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1.
Sci Rep ; 11(1): 20213, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642361

RESUMO

Gut barrier dysfunction is often implicated in pathology following alcohol intoxication and burn injury. MicroRNAs (miRNAs) are negative regulators of gene expression that play a central role in gut homeostasis, although their role after alcohol and burn injury is poorly understood. We performed an integrated analysis of miRNA and RNA sequencing data to identify a network of interactions within small intestinal epithelial cells (IECs) which could promote gut barrier disruption. Mice were gavaged with ~ 2.9 g/kg ethanol and four hours later given a ~ 12.5% TBSA full thickness scald injury. One day later, IECs were harvested and total RNA extracted for RNA-seq and miRNA-seq. RNA sequencing showed 712 differentially expressed genes (DEGs) (padj < 0.05) in IECs following alcohol and burn injury. Furthermore, miRNA sequencing revealed 17 differentially expressed miRNAs (DEMs) (padj < 0.1). Utilizing the miRNet, miRDB and TargetScan databases, we identified both validated and predicted miRNA gene targets. Integration of small RNA sequencing data with mRNA sequencing results identified correlated changes in miRNA and target expression. Upregulated miRNAs were associated with decreased proliferation (miR-98-3p and miR-381-3p) and cellular adhesion (miR-29a-3p, miR-429-3p and miR3535), while downregulated miRNAs were connected to upregulation of apoptosis (Let-7d-5p and miR-130b-5p) and metabolism (miR-674-3p and miR-185-5p). Overall, these findings suggest that alcohol and burn injury significantly alters the mRNA and miRNA expression profile of IECs and reveals numerous miRNA-mRNA interactions that regulate critical pathways for gut barrier function after alcohol and burn injury.

2.
Zhonghua Nei Ke Za Zhi ; 60(7): 650-655, 2021 Jul 01.
Artigo em Chinês | MEDLINE | ID: mdl-34619843

RESUMO

Objective: To explore the difference of coagulation function and its correlation with prognosis in patients with acute respiratory distress syndrome (ARDS) caused by extrapulmonary sepsis and pulmonary infection. Methods: ARDS patients caused by extrapulmonary sepsis and pulmonary infection admitted to the ICU were retrospectively analyzed at the First Affiliated Hospital of China Medical University from July 2017 to June 2019. The clinical characteristics were collected including sequential organ failure assessment (SOFA), coagulation parameters [prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (Fib), D-Dimer (D-D), fibrinogen degradation product (FDP), antithrombin Ⅲ(AT-Ⅲ), platelet (PLT)], duration of mechanical ventilation, length of stay (LOS) in ICU and 28-day mortality. According to the risk factors, the patients were divided into extrapulmonary sepsis group and pulmonary infection group. The correlation analysis between coagulation parameters and the prognosis of ARDS patients were analyzed by multivariate logistic regression analysis. Results: A total of 268 ARDS patients were screened and 28 cases were excluded. Finally, 240 ARDS patients were enrolled, including 145 caused by extrapulmonary sepsis and 95 by pulmonary infection. PT, INR and APTT in the extrapulmonary sepsis group were significantly higher than those in pulmonary infection group (P<0.05). AT-Ⅲ level was lower than that in pulmonary infection group (P<0.05). Ninty-three patients survived at 28 days in the non-pulmonary sepsis group, the mortality rate was 35.9% (52/145). PT, INR, APTT in patients who died at 28 days were significantly higher than those of the patients who survived (P<0.05), while AT-Ⅲ level was lower than those of the patients who survived (P<0.05). 49 patients survived at 28 days in the pulmonary infection group, the mortality rate was 48.4% (46/95). There was no significant difference in the coagulation parameters between two groups. Multivariate logistic regression analysis showed that SOFA score without PLT(OR=1.210,95%CI 1.067-1.372,P=0.003) and INR (OR=2.408,95%CI 1.007-5.760,P=0.048) were independent risk factors for 28-day mortality in extrapulmonary sepsis group. Coagulation parameters are not independent risk factors for 28-day mortality in ARDS patients related to pulmonary infection. Conclusion: There are significant differences in coagulation function between ARDS patients caused by extrapulmonary sepsis or pulmonary infection. INR is an independent risk factor for 28-day mortality in extrapulmonary sepsis group.


Assuntos
Pneumonia , Síndrome do Desconforto Respiratório , Sepse , Humanos , Prognóstico , Estudos Retrospectivos
3.
Zhonghua Yu Fang Yi Xue Za Zhi ; 55(9): 1139-1144, 2021 Sep 06.
Artigo em Chinês | MEDLINE | ID: mdl-34619934

RESUMO

The liquid chromatography tandem mass spectrometry was used to detect the urinary proteomics of 223 residents aged 40-69 years old who participated in the National Upper Gastrointestinal Cancer Early Detection Program in Linqu County, Shandong Province from November 22 to December 7, 2018, and analyze the alcohol consumption related proteomic profiles and individual urinary protein. There were significant differences in urinary protein profiles between alcohol consumption group and non-alcohol consumption group. The expression of 26 urinary proteins was up-regulated and 20 urinary proteins were down-regulated in alcohol consumption group (P<0.05). The differentially expressed proteins had enzyme inhibitor activity and phospholipid binding function, and mainly enriched in pathways involving proximal tubule bicarbonate regeneration, complement and coagulation cascade, and cholesterol metabolism. The protein expressions of complement factor I (CFI), angiotensin converting enzyme 2 (ACE2) and protein C inhibitor (SERPINA5) were positively correlated with daily alcohol consumption.


Assuntos
Neoplasias Gastrointestinais , Proteômica , Adulto , Idoso , Consumo de Bebidas Alcoólicas , Cromatografia Líquida , Detecção Precoce de Câncer , Humanos , Pessoa de Meia-Idade
4.
Rev Sci Instrum ; 92(9): 094707, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598505

RESUMO

A high output impedance current source with a wide bandwidth is needed in electrical impedance tomography systems. Limitations appear mainly at higher frequencies and non-simple loads. In order to adjust the output current, the amplitude and phase are made to achieve the expected value automatically. A current source based on the field programmable gate array is designed. In this paper, we proposed a double DAC differential current source structure. By measuring the voltage of the sampling resistor in series with the load and using the proposed dynamic reference point demodulation algorithm, the actual current amplitude and phase on the load can be quickly obtained. Through the adaptive compensation module, the output current is adjusted to the expected value. The experimental results show that the output resistance of the current source can reach 10 MΩ and the output capacitance can be less than 0.8 pF in the frequency range of 10 kHz-1.28 MHz. At the same time, the current amplitude attenuation is less than 0.016%, and the phase error is less than 0.0025° after compensation. Therefore, the proposed current source achieves widebands, biocompatibility, and high precision.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34620585

RESUMO

BACKGROUND AND PURPOSE: Arterial sclerosis resulting from hypertension slows CSF transportation in the perivascular spaces, showing the intrinsic relationship between the CSF and the blood vasculature. However, the exact effect of hypertension on human CSF flow dynamics remains unclear. The present study aimed to evaluate CSF flow dynamics in treatment-naive patients with essential hypertension using phase-contrast cine MR imaging. MATERIALS AND METHODS: The study included 60 never-treated patients with essential hypertension and 60 subjects without symptomatic atherosclerosis. CSF flow parameters, such as forward flow volume, forward peak velocity, reverse flow volume, reverse peak velocity, average flow, and net flow volume, were measured with phase-contrast cine MR imaging. Differences between the 2 groups were assessed to determine the independent determinants of these CSF flow parameters. RESULTS: Forward flow volume, forward peak velocity, reverse flow volume, reverse peak velocity, and average flow in the patients with hypertension significantly decreased (all, P < .05). Increasing systolic blood pressure was significantly associated with lower forward flow volume (ß = -0.44 mL/mL/mm Hg; 95% CI, -0.83 to -0.06 mL/mL/mm Hg), forward peak velocity (ß = -0.50 cm/s/mm Hg; 95% CI, -0.88 to -0.12 cm/s/mm Hg), reverse flow volume (ß = -0.61 mL/mL/mm Hg; 95% CI, -0.97 to -0.26 mL/mL/mm Hg), reverse peak velocity (ß = -0.55 cm/s/mm Hg; 95% CI, -0.91-0.18 cm/s/mm Hg), and average flow (ß = -0.50 mL/min/mm Hg; 95% CI, -0.93 to -0.08 mL/min/mm Hg). CONCLUSIONS: The CSF flow dynamics in patients with hypertension are decreased, and increasing systolic blood pressure is strongly associated with lower CSF flow dynamics.

6.
Clin Exp Dermatol ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34610158

RESUMO

Monilethrix is a rare hereditary disorder, characterized by beaded appearance of hair that breaks easily, resulting localized or diffused sparse1 . Dermoscopic feature of monilethrix is described as "regularly bended ribbon sign"2 . It is usually caused by autosomal dominant mutations in the type II hair keratin genes KRT 81, KRT 83 and KRT 861 . Here, we reported a 2 years old girl with monilethrix due to a novel heterozygous deletion mutation in KRT86.

7.
Zhonghua Bing Li Xue Za Zhi ; 50(10): 1151-1156, 2021 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-34619869

RESUMO

Objective: To investigate the clinicopathological and molecular features, diagnosis and differential diagnosis of TFE3-rearranged epithelioid hemangioendothelioma (EHE). Methods Two cases of TFE3-rearranged EHE arising from soft tissues, diagnosed by the Pathology Department of the First Affiliated Hospital of Nanjing Medical University from 2013 to 2020 were observed. EnVision method was used for immunophenotyping, fluorescence in situ hybridization (FISH) was used to test TFE3 gene rearrangements and WWTR1-CAMTA1 fusion gene,and next-generation sequencing (NGS) was used to delineate the fusion transcripts. Results: Details of these two cases were as follows: case 1, male, 51 years old, with tumor in the right temporal region; case 2, female, 42 years old, with tumor in the right neck. The tumors showed progressive painless enlargement. Grossly, the tumor of case 1 was multinodular with unclear boundary and grayish red cut surface, while the tumor of case 2, originating from a vein, appeared as a firm, tan mass within vessel wall. Microscopically, both tumors showed moderate cellularity and were consisted of plump, epithelioid, or histiocytoid cells with eosinophilic cytoplasm and mild-to-moderate nuclear pleomorphism. Most of the tumor cells were arranged in solid or alveolar growth patterns, while some tumor cells showed intraluminal papillary growth pattern in case 1 and anastomosing vascular channels and extramedullary hematopoiesis in case 2. Immunohistochemically, the tumor cells showed diffuse positivity for CD31, CD34, ERG, and TFE3. FISH revealed TFE3 break-apart signals in two cases, but WWTR1-CAMTA1 gene fusion was not detected. NGS identified YAP1 (exon1)-TFE3 (exon6) fusion gene in case 2. Clinical follow-up information was available in both cases for a follow-up period of 15 and 59 months respectively. Patient 1 had a relapse 22 months after surgery, and was currently alive with the tumor. Patient 2 remained disease-free. Conclusions: TFE3-rearranged EHE is a rare molecular subtype of EHE, with accompanying characteristic morphologic features. However the morphologic spectrum remains under-recognized, and more experience is needed. Immunohistochemical and molecular examinations are helpful for the diagnosis and differential diagnosis of the disease.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Hemangioendotelioma Epitelioide , Neoplasias de Tecido Vascular , Adulto , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Proteínas de Ligação ao Cálcio , Feminino , Hemangioendotelioma Epitelioide/diagnóstico , Hemangioendotelioma Epitelioide/genética , Hemangioendotelioma Epitelioide/cirurgia , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade
8.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(3): 230-239, 2021 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-34645167

RESUMO

Objective: Peritoneal carcinomatosis refers to a group of heterogeneous (primary or secondary) malignancies in the surface of the peritoneum. Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is a comprehensive treatment strategy aiming at peritoneal carcinomatosis. This study analyzed the efficacy and safety of CRS+HIPEC in patients with peritoneal carcinomatosis, and explored prognostic factors. Methods: In this descriptive case-series study, the clinicopathological data of 1384 consecutive patients with peritoneal carcinomatosis treated in Zhongnan Hospital of Wuhan University (330 patients) and Shijitan Hospital of Capital Medical University (1054 patients) from January 2004 to January 2020 were collected retrospectively. Treatment patterns of CRS+HIPEC characteristics (operative time, number of resected organs, number of stripped peritoneum, number of anastomosis, and HIPEC regimens), safety [blood loss volume, postoperative severe adverse event (SAE) and treatment outcome], survival time and prognostic factors influencing survival were analyzed. The SAE was defined as grade III-IV adverse event according to the Peritoneal Surface Oncology Group International Textbook. Perioperative period was defined from the day of CRS+HIPEC to postoperative 30th day. OS was calculated from the day of CRS+HIPEC to the date of death or the last follow-up. Kaplan-Meier method was used for survival analysis, and log-rank test was used for comparison between groups. Cox regression model was used to identify the prognostic factors. Results: Among 1384 peritoneal carcinomatosis patients, 529 (38.2%) were male; median age was 55 (10-87) years old; median body mass index (BMI) was 22.6 kg/m(2); peritoneal carcinomatosis of 164 (11.8%) patients were from gastric cancer, 287 (20.7%) from colorectal cancer, 356 (25.7%) from pseudomyxoma peritonei, 90 (6.5%) from malignant peritoneal mesothelioma, 300 (21.7%) from gynecological cancer or primary peritoneal carcinoma, and 187 (13.5%) from retroperitoneal sarcoma, lung cancer, breast cancer, and other rare tumors. The median duration of CRS+HIPEC was 595 (90-1170) minutes, median number of resected organs was 2 (0-10), median number of resected peritoneal area were 4 (0-9), median peritoneal cancer index (PCI) was 21(1-39). Completeness of cytoreduction (CC) score of 0-1 was observed in 857 cases (61.9%). Regarding HIPEC regimens, there were 917 cases (66.3%) with cisplatin plus docetaxel, 183 cases (13.2%) with cisplatin plus mitomycin, 43 cases (3.1%) with adriamycin plus ifosfamide, and the other 240 cases (17.3%) with modified regimens. Perioperative SAE developed in 331 peritoneal carcinomatosis patients (23.9%) with 500 cases, of whom 21 patients (1.5%) died during the perioperative period due to ineffective treatment, while the others recovered after active treatment. During median follow-up time of 8.6 (0.3-82.7) months, there were 414 deaths (29.9%). The median OS was 38.2 months (95% CI: 30.6-45.8), and the 1-, 3-, 5-year survival rate was 73.5%, 50.4% and 39.3%, respectively. The median OS of peritoneal carcinomatosis patients from gastric cancer, colorectal cancer, pseudomyxoma peritonei, malignant peritoneal mesothelioma and female genital cancer or primary peritoneal carcinomatosis was 11.3 months (95% CI: 8.9-13.8), 18.1 months (95% CI: 13.5-22.6), 59.7 months (95% CI: 48.0-71.4), 19.5 months (95% CI: 6.0-33.0) and 51.7 months (95% CI: 14.6-88.8), respectively, and the difference among groups was statistically significant (P<0.001). Univariate and multivariate analyses revealed that the primary gastric cancer (HR=4.639, 95% CI: 1.692-12.724), primary colorectal cancer (HR=4.292, 95% CI: 1.957-9.420), primary malignant peritoneal mesothelioma (HR=2.741, 95% CI: 1.162-6.466), Karnofsky performance status (KPS) score of 60 (HR=4.606, 95% CI: 2.144-9.895), KPS score of 70 (HR=3.434, 95% CI: 1.977-5.965), CC score of 1 (HR=2.683, 95% CI: 1.440~4.999), CC score of 2-3 (HR=3.661,95% CI: 1.956-6.852) and perioperative SAE (HR=2.588, 95% CI: 1.846-3.629) were independent prognostic factors influencing survival with statistically significant differences (all P<0.05). Conclusions: CRS+HIPEC is an effective integrated treatment strategy for patients with peritoneal carcinomatosis, which can prolong survival with acceptable safety. Preoperative evaluation of patients' general condition is necessary and CRS+HIPEC should be carefully considered to perform for patients with preoperative KPS score <80. During the operation, the optimal CRS should be achieved on condition that safety is granted. In addition, it is necessary to prevent perioperative SAE to reduce the risk of death in peritoneal carcinomatosis patients.

9.
10.
Zhonghua Yi Xue Za Zhi ; 101(37): 3012-3017, 2021 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-34638193

RESUMO

Objective: To explore the effects of gut microbiota and the serum level of folicacid on psychiatric symptoms in first-episode, drug-free schizophrenic (SCZ) patients. Methods: A total of 100 first-episode, drug-free SCZ patients (SCZ group) from the First Affiliated Hospital of Zhengzhou University and 90 demographically matched healthy individuals (healthy control group) were enrolled. The serum level of folic acid was measured by the electrochemical luminescence method.Positive and Negative Syndrome Scale (PANSS) was used to assess the psychiatric symptoms and Matrics Consensus Cognitive Battery (MCCB) was used to evaluate cognitive function. Bacterial DNA was extracted from the fecal samples for high-through put sequencing of the 16S rRNA.The effects of gut microbiota and folic acid on the psychiatric symptoms and cognitive function in SCZ patients were explored. Results: A total of 41 males and 59 females, with an age of (22.6±8.2) years were included in the patient group, and 32 males and 58 females with an age of (23.0±3.0) years were included in the healthy control group. The fasting folic acid level inserum of the SCZ group was lower than that of healthy control group [6.92(4.98, 8.49) µg/L vs 8.93(7.13, 13.37) µg/L,P<0.001]. The relative abundance of genus Bifidobacterium[0.005(0.003, 0.013) vs 0.014(0.004, 0.031)] and genus Bacteroides[0.015(0.001, 0.091) vs 0.083(0.029, 0.193)]was lower in the SCZ group than that of the healthy control group (both P<0.001). In comparison with the healthy control group, scores of cognitive function in the seven domains were significantly lower in the SCZ group (all P<0.05). In the patient group, the serum level of folic acid was negatively related to the negative symptom score(r=-0.378, P<0.001), but had a positive correlation with the score of speed of processing (r=0.310, P=0.011).In the SCZ group, the relative abundance of the genus Bifidobacterium was positively correlated with the serum level of folic acid (r=0.374,P<0.001) and the score of speed of processing(r=0.330,P=0.003) respectively, but was negatively correlated with the general psychopathology score (r=-0.326, P=0.001). The results of multiple linear regression analysis showed that the interaction term between folic acid and genus Bifidobacteriumin in SCZ patients were correlated with the general psychopathology score, with a regression coefficient of -29.240 (F=8.655, P=0.007). There was no statistical correlation between the aforementioned interaction term and cognitive function (both P>0.05). Conclusion: In first-episode, drug-free SCZ patients, there were decreases in the serum folic acid level and the relative abundance of genus Bifidobacterium, which were related to the psychiatric symptoms, suggesting that these two substances can be used as potential objective indicators for evaluating psychiatric symptoms.


Assuntos
Microbioma Gastrointestinal , Esquizofrenia , Adolescente , Adulto , Cognição , Feminino , Ácido Fólico , Humanos , Masculino , RNA Ribossômico 16S , Adulto Jovem
11.
Zhonghua Gan Zang Bing Za Zhi ; 29(9): 855-860, 2021 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-34638204

RESUMO

Objective: To analyze the clinical value and predictive difference of serum Golgi protein 73 (GP73) and serum autophagy-related protein p62 levels in the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (ACLF). Methods: Clinical data of admitted cases to our hospital from October 2018 to April 2020 were retrospectively analyzed. Simultaneously, there were 32 cases with HBV-related ACLF in group A, 65 cases with hepatitis B virus-related cirrhosis in group B and C (Child-Pugh Class A, 34 cases as B group, and Child-Pugh B/C class, 31 cases as group C), and another 30 healthy subjects served as the control group (group D). The serum GP73 and p62 levels of the four selected groups were measured. ACLF group patients were followed up for 3 months to analyze the prognosis of the patients. The serum GP73 and p62 levels of patients who died and survived during hospitalization were compared. The data were analyzed by one-way analysis of variance, independent sample t-test, and Pearson's correlation analysis. Receiver operating characteristic curve (ROC) was used to analyze the predictive value of GP73 and p62 levels in surviving patients. Results: GP73 levels in the four groups A, B, C and D were (284.30 ± 70.55) ng/ml, (125.33 ± 20.57) ng/ml, (159.82 ± 31.20) ng/ml, and (45.46 ± 10.22) ng/ml, respectively. The p62 levels were (1.30 ± 0.35) ng/ml, (2.88 ± 0.58) ng/ml, (2.02 ± 0.545) ng/ml, and (4.68 ± 1.03) ng/ml, respectively. GP73 detection value was significantly higher in group A than the other three groups (P < 0.05). Group D had significantly lower value than the other three groups (P < 0.05), and group C had significantly higher value than group B (P < 0.05). The detection value of p62 in group A was significantly lower than the other three groups (P < 0.05). Group D had significantly higher value than the other three groups (P < 0.05), and group B had slightly higher value than group C, and the differences were statistically significant (P < 0.05). There was a negative correlation between GP73 and p62 (r = -0.695, P < 0.001). Survived patients GP73 level in the ACLF group was significantly lower than dead patients [(212.17 ± 22.47) ng/ml and (340.08 ± 32.91) ng/ml, t = 12.493, P < 0.05], and p62 level was significantly higher than dead patients [(1.46 ± 0.28) ng/ml and (1.18 ± 0.35) ng/ml, t = 2.445, P < 0.05]. According to the ROC curve analysis results, the area under the curve (AUC) of GP73 was 0.865, the AUC of p62 was 0.750, and the combined AUC of the both was 0.968. Conclusion: Both GP73 and p62 have a certain predictive value for the short-term prognosis of HBV-related ACLF patients, but the combination of the two indicators has a higher predictive value.


Assuntos
Insuficiência Hepática Crônica Agudizada , Carcinoma Hepatocelular , Neoplasias Hepáticas , Insuficiência Hepática Crônica Agudizada/diagnóstico , Vírus da Hepatite B , Humanos , Proteínas de Membrana , Prognóstico , Estudos Retrospectivos
12.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(9): 1310-1318, 2021 Aug 31.
Artigo em Chinês | MEDLINE | ID: mdl-34658344

RESUMO

OBJECTIVE: To optimize the protocol of meniscus cell extraction to enhance the efficiency of cell suspension preparation and maintain a high cell viability for single-cell RNA sequencing. METHODS: We compared the efficiency of the routine cell extraction methods (short-time digestion and long-time digestion) and the optimized protocol for obtaining meniscus cell suspensions by evaluating the cell number obtained and the cell viability. Single-cell RNA sequencing datasets were analyzed to evaluate the stability of the cell suspension prepared using the optimized protocol. The reliability of the optimized protocol was assessed by comparing the single-cell RNA sequencing dataset obtained by the optimized protocol with published single-cell RNA sequencing datasets of the meniscus. RESULTS: The optimized protocol harvested a greater number of cells (over 1×105) than the routine protocols. The cell suspension prepared with the optimized protocol showed a cell viability higher than 80%, the highest among the 3 methods. Analysis of single-cell RNA sequencing datasets showed that the ratio of the mitochondrial genes was below 20% in over 80% of the cells. CD34+ cells, MCAM+ cells and COL1A1+ cells were identified in the datasets. Comparison with the publish datasets showed that the optimized protocol was capable of harvesting COL3A1+, COL1A1+, MYLK+, BMP2+, CD93+ and CDK1+ cells. CONCLUSION: Single-cell suspension prepared from the meniscus can be stably obtained using the optimized protocol for single-cell RNA sequencing using the 10× Genomics platform.


Assuntos
Menisco , Reprodutibilidade dos Testes , Análise de Sequência de RNA
13.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(9): 1319-1328, 2021 Aug 31.
Artigo em Chinês | MEDLINE | ID: mdl-34658345

RESUMO

OBJECTIVE: To explore the molecular mechanism mediating the inhibitory effect of Chuanxiong Rhizoma against brain metastasis of lung cancer using network pharmacology methods and molecular docking. METHODS: The chemical components of Chuanxiong Rhizoma and their targets were obtained through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The relevant targets for brain metastasis of lung cancer were screened using the GeneCards database. Clusterpro-filerR package was used to perform GO and KEGG enrichment analysis. Cytoscape and STRING database were used to construct the "active ingredient-target-disease" network and protein-protein interaction (PPI) network of Chuanxiong Rhizoma. The core components of Chuanxiong Rhizoma and their targets in the treatment of lung cancer brain metastasis were screened based on the topological parameters, and the results were verified using molecular docking and in Chuanxiong extract- treated human lung cancer PC9 cells by detecting the core target with Western blotting. RESULTS: Forty-eight active ingredients of Chuanxiong Rhizoma including (Z)-ligustilide, butylphthalide, oleic acid, and myricetone were screened, which target 49 proteins including INS, BDNF, FOS, VEGFA, PTGS2, ESR1, MAPK14, and PTGS1. These proteins participated in 57 biological functions such as nuclear receptor activity, ligand activation, and transcription factor activity, involving 40 signaling pathways such as prolactin signaling pathway, breast cancer, and etrogen signaling. The results of molecular docking showed that myricetone, butylphthalide, 4-hydroxy-3 butylphthalide, (Z)-ligustilide, and ligustalide-E, among others, had strong affinities to 7 cores targets including BDNF, FOS, PTGS2, and MAPK14. In PC9 cells, treatment with Chuanxiong Rhizoma extract resulted in significant reductions in the phosphorylation levels of PI3K, Akt and VEGF (P < 0.01). CONCLUSION: Chuanxiong Rhizoma contains multiple active ingredients against brain metastasis lung cancer, and these ingredients act on multiple targets involving multiple signal pathways and biological functions.


Assuntos
Neoplasias Encefálicas , Medicamentos de Ervas Chinesas , Neoplasias Pulmonares , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular
14.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(9): 1409-1414, 2021 Aug 31.
Artigo em Chinês | MEDLINE | ID: mdl-34658357

RESUMO

OBJECTIVE: To explore the effect of melatonin (MT) on 2, 2', 4, 4'-tetrabromodiphenylether (PBDE-47)-induced abnormal autophagy and apoptosis in rat adrenal medullary pheochromocytoma PC12 cells. METHODS: PC12 cells were pretreated with a concentration gradient (12.5, 25, 50, 100, and 200 µmol/L) of melatonin for 2 h before exposure to 20 µmol/L PBDE-47 for 24 h to determine the optimal concentration of melatonin for cell treatment. In subsequent experiments, PC12 cells were treated with 0.5‰ DMSO (control group), 20 µmol/L PBDE-47, 25 µmol/L melatonin, or both PBDE-47 and melatonin. Immunofluorescence assay was used to detect the positive staining of microtubule associated protein 1 light chain 3 (LC3; a marker protein of autophagy); Western blotting was performed to determine the expression levels of the key autophagic proteins including autophagy-related protein 7 (ATG7), LC3-Ⅱ and autophagy substrate p62, and the key apoptotic proteins including active cysteine-containing aspartate specific protease-3 (active caspase-3) and cleaved poly(ADP ribose) polymerase (cleaved PARP). RESULTS: PBDE-47 treatment significantly reduced the viability of PC12 cells (P=0.001), but pretreatment with 25 µmol/L melatonin maintained a cell viability over 80% following exposure to PBDE-47 (P=0.023). PBDE-47-treated PC12 cells showed obviously enhanced immunofluorescent staining of LC3 protein, a significantly decreased expression of ATG7 and increased expression levels of p62, LC3-Ⅱ, active caspase-3 and cleaved PARP (P < 0.001). The cells treated with both PBDE-47 and melatonin showed obviously reduced staining of LC3 protein with a signficantly increased expression level of ATG7 (P=0.034) and decreased expressions of p62 (P=0.048), LC3-Ⅱ (P=0.018), active caspase-3 (P < 0.001) and cleaved PARP (P=0.032). CONCLUSION: PBDE-47 exposure impairs autophagy to cause autophagosome accumulation and promote apoptosis of PC12 cells. Melatonin can improve PBDE-47-induced abnormal autophagy and apoptosis and thus promote the survival of PC12 cells.


Assuntos
Melatonina , Animais , Apoptose , Autofagia , Éteres Difenil Halogenados , Melatonina/farmacologia , Células PC12 , Ratos
15.
Artigo em Chinês | MEDLINE | ID: mdl-34666436

RESUMO

Objective: To explore the method and plausibility of using free rectus abdominis flap (FRAF) to reconstruct the major and complex defects in the craniofacial regions after ablation of advanced sinonasal carcinoma. Methods: From 2007 to 2018 at No. 980 Hospital of Joint Logistic Supportive Force of People's Liberation Army of China, 13 patients with advanced carcinoma of nasal cavity and paranasal sinuses, including 11 males and 2 females, aged from 33 to 67 years, were treated with FRAF to repair the invasion of skull base, face and orbit. Based on adequate and meticulous preoperative evaluations on patients and tumors, complete resection of tumor bulks was performed. According to the sites, characters and extents of the defects, FRAF was introduced in different ways into reconstruction of major and complex defects in the craniofacial regions after resection of advanced sinonasal carcinomas, restoring the structure and contour of the craniofacial region. Results: Complete resection of tumors was achieved in all cases. For repairing the major and complex defects resulted from tumor ablation, FRAF graft was conducted in 13 patients with advanced sinonasal carcinomas. The recipient vessels were facial artery and vein in 9 cases, superficial temporal artery and vein in 4 cases. Vascular bridging with the external jugular vein was carried out in 2 cases who underwent submandibular neck dissections, in which facial artery and vein were used as recipient vessels. Free fibular flap was used along with FRAF in a case undergone bilateral maxillectomy. Pedicled galea capitis and periosteal flap were applied simultaneously in 3 cases with dura defects at the skullbase resulted from tumor resection. All flaps used in 13 cases survived uneventfully without major complications, with successful repair of defects, reconstruction of structures and restoration of contour of craniofacial regions. Conclusion: With adequate evaluation of resectability of tumors as well as nature and extent of defects after tumor removal, FRAF transplantation is an ideal method and strategy of choice for reconstructing the major and complex defects in craniofacial regions resulted from tumor ablation of advanced sinonasal carcinomas.

16.
Artigo em Chinês | MEDLINE | ID: mdl-34666446

RESUMO

Objective: To analyze the clinical manifestations of a patient with branchiootic syndrome(BOS) and her families and to carry out genetic testing in order to specify the biological pathogenesis. Methods: Clinical data of the patient and her families were collected. Genomic DNA in the peripheral blood of the proband and her family members was extracted. All exons of 406 deafness-related susceptible genes as well as their flanking regions were sequenced by high-throughput sequencing, and the mutation sites of the proband and her parents were validated by Sanger sequencing. Results: There were nine members in three generations, of whom four presented with hearing loss, preauricular fistula and branchial fistula which met the diagnostic criteria of BOS. Proband and her mother presented with auricle malformation and inner ear malformation. And no one had abnormalities in the kidneys of all the patients. Pedigree analysis revealed that the mode of inheritance in the family was consistent with the autosomal dominant pattern. Mutational analysis showed that all the affected patients detected a heterozygous frameshift variation c.1255delT in the EYA1 gene, which had not been reported. Genotype and phenotype were co-isolated in this family. Such a frameshift variation produced a premature termination codon, thereby causing premature termination of translation (p.C419VFS*12). ACMG identified that the mutation was pathogenic. This mutation was novel and not detected in controls. A heterozygous missense variation mutation c.403G>A(p.G135S) in EYA1 gene was also detected in three members of this family. ACMG identified that the mutation clinical significance was uncertain. However, two of whom were normal, which seemed the disease was not caused by this mutation in this family. Conclusions: A novel frameshift mutation in EYA1(c.1255delT) is the main molecular etiology of BOS in the Chinese family. This study expands the mutational spectrum of EYA1 gene. The clinical manifestations are heterogeneous among patients in this family. The diagnosis of BOS should combine gene tests with clinical phenotypes analysis.

17.
Artigo em Chinês | MEDLINE | ID: mdl-34666447

RESUMO

Objective: To investigate the clinical diagnosis and treatment of congenital laryngotracheoesophageal cleft (LTEC) in children. Methods: The clinical data of 8 children (including 7 males and 1 female)with congenital laryngotracheoesophageal cleft from January 2016 to June 2020 were retrospectively analyzed. The median diagnosing age was 3.75 months (5 days to 12 months). According to the modified Benjamin Inglis classification proposed by Sandu in 2006,there were 3 cases of type Ⅱ, 3 cases of type Ⅲa, 1 case of type Ⅲb and 1 case of type Ⅳa. All children were followed up regularly. Results: Six patients were treated for recurrent bronchopneumonia and aspiration during feeding. The patients were first treated in the pneumology departmentt or intensive care unit. Six patients combined with other malformations. Endoscopic repair operations were performed in 6 cases (3 cases of type Ⅱ, 3 cases of type Ⅲ a), 1 case of LTEC was operated through cervical approach, and 1 case of type IVa LTEC associated with VACTERL was repaired under thoracoscope combined with suspension laryngoscope. Seven patients underwent tracheotomy before or during the repair operations. Gastrostomy was performed in 2 children. The operations were successfully performed in all cases. Three children with type Ⅱ LTEC recovered well and decannulated. One case of type Ⅲa was followed up for 5 months with occasionally choking while feeding. Two cases of type Ⅲa, 1 case of type Ⅲb and 1 case of type Ⅳa died due to severe reflux, tracheomalacia or respiratory failure. Conclusions: Congenital LTEC is a rare congenital malformation which is difficult to diagnose for the poor specificity of clinical manifestations. LTEC needs to be classified by endoscopy examination under general anesthesia. Severe cases of LTEC have poorer outcomes than the mild cases, and the perioperative managements need multi-disciplinary cooperation to reduce the mortality.

19.
QJM ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34668535

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic. Age is an independent factor in death from the disease, and predictive models to stratify patients according to their mortality risk are needed. AIM: To compare the laboratory parameters of the younger (≤70) and the elderly (>70) groups, and develop death prediction models for the two groups according to age stratification. DESIGN: A retrospective, single-center observational study. METHODS: This study included 437 hospitalized patients with laboratory-confirmed COVID-19 from Tongji Hospital in Wuhan, China, 2020. Epidemiological information, laboratory data, and outcomes were extracted from electronic medical records and compared between elderly patients and younger patients. First, recursive feature elimination (RFE) was used to select the optimal subset. Then, two random forest (RF) algorithms models were built to predict the prognoses of COVID-19 patients and identify the optimal diagnostic predictors for patients' clinical prognoses. RESULTS: Comparisons of the laboratory data of the two age groups revealed many different laboratory indicators. Recursive feature eliminatin (RFE) was used to select the optimal subset for analysis, from which 11 variables were screened out for the two groups. The RF algorithm were built to predict the prognoses of COVID-19 patients based on the best subset, and the area under ROC curve (AUC) of the two groups is 0.874 (95% CI : 0.833-0.915) and 0.842 (95% CI: 0.765-0.920). CONCLUSION: Two prediction models for COVID-19 were developed in the patients with COVID-19 based on random forest algorithm, which provides a simple tool for the early prediction of COVID-19 mortality.

20.
Beijing Da Xue Xue Bao Yi Xue Ban ; 53(5): 907-914, 2021 Oct 18.
Artigo em Chinês | MEDLINE | ID: mdl-34650293

RESUMO

OBJECTIVE: To analyze the effects of visual restoration after cataract surgery on plantar pressure and biomechanics of foot in elder individuals. METHODS: Thirty-two patients [male/female 5/27, (70.1±5.2) years old] with age-related cataract were recruited between October 2016 and December 2019. The footscan system was employed to record the data of plantar pressure during level walking before and 1-month after the cataract surgery. Parameters of peak pressure (PP), impulse (I), pressure-time integral (PTI) and time to peak pressure (TPP) from the regions of the 1st toe (T1), 2nd to 5th toes (T2-5), 1st to 5th metatarsal heads (M1-M5), midfoot (MF), medial hindfoot (HM) and lateral hindfoot (HL) were analyzed respectively. RESULTS: Post-operatively, the visual function was effectively reconstructed with improved visual acuity in both eyes (Z=-4.878, -4.801; P < 0.001). The PP (t=2.266, P=0.031) and I (t=2.152, P=0.039) values in M2 region on the dominant side (right foot) increased statistically at post-operative phase, while the changes of pressure and temporal para-meters in other regions remained stable. There was laterality in plantar pressure at pre-operative phase, manifested as greater PP values in M1, M2, MF, and HM regions on the dominant sides (t=-2.414, -2.478, -2.144, -5.269; P < 0.05), greater PP values in T1, M3, M5 and HL regions on the non-dominant sides (t=4.830, 3.155, 2.686, 3.683; P < 0.05), greater I values in M1, MF, and HM regions on the dominant sides (t=-2.380, -2.185, -5.320; P < 0.05) and greater I values in T1, M3, M5 and HL regions on the non-dominant sides (t=4.489, 2.247, 2.838, 3.992; P < 0.05). post-operatively, the pressure tended to be compatible between the two sides in regions of M3 and MF, while the magnitude of laterality in regions of M1 (ZPP△= -2.721, P=0.007; ZI△=-2.581, P=0.010), M2 (ZPP△=-2.674, P=0.007; ZI△=-2.375, P=0.018) and M5 (ZPP△=1.991, P=0.046; ZI△=2.150, P=0.032) was further increased. CONCLUSION: Changes in plantar pressure after cataract surgery were characterized as increased pressure in the 2nd metatarsal head area on the dominant side. Visual restoration might intensify the laterality in the medial of forefoot on the dominant side and the lateral of forefoot on the non-dominant side.


Assuntos
, Idoso , Fenômenos Biomecânicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pressão
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