1.Clinical observation of continuous airway positive pressure ventilation in patients with obstructive sleep apnea hypopnea syndrome and cough syncope
Meixiang HAN ; Jie CAO ; Yan WANG ; Ning ZHOU ; Baoyuan CHEN
Tianjin Medical Journal 2016;44(4):487-489,490
Objective To observe the curative effect of continuous airway positive pressure ventilation (CPAP) in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and cough syncope. Methods Forty-three hospitalized patients with OSAHS and cough syncope were collected in the Department of Respiration of Tianjin General Hospital, and analyzed the related information. They were given CPAP treatment, and were divided into good compliance group (n=26) and poor compliance group (n=17) according to CPAP compliance after a half-year treatment. The apnea hypoventilation index (AHI) and c-reactive protein (CRP) were compared before and after treatment between two groups. Results The positive correlation was found between the frequency of the cough syncope and indicators of OSAHS, such as AHI, body mass index (BMI), CRP, sleepiness score (ESS) and circumference of abdomen and neck (r=0.612, 0.431, 0.224, 0.654, 0.435 and 0.344,P<0.05). All these patients were cured after the treatment of both CPAP and medication for 1 or 2 weeks. During a half-year follow-up, the cough syncope didn’t occur in those patients of good compliance group, otherwise cough syncope still happened but with less frequency in patitents of poor compliance group. Before the treatment , there was no significant difference in AHI (45.00±15.69 vs. 48.70±16.47) and CRP (3.46± 1.15 vs. 3.38±0.72) between the two groups. After treatment, AHI (26.97±14.06 vs. 48.18±15.96) and CRP (1.56±0.76 vs. 3.18± 0.78) were significantly lower in the good compliance group than those of the poor compliance group (P<0.01). Conclusion Timely and sustained treatment of OSAHS may help reduce the incidence of cough syncope and significantly improve AHI, CRP and cough symptoms.
2.MiR-200c/141 methylation inhibits the expression of miR-200c and miR-141 in gastric cancer
Xinliang ZHOU ; Cong ZHANG ; Yudong WANG ; Lianmei ZHAO ; Meixiang SANG ; Baoen SHAN
Chinese Journal of Clinical Oncology 2017;44(2):73-77
Objective:This work aims to detect the levels of miR-200c/141 methylation and miR-200c/141 in gastric cancer tissue and investigate the relationship between miR-200c/141 expression and clinical parameters. Methods:The methylation status of miR-200c/141 CpG island and miR-200c/141 in gastric cancer tissue specimens was evaluated by qRT-PCR or BS-MSP method. We analyzed the relationship among the methylation status of miR-200c/141 CpG island, expression level of miR-200c or miR-141, and clinical parame-ters. Results:The status of miR-200c/141 CpG island methylation in gastric cancer tissue was significantly higher compared with that in paracarcinoma tissue. MiR-200c and miR-141 were markedly decreased in gastric cancer tissue compared with those in adjacent tis-sue. MiR-200c/141 CpG island methylation was negatively related with the expression of miR-200c and miR-141 in gastric cancer speci-mens. Conclusion:The upregulation of miR-200c/141 CpG methylation inhibits miR-200c/141 expression in gastric cancer tissue.
3.Protective effects of myocardium-targeted nanoparticles loaded L-arginineon on sepsis-induced myocardial injury
Zefang PENG ; Ming ZHANG ; Minzhi OUYANG ; Xiangnan OUYANG ; Ganqiong XU ; Jiawei ZHOU ; Meixiang ZHANG
Chinese Critical Care Medicine 2020;32(8):953-959
Objective:To prepare primary cardiomyocyte (PCM) specific peptide-conjugated mesoporous silicon nanoparticles (MSN) with L-arginine (LA) as a core (PCM-MSN@LA), and evaluate its specific protective effect on septic myocardium.Methods:PCM-MSN@LA was prepared by condensation reaction, the characterization of PCM-MSN@LA, the amount of LA modification and release was detected, and the phagocytosis of PCM-MSN@LA and its affinity to myocardial tissue was observed. ① Experiment one: SD neonatal rat cardiomyocytes were divided into control group (Con group), lipopolysaccharide (LPS) group, MSN@LA/LPS group and PCM-MSN@LA/LPS group. The LPS group was stimulated with 5 mg/L LPS for 16 hours, while the MSN@LA/LPS group and PCM-MSN@LA/LPS group were treated with 5 mg/L LPS and 25 mg/L LA-containing nanoparticles (MSN@LA and PCM-MSN@LA) for 16 hours. Cell viability and reactive oxygen species (ROS) production levels were detected. Apoptosis was observed via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method (TUNEL). Western Blot was used to detect the changes in endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) proteins. ② Experiment two: 64 healthy male C57BL/6 mice were divided into Sham group, LPS group, MSN@LA/LPS group and PCM-MSN@LA/LPS group by random number table method, 16 mice in each group. LPS group were injected 50 mg/kg LPS intraperitoneally. MSN@LA/LPS group and PCM-MSN@LA/LPS group were injected with 0.5 mg/kg MSN@LA and PCM-MSN@LA via tail vein immediately after intraperitoneal injection of LPS. Eight animals in each group were used to observe the 24-hour survival rate, and the other 8 mice were used to detect cardiac function by echocardiography at 12 hours after operation; mRNA expressions of interleukin (IL-1, IL-6) and tumor necrosis factor-α (TNF-α) were measured by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR).Results:PCM-MSN@LA was spherical, with particle size of about 180 nm, Zeta potential of about -21 mV, with LA loaded. The amount of LA modification and release rate were 12.3% and 24.3%, respectively. Cell phagocytosis experiments showed that PCM-MSN@LA had the targeting ability of cardiomyocytes and myocardial tissue. Experiment one: after LPS stimulation of myocardial cells, cell viability decreased, while ROS generation, apoptosis, eNOS and iNOS protein expressions increased. Compared with LPS group, MSN@LA/LPS group and PCM-MSN@LA/LPS group had higher cell viability, reduced ROS levels and apoptosis, increased expressions of eNOS and iNOS. PCM-MSN@LA/LPS group changed the above effect further than MSN@LA/LPS group [cell viability ( A value): 0.51±0.08 vs. 0.41±0.03, ROS (relative fluorescence intensity): 28 450±1 941 vs. 35 628±2 551, TUNEL positive cells/total cells: 0.27±0.03 vs. 0.35±0.04, eNOS/β-Tubulin: 1.467±0.046 vs. 1.201±0.131, iNOS/β-Tubulin: 1.700±0.033 vs. 1.577±0.068, all P < 0.05]. Experiment two: the number of 24-hour survive in MSN@LA/LPS group and PCM-MSN@ LA/LPS group were higher than LPS group (number: 2, 4 vs. 1, P values were 0.36 and 0.03 respectively). Compared with Sham group, the cardiac function of LPS group was significantly inhibited and the mRNA expression of inflammatory factors increased. The PCM-MSN@LA/LPS group had higher left ventricular ejection fraction (LVEF) and left ventricular short-axis shortening rate (LVFS) than LPS group, and lower mRNA expressions of IL-1, IL-6, and TNF-α mRNA [LVEF: 0.456±0.019 vs. 0.337±0.017, LVFS: (21.97±1.78)% vs. (15.53±1.67)%, IL-1 mRNA (2 -ΔΔCT): 169.22±8.95 vs. 189.79±6.79, IL-6 mRNA (2 -ΔΔCT): 19.90±1.60 vs. 23.74±1.45, TNF-α mRNA (2 -ΔΔCT): 8.21±0.81 vs. 11.00±1.48, all P < 0.05]. There was no significant difference in each index between the MSN@LA/LPS group and LPS group. Conclusion:PCM-MSN@LA with myocardial targeting characteristic significantly increased the activity of myocardial cells, down-regulated the expression of inflammatory factors and the production of ROS, alleviated cardiac insufficiency in sepsis, and achieved the targeted treatment of myocardial injury in sepsis.
4.Expression of miR-133a-3p in gastric cancer tissues and plasma and its effect on proliferation of gastric cancercells
ZHOU Xinliang ; WU Hao ; LI Dan ; WANG Feifei ; CUI Yanzhi ; ZHAO Lianmei ; SANG Meixiang ; SHAN Baoen
Chinese Journal of Cancer Biotherapy 2018;25(6):613-619
Objective: To detect the expression of miR-133a-3p in gastric cancer (GC) tissues and plasma of GC patients, and to investigate its effect on the proliferation of GC cells as well as its correlation toprognosis of GC patients. Methods: 52 cases of cancertissues (non-necrosis part) and corresponding adjacent tissues as well as the pre-operative peripheral blood samples from GC patients, who underwent surgery at Department of General Surgery, the Forth Hospital of Hebei Medical University(Shijiazhuang, China) between May 2012 and May 2013, were collected for this study. The plasma sample (n=35) from healthy donors were obtained during their physical examination. RT-qPCR was adopted to detect the expression of miR-133a-3p in gastric cancer tissues, adjacent tissuesand plasma samples of GC patients and healthy volunteers. The relationships between miR-133a-3p expression and the median DFS as well as clinicopathological parameters were also analyzed. CCK-8 assay was adopted to detect the effect of miR-133a-3p silence or over-expression on proliferation of gastric cancer SGC7901 cells. Results: miR-133a-3p was dramatically decreased in gastric cancer tissues (P<0.01), and its expression was associated with TNM stage, tumor infiltration (T), lynphonode metastasis (N), and vascular tumor thrombus (all P<0.01); miR-133a-3p was significantly increased in the plasma of GC patients (P<0.01), and its expression was associated with TNM stage, lynphonode metastasis (N), and vascular tumor thrombus (all P<0.05). miR-133a-3p expression was positively correlated with serum CA199 level of GC patients (P<0.01). The median DFS of patients with high miR-133a-3pexpression in cancer tissues was significantly longer than that of the patients with low expression(20.8 vs 14.8 months, P<0.05); The median DFS of patients with high plasma miR-133a-3p expression was significantly shorter than that of the patients with low expression (14.4 vs 20.3 months, P<0.05). Over-expression of miR-133a-3p could significantly inhibit the proliferation of gastric cancer SGC7901 cells, while miR-133a-3p silence could significantly promote the proliferation (all P<0.05). Conclusion: miR-133a-3p could significantlyinhibit the proliferation of SGC7901 cells; miR-133a-3p aberrantlyexpressed in gastric cancer tissues and plasma, and obviously correlated with prognosis of gastric cancer patients, which may be used as a potential clinical bio-maker for early diagnosis and treatment as well as the prognosis prediction of gastric cancer.
5.WGCNA-based identification of novel T-cell exhaustion-related gene signatures to predict the prognosis and response to immunotherapy of osteosarcoma patients
Huidong CHEN ; Tianqi XIA ; Kun HAN ; Xingxing SUN ; Meixiang ZHOU ; Cong TIAN ; Mengyi JIANG ; Daliu MIN
Tumor 2023;43(10):763-780
Objective:To screen T-cell exhaustion-related signature genes as the prognostic marker for osteosarcoma and establish a prognostic model for osteosarcoma patients based on weighted gene co-expression network analysis(WGCNA)and Least absolute shrinkage and selection operator(LASSO)-COX regression analysis. Methods:GSE21257 dataset was downloaded from Gene Expression Omnibus(GEO)database for the establishment of the prognostic model for osteosarcoma.4 T-cell exhaustion-related gene sets were downloaded from The Molecular Signatures Database(MisgDB)and their enrichment scores in GSE21257 samples were calculated by single sample gene set enrichment analysis(ssGSEA).WGCNA was carried out to screen the gene module that is highly associated with T-cell exhaustion based on ssGSEA results followed by GO(Gene Ontology)and KEGG(Kyoto Encyclopedia of Genes and Genomes)analysis of the biological processes and signaling transduction pathways that those genes are involved in.The signature genes that are highly associated with the prognosis of osteosarcoma patients were obtained through LASSO-COX regression and a prognostic model was established based on these signature genes.Osteosarcoma-related expression profile data from the GSE21257 and TAEGET datasets on XENA were downloaded from the Gene Expression Omnibus.Clinical information for the training and validation sets was obtained.T-cell exhaustion-related genes were screened using a weighted correlation network analysis.Realtime fluorescence quantitative PCR,COX regression analysis,external dataset and nomogram were used to evaluate the reliability and accuracy of the prognostic model.A immunotherapy-related dataset was used to assess the efficacy of this prognostic model for the prediction of patients'responses to immunotherapy. Results:Analysis results based on the ssGSEA scores showed that T-cell exhaustion-related genes were related to the metastasis and age of osteosarcoma patients.Many T-cell exhaustion-related genes were found to be differentially expressed in metastatic and non-metastatic osteosarcoma patients.1 256 T-cell exhaustion-related genes were identified through WGCNA and these candidate markers were mainly distributed in structures like secretory granule membranes and endocytic vesicles and were involved in T-cell activation.COX regression analysis screened 68 significant prognostic markers out of the 1 256 genes,and 12 signature genes were further confirmed with LASSO-COX regression analysis.A prognostic model was established based on the 12 signature genes.Results of real-time fluorescence quantitative PCR showed a similar trend in the expression of most of the signature genes in different osteosarcoma cell lines.COX regression analysis of the internal and external datasets verified that the risk score calculated with the prognostic model was an independent prognostic factor for osteosarcoma patients,and high-risk score was associated with poor prognosis of the patients.Receiver operating characteristic(ROC)curves demonstrated excellent prognostic efficacy of the model.Nomogram analysis verified the prognostic model is highly accurate and reliable in predicting the prognosis of osteosarcoma patients.Analysis using the immunotherapy-related dataset indicated that this prognostic model could also be used to predict patients'responses to immunotherapy. Conclusion:The 12 signature gene(CD300LB,TRO,SNX3,VENTX,PPM1M,DOT1L,CDC37,NAT9,TRMT1,PPP1R3C,CHTF18 and NSUN5)-based prognostic model can effectively predict the prognosis and responses to immune check-point inhibitors for osteosarcoma patients,which may provide evidence for the prediction of prognosis as well as the selection of immunotherapy plans in clinical practice.