الملخص
ObjectiveTo investigate the effect of oxaliplatin on the activation of hepatic stellate cells （HSCs）， as well as the association of oxaliplatin with microRNA-30a-5p and autophagy. MethodsHSC-LX2 cells were cultured and divided into groups according to the following three protocols： control group， PDGF treatment group， oxaliplatin treatment group， oxaliplatin+PDGF treatment group； control group， microRNA-30a-5p transfection group， PDGF treatment group， microRNA-30a-5p transfection+PDGF treatment group； control group， 3-MA group， microRNA-30a-5p inhibitor group， microRNA-30a-5p inhibitor+3-MA group. Western Blot was used to measure the expression of HSC activation-related proteins （Collagen-I and alpha-smooth muscle actin ［α- SMA］） and HSC autophagy-related proteins （Beclin-1， P62， and LC3B）； LysoTracker staining and immunofluorescence assay were used to measure the expression of LC3B autophagosomes； RT-PCR was used to measure the expression level of microRNA-30a-5p； bioinformatics techniques were used to predict the potential targets of microRNA-30a-5p in HSCs. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsAfter the cells were treated with oxaliplatin， RT-PCR results showed that the oxaliplatin treatment group had a significantly higher expression level of microRNA-30a-5p than the control group （P<0.01）； Western Blot showed that the oxaliplatin treatment group had significant reductions in the expression levels of the HSC activation-related proteins α-SMA and Collagen-Ⅰ and the autophagy-related proteins Beclin 1 and LC3BⅡ/Ⅰ （all P<0.001）； immunofluorescence assay showed that the oxaliplatin treatment group had a significantly lower number of autophagosomes than the control group （P<0.05）. After HSC-LX2 cells were transfected with microRNA-30a-5p mimic， compared with the control group， the microRNA-30a-5p mimic group had significant reductions in the expression levels of the autophagy-related proteins Beclin 1 and LC3BⅡ/Ⅰ （P<0.05） and the HSC activation-related protein Collagen-Ⅰ （P<0.001）； after HSC-LX2 cells were transfected with microRNA-30a-5p inhibitor， Western Blot showed that compared with the control group， the microRNA-30a-5p inhibitor group had significant increases in the expression levels of the HSC activation-related proteins Collagen-Ⅰ and α-SMA and the autophagy-related protein Beclin 1 （t=2.41， 2.32， and 4.57， all P<0.05）. Western Blot showed that compared with the control group， the microRNA-30a-5p inhibitor group had significant increases in the expression levels of the HSC autophagy-related protein Beclin 1 and the HSC activation-related protein α-SMA （both P<0.05）， and after the treatment with the autophagy inhibitor 3-MA， there were no significant differences in the expression of these proteins between the two groups （P>0.05）. The bioinformatics analysis using TargetScan， PicTar， and miRanda databases showed that the autophagy-related protein Beclin-1 might be a potential target of miRNA-30a-5p. ConclusionOxaliplatin can inhibit the activation of HSCs by upregulating the expression of microRNA-30a-5p， which provides new ideas and a new target for the treatment of liver fibrosis.
الملخص
BACKGROUND@#Transcription factor (TF) can bind specific sequences that either promotes or represses the transcription of target genes, and exerts important effects on tumorigenesis, migration, invasion. Staphylococcal nuclease-containing structural domain 1 (SND1), which is a transcriptional co-activator, is considered as a promising target for tumor therapy. However, its role in lung adenocarcinoma (LUAD) remains unclear. This study aims to explore the role of SND1 in LUAD.@*METHODS@#Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) database was obtained to explore the association between SND1 and the prognosis, as well as the immune cell infiltration, and subcellular localization in LUAD tissues. Furthermore, the functional role of SND1 in LUAD was verified in vitro. EdU assay, CCK-8 assay, flow cytometry, scratch assay, Transwell assay and Western blot were performed.@*RESULTS@#SND1 was found to be upregulated and high expression of SND1 is correlated with poor prognosis of LUAD patients. In addition, SND1 was predominantly present in the cytoplasm of LUAD cells. Enrichment analysis showed that SND1 was closely associated with the cell cycle, as well as DNA replication, and chromosome segregation. Immune infiltration analysis showed that SND1 was closely associated with various immune cell populations, including T cells, B cells, cytotoxic cells and dendritic cells. In vitro studies demonstrated that silencing of SND1 inhibited cell proliferation, invasion and migration of LUAD cells. Besides, cell cycle was blocked at G1 phase by down-regulating SND1.@*CONCLUSIONS@#SND1 might be an important prognostic biomarker of LUAD and may promote LUAD cells proliferation and migration.
الموضوعات
Humans , Prognosis , Proteomics , Lung Neoplasms/genetics , Oncogenes , Adenocarcinoma of Lung/genetics , Biomarkers , Endonucleases/geneticsالملخص
Objective:To investigate the role of miR-765 in papillary thyroid carcinoma (PTC) cells and further uncover the associated signaling mechanism.Methods:qPCR was used to assess miR-765 expression in normal human thyroid cell line (Nthy-ori 3-1) and human PTC cell lines (B-CPAP and TPC-1). PTC cells were divided into blank control group (BC) without special treatment, negative control group (NC) that was transfected with negative control sequences, and miR-mimic group that was transfected with miR-mimic. Transfection with miR-mimic was used to up-regulate the expression of miR-765 in PTC cells. CCK-8, plate colony formation, wound-healing, and Transwell invasion assays were used to assess the proliferation, migration, and invasion of PTC cells, respectively. Western blot assay was used to assess the level of nuclear β-catenin, the key protein of the Wnt/β-catenin pathway, in PTC cells.Results:The level of miR-765 expression of PTC cells was significantly lower than that of Nthy-ori 3-1 cells (B-CPAP, P=0.0003; TPC-1, P=0.0003). Transfection with miR-mimic significantly up-regulated miR-765 expression in PTC cells (B-CPAP, P<0.0001; TPC-1, P<0.0001). Results of CCK-8 assay (B-CPAP, P<0.05; TPC-1, P<0.05), plate colony formation assay (B-CPAP, P=0.0001; TPC-1, P<0.0001), wound-healing assay, and Transwell invasion assay (B-CPAP, P=0.001; TPC-1, P=0.0014) showed that up-regulating the expression of miR-765 significantly inhibited the proliferation, migration, and invasion of PTC cells. Western blot results showed that up-regulating the expression of miR-765 significantly reduced nuclear β-catenin (B-CPAP, P=0.0039; TPC-1, P=0.0004) . Conclusion:up-regulating the expression of miR-765 inhibits the proliferation, migration, and invasion of PTC cells and the Wnt/β-catenin signaling pathway, which not only proposes miR-765 as a novel potential therapeutic target for PTC, but also further revealed the associated mechanism.
الملخص
Lung cancer remains the leading cause of cancer-related death world-wide. Therapy resistance and relapse are considered major reasons contributing to the poor survival rates of lung cancer. Accumulated evidences have demonstrated that a small subpopulation of stem-like cells existed within lung cancer tissues and cell lines, possessing the abilities of self-renewal, multipotent differentiation and unlimited proliferation. These lung cancer stem-like cells (LCSCs) can generate tumors with high effeciency in vivo, survive cytotoxic therapies, and eventually lead to therapy resistance and recurrence. In this review, we would like to present recent knowledges on LCSCs, including the origins where they come from, the molecular features to identify them, and key mechanisms for them to survive and develop resistance, in order to provide a better view for targeting them in future clinic. .
الموضوعات
Humans , Cell Line, Tumor , Drug Resistance , Drug Resistance, Neoplasm , Lung/pathology , Lung Neoplasms/metabolism , Neoplasm Recurrence, Local , Neoplastic Stem Cells/pathologyالملخص
Objective:To investigate the application value of 'N' shaped Trocar placement in Da Vinci robotic bariatric and metabolic surgery.Methods:The retrospective and descriptive study was conducted. The clinical data of 69 patients who underwent Da Vinci robotic bariatric and metabolic surgery in the China-Japan Union Hospital of Jilin University from March to October 2020 were collected. There were 18 males and 51 females, aged from 12 to 67 years, with a median age of 34 years. The surgery was performed with the 'N' shaped Trocar placement by the same team of surgeons. The Da Vinci robotic sleeve gastrectomy, Da Vinci robotic single-anastomosis duodenal-ileal bypass with sleeve gastrectomy or Da Vinci robotic biliopancreatic diversion with duodenal switch was selected according to the patient's condition. Observation indicators: (1) surgical and post-operative conditions; (2) follow-up. Follow-up using the outpatient examination, telephone interview and WeChat to detect the body weight, body mass index, fasting blood glucose, glycosylated hemoglobin, total cholesterol, Trocar-related complications of patients at postoperative 3 months. The follow-up was up to November 2020. Measurement data with normal distribution were represented as Mean± SD, and comparison of general data before and after surgery was analyzed using the paired t test. Measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers. Results:(1) Surgical and postoperative conditions: of the 69 patients, 34 cases received Da Vinci robotic sleeve gastrectomy, 34 cases received Da Vinci robotic single-anastomosis duodenal-ileal bypass with sleeve gastrectomy, and 1 case received Da Vinci robotic biliopancreatic diversion with duodenal switch. There was no conversion to open surgery or laparoscopic surgery. The operation time of 69 patients was (161±52)minutes, and the volume of intraoperative blood loss was 30 mL(range, 10-100 mL). Two of 69 patients had post-operative complications. One of them with postoperative abdominal hemorrhage was cured after symptomatic treatment and discharged on the 10th day after surgery. The other one patient with postoperative peritoneal effusion was cured and discharged from hospital after puncture drainage and symptomatic treatment. No Trocar-related complication such as Trocar foramen bleeding and Trocar foramen hernia occurred in the 69 patients. The duration of postoperative hospital stay of 69 patients was (6±3)days. (2) Follow-up: 47 of 69 patients were followed up for 3 months. The body mass, body mass index, fasting blood glucose, glycosylated hemoglobin, and total cholesterol were (86±19)kg, (30±5)kg/m 2, (5.2±0.7)mmol/L, 5.3%±0.6%, (4.3±1.3)mmol/L at postoperative 3 months, which had significant differences compared with the preoperative indicators ( t=6.101, 8.261, 2.973, 2.567, 2.098, P<0.05). All the 47 patients had no Trocar-related complications during the follow-up. Conclusion:The 'N' shaped Trocar placement method is safe and feasible in the Da Vinci robotic bariatric and metabolic surgery, with good efficacy.
الملخص
Objective:To analyze the effect of long-acting somatostatin treatment on blood glucose, blood lipid, insulin resistance and islet function in patients with acromegaly after surgical treatment.Methods:Self-control study before and after treatment was used. A total of 30 subjects who were diagnosed as acromegalyand received surgical treatment in Beijing Tiantan Hospital from January 2016 to January 2018 were enrolled in this study. Because patients′ growth hormone (GH) level was notc ompletely controlled after surgery, all the patients were treated with long-acting octreotide for more than 1 year. Before and 1 year after treatment, oral glucose tolerance testing (OGTT) was performed at pretreatment and 1 year after initiation of treatment with long-acting octreotide. Homeostatic model assessment (HOMA) was used to estimate insulin resistance (HOMA-IR) and β-cell function (HOMA-β). The HOMA-IR and HOMA-β were detected by 75 g glucose, insulin, C peptide release test and growth hormone suppression test to evaluate the therapy effects on insulin resistance and islet function.Results:The levels of GH, insulin-like growth factor 1(IGF-1), HOMA-IR, HOMA-β, and triacylglycerol(TG) were all decreased after 1 year of octreotide treatment compared with that before treatment: (2.8 ± 2.5) μg/L vs. (12.1 ± 10.5) μg/L, (356.8 ± 209.2) μg/L vs. (698.1 ± 207.3) μg/L, 1.56 ± 1.08 vs. 2.71 ± 1.52, 1.01 ± 0.97 vs. 4.87 ± 3.57, (1.12 ± 0.49) mmol/L vs. (1.76 ± 0.92) mmol/L, and the differences were statistically significant ( P<0.05). After treatment, the level of fasting blood glucose was increased compared with that before treatment: (5.83 ± 1.19) mmol/L vs.(5.11 ± 1.73) mmol/L, and the difference was statistically significant ( P<0.05). While there were no significant changes in postprandial 2 h blood glucose and glycosylated hemoglobin (GHb), total cholesterol (TC), low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels before and after treatment ( P>0.05). Conclusions:Long-acting somatostatin therapy can effectively improve the insulin sensitivity of acromegaly patients, reduce β cell function, and slightly increase fasting blood glucose. It has no adverse effect on GHb, and can reduce the level of TG of the patients.
الملخص
BACKGROUND@#Lung cancer is a malignant with high incidence and mortality and adenocarcinoma is among the most popular subtypes. Epidermal growth factor receptor (EGFR) mutation is one of the most important driver mutations for lung adenocarcinoma and EGFR-tyrosine kinase inhibitor (TKI) will benefit those patients with sensitive EGFR mutations. Recently, immune checkpoint inhibitor (ICI) therapy, provide a new breakthrough treatment for lung cancer patients. Whereas immunotherapy as an emerging treatment does not benefit patients with EGFR mutations, for which mechanistic studies are poorly defined and focused on the link of EGFR mutations and programmed cell death-ligand 1 (PD-L1) expression, we speculate that the different immune microenvironment associated with the two classes of patients.@*METHODS@#Lung adenocarcinoma datasets were collected from the Cancer Genome Atlas (TCGA) database, and clinical information and gene expression profiles were downloaded. The immune related lymphocyte infiltration in TCGA database were generated through timer 2.0 GSEA was used to analyze the difference of pathway expression between EGFR mutant patients and wild type patients.@*RESULTS@#EGFR mutation was more frequently among women and never smokers. Immunoinfiltration analysis showed that patients with EGFR mutation tends to have more tumor associated fibroblasts, common myeloid progenitor cells, hematopoietic stem cells, effector CD4⁺ T cells and natural killer T cells infiltration, and less memory B cells, naïve B cells, plasma B cells, plasmacytoid dendritic cells, memory CD4⁺ T cells, CD4⁺ helper T cells 2, naive CD8⁺ T cells, CD8⁺ T cells and central memory CD8⁺ T cells infiltration. Moreover, patients with more infiltration of CD8⁺ T cells, natural killer T cells, memory B cells and hematopoietic stem cells, tends have better prognosis (Log-rank test, P=0.017, 0.0093, 0.018, 0.016). However, the patients with more CD4⁺ T th2 infiltration in the tumor tends to have worse prognosis (Log-rank test, P=0.016). Furthermore, the results of gene set enrichment analysis showed that compared with the lung adenocarcinoma patients with EGFR wild type, the three pathways positive regulation of natural killer (NK) cell-mediated immune response to tumor cells, NK cell activation involved in immune response, and NK cell-mediated immune response to tumor cells related to natural killer cells in patients with EGFR mutation were down regulated, while the pathway the positive regulation of cytokine secretion involved in immune response was up-regulated in EGFR mutation patients.@*CONCLUSIONS@#The tumour microenvironment of patients with EGFR mutations lacks potent tumour killing effector cells and appears dysfunctional with effector cells. This may be a potential reason for the poor efficacy of immunotherapy in patients with EGFR mutations.
الملخص
Preeclampsia is the main cause of poor maternal-fetal outcomes. A series of cell and animal experiments, and a small number of clinical studies have shown that pravastatin can prevent and treat preeclampsia by regulating angiogenesis, increasing the expression of heme oxygenase, and stimulating the production of nitric oxide without any reported adverse effects during pregnancy. We review the latest progress on the mechanism, effect, and safety of pravastatin in the prevention and treatment of preeclampsia.
الملخص
Epigenetic modification is closely related to the occurrence and development of tumors. It mainly regulates gene function and expression level through DNA methylation, histone modification, regulation of non-coding RNA and chromatin structure reconstruction. At present, epigenetic drugs have been gradually applied to the treatment of malignant tumors. Common drug types include: DNA methyltransferase inhibitors and histone deacetylase inhibitors. However, these drugs still have many shortcomings and a wide range of clinical applications need further research. Encouragingly, the epigenetic drugs in combination with various anti-tumor drugs have shown great application potential. In this paper, we summarized the development mechanism of epigenetics in malignant tumors and the progress of related drugs.
الملخص
Objective:To evaluate the efficacy of Dihuang-Yinzi Decoction combined with donepezil hydrochloride in the treatment of mild to moderate Alzheimer's disease (AD). Methods:114 patients with mild to moderate AD in the First Hospital of Yulin in Suide District from February 2017 to February 2019 were divided into two groups according to the method of random number table, with 57 cases in each group. The control group took donepezil hydrochloride tablets orally, and the study group took Dihuang-Yinzi Decoction based on the control group. Both groups were treated continuously for 3 months. The activities of daily living scale (ADL), Mini-Mental State Examination (MMSE) and the Alzheimer’s disease assessment scale-cognitive section (ADAS-cog) were used to evaluate the life ability and cognitive function of patients. The concentrations of Notch 1 signaling protein, a disintegrin and metalloproteinase 10 (ADAM10) and β-amyloid precursor protein endonuclease 1 (BACE1) in serum were detected by Western blot. The levels of acrolein were detected by ELISA, the adverse reactions during the treatment were recorded, and the clinical efficacy was evaluated. Results:The total effective rate was 84.2% (48/57) in the study group and 64.9% (37/57) in the control group. The difference between the two groups was statistically significant ( χ2=5.596, P=0.018). After the treatment, the ADL and ADAS-cog scores of the study group were lower than those of the control group ( t values were 5.939, 6.124, respectively, all Ps<0.01), and MMSE scores were higher than that of the control group ( t=6.087, P<0.01). The levels of Notch1 signaling protein (3.43 ± 0.58 vs. 1.31 ± 0.47, t=21.440) and ADAM10 (1.86 ± 0.23 vs. 1.12 ± 0.25, t=16.446) in the study group were higher than those of the control group ( P<0.01), and the levels of BACE1 (0.62 ± 0.15 vs. 0.98 ± 0.17, t=11.988) and acrolein (2.19 ± 0.39 nmol/mg vs. 4.76 ± 0.54 nmol/mg, t=12.354) were lower than those of the control group ( P<0.01). The adverse reaction rate was 14.7% (11/57) in the study group and 14.0% (8/57) in the control group, and there was no significant difference between the two groups ( χ2=0.568, P=0.451). Conclusions:Dihuang-Yinzi Decoction combined with donepezil hydrochloride tablets can effectively improve the cognitive function and life ability of patients with mild to moderate AD, with clinical efficacy.
الملخص
BACKGROUND@#The incidence and mortality of lung cancer often rank first in all malignant tumors. DNA methylation, as one of epigenetics, often participates in the development and progression of tumors. CDO1 as a tumor suppressor gene always undergoes methylation changes early in tumor development. Therefore, this study aims to discuss the value of CDO1 methylation in the early diagnosis of lung cancer.@*METHODS@#Peripheral blood samples were collected from tumor patients and healthy people. Detection of the methylation level of CDO1 in plasma by sulfite modification and quantitative real-time PCR.@*RESULTS@#The level of gene methylation in peripheral blood of lung cancer patients was significantly higher than that of benign lung disease patients and healthy people. The methylation level of CDO1 was significantly different in the stratified comparison of gender, lymph node metastasis and tumor-node-metastasis (TNM) stage (P<0.05). The sensitivity and specificity of CDO1 were 52.2% and 78.6%, respectively. The overall accuracy of the diagnosis was significantly higher than that of the clinical tumor markers, and the sensitivity of CDO1 to stage I and II patients was the highest (40.8%, 47.1%). In addition, CDO1 could effectively increase the sensitivity of diagnosis in multiple joint examinations.@*CONCLUSIONS@#Detecting the methylation level of CDO1 has a potentially huge advantage for the early diagnosis of lung cancer.
الملخص
OBJECTIVE@#To study the distribution of α- and β -thalassemia-related mutations in Pingxiang area of Jiangxi Province, China.@*METHODS@#PCR and reverse dot blotting (PCR-RDB) were carried out to detect common mutations of α and β globin genes among 2558 individuals with positive results of primary screening.@*RESULTS@#The PCR-RDB assay has identified 1222 carriers of thalassemia-related mutations, which yielded a detection rate of 47.8%. Among these, 645 individuals (including homozygous patients) have carried α globin gene mutations, with the common types including -αSEA/αα, -α/αα and -α/αα. 539 individuals have carried β globin gene mutations, with the common types including IVS-Ⅱ-654, CD41-42, CD17, CD28, CD27-28, βE, and CD71-72. Thirty eight individuals (1.5%) have carried α and β globin gene mutations simultaneously.@*CONCLUSION@#The carrier rate for α and β globin gene mutations in Jiangxi is high. Attention should be paid to newborn screening as part of the birth defect prevention and control program in order to reduce the birth rate of thalassemia in this region.
الملخص
BACKGROUND@#Lung cancer is the most common malignancy world-wide. Small cell lung cancer is the deadliest subtype of lung cancer, which features such as rapid growth, early metastasis, and high vascularization. Apatinib is a vascular endothelial growth factor receptor 2 inhibitor independently developed in China, which has a significant inhibition in a variety of solid tumors. The purpose of this study is to investigate the effects of Apatinib alone or Apatinib combined with mammalian target of rapamycin (mTOR) inhibitor, CCI-779, on small cell lung cancer cell line NCI-H446 in vitro.@*METHODS@#The small cell lung cancer cell line NCI-H446 was grew in vitro. The effects of Apatinib alone or Apatinib combined with CCI-779 on proliferation, apoptosis, cell cycle and migration of NCI-H446 small cell lung cancer cells were detected by CCK8; FACS and transwell assays were also carried out; Western blot assays were used to detect vascular endothelial growth factor and cell cycle related protein expression.@*RESULTS@#CCK8 assays showed that high concentration of Apatinib could inhibit the proliferation of NCI-H446 cells. Apoptosis assays showed that high concentration of Apatinib could induce NCI-H446 cell apoptosis. Transwell assays showed that high concentration of Apatinib could inhibit NCI-H446 cell migration. After combined with mTOR inhibitor CCI-779, low concentration of Apatinib could inhibit the proliferation and migration of NCI-H446 small cell lung cancer cells and induce apoptosis.@*CONCLUSIONS@#Apatinib has a concentration-dependent effect on the small cell lung cancer cell line NCI-H446. High concentration of Apatinib can inhibit the proliferation and migration of NCI-H446 small cell lung cancer cells, induce apoptosis. Apatinib combined with the mTOR inhibitor CCI-779 can sensitize the NCI-H446 cells to Apatinib.
الملخص
Objective@#To investigate the blood lead level of outpatient children and associated factors in Zhuzhou, and to offer targeted advice for the prevention and control of lead exposure.@*Methods@#The lead level in blood of 1 600 children aged ≤14 years old and the content of serum calcium, iron, zinc, magnesium, copper were tested, and the children and their parents were given a questionnaire regarding influencing factors of blood lead exposure.@*Results@#The average blood lead level of the children was (95.2±46.5)μg/L, The proportion of children with blood lead level ≥100 μg/L was 25.7%. The blood lead level between boys and girls had a statistical differences(Z=1.85, 2.85, P<0.05). The blood lead level was negatively correlated with serum calcium, iron, zinc, magnesium and copper(F=16.80，P<0.01). The risk factors for lead exposure included frequently drinking canned or bottled soft drinks, failing to wash one’s hands before meals, taking popcorn frequently, using coal for heat and for cooking, and constantly sucking fingers or biting fingernails (OR=2.12, 1.57, 1.46, 1.78, 3.24, P<0.01).@*Conclusion@#The blood lead levels of children in Zhuzhou is higher than national average level. We should strengthen environmental protection and behavioral interventions, and regularly monitor lead exposure among children.
الملخص
Objective To describe the level of depressive symptoms in elderly patients with chronic diseases and analyze the influencing factors. Methods This study was based on the data of CHARLS (2015), chronic disease patients aged 60 years and over were selected as the study subjects. CES-D was used to evaluate the level of depressive symptoms in elderly patients with chronic diseases. Chi-square test and the binary logistic regression were used to analyze the factors that affect the level of depressive symptoms. Results The detection rate of depressive symptoms in elderly patients with chronic diseases was 43.1％(2431/5645). Gender, age, marital status, region,place of residence, species of chronic disease, disabled presence, adequate sleep, alcohol consumption, and satisfaction with life were all factors influencing depressive symptoms (P<0.05). Conclusion The detection rate of depressive symptoms in elderly patients with chronic diseases is high, and there are differences among different characteristic groups. The psychological evaluation of elderly patients with chronic diseases should be strengthened to prevent the occurrence of depressive symptoms.
الملخص
BACKGROUND@#Lung cancer is a malignant tumor disease with high morbidity and high mortality. The non-small cell lung cancer (NSCLC) is the most common type, among them, lung squamous cell carcinoma own special pathological type and specific treatment, is a subtype of non-small cell lung cancer and can be divided into peripheral type and central type according to clinical phenotype. This study explores the differences in gene levels and their potential values based on clinical differences between central and peripheral in lung squamous cell carcinoma.@*METHODS@#The lung squamous cell carcinoma dataset was collected from The Cancer Genome Atlas (TCGA) database, clinical information and the corresponding gene expression profiles were downloaded. Then we further sort and analyze all these data.@*RESULTS@#In clinical characteristics analysis, result showed that central lung squamous cell carcinoma was more likely to metastasis with lymph node than peripheral lung squamous cell carcinoma (46.2%, 67/145 vs 28.9%, 26/90; P=0.019), while there were no significant differences in gender, age, tumor size, distant metastasis, tumor node metastasis (TNM) stage, and EGFR mutation. Gene expression analysis showed 1,031 differentially expressed genes between central and peripheral lung squamous cell carcinoma, of which 629 genes were up-regulated and 402 genes were down-regulated (peripheral vs central). Further enrichment analysis showed differentially expressed genes were mainly riched in 6 signaling pathways. Among them, the neuroactive ligand-receptor interaction pathway was the main enrichment pathway of differentially expressed genes, and other differential expressed genes were mainly involved in lipid metabolism and glucose metabolism. The analysis of interaction network showed that hepatocyte nuclear factor 1 homeobox A (HNF1A) and cytochrome p450 family, Cytochrome P450 3A4 (CYP3A4) own widely effect in up-regulated genes, while ALB and APOA1 at the key positions of the network in down-regulated genes were CONCLUSIONS: Central and peripheral lung squamous cell carcinoma showed clinical phenotype difference not only reflected in the incidence of lymph node metastasis, but also in gene expression profiles. Among them, HNF1A, CYP3A4, ALB, APOA1 at the key position of the differential gene interaction network and maybe as regulatory factors in the phenotypic difference.
الموضوعات
Aged , Female , Humans , Male , Middle Aged , Carcinoma, Squamous Cell , Genetics , Databases, Genetic , Gene Expression Profiling , Gene Regulatory Networks , Kaplan-Meier Estimate , Lung Neoplasms , Genetics , Smoking , Geneticsالملخص
BACKGROUND@#Lung cancer is one of the most deadly cancers in the world for human. In recent years, the effect of targeted therapy has become increasingly significant. Apatinib is a multi-target anti-tumor drug that is currently under study. The purpose of this study is to investigate the effects of Apatinib on the biological characteristics of lung cancer cells and its possible mechanism.@*METHODS@#Lung cancer cell lines H1299 and H3255 were cultured in vitro. The effects of Apatinib on proliferation, migration and invasion of H1299 and H3255 cells were detected by cell proliferation assays wound healing assays and Transwell assays. The protein expression related to cancer angiogenesis and invasion was detected by Western blot.@*RESULTS@#Apatinib significantly inhibited the proliferation, migration and invasion of H1299 and H3255 in a concentration-dependent manner. Western blot showed that with the increasing of drug concentration, VEGF, VEGFR2, N-cadherin, MMP9, MMP2 and Vimentin were down-regulated, and E-cadherin were up-regulated.@*CONCLUSIONS@#Apatinib can inhibit the invasion and migration of lung adenocarcinoma cells H1299 and H3255. By regulation of epithelial-mesenchymal transition and the expression of matrix metalloproteinase-related proteins.
الموضوعات
Humans , Antineoplastic Agents , Pharmacology , Cell Line, Tumor , Cell Movement , Lung Neoplasms , Pathology , Neoplasm Invasiveness , Pyridines , Pharmacologyالملخص
BACKGROUND@#Lung cancer is one of the common malignant tumors that impair human health. With the development of epigenetics, the researchers found that enhancer of Zeste homolog 2 (EZH2) is highly expressed in lung cancer tissue and its expression is closely related to the prognosis. EZH2 inhibitor can also enhance the sensitivity of tumor cells to a variety of anti-tumor drugs. The purpose of this study is to investigate the effect of combination of EZH2 inhibitor and gefitinib on the proliferation, apoptosis and migration of Gefitinib-resistant lung cancer cells.@*METHODS@#PC9 and PC9/AB2 cells were used for this study. CCK-8 and EdU experiment were used to detect combined treatment on cell viability and proliferation activity; Wound healing assay and Transwell chamber experiment were used to determine the effects of combination therapy on cell migration ability; Flow cytometry was used to detect the effect of combination therapy on EZH2 and apoptosis; Western blot was used to observe the effect of combination therapy on epidermal growth factor receptor (EGFR) signaling pathway-related proteins expression.@*RESULTS@#In gefitinib-resistant cell line PC9/AB2, gefitinib combined with EZH2 inhibitor GSK343 can significantly inhibit cell viability, reduce cell migration and increase cell apoptosis. At the same time, combination therapy can significantly inhibit the expression of EZH2 and phosphorylation EGFR proteins.@*CONCLUSIONS@#The combination of EZH2 inhibitor GSK343 and gefitinib sensitize PC9/AB2 cell to gefitinib response. This study also suggests that synergistic therapy plays a role in the reversal of EGFR-tyrosine kinase inhibitor (EGFR-TKIs) resistance in lung cancer.
الموضوعات
Humans , Antineoplastic Agents , Pharmacology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cell Survival , Drug Resistance, Neoplasm , Drug Synergism , Enhancer of Zeste Homolog 2 Protein , ErbB Receptors , Gefitinib , Pharmacology , Lung Neoplasms , Pathology , Protein Kinase Inhibitors , Pharmacologyالملخص
BACKGROUND@#Angiogenesis is an important process in the development of tumor. PD 0332991, a cell cycle inhibitor, can specifically inhibit CD4/6 phosphorylation and cell cycle progression. In xeongraft mice models, PD 0332991 treated mice had significantly decreased angiogenesis and vascular density compared with the control group, but the mechanism remains unknown. The purpose of this study is to investigate the role and molecular mechanism of PD 0332991 on vascular endothelial cells.@*METHODS@#EA.hy926 cells, a kind of vascular endothelial cell, were used as the research model. The effects of PD 0332991 on the activity and proliferation of EA.hy926 cells were detected by the MTT, EdU assays. Wound-healing assays and transwell assays were used to determine the effects of PD 0332991 on the mobility of EA.hy926. The influence of PD 0332991 on cell cycle and apoptosis of endothelial cells was tested by flow cytometry, and the Western blot was applied to observe the expression of cell cycle related proteins in EA.hy926 cells treated by PD 0332991.@*RESULTS@#PD 0332991 significantly inhibited the proliferation and mobility of EA.hy926 cells, caused cell cycle arrest and apoptosis. At the same time, PD 0332991 inhibited the expression of CDK4/6 and phosphorylation of Rb, and thus inhibited the cell cycle progression of EA.hy926 cells.@*CONCLUSIONS@#PD 0332991 can inhibit the proliferation and activity of endothelial cells and induces apoptosis.
الموضوعات
Animals , Humans , Mice , Angiogenesis Inhibitors , Pharmacology , Apoptosis , Cell Line, Tumor , Cell Proliferation , Cell Survival , Cyclin-Dependent Kinase 4 , Genetics , Metabolism , Cyclin-Dependent Kinase 6 , Genetics , Metabolism , Endothelial Cells , Cell Biology , Metabolism , Lung Neoplasms , Drug Therapy , Genetics , Metabolism , Piperazines , Pharmacology , Pyridines , Pharmacologyالملخص
Objective To analyze retrospectively the results of single-patch with elevation of the left-sided atrioventricular valve repair for complete atrioventricular septal defect(CAVSD) in therapeutic effects and safety.Methods Fourteen consecutive patients (2 males and 12 females) with CAVSD were enrolled in the study from April 2012 to December 2017.All patients underwent single-patch with the elevation of left-sided atrioventricular valve repair for CAVSD by regular sternotomy.The median age at operation was 12.5 months(range,11.7 months to 63 months) and the duration of follow-up was(3.27 ± 2.02)years.Echocardiography and electrocardiogram were used during follow-up according to the protocol.Results Compared with pulmonary arterial pressure(PAP) during pre-and post-operation (65.92 ± 6.91 and 62.97 ± 17.29) mmHg (1 mmHg =0.133 kPa),PAP(53.29 ± 20.99) mmHg decreased significantly during follow-up period.There were significant difference during post-operation and follow-up for LAVVR and RAVVR.The extent of regurgitation of atrioventricular valve statistically decreased during follow-up period.None of patients suffered from atrioventricular block and reoperation during follow-up.Conclusion Single-patch with elevation of the left-sided atrioventricular valve repair for CAVSD yields good outcomes,without occurrence of severe LAVVR,during early and mid-term follow-up period.