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Ji Young Yoon,1 Keum-Jin Yang,2 Shi-Nae Park,3 Dong-Kee Kim,3 Jong-Duk Kim1 1Department of Chemical and Biomolecular Engineering, BK 21 Plus Program, Korea Advanced Institute of Science and Technology, Guseong-Dong, Yuseong-Gu, Daejeon, 2Clinical Research Institute, St Mary’s Hospital, Daejeon, 3Department of Otolaryngology – Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Abstract: Dexamethasone (Dex)-loaded PHEA-g-C18-Arg8 (PCA) nanoparticles (PCA/Dex) were developed for the delivery of genes to determine the synergistic effect of Dex on gene expression. The cationic PCA nanoparticles were self-assembled to create cationic micelles containing an octadecylamine (C18) core with Dex and an arginine 8 (Arg8) peptide shell for electrostatic complexation with nucleic acids (connexin 26 [Cx26] siRNA, green fluorescent protein [GFP] DNA or brain-derived neurotrophic factor [BDNF] pDNA). The PCA/Dex nanoparticles conjugated with Arg8, a cell-penetrating peptide that enhances permeability through a round window membrane in the inner ear for gene delivery, exhibited high uptake efficiency in HEI-OC1 cells. This potential carrier co-delivering Dex and the gene into inner ear cells has a diameter of 120–140 nm and a zeta potential of 20–25 mV. Different types of genes were complexed with the Dex-loaded PCA nanoparticle (PCA/Dex/gene) for gene expression to induce additional anti-inflammatory effects. PCA/Dex showed mildly increased expression of GFP and lower mRNA expression of inflammatory cytokines (IL1b, IL12, and INFr) than did Dex-free PCA nanoparticles and Lipofectamine® reagent in HEI-OC1 cells. In addition, after loading Cx26 siRNA onto the surface of PCA/Dex, Cx26 gene expression was downregulated according to real-time polymerase chain reaction for 24 h, compared with that using Lipofectamine reagent. After loading BDNF DNA into PCA/Dex, increased expression of BDNF was observed for 30 h, and its signaling pathway resulted in an increase in phosphorylation of Akt, observed by Western blotting. Thus, Dex within PCA/Dex/gene nanoparticles created an anti-inflammatory effect and enhanced gene expression. Keywords: cell-penetrating peptide, nanoparticle, dexamethasone, gene delivery, brain-derived neurotrophic factor

OBJECTIVE: We investigated the anti-osteoporotic effects of Polycan, a beta-glucan from Aureobasidium pullulans, in ovariectomized mice at doses of 31.25, 62.5, and 125 mg/kg. METHODS: Polycan was administered orally once a day for 28 d to bilateral ovariectomized mice, beginning 4 wk after surgery. Changes in body weight, bone weight, bone mineral content, bone mineral density, failure load, histologic profiles, and histomorphometric analyses were determined, in addition to serum osteocalcin, calcium, and phosphorus levels. Alendronate was used as a reference drug. RESULTS: Polycan significantly and dose-dependently suppressed decreases in bone weight, bone mineral content, failure load, bone mineral density, and serum calcium and phosphorus levels and the increase in serum osteocalcin levels. In addition, Polycan significantly suppressed decreases in histomorphometric parameters such as volume, length, and thickness of trabecular bone and thickness of cortical bone and the increase in osteoclast cells in the femur and tibia. CONCLUSION: Although the effects of Polycan were generally modest and smaller than those of alendronate, the effects on cortical bone thickness were more favorable for Polycan than for alendronate. In addition, Polycan exhibited favorable effects on ovariectomy-induced osteoporosis. However, more long-term studies are needed to confirm the effects of Polycan on osteoporosis. [ABSTRACT FROM AUTHOR]

Purpose of Review: The anesthetic management of patients with Moyamoya disease (MMD) is challenging and continues to evolve. The goal of this review is to provide updated recommendations on the anesthetic management of adult MMD patients based on the relevant existing literature., Recent Findings: Key findings include the importance of aggressive hydration preoperatively to sustain cerebral perfusion. Hypertension induced intraoperatively may prevent cerebral hypoperfusion. Vigilance against cerebral hyperperfusion after revascularization is necessary, with specific blood pressure targets recommended. Fluid management should aim for normovolemia to mild hypervolemia. Maintaining body temperature helps prevent cerebral vasospasm induced by hypothermia. Maintaining adequate oxygen supply during surgery is crucial. In cases of ischemic stroke, managing hematocrit and oxygen carrying capacity is essential to prevent further ischemia. Extubation decisions should consider baseline neurological function, while postoperative normocapnia helps prevent cerebral hyperperfusion and hypertension. In intensive care, cautious blood pressure management is crucial to prevent secondary complications., Summary: Strategies in the preoperative, intraoperative, and postoperative anesthetic management of MMD patients should aim to maintain adequate cerebral perfusion to prevent cerebral ischemia., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Herein, dexamethasone (DEX) nanocrystalline suspension (NS)-embedded hydrogel (NS-G) was constructed using a hydroxypropyl methylcellulose (HPMC) polymer to enhance cochlear delivery and attenuate hearing loss following intratympanic (IT) injection. Hydrophobic steroidal nanocrystals were prepared using a bead milling technique and incorporated into a polysaccharide hydrogel. The NS-G system with HPMC (average molecular weight, 86,000 g/mol; 15 mg/mL) was characterized as follows: rod-shaped drug crystalline; particle size <300 nm; and constant complex viscosity ≤1.17 Pa·s. Pulverization of the drug particles into submicron diameters enhanced drug dissolution, while the HPMC matrix increased the residence time in the middle ear cavity, exhibiting a controlled release profile. The IT NS-G system elicited markedly enhanced and prolonged drug delivery (> 9 h) to the cochlear tissue compared with that of DEX sodium phosphate (DEX-SP), a water-soluble prodrug. In mice with kanamycin- and furosemide-induced ototoxicity, NS-G markedly enhanced hearing preservation across all frequencies (8-32 kHz), as revealed by an auditory brainstem response test, compared with both saline and DEX-SP. Moreover, treatment with NS-G showed enhanced anti-inflammatory effects, as evidenced by decreased levels of inflammation-related cytokines. Therefore, the IT administration of DEX NS-loaded HPMC hydrogels is a promising strategy for treating hearing loss., 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 Ltd. All rights reserved.)

Objective: Baicalin has antioxidative, antiviral, and anti-inflammatory properties. However, its ability to alleviate oxidative stress (OS) and DNA damage in liver cells exposed to aflatoxin B 1 (AFB 1 ), a highly hepatotoxic compound, remains uncertain. In this study, the protective effects of baicalin on AFB 1 -induced hepatocyte injury and the mechanisms underlying those effects were investigated., Methods: Stable cell lines expressing CYP3A4 were established using lentiviral vectors to assess oxidative stress levels by conducting assays to determine the content of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Additionally, DNA damage was evaluated by 8-hydroxy-2-deoxyguanosine (8-OHdG) and comet assays. Transcriptome sequencing, molecular docking, and in vitro experiments were conducted to determine the mechanisms underlying the effects of baicalin on AFB 1 -induced hepatocyte injury. In vivo, a rat model of hepatocyte injury induced by AFB 1 was used to evaluate the effects of baicalin., Results: In vitro, baicalin significantly attenuated AFB 1 -induced injury caused due to OS, as determined by a decrease in ROS, MDA, and SOD levels. Baicalin also considerably decreased AFB 1 -induced DNA damage in hepatocytes. This protective effect of baicalin was found to be closely associated with the TP53-mediated ferroptosis pathway. To elaborate, baicalin physically interacts with P53, leading to the suppression of the expression of GPX4 and SLC7A11, which in turn inhibits ferroptosis. In vivo findings showed that baicalin decreased DNA damage and ferroptosis in AFB 1 -treated rat liver tissues, as determined by a decrease in the expression of γ-H2AX and an increase in GPX4 and SLC7A11 levels. Overexpression of TP53 weakened the protective effects of baicalin., Conclusions: Baicalin can alleviate AFB 1 -induced OS and DNA damage in liver cells via the TP53-mediated ferroptosis pathway. In this study, a theoretical foundation was established for the use of baicalin in protecting the liver from the toxic effects of AFB 1 ., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: Best medical therapy (BMT) for acute uncomplicated type B intramural hematoma (TBIMH) is the current treatment guideline, but there is considerable controversy about subsequent clinical course and outcome, which may be associated with a significant failure rate. The purpose of this study was to identify potential risk factors for BMT failure and to develop a risk score to guide clinical decision making., Methods: Patients with acute uncomplicated TBIMH between 2011 January and 2020 December were retrospectively studied. Logistic regression was applied to univariately assess potential risk predictors, and multivariable model results were then used to formulate a simplified predictive model for BMT failure., Results: In a total of 61 patients, the overall rate of BMT failure was 57.4% (35/61), of which 48.6% (17/35) occurred within 28 days of onset. Logistic regression identified maximum descending aortic diameter (HR ​= ​1.99 CI ​= ​1.16-3.40, p ​= ​0.012), initial IMH thickness (HR ​= ​3.29, CI ​= ​1.28-8.46, p ​= ​0.013) and presence of focal contrast enhancement (HR ​= ​3.12, CI ​= ​1.49-6.54, p ​= ​0.003) as potential risk predictors of BMT failure. A risk score was calculated as follows: [Max DTA diameter (mm)∗0.6876 ​+ ​Max IMH thickness (mm)∗1.1918 ​+ ​PAU/ULP ∗1.1369]. Freedom from BMT failure at 1 year was 72% in patients with a risk score ​< ​4.12, compared with only 35.1% in those with a risk score ​≧ ​4.12., Conclusions: In a substantial proportion of patients with acute uncomplicated TBIMH, initial BMT failed. Based on the three initial computed tomographic imaging variables, this risk score could help stratify patients at high or low risk for BMT failure and provided additional information for early intervention., Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest., (Copyright © 2024 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

Xanthine oxidoreductase (XOR) contributes to reactive oxygen species production. We investigated the cytoprotective mechanisms of XOR inhibition against high glucose (HG)-induced glomerular endothelial injury, which involves activation of the AMP-activated protein kinase (AMPK). Human glomerular endothelial cells (GECs) exposed to HG were subjected to febuxostat treatment for 48 h and the expressions of AMPK and its associated signaling pathways were evaluated. HG-treated GECs were increased xanthine oxidase/xanthine dehydrogenase levels and decreased intracellular AMP/ATP ratio, and these effects were reversed by febuxostat treatment. Febuxostat enhanced the phosphorylation of AMPK, the activation of peroxisome proliferator-activated receptor (PPAR)-gamma coactivator (PGC)-1α and PPAR-α and suppressed the phosphorylation of forkhead box O (FoxO)3a in HG-treated GECs. Febuxostat also decreased nicotinamide adenine dinucleotide phosphate oxidase (Nox)1, Nox2, and Nox4 expressions; enhanced superoxide dismutase activity; and decreased malondialdehyde levels in HG-treated GECs. The knockdown of AMPK inhibited PGC-1α-FoxO3a signaling and negated the antioxidant effects of febuxostat in HG-treated GECs. Despite febuxostat administration, the knockdown of hypoxanthine phosphoribosyl transferase 1 (HPRT1) also inhibited AMPK-PGC-1α-FoxO3a in HG-treated GECs. XOR inhibition alleviates oxidative stress by activating AMPK-PGC-1α-FoxO3a signaling through the HPRT1-dependent purine salvage pathway in GECs exposed to HG conditions., (© 2024. The Author(s).)

Objective: Participation in athletics is essential for the overall well-being of transgender athletes and should be included as part of gender-affirming care. Surveys show physicians and athletic trainers want to provide appropriate care for transgender athletes but lack the proper knowledge and training to do so. Gender Affirming Hormone Therapy (GAHT) is part of gender-affirming care, yet the effects of GAHT on the cardiovascular and musculoskeletal health of transgender athletes is not well-understood. The purpose of this review was to discuss important musculoskeletal and cardiovascular considerations unique to transgender athletes and improve physician understanding in caring for transgender athletes., Methods: A representative selection of literature on the effects of GAHT on cardiovascular and musculoskeletal health was included in this review., Results: Estrogen therapy may increase the risk of venous thromboembolism (VTE) and stroke, and decrease blood pressure levels among transgender women, while studies on lipid profile are inconsistent among both transgender men and women. Transgender women receiving GAHT may also be at greater risk for bone fracture and ligamentous injuries., Conclusion: Exercise is essential for the well-being of transgender individuals and special considerations regarding the cardiovascular and musculoskeletal health of transgender athletes should be incorporated into standard medical education. Educational programs for transgender patients and their support team should focus on preventative measures that can be taken to reduce the risk of adverse musculoskeletal and cardiovascular events. The PPE is an invaluable tool available to physicians to monitor the health and safety of transgender athletes and should be regularly updated as research on the health of transgender individuals continues to grow. Longitudinal and prospective studies should examine the effects of GAHT on the musculoskeletal and cardiovascular health of transgender athletes. Lastly, health care providers play an important role in the advancement of gender-neutral policies.

Background: We used computer-assisted image analysis to determine whether preexisting histological features of the cephalic vein influence the risk of non-maturation of wrist fistulas., Methods: This study focused on patients aged 20-80 years who underwent their first wrist fistula creation. A total of 206 patients participated, and vein samples for Masson's trichrome staining were collected from 134 patients. From these, 94 patients provided a complete girth of the venous specimen for automatic image analysis. Maturation was assessed using ultrasound within 90 days after surgery., Results: The collagen to muscle ratio in the target vein, measured by computer-assisted imaging, was a strong predictor of non-maturation in wrist fistulas. Receiver operating characteristic analysis revealed an area under the curve of 0.864 (95% confidence interval of 0.782-0.946, p < 0.001). The optimal cut-off value for the ratio was 1.138, as determined by the Youden index maximum method, with a sensitivity of 89.0% and specificity of 71.4%. For easy application, we used a cutoff value of 1.0; the non-maturation rates for patients with ratios >1 and ≤ 1 were 51.7% (15 out of 29 patients) and 9.2% (6 out of 65 patients), respectively. Chi-square testing revealed significantly different non-maturation rates between the two groups (X 2 (1, N = 94) = 20.9, p < 0.01)., Conclusion: Computer-assisted image interpretation can help to quantify the preexisting histological patterns of the cephalic vein, while the collagen-to-muscle ratio can predict non-maturation of wrist fistula development at an early stage., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Objective: The use of RDV in SAVR is associated with risk of conduction abnormality requiring PPM implantation, when compared to conventional bioprosthetic valves. We aimed to evaluate the outcome after selective placement of annular compression sutures during surgical aortic valve replacement (SAVR) using Intuity rapid deployment valve (RDV)., Methods: This is a retrospective study of prospectively enrolled patients receiving SAVR using Intuity RDV. Selective placement of commissural compression suture was assessed for all patients based on their annular morphology. Outcomes including operative mortality, rate of pacemaker rate, paravalvular leak and change in trans-valvular pressure gradient were analyzed., Results: 56 consecutive patients underwent SAVR with the INTUITY RDV at our institution from January 2020 to November 2021. The Mean age of our cohort was 69.9 ± 10.6 years with a EuroSCORE II of 3.4 ± 2.4%. 28.6% (16/56) of patients had notable conduction abnormalities pre-operatively, which included atrial fibrillation and left/right bundle branch block. Compression sutures were selectively applied in 19/56 (33.9%) patients. Of which, 13 were bicuspid aortic valve. Post-operatively, we observed no conduction abnormality requiring PPM implantation. In addition, only 3 of the 56 (5.4%) had any degree of paravalvular leak on post-operative echocardiography (all ≤ mild). The mean reduction in trans-valvular gradient was 29.9 mmHg and the mean pressure gradient at 1 month and 1 year follow-up were 9.3 ± 3.6 mmHg and 10.2 ± 4.1 mmHg, respectively., Conclusions: Selective placement of compression suture helps to avoid unnecessary oversizing, which may reduce the risk of paravalvular leak and post-operative PPM implantation., Competing Interests: Declaration of competing interest A conflict of interest occurs when an individual's objectivity is potentially compromised by a desire for financial gain, prominence, professional advancement or a successful outcome. JFMA Editors strive to ensure that what is published in the Journal is as balanced, objective and evidence-based as possible. Since it can be difficult to distinguish between an actual conflict of interest and a perceived conflict of interest, the Journal requires authors to disclose all and any potential conflicts of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Objectives: Taxi drivers experience chronic neck pain owing to their posture while driving. The aim of this study was to investigate the effect of self-stretching exercises with kinesio taping on pain, stress, pressure pain threshold (PPT), disability, cervical range of motion (CROM) in this population., Design: A single-blind, randomized controlled trial SETTING: Forty-three taxi drivers with nonspecific chronic nonspecific neck pain were randomly assigned to experimental (n = 22) and control (n = 21) groups., Methods: In the experimental group, self-stretching exercises were performed 3 times a day, 5 days per week, for 4 weeks, with kinesio taping applied while driving. In the control group, only kinesio taping was applied while driving for 4 weeks. Pain intensity, stress intensity, PPT, neck disability, and CROM were assessed pre-intervention, post-intervention, and at 4 weeks post-intervention., Results: Significant time and group interactions were observed in pain intensity at rest (p = 0.048) and while driving (p = 0.001). In the experimental group, the Pre - Post - Follow-up mean (95% CI) was 4.41 (4.14 to 4.68) - 3.82 (3.57 to 4.07) - 3.78 (3.55 to 3.99). In the control group, the Pre - Post - Follow-up mean (95% CI) was 4.29 (4.01 to 4.56) - 3.86 (3.60 to 4.11) - 4.05 (3.82 to 4.27) for pain at rest. In the experimental group, the Pre - Post - Follow-up mean (95% CI) was 4.91 (4.63 to 5.19) - 4.00 (3.76 to 4.24) - 3.69 (3.69 to 4.22), while in the control group, the Pre - Post - Follow-up mean (95% CI) was 4.81 (4.53 to 5.09) - 4.38 (4.13 to 4.63) - 4.57 (4.30 to 4.85) for pain while driving. PPT on the right (p = 0.029) and left (p < 0.001) sides, and neck disability (p = 0.001) also showed significant time and group interactions. NDI was not clinically significant based on the minimum clinically important difference. All CROM showed significant time and group interactions (flexion, p = 0.008; right lateral flexion, p = 0.009; left lateral flexion, p = 0.004; right rotation, p = 0.001; left rotation, p = 0.001), except for extension., Conclusion: This study showed that self-stretching exercises with kinesio taping provided benefits over kinesio taping alone on pain intensity, PPT, disability, and CROM in taxi drivers with nonspecific chronic neck pain., Clinical Trial Registration: This study registered with the Clinical Research Information Service (WHO International Clinical Trials Registry Platform) on September 22, 2020 (KCT0005406)., 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 Ltd.. All rights reserved.)

This study investigated the efficacy and safety of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in relapse prevention of bipolar disorder (BD), addressing the shortcomings of current medications. Thirty-one stable BD patients were randomized to receive n-3 PUFAs or placebo for 6 months and intergroup differences in the incidence of the recurrence of bipolar depression were assessed. Differences in depression severity, manic symptoms, and routine biochemical parameters were also assessed. Interestingly, n-3 PUFAs demonstrated a favorable preventive effect on bipolar depression recurrence (p=0.005; Log-Rank) and reduced depression severity compared to placebo, and were well-tolerated, suggesting their potential as a safe prophylactic therapy for BD., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: To compare the late outcomes between mechanical and bioprostheses after isolated mitral valve replacement (MVR) in dialysis-dependent patients., Methods: A nationwide propensity-matched retrospective cohort study was conducted involving dialysis patients who underwent primary mitral replacement between 2001 and 2018. Ten-year postoperative outcomes were compared between mitral bioprosthesis and mechanical prosthesis using the Cox proportional hazard model and restricted mean survival time (RMST)., Results: The all-cause mortality was 20.8 and 13.0 events per 100 person-years, with a 10-year RMST of 7.40 and 7.31 years for bioprosthesis and mechanical prosthesis, respectively. Major bleeding was the most common adverse event for both bioprosthesis and mechanical prosthesis, with an incidence rate of 19.5 and 19.1 events per 100 person-years, respectively. The incidence of valve reoperation was higher among those who received bioprosthesis (0.55 events per 100 person-years). After 1:1 matching, the all-cause mortality was 15.45 and 14.54 events per 100 person-years for bioprosthesis and mechanical prosthesis, respectively. The RMST at 10 years was comparable between the two groups after matching (5.10 years for bioprosthesis vs. 4.59 years for mechanical prosthesis), with an RMST difference of -0.03. Further, no difference was observed in the incidence of major adverse valve-related events between bioprosthesis and mechanical valves. However, bioprosthesis was associated with a higher incidence of mitral valve reoperation among all major adverse events (RMST difference -0.24 years, 95% CI -0.48 to -0.01, P =0.047)., Conclusions: This study found no association between valve selection and long-term survival outcomes in dialysis patients after MVR. However, bioprosthetic valves may be associated with a slightly higher incidence of reoperation, while other valve-related adverse events, including major bleeding and stroke, were comparable between the two types of prostheses., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Sepsis is a major disease that threatens human life and health. Clinically, it is mainly based on supportive treatment and lacks specific treatment methods. Acupuncture has important clinical significance in the prevention and treatment of sepsis. In the present paper, we systematically searched CNKI and PubMed databases, included the clinical trials and animal experiments on the prevention and treatment of sepsis with acupuncture, summarized the clinical efficacy and the mechanism of acupuncture. Results indicate that the role of acupuncture therapies in improving sepsis involves inhibiting systemic inflammatory response, alleviating oxidative stress, regulating immune system, and resisting cell apoptosis, thus having a protective effect on multiple organs. The mechanism involves multiple signaling pathways and related factors.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. HCC with liver fluke infection could harbor unique biological behaviors. This study was aimed at investigating radiomics features of HCC with liver fluke infection and establishing a model to predict the expression of cytokeratin 7 (CK7) and cytokeratin 19 (CK19) as well as prognosis at the same time. A total of 134 HCC patients were included. Gadoxetic acid-enhanced magnetic resonance imaging (MRI) images of all patients were acquired. Radiomics features of the tumor were extracted and then data dimensionality was reduced. The radiomics model was established to predict liver fluke infection and the radiomics score (Radscore) was calculated. There were 11 features in the four-phase combined model. The efficiency of the combined model increased significantly compared to each single-phase MRI model. Radscore was an independent predictor of liver fluke infection. It was also significantly different between different expression of CK7/ CK19. Meanwhile, liver fluke infection was associated with CK7/CK19 expression. A cut-off value was set up and all patients were divided into high risk and low risk groups of CK7/CK19 positive expression. Radscore was also an independent predictor of these two biomarkers. Overall survival (OS) and recurrence free survival (RFS) of negative liver fluke infection group were significantly better than the positive group. OS and RFS of negative CK7 and CK19 expression were also better, though not significantly. Positive liver fluke infection and CK19 expression prediction groups harbored significantly worse OS and RFS, survival of positive CK7 expression prediction was unsatisfying as well. A radiomics model was established to predict liver fluke infection among HCC patients. This model could also predict CK7 and CK19 expression. OS and RFS could be foreseen by this model at the same time., (© 2023. Springer Nature Limited.)

To establish a pre-test probability model of coronary heart disease (CHD) combined with cardiopulmonary exercise test (CPET) indexes and to compare the clinical effectiveness with Duke clinical score (DCS) and updated Diamond-Forrester model (UDFM), thus further explore the predictive value. 342 cases were used to establish the prediction model equation and another 80 cases were used to verify the effectiveness. The patients were divided into CHD group (n = 157) and non-CHD group (n = 185) according to coronary artery stenosis degree >50% or not. Combining DCS and UDFM as reference models with CPET indexes, a multivariate logistic regression model was established. The area under the ROC curve of the three models were calculated to compare the predictive effectiveness. There were significant differences in gender, chest pain type, myocardial infarction history, hypertension history, smoking, pathological Q wave and ST-T change between two groups (P < 0.01), as well as age, LVEF, heart rate at anaerobic domain, peak oxygen uptake in kilograms of body weight, percentage of peak oxygen uptake to the predicted value, the oxygen uptake efficiency slope and carbon dioxide ventilation equivalent slope (P < 0.05). Multivariate analysis showed gender, age, chest pain type, myocardial infarction history, hypertension history, smoking, pathological Q wave, ST-T change, and peak oxygen pulse were independent risk factors of CHD. The pre-test probability model of CHD combined with CPET indexes has good distinguish and calibrate ability, its prediction accuracy is slightly better than DCS and UDFM, which still needs to be verified externally in more samples., (© 2023. Springer Nature Limited.)

Viruses encode transcriptional regulatory proteins critical for controlling viral and host gene expression. Given their multifunctional nature and high sequence divergence, it is unclear which viral proteins can affect transcription and which specific sequences contribute to this function. Using a high-throughput assay, we measured the transcriptional regulatory potential of over 60,000 protein tiles across ∼1,500 proteins from 11 coronaviruses and all nine human herpesviruses. We discovered hundreds of transcriptional effector domains, including a conserved repression domain in all coronavirus Spike homologs, dual activation-repression domains in viral interferon regulatory factors (VIRFs), and an activation domain in six herpesvirus homologs of the single-stranded DNA-binding protein that we show is important for viral replication and late gene expression in Kaposi's sarcoma-associated herpesvirus (KSHV). For the effector domains we identified, we investigated their mechanisms via high-throughput sequence and chemical perturbations, pinpointing sequence motifs essential for function. This work massively expands viral protein annotations, serving as a springboard for studying their biological and health implications and providing new candidates for compact gene regulation tools., Competing Interests: Declaration of interests C.H.L., A.R.T., J.T., M.C.B., and L.B. have filed a provisional patent related to this work through Stanford University. C.H.L. is an employee and shareholder of Octant Inc. J.T., M.C.B., and L.B. are co-founders of Stylus Medicine. M.C.B. and L.B. are members of the scientific advisory board of Stylus Medicine. B.A.G. is a member of the scientific advisory board of Imunon., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To assess the diagnostic value and clinical significance of nucleoporin 107 (NUP107) in hepatocellular carcinoma (HCC), and explore the possible mechanisms., Methods: The transcriptomic and clinical data of HCC patients were retrieved from The Cancer Genome Atlas (TCGA) and GEO databases. Tissue specimens were collected from HCC patients in the Guangxi area. According to the expression levels and prognostic characteristics of NUP107, ROC curves and nomogram models were constructed using the R package., Results: NUP107 was highly expressed in 26 human cancers including HCC, and was associated with advanced HCC staging and worse prognosis. NUP107 showed satisfactory ability to predict the prognosis of HCC patients (AUC >0.8). Results of gene set enrichment analysis (GSEA) further showed that NUP107 was mainly associated with cell cycle-related pathways such as the cell cycle, DNA replication, G2M checkpoint, E2F target, and mitotic spindle. In addition, NUP107 was also associated with immune infiltration in HCC and showed significant positive correlation with immune checkpoints (PD-L1 and TIM-3)., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: To treat Neisseria gonorrhoeae infection, the Centers for Disease Control and Prevention recommends a single oral dose of cefixime as an alternative to injectable ceftriaxone., Methods: We conducted a systematic review and meta-analysis to describe the effectiveness of cefixime in treating N. gonorrhoeae infection at 3 different anatomic sites.We searched PubMed and Embase database to abstract treatment success rates and cefixime dosage/frequency for studies that reported the anatomical site of infection. We included reports published between January 1, 1980, and December 7, 2021. Twenty studies published between 1989 and 2015 were included in our meta-analysis. We calculated pooled treatment success percentages and 95% confidence intervals (CIs) using random-effects models., Results: Of patients who received a 400-mg single dose of cefixime, 824 of 846 (97%; 95% CI, 96%-98%) patients with urogenital infection, 107 of 112 (97%; 95% CI, 84%-100%) patients with rectal infection, and 202 of 242 (89%; 95% CI, 76%-96%) patients with pharyngeal infection were cured. Of patients who received an 800-mg single dose of cefixime, 295 of 301 (98%; 95% CI, 96%-99%) patients with urogenital infection and 21 of 26 (81%; 95% CI, 61%-92%) patients with pharyngeal infection were cured., Conclusions: Our meta-analysis found that cefixime is highly effective at treating urogenital infections and less effective at treating pharyngeal infections. We recommend more investigation into the effectiveness of cefixime in treating rectal infections and studying multidose therapy for the cefixime treatment of pharyngeal infection., Competing Interests: Conflict of Interest and Sources of Funding: All authors report no conflicts of interest. This study was supported by the National Institutes of Health (grant no. 5R21AI157817-03) and an award from the IDSA Foundation and HIV Medicine Association Grants for Emerging Researcher/Clinician Mentorship (G.E.R.M.) Program 2022. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association.)

There is growing evidence that the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risks of psychiatric sequelae. Depression, anxiety, cognitive impairments, sleep disturbance, and fatigue during and after the acute phase of COVID-19 are prevalent, long-lasting, and exerting negative consequences on well-being and imposing a huge burden on healthcare systems and society. This current review presented timely updates of clinical research findings, particularly focusing on the pathogenetic mechanisms underlying the neuropsychiatric sequelae, and identified potential key targets for developing effective treatment strategies for long COVID. In addition, we introduced the Formosa Long COVID Multicenter Study (FOCuS), which aims to apply the inflammation theory to the pathogenesis and the psychosocial and nutrition treatments of post-COVID depression and anxiety.

Xanthine oxidase (XO) is an important source of reactive oxygen species. This study investigated whether XO inhibition exerts renoprotective effects by inhibiting vascular endothelial growth factor (VEGF) and NADPH oxidase (NOX) in diabetic kidney disease (DKD). Febuxostat (5 mg/kg) was administered to streptozotocin (STZ)-treated 8-week-old male C57BL/6 mice via intraperitoneal injection for 8 weeks. The cytoprotective effects, its mechanism of XO inhibition, and usage of high-glucose (HG)-treated cultured human glomerular endothelial cells (GECs) were also investigated. Serum cystatin C, urine albumin/creatinine ratio, and mesangial area expansion were significantly improved in febuxostat-treated DKD mice. Febuxostat reduced serum uric acid, kidney XO levels, and xanthine dehydrogenase levels. Febuxostat suppressed the expression of VEGF mRNA, VEGF receptor (VEGFR)1 and VEGFR3, NOX1, NOX2, and NOX4, and mRNA levels of their catalytic subunits. Febuxostat caused downregulation of Akt phosphorylation, followed by the enhancement of dephosphorylation of transcription factor forkhead box O3a (FoxO3a) and the activation of endothelial nitric oxide synthase (eNOS). In an in vitro study, the antioxidant effects of febuxostat were abolished by a blockade of VEGFR1 or VEGFR3 via NOX-FoxO3a-eNOS signaling in HG-treated cultured human GECs. XO inhibition attenuated DKD by ameliorating oxidative stress through the inhibition of the VEGF/VEGFR axis. This was associated with NOX-FoxO3a-eNOS signaling.

Diabetic kidney disease is the most common primary disease of end-stage kidney disease globally; however, a sensitive and accurate biomarker to predict this disease remains awaited. microRNAs are endogenous single-stranded noncoding RNAs that have intervened in different post-transcriptional regulations of various cellular biological functions. Previous literatures have reported its potential role in the pathophysiology of diabetic kidney disease, including regulation of Transforming Growth Factor-β1-mediated fibrosis, extracellular matrix and cell adhesion proteins, cellular hypertrophy, growth factor, cytokine production, and redox system activation. Urinary microRNAs have emerged as a novel, non-invasive liquid biopsy for disease diagnosis. In this review, we describe the available experimental and clinical evidence of urinary microRNA in the context of diabetic kidney disease and discuss the future application of microRNA in routine practice.

Systemic lupus erythematosus (SLE) is associated with multi-organ damage including cardiac valve, which may need valvular operation. However, methods for outcome prediction and prosthetic valve selection are unclear in SLE patients undergoing cardiac valve surgery. Twenty-five SLE patients receiving valvular operation in a single institute between 2002 and 2020 were enrolled. Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SLICC/ACR damage index, SDI) was applied to evaluate the damage severity. Clinical outcomes were compared between patients with different SDI. The hospital survival rate was 88%, and long-term survival rate was 59.5% and 40.2% at 5 and 10 years. The median SDI was 4 (interquartile range 3-6) in our study, patients were then grouped into higher SDI (defined as SDI ≥ 5, n = 11) and lower SDI group (defined as SDI < 5, n = 14). The in-hospital survival rate (72.2% vs 100%, P = 0.074) and 5-year survival rate (18.2% vs 92.9%, P < 0.001) were lower in higher SDI group, compared to lower SDI group. SDI score was associated with long-term outcome for SLE patients receiving cardiac valve surgery. SDI ≥ 5 was associated with very poor long-term outcomes. This finding implicates that xenograft might be a reasonable choice for SLE patients with SDI ≥ 5., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: Animal studies have demonstrated that an oral absorbent AST-120 modulates gut environment. However, this phenomenon remains unclear in humans. This study aimed to assess the effects of AST-120 on the gut microbiota, related functional capability and metabolomic profiling in advanced chronic kidney diseases (CKD) patients. Methods: Eight advanced CKD patients with AST-120 (CKD+AST), 24 CKD patients (CKD), and 24 non-CKD controls were enrolled. We analyzed 16S rRNA pyrosequencing of feces and serum metabolomics profiling. Results: The CKD+AST group exhibited dispersed microbial community structure (β-diversity, p < 0.001) compared to other groups. The relative abundances of at least 16 genera were significantly different amongst the three groups. Increases of fatty acids-producing bacteria (Clostridium&#95;sensu&#95;stricto&#95;1, Ruminococcus&#95;2, Eubacterium&#95;nodatum and Phascolarctobacterium) associated with elevated serum acetic acid and octanoic acid levels were found in CKD+AST group. Analysis of microbial gene function indicated that pathway modules relevant to metabolisms of lipids, amino acids and carbohydrates were differentially enriched between CKD+AST and CKD groups. Specifically, enrichments of gene markers of the biosynthesis of fatty acids were noted in the CKD+AST group. Conclusion: Advanced CKD patients exhibited significant gut dysbiosis. AST-120 can partially restore the gut microbiota and intervenes in a possible signature of short- and medium-chain fatty acids metabolism.

In this study, we investigated the effect of the stacking order of metal precursors on the formation of volume defects, such as blisters and nanopores, in CZTSSe thin-film solar cells. We fabricated CZTSSe thin films using three types of metal-precursor combinations, namely, Zn/Cu/Sn/Mo, Cu/Zn/Sn/Mo, and Sn/Cu/Zn/Mo, and studied the blister formation. The blister-formation mechanism was based on the delamination model, taking into consideration the compressive stress and adhesion properties. A compressive stress could be induced during the preferential formation of a ZnSSe shell. Under this stress, the adhesion between the ZnSSe film and the Mo substrate could be maintained by the surface tension of a metallic liquid phase with good wettability, or by the functioning of ZnSSe pillars as anchors, depending on the type of metal precursor used. Additionally, the nanopore formation near the back-contact side was found to be induced by the columnar microstructure of the metal precursor with the Cu/Zn/Mo stacking order and its dezincification. Based on the two volume-defect-formation mechanisms proposed herein, further development of volume-defect-formation suppression technology is expected to be made.

This study was designed to investigate the potential key genes of ADP-ribosylation factor-like 15 (ARL15) regulating glycolysis and lipogenesis in colon cancer. Hematoxylin-eosin (HE) staining and immunohistochemistry were used to observe the expression of ARL15 in 10 normal colon tissues and 10 colon cancer tissues. Immunofluorescence staining was used to observe the expression position of ARL15 in normal human colorectal mucosa cells (FHC) and colon cancer cells (HCT116 and SW620) with a confocal microscope. The ARL15 plasmid and small interfering RNA (siRNA) were constructed. After transfection, the expression levels of glycolysis and lipogenesis regulatory enzymes and messenger RNA (mRNA) transcription of ARL15 in over-expressed and silenced colon cancer cells were detected by Western blotting and real-time quantitative PCR (qRT-PCR). High expression of ARL15 in colon cancer tissue and low expression in normal colon tissue, and all expression are in the cytosol. The expression position of ARL15 in the FHC, HCT116, and SW620 cells was consistent and mainly distributed in the cytosol. After the pCMV-3Tag-2-ARL15 plasmid was transfected in HCT116, the protein expressions of FASN, AKT, P-AKT, P-GSK, SREBP-1 (p125) (p<0.01), and AMPK (p<0.001) were higher than those in the control group. The mRNA transcription level of FASN, GSK, AMPKa1, and SREBP-1 gene was higher than control group after the over-expression of ARL15. After the ARL15-siRNA was transfected in HCT116, the protein expression levels of PKM2, PFK, FASN, AKT, P-AKT, P-GSK, and AMPK decreased compared with the control group, (p<0.05). The mRNA transcription level of FASN, GSK, AMPKα1 gene was lower than control group after the low-expression of ARL15 (p<0.05). After adding 2 μM JIB-04, ARL15 in HCT116 showed statistical differences compared with the control group at 12 h, 24 h and 36 h (p<0.05). After adding 2 μM JIB-04, the protein expression levels of AKT, p-GSK, FASN, AMPK and SREBP-1 in HCT116 cells decreased significantly after 24 h. It was also found that the expression levels of AKT, P-GSK, FASN, AMPK and SREBP-1 genes in the dose-adding group were significantly lower than those in the control group. In summary, ARL15 may promote the occurrence of colon cancer by increasing the expression of protein kinase B/AMP-activated protein kinase (AKT/AMPK) downstream regulatory enzymes for glycogenesis and lipogenesis. JIB-04 can target ARL15 and affect its expression as well as the expressions of glucose and lipid metabolity-related proteins in AKT and AMPK signaling pathways.

While traditional methods for studying large DNA viruses allow the creation of individual mutants, CRISPR/Cas9 can be used to rapidly create thousands of mutant dsDNA viruses in parallel, enabling the pooled screening of entire viral genomes. Here, we applied this approach to Kaposi's sarcoma-associated herpesvirus (KSHV) by designing a sgRNA library containing all possible ~22,000 guides targeting the 154 kilobase viral genome, corresponding to one cut site approximately every 8 base pairs. We used the library to profile viral sequences involved in transcriptional activation of late genes, whose regulation involves several well characterized features including dependence on viral DNA replication and a known set of viral transcriptional activators. Upon phenotyping all possible Cas9-targeted viruses for transcription of KSHV late genes we recovered these established regulators and identified a new required factor (ORF46), highlighting the utility of the screening pipeline. By performing targeted deep sequencing of the viral genome to distinguish between knock-out and in-frame alleles created by Cas9, we identify the DNA binding but not catalytic domain of ORF46 to be required for viral DNA replication and thus late gene expression. Our pooled Cas9 tiling screen followed by targeted deep viral sequencing represents a two-tiered screening paradigm that may be widely applicable to dsDNA viruses., Competing Interests: The authors have declared that no competing interests exist.

Based on the structural modification of regorafenib, 28 pyrazinyl-aryl urea derivatives were synthesized and their in vitro antiproliferative activities were evaluated. Six compounds (5-16, 5-17, 5-18, 5-19, 5-22, and 5-23) exhibited favorable inhibitory activity against the human bladder cancer T24 cell line, and 5-23 demonstrated the strongest inhibitory activity (IC 50 = 4.58 ± 0.24 μM) with high selectivity. Compound 5-23 induced apoptosis in the low concentration range (≤7.5 μM) combined with shorter incubation time (≤10 h) via the activation of caspases, while high concentrations and prolonged incubation times led to necroptotic cell death by activating the RIPK1/RIPK3/MLKL signaling pathway. Induced apoptosis and necroptosis were closely associated with intracellular reactive oxygen species generation and decreased mitochondrial membrane potential. Compared with regorafenib, 5-23 displayed improved pharmacokinetic profiles in an in vivo rat model. Molecular docking and structure-activity relationship analyses were in agreement with the biological data. Compound 5-23 may be a potent anti-bladder cancer agent and this small molecule can be considered as a promising structure for further optimization., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Introduction: Pyoderma gangrenosum (PG) is a relatively uncommon necrotizing and ulcerative cutaneous disorder. It is often associated with a systemic inflammatory disease but may also present following trauma to the skin due to pathergy. Given its rare occurrence and nonspecific histology, PG is primarily a diagnosis of exclusion, which often results in delayed treatment. Very few cases of PG following autologous breast reconstruction have been reported in the literature, particularly in the absence of systemic disease., Case Report: Presented is the case of a 62-year-old female with a history of ductal carcinoma in situ who underwent a left breast mastectomy with immediate deep inferior epigastric perforator flap breast reconstruction complicated by fever and leukocytosis as well as erythema, edema, and bullae involving the mastectomy flaps. Initially, necrotizing soft-tissue infection was suspected, and 2 debridements were performed. A diagnosis of PG was made on postoperative day 7, and the patient responded favorably to high-dose prednisone. Reconstruction was performed with a bilayer wound matrix and delayed skin grafting. Despite significant loss of mastectomy skin flap, the free flap was preserved., Conclusions: Although PG is a rare complication, it should be considered in the differential diagnosis for patients with atypical presentation of infection following breast reconstruction, even in the absence of systemic inflammatory disease. Early diagnosis and multidisciplinary management may prevent unnecessary surgical intervention and enable flap preservation. Furthermore, bilayer wound matrix placement may be useful as an intermediate reconstruction to determine if it is safe to proceed with skin grafting to avoid further pathergy. The findings in this case suggest that final reconstruction may be safely performed sooner than noted in the literature.

Background: Although associations between low protein diet (LPD) and changes of gut microbiota have been reported; however, systematic discernment of the effects of LPD on diet-microbiome-host interaction in patients with chronic kidney disease (CKD) is lacking. Methods: We searched PUBMED and EMBASE for articles published on changes of gut microbiota associated with implementation of LPD in CKD patients until July 2021. Independent researchers extracted data and assessed risks of bias. We conducted meta-analyses of combine p-value, mean differences and random effects for gut microbiota and related metabolites. Study heterogeneity was measured by Tau 2 and I 2 statistic. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Five articles met inclusion criteria. The meta-analyses of gut microbiota exhibited enrichments of Lactobacillaceae (meta- p = 0.010), Bacteroidaceae (meta- p = 0.048) and Streptococcus anginosus (meta- p < 0.001), but revealed depletion of Bacteroides eggerthii ( p =0.017) and Roseburia faecis (meta- p =0.019) in LPD patients compared to patients undergoing normal protein diet. The serum IS levels (mean difference: 0.68 ug/mL, 95% CI: -8.38-9.68, p = 0.89) and pCS levels (mean difference: -3.85 ug/mL, 95% CI: -15.49-7.78, p < 0.52) did not change between groups. We did not find significant differences on renal function associated with change of microbiota between groups (eGFR, mean difference: -7.21 mL/min/1.73 m 2 , 95% CI: -33.2-18.79, p = 0.59; blood urea nitrogen, mean difference: -6.8 mg/dL, 95% CI: -46.42-32.82, p = 0.74). Other clinical (sodium, potassium, phosphate, albumin, fasting sugar, uric acid, total cholesterol, triglycerides, C-reactive protein and hemoglobin) and anthropometric estimates (body mass index, systolic blood pressure and diastolic blood pressure) did not differ between the two groups. Conclusions: This systematic review and meta-analysis suggested that the effects of LPD on the microbiota were observed predominantly at the families and species levels but minimal on microbial diversity or richness. In the absence of global compositional microbiota shifts, the species-level changes appear insufficient to alter metabolic or clinical outputs., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The efficiency of thin-film chalcogenide solar cells is dependent on their window layer thickness. However, the application of an ultrathin window layer is difficult because of the limited capability of the deposition process. This paper reports the use of atomic layer deposition (ALD) processes for fabrication of thin window layers for Cu(In x ,Ga 1-x )Se 2 (CIGS) thin-film solar cells, replacing conventional sputtering techniques. We fabricated a viable ultrathin 12 nm window layer on a CdS buffer layer from the uniform conformal coating provided by ALD. CIGS solar cells with an ALD ZnO window layer exhibited superior photovoltaic performances to those of cells with a sputtered intrinsic ZnO (i-ZnO) window layer. The short-circuit current of the former solar cells improved with the reduction in light loss caused by using a thinner ZnO window layer with a wider band gap. Ultrathin uniform A-ZnO window layers also proved more effective than sputtered i-ZnO layers at improving the open-circuit voltage of the CIGS solar cells, because of the additional buffering effect caused by their semiconducting nature. In addition, because of the precise control of the material structure provided by ALD, CIGS solar cells with A-ZnO window layers exhibited a narrow deviation of photovoltaic properties, advantageous for large-scale mass production purposes.

Objective: The optimal treatment modality for retrograde type A intramural hematoma (IMH) remains debatable. This study evaluated and compared surgical outcomes and aortic remodeling after open aortic repair and thoracic endovascular aortic repair (TEVAR) in patients with retrograde type A IMH with a primary intimal tear or ulcer like projection in the descending aorta. Methods: A single center, retrospective observational study was performed on patients with retrograde type A IMH undergoing either open aortic repair and TEVAR. From June 2009 and November 2019, 46 patients with retrograde type A IMH who received either open aortic repair or TEVAR at our institution were reviewed for clinical outcomes, including post-operative mortality/morbidity, re-intervention rate and aortic remodeling. Results: 33 patients underwent open aortic repair and 13 underwent TEVAR. Median age was 68 years (interquartile range [IQR] 15.2 years) and 63 years (IQR 22.5 years) for the open repair group and TEVAR group, respectively. The median duration of follow-up for TEVAR patients was 37.6 months and 40.3 months for open aortic repair. No difference in the 5-year estimated freedom from all-cause mortality (82.1 vs. 87.8%, p = 0.34), re-intervention (82.5 vs. 93.8%, p = 0.08), and aortic-related mortality (88.9 vs. 90.9%, p = 0.88) were observed between the TEVAR and open repair group, respectively; however, the open repair group had a significantly higher 30-day composite morbidity (39.4 vs. 7.7%, p = 0.037). All patients from both treatment groups had complete resolution of the IMH in the ascending aorta. With regard to the descending thoracic aorta, TEVAR group had a significantly greater regression in the diameter of the false lumen or IMH thickness when compared to the open repair group [median 14mm (IQR 10.1) vs. 5mm (IQR 9.5), p < 0.001]. Conclusion: TEVAR and open aortic repair were both effective treatments for retrograde type A IMH, in which no residual ascending aortic IMH was observed during follow-up. TEVAR was also associated with lower post-operative composite morbidities and better descending aortic remodeling. In selected patients with retrograde type A IMH, TEVAR might be a safe, effective alternative treatment modality., 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 © 2021 Yang, Chi, Yu, Chen, Wang and Wu.)

To assess real-world effectiveness of hyperbaric oxygen therapy (HBOT) on delayed neuropsychiatric sequelae (DNS) after carbon monoxide (CO) poisoning we conducted a retrospective review of patients with CO poisoning admitted to Linkou Chang-Gung Memorial Hospital, Taiwan's largest medical center, during 2009-2015. We included patients developing DNS after CO poisoning and compared improvements in neuropsychiatric function, with and without HBOT, after 12 months post-DNS to understand differences in recovery rates. DNS improvement-associated factors were also evaluated. We used receiver operating characteristic (ROC) curve analysis to assess the role of time elapsed between DNS diagnosis and HBOT initiation in predicting DNS improvement. A total of 62 patients developed DNS, of whom 11 recovered while the rest did not. Possible factors predicting DNS improvement included receiving HBOT post-DNS (72.7% vs 25.5%; P = 0.006), and treatment with more than three HBOT sessions during acute stage CO poisoning (81.8% vs 27.5%; P = 0.003). The relevant area under the ROC curve was 0.789 (95% CI 0.603-0.974), and the best cut-off point was 3 days post-DNS diagnosis, with 87.5% sensitivity and 61.5% specificity. Early HBOT in patients who developed DNS after CO poisoning significantly improved their DNS symptoms, with treatment effects sustained for 1 year after DNS diagnosis., (© 2021. The Author(s).)

Objective: We aimed to investigate the annual incidence and direct medical cost of adjustment disorder in general population using the National Health Insurance Service Database (NHID) in Korea., Methods: To examine the incidence, we selected patients who had at least one medical claim for adjustment disorder and had not been diagnosed in the previous 365 days, from 2010 to 2017., Results: The number of newly diagnosed cases of adjustment disorder from 2011 to 2017 were total 101,922. Annual incidence of adjustment disorder was ranged from 22.0 to 36.8 per 100,000 persons. The incidence of adjustment disorder was found more in female and highest among 70-79 years of age group and medical aid beneficiaries group. Annual prevalence of adjustment disorder was in the range from 95.4 to 116.4 per 100,000 persons. Estimated annual medical cost per person of adjustment disorder was ranged from 162 to 231.4 US dollars., Conclusion: From 2011 to 2017, the annual incidence and direct medical cost of adjustment disorder in Korea were increased. Proper information on adjustment disorder will not only allows us to accumulate more knowledge but also lead to more appropriate therapeutic interventions.

Rather than using wooden sticks to simulate the breakage of trees in high winds as in most research, we employ fresh samples from camphor and Formosa gum with branches and leaves to certify the crucial role of the tree crown. By using a blowdown wind tunnel with a maximum wind speed of 50 m/s, we purposely reduce the number of leaves and show that the drag force will drop by as much as two thirds when half pruned. Based on real observations, we model the leaf by an open and full cone in the presence of light and strong winds, and calculate how their corresponding cross-sectional area A and drag force F vary with wind speed v. Different slopes before and after the formation of a full cone are predicted and confirmed when these two quantities are plotted in full-log scale. Compared to the empirical value, our simple model gave α=2/5 and 2/3 for A∝v^{-α} and β=4/5 and 2/3 for F∝v^{β} at low and high winds. Discrepancies can be accounted for by including further details, such as the reorientation of open cones and the movement of branches.

Although the basic mechanism of acupuncture-moxibustion has been revealed from many aspects, there are still many shackles in the transformation of the related research achievements. The transformation of academic achievements of experimental acupunctology is an urgent issue to be solved at present. Network regulation is the basic action mode of acupuncture therapy. In the present paper, we proposed that the "acupuncture network drug" could carry a variety of effective active ingredients which may be the core component of network regulation of acupuncture therapy. The "exosomes", polyvesicle derived from the intracellular lysosomal microparticles invagination, contain complex RNAs and proteins and exist in the body fluids and function in secreting abundant activate substances to participate in intercellular communication, which is the research hotspot in the field of frontier life science in the world. They play an important role in the diagnosis and treatment of diseases, and drug development, etc.. Our studies using rats with adjuvant arthritis and mice with sepsis displayed that after intraperitoneal administration of serum exosomes derived from normal animals receiving acupuncture intervention, an acupuncture-like analgesic effect and an anti-inflammatory effect were achieved, respectively. It is thus possible that acupuncture network drugs could be developed from serum exosomes secreted by exosome autogenous living cells after acupuncture intervention by virtue of the characteristics of low immunogenicity and may have great advantages in drug development and modification. It is also expected to provide new ideas for the transformation of experimental research results and to in depth give explanations about the underlying mechanisms of acupuncture therapy.

Background: EPHB4 and its ligand, ephrin B2, which are receptor tyrosine kinases of the erythropoietin-producing hepatocellular (EPH) family, are known to be linked to several human cancers. The aim of this study was to investigate their expression patterns in cutaneous squamous cell carcinoma (CSCC) in association with tumor differentiation and other variable clinical characteristics., Materials and Methods: Immunohistochemical staining for EPHB4 and ephrin B2 was performed in 32 cases of CSCC with different histologic grades. The clinical characteristics and histologic grades of CSCC were evaluated in association with EPHB4 and ephrin B2 expression patterns., Results: EPHB4 and ephrin B2 expression levels were significantly inversely proportional to the grade of differentiation of CSCC (P < 0.001 and P < 0.001, respectively)., Conclusion: These results indicated that EPHB4 and ephrin B2 can be useful markers for poorly differentiated CSCC., (© 2021 the International Society of Dermatology.)

Background/aims: Connective tissue growth factor (CTGF) is a profibrotic factor implicated in pressure overload-mediated myocardial fibrosis. In this study, we determined the role of predicted CTGF-targeting microRNAs (miRNAs) in rat models of aortic stenosis and reverse cardiac remodeling., Methods: Minimally invasive ascending aortic banding was performed in 24 7-week-old male Sprague-Dawley rats, which were divided into three groups. The banding group consisted of eight rats that were sacrificed immediately after 6 weeks of aortic constriction. The debanding group underwent aortic constriction for 4 weeks and was sacrificed 2 weeks after band removal. The third group underwent sham surgery. We investigated the expression of CTGF, transforming growth factor-β1 (TGFβ1), and matrix metalloproteinase-2 using ELISA and examined miRNA-26b, miRNA-133a, and miRNA-19b as predicted CTGF-targeting miRNAs based on miRNA databases in 24-hour TGFβ-stimulated and TGFβ- washed fibroblasts and myocardial tissues from all subjects., Results: CTGF was elevated in 24-hour TGFβ-stimulated fibroblasts and decreased in 24-hour TGFβ-washed fibroblasts. miRNA-26b was significantly increased in TGFβ-washed fibroblasts compared with control and TGFβ-stimulated fibroblasts (p < 0.05). CTGF expression was significantly higher in the banding group than that in the sham and debanding groups. The relative expression levels of miRNA-26b were higher in the debanding group than in the banding group., Conclusion: The results of our study using models of aortic banding and debanding suggested that miRNA-26b was significantly increased after aortic debanding. The in vitro model yielded the same results: miRNA-26b was upregulated after removal of TGFβ from fibroblasts.

A red fluorescent material, 1,3,7,9-tetrakis(4-( tert -butyl)phenyl)-5,5-difluoro-10-(2-methoxyphenyl)-5 H -4l4,5l4-dipyrrolo[1,2- c :2',1'- f ][1,3,2]diazaborinine (4tBuMB), as an emitting dopant in a thermally activated delayed fluorescence (TADF) sensitized hyperfluorescence organic light-emitting diode (HFOLED) is reported. The 4tBuMB shows a high photoluminescence quantum yield (PLQY) of 99% with an emission maximum at 620 nm and a full width at half-maximum (fwhm) of 31 nm in solution. Further, it shows a deep lowest unoccupied molecular orbital (LUMO) of 3.83 eV. Thus, two TADF materials, 4CzIPN and 4CzTPN, as sensitizing hosts, are selected on the basis of a suitable LUMO level and spectrum overlap with 4tBuMB. The fabricated HFOLED device with 4CzTPN as a sensitizing host and 4tBuMB as an emitting dopant shows a maximum external quantum efficiency (EQE), an emission maximum, an fwhm, and CIE coordinates of 19.4%, 617 nm, 44 nm, and (0.64, 0.36), respectively. The electroluminance performances of the 4CzTPN sensitized device are higher than those of the 4CzIPN-based device, which is attributed to a higher Förster resonance energy transfer (FRET) rate and reduced intersystem crossing/reverse intersystem crossing (ISC/RISC) cycles of the former. Also, the 4CzTPN-based HF device shows a longer device lifetime (LT 90 ) of 954 h than the 4CzIPN-baed device (LT 90 of 57 h) at 3000 cd m -2 . The higher device stability is due to the higher bond dissociation energies (BDEs) of 4CzTPN and 4tBuMB than that of 4CzIPN.

We used antioxidant-containing nanoparticles (NPs) to treat acute hearing loss. Alpha-lipoic acid (ALA) served as the antioxidant; we employed Pluronic F127 to fabricate NPs. In vitro, ALA-NPs protected cells of the organ of Corti in HEI-OC1 mice, triggering nuclear translocation of NRF2 and increases in the levels of antioxidant proteins, including Nrf2, HO-1, SOD-1, and SOD-2. In vivo, the hearing of mice that received ALA-NP injections into the middle ear cavity was better preserved after induction of ototoxicity than in control animals. The cochlear Nrf2 level increased in test mice, indicating that the ALA-NPs protected hearing via the antioxidant mechanism observed in vitro. ALA-NPs effectively protected against acute hearing loss by activating the Nrf2/HO-1 pathway., (Copyright © 2020 Elsevier Inc. All rights reserved.)