Association of oily fish and nonoily fish intakes with all-cause mortality and cause-specific mortality: a large population-based prospective study.

BACKGROUND: There are inconsistent results of cohort studies analyzing the association between fish intake and mortality. OBJECTIVE: This study was performed to explore the association of oily fish consumption and nonoily fish consumption with all-cause mortality and cause-specific mortality. METHODS: A total of 431,062 participants from the UK Biobank who were without cancer or cardiovascular disease (CVD) at baseline between 2006 and 2010 were included in this study, and they were followed up through 2021. We constructed Cox proportional hazard models to calculate the hazard ratio (HR) and 95% confidence interval (CI) to assess the correlation of oily fish and nonoily fish intakes with mortality. Then, we performed subgroup analyses, and sensitivity analyses were developed and performed to examine the robustness of this study. RESULTS: Among the participants, 383,248 (88.9%) and 410,499 (95.2%) consumed oily fish and nonoily fish, respectively. Compared with the participants who did not consume oily fish, the adjusted HRs for the association of oily fish consumption (1 serving/week) with all-cause mortality and CVD mortality were 0.93 (0.87 to 0.98; p < 0.05) and 0.85 (0.74 to 0.98; p < 0.05), respectively. The multivariable-adjusted HRs of all-cause mortality for those who reported consuming < 1 serving/week of oily fish were 0.92 (0.86 to 0.98; p < 0.05). CONCLUSION: Compared with participants who reported never consuming oily fish, the consumption of oily fish with 1 serving/week was more beneficial for all-cause and CVD mortality.

Prognostic significance of long non-coding RNA five prime to XIST in various cancers.

BACKGROUND: To observe the clinicopathological and prognostic value of long non-coding RNA five prime to X inactive specific transcript (lncFTX) in multiple tumors. METHODS: Eligible studies for lncFTX were identified by searching PubMed, Embase, Web of Science and Cochrane Library databases from inception to December 01, 2020. Stata 12.0 software was used to calculate the odds ratio (OR)/hazard ratio (HR) and 95% confidence interval (95% CI). We used The Cancer Genome Atlas (TCGA) dataset to further investigate the differential expression and prognostic value of lncFTX. RESULTS: We included 11 studies involving a total of 1633 patients. The results showed that the expression of lncFTX was positively associated with advanced TNM stage (III-IV versus I-II) (OR = 2.30, 95% CI: 1.74-3.03, P < 0.05), lymph nodes metastasis (OR = 3.01, 95% CI: 2.00-4.52, P < 0.05), distant metastasis (OR = 3.68, 95% CI: 2.13-6.34, P < 0.05), and cancer mortality (HR = 1.83, 95% CI: 1.20-2.81, P < 0.05). However, the expression of lncFTX was not associated with tumor differentiation (poor differentiation versus well or moderate differentiation) and vessel invasion of cancer. Subgroup analysis showed that the higher lncFTX expression was associated with shorter overall survival in cancer patients, regardless of the sample size and cancer type. No publication bias was found, and the sensitivity analysis results suggested that the main findings were robust. Elevated expression and prognostic significance of FTX were confirmed using TCGA dataset. CONCLUSIONS: This study found that the expression of lncFTX was positively associated with advanced tumor node metastasis (TNM) stage, lymph nodes, distant metastasis and, cancer mortality, suggesting that lncFTX might be a potential prognostic biomarker for tumors.

The relationship between the expression of Ki-67 and the prognosis of osteosarcoma.

BACKGROUND: A number of studies have linked positive Ki-67 expression with the prognosis of osteosarcoma (OS) patients. However, the results have been conflicting. To address this controversy, we conducted an analysis using a meta-analysis and a TCGA dataset to estimate the value of Ki-67 expression in the prognosis of OS. METHODS: A comprehensive search for relevant papers was conducted using NCBI PubMed, Embase, Springer, ISI Web of Knowledge, the Cochrane Library, and CNKI regardless of the publication year. The associations between Ki-67 expression and the clinical features and main prognostic outcomes of OS were measured. The TCGA dataset was also analyzed. The pooled odds ratio (OR) and its 95% confidential intervals (CIs) were utilized for statistical analysis. RESULTS: Overall, a total of 12 studies with 500 cases were included, and the results indicated that the expression of Ki-67 was significantly associated with Enneking stage (OR = 6.88, 95% CI: 2.92-16.22, p < 0.05), distant metastasis (OR = 3.04, 95% CI: 1.51-6.12, p < 0.05) and overall survival (OR = 8.82, 95% CI: 4.68-16.65, p < 0.05) in OS patients. Additionally, we observed no significant heterogeneity among all retrieved studies. Associations between Ki-67 expression and overall survival and disease-free survival of sarcoma were confirmed using the TCGA and Kaplan-Meier plotter datasets. CONCLUSION: The present study strongly suggests that positive Ki-67 expression was associated with Enneking stage, distant metastasis, and overall survival of OS, and it may be used as a potential biomarker to predict prognosis and guide clinical therapy for OS.

Expression of autophagy related gene 5 and cyclin E in coronary heart disease and its clinical significance. / è‡ªå™¬ç›¸å ³åŸºå› 5å’Œç»†èƒžå‘¨æœŸç´ Eåœ¨å† å¿ƒç— ä¸­çš„è¡¨è¾¾åŠå ¶ä¸´åºŠæ„ä¹‰.

OBJECTIVES: To explore the expression of autophagy related genes 5 (ATG5) and cyclin E in coronary heart disease (CHD) and its clinical significance. METHODS: From April 2018 to August 2018, 80 patients diagnosed with CHD in the Second Xiangya Hospital, Central South University were selected as an observation group, and another 80 healthy subjects were selected as a control group. The expression of ATG5 and cyclin E mRNA in nucleate cells and the plasma protein in the 2 groups were detected and analyzed. The model of macrophage-derived foam cells induced by oxidized low density lipoprotein (ox-LDL) was used to simulate atherosclerosis. The proliferation of macrophage- derived foam cells and the protein levels of ATG5 and cyclin E induced by ox-LDL at different concentrations were examined. RESULTS: Compared with the control group, the levels of ATG5 mRNA and protein in the blood in the observation group were decreased, and the cyclin E mRNA and protein levels were increased, there were statistically difference (both P<0.05). Receiver operating characteristic (ROC) curve showed that the area under curve (AUC) of ATG5 mRNA, cyclin E mRNA, ATG5 protein and cyclin E protein were 0.739, 0.780, 0.671 and 0.807, respectively. Pearson analysis showed that the ATG5 mRNA was negatively correlated with the cyclin E mRNA (r=-0.734, P<0.05),while the plasma ATG5 protein was negatively correlated with the plasma cyclin E protein (r=-0.746, P<0.05). Macrophage-derived foam cell model induced by ox-LDL showed that the proliferation of foam cells and the expression levels of cyclin E protein were increased in a concentration and time-dependent manner, and the expression levels of ATG5 protein were decreased in a concentration-dependent manner. CONCLUSIONS: The levels of ATG5 mRNA and protein are lowly expressed while the levels of cyclin E mRNA and protein are highly expressed in the patients with CHD.The ATG5 protein levels are lowly expressed in ox-LDL-treated macrophage-derived foam cells while the cyclin E protein levels are highly expressed in ox-LDL-treated macrophage-derived foam cells. Based on these observations, we conclude that ATG5 inhibits the degradation of the cyclin E and promotes the proliferation of macrophages, involving in the occurrence and development of CHD.

Effect of Inducible Co-Stimulatory Molecule siRNA in Cerebral Infarction Rat Models.

BACKGROUND: T cell-induced inflammatory response and related cytokine secretion at the injury site may participate in the pathogenesis of cerebral infarction. Recent studies established inducible co-stimulatory molecule (ICOS) as a novel T cell-related factor for its activation and functions. We thus investigate the role of ICOS in cerebral infarction. MATERIAL AND METHODS: The siRNA of ICOS was first used to suppress the gene expression in cultured lymphocytes. An in vivo study was then performed by intravenous application of ICOS siRNA in cerebral infarction rats. Survival rates, neurological scores, serum tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-17 levels were observed. RESULTS: The expression of ICOS in cultured lymphocytes was significantly suppressed by siRNA. In the in vivo study, the application of siRNA effectively lowered mortality rates of rats, in addition to the improvement of neurological behaviors and amelioration of cerebral tissue damage. Serum levels of TNF-α, IL-1 and IL-17 were all significantly suppressed after siRNA injection. CONCLUSIONS: ICOS siRNA can protect brain tissues from ischemia injuries after cerebral infarction, improve limb movement and coordination, lower the mortality rate of rats, and inhibit T cell-induced cytokines. These results collectively suggest the potential treatment efficacy of ICOS siRNA against cerebral infarction.

Elevated fractalkine in patients with obstructive sleep apnea hypopnea syndrome.

BACKGROUND: Obstructive sleep apnea hypopnea syndrome (OSAHS) has been increasingly linked to cardiovascular disease. Inflammatory processes associated with OSAHS may contribute to atherosclerosis in these patients. Fractalkine is a unique chemokine which has both adhesive and chemoattractant functions. We tested the hypothesis that OSAHS patients have increased fractalkine. METHODS AND RESULTS: We studied 20 patients (18 males and 2 females) with newly diagnosed OSAHS, who were free of other diseases, had never been treated for OSAHS, and were taking no medications. We compared fractalkine measurements in these patients to measurements obtained in 15 control subjects (14 males and 1 female) who were matched for age and body mass index, and in whom occult OSAHS was excluded. Plasma fractalkine levels were significantly higher in patients with OSAHS than in controls (463.15 ± 110.78 versus 364.67 ± 64.81 pg/mL, F = 2.58, P = 0.004). Fractalkine were associated with AHI (r = 0.756, P < 0.0001), lowest oxygen saturation (r = -0.466, P = 0.005), and mean oxygen saturation (r = -0.344, P = 0.043). Plasma fractalkine levels were significantly decreased in patients with OSAHS after four nights nCPAP (463.15 ± 110.78 versus 416.75 ± 97.67 pg/mL, P = 0.001). CONCLUSIONS: OSAHS is associated with elevated levels of fractalkine, a marker of inflammation related to atherosclerosis. The severity of OSAHS is proportional to the fractalkine level.

[Effect of chronic intermittent hypoxia on the expression of fractalkine in rat liver].

OBJECTIVE: To investigate the effect of chronic intermittent hypoxia (CIH) on liver injury and the expression of fractalkine in rats and explore its possible mechanism. METHODS: A CIH murine model was established to mimic the pathophysiology of obstructive sleep apnea-hypopnea syndrome (OSAHS) in humans. Thirty healthy male Spraque-Dawley rats were randomly assigned to 3 groups: a 5% CIH group, a 5% CIH+RH (removal of hypoxia) group and a control group ( 10 rats in each group). The 5% CIH and 5% CIH+RH groups were exposed to CIH for 3 weeks, 8 h/d, and the frequency of hypoxia was 20 times/h. The 5% CIH+RH group was then exposed to normal gaseous environment for another 3 weeks. After the experiment, liver sections were stained with hematoxylin-eosin (HE) and the liver pathology was observed. The expression of fractalkine in the liver tissues was detected by immunohistochemical method. RESULTS: 1) Compared with the control group, the hepatic steatosis and inflammatory activities in the 5% CIH and 5% CIH+RH groups were more severe (all P<0.01 ); compared with the 5% CIH group, the hepatic steatosis and inflammatory activity in the 5% CIH+RH group were dramatically reduced (P<0.01 ). 2) Compared with the control group, the fractalkine expression in the 5% CIH and 5% CIH+RH groups was increased (both P<0.01). The fractalkine expression in the 5% CIH+RH group was dramatically downregulated compared with that in the 5% CIH group (P<0.01). CONCLUSION: CIH can induce liver injury and high fractalkine expression in rat liver tissues.

Investigation of the clinicopathological and prognostic role of circMTO1 in multiple cancers.

OBJECTIVE: To observe the prognostic value of circular RNA mitochondrial tRNA translation optimization 1 (circMTO1) in human tumors. METHODS: We searched multiple databases for related reports published before November 01, 2021. The OR/HR and 95% CI were extracted to explore the correlation between circMTO1 expression and clinicopathological features in various cancers. The stability of the results from meta-analysis was estimated via sensitivity analysis. We adopted Begg's funnel plots and Egger's test to appraise the potential bias of publication. Subgroup analysis for overall survival (OS) were also performed. RESULTS: 11 studies containing 1383 patients and 4 articles including 536 patients were enrolled. We found that low expression status of circMTO1 was significantly related to big tumor size (OR=2.11, 95% CI: 1.26-3.56, P<0.05), poor differentiation tumors (OR=2.09, 95% CI: 1.46-2.98, P<0.05), OS (HR=2.02, 95% CI: 1.63-2.50, P<0.05), disease-free survival (DFS) (HR=1.83, 95% CI: 1.27-2.56, P<0.05) of cancers. Subgroup analysis indicated that low expression status of circMTO1 was correlated with OS, regardless of analysis method, cut-off value, case number and NOS score. CONCLUSIONS: The low expression of circMTO1 may predict big tumor size, poor differentiation and worse outcome of cancer, presenting that circMTO1 may be a useful biomarker for prognosis of tumors.

[Effect of nasal intermittent positive pressure ventilation on N-terminal pro-brain natriuretic peptide in patients with acute exacerbations of chronic obstructive pulmonary disease and type II respiratory failure].

OBJECTIVE: To investigate the effect of nasal intermittent positive pressure ventilation (NIPPV) on N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and type II respiratory failure. METHODS: Forty patients with AECOPD and type II respiratory failure and 40 patients with stable phase chronic obstructive pulmonary disease were randomly assigned into study. Plasma levels of NT-proBNP, arterial blood gas, APACHE II scores, and pulmonary artery pressures were measured. The plasma level of NT-proBNP was compared between the two groups. Effect of NIPPV on NT-proBNP was studied in patients with AECOPD and type II respiratory failure. RESULTS: There were negative correlations between NT-proBNP and pH, and between NT-proBNP and PaO2 (r=-0.691,r=-0.704,respectively;P<0.001),positive correlations between NT-proBNP and PaCO2, and between NT-proBNP and APACHE II scores (r=0.774, r=0.810, respectively, P< 0.001), and positive correlation between NT-proBNP and PAP (r=0.965, P<0.001) in all patients. In patients with AECOPD and type II respiratory failure, there were negative correlations between NT-proBNP and pH,and between NT-proBNP and PaO2 (r=-0.636, r=-0.616,respectively; P<0.001); there were positive correlations between NT-proBNP and PaCO2, and between NTproBNP and APACHE II scores (r=0.545, r=0.475, respectively; P=0.001, P=0.002); and there were positive correlation between NT-proBNP and pulmonary artery pressure (r=0.833,P<0.001). The plasma levels of NT-proBNP were significantly higher in patients with AECOPD and type II respiratory failure than in control subjects [(939.60 ± 250.00) pg/mL vs (151.55 ± 111.20) pg/mL;P<0.01]. NIPPV decreased plasma levels of NT-proBNP [(229.15 ± 98.26) pg/mL vs (939.60 ± 250.00) pg/mL; P<0.01] in patients with AECOPD and type II respiratory failure, as well as improved arterial blood gas and APACHE II scores. Although NIPPV appeared to decrease pulmonary artery pressure somewhat between pre-treatment and post-treatment groups, the differences were not statistically significant (P=0.056). CONCLUSION: The plasma level of NT-proBNP reflects the severity of patients with AECOPD and type II respiratory failure. NIPPV can decrease a patient's splasma level of NT-proBNP, which has clinical value for evaluating the effect of NIPPV.

[Mechanisms of sympathetic activity in rats exposed to different patterns of hypoxia and the correlation with blood pressure].

OBJECTIVE: To observe the effects of two different hypoxia patterns on blood pressure and the underlying mechanisms. METHODS: Eighteen male SD rats were randomly divided into three groups: the intermittent hypoxia group (IH group), the continuous hypoxia group (CH group) and the normal control group (NC group). The rats of the IH and CH group were subjected to intermittent hypoxia (7 h/d) and continuous hypoxia (7 h/d) for 42 days respectively. The NC group rats were untreated. The levels of arteria caudilis systolic pressure (ACSP) were measured with noninvasive rats arteria caudilis gauge before the experiment, at the end of 3rd, 6th week of the experiment. The concentrations of norepinephrine (NE) in serum and neuropeptide Y (NPY) in plasma were respectively measured by enzyme-linked-immunosorbent assay (ELISA) and radioimmunoassay. The contents of malondialdehyde (MDA) and the ability of inhibiting hydroxyl free radical in serum were analyzed by thiobarbituric acid colorimetric analysis (TBAR) at the end of 6th week. RESULTS: At the end of 3rd week, the levels of ACSP were considerably higher than those before the treatment (P<0.05). The concentrations of ACSP, NE, MDA, NPY in the IH group were significantly higher than those in the other two groups at the end of 6th week (all P<0.01). The ability of inhibiting hydroxyl free radical were decreased by the intermittent hypoxia treatment (all P<0.01). However, there was no significant difference in ACSP, NE, MDA, NPY between CH and NC group (all P>0.05). The levels of NE, NPY and MDA were positively related with ACSP (r=0.873, P<0.01; r=0.671, P<0.01; r=0.582, P<0.05). The correlation between the ability of inhibiting hydroxyl free radical and ACSP was negative (r=-0.790, P<0.01). the concentrations of MDA were positively related with NE and NPY respectively (r=0.843, 0.777, P<0.01) and the ability of inhibiting hydroxyl free radical was negatively related with NE and NPY respectively (r=-0.864, -0.717, P<0.01). CONCLUSION: Intermittent hypoxia can induce high blood pressure, which may be related to the sympathetic over-activity and the oxidative stress.

The role of Livin expression in the clinicopathological features and prognosis of lung cancer: a meta-analysis.

BACKGROUND: While the impact of Livin expression on patients with lung cancer was evaluated in previous studies, the results remained debatable. The relationship between Livin expression and clinicopathological features and prognosis in lung cancer was assessed in the present meta-analysis. METHODS: Web of Science, PubMed, Embase, Springer, Cochrane Library, China National Knowledge Internet database (CNKI), Wanfang database, Chinese VIP database and Chinese Biological Medical Database (CBM) were searched for relevant publications analyzing the role of Livin in prognosis and clinicopathological features of lung cancer before September 2020. The results were evaluated using pooled odds ratio (OR) and 95% confidence intervals (CIs) calculated by STATA 12.0 software. RESULTS: Twenty studies with a total of 1,395 patients were enrolled in this meta-analysis based on inclusion and exclusion criteria. Livin expression was significantly associated with smoking status (OR =2.51, 95% CI: 1.70-3.72, P<0.05), lung adenocarcinomas (LAC) (OR =2.16, 95% CI: 1.60-2.92, P<0.05), TNM stage (OR =2.49, 95% CI: 1.63-3.69, P<0.05) and poor differentiation (OR =2.04, 95% CI: 1.35-3.08, P<0.05). Livin expression was significantly related to metastasis (OR =4.22, 95% CI: 2.68-6.64, P<0.05) and lower 5-year overall survival (OR =4.23, 95% CI: 2.60-6.88, P<0.05) of patients with lung cancer. CONCLUSIONS: The results of our study manifested that Livin expression was significantly related to smoking status, LAC, high TNM stage, poor differentiation, metastasis and 5-year overall survival rate, which indicated that Livin may be a potential biomarker for prognosis of lung cancer.

Clinicopathologic and prognostic roles of circular RNA plasmacytoma variant translocation 1 in various cancers.

OBJECTIVE: To explore the clinicopathologic and prognostic significance of circular RNA plasmacytoma variant translocation 1 (circPVT1) in various cancers. METHODS: Several databases were searched for eligible studies published before March 01, 2021. The pooled odds ratios (ORs) with 95% confidence interval (95% CI) were calculated to assess the association between circPVT1 expression and prognostic outcomes of tumor including age, gender, clinical stage, tumor size, metastasis and overall survival. Begg's funnel plots and Egger's test were used to evaluate the publication bias. The robustness of our results was assessed using sensitivity analysis. RESULTS: Ten studies comprising a total of 878 patients with cancer were included in this meta-analysis. The results showed that the high expression of circPVT1 was significantly related to clinical stage (OR=3.44, 95% CI: 2.40-4.94, P<0.05), tumor size (OR=2.29, 95% CI: 1.38-3.79, P<0.05), metastasis (OR=2.97, 95% CI: 2.06-4.28, p<0.05) and overall survival of cancer (OR=3.30, 95% CI: 2.26-4.84, p<0.05), but not associated with age and gender of patients with tumor. No publication bias was found. CONCLUSIONS: High expression of circPVT1 may predict an advanced clinical stage and poor prognosis of tumor, suggesting that circPVT1 may serve as a potential prognostic marker in cancers.

Clinical expert consensus on standard care of blood glucose for residents in senior care facility in China (2021 edition).

With the demographic changes, more and more elderly people have chosen to spend their retirement life in a senior care facility. The elderly people in senior care facility are commonly suffering from various geriatric syndromes, including declined daily living activities, cognitive dysfunction, frailty, comorbidities, and polypharmacy, which make them vulnerable to adverse effects, like hypoglycemia and fall. Therefore, layered management is necessary for this population with group disparities. However, the staff in senior care facility vary greatly in concepts and skills on management of senile diabetic population, which needs urgently to be standardized and improved. For this purpose, based on literature review and panel discussion, 28 recommendations are proposed in respect of the standardized management of blood glucose, covering the comprehensive assessment, layered management and grouping, exercise, nutrition, glucose monitoring, identification and treatment of severe hyperglycemia, identification of macrovascular and microvascular complications, management of hypoglycemic drugs, falls and choking and other common problems, blood glucose screening, hypoglycemia prevention, and blood glucose management in major public health events or serious natural disasters. This guideline aims to standardize management skills of medical staff and caregivers in senior care facility for the blood glucose of elderly people and improve their quality of life.

Prognosis and Immune Infiltration of Chromobox Family Genes in Sarcoma.

BACKGROUND: Chromobox family genes (CBXs) are known to play roles in numerous modifications of the chromatin in order to inhibit the transcription of target genes. CBXs have been shown to be expressed at high levels in many types of cancer and can also serve as a target gene for therapeutic purposes. However, little is known about the expression and prognostic value of CBXs in human sarcomas. METHODS: The transcription level of CBXs was analyzed using the Oncomine dataset, and the differential expression of CBXs in sarcoma was reported by the Gene Expression Profiling Interactive Analysis (GEPIA) dataset. We also used the CCLE dataset to evaluate the expression of CBXs in a sarcoma cell line. The prognostic value of CBXs was analyzed using GEPIA and Kaplan-Meier analysis. In addition, the corrections between CBXs and their co-expressed genes were reported using Oncomine and GEPIA datasets. DAVID was used to perform GO function enrichment analysis for the CBXs and their co-expression genes. Finally, TIMER was used to analyze the immune cell infiltration of CBXs in patients with sarcoma. RESULTS: HP1-α/ß/γ (CBX1/3/5) and CBX4/6/8 were found to be overexpressed in human sarcoma, and CBXs were upregulated in almost all the sarcoma cell line. The expression levels of HP1-α/ß/γ (CBX1/3/5) and CBX7 were associated with overall survival (OS) in patients with sarcoma, while high expression levels of CBX7 were related to disease-free survival (DFS). In addition, the expression levels of CBX2/6/7 were related to recurrence-free survival (RFS). We also found that the CBX family was positively correlated with the infiltration of immune cells, including CD8+ T cells, CD4+ T cells, B cells, macrophages, neutrophils, and dendritic cells, in sarcoma. CONCLUSIONS: The results from the present study indicated that CBXs were significantly associated with prognosis and immunological status in sarcoma. These data suggest that CBXs could serve as potential biomarkers for prognosis and immune infiltration in human sarcoma.

[A study of the related pathways of oxidative stress in chronic intermittent hypoxia rats and the effect of N-acetylcysteine].

OBJECTIVE: To study the relation of oxidative stress with systolic blood pressure (SBP) and renin-agiotensin system (RAS) in a rat model of chronic intermittent hypoxia (CIH), and to investigate the preventive effect and mechanism of N-acetylcysteine (NAC) in CIH-induced hypertension. METHODS: Twenty-four male Sprague-Dawley (SD) rats were divided into 4 groups: CIH+NAC group (CIH1), CIH+normal saline (NS) group (CIH2), CIH control group (CIH3) and blank control group (UC). CIH rats were subjected to alternating cycles of hypoxia (6%-8% O2 in N2 for 20-25 s) and normoxia (21% O2 in N2 for 2 min) every 180 s for 7 h per day. Rats in the CIH1 group were treated with NAC (800 ml×kg(-1)×d(-1)) by intraperitoneal injection, and those in the CIH2 group were treated with NS (5 ml×kg(-1)×d(-1)). RESULTS: SBP in the CIH2 and CIH3 groups at the end of 6th week was significantly elevated compared with the baseline SBP (P<0.001) and those in the CIH1 and the UC groups (P<0.05). The expression of angiotensin-converting enzyme (ACE) and ACE2 in renal arterioles was significantly different (P<0.05), and the levels of angiotensin II (AngII) in the serum and kidney tissues, oxidation of low density lipoprotein (ox-LDL) and malondialdehyde (MDA) in the serum were increased. Ang-(1-7) and the inhibitory capability for hydroxyl free radicals in the serum were decreased significantly in CIH2 and CIH3 groups compared with CIH1 and UC (P<0.05) groups at the end of 6th week. SBP showed a positive correlation with AngII in serum and kidney tissues, but showed a negative correlation with Ang-(1-7) in serum and kidney tissues. The levels of MDS and ox-LDL in serum showed a positive correlation with AngII in serum and kidney tissues respectively, but showed a negative correlation with Ang-(1-7) in serum and kidney tissues respectively. The inhibitory capability for hydroxyl free radicals in serum showed a positive correlation with Ang-(1-7), but a negative correlation with AngII. The level of ox-LDL showed a positive correlation with MDA, but a negative correlation with the inhibitory capability for hydroxyl free radicals. There were no significant difference between CIH1 and UC groups in parameters except of SBP and AngII (P<0.05). All the data were not different between CIH2 and CIH3 groups (P>0.05). CONCLUSIONS: CIH caused oxidative stress and RAS imbalance in rats. The imbalance of RAS in CIH rats was related with oxidative stress. The imbalance of RAS and oxidative stress may be one of the important mechanisms for CIH-induced hypertension. NAC can prevent CIH-induced hypertension through modulation of RAS by its anti-oxidative effect.

Targeting nerve growth factor, a new option for treatment of osteoarthritis: a network meta-analysis of comparative efficacy and safety with traditional drugs.

OBJECTIVE: Osteoarthritis (OA) is the most common joint disease and leading cause of pain and disability in the elderly population. Most guidelines recommend the use of non-steroidal anti-inflammatory drugs (NSAIDs) and opioids for the non-operative treatment of OA. Monoclonal nerve growth factor (NGF) antibodies are new drugs with the potential to provide pain relief and functional improvement in OA. We compared the efficacy (pain reduction and functional improvement), and safety of monoclonal NGF antibodies with NSAIDs and opioids in the treatment of OA with a Bayesian network meta-analysis. RESULTS: 38 articles, comprising 41 trials and 20489 patients with OA were included. Overall from the network meta-analysis, anti-NGFs were the most effective drugs for pain relief (Standardized Mean Difference or SMD compared with placebo 4.25, 95% CI 2.87 to 5.63, Surface Under the Cumulative RAnking curve or SUCRA=93.7%) and for functional improvement (SMD 4.90, 95% CI 3.46 to 6.33, SUCRA=98.3%). Although anti-NGFs were associated with higher risk of peripheral sensation abnormality (paresthesia and pruritus), they were not associated with higher risk of other AEs (headaches and nausea) or with higher withdrawal rates related to AEs. CONCLUSIONS: Monoclonal NGF antibodies provide significantly greater pain relief and functional improvement in OA compared to NSAIDs and opioids. Monoclonal NGF antibodies are not associated with severe AEs. More studies are needed to confirm these findings. METHODS: PubMed, CNKI, Web of Science, Scopus, Embase and Cochrane Library databases were searched for relevant studies (OA treated with anti-NGFs, opioids, selective COX-2 inhibitors or NSAIDs) published between January 1999 to January 2020. Bayesian network and conventional meta-analyses were conducted. Pain relief, functional improvement and AEs were assessed.

Prognostic relevance of SMC family gene expression in human sarcoma.

OBJECTIVE: To explore the prognostic value of the expression of genes encoding structural maintenance of chromosomes (SMCs) in human sarcoma. RESULTS: We found that the levels of SMC1A, SMC2, SMC3, SMC4, SMC5 and SMC6 mRNA were all higher in most tumors compared to normal tissues, and especially in sarcoma. According to the Cancer Cell Line Encyclopedia (CCLE), SMC1A, SMC2, SMC3, SMC4, SMC5 and SMC6 are also highly expressed in sarcoma cell lines. Results of Gene Expression Profiling Interactive Analysis (GEPIA) indicated that high expression of SMC1A was significantly related to poor overall survival (OS) (p<0.05) and disease-free survival (DFS) in sarcoma (p<0.05). Additionally, strong expression of SMC2 was significantly related to poor OS in sarcoma (p<0.05). In contrast, SMC3, SMC4, SMC5, and SMC6 expression had no significant impact on OS or DFS in sarcoma. CONCLUSIONS: Expression of SMC family members is significantly different in sarcoma relative to normal tissues, and SMC1A and SMC2 may be useful as prognostic biomarkers. METHODS: We performed a detailed comparison of cancer and normal tissues regarding the expression levels of mRNA for SMC family members in various cancers including sarcoma through ONCOMINE and GEPIA (Gene Expression Profile Interactive Analysis) databases.

Inhibitory effect of alpinetin on IL-6 expression by promoting cytosine methylation in CpG islands in the IL-6 promoter region.

BACKGROUND: Alpinetin is a flavonoid which exerts antibacterial and anti-inflammatory functions. In order to prove that the induced methylation is an important mechanism for alpinetin in regulating the expression of inflammatory factor Interleukin-6 (IL-6), we detected the dinucleotide methylation status of CpG islands in the IL-6 promoter region and IL-6 level after treatment of RAW246.7 murine macrophages with alpinetin. METHODS: After RAW246.7 murine macrophages were treated with alpinetin, alpinetin + GW9662 (the peroxisome proliferator-activated receptor (PPAR) antagonist), and alpinetin + DNA methyltransferase 3 alpha (DNMT3A) siRNA for 96 hr, CpG islands were analyzed using time-of-flight mass spectrophotometry (TOF-MS) and bisulfite sequencing polymerase chain reaction (BSP). Dinucleotide methylation status of the CpG islands in the IL-6 promoter region was analyzed by methylation-specific Polymerase Chain Reaction (PCR). IL-6 level was detected using the enzyme-linked immunosorbent assay (ELISA) method. Pearson's correlation analysis was conducted to test for potential correlation between the methylation status of CpG islands in the IL-6 promoter region and IL-6 level in RAW 246.7 cells. RESULTS: Alpinetin promoted dinucleotide methylation status of two CpG islands in the IL-6 promoter region stretching 500-2500 bp upstream of the transcriptional start site (TSS) (p < .05). This promoting effect was more significant for the CpG island stretching 500-1500 bp long. The methylation ratio of dinucleotide at this position was significantly inversely correlated with the level of IL-6 (p < .05). PPAR antagonist GW9662 and interference of DNMT3A could reverse both the alpinetin-induced methylation and inhibitory effects on IL-6 expression. CONCLUSION: Alpinetin could induce dinucleotide methylation status of CpG islands in the IL-6 promoter region by activating methyltransferase, thus inhibiting IL-6 expression in murine macrophages.

Expression of HER-2 in surgical specimen and biopsy as a biomarker of metastasis in patients with osteosarcoma: a meta-analysis.

BACKGROUND: Previous studies have evaluated the effect of human epidermal growth factor receptor 2 (HER-2) expression on the metastasis of patients with osteosarcoma (OS) while the results remain conflicting. Here we performed a systematic review and meta-analysis to determine the value of HER-2 in prognosis of OS. METHODS: A comprehensive search using NCBI PubMed, the Cochrane library, Embase, ISI Web of Knowledge, Springer, China National Knowledge Internet database (CNKI), Wanfang database, Chinese VIP database and Chinese Biological Medical Database (CBM) from inception through Aug 28, 2018 was conducted to investigate HER-2 expression and OS metastasis. We evaluated the quantity of the studies using Newcastle-Ottawa quality assessment scale (NOS). RESULTS: There were 15 studies with 652 OS patients involved. The results of meta-analysis showed that positive expression of HER-2 was associated with OS metastasis (OR =4.42; 95% CI, 2.91-6.71; P<0.0001). No significant heterogeneity or publication bias was observed among all studies. CONCLUSIONS: The results of this study suggest that HER-2 positive expression indicates OS metastasis, while it's needed to perform more prospective studies to confirm the prognostic value of HER-2 in patients with OS.