Background: The authors compare the effectiveness and safety of endovascular treatment (EVT) versus best medical management (BMM) in strokes attributable to acute basilar artery occlusion (BAO). Methods: The present analysis was based on the ongoing, prospective, multicenter ATTENTION (Endovascular Treatment for Acute Basilar Artery Occlusion) trial registry in China. Our analytic sample comprised 2134 patients recruited at 48 sites between 2017 and 2021 and included 462 patients who received BMM and 1672 patients who received EVT. We performed an inversed probability of treatment weighting analysis. Qualifying patients had to present within 24 hours of estimated BAO. The primary clinical outcome was favorable functional outcome (modified Rankin Scale score, 0–3) at 90 days. We also performed a sensitivity analysis with the propensity score matching–based and the instrumental variable–based analysis. Results: In our primary analysis using the inversed probability of treatment weighting–based analysis, there was a significantly higher rate of favorable outcome at 90 days among EVT patients compared with BMM-treated patients (adjusted relative risk, 1.42 [95% CI, 1.19–1.65]; absolute risk difference, 11.8% [95% CI, 6.9–16.7]). The mortality was significantly lower (adjusted relative risk, 0.78 [95% CI, 0.69–0.88]; absolute risk difference, −10.3% [95% CI, −15.8 to −4.9]) in patients undergoing EVT. Results were generally consistent across the secondary end points. Similar associations were seen in the propensity score matching–based and instrumental variable–based analysis. Conclusions: In this real-world study, EVT was associated with significantly better functional outcomes and survival at 90 days. Well-designed randomized studies comparing EVT with BMM in the acute BAO are needed. Registration: URL: www.chictr.org.cn ; Unique identifier: ChiCTR2000041117.

Long non-coding RNA zinc finger antisense 1 (ZFAS1) has been probed in cerebral ischemia, while the regulatory mechanism of ZFAS1 in focal cerebral ischemia (FCI) via binding to microRNA (miR)-144-5p remains rarely explored. This study aims to decipher the function of ZFAS1 on FCI via sponging miR-144-5p to modulate fibroblast growth factor 7 (FGF7). The focal cerebral ischemia rat model was established by occlusion of the middle cerebral artery (MCAO) Lentivirus vectors altering ZFAS1, miR-144-5p or FGF7 expression were injected into rats before MCAO. Then, ZFAS1, miR-144-5p, and FGF7 levels were detected, the inflammatory factor level, oxidative stress level, angiogenesis, neurological function injury and neuronal apoptosis were assessed. The binding relations among ZFAS1, miR-144-5p and FGF7 were validated. ZFAS1 and FGF7 expression was elevated, while miR-144-5p expression was reduced in FCI rats. Decreased ZFAS1 or FGF7 or enriched miR-144-5p repressed the inflammatory response, oxidative stress, neuronal apoptosis, while it improved angiogenesis, and neurological function recovery; while up-regulated ZFAS1 exerted opposite effects. The augmented miR-144-5p or silenced FGF7 reversed the effects of enriched ZFAS1. ZFAS1 sponged miR-144-5p that targeted FGF7. Inhibition of lncRNA ZFAS1 improves functional recovery and angiogenesis after FCI via miR-144-5p/FGF7 axis. This study provides novel therapeutic targets for FCI treatment.

Renal cell carcinoma (RCC) is one of the most common urological malignancies with high incidence and metastatic relapse. Clear cell RCC (ccRCC) comprises nearly 70% of all RCC cases and is responsible for the majority of morbidity and mortality of RCC. Due to the poor diagnosis strategy and unsatisfactory clinical intervention, ccRCC causes a huge economic burden and poor patient quality of life; therefore, novel diagnostic or therapeutic targets for ccRCC are urgently needed. This study investigated the biological role of circFOXO3 in ccRCC development, showing that circFOXO3 is highly expressed in RCC cells and tissues and inhibits the viability of ccRCC cells. circFOXO3 dysregulation regulates NK cell cytotoxicity towards RCC cells by directly sponging miR-29a-3p and miR-122-5p. Overexpression of miR-29a-3p or miR-122-5p attenuated NK cell toxicity towards RCC cells and the transcriptional factor Kruppel-Like Factor 16 (KLF16) regulates circFOXO3 expression in RCC cells. In conclusion, this study has partially elucidated the function of circFOXO3 in ccRCC development, providing potential novel therapeutic targets for ccRCC.

The present study was undertaken to study the function of miRNA-199-3p in the regulation of human lung cancer growth and metastasis. The results showed significant (P < 0.05) downregulation of miRNA-199-3p in lung cancer tissues and cell lines. Overexpression of miR-197 caused considerable inhibition of the viability and colony formation of the lung cancer cells. The inhibition of proliferation was found to be due to the arrest of the SK-LU-1 lung cancer cells. At the G2/M phase of the cell cycle. In silico analysis and subsequent the dual-luciferase assays showed that miR-199-3p targets Sp1 at molecular. The expression of Sp1 was significantly (P < 0.05) upregulated in lung cancer cells and tissues. Nonetheless, miR-199-3p overexpression could cause post-transcriptional suppression of Sp1. Silencing of Sp1suppress the proliferation of SK-LU-1 lung cancer cells. However, overexpression Sp1 transcription factor prevents the tumor-suppressive effects of miR-199-3p on lung cancer cells. Additionally, miR-199-3p was found to suppresses the migration, invasion and epithelial-to-mesenchymal transition of human lung cancer cells. Summing up, miRNA-199-3p/SP1 axis controls the growth and metastasis of SK-LU-1 lung cancer cells.

Hepatocellular carcinoma (HCC) is highly malignant; nearly half of the new cases and deaths are in China. The poor prognosis of HCC is mainly due to late diagnosis; many new biomarkers have been developed for HCC diagnosis. However, few markers are quickly translated into clinical practice; early and differential diagnosis of HCC from cirrhosis and/or hepatitis is still a clinical challenge. Metabolomics and biochemical methods were used to reveal specific serum biomarkers of HCC. Most of the elevated metabolites in HCC and HBV patients were overlapped compared with controls. Urea was the specifically elevated serum biomarker of HCC patients. Moreover, urea combined with AFP and CEA can improve the sensitivity of HCC diagnosis. The plasma ammonia of HCC patients was significantly higher than healthy controls. Co-culture cell model revealed normal liver cells cooperated with cancer cells to metabolize ammonia into urea. The urea metabolism in cancer cells marginally depended on the expression of CPS1. However, the expression of CPS1 did not change with ammonium chloride, which might regulate the urea cycle through enzyme activity. The urea cycle could detoxify high concentrations of ammonia to promote cancer cell proliferation. Therefore, urea was a by-product of ammonia metabolism and could be a potential serum biomarker for HCC. The combined application of metabolomics and biochemical methods can discover new biomarkers for the early diagnosis of HCC and be quickly applied to clinical diagnosis.

BACKGROUND Gallbladder cancer (GBC) is one of the common malignant tumors of the biliary tract. There is no report that miR-197 is involved in GBC. OBJECTIVES The relationship between miR-197 expression and survival time of GBC patients was analyzed. Furthermore, the role and mechanism of miR-197 in GBC was explored. MATERIAL AND METHODS A total of 39 GBC patients (21 males, 18 females; average age 56.1 ±8.5 years) were included from December 2013 to November 2014. All patients were admitted to our hospital for surgical treatment (excluding patients with preoperative chemotherapy). The expression of miR-197 in GBC tissues was examined, and the relationship between miR-197 and patient survival time was analyzed. Cell Counting Kit-8 (CCK-8) and colony formation assays were used to detect cell proliferation. Flow cytometry and TUNEL staining were used to detect apoptosis. Expressions of proteins related with proliferation and apoptosis were detected. The target of miR-197 was predicted through bioinformatics website and verified using the dual luciferase reporter gene assay. The target gene was interfered to so that the effect of miR-197 on the regulation of GBC cell proliferation and apoptosis could be observed. RESULTS MiR-197 was highly expressed in GBC tissues, and the expression was closely related to the poor prognosis of GBC. Downregulation of miR-197 inhibited the proliferation and promoted the apoptosis of GBC cells; it also decreased the expressions of proliferation-related proteins p-ERK1/2 and p-AKT, and increased that of apoptosis pathway-related proteins Bax/Bcl-2 and c-caspase-3. The upregulation of miR-197 induced an opposite trend. MiR-197 directly regulated IGFBP3. CONCLUSIONS Our study proved that the expression of miR-197 is closely related to the poor prognosis of GBC. The miR-197-IGFBP3 axis regulates the proliferation and apoptosis of GBC cells. Downregulation of miR-197 inhibited the proliferation and promoted the apoptosis of GBC cells, indicating potential therapeutic effects.

BACKGROUND AND OBJECTIVES:This study aimed to explore the correlation between population-based iodine intake from iodized salt (iodine-IS) and thyroid cancer (TC) incidence.METHODS AND STUDY DESIGN:The TC incidence data were collected from the annual reports issued by China's National Central Cancer Registry. The iodine- IS data were extracted from the National Iodized Salt Surveys and National IDD Surveys (NIDDs). The time lag effect of iodine-IS on TC incidence was examined by using a polynomial distributed lag (PDL) model.RESULTS:Iodine-IS consumption peaked in 1999, declined to approximately 60% of 1999 in 2018, but remained close to 142.2 μg/person/day. After 2000, TC incidence increased notably on an annual basis. Iodine-IS and the age-standardized rate adjusted to the world population of TC incidence were significantly negatively correlated (p<0.05). The PDL model revealed that iodine-IS had a significant 6-year time lag effect on TC incidence (p<0.05).CONCLUSIONS:Iodine nutrition, as indicated by iodine-IS, exhibited a steady decline. The populationbased iodine-IS was adequate, however, TC incidence continued increasing. Although the 6-year cumulative effect of iodine-IS was considered, a negative correlation between iodine-IS and TC incidence was observed. Iodine- IS may not be a major risk factor for TC because universal salt iodization is maintaining adequate iodine nutrition in the population. The increasing TC incidence may reduce public willingness to consume iodized salt.

Circular RNAs (circRNAs) are involved in many courses of atherosclerosis and coronary artery disease (CHD). However, the role and effect of circRNAs in vascular restenosis after PCI remains unclear. Human aortic vascular smooth muscle cell (HA-VSMC) was cultured and stimulated with PDGF-BB. The expression profile of circRNAs in HA-VSMCs was screened using microarray analysis. A total 257 aberrantly expressed circRNAs were screened with 2 fold change. Has_circ_0113656 (also called circDHCR24) was validated by qRT-PCR to be significantly up-regulated in PDGF-BB induced HA-VSMCs. CircDHCR24 silencing obviously inhibited the proliferation, migration and phenotypic switch. Moreover, bioinformatics analysis predicted that miR-149-5p had complementary binding sites in 3′-UTR of circDHCR24. Luciferase reporter assay and RIP assay further verified the circDHCR24 acts as a spong for miR-149-5p in HA-VSMCs. Besides, bioinformatics analysis, luciferase reporter assay and RIP assay proved MMP9 was a directly target of miR-149-5p. Finally, cells were transfected with si-circDHCR24 with or without miR-149 inhibitor, and the results showed that co-transfection si-circDHCR24 and miR-149 inhibitor reversed the effect of si-circDHCR24 on cell proliferation, migration and phenotypic switch. Taken together, our study suggested for the first time that the knockdown of circDHCR24 alleviates HA-VSMCs proliferation, migration and phenotypic switching, thereby preventing vascular restenosis.

Objective To analyze the impact of the comprehensive reform of public hospitals in Tianjin on the cost structure of inpatients at a tertiary general hospital.Methods Homepage data of the medical records from January 2015 to June 2018 were selected from a tertiary general hospital in Tianjin.The Beijing version of diagnosis related groupings(BJ-DRGs) was used to compare the expense structure of these inpatients before and after such a reform.Wilcoxon signed rank sum test,Z test and Pearson correlation analysis were performed for each index.Results Since the reform,the number of hospital discharges and that of DRGs had remained basically stable,while the case mixed index(CMI) weight increased slightly(from 1.0065 to 1.0386);the total hospitalization expenses,medical expenses,nursing expenses,management expenses and consumables expenses had increased.On the other hand,the expenses of medication and medical technology decreased,and the differences of these expenses were statistically significant (P ＜0.05).The time consumption index (0.87) and drug consumption index (0.80) were always lower than average,but the cost consumption index (1.38) remains above average with a slight rise.Conclusions The reform of public hospitals in Tianjin has encouraged such hospitals to improve their service procedures by adjusting such measures as pricing of medical services,and promoted their proactive management of hospitals.Hence the initial goal of "controlling costs,adjusting structure,and reducing costs" has been met.However,cost rise control still deserves major attention.

HighlightsThis study is the first study to confirm that the neutrophil–lymphocyte ratio (NLR) is an independent predictive factor for kidney function decline among individuals with diabetes and prediabetes.Calculating the NLR is easy and inexpensive, so we believe that with more research support the NLR will be used as an effective indicator in the clinical management of individuals with diabetes and prediabetes.

Objective This study aims to determine whether and how the enriched metabolites of endothelial extracellular vesicles (eEVs) are critical for cigarette smoke-induced direct injury of endothelial cells and the development of pulmonary hypertension, rarely explored in contrast to long-investigated mechanisms secondary to chronic hypoxemia. Approach and Results Metabonomic screen of eEVs from cigarette-smoking human subjects reveals prominent elevation of sperminea polyamine metabolite with potent agonist activity for the extracellular CaSR (calcium-sensing receptor). CaSR inhibition with the negative allosteric modulator Calhex231 or CaSR knockdown attenuates cigarette smoke-induced pulmonary hypertension in rats without emphysematous changes in lungs or chronic hypoxemia. Cigarette smoke exposure increases the generation of spermine-positive eEVs and their spermine content. Immunocytochemical staining and immunogold electron microscopy recognize the spermine enrichment not only within the cytosol but also on the outer surface of eEV membrane. The repression of spermine synthesis, the inhibitory analog of spermine, N-1-dansyl-spermine, Calhex231, or CaSR knockdown profoundly suppresses eEV exposure-mobilized cytosolic calcium signaling, pulmonary artery constriction, and smooth muscle cell proliferation. Confocal imaging of immunohistochemical staining demonstrates the migration of spermine-positive eEVs from endothelium into smooth muscle cells in pulmonary arteries of cigarette smoke-exposed rats. The repression of spermine synthesis or CaSR knockout results in attenuated development of pulmonary hypertension induced by an intravascular administration of eEVs. Conclusions Cigarette smoke enhances eEV generation with spermine enrichment at their outer surface and cytosol, which activates CaSR and subsequently causes smooth muscle cell constriction and proliferation, therefore, directly leading to the development of pulmonary hypertension.

Stress in the endoplasmic reticulum (ER) triggers the unfolded protein response (UPR), which attempts to restore normal function of the ER. Both autophagy and miRNAs have been reported to participate in the process of ER stress, but the relationship between these two factors is still obscure. In this study, we demonstrated that miR-346, which was induced under ER stress, modulated autophagic flux in HeLa cells. By regulating the process of autophagy, miR-346 reduced the ROS level in the cells, thus protecting them from death following ER stress. Furthermore, we demonstrated that GSK3B was the target of miR-346 and participated in ER stress-related autophagy. miR-346 activated autophagy by interrupting the association between BCL2 and BECN1 in a GSK3B-dependent manner. Our findings shed new light on the role of miRNAs during ER stress and suggest a new mechanism for the induction of autophagy under ER stress.

Nonischemic cardiomyopathy (NICM) is a group of noncoronary heterogonous myocardial diseases. The heterogonous nature of NICM has impeded its diagnosis. In the present case series, we demonstrate the added value of using contrast echocardiography in the characterization of NICM. Two patients of advanced age were admitted for possible acute coronary syndrome, which was subsequently excluded by coronary angiography. Conventional and contrast echocardiography revealed characteristic structural and dynamic features of the left ventricle that were compatible with two distinct NICM diseases: stress-induced cardiomyopathy and noncompaction of the ventricular myocardium. Contrast echocardiography characterizes the cardiac structure and allows for real-time assessment of myocardial motion and perfusion. It may help to distinguish diseases with different etiologies.

Objective To compare the perioperative characteristics and long term outcomes between extracorporeal membrane oxygenation (ECMO)-conventional cardiopulmonary switch (experimental group,26 cases) and off-pump high-risk coronary artery bypass grafting (OPCABG group,24cases).Methods Perioperative characteristics and survival rate were retrospectively analyzed between experimental group and OPCABG group.Long term survival rates without major cardiovascular adverse events (MACE) were comparatively analyzed via Kaplan-Meier curves.Results The average Euroscore value were 11.7 ± 2.4 and 10.9 ± 2.0,respectively(P =0.208).The experimental group had a higher complete revascularization rate (96.2％ vs.66.7％,P =0.009),a shorter length of postoperative ECMO support [(33.1±23.6)h vs.(80.8±18.5)h],an intensive care unit stay[(4.8±1.1)d vs.(10.2±9.0)d]and a hospital stay [(17.7±6.3)d vs.(28.2±17.5)d] (all P＜0.05) as compared with OPCABG group.Preoperative New York Heart Association (NYHA) grading of cardiac function (r =0.511,P =0.008) and intraoperative ultrafiltration volume (r =-0.442,P =0.024) were significantly correlated with postoperative ECMO continuation in the experimental group.The follow-up period was (45.4 ± 15.2) months.The experimental group had a higher survival rate without MACE than had the OPCABG group (Log-rank test:x2=4.828,P=0.028).Conclusions The ECMO-conventional cardiopulmonary switch mode might facilitate a higher complete revascularization,a lower incidence of postoperative morbidities and improve the longterm survival rate without MACE for patients with high risks.

Objective To evaluate the relationship of the plasma levels of osteopontin(OPN),lipoprotein (a) [Lp (a)] and apolipoproteinA/apolipoproteinB (ApoB/ApoA1) ratio with atherosclerosis.Methods 120 elderly patients with atherosclerosis (observation group) and another 120 healthy elderly subjects (control group) from Health Check Department in Tianjin Third Center Hospital were enrolled from Mar.2014 to Nov.2015.The levels of plasma OPN,Lp(a) and ApoB / ApoA1 ratio were measured and their relationship with atherosclerosis was analyzed.Results In observation group versus control group,the levels of plasma OPN[(33.2±10.1) μg/L vs.(30.6± 9.1) μg/L],ApoB/ApoA1 ratio[(0.8±0.7) vs.(0.6±0.1)]and Lp(a)[(357.6±66.5) mg/L vs.(120.5±35.7) mg/L] were increased with statistically significant differences (t =8.91,8.43,6.01;P=0.021,0.035,0.041).The concentrations of plasma OPN,ApoB/ApoA1 ratio and Lp (a) were increased along with aggravation of artery lesion,with statistically significant differences (F =8.50,7.38,6.41;P=0.031,0.039,0.037).Conclusions The plasma levels of OPN,Lp(a) and ApoB/ ApoA1 ratio are increased in patients with atherosclerosis and increased along with the lesion aggravation.

Hepatocellular carcinoma (HCC) is the fifth most commonly diagnosed type of cancer. The tumor inflammatory microenvironment regulates almost every step towards liver tumorigenesis and subsequent progression, and regulation of the inflammation-related signaling pathways, cytokines, chemokines and non-coding RNAs influences the proliferation, migration and metastasis of liver tumor cells. Inflammation fine-tunes the cancer microenvironment to favor epithelial-mesenchymal transition, in which cancer stem cells maintain tumorigenic potential. Emerging evidence points to inflammation-related microRNAs as crucial molecules to integrate the complex cellular and molecular crosstalk during HCC progression. Thus understanding the mechanisms by which inflammation regulates microRNAs might provide novel and admissible strategies for preventing, diagnosing and treating HCC. In this review, we will update three hypotheses of hepatocarcinogenesis and elaborate the most predominant inflammation signaling pathways, i.e. IL-6/STAT3 and NF-κB. We also try to summarize the crucial tumor-promoting and tumor-suppressing microRNAs and detail how they regulate HCC initiation and progression and collaborate with other critical modulators in this review.

在实际污水处理厂运行过程中,其最终出水水质会受多种因素影响制约,而基于生物反应机理的活性污泥数学模型(ASM)并未将这些生物反应以外的因素考虑在内,由此带来一些不足.对此,本文提出可通过基于数据挖掘技术的黑箱模型对污水厂处理效果进行模拟预测.结合具体实际分析,提出可将BP神经网络与马尔可夫链组合应用于污水处理脱氮效果预测中.首先,通过BP神经网络模型对北京某大型污水处理厂实际进出水数据和工艺参数进行粗略拟合;其次,利用马尔可夫链对拟合结果及误差进行状态划分以进一步提高预测精确度;最后,运用基于BP神经网络与马尔可夫链的组合模型预测分析了该厂的实际出水水质.试验结果表明,BP神经网络适用于污水处理脱氮过程的拟合计算,而通过与马尔可夫链组合,可以提高模拟预测的精度和可靠性.

Purpose: To evaluate midazolam sequential with dexmedetomidine for agitated patients undergoing weaning to implement light sedation in ICU.Methods: This randomized, prospective study was conducted in Tianjin Third Central Hospital, China. Using a sealed-envelope method, the patients were randomly divided into 2 groups (40 patients per group). Each patient of group A received an initial loading dose of midazolam at 0.3-3 mg/kg.h 24 h before extubation, followed by an infusion of dexmedetomidine at a rate of 0.2-1 mg/kg.h until extubation. Each patient of group B received midazolam at a dose of 0.3-3 mg/kg.h until extubation. The dose of sedation was regulated according to RASS sedative scores maintaining in the range of -2-1. All patients were continuously monitored for 60 min after extubation. During the course, heart rate (HR), mean artery pressure (MAP), extubation time, adverse reactions, ICU stay, and hospital stay were observed and recorded continuously at the following time points: 24 h before extubation (T1), 12 h before extubation (T2), extubation (T3), 30 min after extubation (T4), 60 min after extubation (T5).Results: Both groups reached the goal of sedation needed for ICU patients. Dexmedetomidine was associated with a significant increase in extubation quality compared with midazolam, reflected in the prevalence of delirium after extubation (20% (8/40) vs 45% (18/40)), respectively (p = 0.017). There were no clinically significant decreases in HR and MAP after infusing dexmedetomidine or midazolam. In the group A, HR was not significantly increased after extubation; however, in the group B, HR was significantly increased compared with the preextubation values (p < 0.05). HR was significantly higher in the group B compared with the group A at 30 and 60 min after extubation (both, p < 0.05). Compared with preextubation values, MAP was significantly increased at extubation in the group B (p < 0.05) and MAP was significantly higher at T3, T4, T5 in the group B than group A (p < 0.05). There was a significant difference in extubation time ((3.0 +/- 1.5) d vs (4.3 +/- 2.2) d, p < 0.05), ICU stay ((5.4 +/- 2.1) d vs (8.0 +/- 1.4) d, p < 0.05), hospital stay ((10.1 +/- 3.0) d vs (15.3 +/- 2.6) d, p < 0.05) between group A and B.Conclusion: Midazolam sequential with dexmedetomidine can reach the goal of sedation for ICU agitated patients, meanwhile it can maintain the respiratory and circulation parameters and reduce adverse reactions. (c) 2016 Production and hosting by Elsevier B.V. on behalf of Daping Hospital and the Research Institute of Surgery of the Third Military Medical University.