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Samuel Multack,1 Li-Chen Pan,2 Sean K Timmons,2 Manasi Datar,2 Chia-Wen Hsiao,3 Raiju Babu,3 Sun-Ming Pan,3 Lawrence Woodard4 1Multack Eye Care and Associates, Olympia Fields, IL, USA; 2Commercial Strategy and Market Access, Boston Healthcare Associates (a Veranex Company), Boston, MA, USA; 3Health Economics and Outcomes Research, Alcon, Fort Worth, TX, USA; 4Atlanta Eye Surgery Center, Atlanta, GA, USACorrespondence: Samuel Multack, Multack Eye Care and Associates, 20303 Crawford Ave, Olympia Fields, IL, 60461, USA, Tel +1-708-898-1858, Email smultack@mecvision.comPurpose: This study aims to assess the time impact of ARGOS® (image-guided swept-source optical coherence tomography biometer integrated with operating room (OR) technologies (SS-OCT w/ORT)) compared to LENSTAR LS 900 (optical low-coherence reflectometry (OLCR)), IOLMaster 500 (partial coherence interferometry (PCI)), and IOLMaster 700 (SS-OCT) on efficiency in the cataract evaluation and surgery.Patients and Methods: Data from 212 patients (two study sites) who underwent evaluation and/or cataract surgery were collected. The primary objective was to compare the performance of four biometers; statistical analyses were conducted to compare 1) biometer measurement times for all patients (ANOVA w/post-hoc Dunnett’s test) and stratified by cataract density (ANOVA) and 2) rate of biometer acquisition failure (Chi-square test w/post-hoc Bonferroni correction). Real-world observational data collected were then used to develop a practice-based time-efficiency model to demonstrate the combined effect that adopting an SS-OCT w/ORT has on a practice’s cataract workflow. Real-world data inputs included assessment of patient’s eyes’ cataract grade density, time taken for optical biometry, Manual A-scan (ultrasound biometer) when acquisition failed, and measurement times associated with other devices used in cataract evaluation and surgery.Results: For 208 patients (56% non-dense, 44% dense), the SS-OCT w/ORT biometer had a 0% acquisition failure (SS-OCT: 3% (p = 0.05); OLCR: 5% (p = 0.004); PCI: 15% (p < 0.0001)) and an average time savings of 30 seconds/patient compared to the other biometers in this study (p < 0.05). When acquisition failed, ultrasound biometry resulted in an additional 2.5 minutes/patient. For a cohort of 1000 patients, an SS-OCT w/ORT and an image-guidance system adopted at a practice using an SS-OCT, femtosecond laser, and intraoperative aberrometer offer up to 58% efficiency gain across the cataract workflow.Conclusion: Results from this study demonstrate an SS-OCT w/ORT’s efficiencies in cataract evaluation and surgery driven by faster measurement times, reducing the need for ultrasound biometry, and its integration benefits with other devices.Keywords: cataract surgery, swept-source optical coherence tomography biometer, time-and-motion study, preoperative evaluation phase

Carboxylesterase 1 (CES1), a member of the serine hydrolase superfamily, is involved in a wide range of xenobiotic and endogenous substances metabolic reactions in mammals. The inhibition of CES1 could not only alter the metabolism and disposition of related drugs, but also be benefit for treatment of metabolic disorders, such as obesity and fatty liver disease. In the present study, we aim to develop potential inhibitors of CES1 and reveal the preferred inhibitor structure from a series of synthetic pyrazolones (compounds 1-27). By in vitro high-throughput screening method, we found compounds 25 and 27 had non-competitive inhibition on CES1-mediated N-alkylated d-luciferin methyl ester (NLMe) hydrolysis, while compound 26 competitively inhibited CES1-mediated NLMe hydrolysis. Additionally, Compounds 25, 26 and 27 can inhibit CES1-mediated fluorescent probe hydrolysis in live HepG2 cells with effect. Besides, compounds 25, 26 and 27 could effectively inhibit the accumulation of lipid droplets in mouse adipocytes cells. These data not only provided study basis for the design of newly CES1 inhibitors. The present study not only provided the basis for the development of lead compounds for novel CES1 inhibitors with better performance, but also offered a new direction for the explore of candidate compounds for the treatment of hyperlipidemia and related diseases., 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 Inc. All rights reserved.)

Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1-14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48-0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile., (© 2024. The Author(s).)

Ethnophamacological Relevance: Morinda officinalis oligosaccharides (MOs) is a mixture of oligosaccharides extracted from the roots of Morinda officinalis (MO). It is approved by Chinese Food and Drug Administration (CFDA) for depression treatment. MOs could improve the antidepressant efficacy of escitalopram in clinic., Aim of the Study: We aim to explore the antidepressant activity and potential mechanism of the combination usage of MOs and escitalopram on animal model of depression., Materials and Methods: Depressive animal model was induced by chronic mild stress (CMS). Behavioral tests were conducted to evaluate the antidepressant efficacy of MOs and escitalopram. Serum neurotransmitter levels were detected by High-performance liquid chromatography (HPLC). Quantitative real-time PCR and Western blotting were applied to assay the hippocampus neurotrophic factors' mRNA and protein levels. Peripheral cytokines levels were measured through Enzyme-Linked Immunosorbent Assay (ELISA). Micorglia polization phenotype was assayed by immunofluorescence and flow cytometry., Results: MOs and escitalopram obviously attenuated depression-like behaviors of CMS mice. Importantly, MOs plus escitalopram exhibited better antidepressant activity on CMS mice than monotherapy. At the same time, MOs combined escitalopram treatment significantly increased hippocampus neurotransmitters and neurotrophic factor levels, stimulated hippocampus neurogenesis and relieved central nervous system (CNS) microglia over-activation of CMS mice. The combination therapy had greater effect on neuroprotection and inflammation attenuation of CMS mice than monotherapy., Conclusion: Our results indicates MOs combined escitalopram might produce antidepressant activity through protecting neuron activity, relieving inflammation and modulating microglia polarization 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 Elsevier B.V. All rights reserved.)

Non-healing wounds are one of the chronic complications of diabetes and have remained a worldwide challenge as one of the major health problems. Hyperbaric oxygen (HBO) therapy is proven to be very successful for diabetic wound treatment, for which the molecular basis is not understood. Adipocytes regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes. Endothelial cell-derived extracellular vesicles could promote wound healing in diabetes. To study the mechanism by which HBO promotes wound healing in diabetes, we investigated the effect of HBO on fat cells in diabetic mice. A diabetic wound mouse model was established and treated with HBO. Haematoxylin and eosin (H&E) staining and immunofluorescence were used for the analysis of wound healing. To further explore the mechanism, we performed whole-genome sequencing on extracellular vesicles (EVs). Furthermore, we conducted in vitro experiments. Specifically, exosomes were collected from human umbilical vein endothelial cell (HUVEC) cells after HBO treatment, and then these exosomes were co-incubated with adipose tissue. The wound healing rate in diabetic mice treated with HBO was significantly higher. HBO therapy promotes the proliferation of adipose precursor cells. HUVEC-derived exosomes treated with HBO significantly promoted fat cell browning. These data clarify that HBO therapy may promote vascular endothelial cell proliferation and migration, and promote browning of fat cells through vascular endothelial cells derived exosomes, thereby promoting diabetic wound healing. This provides new ideas for the application of HBO therapy in the treatment of diabetic trauma., (© 2024 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Purpose: To evaluate time efficiencies in the laser room for 2 different femtosecond laser systems., Setting: 1 private practice in Atlanta, Georgia, and 1 private practice in Los Angeles, California., Design: Prospective, observational, single-masked study., Methods: Patients scheduled to receive femtosecond laser-assisted cataract surgery (FLACS) included those who were not pregnant, had no previous eye surgeries, and were not scheduled to undergo additional surgical procedures at the time of treatment; patients who received a standard, monofocal lens without undergoing arcuate incisions were excluded. Patients taking Flomax or any tamsulosin were also excluded from the study. Each comparable step in the LenSx and CATALYS workflow was identified and clearly defined. Time for each step was evaluated and compared using t tests and regression analyses to control for patient and site-specific differences between the 2 groups., Results: Time data were collected for 89 patients (89 eyes). The overall procedure was 2.86 minutes shorter for the LenSx system when compared with the CATALYS system ( P < .05). Per patient, the LenSx system had significantly shorter time for patient positioning (57.26 vs 122.00 seconds; P < .05), imaging (33.23 vs 42.17 seconds; P < .05), laser treatment (21.57 vs 39.67 seconds; P < .05), and undocking/transition (67.13 vs 185.30 seconds; P < .05) compared with the CATALYS system. Regression analyses yielded similar results, with the LenSx system being over 35% (3.21 minutes; P < .05) shorter overall than the CATALYS system controlling for location, age, sex, lens thickness, cataract grade, fragmentation pattern, and arcuate incisions., Conclusions: LenSx procedures were significantly shorter than the CATALYS procedures overall, which can enable ophthalmology practices to increase efficiency., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of ASCRS and ESCRS.)

Ethnopharmacological Relevance: Ulcerative colitis (UC) is one of non-specific inflammatory bowel disease that mainly affects the colon. Recently, UC has become a significant social and economic problem worldwide. Baitouweng decoction (BD), a traditional Chinese medicine described in the "Treatise on Febrile Diseases", has been used for centuries to treat intestinal diseases. However, its underlying mechanism remains largely unexplored., Aim of Study: In this study, we aimed to investigate the effect of BD on autophagy for repairing the colonic barrier in DSS-induced colitis mice and explored its role in regulating the autophagic signaling pathway AMPK/mTOR., Materials and Methods: Mice with colitis were treated with 3% dextran sulfate sodium (DSS) for 7 days. The effectiveness of BD in treating DSS-induced colitis was evaluated through body weight, disease activity index (DAI), colon length, pathological changes, organ index, and proportion of blood cells. Moreover, intestinal epithelial permeability was analyzed by examining FITC-dextran leakage, the bacterial load of mesenteric lymph nodes (MLNs), and bacterial infiltration of colon tissues. Barrier function was evaluated by assessing the number and proportion of colonic goblet cells and the expression of tight junction proteins, including ZO-1, claudin-1, and occludin. Furthermore, the levels of autophagy were assessed by examining the number of autophagosomes and the expression of the autophagy-related proteins LC3, Beclin1, and P62. Additionally, network pharmacology research was conducted to analyze the potential mechanisms underlying the medicinal effects, as indicated by the role of AMPK/mTOR in regulating the autophagic signaling pathway., Results: BD improved colitis symptoms in mice by restoring body weight and colon length and reducing inflammatory cell infiltration. Additionally, BD decreased the diffusion of FITC-dextran and bacterial translocation in MLNs, as well as bacterial infiltration of the colonic mucosa. The number and proportion of colonic goblet cells, the expression of ZO-1, Claudin-1, and Occludin, and the levels of autophagy were also increased by BD. Network pharmacology analysis suggested that BD might affect intestinal autophagy through the AMPK signaling pathway, which was confirmed by the activation of AMPK phosphorylation and the downregulation of mTOR expression following BD treatment., Conclusion: Our study demonstrated that BD repaired the intestinal epithelial barrier in DSS-induced colitis mice by activating AMPK phosphorylation and inhibiting mTOR expression to promote autophagy., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Antidepressant fluoxetine can affect cerebral glucose metabolism in clinic, but the underlying molecular mechanism remains poorly understood. Here, we examined the effect of fluoxetine on brain regional glucose metabolism in a rat model of depression induced by repeated corticosterone injection, and explored the molecular mechanism. Fluoxetine was found to recover the decrease of 18 F-fluorodeoxyglucose ( 18 F-FDG) signal in prefrontal cortex (PFC), and increased 2-[ N -(7-Nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose (2-NBDG, a fluorescent glucose analog) uptake in an astrocyte-specific manner in ex vivo cultured PFC slices from corticosterone-induced depressive rats, which were consistent with its improvement of animal depressive behaviors. Furthermore, fluoxetine restricted nuclear translocation of glucocorticoid receptor (GR) to suppress the transcription of thioredoxin interacting protein ( TXNIP ). Subsequently, it promoted glucose transporter 1 (GLUT1)-mediated glucose uptake and glycolysis of PFC astrocytes through suppressing TXNIP expression under corticosterone-induced depressive state. More importantly, fluoxetine could improve glucose metabolism of corticosterone-stimulated astrocytes via TXNIP-GLUT1 pathway. These results demonstrated that fluoxetine increased astrocytic glucose uptake and glycolysis in corticosterone-induced depression via restricting GR-TXNIP-GLUT1 pathway. The modulation of astrocytic glucose metabolism by fluoxetine was suggested as a novel mechanism of its antidepressant action., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pan, Zhou, Zuo, Jiao, Kong and Pan.)

Background: The aim of our study was to translate and validate the mainland Chinese version of the short health scale (SHS), a disease-specific quality-of-life (QoL) scale for patients with inflammatory bowel disease (IBD)., Methods: The SHS was translated and validated according to the standard process: a translation and back-translation procedure and a reliability and validation study. Patients with IBD were enrolled, and their QoL was assessed using the SHS, the short inflammatory bowel disease questionnaire (SIBDQ), and the Bristol stool form scale. Reliability (internal consistency reliability, split-half reliability, and test-retest reliability) and validity analyses were performed to evaluate the psychometric characteristics of the SHS. The impacts of different severity of major symptoms on QoL were analyzed by comparing the scores of SHS., Results: A total of 112 patients with IBD (69 with ulcerative colitis and 43 with Crohn's disease) completed the mainland Chinese version of the SHS, and 34 patients completed the SHS a second time within one to two weeks. Cronbach's alpha value of the SHS was 0.90, and its split-half coefficient was 0.83. Intraclass correlation coefficients of the four items ranged from 0.52 to 0.72. All four items of the SHS were significantly associated with the corresponding domains of the SIBDQ, with correlation coefficients ranging from -0.52 to -0.69 ( p  < 0.001). The results of confirmatory factor analysis indicated a good fit of the one-factor model, with comparative fit index (CFI) = 0.878, normed fit index (NFI) = 0.874, incremental fit index (IFI) = 0.880, and goodness of fit index (GFI) = 0.842. The patients with severe symptoms had higher scores in the SHS than those with no or mild symptoms., Conclusions: The SHS was simple and quick to be used. The SHS had good validity and reliability and was suitable for evaluating the QoL of patients with IBD in mainland China., Competing Interests: No competing financial interests exist., (© Jiang-tao Hou et al., 2022; Published by Mary Ann Liebert, Inc.)

Background: Sexual violence is a global health and human rights issue that impacts the physical and mental health of victims and increases healthcare costs., Purpose: This research was developed to investigate the prevalence of sexual violence against women in Taiwan and the help-seeking behavior of these women. Based on the findings, suggestions are provided for both government policymakers and frontline medical staffs., Methods: Data for this study were collected using a face-to-face interview survey conducted with women aged 18 to 74 years nationwide., Results: Of the 1,504 women surveyed, 87 (5.76%) reported having suffered from sexual violence. The one-year prevalence was 1.41%, while the lifetime prevalence was 5.76%. Although sexual violence is known to impact physical and mental health, most victims are reluctant to seek help from formal support systems., Conclusions: Victims of sexual violence often delay seeking help from medical settings. Although the victims identified in this study endured chronic symptoms and psychological trauma, few had made formal disclosures of intimate partner sexual violence (IPSV) incidents. Frontline medical staffs have the opportunity to play an important role in sexual-violence response if they are made aware of incidents of IPSV / non-IPSV. Thus, to facilitate disclosure, screening for IPSV and non-IPSV should be made standard practice in high-risk medical settings.

Objective: To develop and validate a radiomic prediction model using initial noncontrast computed tomography (CT) at admission to predict in-hospital mortality in patients with traumatic brain injury (TBI)., Methods: A total of 379 TBI patients from three cohorts were categorized into training, internal validation, and external validation sets. After filtering the unstable features with the minimum redundancy maximum relevance approach, the CT-based radiomics signature was selected by using the least absolute shrinkage and selection operator (LASSO) approach. A personalized predictive nomogram incorporating the radiomic signature and clinical features was developed using a multivariate logistic model to predict in-hospital mortality in patients with TBI. The calibration, discrimination, and clinical usefulness of the radiomics signature and nomogram were evaluated., Results: The radiomic signature consisting of 12 features had areas under the curve (AUCs) of 0.734, 0.716, and 0.706 in the prediction of in-hospital mortality in the internal and two external validation cohorts. The personalized predictive nomogram integrating the radiomic and clinical features demonstrated significant calibration and discrimination with AUCs of 0.843, 0.811, and 0.834 in the internal and two external validation cohorts. Based on decision curve analysis (DCA), both the radiomic features and nomogram were found to be clinically significant and useful., Conclusion: This predictive nomogram incorporating the CT-based radiomic signature and clinical features had maximum accuracy and played an optimized role in the early prediction of in-hospital mortality. The results of this study provide vital insights for the early warning of death in TBI patients., (© 2022. Fondazione Società Italiana di Neurologia.)

Background: Induction chemotherapy (IC) can alleviate locoregionally advanced nasopharyngeal carcinoma (LA-NPC), but effectiveness differs between patients, toxicity is problematic, and effective blood-based IC efficacy predictors are lacking. Here, we aimed to identify biomarkers for early identification of IC beneficiaries., Methods: Sixty-four pairs of matched plasma samples collected before and after IC from LA-NPC patients including 34 responders and 30 non-responders, as well as 50 plasma samples of healthy individuals, were tested using data-independent acquisition mass spectrometry. The proteins associated with clinical traits or IC benefits were investigated by weighted gene co-expression network analysis (WGCNA) and soft cluster analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional annotations were performed to determine the potential function of the identified proteins. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of candidate biomarkers in predicting IC beneficiaries., Results: Compared with healthy individuals, 1027 differentially expressed proteins (DEPs) were found in the plasma of LA-NPC patients. Based on feedback from IC outcomes, 463 DEPs were identified in the pre-IC plasma between responders and non-responders. A total of 1212 DEPs represented the proteomic changes before and after IC in responders, while 276 DEPs were identified in post-IC plasma between responders and non-responders. WGCNA identified nine protein co-expression modules correlated with clinical traits. Soft cluster analysis identified four IC benefits-related protein clusters. Functional enrichment analysis showed that these proteins may play a role in IC via immunity, complement, coagulation, glycosaminoglycan and serine. Four proteins differentially expressed in all group comparisons, paraoxonase/arylesterase 1 (PON1), insulin-like growth factor-binding protein 3 (IGFBP-3), rheumatoid factor D5 light chain (v-kappa-3) and RNA helicase (DDX55), were associated with clinical traits or IC benefits. A four-protein model accurately identified potential IC beneficiaries (AUC=0.95) while diagnosing LA-NPC (AUC=0.92), and the prediction performance was verified using the models to confirm the effective IC (AUC=0.97) and evaluate IC outcome (AUC=0.94)., Conclusion: The plasma protein profiles among IC responders and non-responders were different. PON1, IGFBP3, v-kappa-3 and DDX55 could serve as potential biomarkers for early identification of IC beneficiaries for individualised treatment of LA-NPC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Pan, Lai, Situ, Liu, Dai, Liang, Zhou, Lu, Ke, Zhang, Chen and Li.)

Rationale: Stress is a major risk factor for the development of depression. However, the underlying molecular mechanisms of stress vulnerability in depression are largely uncharacterized. Methods: P2X2 receptors (a major receptor for gliotransmitter-ATP) in the medial prefrontal cortex (mPFC) were identified by real-time qPCR, western blots and RNAscope in situ hybridization in chronic social defeat stress model (CSDS). We generated P2X2 conditional knockout mice and overexpressed AAV-P2X2 in CamkIIα-Cre mice. The depression-like behaviors were assessed via CSDS, subthreshold social defeat stress (SSDS), social interaction test (SI), forced interaction test (FIT), forced swimming test (FST), sucrose preference test (SPT), novel stressed feeding (NSF) and open field test (OFT). The neuronal activity and synapse function of P2X2 receptors in the mPFC were detected by in vivo fiber-photometry, patch-clamp techniques and neuronal morphometric analysis. Results: We identified that P2X2 receptors were increased in the mPFC of susceptible mice in CSDS. Conditional knockout of P2X2 receptors in pyramidal neurons promoted resilience of chronic stress-induced depressive-like behaviors, whereas pyramidal neurons - specific gain of P2X2 in the mPFC increased vulnerability to depressive-like behaviors. In vivo fiber-photometry, electrophysiology and neuronal morphometric analysis showed P2X2 receptors regulated neuronal activity and synapse function in the mPFC. Conclusions: Overall, our studies reveal a critical role of P2X2 in mediating vulnerability to chronic stress and identify P2X2 as a potential therapeutic target for treatment of stress-related mood disorders., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

We propose the use of optical films to enhance the light extraction efficiency (LEE) and wide-angle emission of traditional packaged deep-ultraviolet light-emitting diodes (DUV-LEDs). Total internal reflection occurs easily in DUV-LEDs because they contain sapphire, which has a high refractive index. DUV-LEDs also contain an aluminum nitride (AlN) ceramic substrate, which has high light absorption in the ultraviolet band. Photons are absorbed by the sapphire and AlN ceramic substrate, which reduces the LEE of DUV-LEDs. By adding a brightness enhancement film (BEF) on the sapphire surface and a high-reflection film (HRF) on the surface of the AlN ceramic substrate, the LEE of DUV-LEDs can be increased. Moreover, we designed a single-layer metal reflective film (SMRF) on the upper surface of the quartz glass in order to achieve wide-angle emission. Experimental results indicated that compared with traditional packaged DUV-LEDs, the light output power and external quantum efficiency of DUV-LEDs with a plated BEF, HRF, and SMRF increased by 18.3% and 18.2%, respectively. Moreover, an emission angle of 160° was achieved. In a reliability test, DUV-LEDs maintained more than 95% of the initial forward voltage and light output power after 1000 h of operation at 25°C, which indicated that the addition of an optical film can improve the light efficiency and long-term reliability of DUV-LEDs.

Brain energetics disturbance is a hypothesized cause of depression. Glucose is the predominant fuel of brain energy metabolism; however, the cell-specific change of glucose metabolism and underlying molecular mechanism in depression remains unclear. In this study, we firstly applied 18 F-FDG PET and observed brain glucose hypometabolism in the prefrontal cortex (PFC) of corticosterone-induced depression of rats. Next, astrocytic glucose hypometabolism was identified in PFC slices in both corticosterone-induced depression of rats and cultured primary astrocytes from newborn rat PFC after stress-level corticosterone (100 nM) stimulation. Furthermore, we found the blockage of glucose uptake and the decrease of plasma membrane (PM) translocation of glucose transporter 1 (GLUT1) in astrocytic glucose hypometabolism under depressive condition. Interestingly, thioredoxin interacting protein (TXNIP), a glucose metabolism sensor and controller, was found to be over-expressed in corticosterone-stimulated astrocytes in vivo and in vitro. High TXNIP level could restrict GLUT1-mediated glucose uptake in primary astrocytes in vitro. Adeno-associated virus vector-mediated astrocytic TXNIP over-expression in rat medial PFC suppressed GLUT1 PM translocation, consequently developed depressive-like behavior. Conversely, TXNIP siRNA facilitated GLUT1 PM translocation to recover glucose hypometabolism in corticosterone-exposed cultured astrocytes. Notably, astrocyte-specific knockdown of TXNIP in medial PFC of rats facilitated astrocytic GLUT1 PM translocation, showing obvious antidepressant activity. These findings provide a new astrocytic energetic perspective in the pathogenesis of depression and, more importantly, provide TXNIP as a promising molecular target for novel depression therapy., (© 2021 International Society for Neurochemistry.)

Data mining is an important method to obtain the key information from a large amount of data, and it is widely applied in the research on the modernization of traditional Chinese medicine(TCM). The compatibility law of herbs is a key issue in the research of TCM prescriptions. This reflects the flexibility and effectiveness of TCM prescriptions, and it is also a crucial link to the development of TCM modernization. Therefore, it is the core purpose of the research on TCM prescriptions to find the compatibility law of herbs and clarify the scientific connotation. Data mining, as an effective method and an important approach, has formed a standardized system in the research of compatibility law of herbs, which can reveal the relationship between different Chinese herbs and summarize the internal rules in compatibility. Two hundred and twenty two effective papers were sorted out and categorized in this article. The results showed that data mining was mainly applied in finding the core Chinese herb pairs, summarizing the utility and attributes of TCM prescriptions, revealing the relationship between prescriptions, Chinese herbs and syndromes, finding the optimal dose of Chinese herbs, and producing the new prescriptions. The problems of data mining in research of herbs compatibility rules were summarized, and its development and trend in current researches were discussed in this article to provide useful references for the in-depth study of data mining in the compatibility law of Chinese herbs.

Purpose: Previous studies have elucidated the unique macroscopic and histological properties of buccal mucosa that make it a viable and durable graft for urethral augmentation. However, no prior literature has directly investigated the impact of preoperative oral health on these features., Materials and Methods: We analyzed all consenting patients who underwent buccal mucosal graft (BMG) urethroplasty at our institution from 2018 to 2020. Validated oral health surveys, the Oral Health Impact Profile (OHIP-14) and the Kayser-Jones Brief Oral Health Status Examination (BOHSE) were completed preoperatively. A staff pathologist analyzed BMG histology and quantified oral mucositis using a modified Oral Mucosa Rating Scale., Results: We analyzed 51 patients with a median age of 40 years (IQR 31-58). Mean BOHSE score was 1.1 and OHIP-14 score was 1.4. Median epithelial thickness was 530 μm and lamina propria thickness was 150 μm. On age-adjusted analysis, increasing BOHSE and OHIP-14 were associated with decreasing epithelial thickness (p values <0.05). Higher BOHSE scores also correlated with thinner lamina proprias (p=0.05) and increased graft stretch (p=0.03). The 2 patients with postoperative urine leaks and available graft histology had lamina propria thicknesses well below the cohort median, at 50 μm and 60 μm., Conclusions: This is the first study to demonstrate that oral health conditions impact graft histology and stretch. Although much remains to be learned, our findings shed light on the potential importance of optimizing oral health prior to BMG urethroplasty, and raise the question of if preoperative mucosal biopsy could help inform surgical decision making and discussions regarding surgical success.

As a malignant tumor type, nasopharyngeal carcinoma (NPC) is characterized by distinct geographical, ethnic and genetic differences; presenting a major threat to human health in many countries, especially in Southern China. At present, no accurate and effective methods are available for the early diagnosis, efficacious evaluation or prognosis prediction for NPC. As such, a large number of patients have locoregionally advanced NPC at the time of initial diagnosis. Many patients show toxic reactions to overtreatment and have risks of cancer recurrence and distant metastasis owing to insufficient treatment. To solve these clinical problems, high‑throughput '‑omics' technologies are being used to screen and identify specific molecular biomarkers for NPC. Because of the lack of comprehensive descriptions regarding NPC biomarkers, the present study summarized the research progress that has been made in recent years to discover NPC biomarkers, highlighting the existing problems that require exploration. In view of the lack of authoritative reports at present, study design factors that affect the screening of biomarkers are also discussed here and prospects for future research are proposed to provide references for follow‑up studies of NPC biomarkers.

Purpose: We utilized the National Trauma Data Bank® database to report practice patterns in managing blunt traumatic ureteral injuries and assess the consistency with current guidelines/literature., Materials and Methods: Between 2007 and 2016 all National Trauma Data Bank database patients with blunt traumatic ureteral injuries were identified using ICD-9 and Abbreviated Injury Scale codes. Penetrating trauma and missing data were excluded. Patients were unstable if Injury Severity Score was above 15 or systolic blood pressure was 90 mmHg or less. Abbreviated Injury Scale severity score 2 or less was a low severity ureteral injury. Treatment options were minimally invasive methods or ureteral reconstruction. Patients who underwent laparotomy for associated injuries were identified. Chi-square, Fisher exact or 2-tailed t-test was utilized to evaluate differences. Univariable logistic regression identified independent variables that favored a specific treatment., Results: A total of 147 blunt traumatic ureteral injuries were used for analysis. Of the patients 98 (66.7%) were unstable and 51 (34.7%) had a high severity ureteral injury. Patients with low and high severity ureteral injuries were treated more frequently with minimally invasive methods over ureteral reconstruction. Laparotomy for associated injuries resulted in a higher frequency of ureteral reconstruction (15 of 55, 27.3%) vs laparotomy for ureteral reconstruction alone (9 of 55, 16.4%; p=0.0012). On univariable analysis patients who underwent exploratory laparotomy or underwent an associated injury repair that facilitated retroperitoneal exploration had significantly higher odds of receiving ureteral reconstruction over minimally invasive methods., Conclusions: Contrary to guidelines, practice patterns favor treating severe blunt traumatic ureteral injuries with minimally invasive methods over ureteral reconstruction. Ureteral reconstruction is favored when patients undergo laparotomy for associated injuries.

Objective: In this study, we investigated whether certain types of lipid profiles are major contributors of acute ischemic stroke (AIS)., Patients and Methods: We screened 13,285 hospitalized patients in two stroke medical centers treated with thrombolysis, thrombectomy, or conventional care for anterior cerebral artery-occluded AIS, and found 266 patients. We examined their plasma lipid profiles using the cutoff values from a receiver operating characteristic (ROC) curve. We applied a multivariate logistic regression or Fisher's exact test to compare their outcomes and risk factors. We used the modified Rankin scale (mRS) score to assess the major clinical outcome of the patients 3 months after disease onset. Mortality and symptomatic intracranial hemorrhage (sICH) were both evaluated as risk factors. We analyzed symptoms' improvements at discharge as a disease outcome measure., Results: In the patients with anterior cerebral artery-occluded AIS (NIHSS ≥ 10) treated by intravenous (IV) thrombolysis, a total cholesterol (TC) level greater than 5.07 mmol/L predicted a poor outcome (OR 3.55, 95% CI 1.21,10.46, p=0.021)., Conclusions: In patients with anterior cerebral artery-occluded AIS, the TC level is a promising prognosis marker for the IV thrombolysis outcome.

Background: Hospital mortality rates are higher among patients with sepsis-associated acute kidney injury (SA-AKI) than among patients with sepsis. However, the pathogenesis underlying SA-AKI remains unclear. We hypothesized that the source of infection affects development of SA-AKI. We aim to explore the relationship between the anatomical source of infection and outcome in patients with SA-AKI., Methods: Between January 2013 and January 2018, 113 patients with SA-AKI admitted to our Emergency Center were identified and divided into two groups: those with pulmonary infections and those with other sources of infection. For each patient, we collected data from admission until either discharge or death. We also recorded the clinical outcome after 90 days for the discharged patients., Results: The most common source of infection was the lung (52/113 cases, 46%), followed by gastrointestinal (GI) (25/113 cases, 22.1%) and urinary (22/113, 19.5%) sources. Our analysis showed that patients with SA-AKI had a significantly worse outcome (30/52 cases, P <0.001) and poorer kidney recovery ( P =0.015) with pulmonary sources of infection than those infected by another source. Data also showed that patients not infected by a pulmonary source more likely experienced shock (28/61 cases, P =0.037)., Conclusion: This study demonstrated that the source of infection influenced the outcome of SA-AKI patients in an independent manner. Lung injury may influence renal function in an as-yet undetermined manner as the recovery of kidney function was poorer in SA-AKI patients with a pulmonary source of infection., Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare., (Copyright: © 2020 World Journal of Emergency Medicine.)

Excessive fructose consumption induces oxidative stress and myocardial fibrosis. Antioxidant compound pterostilbene has cardioprotective effect in experimental animals. This study is aimed at investigating how fructose drove fibrotic responses via oxidative stress in cardiomyocytes and explored the attenuation mechanisms of pterostilbene. We observed fructose-induced myocardial hypertrophy and fibrosis with ROS overproduction in rats. Paired-like homeodomain 2 (Pitx2c) increase, microRNA-15b (miR-15b) low expression, and p53 phosphorylation (p-p53) upregulation, as well as activation of transforming growth factor- β 1 (TGF- β 1)/drosophila mothers against DPP homolog (Smads) signaling and connective tissue growth factor (CTGF) induction, were also detected in fructose-fed rat hearts and fructose-exposed rat myocardial cell line H9c2 cells. The results from p53 siRNA or TGF-β1 siRNA transfection showed that TGF- β 1-induced upregulation of CTGF expression and p-p53 activated TGF- β 1/Smads signaling in fructose-exposed H9c2 cells. Of note, Pitx2c negatively modulated miR-15b expression via binding to the upstream of the miR-15b genetic loci by chromatin immunoprecipitation and transfection analysis with pEX1-Pitx2c plasmid and Pitx2c siRNA, respectively. In H9c2 cells pretreated with ROS scavenger N-acetylcysteine, or transfected with miR-15b mimic and inhibitor, fructose-induced cardiac ROS overload could drive Pitx2c-mediated miR-15b low expression, then cause p-p53-activated TGF- β 1/Smads signaling and CTGF induction in myocardial fibrosis. We also found that pterostilbene significantly improved myocardial hypertrophy and fibrosis in fructose-fed rats and fructose-exposed H9c2 cells. Pterostilbene reduced cardiac ROS to block Pitx2c-mediated miR-15b low expression and p-p53-dependent TGF- β 1/Smads signaling activation and CTGF induction in high fructose-induced myocardial fibrosis. These results firstly demonstrated that the ROS-driven Pitx2c/miR-15b pathway was required for p-p53-dependent TGF- β 1/Smads signaling activation in fructose-induced myocardial fibrosis. Pterostilbene protected against high fructose-induced myocardial fibrosis through the inhibition of Pitx2c/miR-15b pathway to suppress p-p53-activated TGF- β 1/Smads signaling, warranting the consideration of Pitx2c/miR-15b pathway as a therapeutic target in myocardial fibrosis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 Lin-Lin Kang et al.)

Background: 8-Hydroxyquinoline derivatives have highly sensitive fluorescent chemosensors for metal ions, which are associated with anti-oxidant, anti-tumor and anti-HIV-1 properties. Head and neck squamous cell carcinoma (HNSCC) is associated with a high rate of mortality and novel anti-HNSCC drugs must be developed. Therefore, effective chemotherapy agents are required to address this public health issue., Hypothesis/purpose: The aim of this study was to investigate the inhibitory effect of tris(8-hydroxyquinoline)iron (Feq 3 ) on the HNSCC and the underlying mechanism., Study Design/methods: A novel 8-hydroxyquinoline derivative, Feq 3 , was synthesized. The cell viabilities were analyzed using MTT reagent. Apoptosis and the cell cycle distributions were determined by flow cytometer. Reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence, western blot, MitoSOX and CellROX stain assay were used to study the mechanism of Feq 3 . Feq 3 combined with antioxidants NAC (N-acetylcysteine) and BSO (buthionine sulfoximine) measured the cell viability and intracellular ROS., Results: Feq 3 induced the death of HNSCC cells and caused them to exhibit the morphological features of apoptosis. Feq 3 also induced apoptosis of SCC9 cells by cell cycle arrest during the G 2 /M phase and the induced arrest of SCC25 cells in the G 0 /G 1 and G 2 /M phases, which was associated with decreased cyclin B1/cdc2 and cyclin D/cdk4 expressions. Feq 3 increases reactive oxygen species (ROS) and reduces glutathione (GSH) levels, and responds to increased p53 and p21 expressions. Feq 3 induced apoptosis by mitochondria-mediated Bax and cytochrome c up-expression and down-expression Bcl-2. Feq 3 also up-regulated tBid, which interacts with the mitochondrial pathway and tumor necrosis factor-α (TNF-α)/TNF-Rs, FasL/Fas, and TNF-related apoptosis inducing ligand receptors (TRAIL-Rs)/TRAIL-dependent caspases apoptotic signaling pathway in HNSCC cells. However, Feq 3 activates Fas but not FasL in SCC25 cells. Feq 3 arrests the growth of HNSCC cells and is involved in the mitochondria- and death receptor (DR)-mediated caspases apoptotic pathway., Conclusion: This study is the first to suggest that apoptosis mediates the anti-HNSCC of Feq 3 . Feq 3 has potential as a cancer therapeutic agent against HNSCC., (Copyright © 2019. Published by Elsevier GmbH.)

The diverse expression pattern of CD36 reflects its multiple cellular functions. However, the roles of CD36 in colorectal cancer (CRC) remain unknown. Here, we discover that CD36 expression is progressively decreased from adenomas to carcinomas. CD36 loss predicts poor survival of CRC patients. In CRC cells, CD36 acts as a tumor suppressor and inhibits aerobic glycolysis in vitro and in vivo. Mechanically, CD36-Glypcian 4 (GPC4) interaction could promote the proteasome-dependent ubiquitination of GPC4, followed by inhibition of β-catenin/c-myc signaling and suppression of downstream glycolytic target genes GLUT1, HK2, PKM2 and LDHA. Moreover, disruption of CD36 in inflammation-induced CRC model as well as Apc Min/+ mice model significantly increased colorectal tumorigenesis. Our results reveal a CD36-GPC4-β-catenin-c-myc signaling axis that regulates glycolysis in CRC development and may provide an intervention strategy for CRC prevention.

Purpose: To investigate the changes and underlying mechanisms in parents' safety awareness and the use of child safety seats after the mandatory legislation in Shanghai city, China., Methods: This study was carried out by Shanghai Key Laboratory of Environment and Children's Health using a multi-stage, simple random sampling method. Volunteers with children aged 0-12 months were recruited. Child safety seats were sent to each volunteer's family. Telephone encounters and/or on-site visits were used to collect data from parents using a phased survey on children's safety during car use., Results: Among all respondents, 91.2% had heard of motor vehicle accidents involving children, and 97.2% could describe the appropriate use of a safety seat to minimize the risk of child injury in a collision. Among 1078 families with newborns, awareness of child safety seats was 91.9%. There were 86% patients aware that new laws and regulations have been released regarding the use of child safety seats, and 98.5% of them plan to comply with the new laws. Moreover, 61% patients think that taxis should be routinely equipped with child safety seats., Conclusion: The parents in Shanghai obtained a high level of awareness of children's traffic safety after the introduction of child safety seats legislation, and had a positive experience related to the use of child safety seats. Taxi may be an important area of focus for implementation of child traffic safety. Traffic safety laws and regulations with further impact should be continuously studied., (Copyright © 2019. Production and hosting by Elsevier B.V.)

The poor prognosis of hepatocellular carcinoma (HCC) is resulted from tumor metastasis. Signaling pathways triggered by deregulated receptor tyrosine kinases (RTKs) were the promising therapeutic targets for prevention of HCC progression. However, RTK-based target therapy using conventional kinase-based inhibitors was often hampered by resistances due to compensatory RTKs signaling. Herein, we report that Ling-Zhi-8 (LZ-8), a medicinal peptide from Ganoderma lucidium , was effective in suppressing cell migration of HCC413, by decreasing the amount and activity of various RTKs. These led to the suppression of downstream signaling including phosphorylated JNK, ERK involved in HCC progression. The capability of LZ-8 in targeting multiple RTKs was ascribed to its simultaneous binding to these RTKs. LZ-8 may bind on the N -linked glycan motif of RTKs that is required for their maturation and function. Notably, pretreatment of the N -glycan trimming enzyme PNGase or inhibitors of the mannosidase ( N -glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN), prevented LZ-8 binding on the aforementioned RTKs and rescued the downstream signaling and cell migration suppressed by LZ-8. Moreover, pretreatment of KIF prevented LZ-8 triggered suppression of tumor growth of HCC413. Our study suggested that a specific type of N -glycan is the potential target for LZ-8 to bind on multiple RTKs for suppressing HCC progression.

Postcardiac arrest syndrome yields poor neurological outcomes, but the mechanisms underlying this condition remain poorly understood. Autophagy plays an important role in neuronal apoptosis induced by ischemia. However, whether autophagy is involved in neuron apoptosis induced by cardiac arrest has been less studied. This study found that TRPML1 participates in cerebral ischemic reperfusion injury. Primary neurons were isolated and treated with mucolipin synthetic agonist 1 (ML-SA1), as well as infected with the recombinant lentivirus TRPML1 overexpression vector in vitro . ML-SA1 was delivered intracerebroventricularly in transient global ischemia model. Protein expression levels were determined by western blot. Neurological deficit score and the infarct volume were analyzed for the detection of neuronal damage. We found that TRPML1 was significantly downregulated in vivo and in vitro ischemic reperfusion model. We also observed that TRPML1 overexpression or treatment with the ML-SA1 attenuated neuronal death in primary neurons and ameliorated neurological dysfunction in vivo. Our findings suggested that autophagy and apoptosis were activated after transient global ischemia. Administration of ML-SA1 before transient global ischemia ameliorated neurological dysfunction possibly through the promotion of autophagy and the inhibition of apoptosis.

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is revolutionizing the management of brain metastases (BMs). This study was to explore the value of upfront cranial radiotherapy (RT) in EGFR-mutated non-small cell lung cancer (NSCLC) with BMs compared with EGFR-TKIs alone. Methods: We searched all topic-related comparative articles in public databases (MEDLINE, EMBASE, Cochrane Library, and Web of Science) and conference proceedings. Outcomes of interest were intracranial objective response rate (ORR), overall survival (OS), and intracranial progression-free survival (PFS). Statistical analyses were calculated using Review Manager 5.3 software. Results: Thirteen comparative studies that included a total of 1,456 patients were eligible. Upfront brain RT had significantly higher OS (HR = 0.78, 95% CI = 0.65-0.93, P = 0.005) than EGFR-TKI alone. Upfront RT plus TKI had superior OS (HR = 0.71, 95% CI = 0.58-0.86, P = 0.0005) and intracranial PFS (HR = 0.69, 95% CI = 0.49-0.99, P = 0.04). The pooled data favored upfront whole brain RT (WBRT) plus TKI in terms of intracranial PFS (HR = 0.64, 95% CI = 0.48-0.85, P = 0.002) and OS (HR = 0.75, 95% CI = 0.57-1, P = 0.05). Upfront stereotactic radiosurgery (SRS) was associated with better OS (HR = 0.37, 95% CI = 0.26-0.54, P < 0.00001). Similar results were observed when analysis was restricted to the use of erlotinib or geftinib. Conclusions: The upfront use of brain RT seemed critical, especially for SRS. Upfront administration of upfront WBRT plus EGFR-TKI had better survival outcomes and seemed superior to EGFR-TKI alone.

Depression is a mental illness comorbid risk factor for glucose intolerance worldwide. Chaihu-shugan san, a 'Shu-Gan' formula in traditional Chinese medicine, is clinically used in the treatment of depression. The aim of this study was to investigate whether Chaihu-shugan san improved glucose tolerance with its antidepressant activity in rat model of depression and explore the mechanisms underlying its action on liver-brain inflammation axis. After 6 weeks of chronic unpredictable mild stress (CUMS) procedure, male Wistar rats were given Chaihu-shugan san water extract (925 and 1850 mg/kg) by gavage for the next 6 consecutive weeks. Sucrose consumption test was used to assess animal depressive-like behaviors. Oral glucose tolerance test (OGTT) was employed to define the status of glucose tolerance in rats. Serum alanine aminotransferase (ALT) and interleukin-1 beta (IL-1β) were measured by commercial kits, respectively. Western blot was used to detect the expression of key proteins in inflammatory signaling cascades including toll-like receptor 4 (TLR4), myeloid differentiation protein 88 (MyD88), nuclear factor-kappa B (NF-κB), Nod-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), cysteinyl aspartate specific proteinase-1 (Caspase-1) and IL-1β, as well as insulin signaling in liver and prefrontal cortex of rats. Immunohistochemical staining or immunofluorescence staining of NF-κB, and nuclear/cytoplasmic ratio of NF-κB by Western blot were used to describe its nuclear entry in liver and prefrontal cortex of rats. RT-qPCR and Western blot analysis, as well as microRNA-155 (miR-155) mimic or inhibitor transfection were used to explore possible association of MyD88 and miR-155. In this study, Chaihu-shugan san increased sucrose consumption and reduced serum glucose levels in CUMS rats, showing its antidepressant activity with glucose tolerance improvement. Chaihu-shugan san reduced serum levels of ALT and IL-1β in this animal model. Furthermore, this formula inhibited hepatic and prefrontal cortical inflammatory response by suppressing TLR4/MyD88/NF-κB pathway and NLRP3 inflammasome activation, and improved insulin signaling in CUMS rats. More importantly, Chaihu-shugan san up-regulated miR-155 expression in liver and prefrontal cortex of CUMS rats. These results provide direct evidence that Chaihushugan San can ameliorate depressive-like behaviors by inhibiting liver-brain inflammation axis., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

This paper discusses the need to incorporate equity assessment into the planning and monitoring of sanitation service delivery to South African informal settlements. Equity assessment criteria were drawn from literature and a study of sanitation service delivery to informal settlements in three South African municipalities (Cape Town, Johannesburg and eThekwini) over the period 2012-2015. Three key dimensions of equity - resource allocation, access and stakeholder perceptions - were identified. These had eight associated criteria: (1) funds allocated for basic sanitation, (2) number of staff allocated to informal settlements, (3) disparities in access, (4) proportion of functioning sanitation facilities, (5) menstrual hygiene management (MHM) inclusion, (6) access to information, (7) meets users' notions of dignity, and (8) integration of the perspectives of key stakeholders. Key findings of the study indicate that the current focus on reducing service backlogs largely ignores equity and there is a need to better address this through the incorporation of: equity assessments, improving access to information, and the inclusion of marginalised communities in the planning of sanitation services., (© 2018 The Authors.)

Using data of 200, 522, 572, and 287 Chinese from Australia, China, Hong Kong and Taiwan respectively, this study aimed at comparing the mental health literacy of Chinese people from different communities, and between Chinese communities and the Australian general public. The participants were asked questions that assessed their recognition of depression and schizophrenia. Compared with the Australians, much lower percentages of Chinese in the four Chinese communities could correctly identify depression and early schizophrenia. Commonalities in the preference for 'psychiatrist', 'psychologist', 'Chinese medical doctor', and 'Chinese traditional healer', a lack of knowledge of medications, and a higher likelihood of endorsement of traditional Chinese medicines were found among the four Chinese communities. Differences in the preference for 'general practitioner' and 'social worker', and a higher percentage of endorsement of herbal medicines were observed among the different Chinese communities. Cultural factors such as Chinese perceptions of mental illness, and socio-contextual factors such as differences in mental health care system in the four communities were offered to explain these commonalities and differences. Mental health promotion programmes for Chinese people may need to consider the above-mentioned cultural and socio-contextual factors so that specific promotion programmes can be developed., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Few studies have been performed to explore mental health literacy and stigmatising attitudes towards mental illness and their relationships with causal beliefs about mental illness among Chinese people in Taiwan., Aims: Using a comparative approach, this study attempted to compare the mental health literacy and stigmatising attitudes of Taiwanese Chinese with those found among Australian and Japanese participants in other studies and to explore how mental health literacy and stigmatising attitudes relate to different perceptions of causes of mental illness., Methods: A convenience sample of 287 participants completed a battery of standardised questionnaires., Results: A much lower percentage of Taiwanese people than Australians could correctly identify depression and schizophrenia. The Taiwanese respondents rated psychiatrists and clinical psychologists as more helpful than social workers and general practitioners (GPs) and expressed more uncertainty about the usefulness of certain medications when compared to the Australian and Japanese samples. Interestingly, Taiwanese Chinese hold similarly high levels of stigma towards schizophrenia, but lower levels of stigma towards depression when compared to the Japanese respondents. Taiwanese respondents who have higher levels of mental health literacy about schizophrenia were less willing to interact with people with schizophrenia than those with lower levels of mental health literacy., Conclusion: This study underlines the need for public education programmes to improve knowledge of various mental illnesses and to reduce stigmatising attitudes among Taiwanese Chinese. The aforementioned socially and culturally driven beliefs must be taken into consideration so that culturally relevant education programmes can be developed.

Pathologic complete remission after neoadjuvant chemotherapy has a role in guiding the management of breast cancer. The present meta-analysis examined the accuracy of contrast-enhanced magnetic resonance imaging (CE-MRI) and diffusion-weighted magnetic resonance imaging (DW-MRI) in detecting the response to neoadjuvant chemotherapy and compared CE-MRI with ultrasonography, mammography, and positron emission tomography/computed tomography (PET/CT). Medical subject heading terms and related keywords were searched to generate a compilation of eligible studies. The pooled sensitivity, specificity, diagnostic odds ratio, area under summary receiver operating characteristic curve (AUC), and Youden index (Q* index) were used to estimate the diagnostic efficacy of CE-MRI, DW-MRI, ultrasonography, mammography, and PET/CT. A total of 54 studies of CE-MRI and 8 studies of DW-MRI were included. The overall AUC and the Q* index values for CE-MRI and DW-MRI were 0.88 and 0.94 and 0.80 and 0.85, respectively. According to the summary receiver operating characteristic curves, CE-MRI resulted in a higher AUC value and Q* index compared with ultrasonography and mammography but had values similar to those of DW-MRI and PET/CT. CE-MRI accurately assessed pathologic complete remission in specificity, and PET/CT and DW-MRI accurately assessed pathologic complete remission in sensitivity. The present meta-analysis indicates that CE-MRI has high specificity and DW-MRI has high sensitivity in predicting pathologic complete remission after neoadjuvant chemotherapy. CE-MRI is more accurate than ultrasonography or mammography. Additionally, PET/CT is valuable for predicting pathologic complete remission. CE-MRI, combined with PET/CT or DW-MRI, might allow for a more precise assessment of pathologic complete remission., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Isoquercetin has exhibited a wide range of therapeutic properties, including antioxidant, anti-inflammatory and anti-allergic activities. The aim of the present study was to investigate the effect of isoquercetin on rats with 2 h middle cerebral artery occlusion (MCAO) and evaluate the neuroprotective effect of isoquercetin on a primary culture of rat hippocampal neuronal cells subjected to oxygen-glucose deprivation followed by reoxygenation (OGD/R). In vivo , the rats treated with isoquercetin exhibited a lower degree of neurological dysfunction and smaller infarct volume than the vehicle-treated rats. In vitro , it was found that isoquercetin prevented the OGD/R-induced increase in apoptosis, lactate dehydrogenase release and reduction in cell viability. Additionally, isoquercetin induced the upregulation of nuclear factor erythroid 2-related factor 2 gene and protein expression, and increased extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation. This indicates that the ERK1/2 pathway may contribute to the neuroprotective effect of isoquercetin against OGD/R-induced oxidative damage in rat hippocampal neurons. These findings suggest the potential importance of isoquercetin in the treatment of ischemia/reperfusion-related brain injury and associated diseases.

Objective: To identify specific miRNAs involved in sepsis-induced AKI and to explore their targeting pathways., Methods: The expression profiles of miRNAs in serum from patients with sepsis-induced AKI (n = 6), sepsis-non AKI (n = 6), and healthy volunteers (n = 3) were investigated by microarray assay and validated by quantitative PCR (qPCR). The targets of the differentially expressed miRNAs were predicted by Target Scan, mirbase and Miranda. Then the significant functions and involvement in signaling pathways of gene ontology (GO) and KEGG pathways were analyzed. Furthermore, eight miRNAs were randomly selected out of the differentially expressed miRNAs for further testing by qPCR., Results: qPCR analysis confirmed that the expressions levels of hsa-miR-23a-3p, hsa-miR-4456, hsa-miR-142-5p, hsa-miR-22-3p and hsa-miR-191-5p were significantly lower in patients with sepsis compared with the healthy volunteers, while hsa-miR-4270, hsa-miR-4321, hsa-miR-3165 were higher in the sepsis patients. Statistically, miR-4321; miR-4270 were significantly upregulated in the sepsis-induced AKI compared with sepsis-non AKI, while only miR-4321 significantly overexpressed in the sepsis groups compared with control groups. GO analysis showed that biological processes regulated by the predicted target genes included diverse terms. They were related to kidney development, regulation of nitrogen compound metabolic process, regulation of cellular metabolic process, cellular response to oxidative stress, mitochondrial outer membrane permeabilization, etc. Pathway analysis showed that several significant pathways of the predicted target genes related to oxidative stress. miR-4321 was involved in regulating AKT1, mTOR and NOX5 expression while miR-4270 was involved in regulating PPARGC1A, AKT3, NOX5, PIK3C3, WNT1 expression. Function and pathway analysis highlighted the possible involvement of miRNA-deregulated mRNAs in oxidative stress and mitochondrial dysfunction., Conclusion: This study might help to improve understanding of the relationship between serum miRNAs and sepsis-induced AKI, and laid an important foundation for further identification of the potential mechanisms of sepsis-induced AKI and oxidative stress and mitochondrial dysfunction.

Objective: Transforming growth factor β (TGF-β) plays crucial roles in Ang II-induced cardiac fibrosis (CF). Phosphocreatine (PCr), one of the important players involved in cellular energy metabolism, is widely used in the treatment of clinical heart failure. However, whether it participates in CF is still unclear. This study aimed to identify the mechanisms involved in PCr and CF., Materials and Methods: Rat cardiomyocytes (H9C2) were induced by Ang II followed by treatment of PCr. ERK1 siRNA, ERK2 siRNA and NF-κB siRNA were applied to identify the molecular mechanism. Then CF-related proteins were analyzed by western blot and real-time PCR to confirm the influence of the mechanisms involved in PCr., Results: PCr did protect cardiomyocytes from Ang II-induced fibrosis. Meanwhile, PCr suppressed Ang II-induced up-regulation of TGF-β. By detecting TGFβ-mediated or MAPK pathway associated proteins, PCr inhibited MAPK and NF-κB pathway, thus suppressed Ang II-induced cardiac fibrosis, which was further confirmed by siRNA transfection., Conclusions: Our study determined that PCr protected cardiomyocytes from Ang II-induced CF through inhibition of MAPK and NF-κB pathway.

Background: Acute ischemic stroke (AIS) is a worldwide serious health problem. Intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rt-PA) is the standard treatment; however, only a small number of patients benefit from it due to the strict application restrictions. Recently, more and more evidence prove mechanical thrombectomy is an effective and safe therapy of AIS., Patients and Methods: From December 2010 to March 2015, 83 patients who underwent mechanical thrombectomy were collected as a sample pool. All patients met the following criteria: National Institutes of Health Stroke Scale (NIHSS) score ≥10, treatment performed within 6 h from the onset of symptoms, no large hypodensity on CT or multimodal MRI, and angiography revealed occlusion of a major cerebral artery. Recanalization rates were assessed immediately post-procedure by follow-up angiography according to the thrombolysis in cerebral infarction score criteria. Assessment of the modified Rankin Scale was performed 90 days after treatment., Results: The mean age of patients was 63.3 years, and NIHSS scores 19.12 ± 4.60 at presentation. The vessel occlusions occurred in the middle cerebral artery (68.7%), distal internal carotid artery (7.2%), internal carotid artery with tandem middle cerebral artery occlusion (14.5%), basilar artery (2.4%), and vertebral artery (7.2%). Successful recanalization (TICI 3/2b) was achieved in 56 of 83 patients (67.5%). At 90-day follow-up, good clinical outcome (mRS ≤ 2) was achieved in 33 of 83 patients (39.8%), while 20 patients died (24.1%)., Conclusions: This study revealed mechanical thrombectomy with Solitaire stent device was an effective and safe therapy, which achieved a high rate of angiographic recanalization and independent outcome accompanied by a low mortality rate., (Copyright © 2016. Published by Elsevier Ltd.)

Hepatocyte growth factor (HGF) and its receptor c-Met were frequently deregulated in hepatocellular carcinoma (HCC). Signaling pathways activated by HGF-c-Met are promising targets for preventing HCC progression. HGF can induce the reactive oxygen species (ROS) signaling for cell adhesion, migration and invasion of tumors including HCC. On the other hand, extracellular signal-regulated kinases (ERK), member of mitogen activated kinase, can be activated by ROS for a lot of cellular processes. As expected, HGF-induced phosphorylation of ERK and progression of HCC cell HepG2 were suppressed by ROS scavengers. By N-(biotinoyl)-N'-(iodoacetyl)-ethylenediamine (BIAM) labeling method, a lot of cysteine (-SH)-containing proteins with M.W. 50-75 kD were decreased in HepG2 treated with HGF or two other ROS generators, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and phenazine methosulfate. These redox sensitive proteins were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Among them, two chaperones, heat shock protein 60 (HSP60) and protein disulfide isomerase (PDI), were found to be the most common redox sensitive proteins in responding to all three agonists. Affinity blot of BIAM-labeled, immunoprecipitated HSP60 and PDI verified that HGF can decrease the cysteine (-SH) containing HSP60 and PDI. On the other hand, HGF and TPA increased cysteinyl glutathione-containing HSP60, consistent with the decrease of cysteine (-SH)-containing HSP60. Moreover, depletion of HSP60 and PDI or expression of dominant negative mutant of HSP60 with alteration of Cys, effectively prevented HGF-induced ERK phosphorylation and HepG2 migration.In conclusion, the redox sensitive HSP60 and PDI are required for HGF-induced ROS signaling and potential targets for preventing HCC progressions.

The aim of the present study was to investigate the effects of high mobility group protein B1 (HMGB1), which is expressed in the serum of patients with sepsis, on vascular endothelial permeability. Sera from patients with sepsis were used to treat endothelial cells (ECs), and the effect on endothelial permeability was evaluated using immunofluorescence. The morphologies of endothelial cytoskeletal actin and vascular endothelial (VE)‑cadherin were assessed using laser scanning confocal microscopy. The protein expression levels of HMGB1, B‑cell lymphoma 2 (BCL‑2) and BCL‑2‑associated X protein (BAX) were detected using western blotting. EC apoptosis was measured using flow cytometry. The results demonstrated that HMGB1 was significantly expressed in the serum 24 h following the onset of sepsis, and the expression levels peaked at 48 h, which were sustained until 96 h post‑onset. Compared with the control group, treatment of the ECs with 20% septic serum in vitro significantly increased endothelial monolayer permeability (P<0.01), markedly induced transcellular filamentous (F)‑actin rearrangement with stress fiber formation, and resulted in the localization of VE‑cadherin fragmentations at the cell borders with increased gaps between ECs. Furthermore, flow cytometry showed that the apoptotic rate of ECs was significantly increased following treatment with septic serum. In addition, the expression levels of BAX were significantly increased, whereas the expression levels of BCL‑2 were significantly decreased. Pretreatment with an HMGBI inhibitor (ethyl pyruvate; 5 µM) 24 h prior to treatment with the septic serum attenuated the effects of septic serum treatment. Together, these findings suggested that treatment of ECs with sera from patients with sepsis may induce the loss of vascular endothelial monolayer integrity, elicit the formation of endothelial F‑actin stress fibers and initiate VE‑cadherin redistribution, which may be attributed to high levels of HMGB1 in the serum. This mechanism also appears to involve changes in the activation of BAX and BCL‑2, resulting in EC apoptosis.

One of the signaling components involved in hepatocellular carcinoma (HCC) progression is the focal adhesion adaptor paxillin. Hydrogen peroxide inducible clone-5 (Hic-5), one of the paralogs of paxillin, exhibits many biological functions distinct from paxillin, but may cooperate with paxillin to trigger tumor progression. Screening of Hic-5 in 145 surgical HCCs demonstrated overexpression of Hic-5 correlated well with intra- and extra-hepatic metastasis. Hic-5 highly expressed in the patient derived HCCs with high motility such as HCC329 and HCC353 but not in the HCCs with low motility such as HCC340. Blockade of Hic-5 expression prevented constitutive migration of HCC329 and HCC353 and HGF-induced cell migration of HCC340. HCC329Hic-5(-), HCC353Hic-5(-), HCC372Hic-5(-), the HCCs stably depleted of Hic-5, exhibited reduced motility compared with each HCC expressing Scramble shRNA. Moreover, intra/extrahepatic metastasis of HCC329Hic-5(-) in SCID mice greatly decreased compared with HCC329Scramble. On the other hand, ectopic Hic-5 expression in HCC340 promoted its progression. Constitutive and HGF-induced Hic-5 expression in HCCs were suppressed by the reactive oxygen species (ROS) scavengers catalase and dithiotheritol and c-Jun N-terminal kinase (JNK) inhibitor SP600125. On the contrary, depletion of Hic-5 blocked constitutive and HGF-induced ROS generation and JNK phosphorylation in HCCs. Also, ectopic expression of Hic-5 enhanced ROS generation and JNK phosphorylation. These highlighted that Hic-5 plays a central role in the positive feedback ROS-JNK signal cascade. Finally, the Chinese herbal derived anti-HCC peptide LZ-8 suppressed constitutive Hic-5 expression and JNK phosphorylation. In conclusion, Hic-5 mediates ROS-JNK signaling and may serve as a therapeutic target for prevention of HCC progression.

Background: Nonverbal pediatric patients such as infants are unable to describe their pain, which leads to the lack of a gold standard scale for their pain assessment. The aim of this study was to estimate the diagnostic performance of Face, Legs, Activity, Cry, and Consolability (FLACC) scale and Neonatal Infant Pain Scale (NIPS) for infants' pain in the absence of a gold standard., Methods: This prospective observational study recruited 202 postoperative infants, aged <12 months. Postoperative pain intensity was evaluated using FLACC and NIPS scales. The diagnostic performance of these two scales was to estimate using a Bayesian latent class model with conditional dependence. McNemar's test was applied to test whether NIPS and FLACC tests differ from each other., Results: Under a combined model with conditional dependence, the median posterior sensitivity and specificity of the FLACC were 89.94% (95% CI: 78.48-96.83%) and 87.82% (95% CI: 78.6-95.23%), respectively. The sensitivity and specificity of the NIPS were 85.94% (95% CI: 72.15-95.6%) and 92.61% (84.05-97.52%), respectively. McNemar's test demonstrated no significant difference between FLACC and NIPS in either sensitivity or specificity., Conclusion: Both the FLACC and NIPS have excellent sensitivity and specificity for pain assessment in infants. The comparison test showed that the FLACC scale was no different to the NIPS scale in sensitivity and specificity., (© 2015 John Wiley & Sons Ltd.)

We aimed to compare the therapeutic effect of recombinant tissue plasminogen activator (rt-PA) administered at different time windows within the first 6 hours after onset of acute ischemic stroke (AIS). A retrospective analysis was performed of data collected from 194 patients who received rt-PA thrombolysis within 4.5 hours after AIS onset and from 29 patients who received rt-PA thrombolysis between 4.5-6 hours after AIS onset. The National Institutes of Health Stroke Scale (NIHSS) scores were statistically decreased in both groups (P < 0.05) at 24 hours and 7 days after onset. There was no statistical difference in the modified Rankin score or mortality at day 90 after treatment between the two groups (P > 0.05). In conclusion, AIS patients who received rt-PA treatment between 4.5-6 hours after onset were similar in therapeutic efficacy to those who received rt-PA within 4.5 hours after onset. Our results suggest that intravenous thrombolytic therapy for AIS within 4.5-6 hours after onset is effective and safe.

Hepatocyte growth factor (HGF) induced c-Met signaling play critical roles in the progression of hepatocellular carcinoma (HCC). However, c-Met targeting approaches suffered resistance and side effect, thus identification of more suitable downstream targets is needed. Recently, we demonstrated HGF-induced fluctuant ERK/paxillin signaling within 24h. We further examined the underlying mechanisms for fluctuant c-Met/JNK/paxillin signal cascade within 12h. HGF-induced phosphorylation of c-Met, JNK, and paxillin (Ser178) shared a common fluctuation pattern characterized by an initial peak at 0.5h, a middle drop at 4h, and a later peak at 10h. Dynasore, the inhibitor of dynamin, suppressed HGF-induced c-Met internalization and phosphorylation of JNK and paxillin (Ser178) at 0.5h, indicating that endosome formation is required for initial signal enhancement. Further, depletion of PKCε not only enhanced HGF-induced phosphorylation of JNK and paxillin (Ser178) but also prevented c-Met degradation at 0.5h, suggesting that PKCε mediated c-Met degradation for signal declination. On the other hand, HGF induced colocalizations of both phosphorylated JNK and paxillin with the endosomal recycling protein GGA3 at 10h and depletion of GGA3 abolished membrane recycling of c-Met and phosphorylation of JNK/paxillin at the same time point. Interestingly, HGF induced GGA3 phosphorylation in a PKCε-dependent manner during 0.5-4h, which is associated with c-Met degradation in the same period. Finally, HGF-induced cell migration, invasion and intrahepatic metastasis of HepG2 were prevented by the inhibitors of endocytosis. Our results suggest that critical endosomal components are promising therapeutic targets for preventing HGF-induced progression of HCC., (Copyright © 2015 Elsevier Inc. All rights reserved.)