Meta-analysis and systematic review of the relationship between sex and the risk or incidence of poststroke aphasia and its types.

OBJECTIVE: To analyse and discuss the association of gender differences with the risk and incidence of poststroke aphasia (PSA) and its types, and to provide evidence-based guidance for the prevention and treatment of poststroke aphasia in clinical practice. DATA SOURCES: Embase, PubMed, Cochrane Library and Web of Science were searched from January 1, 2002, to December 1, 2023. STUDY SELECTION: Including the total number of strokes, aphasia, the number of different sexes or the number of PSA corresponding to different sex. DATA EXTRACTION: Studies with missing data, aphasia caused by nonstroke and noncompliance with the requirements of literature types were excluded. DATA SYNTHESIS: 36 papers were included, from 19 countries. The analysis of 168,259 patients with stroke and 31,058 patients with PSA showed that the risk of PSA was 1.23 times higher in female than in male (OR = 1.23, 95% CI = 1.19-1.29, P < 0.001), with a prevalence of PSA of 31% in men and 36% in women, and an overall prevalence of 34% (P < 0.001). Analysis of the risk of the different types of aphasia in 1,048 patients with PSA showed a high risk in females for global, broca and Wenicke aphasia, and a high risk in males for anomic, conductive and transcortical aphasia, which was not statistically significant by meta-analysis. The incidence of global aphasia (males vs. females, 29% vs. 32%) and broca aphasia (17% vs 19%) were higher in females, and anomic aphasia (19% vs 14%) was higher in males, which was statistically significant (P < 0.05). CONCLUSIONS: There are gender differences in the incidence and types of PSA. The risk of PSA in female is higher than that in male.

Expression analysis and antiviral activity of koi carp (Cyprinus carpio) viperin against carp edema virus (CEV).

Viperin, also known as radical S-Adenosyl methionine domain containing 2 (RSAD2), is an IFN stimulated protein that plays crucial roles in innate immunity. Here, we identified a viperin gene from the koi carp (Cyprinus carpio) (kVip). The ORF of kVip is 1047 bp in length, encoding a polypeptide of 348 amino acids with neither signal peptide nor transmembrane protein. The predicted molecular weight is 40.37 kDa and the isoelectric point is 7.7. Multiple sequence alignment indicated that putative kVip contains a radical SAM superfamily domain and a conserved C-terminal region. kVip was highly expressed in the skin and spleen of healthy koi carps, and significantly stimulated in both natural and artificial CEV-infected koi carps. In vitro immune stimulation analysis showed that both extracellular and intracellular poly (I: C) or poly (dA: dT) caused a significant increase in kVip expression of spleen cells. Furthermore, intraperitoneal injection of recombinant kVip (rkVip) not only reduced the CEV load in the gills, but also improved the survival of koi carps following CEV challenge. Additionally, rkVip administration effectively regulated inflammatory and anti-inflammatory cytokines (IL-6, IL-1ß, TNF-α, IL-10) and interferon-related molecules (cGAS, STING, MyD88, IFN-γ, IFN-α, IRF3 and IRF9). Collectively, kVip effectively responded to CEV infection and exerted antiviral function against CEV partially by regulation of inflammatory and interferon responses.

Miro1 improves the exogenous engraftment efficiency and therapeutic potential of mitochondria transfer using Wharton's jelly mesenchymal stem cells.

Mitochondria are important for maintaining cellular energy metabolism and regulating cellular senescence. Mitochondrial DNA (mtDNA) encodes subunits of the OXPHOS complexes which are essential for cellular respiration and energy production. Meanwhile, mtDNA variants have been associated with the pathogenesis of neurodegenerative diseases, including MELAS, for which no effective treatment has been developed. To alleviate the pathological conditions involved in mitochondrial disorders, mitochondria transfer therapy has shown promise. Wharton's jelly mesenchymal stem cells (WJMSCs) have been identified as suitable mitochondria donors for mitochondria-defective cells, wherein mitochondrial functions can be rescued. Miro1 participates in mitochondria trafficking by anchoring mitochondria to microtubules. In this study, we identified Miro1 over-expression as a factor that could help to enhance the efficiency of mitochondrial delivery. More specifically, we reveal that Miro1 over-expressed WJMSCs significantly improved intercellular communications, cell proliferation rates, and mitochondrial membrane potential, while restoring mitochondrial bioenergetics in mitochondria-defective fibroblasts. Furthermore, Miro1 over-expressed WJMSCs decreased rates of induced apoptosis and ROS production in MELAS fibroblasts; although, Miro1 over-expression did not rescue mtDNA mutation ratios nor mitochondrial biogenesis. This study presents a potentially novel therapeutic strategy for treating mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), and other diseases associated with dysfunctional mitochondria, while the pathophysiological relevance of our results should be further verified by animal models and clinical studies.

Risk factors for renal outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis: a nationwide retrospective study in China.

BACKGROUND: Pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a life-threatening systemic vasculitis featured by liability to renal involvement. However, there are few studies on the risk factors and predictive models for renal outcomes of AAV in children. METHODS: Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively. The risk factors and predictive model of end-stage renal disease (ESRD) in AAV were explored. RESULTS: Renal involvement was the most typical manifestation (95.5%), and the crescent was the predominant pathological lesion (84.9%). The estimated glomerular filtration rate (eGFR) was evaluated in 114 patients, of whom 59.6% developed ESRD, and the median time to ESRD was 3.20 months. The eGFR [P = 0.006, odds ratio (OR) = 0.955, 95% confidence interval (CI) = 0.924-0.987] and the percentages of global glomerulosclerosis (pGGS; P = 0.018, OR = 1.060, 95% CI = 1.010-1.112) were independent risk factors for ESRD of renal biopsy. Based on the pGGS and eGFR at renal biopsy, we developed three risk grades of ESRD and one predictive model. The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades (P < 0.001). Compared with serum creatinine at baseline, the predictive model had higher accuracy (0.86 versus 0.58, P < 0.001) and a lower coefficient of variation (0.07 versus 0.92) in external validation. CONCLUSIONS: Renal involvement is the most common manifestation of pediatric AAV in China, of which more than half deteriorates into ESRD. The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children. Supplementary file 2 (MP4 18937 KB).

Diagnostic performance of renal cortical elasticity by supersonic shear wave imaging in pediatric glomerular disease.

PURPOSE: To explore the diagnostic performance of renal cortical elasticity expressed by Young's modulus (YM) using the supersonic shear wave imaging (SSI) technique in pediatric glomerular disease. MATERIALS AND METHODS: Seventy-one children with glomerular disease confirmed by renal biopsy and sixty healthy volunteers were enrolled in this study. Conventional and SSI ultrasound examinations were performed in all individuals for both kidneys. We measured renal length, renal width, renal thickness, parenchyma thickness, interlobar arterial resistive index (RI) and the YM of the middle and lower pole. RESULTS: Regardless of which pole and which side of the kidney, the YM in the disease group was significantly higher than that in the control group (P < 0.001). The YM of the middle pole in the left kidney demonstrated the largest AUC (0.936, P < 0.001), and the corresponding cut-off value was 15.48 kPa with a sensitivity of 87.3% and a specificity of 86.7%. There was no significant difference in the YM among different pathological types of pediatric glomerular disease in the disease group, and the same in different grades of patients with Immunoglobulin A (IgA) nephropathy by Lee classification and the Oxford Classification as well as Henoch-Schonlein purpura nephritis (HSPN) by International Study of Kidney Disease in Children (ISKDC) classification (P > 0.05). We found positive but weak correlations between the YM and renal length (r = 0.299, P = 0.001), renal width (r = 0.408, P < 0.001), renal thickness (r = 0.299, P = 0.001), and parenchyma thickness (r = 0.212, P = 0.015), whereas the YM had no significant correlations with age, sex, BMI, interlobar arterial RI, and laboratory findings (P > 0.05). CONCLUSIONS: SSI technology is a non-invasive and feasible method for the diagnosis of pediatric glomerular disease. However, SSI did not show good performance in distinguishing different pathological types and disease grades in our study.

Impact of delayed veno-venous extracorporeal membrane oxygenation weaning on postoperative rehabilitation of lung transplantation: a single-center comparative study.

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a reliable and effective extracorporeal life support during lung transplantation (LTx). However, the clinical benefit of delayed VV-ECMO weaning remains unclear. The current study aims to investigate whether delayed weaning of VV-ECMO is more beneficial to the rehabilitation for lung transplant patients. Patients who underwent LTx with VV-ECMO between January 2017 and January 2019 were included. Enrollment of patients was suitable for weaning off ECMO immediately after surgery. Randomization was performed in the operating room. Postoperative outcomes were compared between the two groups. Besides, univariate and multivariable logistic regressions were performed to estimate risk of postoperative complications. Compared to VV-ECMO weaning immediately after LTx, delayed weaning was associated with shorter hospital length of stay (days, 31 vs. 46; P < 0.05), lower incidence of noninvasive ventilation (4.3% vs. 24.4%; P < 0.05), primary graft dysfunction (PGD) (6.4% vs. 29.3%; P < 0.05), atrial fibrillation (AF) (4.3% vs. 22%, P < 0.05), and respiratory failure (4.3% vs. 19.5%; P < 0.05). Multivariable logistic regressions revealed that VV-ECMO weaning after LTx was independently correlated with increased risk of developing PGD [odds ratio (OR), 5.97, 95% CI 1.16-30.74], AF (OR, 6.87, 95% CI 1.66-28.47) and respiratory failure (OR, 6.02, 95% CI 1.12-32.49) by comparison of delayed VV-ECMO weaning. Patients with delayed VV-ECMO weaning are associated with lower complications and short hospital length of stay, while it relates to longer mechanical ventilation. These findings suggest that delayed VV-ECMO after LTx can facilitate rehabilitation.

Health-related quality of life measured by EQ-5D-3L for the spouses of breast cancer patients.

To explore factors influencing the health-related quality of life of spouses of breast cancer patients and the suitable questionnaires for this purpose. A cross-sectional study was conducted in the Third Affiliated Hospital of Kunming Medical University. The spouses of breast cancer patients were included and evaluated via face-to-face interviews. Self-designed demographic characteristics and disease-related questionnaires, the 12-item health survey questionnaire (SF-12), the three-level European five-dimensional health status scale (EQ-5D-3L), and the Social Support Rate Scale (SSRS) were used. The internal consistency reliability measure Cronbach's coefficient, criterion-related validity, construct validity, and sensitivity were used to evaluate the applicability of the EQ-5D-3L. Univariate and multivariate analyses were performed to analyze the factors associated with the health-related quality of life of spouses of breast cancer patients. We investigated a total of 100 spouses of breast cancer patients. Cronbach's α, the internal consistency reliability coefficient, was 0.502. The EQ-5D-3L health utility score was moderately correlated with PCS-12 (r=0.46, p=0.0001) and weakly correlated with MCS-12 (r=0.35, p=0.0001). The EQ-5D-3L health utility score for the spouses of breast cancer patients was 0.870, and the EQ-VAS was 78.3. In multivariate analysis, social support and cognition of the treatment effect were factors that influenced the EQ-5D-3L health utility score. The EQ-5D-3L has good reliability, validity, and sensitivity for measuring the physiological aspects of the health-related quality of life of spouses of BC patients. EQ-5D-3L was considered suitable for this study.

Characterization of aroma-active compounds in Dongli by quantitative descriptive analysis, gas chromatography-triple quadrupole tandem mass spectrometry, and gas chromatography-olfactometry.

Dongli, or frozen pear, is a traditional Chinese snack with a unique flavor. This study identified the aroma-active volatile compounds (VOCs) in Dongli using quantitative descriptive analysis (QDA), gas chromatography-triple quadrupole tandem mass spectrometry (GC-MS/MS), and gas chromatography-olfactometry (GC-O). QDA indicated that Dongli of all cultivars presented increased sweet and wine aromas. A total of 21 VOCs were identified by GC-MS/MS. Bidirectional orthogonal partial least square (O2PLS) analysis, GC-O analysis, detection frequency analysis (DFA), and relative odor activity values (ROAV) showed that: estragole and anethole contributing "anise, green" aromas were the key aromatic VOCs of fresh pears, while ethyl butanoate, butyl acetate, heptyl acetate, benzaldehyde, and geranyl acetone contributing "sweet, fruity, green" aromas were the key aromatic VOCs of Dongli. The results revealed that the repeated freezing treatment promoted a unique aroma in pears. This study would contribute to developing new pear products. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05463-8.

Degradation of COD in antibiotic wastewater by a combination process of electrochemistry, hydroxyl-functionalized ball-milled zero-valent iron/Fe3O4 and Oxone.

In this study, the significant iron-based material, hydroxyl-functionalized ball-milled zero-valent iron/Fe3O4 (HFB-ZVI/Fe3O4) was employed for the experiments. The performance of the Electro + HFB-ZVI/Fe3O4 + Oxone system for the degradation of chemical oxygen demand (COD) in antibiotic wastewater was investigated. A direct current was applied between a graphite plate anode and two iron plate cathodes, and a series of operational parameters, such as applied electric current, the dosage of HFB-ZVI/Fe3O4 composite, the dosage of Oxone, and initial solution pH, were explored to evaluate the oxidation process. The application of electric current enhanced the gradual degradation of COD and the increase of current intensity accelerated COD degradation. The neutral condition was favourable for the rapid degradation of COD in a short reaction time by the Electro + HFB-ZVI/Fe3O4 + Oxone process and promoted the degradation efficiency of COD. An increase of electric current gradually decreased the reaction solution pH, the larger the electric current applied in the reaction process, the lower the final pH of the reaction solution. Under the optimal experimental conditions (1 g/L HFB-ZVI/Fe3O4 composite, 0.3 g/L Oxone, current intensity = 500 mA, initial solution pH = 7.85), Electro + HFB-ZVI/Fe3O4 + Oxone achieved 99% COD degradation in antibiotic wastewater. Radicals quenching experiments indicated the contribution to COD degradation by hydroxyl radicals (HO•), sulphate radicals (SO4•-) and other oxidants were 66.03%, 24.014% and 9.756%, respectively. The possible mechanism of COD degradation in the Electro + HFB-ZVI/Fe3O4 + Oxone system was also discussed in this study. The findings in this work provided useful information for the treatment of wastewater.

Uniportal video-assisted thoracic S9+10 segmentectomy using a single-direction approach is good for pulmonary function.

BACKGROUND: Uniportal video-assisted thoracic surgery is still a technical challenge, especially anatomical segmentectomy for the lateral basal segment (S9), posterior basal segment (S10), or both (S9+10). Different surgical procedures determine a variable pulmonary functional reduction depending on the extent of the resection. This study aimed to compare the efficiency of uniportal video-assisted thoracic surgery S9+10 segmentectomy with video-assisted thoracic surgery basal segmentectomy in preserving pulmonary function. METHODS: The patients who had undergone single-port video-assisted thoracic surgery S9+10 segmentectomy using a single-direction approach were age, sex, and pulmonary function matched with those undergoing video-assisted thoracic surgery basal segmentectomy. The pulmonary function tests were performed preoperatively, and at 3 and 6 months postoperatively. The operative details, postoperative complications, and pulmonary function were statistically analyzed. RESULTS: After matching, a total of 46 patients undergoing video-assisted thoracic surgery S9+10 segmentectomy and 58 patients undergoing video-assisted thoracic surgery basal segmentectomy were eligible for analysis. There was no significant difference in the average blood loss, the duration of chest tube, intensive care unit stay, or hospital stay between these 2 groups. There were no major postoperative complications and surgical mortality was found in the 2 groups. The uniportal video-assisted thoracic surgery S9+10 segmentectomy group had a greater preserved pulmonary function (concerning the values of the forced vital capacity, forced expiratory volume in 1 second, forced expiratory volume in 1 second %, and diffusion capacity of carbon monoxide %) than video-assisted thoracic surgery basal segmentectomy group at 1 and 3 months postoperatively. CONCLUSION: Uniportal video-assisted thoracic surgery anatomic S9+10 segmentectomy using a single-direction approach was safe and feasible for early stages of nonsmall cell lung cancer, and it offered significantly better functional preservation compared with basal segmentectomy.

Effects of prolonged cold ischemia on the DCD kidney function and Inflammasome expression in rat kidney transplants.

BACKGROUND: Acute kidney injury (AKI) is the main reason for the bad outcome of the donation of circulatory death (DCD) kidney after transplantation. Prolonged cold storage (CS) is a risk factor for the occurrence of the delayed graft function in DCD kidney. The protein NLR-domain containing receptor 3 (NLRP3) plays a crucial role in renal ischemia reperfusion injury by triggering inflammasome formation. Herein, we investigated whether the NLRP3 signal participate in the CS-induced damage of DCD kidney in rat kidney transplantation models. MATERIALS AND METHODS: DCD kidney and living donor (LD) kidney of SD rats were preserved in UW solution at 4 °C for 2 h or 18 h, and then transplanted into syngeneic recipient. Thus, the animals were randomly divided into 4 groups: 2-h LD group, 2-h DCD group, 18-h LD group and 18-h DCD group. The renal function and pathological changes were determined. The expressions of NLRP3 and inflammatory factor IL-1ß were assessed. The concentration of ferrous iron (Fe2+) was analyzed both in kidneys and in the preservation solution. The renal morphological changes were examined by hematoxylin eosin staining. RESULTS: Our results showed that the levels of Cr and BUN were higher in 18-h LD group as compared to the 2-h LD group, which were remarkably increased in 18-h DCD group. The expression levels of NLRP3 and IL-1ß were increased by 18-h CS compared to 2-h CS in both LD kidney and DCD kidney. In addition, the Fe2+ concentration has significantly increased in 18-h LD group than that in 2-h LD group, and the elevation of Fe2+ was more remarkable in DCD kidneys. CONCLUSION: In conclusion, our study demonstrated that prolonged hypothermic storage of DCD kidney deteriorated the graft function via the increased Fe2+ concentration, which was associated with the upregulation of NLRP3 expression.

Genetic effect of ischemia-reperfusion injury upon primary graft dysfunction and chronic lung allograft dysfunction in lung transplantation: evidence based on transcriptome data.

The unclear mechanism that ischemia-reperfusion injury (IRI) contributes to the development of primary graft dysfunction (PGD) and chronic lung allograft dysfunction (CLAD) remains a major issue in lung transplantation. Differentially expressed PGD-related genes and CLAD-related genes during IRI (IRI-PGD common genes and IRI-CLAD common genes) were identified using GEO datasets (GSE127003, GSE8021, GSE9102) and GeneCards datasets. Enrichment analysis and four network analyses, namely, protein-protein interaction, microRNA (miRNA)-gene, transcription factor (TF)-gene, and drug-gene networks, were then performed. Moreover, GSE161520 was analyzed to identify the differentially expressed core miRNAs during IRI in rats. Finally, Pearson correlation analysis and ROC analysis were performed. Eight IRI-PGD common genes (IL6, TNF, IL1A, IL1B, CSF3, CXCL8, SERPINE1, and PADI4) and 10 IRI-CLAD common genes (IL1A, ICAM1, CCL20, CCL2, IL1B, TNF, PADI4, CXCL8, GZMB, and IL6) were identified. Enrichment analysis showed that both IRI-PGD and IRI-CLAD common genes were significantly enriched in "AGE-RAGE signaling pathway in diabetic complication" and "IL-17 signaling pathway". Among the core miRNAs, miR-1-3p and miR-335 were differentially expressed in IRI rats. Among core TFs, CEBPB expression had a significant negative correlation with P/F ratio (r = -0.33, P = 0.021). In the reperfused lung allografts, the strongest positive correlation was exhibited between PADI4 expression and neutrophil proportion (r = 0.76, P < 0.001), and the strongest negative correlation was between PADI4 expression and M2 macrophage proportion (r = -0.74, P < 0.001). In lung allografts of PGD recipients, IL6 expression correlated with activated dendritic cells proportion (r = 0.86, P < 0.01), and IL1B expression correlated with the neutrophils proportion(r = 0.84, P < 0.01). In whole blood of CLAD recipients, GZMB expression correlated with activated CD4+ memory T cells proportion (r = 0.76, P < 0.001).Our study provides the novel insights into the molecular mechanisms by which IRI contributes to PGD and CLAD and potential targets for therapeutic intervention.

FOXO3-induced lncRNA LOC554202 contributes to hepatocellular carcinoma progression via the miR-485-5p/BSG axis.

Long non-coding RNAs (LncRNAs) have played very important roles in the malignancy behaviors of hepatocellular carcinoma (HCC). LncRNA LOC554202 (LOC554202) was a newly identified tumor-related lncRNA. However, its expression and function in HCC remained unknown. In this study, we firstly reported that LOC554202 expression was distinctly upregulated in HCC specimens and cell lines. Clinical assays indicated that increased LOC554202 expression had a diagnostic value for HCC patients and was positively associated with advanced stages and poor clinical prognosis. Additionally, forkhead box O3(FOXO3) could bind directly to the LOC554202 promoter region and activate its transcription. Functionally, we observed that knockdown of LOC554202 suppressed the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) progress of HCC cells, and promoted apoptosis. Mechanistically, LOC554202 competitively bound to miR-485-5p and prevented the suppressive effects of miR-485-5p on its target gene basigin (BSG), which finally led to HCC metastasis, EMT, and docetaxel chemoresistance. Our data demonstrated that FOXO3-induced LOC554202 contributed to HCC progression by upregulating BSG via competitively binding to miR-485-5p, which suggested that the regulation of the FOXO3/LOC554202/miR-485-5p/BSG axis may have beneficial effects in the treatment of HCC.

Effects of corticosteroids on new-onset atrial fibrillation after cardiac surgery: A meta-analysis of randomized controlled trials.

BACKGROUND: Postoperative atrial fibrillation (POAF) occurs commonly after cardiac surgery. Studies suggest that corticosteroid can reduce the incident of POAF. However, the results remain controversial. This meta-analysis aimed to evaluate the efficacy and safety corticosteroid on the prevention of POAF following cardiac surgery. METHODS: Randomized controlled trials were identified through a systematic literature search. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. Primary outcome was the incidence of POAF as well as length of hospital stay and intensive care unit stay, wound and other infection, mortality, duration of ventilation, myocardial infarction, gastrointestinal complications, high blood sugar, stroke, and postoperative bleeding. RESULTS: Fourteen studies with 13,803 patients were finally involved in the present study. Overall, corticosteroid significantly decreased the risk of POAF (relative risk [RR], 0.7; 95% confidence interval [CI], 0.55-0.89; P = .003). There were no significant differences in the incidence of length of intensive care unit stay (RR, -2.32; 95% CI, -5.44 to 0.80; P = .14) and hospital stay (RR, -0.43; 95% CI, -0.84 to -0.02; P = .04), infections (RR, 1.01; 95% CI, 0.83-1.23; P = .9), mortality (RR, 0.87; 95% CI, 0.71-1.06; P = .16), duration of ventilation (RR, -0.29; 95% CI, -0.65 to 0.07; P = .12), gastrointestinal complications (RR, 1.26; 95% CI, 0.91-1.76; P = .16), high blood sugar (RR, 1.98; 95% CI, 0.91-4.31; P = .09), stroke (RR, 0.9; 95% CI, 0.69-1.18; P = .45), postoperative bleeding (RR -44.54; 95% CI, -115.28 to 26.20; P = .22) and myocardial infarction (RR, 1.71; 95% CI, 0.96-1.43; P = .12). CONCLUSION: Our review suggests that the efficacy of corticosteroid might be beneficial to POAF development in patients undergoing cardiac surgery. The strength of this association remains uncertain because of statistical and clinical heterogeneity among the included studies.

Risk factors for lymph node metastasis in T1 esophageal squamous cell carcinoma: A systematic review and meta-analysis.

BACKGROUND: Lymph node metastasis (LNM) affects the application and outcomes of endoscopic resection in T1 esophageal squamous cell carcinoma (ESCC). However, reports of the risk factors for LNM have been controversial. AIM: To evaluate risk factors for LNM in T1 ESCC. METHODS: We searched Embase, PubMed and Cochrane Library to select studies related to LNM in patients with T1 ESCC. Included studies were divided into LNM and non-LNM groups. We performed a meta-analysis to examine the relationship between LNM and clinicopathologic features. Odds ratio (OR), mean differences and 95% confidence interval (CI) were assessed using a fixed-effects or random-effects model. RESULTS: Seventeen studies involving a total of 3775 patients with T1 ESCC met the inclusion criteria. After excluding studies with heterogeneity based on influence analysis, tumor size (OR = 1.93, 95%CI = 1.49-2.50, P < 0.001), tumor location (OR = 1.46, 95%CI = 1.17-1.82, P < 0.001), macroscopic type (OR = 3.17, 95%CI = 2.33-4.31, P < 0.001), T1 substage (OR = 6.28, 95%CI = 4.93-8.00, P < 0.001), differentiation (OR = 2.11, 95%CI = 1.64-2.72, P < 0.001) and lymphovascular invasion (OR = 5.86, 95%CI = 4.60-7.48, P < 0.001) were found to be significantly associated with LNM. Conversely, sex, age and infiltrative growth pattern were not identified as risk factors for LNM. CONCLUSION: A tumor size > 2 cm, lower location, nonflat macroscopic type, T1b stage, poor differentiation and lymphovascular invasion were associated with LNM in patients with T1 ESCC.

Melatonin Alleviates Cardiac Dysfunction Via Increasing Sirt1-Mediated Beclin-1 Deacetylation and Autophagy During Sepsis.

Cardiac dysfunction is a major cause leading to multiple organ failure in sepsis. Beclin-1-dependent autophagy has been evidenced to exert protective effects on hearts in sepsis. However, the mechanisms on how Beclin-1 and autophagy are regulated remains enigmatic. To explore the detailed mechanisms controlling Beclin-1-dependent autophagy in septic heart and whether melatonin could protect against sepsis via regulating cardiac autophagy, adult Sprague-Dawley (SD) rats were subjected to cecal ligation and puncture (CLP) to induce sepsis. Rats were intraperitoneally administrated with 30 mg/kg melatonin within 5-min post-CLP surgery. Our data showed that sepsis induced Becline-1 acetylation and inhibited autophagy in hearts, resulting in impaired cardiac function. However, melatonin treatment facilitated Beclin-1 deacetylation and increased autophagy in septic hearts, thus improved cardiac function. Moreover, melatonin increased the expression and activity of Sirtuin 1 (Sirt1), and inhibition of Sirt1 abolished the protective effects of melatonin on Beclin-1 deacetylation and cardiac function. In conclusion, increased Beclin-1 acetylation was involved in impaired autophagy in septic hearts, while melatonin contributed to Beclin-1 deacetylation via Sirt1, leading to improved autophagy and cardiac function in sepsis. Our study sheds light on the important role of Beclin-1 acetylation in regulating autophagy in sepsis and suggests that melatonin is a potential candidate drug for the treatment of sepsis.

MicroRNA-92a -mediated endothelial to mesenchymal transition controls vein graft neointimal lesion formation.

PURPOSE: Long-term failure of vein grafts due to neointimal hyperplasia remains an important problem in coronary artery bypass graft surgery. Endothelial to mesenchymal transition (EndMT) contributes to vein graft vascular remodeling. However, there is little study on microRNA-mediated EndMT contributions to neointimal formation in vein graft. We hypothesized that microRNA-92a (miR-92a) might play an important role in determining EndMT contributions to neointimal formation. METHODS: miR-92a and EndMT-related proteins detected by qRT-PCR and Western blot in vitro and in vivo. Adeno-associated virus 6 (AAV6) delivery gene therapy was used to inhibit neointimal formation in vivo. The intimal hyperplasia of vein grafts was measured by HE staining, the expression of EndMT-related protein in vein grafts was measured by immunofluorescence. Immunohistochemistry and luciferase assay were used to detect potential targets of miR-92a. RESULTS: The expression of miR-92a was found to be upregulated in neointimal hyperplasic lesions after vein grafting. Using cultured human umbilical vein endothelial cells (HUVECs), we show that TGF-ß1 treatment of HUVECs significantly increased miR-92a expression and induced EndMT, characterized by suppression of endothelial-specific markers (CD31 and VE-cadherin) and an increase in mesenchymal-specific markers (a-SMA and vimentin), while inhibition of miR-92a expression blunted EndMT in cultured HUVECs. Furthermore, AAV6 mediated miR-92a suppression gene therapy effectively resulted in decreased EndMT and less neointimal formation in vein grafts in vivo. We further identified that integrin alpha 5 (ITGA5) is a potential target gene involved in the development of neointima formation in these vein grafts. CONCLUSION: This data suggests that neointimal formation does not solely rely on vascular smooth muscle cell phenotypic switching but is also related to EndMT, and miR-92a-mediated EndMT is an important mechanism underlying neointimal formation in vein grafts.

IGF-1 inhibits MPTP/MPP+-induced autophagy on dopaminergic neurons through the IGF-1R/PI3K-Akt-mTOR pathway and GPER.

Autophagy dysfunctions are involved in the pathogenesis of Parkinson's disease (PD). In the present study, we aimed to evaluate the involvement of G protein-coupled estrogen receptor (GPER) in the inhibitory effect of insulin-like growth factor-1 (IGF-1) against excessive autophagy in PD animal and cellular models. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment significantly induced mouse movement disorder and decreased the protein level of tyrosine hydroxylase (TH) in the substantia nigra (SN) and dopamine (DA) content in striatum. Along with the dopamine neuron injury, we observed significant upregulations of microtubule-associated light chain-3 II (LC3-II) and α-synuclein as well as a downregulation of P62 in MPTP-treated mice. These changes could be restored by IGF-1 pretreatment. Cotreatment with IGF-1R antagonist JB-1 or GPER antagonist G15 could block the neuroprotective effects of IGF-1. 1-Methy-4-phenylpyridinium (MPP+) treatment could also excessively activate autophagy along with the reduction of cell viability in SH-SY5Y cells. IGF-1 could inhibit the neurotoxicity through promoting the phosphorylation of Akt and mammalian target of rapamycin (mTOR), which could also be antagonized by JB-1 or G15. These data suggest that IGF-1 inhibits MPTP/MPP+-induced autophagy on dopaminergic neurons through the IGF-1R/PI3K-Akt-mTOR pathway and GPER.

Clinical analysis of bone metastasis of gastric cancer: incidence, clinicopathological features and survival.

Aim: We evaluated the incidence, clinicopathological features, prognostic factors and survival of gastric cancer (GC) with bone metastasis in a single large cancer center in China. Patients & methods: Patients with bone metastasis of GC were retrospectively analyzed. Overall survival was estimated using the Kaplan-Meier method. Clinicopathological factors, which were associated with prognostic factors for survival, were evaluated. Results: The incidence of bone metastasis was 11.3% for metastatic GC patients. Median overall survival time was 6.5 months. Multivariate analysis revealed two independent poor prognostic factors: Eastern Cooperative Oncology Group ≥2 (p = 0.023) and lack of palliative chemotherapy (p = 0.018). Conclusion: The incidence of bone metastasis from metastatic GC was underestimated. The prognosis of GC with bone metastasis was poor.