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Chien-Tzu Lee,1 Ping-Lun Hsieh,1,2 Meng-Yueh Chien,1 Jung-Yien Chien,3 Huey-Dong Wu,4 Jia-Shin Lin,1 Hsiao-Chen Lin,1 Pei-Yu Yang,2 Li-Ying Wang1,21School and Graduate Institute of Physical Therapy, College of Medicine, National Taiwan University, Taipei, Taiwan; 2Physical Therapy Center, National Taiwan University Hospital, Taipei, Taiwan; 3Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 4Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital, Taipei, TaiwanBackground: Pulmonary rehabilitation (PR) is now considered fundamental when managing patients with chronic respiratory disease. The individual variation in functional exercise capacity (FEC) response to PR within the cohort is unknown. The purpose of this study was to identify FEC patterns in response to PR in patients with chronic respiratory disease using the trajectory modeling method.Methods: The data of 67 patients with the chronic respiratory disease were retrospectively reviewed and analyzed in this study. All patients received once-weekly supervised training for 8 weeks. Six-minute walk distance (6MWD) was used to measure FEC. Muscle strength and 6MWD were assessed at baseline, Week 4, Week 8 and monthly for two months after PR completion. Group-based trajectory modeling (GBTM) was used to identify patterns in 6MWD in response to PR. The generalized estimating equation method was then used to detect the differences within and between the trajectories of identified groups across time.Results: Patients were grouped into low- (n=13), moderate- (n=34) and high- (n=20) FEC group based on GBTM analysis. All groups demonstrated significant improvements in 6MWD and leg muscle strength after 8-week PR. Compared to the high-FEC group, a greater proportion of the patients in the low-FEC group required oxygen supplementation during training and had worse baseline leg muscle strength.Conclusions: Patients showed distinct patterns of 6MWD changes in response to 8-week PR. Distinct characteristics for the low-FEC group included poor lower extremity strength and a greater proportion of required oxygen use at home and during training.Keywords: chronic respiratory disease, exercise training, functional exercise capacity, trajectory

Li-Ying Wang,1,2 Huey-Dong Wu,3 Kuan-Yu Chen,4 Chen-Hsi Hsieh,5–7 Chung-Chun Lai21School and Graduate Institute of Physical Therapy, College of Medicine, National Taiwan University, Taiwan; 2Physical Therapy Center, National Taiwan University Hospital, Taipei, Taiwan; 3Department of Integrated Diagnostic & Therapeutics, National Taiwan University Hospital, Taipei, Taiwan; 4Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 5Department of Radiation Oncology, Far Eastern Memorial Hospital, Taipei, Taiwan; 6Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 7Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROCBackground: The functional exercise capacity and its correlates in advanced cancer patients in stratified age groups were examined.Materials and methods: A total of 105 patients with advanced lung cancer were recruited prospectively and stratified into young (≤50 years), middle (51–65 years), and old (>65 years) age groups. Respiratory performances, which included maximal inspiratory and expiratory pressure, forced expiratory volume in 1 second, and forced vital capacity were measured. The distance ambulated in a 6-minute walk test was used as an indicator for functional capacity.Results: The young age group had lowest baseline pulmonary function and performed worse on the 6-minute walk test among the three age groups. The risk factors for poor functional capacity were female, lower percent predicted maximal expiratory pressure, worse dyspnea, and lower hemoglobin in the young age group; lower percent predicated forced expiratory volume in 1 second and forced vital capacity, and greater weight loss in the middle age group; and only worse dyspnea in the old age group. The above identified risk factors accounted for 73.6%, 58.5%, and 42.1% variance in 6-minute walk distance for the young, middle, and old age group, respectively.Conclusion: The impacts of these factors on functional exercise capacity should be carefully considered while designing exercise intervention according to age.Keywords: age, 6-minute walk test, advanced lung cancer, respiratory muscle strength, spirometry

Background: The prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with chronic hepatitis B (CHB) has increased in recent clinical practice; however, the relationship between CHB and hepatic steatosis (HS) remains controversial., Aim: To shed light on the potential association between NAFLD and hepatitis B virus (HBV) infection., Methods: We conducted a systematic literature search using multiple databases, including PubMed, the Cochrane Library, Web of Science, and EMBASE, to identify relevant studies. Predefined inclusion criteria were used to determine the eligibility of the studies for further analysis., Results: Comprehensive meta-analysis software was used for statistical analysis, which covered 20 studies. The results indicated a lower NAFLD susceptibility in HBV-infected individuals (pooled OR = 0.87; 95%CI = 0.69-1.08; I 2 = 91.1%), with diabetes ( P = 0.015), body mass index (BMI; P = 0.010), and possibly age ( P = 0.061) as heterogeneity sources. Of note, in four studies (6197 HBV patients), HBV-infected individuals had a reduced NAFLD risk (OR = 0.68, 95%CI = 0.51-0.89, P = 0.006). A positive link between hyperlipidemia and metabolic syndrome emerged in hepatitis B patients, along with specific biochemical indicators, including BMI, creatinine, uric acid, fasting blood glucose, and homeostasis model assessment of insulin resistance., Conclusion: HBV infection may provide protection against HS; however, the occurrence of HS in patients with HBV infection is associated with metabolic syndrome and specific biochemical parameters., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Stretching exercise is generally used for improving flexibility. However, its application to promote orthotic treatment for patients with adolescent idiopathic scoliosis (AIS) remains unknown., Objective: This study was to explore the effect of pre-orthosis stretching exercises on spinal flexibility and initial in-orthosis correction for the patients with AIS., Study Design: A pilot-controlled study., Methods: An experimental group (EG) of 13 subjects (10 girls and 3 boys) with AIS allocating to self-stretching exercises and a control group (CG) of 19 AIS subjects (14 girls and 5 boys) with no stretching before orthosis fitting were recruited. The spinal flexibility of the EG was evaluated with an ultrasound imaging system and physical measurements. The initial in-orthosis correction rates between the 2 groups were compared with the independent t test, and the correlation analysis between the spinal flexibility measured from ultrasound images and physical measurement was performed with the Pearson correlation test., Results: The initial Cobb angle of EG and CG were 25.70° ± 7.30° and 28.09° ± 5.58°, respectively. No significant difference was observed between the initial in-orthosis Cobb angle of EG (11.13° ± 6.80°) and CG (15.65° ± 9.10°) (p = 0.06). However, the spinal flexibility after stretching exercises was improved (p < 0.001), and the spinal flexibility changes measured with ultrasound and physical forward-bending method were significantly correlated (r = 0.57, p < 0.05)., Conclusion: Stretching exercises before orthotic treatment could improve the spinal flexibility but did not cause a better in-orthosis correction. A study with a larger sample size and longer follow-up period should be conducted to investigate the long-term effect of stretching exercises., (Copyright © 2024 International Society for Prosthetics and Orthotics.)

Maintaining blood-brain barrier (BBB) integrity is critical components of therapeutic approach for ischemic stroke. Fibroblast growth factor 17 (FGF17), a member of FGF8 superfamily, exhibits the strongest expression throughout the wall of all major arteries during development. However, its molecular action and potential protective role on brain endothelial cells after stroke remains unclear. Here, we observed reduced levels of FGF17 in the serum of patients with ischemic stroke, as well as in the brains of mice subjected to middle cerebral artery occlusion (MCAO) injury and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced brain microvascular endothelial cells (bEnd.3) cells. Moreover, treatment with exogenous recombinant human FGF17 (rhFGF17) decreased infarct volume, improved neurological deficits, reduced Evans Blue leakage and upregulated the expression of tight junctions in MCAO-injured mice. Meanwhile, rhFGF17 increased cell viability, enhanced trans-endothelial electrical resistance, reduced sodium fluorescein leakage, and alleviated reactive oxygen species (ROS) generation in OGD/R-induced bEnd.3 cells. Mechanistically, the treatment with rhFGF17 resulted in nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear accumulation and upregulation of heme oxygenase-1 (HO-1) expression. Additionally, based on in-vivo and in-vitro research, rhFGF17 exerted protective effects against ischemia/reperfusion (I/R) -induced BBB disruption and endothelial cell apoptosis through the activation of the FGF receptor 3/PI3K/AKT signaling pathway. Overall, our findings indicated that FGF17 may hold promise as a novel therapeutic strategy for ischemic stroke patients., 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 B.V.)

Studies have reported that the hemostatic effect of Sanguisorbae Radix(SR) is significantly enhanced after processing with charcoal. However, the standard components(tannins and gallic acid) specified in the Chinese Pharmacopeia decrease in charcoal-fried Sanguisorbae Radix(CSR), which is contrast to the enhancement of the hemostatic effect. Therefore, this study aimed to optimize the charcoal-frying process of SR based on its hemostatic efficacy and comprehensively analyze the components of SR and its processed products, thus exploring the material basis for the hemostatic effect. The results indicated that SR processed at 250 ℃ for 14 min(14-min CSR) not only complied with the description in the Chinese Pharmacopeia but also demonstrated improved blood-coagulating and blood-adsorbing effects compared with raw SR(P&lt;0.05). Moroever, 14-min CSR reduced the bleeding time in the rat models of tail snipping, liver bleeding, and muscle injury, surpassing both raw and excessively fried SR(16 min processed) as well as tranexamic acid(P&lt;0.05). Ellagitannin, ellagic acid, methyl gallate, pyrogallic acid, protocatechuic acid, Mg, Ca, Mn, Cu, and Zn contributed to the hemostatic effect of CSR over SR. Among these substances, ellagitannin, ellagic acid, Mg, and Ca had high content in the 14 min CSR, reaching(106.73±14.87),(34.86±4.43),(2.81±0.23), and(1.21±0.23) mg·g~(-1), respectively. Additionally, the color difference value(ΔE~*ab) of SR processed to different extents was correlated with the content of the aforementioned hemostatic substances. In summary, this study optimized the charcoal-frying process as 250 ℃ for 14 min for SR based on its hemostatic effect. Furthermore, ellagic acid and/or the powder chromaticity are proposed as indicators for the processing and quality control of CSR.

Background: Cats in respiratory distress have limited tolerance for manipulation, hindering clinical monitoring. Minute volume (MV) can be utilized to rate dyspnea in humans, but its relationship with respiratory distress in cats remains poorly investigated., Hypothesis: Cats with respiratory distress will show higher MV per kg body weight (MV/BW) than normal cats, and the MV/BW increase will correlate with survival., Animals: Fifty-two cats with respiratory distress from lung parenchymal disease, pleural space disease, lower airway obstruction (LAO), or upper airway obstruction were recruited since 2014., Methods: This is a prospective observational study. Study cats were placed in a transparent chamber, allowing clinicians to easily observe their breathing status and record ventilation using barometric whole-body plethysmography (BWBP). Ventilatory variables of the 52 cats were compared with those of 14 historic control cats. Follow-up data, including disease category, clinical outcomes, and survival, were prospectively collected., Results: Cats in respiratory distress demonstrated significantly higher MV/BW (397 mL/kg; range, 158-1240) than normal cats (269 mL/kg; range, 168-389; P < .001). Among the etiologies, cats with LAO, parenchymal, and pleural space disease exhibited higher-than-normal MV/BW trends. A cutoff value of 373 mL/kg (1.4-fold increase) indicated abnormally increased breathing efforts (sensitivity, 67%; specificity, 93%). MV/BW was independently associated with increased cardiorespiratory mortality in cats with respiratory distress (adjusted hazard ratio 1.17, 95% confidence interval [CI] 1.02-1.35; P = .03)., Conclusions and Clinical Importance: Breathing efforts in cats can be noninvasively quantified using BWBP. Measurement of MV/BW could serve as a prognostic index for monitoring cats experiencing respiratory distress., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

NUP155 is reported to be correlated with tumor development. However, the role of NUP155 in tumor physiology and the tumor immune microenvironment (TIME) has not been previously examined. This study comprehensively investigated the expression, immunological function, and prognostic significance of NUP155 in different cancer types. Bioinformatics analysis revealed that NUP155 was upregulated in 26 types of cancer. Additionally, NUP155 upregulation was strongly correlated with advanced pathological or clinical stages and poor prognosis in several cancers. Furthermore, NUP155 was significantly and positively correlated with DNA methylation, tumor mutational burden, microsatellite instability, and stemness score in most cancers. Additionally, NUP155 was also found to be involved in TIME and closely associated with tumor infiltrating immune cells and immunoregulation-related genes. Functional enrichment analysis revealed a strong correlation between NUP155 and immunomodulatory pathways, especially antigen processing and presentation. The role of NUP155 in breast cancer has not been examined. This study, for the first time, demonstrated that NUP155 was upregulated in breast invasive carcinoma (BRCA) cells and revealed its oncogenic role in BRCA using molecular biology experiments. Thus, our study highlights the potential value of NUP155 as a biomarker in the assessment of prognostic prediction, tumor microenvironment and immunotherapeutic response in pan-cancer., (© 2024. The Author(s).)

Aging is a natural process accompanied with a progressive deterioration of cognitive functions. With an aging population, more and more elderly people are suffering from cognitive impairment. Previous studies have paid more attention to the impact of inflammation and oxidative stress on cognitive function during aging. Recently, it has been discovered that neurovascular coupling (NVC), a mechanism regulating cerebral blood flow, may play a significant role in aging-related cognitive impairment. NVC responses regulate the supply of energy substances and oxygen during brain activity, which in turn enhances cognitive function. However, as people grow older, NVC responses gradually weaken, which may be one of the mechanisms underlying aging-induced cognitive impairment. Given the important role of NVC responses in the brain, it is necessary to search for intervention methods that can improve NVC responses and promote cognitive function. Exercise is an effective means to delay aging and improve cognitive function. It also has a certain promoting effect on NVC responses. This article reviews the regulatory mechanisms of NVC responses, the relationship between NVC responses and cognitive function, and explores the effects of aging and exercise intervention on NVC responses, hoping to provide new research ideas for exercise intervention to improve NVC responses and promote cognitive function in the elderly.

Dynamic lower airway obstruction is the primary component of canine bronchomalacia, but the ventilatory function remains underinvestigated. This prospective study analyzed tidal breathing characteristics in 28 dogs, comprising 14 with severe bronchomalacia diagnosed by bronchoscopy versus 14 without respiratory disease. Spirometry was conducted in all dogs. Bronchoscopy with bronchoalveolar lavage or brush under anesthesia was performed in 14 dogs with cough and expiratory effort. Severe bronchomalacia was defined by the severity of collapse and total number of bronchi affected. Ventilatory characteristics were compared between groups. Results revealed that dogs with severe bronchomalacia had lower minute volume (218 vs 338 mL/kg, p = .039) and greater expiratory-to-inspiratory time ratio (1.55 vs 1.35, p = .01) compared to control dogs. The tidal breathing pattern of dogs with bronchomalacia was different from that of normal dogs, and the pattern differed from the concave or flat expiratory curves typical of lower airway obstruction. Compared to control dogs, dogs with severe bronchomalacia had a significantly prolonged low-flow expiratory phase ( p < .001) on the flow-time plot and a more exponential shape of the expiratory curve ( p < .001) on the volume-time plot. Flow-time index ExpLF/Te (>0.14) and volume-time index Vt-AUCexp (≤31%) had a high ROC-AUC (1.00, 95% confidence interval 0.88 to 1.00) in predicting severe bronchomalacia. In conclusion, the tidal breathing pattern identified here indicates abnormal and complicated ventilatory mechanics in dogs with severe bronchomalacia. The role of this pulmonary functional phenotype should be investigated for disease progression and therapeutic monitoring in canine bronchomalacia.

Background: To analyze the predictability of an automatic tube compensation (ATC) screening test compared with the conventional direct liberation test performed before continuous oxygen support for MV liberation., Methods: This retrospective study analyzed tracheostomized patients with prolonged MV in a weaning unit of a medical center in Taiwan. In March 2020, a four-day ATC test to screen patient eligibility for ventilator liberation was implemented, intended to replace the direct liberation test. We compared the predictive accuracy of these two screening methods on the relevant outcomes in the two years before and one year after the implementation of this policy., Results: Of the 403 cases, 246 (61%) and 157 (39%) received direct liberation and ATC screening tests, respectively. These two groups had similar outcomes: successful weaning upon leaving the Respiratory Care Center (RCC), success on day 100 of MV, success at hospital discharge, and in-hospital survival. Receiver operating characteristic curve analysis showed that the ATC screening test had better predictive ability than the direct liberation test for RCC weaning, discharge weaning, 100-day weaning, and in-hospital survival., Conclusion: This closed-circuit ATC screening test before ventilator liberation is a feasible and valuable method for screening PMV patients undergoing ventilator liberation in the pandemic era. Its predictability for a comparison with the open-circuit oxygen test requires further investigation., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Metastasis is a multistep process involving the migration and invasion of cancer cells and is a hallmark of cancer malignancy. Long non-coding RNAs (lncRNAs) play critical roles in the regulation of metastasis. This study aims to elucidate the role of the lncRNA solute carrier organic anion transporter family member 4A1-antisense 1 (SLCO4A1-AS1) in metastasis and its underlying regulatory mechanisms., Methods: A comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify metastasis-associated lncRNAs. Transwell migration and invasion assays, and a tail vein-injection mouse model were used to assess the migration and invasion of cancer cells in vitro and in vivo, respectively. High-throughput screening methods, including MASS Spectrometry and RNA sequencing (RNA-seq), were used to identify the downstream targets of SLCO4A1-AS1. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting, RNA pull-down, RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH), and chromatin immunoprecipitation (ChIp) assays were conducted to identify and validate the underlying regulatory mechanisms of SLCO4A1-AS1., Results: SLCO4A1-AS1 reduced cancer cell migration and invasion by disrupting cytoskeleton filaments, and was associated with longer overall survival in patients with lung adenocarcinoma. SLCO4A1-AS1 directly interacted with the DNA-binding protein, TOX High Mobility Group Box Family Member 4 (TOX4), to inhibit TOX4-induced migration and invasion. Furthermore, RNA-seq revealed that neurotensin receptor 1 (NTSR1) is a novel and convergent downstream target of SLCO4A1-AS1 and TOX4. Mechanistically, SLCO4A1-AS1 functions as a decoy of TOX4 by interrupting its interaction with the NTSR1 promoter and preventing NTSR1 transcription. Functionally, NTSR1 promotes cancer cell migration and invasion through cytoskeletal remodeling, and knockdown of NTSR1 significantly inhibits TOX4-induced migration and invasion., Conclusion: These findings demonstrated that SLCO4A1-AS1 antagonizes TOX4/NTSR1 signaling, underscoring its pivotal role in lung cancer cell migration and invasion. These findings hold promise for the development of novel therapeutic strategies targeting the SLCO4A1-AS1/TOX4/NTSR1 axis as a potential avenue for effective therapeutic intervention in lung cancer., (© 2023. National Science Council of the Republic of China (Taiwan).)

Aims: To investigate the reliability, validity, and level of evidence of applying ultrasound in assessing the lower-limb muscles of patients with cerebral palsy (CP)., Method: Publications in Medline, PubMed, Web of Science, and Embase were searched on May 10, 2023, to identify and examine relevant studies investigating the reliability/validity of ultrasound in evaluating the architecture of CP lower-limb muscles systematically, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 guidelines., Results: Out of 897 records, 9 publications with 111 CP participants aged 3.8-17.0 years were included (8 focused on intra-rater and inter-rater reliability, 2 focused on validity, and 4 were with high quality). The ultrasound-based measurements of muscle thickness (intra-rater only), muscle length, cross-sectional area, muscle volume, fascicle length, and pennation angle showed high reliability, with the majority of intraclass correlation coefficient (ICC) values being larger than 0.9. Moderate-to-good correlations between ultrasound and magnetic resonance imaging measurements existed in muscle thickness and cross-sectional area (0.62 ≤ ICC ≤ 0.82)., Interpretation: Generally, ultrasound has high reliability and validity in evaluating the CP muscle architecture, but this is mainly supported by moderate and limited levels of evidence. More high-quality future studies are needed., (© 2023 Wiley Periodicals LLC.)

Brominated flame-retardants (BFRs) are environmental endocrine disruptors, comprising several pollutants, which potentially affect the endocrine system and cause dysfunction and disease. Widespread BFR exposure may cause multisystem toxicity, including cardiovascular toxicity in some individuals. Studies have shown that BFRs not only increase heart rate, induce arrhythmia and cardiac hypertrophy, but also cause glycolipid metabolism disorders, vascular endothelial dysfunction, and inflammatory responses, all of which potentially induce pre-pathological changes in atherosclerosis. Experimental data indicated that BFRs disrupt gene expression or signaling pathways, which cause vascular endothelial dysfunction, lipid metabolism-related disease, inflammation, and possibly atherosclerosis. Considerable evidence now suggests that BFR exposure may be a pro-atherosclerotic risk factor. In this study, we reviewed putative BFR effects underpinning pro-atherosclerosis mechanisms, and focused on vascular endothelial cell dysfunction, abnormal lipid metabolism, pro-inflammatory cytokine production and foam cell formation. Consequently, we proposed a scientific basis for preventing atherosclerosis by BFRs and provided concepts for further research., 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In this globalization era, institutions are developing strategies including international service-learning pedagogies to integrate global perspectives and dimensions into the learning and teaching processes to develop students' capacity in intercultural competence., Objective: This study aimed to assess the students' intercultural learning outcome through provision of orthotic community service to the less-privileged children., Methods: A Hong Kong-based university collaborated with 2 American universities to conduct an orthotic community service program for the children with cerebral palsy in mainland China. In the process of service delivery, the students with different backgrounds worked closely and students' professional knowledge, intercultural understanding, and communication skills were evaluated. A mixed-method approach was adopted to investigate on how this international program could facilitate meaningful interactions in clinical practices. Preprogram and postprogram surveys and focus group interviews were conducted. Statistical analyses were performed on the quantitative data, while interview data were analyzed thematically., Results: A comparison of preprogram and postprogram surveys showed that the students perceived this community service program important for enhancement of their capabilities to communicate with people from other cultures (n = 39, p < 0.05). It also showed an increase in local students' willingness to work with people from other cultures. Some themes related to intercultural competences were identified from the interview: "intercultural awareness, understanding, and communication" as well as openness to work/socialize with people from other cultures.", Conclusions: This study demonstrated that an international community service program could initiate positive changes in students' intercultural communication capability and interest to work with culturally different people., (Copyright © 2022 International Society for Prosthetics and Orthotics.)

Elabela (ELA), which is the second endogenous peptide ligand of the apelin receptor (APJ) to be discovered, has been widely studied for potential use as a therapeutic peptide. However, its role in ischemic stroke (IS), which is a leading cause of disability and death worldwide and has limited therapeutic options, is uncertain. The aim of the present study was to investigate the beneficial effects of ELA on neuron survival after ischemia and the underlying molecular mechanisms. Primary cortical neurons were isolated from the cerebral cortex of pregnant C57BL/6J mice. Flow cytometry and immunofluorescence showed that ELA inhibited oxygen-glucose deprivation (OGD) -induced apoptosis and axonal damage in vitro. Additionally, analysis of the Gene Expression Omnibus database revealed that the expression of microRNA-124-3p (miR-124-3p) was decreased in blood samples from patients with IS, while the expression of C-terminal domain small phosphatase 1 (CTDSP1) was increased. These results indicated that miR-124-3p and CTDSP1 were related to ischemic stroke, and there might be a negative regulatory relationship between them. Then, we found that ELA significantly elevated miR-124-3p expression, suppressed CTDSP1 expression, and increased p-AKT expression by binding to the APJ receptor under OGD in vitro. A dual-luciferase reporter assay confirmed that CTDSP1 was a direct target of miR-124-3p. Furthermore, adenovirus-mediated overexpression of CTDSP1 exacerbated neuronal apoptosis and axonal damage and suppressed AKT phosphorylation, while treatment with ELA or miR-124-3p mimics reversed these effects. In conclusion, these results indicated that ELA could alleviate neuronal apoptosis and axonal damage by upregulating miR-124-3p and activating the CTDSP1/AKT signaling pathway. This study, for the first time, verified the protective effect of ELA against neuronal injury after ischemia and revealed the underlying mechanisms. We demonstrated the potential for the use of ELA as a therapeutic agent in the treatment of ischemic stroke., (© 2023. The Author(s).)

Glioma is the most common primary malignant brain tumor with poor survival and limited therapeutic options. Chelerythrine (CHE), a natural benzophenanthridine alkaloid, has been reported to exhibit the anti-tumor effects in a variety of cancer cells. However, the molecular target and the signaling process of CHE in glioma remain elusive. Here we investigated the underlying mechanisms of CHE in glioma cell lines and glioma xenograft mice model. Our results found that CHE-induced cell death is associated with RIP1/RIP3-dependent necroptosis rather than apoptotic cell death in glioma cells at the early time. Mechanism investigation revealed the cross-talking between necroptosis and mitochondria dysfunction that CHE triggered generation of mitochondrial ROS, mitochondrial depolarization, reduction of ATP level and mitochondrial fragmentation, which was the important trigger for RIP1-dependent necroptosis activation. Meanwhile, PINK1 and parkin-dependent mitophagy promoted clearance of impaired mitochondria in CHE-incubated glioma cells, and inhibition of mitophagy with CQ selectively enhanced CHE-induced necroptosis. Furthermore, early cytosolic calcium from the influx of extracellular Ca 2+ induced by CHE acted as important "priming signals" for impairment of mitochondrial dysfunction and necroptosis. Suppression of mitochondrial ROS contributed to interrupting positive feedback between mitochondrial damage and RIPK1/RIPK3 necrosome. Lastly, subcutaneous tumor growth in U87 xenograft was suppressed by CHE without significant body weight loss and multi-organ toxicities. In summary, the present study helped to elucidate necroptosis was induced by CHE via mtROS-mediated formation of the RIP1-RIP3-Drp1 complex that promoted Drp1 mitochondrial translocation to enhance necroptosis. Our findings indicated that CHE could potentially be further developed as a novel therapeutic strategy for treatment of glioma., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Background: Patient's acceptance and compliance to spinal orthosis could influence the outcome of orthotic treatment in adolescent idiopathic scoliosis. Two innovative undergarments (thin and thick designs) were designed to improve the patient's orthosis wearing experience and acceptance., Objective: This study aimed to evaluate the effects of patients' self-provided undergarment and 2 newly designed undergarments with respect to the orthosis wearing compliance and quality of life (QoL) measures., Methods: A prospective randomized-controlled study was conducted to compare the effect of three types of undergarments. Thirty-eight subjects with adolescent idiopathic scoliosis were randomly assigned to one of the three groups: self-provided, thin-design, or thick-design undergarment. Wearing compliance logbook, Scoliosis Research Society questionnaire, and Brace Questionnaire were used to document the orthosis wearing period and quantify the health-related and orthosis-related QoL measures. Kruskal-Wallis one-way analysis of variance (ANOVA) and Friedman two-way ANOVA by ranks tests were conducted for intergroup and intragroup comparisons, respectively., Results: The compliance and QoL domains of the subjects in the thin-design undergarment group were significantly higher than those of the other two undergarment groups (P < .05). The intragroup compliance and QoL scores varied significantly in the 4 visits throughout the study period (P < .05)., Conclusions: It was observed that an adaptation period toward the prescribed spinal orthosis is required to help patients gradually achieve a more stable acceptance. The thin-design undergarment was ranked higher than the other two tested undergarments in compliance and QoL measures., (Copyright © 2022 International Society for Prosthetics and Orthotics.)

Background: Patients with influenza-associated acute respiratory distress syndrome (ARDS) requiring venovenous extracorporeal membrane oxygenation (vv-ECMO) support have a high mortality rate. Ventilator settings have been known to have a substantial impact on outcomes. However, the optimal settings of mechanical ventilation during vv-ECMO are still unknown., Methods: This multicenter retrospective cohort study was conducted in the intensive care units (ICUs) of three tertiary referral hospitals in Taiwan between July 2009 and December 2019. It aims to describe the effect of ventilator settings during vv-ECMO on patient outcomes., Results: A total of 93 patients with influenza receiving ECMO were screened. Patients were excluded if they: were receiving venoarterial ECMO, died within three days of vv-ECMO initiation, or were transferred to the tertiary referral hospital >24 hours after vv-ECMO initiation. A total of 62 patients were included in the study, and 24 (39%) died within six months. During the first three days of ECMO, there were no differences in tidal volume (5.1 vs. 5.2 mL/kg, p  = 0.833), dynamic driving pressure (15 vs. 14 cmH2O, p  = 0.146), and mechanical power (11.3 vs. 11.8 J/min, p  = 0.352) between survivors and non-survivors. However, respiratory rates were significantly higher in non-survivors compared with survivors (15 vs . 12 breaths/min, p  = 0.013). After adjustment for important confounders, a higher mean respiratory rate of >12 breaths/min was still associated with higher mortality (adjusted hazard ratio = 3.31, 95% confidence interval = 1.10-9.97, p  = 0.034)., Conclusions: In patients with influenza-associated ARDS receiving vv-ECMO support, we found that a higher respiratory rate was associated with higher mortality. Respiratory rate might be a modifiable factor to improve outcomes in this patient population., Competing Interests: The authors declare there are no competing interests., (©2022 Liao et al.)

Background: Paradoxical upgrading reaction (PUR) indicates the unanticipated deterioration during therapy in patients with tuberculous lymphadenitis. We investigated the diagnostic performance of the ultrasonography and shear wave elastography (SWE) in predicting the therapeutic response of peripheral tuberculous lymphadenitis., Methods: A prospective observational study was conducted from December 2017 to August 2020. Participants diagnosed with peripheral tuberculous lymphadenitis were included for a longitudinal follow-up utilizing ultrasonography with two-dimensional SWE to record sonographic features and the maximum elasticity value (Emax). We defined PUR as the development of any worsening symptoms of the pre-existing lymphadenitis within one month after the previous ultrasonography., Results: A total of 108 sonographic and SWE examinations were performed in 20 enrollees (75% woman), and their mean ( ± standard deviation) age was 49.6 ( ± 22.7) years. The area under the receiver operating characteristic curve of Emax to predict the next-month PUR was 0.906 at the cut-point of 85 kPa, with an accuracy of 87.0%, a sensitivity of 81.1% and a specificity of 87.9%. Multivariate analysis indicated that Emax > 85 kPa (OR: 24.85, 95% CI: 4.01-154.08, p < 0.001), Emax increment rate >2 kPa/month (OR: 15.14, 95% CI: 4.24-54.06, p < 0.001), and heterogeneous echogenicity (OR: 4.37, 95% CI: 1.16-16.43, p = 0.029) were independent sonographic predictors for PUR in the coming month., Conclusion: A high and non-declining Emax level and heterogeneous echogenicity were associated with the next-month PUR of tuberculous lymphadenitis. Ultrasonography with SWE may be a potential radiologic marker to predict the therapeutic response of tuberculous lymphadenitis., Competing Interests: Declaration of competing interest All authors have no conflicts of interest relevant to this article., (Copyright © 2021 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Hip protectors have been widely used for hip fracture prevention in the elderly, but its efficacy remains controversial. Users' compliance to hip protector is an important factor for its efficacy. However, the assessment of users' compliance tended to be subjective and unreliable in the past., Objectives: To quantify the elderly's compliance to hip protectors and investigate the effect of different underpant designs on the elderly's compliance., Study Design: A pilot randomized trial., Methods: Thirty-one participants were recruited and provided with hip protectors in which compliance monitors were installed and delivered with three pairs of either the conventional underpants or the purpose-design underpants randomly. Participants were encouraged to use the hip protectors with the assigned underpants for whole day. After 4 weeks, compliance data were downloaded from the compliance monitors. Participants were also asked to fill a survey form for acceptance analysis. The Spearman correlation coefficient and the Wilcoxon signed-rank test/2 independent samples t test/Mann-Whitney U test were used for the corresponding statistical analyses., Results: Thirty-one participants were recruited initially. Eighteen participants were excluded from instrumented compliance analysis because of limited or no data collection. The data of the resting 13 participants (six in the conventional underpants group and seven in purpose-design underpants group) were analyzed and showed an average instrumented compliance of 77.5% which was lower than the average self-reporting compliance (83.3%) of all the available 23 participants (eight of 31 became wheelchair-bounded). Participants' compliance was positively correlated with their acceptance to the hip protectors and significantly higher in the purpose-design underpants group than in the conventional underpants group ( P < 0.05)., Conclusions: This pilot study demonstrated a feasible protocol for compliance quantification of the elderly to the hip protectors, the importance to have an objective compliance measure to assess users' actual compliance, and purpose-design underpants could improve the users' compliance. Future studies with long-term observation and large sample size deserve further proof of the current findings., (Copyright © 2022 International Society for Prosthetics and Orthotics.)

Background: Iatrogenic pneumothorax is common after thoracic procedures. For patients with pneumothorax larger than 15%, simple aspiration is suggested. Although vacuum bottle plus non-tunneled catheter drainage has been performed in many institutions, its safety and efficacy remain to be assessed., Methods: Through this prospective cohort study (NCT03724721), we evaluated the safety and efficacy of vacuum bottle plus non-tunneled catheter drainage. Patients older than 20 years old who developed post-procedural pneumothorax were enrolled. A non-tunneled catheter was placed at the intersection of the midclavicular line and the second intercostal space. A 3-way stopcock, a drainage set, and a digital pressure gauge were connected. The stopcock was manipulated to connect the pleural space to the pressure gauge for measurement of end-expiration intrapleural pressure or to the vacuum bottle for air drainage. The rate of successful drainage, the end-expiration intrapleural pressure before, during, and after the procedure and the duration of hospitalization were recorded., Results: From August 2018 to February 2020, 21 patients underwent vacuum bottle plus catheter drainage (intervention group) and 31 patients received conservative treatment (control group). The end-expiration intrapleural pressure of all patients remained less than - 20 cmH 2 O during drainage. No procedure related complication was observed. Large pneumothorax (≥ 15%) was associated with higher risk of persistent air leak (Odds ratio 12, 95% CI 1.2-569.7). Vacuum bottle assisted air drainage yielded shorter event-free duration than that of conservative treatment (2 days vs 5 days [interquartile range 1-4 days vs 3-7 days], p < .05). Vacuum bottle assisted air drainage also help identifying patients with persistent pneumothorax and necessitate the subsequent management. The event-free duration of persistent air leak in the intervention group was also comparable with that of conservative treatment (5 days vs 5 days [interquartile range 5-8 days vs 3-7 days], p = .45)., Conclusions: Vacuum bottle plus catheter drainage of iatrogenic pneumothorax is a safe and efficient procedure. It may be considered as an alternative management of stable post-procedural pneumothorax with size larger than 15%. Trial registration The study protocol was approved by the Research Ethics Committee of National Taiwan University Hospital (No. 201805105DINA) on 6th August, 2018. The first participant was enrolled on 23rd August, 2018 after Research Ethics Committee approval. This clinical trial complete registration at U.S. National Library of Medicine clinicaltrials.gov with identifier NCT03724721 and URL: https://clinicaltrials.gov/ct2/show/NCT03724721 on 30th October, 2018., (© 2022. The Author(s).)

It is a challenge for all-optical switching to simultaneous achieve ultralow power consumption, broad bandwidth and high extinction ratio. We experimentally demonstrate an ultralow-power all-optical switching by exploiting chiral interaction between light and optically active material in a Mach-Zehnder interferometer. We achieve switching extinction ratio of 20.0 ± 3.8 and 14.7 ± 2.8 dB with power cost of 66.1 ± 0.7 and 1.3 ± 0.1 fJ/bit, respectively. The bandwidth of our all-optical switching is about 4.2 GHz. Moreover, our all-optical switching has the potential to be operated at few-photon level. Our scheme paves the way towards ultralow-power and ultrafast all-optical information processing.

Background and Purpose: Breast cancer (BRCA) is the most frequent female malignancy and is potentially life threatening. The amino acid metabolism (AAM) has been shown to be strongly associated with the development and progression of human malignancies. In turn, long noncoding RNAs (lncRNAs) exert an important influence on the regulation of metabolism. Therefore, we attempted to build an AAM-related lncRNA prognostic model for BRCA and illustrate its immune characteristics and molecular mechanism. Experimental Design: The RNA-seq data for BRCA from the TCGA-BRCA datasets were stochastically split into training and validation cohorts at a 3:1 ratio, to construct and validate the model, respectively. The amino acid metabolism-related genes were obtained from the Molecular Signature Database. A univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) regression, and a multivariate Cox analysis were applied to create a predictive risk signature. Subsequently, the immune and molecular characteristics and the benefits of chemotherapeutic drugs in the high-risk and low-risk subgroups were examined. Results: The prognostic model was developed based on the lncRNA group including LIPE-AS1, AC124067.4, LINC01655, AP005131.3, AC015802.3, USP30-AS1, SNHG26, and AL589765.4. Low-risk patients had a more favorable overall survival than did high-risk patients, in accordance with the results obtained for the validation cohort and the complete TCGA cohort. The elaborate results illustrated that a low-risk index was correlated with DNA-repair-associated pathways; a low TP53 and PIK3CA mutation rate; high infiltration of CD4 + T cells, CD8 + T cells, and M1 macrophages; active immunity; and less-aggressive phenotypes. In contrast, a high-risk index was correlated with cancer and metastasis-related pathways; a high PIK3CA and TP53 mutation rate; high infiltration of M0 macrophages, fibroblasts, and M2 macrophages; inhibition of the immune response; and more invasive phenotypes. Conclusion: In conclusion, we attempted to shed light on the importance of AAM-associated lncRNAs in BRCA. The prognostic model built here might be acknowledged as an indispensable reference for predicting the outcome of patients with BRCA and help identify immune and molecular characteristics., 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 Dai, Wen, Wu, Wu, Lv, Yan, Liu, Wang and Zheng.)

Background: Small-breed dogs commonly have concurrent myxomatous mitral valve disease (MMVD) and lower respiratory tract disease (LRTD)., Hypothesis: Small-breed dogs with preclinical MMVD and concurrent LRTD have more B-lines on point-of-care lung ultrasound (POC-LUS) compared to dogs without concurrent LRTD and are prone to misdiagnose as cardiogenic pulmonary edema (CPE)., Animals: A total of 114 small-breed dogs with preclinical MMVD., Methods: A prospective study was conducted, in which POC-LUS was obtained and the number of B-lines was calculated by a single clinician using the Veterinary Bedside Lung Ultrasound Examination protocol. The presence/absence of LRTD was assessed by clinicians blinded to the POC-LUS results., Results: Fifty and 64 dogs were in ACVIM stage B1 and B2, respectively. The presence of LRTD was prevalent in 74.6% (85/114) of small-breed dogs with preclinical MMVD. When a previously reported criterion for CPE diagnosis (≥2 sites with >3 B-lines/site) was applied, false-positive results were observed in 15.8% (18/114) of dogs with preclinical MMVD. The summated number of B-lines (3 vs. 1, P = .003), as well as the false-positive rate (20% vs 3%, P = .04), were significantly higher in dogs with LRTD compared with dogs without LRTD. Multivariable logistic regression showed the presence of abnormalities other than B-line on POC-LUS (eg, thickened pleura or consolidation) could predict false-positive results (odds ratio = 3.75, 95% confidence intervals 1.12-12.54; P = .03) after adjustment for other clinical and echocardiographic factors., Conclusions and Clinical Importance: Concurrent LRTD and abnormalities other than B-lines should be considered in the interpretation of POC-LUS in MMVD dogs., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Differences in traits between lianas and trees in tropical forests have been studied extensively; however, few have compared the ecological strategies of lianas from different habitats. Here, we measured 25 leaf and stem traits concerning leaf anatomy, morphology, physiology and stem hydraulics for 17 liana species from a tropical seasonal rainforest and for 19 liana species from a valley savanna in south-west China. We found that savanna lianas had higher vessel density, wood density and lower hydraulically weighted vessel diameter and theoretical hydraulic conductivity than tropical seasonal rainforest lianas. Compared with tropical seasonal rainforest lianas, savanna lianas also showed higher leaf dry matter content, carbon isotope composition (δ13C), photosynthetic water use efficiency, ratio of nitrogen to phosphorus, photosynthetic phosphorus use efficiency and lower leaf size, stomatal conductance and nitrogen, phosphorus and potassium concentrations. Interestingly, no differences in light-saturated photosynthetic rate were found between savanna and tropical seasonal rainforest lianas either on mass or area basis. This is probably due to the higher water and nutrient use efficiencies of savanna lianas. A principal component analysis revealed that savanna and tropical seasonal rainforest lianas were significantly separated along the first axis, which was strongly associated with acquisitive or conservative resource use strategy. Leaf and stem functional traits were coordinated across lianas, but the coordination or trade-off was stronger in the savanna than in the tropical seasonal rainforest. In conclusion, a relatively conservative (slow) strategy concerning water and nutrient use may benefit the savanna lianas, while higher nutrient and water use efficiencies allow them to maintain similar photosynthesis as tropical seasonal rainforest species. Our results clearly showed divergences in functional traits between lianas from savanna and tropical seasonal rainforest, suggesting that enhanced water and nutrient use efficiencies might contribute to the distribution of lianas in savanna ecosystems., (© The Author(s) 2021. Published by Oxford University Press.)

Background and Objectives: The main target of inspiratory muscle training (IMT) is to improve diaphragm function in patients with COPD who have inspiratory muscle weakness. Ventilatory demand is already increased during quiet breathing in patients with COPD, and whether threshold load imposed by IMT would active more accessory muscle remained to be determined. The purpose of this study was to examine diaphragm and sternocleidomastoid (SCM) activation during IMT with intensities of 30% and 50% maximal inspiratory pressure (P Imax )., Methods: Patients with COPD and a P Imax lower than 60 cmH 2 O were recruited for the study. Surface electromyography (EMG) was used to measure diaphragm and SCM activation, and group-based trajectory modeling (GBTM) was used to identify activation patterns during IMT. The generalized estimating equation (GEE) was then used to detect differences of variables between various breathing tasks. Statistical significance was established at p < 0.05., Results: A total of 30 patients with COPD participated in this study. All patients demonstrated significant increases in diaphragm and SCM activation during 30% and 50% P Imax of IMT than during quiet breathing (all p < 0.001). Diaphragm demonstrated two distinct patterns in response to IMT: low activation (n = 8) and high activation (n = 22) group using GBTM analysis., Conclusion: Diaphragm and SCM were substantially activated during IMT in patients with COPD who had inspiratory muscle weakness. Regardless of whether diaphragm activation was high or low, SCM was activated to a greater extent in response to IMT., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The role of end-expiratory lung volume (EELV) during a spontaneous breathing trial (SBT) in patients who were tracheostomized and on prolonged mechanical ventilation is unclear. This study aimed to assess EELV during a 60-min SBT and its correlation with weaning success., Methods: Enrolled subjects admitted to a weaning unit were measured for EELV and relevant parameters before and after the SBT., Results: Of the 44 enrolled subjects, 29 (66%) were successfully liberated, defined as not needing mechanical ventilation for 5 d. The success group had fewer subjects with chronic kidney disease (41% vs 73%, P = .044), stronger mean ± SD maximum inspiratory pressure (41.6 ± 10.4 vs 34.1 ± 7.1 cm H 2 O ; P = .02) and mean ± SD maximum expiratory pressure (46.9 ± 11.7 vs 35.3 ± 16.9 cm H 2 O ; P = .01) versus the failure group. Toward the end of the SBT, the success group had a significant increase in the mean ± SD EELV (before vs after: 1,278 ± 744 vs 1,493 ± 867 mL; P = .040) and a decrease in the mean ± SD rapid shallow breathing index (83.8 ± 39.4 vs 66.3 ± 29.4; P = .02), whereas there were no significant changes in these 2 parameters in the failure group. The Cox regression analysis showed that, at the beginning of SBT, a greater difference between EELV with a PEEP of 0 cm H 2 O and with a PEEP of 5 cm H 2 O was significantly correlated to a higher likelihood of weaning success. Toward the end of the SBT, a greater EELV level at a PEEP of 0 cm H 2 O was also correlated with weaning success. Also, the greater difference of EELV at a PEEP of 0 cm H 2 O between the beginning and the end of the SBT was also correlated with a shorter duration to weaning success., Conclusions: The change in EELV during a 60-min SBT may be of prognostic value for liberation from prolonged mechanical ventilation in patients who had a tracheostomy. Our findings suggest a model to understand the underlying mechanism of failure of liberation from mechanical ventilation in these patients., (Copyright © 2021 by Daedalus Enterprises.)

Molecular switches that respond to a biochemical stimulus in cells have proven utility as a foundation for developing molecular sensors and actuators that could be used to address important biological questions. Developing a molecular switch unfortunately remains difficult as it requires elaborate coordination of sensing and actuation mechanisms built into a single molecule. Here, we rationally designed a molecular switch that changes its subcellular localization in response to an intended stimulus such as an activator of protein kinase A (PKA). By arranging the sequence for Kemptide in tandem, we designed a farnesylated peptide whose localization can dramatically change upon phosphorylation by PKA. After testing a different valence number of Kemptide as well as modulating the linker sequence connecting them, we identified an efficient peptide switch that exhibited dynamic translocation between plasma membranes and internal endomembranes in a PKA activity dependent manner. Due to the modular design and small size, our PKA switch can have versatile utility in future studies as a platform for visualizing and perturbing signal transduction pathways, as well as for performing synthetic operations in cells., (© 2021. The Author(s).)

Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional (3D) deformity, and the plane of maximum curvature (PMC) is proposed to reflect these clinical features, which refers to a vertical plane presenting the maximum projected spinal curvature and its parameters include the PMC Cobb and orientation (angle between PMC and sagittal planes). This study aimed to develop a computational method (CM) for PMC estimation. Twenty-nine patients with AIS and computed tomography (CT) images were recruited. For CT, PMC was determined by rotating a vertical plane about its vertical axis with 5° increment until the maximum Cobb angle was measured. For CM, PMC was estimated via identifying the eight points (the corner points of the superior and inferior endplates of the upper and lower end-vertebrae respectively) in the coronal and lateral CT images. Two experienced raters repeated the PMC estimation three times with one-week interval. The intra-class correlation coefficient (ICC) and Bland-Altman method were used for statistical analysis. Twenty-seven right thoracic curves (RTs) (mean Cobb: 46.1°±12.4°) and 23 left thoracolumbar/lumbar (LTLs/LLs) (mean Cobb: 30.6°±11.1°) were analysed. The intra- and inter-rater ICC values were >0.91 and 0.84 in RTs and LTLs/LLs, respectively. The PMCs obtained from the CM and CT were showed good agreement was also observed between the PMCs obtained from the two methods according to ICC (>0.90) and Bland-Altman method assessments. This purpose-design computational method could provide reliable and valid estimation of PMCs for AIS, which has potential to be used as an alternative for 3D assessment.

Background: Heterogeneity in acute respiratory distress syndrome (ARDS) has led to many statistically negative clinical trials. Etiology is considered an important source of pathogenesis heterogeneity in ARDS but previous studies have usually adopted a dichotomous classification, such as pulmonary versus extrapulmonary ARDS, to evaluate it. Etiology-associated heterogeneity in ARDS remains poorly described., Methods: In this retrospective cohort study, we described etiology-associated heterogeneity in gas exchange abnormality (PaO 2 /FiO 2 [P/F] and ventilatory ratios), hemodynamic instability, non-pulmonary organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score, biomarkers of inflammation and coagulation, and 30-day mortality. Linear regression was used to model the trajectory of P/F ratios over time. Wilcoxon rank-sum tests, Kruskal-Wallis rank tests and Chi-squared tests were used to compare between-etiology differences., Results: From 1725 mechanically ventilated patients in the ICU, we identified 258 (15%) with ARDS. Pneumonia (48.4%) and non-pulmonary sepsis (11.6%) were the two leading causes of ARDS. Compared with pneumonia associated ARDS, extra-pulmonary sepsis associated ARDS had a greater P/F ratio recovery rate (difference = 13 mmHg/day, p = 0.01), more shock (48% versus 73%, p = 0.01), higher non-pulmonary SOFA scores (6 versus 9 points, p < 0.001), higher d-dimer levels (4.2 versus 9.7 mg/L, p = 0.02) and higher mortality (43% versus 67%, p = 0.02). In pneumonia associated ARDS, there was significant difference in proportion of shock (p = 0.005) between bacterial and non-bacterial pneumonia., Conclusion: This study showed that there was remarkable etiology-associated heterogeneity in ARDS. Heterogeneity was also observed within pneumonia associated ARDS when bacterial pneumonia was compared with other non-bacterial pneumonia. Future studies on ARDS should consider reporting etiology-specific data and exploring possible effect modification associated with etiology.

Nitrates primarily cause arterial and venous vasodilation effects, which increases coronary artery blood supply, and decreases cardiac preload and afterload by enhancing nitric oxide (NO) levels. The dosage of nitrates used for angina pectoris widely differs among individuals, and therapeutic resistance and tolerance gradually occur. Increasing doses of nitrates are needed to abolish ischemia chest pain onset in patients with angina pectoris, and to obtain satisfactory therapeutic effects. Here, we report the case of a 37-year-old male who was hospitalized six times, from September 2013 to April 2018, with recurrent angina pectoris. Although the patient was implanted with stents, he still presented with chest pain associated with physical efforts. Diagnosis with acute myocardial infarction was based on his ST-segment changes on electrocardiogram (ECG), elevated troponin-T level and coronary angiography. After the stents were implanted, his chest pain had no relief. Following three times of coronary angiography revealed that distal and small branch vessels still had stenosis, but was not required to revascularization. Due to serious headache resulted from sublingual or oral nitroglycerin; he had to take sublingual isosorbide dinitrate, from 20 mg to 150 mg each time, to obtain rapid relief from angina pectoris without doctor's consent. Followed up to April 2019, the patient has continued to take 100-150 mg sublingual isosorbide dinitrate for angina pectoris onset triggered by physical efforts, and has obtained remarkable relief within a few minutes, without blood pressure decrease and other side effects. Higher than recommend dosage of sublingual isosorbide dinitrate might establish better efficacy for angina pectoris in rarely patient., Competing Interests: The authors declare no competing interests., (Copyright: Hong-Yan Cao et al.)

Adenoid cystic carcinoma of the lacrimal gland (LACC) is a major orbital malignancy. The recurrence rate and mortality rate are higher in LACC high-grade transformation (LACC-HGT) compared with in LACC. The present study aimed to identify the candidate microRNAs (miRNAs/miRs) and construct a competing endogenous RNA (ceRNA) regulatory network for LACC-HGT. A miRNA microarray on paraffin-embedded tissues was performed to identify the differentially expressed miRNAs (DEMs) of LACC-HGT. The overlap with the salivary adenoid cystic carcinoma miRNA/RNA sequencing dataset in the Gene Expression Omnibus was used to identify candidate miRNAs. In order to construct a ceRNA regulatory network of LACC-HGT, a microarray of mRNA and circRNA in primary cell lines was performed. The circRNAs and genes with high expression in LACC-HGT were predicted as targeting miRNAs, and the circRNA-miRNA-mRNA regulatory network was constructed. miR-140-3p was identified as part of the ceRNA network and as a candidate miRNA, therefore this was further analyzed using reverse transcription-quantitative (RT-q)PCR. Overall, the Agilent Human microarray analysis identified a total of 16 DEMs from the LACC-HGT paraffin-embedded tissues. A total of 653 DECs and 9,566 DEGs of LACC-HGT primary cell lines were screened via the microarray of mRNA and circRNA. The ceRNA regulatory network was constructed using the cross-binding of circRNA-miRNA, miRNA-mRNA and the downregulated miRNAs in LACC-HGT to clearly demonstrate the circRNA-miRNA-mRNA interaction relationship. RT-qPCR results confirmed that miR-140-3p was downregulated in LACC-HGT tissues and primary cell lines compared with LACC. Target genes CD200 and parathyroid hormone-related protein were significantly upregulated in LACC-HGT primary cell lines. miR-140-3p and its target genes may play an important role in LACC-HGT pathogenesis. In conclusion, the current bioinformatics study constructed a ceRNA network based on a microarray, which may help identify novel miRNA therapeutic targets for LACC-HGT., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Jiang et al.)

Introduction: Tissue stiffness information may help in the diagnosis of lung lesions. This study aimed to investigate and validate the application of transthoracic two-dimensional shear-wave ultrasound elastography in differentiating malignant from benign subpleural lung lesions., Methods: This study involved one retrospective observational derivation cohort from January 2016 to December 2017 and one prospective observational validation cohort from December 2017 to December 2019. The inclusion criterion was radiographic evidence of pulmonary lesions. The patients were categorised into air bronchogram and hypoechoic groups based on B-mode grayscale images. The elasticity of subpleural lung lesions with acceptable shear-wave propagation was measured. Diagnoses were made on the basis of pathology, microbiological studies or following up the clinical course for at least 6 months., Results: A total of 354 patients were included. Among the 121 patients in the derivation cohort, a receiver operating characteristic curve was constructed and the cut-off point to differentiate benign from malignant lesions was 65 kPa with a Youden index of 0.60 and an accuracy of 84.3%. Among the 233 patients in the validation cohort, the diagnostic performance was maintained, with a Youden index of 0.65 and an accuracy of 86.7%. Upon applying the cut-off point to the air bronchogram group, the Youden index was 0.70 and the accuracy was 85.0%., Conclusions: This study validated the application of transthoracic shear-wave ultrasound elastography for assessing lung malignancy. A cut-off point of 65 kPa is suggested for predicting lung malignancy. Furthermore, for pulmonary air bronchogram lesions with high elasticity, tissue proofing should be considered because of the high possibility of malignancy., Competing Interests: Conflict of interest: Y-L. Chen has nothing to disclose. Conflict of interest: H-D. Wu has nothing to disclose. Conflict of interest: Y-C. Chien has nothing to disclose. Conflict of interest: C-K. Huang has nothing to disclose. Conflict of interest: H-C. Wang has nothing to disclose. Conflict of interest: Y-W. Kuo has nothing to disclose., (Copyright ©ERS 2021.)

Purpose: The coronal Cobb angle is commonly used for assessing the adolescent idiopathic scoliosis (AIS); however, it may underestimate the severity of AIS while the plane of maximum curvature (PMC) could be a promising descriptor for three-dimensional assessment of AIS. This study aimed to develop a computational method (CM) for estimating the PMC based on the coronal and sagittal images of the spine, and to verify the results with computed tomography (CT)., Methods: Twenty-eight thoracic and 24 lumbar curves from 30 subjects with AIS were analysed. For the CM, PMC was estimated via identifying the two corner points at the superior endplate of upper-end vertebra and the inferior endplate of lower-end vertebra in the coronal and sagittal CT images separately (eight corner points in total). For the CT, PMC was determined through rotating the spine images axially until the maximum Cobb angle was found. Intraclass correlation coefficient (ICC), Bland-Altman method and linear regression analysis were used for the statistical analyses., Results: The high ICC values (intra- > 0.91; inter- > 0.84) suggested very good intra- and inter-rater reliability of the CM in PMC estimation. The high ICC values (> 0.91) and assessment of Bland-Altman method demonstrated a good agreement between the PMC acquired using the CM and CT. The generated linear regression equations (R 2  > 0.69) could allow to estimate the PMC (originally measured through the CT) via the CM., Conclusion: The developed computational method could estimate reliable and valid PMC for the patients with AIS, and become feasible for three-dimensional assessment of AIS., Level of Evidence: III.

Objective: Recently, numerous studies have yielded inconsistent results regarding the effect of metformin on esophageal cancer risk in type 2 diabetes mellitus patients. The purpose of this study is to systematically assess this effect using meta-analysis., Methods: We searched clinical studies on metformin and esophageal cancer risk in PubMed, Embase, and the Cochrane Library. After literature screening, a series of meta-analyses were conducted using RevMan 5.3 software. The pooled hazard ratio (HR) and the corresponding 95% confidence interval (CI) were used as the effect size., Results: Five eligible studies (four cohort studies and one case-control study) were included for our meta-analysis using a random-effect model. The analysis showed that metformin could not reduce esophageal cancer risk in type 2 diabetes mellitus patients (HR 0.88, 95% CI 0.60-1.28, P > 0.05). Subgroup analyses by geographic location showed that metformin significantly reduced esophageal cancer risk in Asian patients with type 2 diabetes mellitus (HR 0.59, 95% CI 0.39-0.91, P = 0.02), without heterogeneity between studies (P = 0.80 and I 2  = 0%)., Conclusions: Overall, our systematic review and meta-analysis demonstrate that metformin does not reduce esophageal cancer risk in type 2 diabetes mellitus patients. However, a significant reduction in esophageal cancer risk in Asian populations remains to be clarified.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly identified pathogen causing the coronavirus disease 2019 (COVID-19) pandemic. Hydroxychloroquine (HCQ), an antimalarial and anti-inflammatory drug, has been shown to inhibit SARS-CoV-2 infection in vitro and tested in clinical studies. However, achievement of lung concentrations predicted to have in vivo antiviral efficacy might not be possible with the currently proposed oral dosing regimens. Further, high cumulative doses of HCQ raise concerns of systemic toxicity, including cardiotoxicity. Here, we describe a preclinical study to investigate the pharmacokinetics (PKs) of a novel formulation of liposomal HCQ administered by intratracheal (IT) instillation in Sprague-Dawley rats. Compared with unformulated HCQ administered intravenously, liposomal HCQ showed higher (~ 30-fold) lung exposure, longer (~ 2.5-fold) half-life in lungs, but lower blood exposure with ~ 20% of peak plasma concentration (C max ) and 74% of area under the curve from 0 to 72 hours (AUC 0-72 ) and lower heart exposure with 23% of C max and 58% of AUC 0-24 (normalized for dose). Similar results were observed relative to IT administration of unformulated HCQ. These PKs result in an animal model that demonstrated the proof of concept that inhalable liposomal HCQ may provide clinical benefit and serve as a potential treatment for COVID-19., (© 2020 Taiwan Liposome Company, Ltd. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Circular RNAs (circRNAs), a novel class of endogenous long non-coding RNAs, have attracted considerable attention due to their closed continuous loop structure and potential clinical value. In this study, we investigated the function of circFASTKD1 in vascular endothelial cells. CircFASTKD1 bound directly to miR-106a and relieved its inhibition of Large Tumor Suppressor Kinases 1 and 2, thereby suppressing the Yes-Associated Protein signaling pathway. Under both normal and hypoxic conditions, the ectopic expression of circFASTKD1 reduced the viability, migration, mobility and tube formation of vascular endothelial cells, whereas the downregulation of circFASTKD1 induced angiogenesis by promoting these processes. Moreover, downregulation of circFASTKD1 in mice improved cardiac function and repair after myocardial infarction. These findings indicate that circFASTKD1 is a potent inhibitor of angiogenesis after myocardial infarction and that silencing circFASTKD1 exerts therapeutic effects during hypoxia by stimulating angiogenesis in vitro and in vivo .

Chest ultrasonography has become an indispensable tool for pulmonary specialists in human medicine, but its current use in dogs and cats is primarily for emergency. The diagnostic performances of various ultrasonographic features other than comet-tail artifacts are of limited information in veterinary literatures. Therefore, the aims of this retrospective study were to investigate ultrasonographic findings in feline and canine respiratory patients with lung parenchymal and pleural space diseases, and to assess how ultrasonographic features correspond to specific diagnoses. Sixty-five non-emergency cases with radiographically identified lung parenchymal and pleural space abnormalities were included. Medical records and ultrasound video clips were reviewed, and additional follow-up information was subsequently collected. Common findings such as comet-tail artifacts (87.7% of cases), consolidation (84.6%), and thickened/irregular pleura (69.2%) were not distinguishable for a specific diagnosis. The presence of nodular/mass-like lesion (OR = 212, p < 0.001) and consolidated lesion with heteroechogenicity (OR = 240, p < 0.001) was significantly associated with and strongly predictive of neoplasia after age, body weight and other sonographic findings were adjusted. The finding of nodular/mass-like lesion has the best diagnostic performance (AUC = 0.93) for neoplasia, with sensitivity of 91.7% and specificity of 93.6%. For predicting a diagnosis of pneumonia, although several sonographic features were found to be statistically associated with pneumonia, only a negative finding of nodular/mass-like lesion showed good diagnostic performance (AUC = 0.83, sensitivity 95.7%, specificity 71%). These findings demonstrate the value of chest ultrasonography in predicting diagnosis in non-emergency cases. The application of thoracic ultrasound in small animal respiratory patients as part of non-invasive assessment warrants further investigation., 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 © 2020 Lin, Lo, Lam and Wu.)