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Background and Objective: Our study aimed to evaluate the associations between platelet count (PC) and in-hospital outcomes for patients with stroke after rt-PA intravenous thrombolysis., Methods: We identified patients who had been hospitalized with a primary diagnosis of stroke and had received rt-PA intravenous thrombolysis from June 2015 to July 2019 at participating hospitals in the Chinese Stroke Center Alliance. PC measured before intravenous thrombolysis was categorized into the following four groups: severe thrombocytopenia (PC < 100 × 10 9 /L), mild thrombocytopenia (100 ≤ PC < 150 × 10 9 /L), normal PC (150 ≤ PC ≤ 450 × 10 9 /L), and thrombocythemia (PC > 450 × 10 9 /L). Outcomes were determined from clinical data collected during hospitalization. The primary clinical outcome was symptomatic intracranial hemorrhage (sICH). Secondary outcomes were mortality, bleeding events, gastrointestinal (GI) hemorrhage, and in-hospital stroke recurrence. We used multivariate logistic regression models to evaluate the associations between PC and outcomes., Results: We included 44,882 individuals with a median age of 66 years, of whom 34.7 % were female, 951 (2.1 %) had severe thrombocytopenia, 7218 (16.1 %) had mild thrombocytopenia, 36,522 (81.4 %) had a normal PC, and 191 (0.4 %) had thrombocythemia. Both severe and mild thrombocytopenia groups had higher risks of bleeding events (adjusted OR 1.30; 95 % CI,1.01-1.67; p = 0.045; adjusted OR 1.32; 95 % CI,1.19-1.46; p < 0.001) and sICH (adjusted OR 1.48;95 % CI,1.13-1.94; p = 0.005; adjusted OR 1.43;95 % CI,1.27-1.60; p < 0.001) than the normal PC group. Patients with 100 ≤ PC < 150 × 10 9 /L also had a higher risk of in-hospital stroke recurrence (adjusted OR 1.12; 95 % CI,1.02-1.22; p = 0.02)., Conclusions: Intravenous thrombolysis brings a high risk of sICH given PC < 150 × 10 9 /L, especially PC < 100 × 10 9 /L. It indicated that PC < 100 × 10 9 /L is a reasonable contraindication to thrombolysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease worldwide. Epidemiological studies have reported that exposure of the population to environmental endocrine-disrupting chemicals (EDCs) is associated with NAFLD. However, EDCs are of different types, and there are inconsistencies in the relevant evidence and descriptions, which have not been systematically summarized so far. Therefore, this study aimed to determine the association between population exposure to EDCs and NAFLD. Three databases, including PubMed, Web of science, and Embase were searched, and 27 articles were included in this study. Methodological quality, heterogeneity, and publication bias of the included studies were assessed using the Newcastle-Ottawa scale, I 2 statistics, Begg's test, and Egger's test. The estimated effect sizes of the included studies were pooled and evaluated using the random-effects model (I 2 > 50 %) and the fixed-effects model ( I 2 < 50 %). The pooled-estimate effect sizes showed that population exposure to Phthalates (PAEs) (OR = 1.18, 95 % CI:1.03-1.34), cadmium (Cd) (OR = 1.37, 95 % CI:1.09-1.72), and bisphenol A (OR = 1.43, 95 % CI:1.24-1.65) were positively correlated with the risk of NAFLD. Exposure to mercury (OR =1.46, 95 % CI:1.17-1.84) and Cd increased the risk of "elevated alanine aminotransferase". On the contrary, no significant association was identified between perfluoroalkyl substances (OR =0.99, 95 % CI:0.93-1.06) and NAFLD. However, female exposure to perfluorooctanoic acid (OR =1.82, 95 % CI:1.01-3.26) led to a higher risk of NAFLD than male exposure. In conclusion, this study revealed that EDCs were risk factors for NAFLD. Nonetheless, the sensitivity analysis results of some of the meta-analyses were not stable and demonstrated high heterogeneity. The evidence for these associations is limited, and more large-scale population-based studies are required to confirm these findings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Advanced glycation end products (AGEs), derived from the non-enzymatic glycation reaction, are defined as glycotoxins in various diseases including aging, diabetes and kidney injury. Exploring AGEs as potential biomarkers for these diseases holds paramount significance. Nevertheless, the high chemical structural similarity and great heterogeneity among AGEs present a formidable challenge when it comes to the comprehensive, simultaneous, and accurate detection of multiple AGEs in biological samples. In this study, an UPLC/MS/MS method for simultaneous quantification of 20 free AGEs in human serum was firstly established and applied to quantification of clinical samples from individuals with kidney injury. Simple sample preparation method through protein precipitation without derivatization was used. Method performances including imprecision, accuracy, sensitivity, linearity, and carryover were systematically validated. Intra- and inter- imprecision of 20 free AGEs were 1.93-5.94 % and 2.30-8.55 %, respectively. The method accuracy was confirmed with good recoveries ranging from 96.40 % to 103.25 %. The LOD and LOQ were 0.1-3.13 ng/mL and 0.5-6.25 ng/mL, respectively. Additionally, the 20 free AGEs displayed excellent linearity (R 2 >0.9974) across a wide linear range (1.56-400 ng/mL). Finally, through simultaneous quantitation of 20 Free AGEs in 100 participants including kidney injury patient and healthy controls, we identified six free AGEs, including N 6 -carboxyethyl-L-arginine (CEA), N 6 -carboxymethyl-L-lysine (CML), methylglyoxal-derived hydroimidazolones (MG-H), N 6 -formyl-lysine, N 6 -carboxymethyl-L-arginine (CMA), and glyoxal-derived hydroimidazolone (G-H), could well distinguish kidney injury patients and healthy individuals. Among them, the levels of four free AGEs including CML, CEA, MG-H, and G-H strongly correlate with traditionally clinical markers of kidney disease. The high area under the curve (AUC) values (AUC=0.965) in receiver operating characteristic (ROC) curve indicated that these four free AGEs can be served as combined diagnostic biomarkers for the diagnosis of kidney disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Degeneration of intervertebral discs is considered one of the most important causes of low back pain and disability. The intervertebral disc (IVD) is characterized by its susceptibility to various stressors that accelerate the senescence and apoptosis of nucleus pulposus cells, resulting in the loss of these cells and dysfunction of the intervertebral disc. Therefore, how to reduce the loss of nucleus pulposus cells under stress environment is the main problem in treating intervertebral disc degeneration. Autophagy is a kind of programmed cell death, which can provide energy by recycling substances in cells. It is considered to be an effective method to reduce the senescence and apoptosis of nucleus pulposus cells under stress. However, further research is needed on the mechanisms by which autophagy of nucleus pulposus cells is regulated under stress environments. M6A methylation, as the most extensive RNA modification in eukaryotic cells, participates in various cellular biological functions and is believed to be related to the regulation of autophagy under stress environments, may play a significant role in nucleus pulposus responding to stress. This article first summarizes the effects of various stressors on the death and autophagy of nucleus pulposus cells. Then, it summarizes the regulatory mechanism of m6A methylation on autophagy-related genes under stress and the role of these autophagy genes in nucleus pulposus cells. Finally, it proposes that the methylation modification of autophagy-related genes regulated by m6A may become a new treatment approach for intervertebral disc degeneration, providing new insights and ideas for the clinical treatment of intervertebral disc degeneration., (© 2024 International Federation for Cell Biology.)

Objective: This study investigated whether perinatal exposure to nonylphenol (NP) induces mitochondrial autophagy (i.e., mitophagy) damage in neonatal rat cardiomyocytes (NRCMs) and whether the PINK1/Parkin signaling pathway is involved in NP-induced primary cardiomyocyte injury., Methods and Results: In vivo: Perinatal NP exposure increased apoptosis and mitochondrial damage in NRCMs. Mitochondrial swelling and autophagosome-like structures with multiple concentric membranes were observed in the 100 mg/kg NP group, with an increase in the number of autophagosomes. Disorganized fiber arrangement and elevated serum myocardial enzyme levels were observed with increasing NP dosage. Additionally, NP exposure led to increased MDA levels and decreased SOD activity and ATP levels in myocardial tissue. The mRNA expression levels of autophagy-related genes, including Beclin-1, p62, and LC3B, as well as the expression of mitochondrial autophagy-related proteins (PINK1, p-Parkin, Parkin, Beclin-1, p62, LC3-I, LC3-II, and LC3-II/I) and apoptosis-related proteins (Bax and caspase-3), increased, whereas the expression levels of the mitochondrial membrane protein TOMM20 and the anti-apoptotic protein Bcl-2 decreased. In vitro: NP increased ROS levels, LDH release, and decreased ATP levels in NRCMs. CsA treatment significantly inhibited the expression of autophagy-related proteins (Beclin-1, LC3-II/I, and p62) and apoptosis-related proteins (caspase-3 and Bax), increased the expression levels of TOMM20 and Bcl-2 proteins, increased cellular ATP levels, and inhibited LDH release. The inhibition of the PINK1/Parkin signaling pathway suppressed the expression of mitochondrial autophagy-related proteins (PINK1, p-Parkin, Parkin, Beclin-1, LC3-II/I, and p62) and apoptosis-related proteins (caspase-3 and Bax), increased TOMM20 and Bcl-2 protein expression, increased ATP levels, and decreased LDH levels in NRCMs., Conclusions: This study is novel in reporting that perinatal NP exposure induced myocardial injury in male neonatal rats, thereby inducing mitophagy. The PINK1/Parkin signaling pathway was involved in this injury by regulating mitophagy., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Objective: We here explored whether perinatal nonylphenol (NP) exposure causes myocardial fibrosis (MF) during adulthood in offspring rats and determined the role of the TGF-β1/LIMK1 signaling pathway in NP-induced fibrosis in cardiac fibroblasts (CFs)., Methods and Results: Histopathology revealed increased collagen deposition and altered fiber arrangement in the NP and isoproterenol hydrochloride (ISO) groups compared with the blank group. Systolic and diastolic functions were impaired. Western blotting and qRT-PCR demonstrated that the expression of central myofibrosis-related proteins (collagens Ι and ΙΙΙ, MMP2, MMP9, TGF-β1, α-SMA, IL-1β, and TGF-β1) and genes (Collagen Ι, Collagen ΙΙΙ, TGF-β1, and α-SMA mRNA) was upregulated in the NP and ISO groups compared with the blank group. The mRNA-seq analysis indicated differential expression of TGF-β1 signaling pathway-associated genes and proteins. Fibrosis-related protein and gene expression increased in the CFs stimulated with the recombinant human TGF-β1 and NP, which was consistent with the results of animal experiments. According to the immunofluorescence analysis and western blotting, NP exposure activated the TGF-β1/LIMK1 signaling pathway whose action mechanism in NP-induced CFs was further validated using the LIMK1 inhibitor (BMS-5). The inhibitor modulated the TGF-β1/LIMK1 signaling pathway and suppressed the NP-induced increase in fibrosis-related protein expression in the CFs. Thus, the aforementioned pathway is involved in NP-induced fibrosis., Conclusion: We here provide the first evidence that perinatal NP exposure causes myocardial fibrosis in growing male rat pups and reveal the molecular mechanism and functional role of the TGF-β1/LIMK1 signaling pathway in this process., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to investigate the effects of exposure to nonylphenol (NP) on anxiety/depression-like behaviors in rats and alleviation of those effects via green tea and zinc selenium (Zn-Se) tea interventions., Material and Methods: Totally, 40 male specific-pathogen free (SPF) Sprague-Dawley (SD) male rats were randomly divided into four groups (n = 10 rats per group): control group (5 ml/kg corn oil), NP group (40 mg/kg NP), NP + GT group (40 mg/kg NP + 1 g/kg/day green tea), and NP + Zn-Se tea group (40 mg/kg NP + 1 g/kg/day ZST). All dose-based groups received oral gavage of either corn oil or drugs over a 6-month period: NP at a dosage of 40 mg/kg/day was administered to rats for the initial 3 months, followed by a combination of NP with green tea and NP with Zn-Se tea for the subsequent 3 months., Results: Tea intervention resulted in weight loss in rats. The hippocampal tissue NP level in the tea group was slightly lower than that in the NP group. Following tea intervention, compared with the NP group, the residence time in the light-dark box test was shortened P GT  = 0.048, P  < 0.001), and the number of entries into the closed arm in the elevated plus maze test in the tea-treated group was significantly reduced. In addition, the immobility time in the central square in the open field test decreased. The sucrose preference index score in the sucrose preference test increased, and the immobility time in the forced swimming test was reduced ( P GT = 0.049, P ZST  < 0.001). The effects of Zn-S e tea were superior to green tea. The damage to the hippocampal tissues in the group treated with tea was less than that in the NP group. The cellular arrangement was tighter with degeneration, deepstaining, and pyknotic nerve cells were visible. The nuclei in the NP group were atrophied, and the cells were sparsely arranged. Compared with the control group, serum brain-derived neurotrophic factor (BDNF) level was lower in the NP group. The serum corticosterone level in the NP group was elevated. Compared with the NP group, serum corticosterone level was reduced in the NP + Zn-Se tea group., Conclusion: Chronic NP exposure induced anxiety/depression-like behaviors in rats. Green tea effectively reduced the damage to the hippocampus and prefrontal cortex induced by NP. The effects of Zn-Se tea were slightly more noticeable than those of conventional green tea., Highlights: 1) Chronic NP exposure induced anxiety/depression-like behaviors in rats.2) Zn-Se tea reduced the damage of hippocampal and prefrontal cortex induced by NP.3) NP-induced depression accompanied by the changes of BDNF, CORT and neuropathology., Competing Interests: The authors declare that they have no competing interests., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Ferroptosis has been proven critical for survival following bone marrow mesenchymal stem cells (BMSCs) explantation. Suppression of ferroptosis in BMSCs will be a valid tactic to elevate the therapeutic potential of engrafted BMSCs. Prominin2 is a pentaspanin protein involved in mediating iron efflux and thus modulates resistance to ferroptosis, but its role in tert-butyl hydroperoxide (TBHP)-induced BMSCs ferroptosis remains elusive. We examined the biological effect of prominin2 in vitro and in vivo by using cell proliferation assay, iron assay, reactive oxygen species (ROS) examination, malondialdehyde assay, glutathione (GSH) examination, Western blot, quantitative reverse transcription-PCR, immunofluorescence staining assay, gene expression inhibition and activation, co-immunoprecipitation (CO-IP) assay, radiographic analysis, and histopathological analysis. Our study demonstrated that prominin2 activity was impaired in TBHP-induced BMSCs ferroptosis. We found that PROM2 (encoding the protein prominin2) activation delayed the onset of ferroptosis and PROM2 knockdown deteriorated the course of ferroptosis. CO-IP, Western blot, and immunofluorescence demonstrated that prominin2 exerts antiferroptosis effects by inhibiting BTB and CNC homology 1 (BACH1) that promotes ROS generation, and thus exerts potent antioxidant effects in oxidative stress (OS)-induced BMSCs ferroptosis, including elevating BMSCs' survival rate and enhancing GSH contents. BMSCs with PROM2 overexpression also partially delayed the progression of intervertebral disk degeneration in vivo, as illustrated by less loss of disk height and lower histological scores. Our findings revealed a mechanism that the prominin2/BACH1/ROS axis participates in BMSCs ferroptosis and the strengthening of this axis is promising to maintain BMSCs' survival after explantation. NEW & NOTEWORTHY We found that prominin2 might be a potential biomarker and is expected to be utilized to augment engrafted bone marrow mesenchymal stem cells (BMSCs) survival rate. The prominin2/BTB and CNC homology 1 (BACH1)/reactive oxygen species (ROS) axis, which participates in the regulation of BMSCs ferroptosis induced by tert-butyl hydroperoxide (TBHP), is uncovered in our study. The therapeutic targeting of the prominin2/BACH1/ROS axis components is promising to elevate the survival of transplanted BMSCs in clinical practice.

Lung cancer is the most common type of malignant tumor that affects people in China and even across the globe, as it exhibits the highest rates of morbidity and mortality. Lung adenocarcinoma (LUAD) is a type of lung cancer with a very high incidence. The purpose of this study was to identify potential biomarkers that could be used to forecast the prognosis and improve the existing therapy options for treating LUAD. Clinical and RNA sequencing data of LUAD patients were retrieved from the TCGA database, while the mitochondria-associated gene sets were acquired from the MITOMAP database. Thereafter, Pearson correlation analysis was carried out to screen mitochondria-associated lncRNAs. Furthermore, univariate Cox and Lasso regression analyses were used for the initial screening of the target lncRNAs for prognostic lncRNAs before they could be incorporated into a multivariate Cox Hazard ratio model. Then, the clinical data, concordance index, Kaplan-Meier (K-M) curves, and the clinically-relevant subjects that were approved by the Characteristic Curves (ROC) were employed for assessing the model's predictive value. Additionally, the differences in immune-related functions and biological pathway enrichment between high- and low-risk LUAD groups were examined. Nomograms were developed to anticipate the OS rates of the patients within 1-, 3-, and 5 years, and the differences in drug sensitivity and immunological checkpoints were compared. In this study, 2175 mitochondria-associated lncRNAs were screened. Univariate, multivariate, and Lasso Cox regression analyses were carried out to select 13 lncRNAs with an independent prognostic significance, and a prognostic model was developed. The OS analysis of the established prognostic prediction model revealed significant variations between the high- and low-risk patients. The AUC-ROC values after 1, 3, and 5 years were seen to be 0.746, 0.692, and 0.726, respectively. The results suggested that the prognostic model riskscore could be used as an independent prognostic factor that differed from the other clinical characteristics. After analyzing the findings of the study, it was noted that both the risk groups showed significant differences in their immune functioning, immunological checkpoint genes, and drug sensitivity. The prognosis of patients with LUAD could be accurately and independently predicted using a risk prediction model that included 13 mitochondria-associated lncRNAs., (© 2023. The Author(s).)

Objective: To review the clinical research progress of spinal epidural lipomatosis (SEL)., Methods: The clinical studies on SEL at home and abroad in recent years were extensively reviewed, and the pathogenesis, clinical and imaging manifestations, and treatment status of SEL were summarized and analyzed., Results: SEL is a disease characterized by compression of the spinal cord and nerve roots due to abnormal accumulation of epidural adipose tissue in the spinal canal. Its prevalence and diagnosis rate are low and the pathogenesis is not fully understood. MRI is the most sensitive and specific diagnostic test for SEL. Surgical decompression and removal of excess adipose tissue are the only options for patients with acute SEL or those who have failed conservative management, and conservative management should be considered for other patients., Conclusion: SEL is a rare disease and related research still needs to be improved. In the future, high-quality, multi-center and large-sample studies will be of great significance for evaluating the choice of treatment methods and effectiveness of SEL patients.

DFT computational investigations were carried out to explore the mechanism of enantioselective Cu/Pd-catalyzed allylation of an α-CF 3 amide. A kinetically favored chiral Cu(I)-enolate species undertakes facile allylation with racemic π-allyl-Pd(II) species to stereoconvergently deliver a stereocenter. Computational models and distortion/interaction analyses unveil versatile modes of stereoinduction wherein the reactive site of ( R,R p )-Walphos/copper(I)-enolate cis to the -PPh 2 moiety has more space for the nucleophilic reaction, and can face-selectively capture π-allyl-palladium(II) intermediates using sterically affected distortions.

Surgical site infection (SSI) is a common and serious complication of transforaminal lumbar interbody fusion (TLIF), and the occurrence of SSI usually leads to prolonged hospitalisation, increased medical costs, poor prognosis, and even death. The objectives of this study were to compare the incidence of SSI in patients with type 2 diabetes, investigate the correlation between perioperative glycemic variability and postoperative SSI, and develop a nomogram model to predict the risk of SSI. This study retrospectively analysed 339 patients with type 2 diabetes who underwent TLIF in the spinal surgery department of the Affiliated Zhongda Hospital of Southeast University from January 2018 to September 2021. The medical records of all patients were collected, and postoperative infection cases were determined according to the diagnostic criteria of surgical site infection. The risk factors for postoperative SSI were analysed by univariate and multivariate logistic regression. And Nomogram prediction model was established and validated. The nomogram incorporated seven independent predictors. Preoperative FPG-CV was the most important independent risk predictor of SSI, followed by preoperative MFBG, duration of drain placement, postoperative FPG-CV, preoperative blood glucose control scheme, duration of diabetes >5 years, and the number of fused vertebrae ≥2. The nomogram showed good diagnostic accuracy for the SS of both the training cohort and the validation cohort (AUC = 0.915 and AUC = 0.890). The calibration curves for the two cohorts both showed optimal agreement between nomogram prediction and actual observation. In conclusion, preoperative and postoperative glycemic variability is closely related to the occurrence of SSI. We developed and validated a nomogram to accurately predict the risk of SSI after TLIF surgery. It's helpful for spinal surgeons to formulate reasonable treatment plans and prevention strategies for type 2 diabetes patients., (© 2022 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

N6-methyladenosine (m6A) is an abundant eukaryotic mRNA modification involved in regulating the formation and metastasis of nonsmall cell lung cancer (NSCLC). We collected clinical NSCLC tissue and paracarcinoma tissue. Then methyltransferase-like 14 (METTL14), pleomorphic adenoma gene like-2 (PLAGL2), and β -catenin expressions were assessed using quantitative real-time PCR and western blot. PLAGL2, and β -catenin (nuclear) expressions were increased in NSCLC tissues. Cell proliferation, migration, invasion, and death were examined. PLAGL2 could activate β -catenin signaling to affect cell proliferation and migration abilities. RNA immunoprecipitation assay was operated to identify m6A modification levels of PLAGL2 after knockdown and overexpression of METTL14. PLAGL2 was regulated by METTL14-mediated m6A modification. Knockdown of METTL14 repressed cell proliferation, migration, and invasion, and promoted cell death. Interestingly, these effects were reversed when PLAGL2 was overexpressed. Finally, tumor formation in nude mice was performed to verify the role of the METTL14/PLAGL2/ β -catenin signaling axis. Tumor formation in nude mice demonstrated METTL14/PLAGL2/ β -catenin axis promoted NSCLC development in vivo . In brief, METTL14 promoted NSCLC development by increasing m6A methylation of PLAGL2 to activate β -catenin signaling. Our research provided essential clues for in-depth comprehension of the mechanism of NSCLC occurrence and development and also provided the basis for NSCLC treatment., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2023 Qianhui Zhou et al.)

Ex vivo culture-amplified mesenchymal stem cells (MSCs) have been studied because of their capacity for healing tissue injury. MSC transplantation is a valid approach for promoting the repair of damaged tissues and replacement of lost cells or to safeguard surviving cells, but currently the efficiency of MSC transplantation is constrained by the extensive loss of MSCs during the short post-transplantation period. Hence, strategies to increase the efficacy of MSC treatment are urgently needed. Iron overload, reactive oxygen species deposition, and decreased antioxidant capacity suppress the proliferation and regeneration of MSCs, thereby hastening cell death. Notably, oxidative stress (OS) and deficient antioxidant defense induced by iron overload can result in ferroptosis. Ferroptosis may inhibit cell survival after MSC transplantation, thereby reducing clinical efficacy. In this review, we explore the role of ferroptosis in MSC performance. Given that little research has focused on ferroptosis in transplanted MSCs, further study is urgently needed to enhance the in vivo implantation, function, and duration of MSCs.

Background: Successful mechanical thrombectomy (MT) requires reliable, noninvasive selection criteria. We aimed to investigate the association of collateral status and clinical outcomes after MT in patients with ischemic stroke due to anterior circulation occlusion., Methods: 109 patients with poor collaterals and 110 aged, sex-matched patients with good collaterals were enrolled in the study. Collateral circulation was estimated by the CT angiography with a 0-3 scale. The collateral status was categorized as poor collaterals (scores 0-1) and good collaterals (scores 2-3). The reperfusion was assessed by the modified Treatment in Cerebral Infarction scale (mTICI, score 0/1/2a/2b/3). The clinical outcomes included the scores on the modified Rankin scale (mRS, ranging from 0 to 6) and death 90 days after mechanical thrombectomy., Results: Patients with greater scores of collateral status were more likely to achieve successful reperfusion (mTICI 2b/3). Patients with good collaterals were significantly associated with a higher chance of achieving mRS of 0-1 at 90 days (adjusted ORs: 4.55; 95% CI: 3.17-7.24; and P  < 0.001) and a lower risk of death at 90 days (adjusted ORs: 0.87; 95% CI: 4.0%-28.0%; and P  = 0.012) compared to patients with poor collaterals. In subgroup analyses, patients with statin use seem to benefit more from the effect of collateral status on good mRS (≤2)., Conclusion: Among patients with acute ischemic stroke caused by anterior circulation occlusion, better collateral status is associated with higher scores on mRS and lower mortality after mechanical thrombectomy. Statin use might have an interaction with the effect of collateral status., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Yuzhu Xu et al.)

Microtubule target agents (MTAs) are widely-used clinical anti-cancer drugs for decades, but the acquired drug resistance severely restricted their application. Thioredoxin reductases (TrxR) was reported to be overexpressed in most tumors and closely related to high risk of cancer recurrence and drug resistance, making it a potential target for anticancer drug discovery. Multi-target-directed ligands (MTDLs) by a single molecule provide a logical and alternative approach to drug combinations. In this work, based on the structure-activity relationships obtained in our previous study, some structure modifications were performed. On one hand, the retained skeleton structure of MTAs endowed its tubulin polymerization inhibition activity, on the other hand, the selenium-containing structure and α,β-unsaturated ketone moiety endowed the TrxR inhibition activity. As results, the newly obtained compounds exhibited superior anti-proliferative activities towards various human cancer cells and drug-resistance cells, and displayed high selectivity towards various human normal cells. The mechanism study revealed that the dual effect of cell cycle arrest triggered by targeting tubulin and the abnormal accumulation of ROS caused by TrxR inhibition eventually lead to cell apoptosis. Notably, compared with the MTA agents CA-4P, and the TrxR inhibitor Ethaselen, the optimized compound 14c, which served as dual-targeting inhibitor of tubulin and TrxR, exerted greatly improved in vivo anti-tumor activity. In summary, 14c deserved further consideration for cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Masson SAS.)

Objective: To explore the value of modified subcutaneous lumbar spine index (MSLSI) as a predictor for short-term effectiveness of transforaminal lumbar interbody fusion (TLIF) in treatment of lumbar degenerative disease (LDD)., Methods: Between February 2014 and October 2019, 450 patients who were diagnosed as LDD and received single-segment TLIF were included in the study. Based on the MSLSI measured by preoperative lumbar MRI, the patients were sorted from small to large and divided into three groups ( n =150). The MSLSI of group A was 0.11-0.49, group B was 0.49-0.73, and group C was 0.73-1.88. There was no significance in gender, age, disease duration, diagnosis, surgical segment, and improved Charlson comorbidity index between groups ( P >0.05). There were significant differences in the subcutaneous adipose depth of the L 4 vertebral body and body mass index (BMI) between groups ( P <0.05). The operation time, intra-operative blood loss, length of incision, drainage tube placement time, drainage volume on the 1st day after operation, drainage volume on the 2nd day after operation, total drainage volume, antibiotic use time after operation, walking exercise time after operation, hospital stay, the incidences of surgical or non-surgical complications in the three groups were compared. Pearson correlation analysis was used to analyze the correlation between MSLSI and BMI, and partial correlation analysis was used to study the relationship between MSLSI, BMI, improved Charlson comorbidity index, subcutaneous adipose depth of the L 4 vertebral body and complications. The Receiver Operating Characteristic (ROC) curve was used to evaluate the value of SLSI and MSLSI in predicting the occurrence of complications after TLIF in treatment of LDD., Results: There was no significant difference in operation time, length of incision, antibiotic use time after operation, walking exercise time after operation, drainage tube placement time, drainage volume on the 1st day after operation, drainage volume on the 2nd day after operation, and total drainage volume between groups ( P >0.05). The amount of intra-operative blood loss in group C was higher than that in groups A and B, and the hospital stay was longer than that in group B, with significant differences ( P <0.05). Surgical complications occurred in 22 cases (14.7%), 25 cases (16.7%), and 39 cases (26.0%) of groups A, B, and C, respectively. There was no significant difference in the incidence between groups ( χ 2 =0.826, P =0.662). The incidences of nerve root injury and wound aseptic complications in group C were higher than those in groups A and B, and the incidence of nerve root injury in group B was higher than that in group A, with significant differences ( P <0.05). There were 13 cases (8.7%), 7 cases (4.7%), and 11 cases (7.3%) of non-surgical complications in groups A, B, and C, respectively, with no significant difference ( χ 2 =2.128, P =0.345). There was no significant difference in the incidences of cardiovascular complications, urinary system complications, central system complications, and respiratory system complications between groups ( P >0.05). There was a correlation between MSLSI and BMI in 450 patients ( r =0.619, P =0.047). Partial correlation analysis showed that MSLSI was related to wound aseptic complications ( r =0.172, P =0.032), but not related to other surgical and non-surgical complications ( P >0.05). There was no correlation between BMI, improved Charlson comorbidity index, subcutaneous adipose depth of the L 4 vertebral body and surgical and non-surgical complications ( P >0.05). ROC curve analysis showed that the area under ROC curve (AUC) of MSLSI was 0.673 (95%CI 0.546-0.761, P =0.025), and the AUC of SLSI was 0.582 (95%CI 0.472-0.693, P =0.191)., Conclusion: MSLSI can predict the short-term effectiveness of TLIF in treatment of LDD. Patients with high MSLSI suffer more intra-operative blood loss, longer hospital stay, and higher incidence of nerve root injury and postoperative incision complications.

Objective: To review the effect of obesity on the effectiveness of posterior lumbar fusion in patients with lumbar degenerative diseases (LDD)., Methods: The related literature at home and abroad was extensively reviewed. And the difficulty of operation, risk of complications, and long-term effectiveness of posterior lumbar fusion for obese patients with LDD were summarized., Results: Although some relevant literature suggest that the posterior lumbar fusion for obese patients is difficult and the risk of postoperative complications is high, the overall research results do not suggest that obesity is a risk factor for the implementation of posterior lumbar fusion. By assessing the physical condition of patients and strictly grasping the surgical indications, obese patients can obtain good surgical efficacy., Conclusion: Posterior lumbar fusion is an effective method for the treatment of LDD in obese patients. However, relevant studies need to be completed to further evaluate the safety and efficacy of posterior lumbar fusion for obese patients.

Introduction: Circular RNAs (circRNAs) are an endogenous mircoRNA sponge that could act as potential biomarkers for the diagnosis and treatment of diseases. However, the role of circRNAs in asthma is far from clear., Objective: The aim of this study is to assess the diagnostic and therapeutic value of hsa&#95;circ&#95;0002594 for T helper (Th) 2-mediated allergic asthma., Methods: The expression profiles of hsa&#95;circ&#95;0002594 in CD4+ T cells were revealed by circRNA microarray. Hsa&#95;circ&#95;0002594 expression was confirmed via quantitative real-time PCR (qRT-PCR) in asthmatic patients and healthy subjects. Hsa&#95;circ&#95;0002594 levels were compared between subgroups. The clinical diagnostic abilities and therapeutic response of hsa&#95;circ&#95;0002594 were evaluated. The analyses utilized included a student's t test, nonparametric tests, Spearman's rank-order correlation, Fisher's exact test, and the generation of receiver operating characteristic (ROC) curves., Results: Hsa&#95;circ&#95;0002594 was upregulated and positively correlated with fraction of exhaled nitric oxide while negatively correlated with methacholine dose producing a decrease of 20% from baseline in forced expiratory volume in the first second (PD20) in CD4+ T cells of asthma. Furthermore, hsa&#95;circ&#95;0002594 expression was higher in subgroups with a family history, skin pricking test (SPT)-positive, or Th2-high. The hsa&#95;circ&#95;0002594-high subgroup was more frequently associated with Th2-high biomarker profiles and positive SPT. Hsa&#95;circ&#95;0002594 was decreased after inhaled corticosteroids (ICS) treatment. ROC curve analyses of hsa&#95;circ&#95;0002594 showed high area under the curve values in the presence of ICS or not., Conclusions: Our data suggested that hsa&#95;circ&#95;0002594 was upregulated in CD4+ T cells and might have potential value in the diagnosis and treatment of Th2-mediated allergic asthma., (© 2020 S. Karger AG, Basel.)

Background: Circular RNAs (circRNAs) are a novel class of noncoding RNAs that regulate gene expression at the transcriptional or posttranscriptional level. According to recent studies, circRNAs are involved in the pathogenesis of cancer, but the roles of circRNAs in lung adenocarcinoma are largely unknown., Methods: In this study, we identified a novel upregulated circRNA, hsa&#95;circ&#95;0000326, in human lung adenocarcinoma tissues using microarray analysis and qRT-PCR. We then explored the biological role of hsa&#95;circ&#95;0000326 using gain- and loss-of-function assays in adenocarcinoma cells. Bioinformatics databases were used to screen for potential target miRNAs and the luciferase reporter assays and RNA-FISH further validated the interaction. Downstream protein was detected by western blot. Finally, we established xenografts in nude mice to assess the function of hsa&#95;circ&#95;0000326 in vivo., Results: We found that high expression of hsa&#95;circ&#95;0000326 was correlated with tumor size, regional lymph node status and differentiation in human lung adenocarcinoma. Additionally, we conducted gain- and loss-of-function assays and found that hsa&#95;circ&#95;0000326 acted as a positive regulator of cell proliferation and migration and a negative regulator of apoptosis. Mechanistic studies showed that hsa&#95;circ&#95;0000326 acted as a miR-338-3p sponge and altered the function of miR-338-3p, which in turn upregulated the expression of the downstream target RAB14 and affected the proliferation, migration and apoptosis of lung adenocarcinoma cells., Conclusions: Collectively, our study results reveal crucial roles for hsa&#95;circ&#95;0000326 in the proliferation, migration and apoptosis of lung adenocarcinoma cells and suggest that hsa&#95;circ&#95;0000326 may represent a potential therapeutic target in patients with lung adenocarcinoma.

Glucocorticoids are the primary anti-inflammatory therapy for asthma, but their effects are characterized by some interindividual variability that might have a genetic basis.We aimed to determine the relationship between pulmonary function change and the variant of the glucocorticoid-induced transcript 1 (GLCCI1) gene in patients with asthma receiving long-term ICS treatment, the association of GLCCI1 genotypes and the level of GLCCI1 expression and cytokines production.A total of 418 patients with asthma, including 25 individuals from 11 families with a history of asthma, were enrolled. The effects of single-nucleotide polymorphisms (SNPs) in GLCCI1 on changes in lung function in response to inhaled glucocorticoids were assessed. The expression levels of GLCCI1 mRNA and cytokines were also measured.The SNP rs37973 in GLCCI1 was independently associated with changes in forced expiratory volume at one second (FEV1) and FEV1%pred. Individuals homozygous for the wild-type allele who had a percent FEV1 change greater than 5% were more common than individuals homozygous for the rare allele. When patients were stratified according to genotype, GLCCI1 expression was enhanced upon administration of low-dose dexamethasone among patients with the rs37973 A allele; however, GG homozygotes required high-dose dexamethasone to achieve enhanced GLCCI1 expression. Furthermore, the levels of some cytokines were significantly reduced after glucocorticoid treatment in individuals with the AA and AG genotypes.The genetic variant rs37973 in GLCCI1 is associated with poorer clinical therapeutic response to inhaled glucocorticoids in a Chinese asthma population., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Asthma is a chronic T helper type 2 (Th2) cell-mediated inflammatory disease characterized by airway hyperresponsiveness (AHR) and airway inflammation. Although the majority of patients with asthma can achieve a good level of control with existing treatments, asthma runs a chronic course and the effectiveness of current treatment is not satisfactory for certain patients. MicroRNAs (miRNAs) are short noncoding RNAs that suppress gene expression at the post-transcriptional level; their role in regulating allergic inflammation remains largely unknown. The present study aimed to explore the role of miRNA-155 in the pathogenesis of asthma and its potential as a target for treatment. The expression of miRNA-155 increased in ovalbumin-sensitized and challenged mice compared with control mice, and lentiviral vector-delivered small interfering (si)RNA targeting miRNA-155 resulted in reduced AHR, airway inflammation and Th2 cytokine production. The data from the present study indicate that miRNA-155 serves an important role in the pathogenesis of asthma, and that lentiviral vector-delivered siRNA targeting miRNA-155 may serve as a novel approach for the treatment of allergic asthma.

Background: To identify COPD associated gene susceptibility and lung function in a longitudinal cohort including COPD and subjects who were at risk for developing COPD, and to replicate this in two cross-sectional and longitudinal populations in Chinese Han population., Methods: Three cohorts were recruited in this study, including an 18-year follow-up population (306 COPD and 743 control subjects) in one village in 1992 and it changed to 409 COPD and 611 controls in 2010, a 2 year follow-up study in another village (374 COPD and 377 controls) and another 2 year follow-up one in a city (541 COPD and 560 controls) in 2010. Sixteen candidate single nucleotide polymorphisms (SNPs) were selected for genotyping. Among them, 5SNPs in or near HHIP, 1SNP in IREB2 and 1SNP in FAM13A were previously reported to be associated with COPD susceptibility or lung function decline. And another 9SNPs were selected from HapMap website as HHIP tags. In 2010, totaling 1,324 COPD patients and 1,548 healthy controls were finally included in our genetic susceptibility analyses., Results: We identified two new regions showing an association with COPD susceptibility in the Human Hedgehog interacting protein (HHIP) rs11100865 and rs7654947, and we confirmed that the family with sequence similarity 13 member A gene (FAM13A) rs7671167 was associated with the development of COPD in Chinese Han population. And the HHIP rs7654947 and FAM13A rs7671167 were associated with lung function decline, and this result was replicated in other two populations., Conclusions: These results suggest an important role of the HHIP and FAM13A regions as genetic risk factors for COPD development and lung function decline in Chinese Han population. Future research on these genes should focus on the molecular mechanisms of these genes on developing COPD and creating therapies to alleviate reduced lung function.

Background: Although it is recognized that IL-33 plays a key role in the onset of asthma, it is currently unclear whether IL-33 acts on any other target cells besides mast cells and Th2 cells in asthma. We investigated that whether airway smooth muscle cells (ASMCs) could contribute to asthma via stimulation with IL-33., Methods: To create a mouse model of acute asthma, murine ASMCs were isolated and cultured in vitro with IL-33. The ASMCs were divided into two groups, ASMCs from normal mice and ASMCs from ovalbumin-sensitized mice. The release of mouse KC was analyzed by PCR and ELISA. Immunocytochemical Staining of murine ASMCs for ST2 and IL-1RAcP was performed., Results: IL-33 promoted KC expression, both in terms of mRNA and protien levels, in ASMCs from ovalbumin-sensitized mice. ST2 and IL-1RAcP were expressed in the membrane of ASMCs in ovalbumin-sensitized mice., Conclusion: IL-33 may contribute to the inflammation in the airways by acting on airway smooth muscle cells. IL-33 and ST2 may play important roles in allergic bronchial asthma.

Purpose: Matrix metalloproteinase (MMP) 1, MMP2, MMP3 and MMP9 are important members of the MMP family. Recently, many studies have been carried out on the association between polymorphisms of MMP1-1607 1G/2G, MMP2-735 C/T, MMP2-1306 C/T, MMP3-1171 5A/6A and MMP9-1562 C/T and lung cancer risk. However the results of these studies remained inconclusive due to conflicting results from different case-control studies. To clarify these associations, we conducted a meta-analysis., Methods: We conducted a comprehensive search in Medline, EMBASE, OVID and Chinese Biomedical Literature Database (date from Jan 2000 to Aug 2012). Overall and subgroup analysis by the ethnicity of study population was carried out. Odds ratio (OR) with 95% confidence interval (95%CI) was used to assess the strength of the association., Results: There were 17 studies involving five polymorphic sites in four MMP genes. For MMP1-1607,increased lung cancer risk was found under dominant model (MMP1-1607 1G/2G: OR=1.14, 95%CI=1.03-1.26, P=0.01), but not in the Caucasian population. For MMP2-1306 C/T, T polymorphism decreased lung cancer risk under dominant and recessive models (dominant, OR=0.63, 95%CI=0.46-0.88, P=0.0006; recessive, OR=0.61, 95%CI=0.38-0.99, P=0.04). For MMP9-1562 C/T, TT genotype decreased this risk under the recessive model (OR=0.38, 95%CI=0.19-0.75, P=0.005), but not in the Asian population. For MMP2-735 C/T and MMP3-1171 5A/6A, there was no association between this polymorphism and lung cancer risk under the dominant and recessive models., Conclusions: MMP1-1607 1G/2G polymorphism increased lung cancer risk in Asians. It was also found that MMP2-1306 C/T polymorphism decreased lung cancer risk in Asians, while MMP9-1562 C/T polymorphism decreased lung cancer risk in Caucasians. No significant difference was found in any genotype of MMP2-735 C/T and MMP3-1171 5A/6A. Further studies with larger sample sizes should be carried out., (Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.)