Assuntos
Osteocondrodisplasias , Peixe-Zebra , Animais , Colágeno Tipo II/genética , Humanos , Mutação/genética , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/genética , Fenótipo , Peixe-Zebra/genética
18.
Biomed Res Int ; 2021: 5568696, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34337028

RESUMO

Introduction: To date, identifying emergent large vessel occlusion (ELVO) patients in the prehospital stage is important but still challenging. In this present study, we aimed to design a modified prehospital acute stroke severity (mPASS) scale to identify ELVO patients and compared the scale to the PASS scale which has been published. Methods: We retrospectively evaluated a consecutive cohort of acute ischemic stroke (AIS) in our stroke unit who visited the emergercy department. These patients underwent CT angiography (CTA), MR angiography (MRA), or digital subtraction angiography (DSA) at admission. The mPASS scale was calculated based on the National Institutes of Health Stroke Scale (NIHSS) items retrospectively, including the level of consciousness commands, gaze, arm weakness, and aphasia/dysarthria. Receiver operating characteristic (ROC) analysis was used to obtain the area under the curve (AUC) of the mPASS scale, NIHSS, and PASS scale. U-statistics was used to compare the AUC of the mPASS scale to the NIHSS and PASS scale. Results: A total of 382 AIS patients were enrolled. The AUC and specificity of the mPASS scale (0.92, 84.4) were all higher than those of the PASS scale. Cortical symptoms such as gaze palsy and consciousness disorder were more specific indicators for ELVO than motor deficits. Conclusions: The mPASS scale had a better discrimination for identifying ELVO than the PASS scale in our retrospective cohort. It might predict ELVO in an effective and simple way for paramedics in the prehospital triage stage or emergency stage. Moreover, cortical symptoms might have relatively high specificities to predict ELVO on their own.


Assuntos
Arteriopatias Oclusivas/diagnóstico , Hospitalização , Índice de Gravidade de Doença , Acidente Vascular Cerebral/patologia , Idoso , Análise Discriminante , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Sensibilidade e Especificidade
20.
PLoS One ; 16(8): e0256334, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34407117

RESUMO

Natural resources are scarce in the Loess Plateau, and the ecological environment is fragile. Sustainable development requires special attention to resource and environmental carrying capacity (RECC). This study selected 24 representative cities in five natural areas of the Loess Plateau; used the entropy-weight-based TOPSIS method to evaluate and analyze the RECC of each city and region from 2013 to 2018; established a diagnosis model to identify the obstacle factors restricting the improvement of RECC; and constructed the theoretical framework of the RECC system mechanism. The results show that the RECC of the Loess Plateau is increasing in general but is relatively small. The environmental and social subsystems have the highest and lowest carrying capacities, respectively. There is an evident contradiction between economic development and the environment. Population density, investment in technological innovation, per capita sown area, and per capita water resources are the main obstacles affecting the improvement of RECC in the Loess Plateau. Such evaluations and diagnoses can support ecological civilization and sustainable development.

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