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Cavitation may occur in water-jet pump during operation of water-jet propulsion vessel, and once cavitation occurs, the tip clearance pulsating pressure of the impeller may be intensified, resulting in increased vibration of the water-jet propulsion unit. In this paper, the cavitation pulsating pressure characteristics at different positions in the pump are studied by experiment and numerical simulation, and the pulsating pressure characteristics in tip clearance are mainly researched. Based on Star-CCM+ commercial software, unsteady Reynolds-averaged Navier-Stokes equations(RANS) numerical simulation is carried out, and the feasibility of the numerical simulation method is verified by uncertainty analysis. The results show that the cavitation pulsating pressure near the leading edge of the impeller in the tip clearance is the largest. The variation of the tip clearance pulsating pressure with the intensification of cavitation is studied by numerical simulation, and its mechanism is revealed. A dimensionless coefficient of net positive suction head (CNPSH) is proposed, and the study shows that the cavitation pulsation pressure coefficients of pumps of different scales are equal when the working conditions are similar and the CNPSH are equal, which indicates that the cavitation pulsating pressure performance of full scale pump can be predicted by model scale. It is of great significance to evaluate the vibration performance of the full scale water-jet propulsion., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Qiu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: To comprehensively assess the neurologic recovery potential of chondroitinase ABC (ChABC) in rats after spinal cord injury (SCI)., Methods: The PubMed, Embase, ScienceDirect, Web of Science, and China National Knowledge Infrastructure databases were searched for animal experiments that evaluated the use of ChABC in the treatment of SCI up to November 2022. Studies reporting neurological function using the Basso, Beattie, and Bresnahan (BBB) scale, as well as assessments of cavity area, lesion area, and glial fibrillary acidic protein (GFAP) levels, were included in the analysis., Results: A total of 46 studies were ultimately selected for inclusion. The results of the study showed that rats with SCI that received ChABC therapy exhibited a significant improvement in locomotor function after 7 days compared with controls (32 studies, weighted mean difference (WMD) = 0.58, [0.33, 0.83], p  < 0.00001). Furthermore, the benefits of ChABC therapy were maintained for up to 28 days according to BBB scale. The lesion area was reduced by ChABC (5 studies, WMD = -20.94, [-28.42, -13.46], p  < 0.00001). Meanwhile, GFAP levels were reduced in the ChABC treatment group (8 studies, WMD = -29.15, [-41.57, -16.72], p <  0.00001). Cavity area is not statistically significant. The subgroup analysis recommended that a single injection of 10 μL (8 studies, WMD = 2.82, [1.99, 3.65], p <  0.00001) or 20 U/mL (4 studies, WMD = 2.21, [0.73, 3.70], p =  0.003) had a better effect on improving the function. The funnel plot of the BBB scale was found to be essentially symmetrical, indicating a low risk of publication bias., Conclusions: This systematic review and meta-analysis has indicated that ChABC could improve functional recovery in rats after SCI.

Background: The National Chest Pain Center Program (NCPCP) is a nationwide, quality enhancement program aimed at raising the standard of care for patients experiencing acute chest pain in China. The benefits of chest pain center (CPC) accreditation on acute coronary syndrome have been demonstrated. However, there is no evidence to indicate whether CPC accreditation improves outcomes for patients with acute aortic dissection (AAD)., Methods: We conducted a retrospective observational study of patients with AAD from 1671 hospitals in China, using data from the NCPCP spanning the period from January 1, 2016 to December 31, 2022. The patients were divided into 2 groups: pre-accreditation and post-accreditation admissions. The outcomes examined included in-hospital mortality, misdiagnosis, and Stanford type A AAD surgery. Multivariate logistic regression was employed to explore the relationship between CPC accreditation and in-hospital outcomes. Furthermore, we stratified the hospitals based on their geographical location (Eastern/Central/Western regions) or administrative status (provincial/non-provincial capital areas) to assess the impact of CPC accreditation on AAD patients across various regions., Results: The analysis encompassed a total of 40,848 patients diagnosed with AAD. The post-accreditation group exhibited significantly lower rates of in-hospital mortality and misdiagnosis (12.1% vs. 16.3%, P < 0.001 and 2.9% vs. 5.4%, P < 0.001, respectively) as well as a notably higher rate of Stanford type A AAD surgery (61.1% vs. 42.1%, P < 0.001) compared with the pre-accreditation group. After adjusting for potential covariates, CPC accreditation was associated with substantially reduced risks of in-hospital mortality (adjusted OR 0.644, 95% CI 0.599-0.693) and misdiagnosis (adjusted OR 0.554, 95% CI 0.493-0.624), along with an increase in the proportion of patients undergoing Stanford type A AAD surgery (adjusted OR 1.973, 95% CI 1.797-2.165). Following CPC accreditation, there were significant reductions in in-hospital mortality across various regions, particularly in Western regions (from 21.5 to 14.1%). Moreover, CPC accreditation demonstrated a more pronounced impact on in-hospital mortality in non-provincial cities compared to provincial cities (adjusted OR 0.607 vs. 0.713)., Conclusion: CPC accreditation is correlated with improved management and in-hospital outcomes for patients with AAD., (© 2024. The Author(s).)

Precise tuning the structure of catalytic center is of great importance for the construction of enhanced electrochemiluminescence (ECL) emitters and the development of ECL amplification strategies, which is a key factor in improving the sensitivity of biosensors. In this work, we report the enhanced ECL emitters based on the porphyrin-based paddlewheel framework (PPF) with axial coordinated imidazole-like ligands (PPF/X, X = 2-methylimidazole (MeIm), imidazole (Im), benzimidazole (BIM)). In this system, the electron-donating ability of the axial ligands is positively correlated to its coordination ability to the paddlewheel units and the catalytic ability of the axially coordinated paddlewheel units. In addition, the electrochemical and ECL behavior of PPF/X (X = MeIm, Im, BIM) with different axial coordinated ligands are explored., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Efficient and robust electrochemiluminescence (ECL) emitters are crucial for enhancing the ECL immunosensor sensitivity. This study introduces a novel ECL emitter, CoBIM/Cys, featuring a hierarchical core-shell structure. The core of the structure is created through the swift coordination between the sulfhydryl and carboxyl groups of l-cysteine (l-Cys) and cobalt ions (Co 2+ ), while the shell is constructed by sequentially coordinating benzimidazole (BIM) with Co 2+ . This design yields a greater specific surface area and a more intricate porous structure compared to CoBIM, markedly enhancing mass transfer and luminophore accessibility. Moreover, the l-Cys and Co 2+ core introduces Co-S and Co-O catalytic sites, which improve the catalytic decomposition of H 2 O 2 , leading to an increased production of hydroperoxyl radicals (OOH • ). This mechanism substantially amplifies the ECL performance. Leveraging the competitive interaction between isoluminol and BIM for OOH • during ECL emission, we developed a ratiometric immunosensor for cardiac troponin I (cTnI) detection. This immunosensor demonstrates a remarkably broad detection range (1 pg mL -1 to 10 ng mL -1 ), a low detection limit (0.4 pg mL -1 ), and exceptional reproducibility and specificity.

Introduction: Magnetic Resonance Imaging (MRI) is essential in diagnosing cervical spondylosis, providing detailed visualization of osseous and soft tissue structures in the cervical spine. However, manual measurements hinder the assessment of cervical spine sagittal balance, leading to time-consuming and error-prone processes. This study presents the Pyramid DBSCAN Simple Linear Iterative Cluster (PDB-SLIC), an automated segmentation algorithm for vertebral bodies in T2-weighted MR images, aiming to streamline sagittal balance assessment for spinal surgeons. Method: PDB-SLIC combines the SLIC superpixel segmentation algorithm with DBSCAN clustering and underwent rigorous testing using an extensive dataset of T2-weighted mid-sagittal MR images from 4,258 patients across ten hospitals in China. The efficacy of PDB-SLIC was compared against other algorithms and networks in terms of superpixel segmentation quality and vertebral body segmentation accuracy. Validation included a comparative analysis of manual and automated measurements of cervical sagittal parameters and scrutiny of PDB-SLIC's measurement stability across diverse hospital settings and MR scanning machines. Result: PDB-SLIC outperforms other algorithms in vertebral body segmentation quality, with high accuracy, recall, and Jaccard index. Minimal error deviation was observed compared to manual measurements, with correlation coefficients exceeding 95%. PDB-SLIC demonstrated commendable performance in processing cervical spine T2-weighted MR images from various hospital settings, MRI machines, and patient demographics. Discussion: The PDB-SLIC algorithm emerges as an accurate, objective, and efficient tool for evaluating cervical spine sagittal balance, providing valuable assistance to spinal surgeons in preoperative assessment, surgical strategy formulation, and prognostic inference. Additionally, it facilitates comprehensive measurement of sagittal balance parameters across diverse patient cohorts, contributing to the establishment of normative standards for cervical spine MR imaging., 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 © 2024 Zhong, Dai, Li, Zhu, Lin, Ran, Chen, Ruan, Yu, Li, Li, Xu, Sun, Weber, Kong, Yang, Lin, Chen, Chen, Jiang, Zhou, Sheng, Wang, Tian and Sun.)

Background: Cervical spondylotic myelopathy (CSM) is a degenerative pathology that affects both upper and lower extremity mobility and sensory function, causing significant pressure on patients and society. Prior research has suggested that ginsenosides may have neuroprotective properties in central nervous system diseases. However, the efficacy and mechanism of ginsenosides for CSM have yet to be investigated., Purpose: This study aims to analyze the composition of ginsenosides using UPLC-MS, identify the underlying mechanism of ginsenosides in treating CSM using network pharmacology, and subsequently confirm the efficacy and mechanism of ginsenosides in rats with chronic spinal cord compression., Methods: UPLC-Q-TOF-MS was utilized to obtain mass spectrum data of ginsenoside samples. The chemical constituents of the samples were analyzed by consulting literature reports and relevant databases. Ginsenoside and CSM targets were obtained from the TCMSP, OMIM, and GeneCards databases. GO and KEGG analyses were conducted, and a visualization network of ginsenosides-compounds-key targets-pathways-CSM was constructed, along with molecular docking of key bioactive compounds and targets, to identify the signaling pathways and proteins associated with the therapeutic effects of ginsenosides on CSM. Chronic spinal cord compression rats were intraperitoneally injected with ginsenosides (50 mg/kg and 150 mg/kg) and methylprednisolone for 28 days, and motor function was assessed to investigate the therapeutic efficacy of ginsenosides for CSM. The expression of proteins associated with TNF, IL-17, TLR4/MyD88/NF-κB, and NLRP3 signaling pathways was assessed by immunofluorescence staining and western blotting., Results: Using UPLC-Q-TOF-MS, 37 compounds were identified from ginsenoside samples. Furthermore, ginsenosides-compounds-key targets-pathways-CSM visualization network indicated that ginsenosides may modulate the PI3K-Akt signaling pathway, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, Toll-like receptor signaling pathway and Apoptosis by targeting AKT1, TNF, MAPK1, CASP3, IL6, and IL1B, exerting a therapeutic effect on CSM. By attenuating neuroinflammation through the TNF, IL-17, TLR4/MyD88/NF-κB, and MAPK signaling pathways, ginsenosides restored the motor function of rats with CSM, and ginsenosides 150 mg/kg showed better effect. This was achieved by reducing the phosphorylation of NF-κB and the activation of the NLRP3 inflammasome., Conclusions: The results of network pharmacology indicate that ginsenosides can inhibit neuroinflammation resulting from spinal cord compression through multiple pathways and targets. This finding was validated through in vivo tests, which demonstrated that ginsenosides can reduce neuroinflammation by inhibiting NLRP3 inflammasomes via multiple signaling pathways, additionally, it should be noted that 150 mg/kg was a relatively superior dose. This study is the first to verify the intrinsic molecular mechanism of ginsenosides in treating CSM by combining pharmacokinetics, network pharmacology, and animal experiments. The findings can provide evidence for subsequent clinical research and drug development., Competing Interests: Declaration of competing interest There are no conflicts of interest associated with this publication., (Copyright © 2023. Published by Elsevier GmbH.)

Aspercitrininone A (1), a novel polyketide featuring an unprecedented tetracyclic 6/6/6/5 spiral skeleton, was obtained from the rice fermentation cultures of the fungus Aspergillus cristatus together with five known compounds (2-6). Their structures were determined by HRESIMS data, 1D and 2D NMR spectroscopic analysis, and electronic circular dichroism (ECD) calculations. Aspercitrininone A was revealed as a new type of C/D cycle spiral structure and an unusual addition product of o-quinoid form citrinin with 2-methylterrefuranone. Compounds 1, 4, and 5 exhibited potent antibacterial activities with minimal inhibitory concentration (MIC) values from 13.2 to 67.3 μg/mL against four strains of human pathogenic bacteria in vitro., 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.)

Diabetic retinopathy (DR) is a leading cause of irreversible vision loss in working-age populations. Fat mass and obesity-associated protein (FTO) is an N 6 -methyladenosine (m 6 A) demethylase that demethylates RNAs involved in energy homeostasis, though its influence on DR is not well studied. Herein, we detected elevated FTO expression in vitreous fibrovascular membranes of patients with proliferative DR. FTO promoted cell cycle progression and tip cell formation of endothelial cells (ECs) to facilitate angiogenesis in vitro, in mice, and in zebrafish. FTO also regulated EC-pericyte crosstalk to trigger diabetic microvascular leakage, and mediated EC-microglia interactions to induce retinal inflammation and neurodegeneration in vivo and in vitro. Mechanistically, FTO affected EC features via modulating CDK2 mRNA stability in an m 6 A-YTHDF2-dependent manner. FTO up-regulation under diabetic conditions was driven by lactate-mediated histone lactylation. FB23-2, an inhibitor to FTO's m 6 A demethylase activity, suppressed angiogenic phenotypes in vitro. To allow for systemic administration, we developed a nanoplatform encapsulating FB23-2 and confirmed its targeting and therapeutic efficiency in mice. Collectively, our study demonstrates that FTO is important for EC function and retinal homeostasis in DR, and warrants further investigation as a therapeutic target for DR patients., (© 2024. The Author(s).)

Selective and sensitive detection of nitrite has important medical and biological implications. In the present work, to obtain an enhanced electrochemiluminescence (ECL) determination of nitrite, a novel nano-ECL emitter CoBIM/cetyltrimethylammonium bromide (CTAB) was prepared via a micelle-assisted, energy-saving, and ecofriendly method based on benzimidazole (BIM) and CTAB. Unlike conventional micelle assistance, the deprotonated BIM (BIM - ) preferential placement was in the palisade layer of cationic CTAB-based micelles. Enriching the original CTAB micelle with BIM - disrupted its stability and resulted in the formation of considerably smaller BIM/CTAB-based micelles, providing a confined coordination environment for BIM - and Co 2+ . As a result, the growth of CoBIM/CTAB was also limited. Owing to the unusual nitration reaction between BIM and nitrite, the prepared CoBIM/CTAB was successfully applied as a novel ECL probe for the detection of nitrite with a wide linear range of 1-1500 μM and a low detection limit of 0.67 μM. This work also provides a promising ECL platform for ultrasensitive monitoring of nitrite and it was applied with sausages and pickled vegetables.

The G-quadruplex (G4) is a distinct geometric and electrophysical structure compared to classical double-stranded DNA, and its stability can impede essential cellular processes such as replication, transcription, and translation. This study focuses on the BsPif1 helicase, revealing its ability to bind independently to both single-stranded DNA (ssDNA) and G4 structures. The unfolding activity of BsPif1 on G4 relies on the presence of a single tail chain, and the covalent continuity between the single tail chain and the G4's main chain is necessary for efficient G4 unwinding. This suggests that ATP hydrolysis-driven ssDNA translocation exerts a pull force on G4 unwinding. Molecular dynamics simulations identified a specific region within BsPif1 that contains five crucial amino acid sites responsible for G4 binding and unwinding. A "molecular wire stripper" model is proposed to explain BsPif1's mechanism of G4 unwinding. These findings provide a new theoretical foundation for further exploration of the G4 development mechanism in Pif1 family helicases., 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 Elsevier Ltd. All rights reserved.)

Background: Inflammatory bowel disease (IBD) is associated with lacrimal gland dysfunction and ocular inflammation. The objective of this research was to elucidate the temporal relationships between IBD, dry eye disease (DED), and corneal surface damage., Methods: In a matched nationwide cohort study, we evaluated the risk of DED and corneal surface damage associated with IBD. Multivariable Cox proportional hazards regression analyses were implemented to estimate the risk of ocular complications., Results: A total of 54,293 matched pairs were included for analyses. The median follow-up time was 8.3 years (interquartile range: 5.5 - 10.5). The period incidence of DED was 8.18 and 5.42 per 1000 person-years in the IBD and non-IBD groups, respectively. After adjusting for confounders, statistically significant associations were found between IBD and DED [adjusted hazard ratio (aHR): 1.43, 95% confidence interval (CI): 1.35 - 1.51, p < 0.0001], Sjögren's syndrome-related (aHR: 1.67, 95% CI:1.46 - 1.90, p < 0.0001) and non-Sjögren's syndrome-related subtypes (aHR: 1.38, 95% CI: 1.30 - 1.46, p < 0.0001). Furthermore, increased risks of corneal surface damage (aHR: 1.13, 95% CI: 1.03 - 1.24, p = 0.0094) among the patients with IBD were observed when compared with the controls. Other independent factors associated with corneal surface damage were age (aHR: 1.003), sex (male vs. female, aHR: 0.85), and monthly insurance premium (501-800 vs. 0-500 U.S. dollars, aHR: 1.45; ≥ 801 vs. 0-500 U.S. dollars, aHR: 1.32)., Conclusions: Our results suggested that IBD was an independent risk factor for DED and ocular surface damage. Clinical strategies are needed to prevent visual impairment or losses in these susceptible patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Territorial ecological restoration planning is a carrier process for carrying out territorial space regulation and ecological restoration. However, current urban planning efforts only focus on ecological processes, and fail to coordinate the development of both ecology and society. Taking Shantou, a city in Guangdong Province, as an example, we focused on the identification of ecological restoration nodes and the development of differentiated planning strategies from a comprehensive ecological-social perspective. By considering ecosystem integrity, we extracted the ecological corridors and key points by identifying ecological sources and constructing resistance surfaces, constructed an ecological recreation service evaluation system from the social perspective in terms of recreational allocation and recreational value to identify key areas for recreation services, and obtained different types of ecological restoration strategies by synthesizing the results of ecology and recreation. The results showed that there were 136 ecological corridors and 77 ecological nodes in Shantou, with a total length of 380.58 km. The most important recreation areas were the coastline, several inland bays, and wetland tidal flats, with an area of 33.78 km 2 and accounting for 1.6% of the total area. Low-level recreation areas was the largest, accounting for 57.3% of the total area. We proposed the composite strategy of "recreation expansion & fishery development", the connectivity strategy of "ecological construction & corridor connection", and the protection strategy of "vegetation restoration & development restriction". This study would provide a comprehensive analysis path for the ecological protection and restoration planning of coastal cities, and would help promote the practicality and maximizing the comprehensive benefits of territorial ecological restoration planning.

Cervical spondylotic myelopathy (CSM) is a severe non-traumatic spinal cord injury (SCI) wherein the spinal canal and cervical cord are compressed due to the degeneration of cervical tissues. To explore the mechanism of CSM, the ideal model of chronic cervical cord compression in rats was constructed by embedding a polyvinyl alcohol-polyacrylamide hydrogel in lamina space. Then, the RNA sequencing technology was used to screen the differentially expressed genes (DEGs) and enriched pathways among intact and compressed spinal cords. A total of 444 DEGs were filtered out based on the value of log 2 (Compression/Sham); these were associated with IL-17, PI3K-AKT, TGF-β, and Hippo signaling pathways according to the GSEA, KEGG, and GO analyses. Transmission electron microscopy indicated the changes in mitochondrial morphology. Western blot and immunofluorescence staining revealed neuronal apoptosis, astrogliosis and microglial neuroinflammation in the lesion area. Specifically, the expression of apoptotic indicators, such as Bax and cleaved caspase-3, and inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, were upregulated. The activation of IL-17 signaling pathway was observed in microglia instead of neurons or astrocytes, the activation of TGF-β and inhibition of Hippo signaling pathways were detected in astrocytes instead of neurons or microglia, and the inhibition of PI3K-AKT signaling pathway was discovered in neurons rather than microglia of astrocytes in the lesion area. In conclusion, this study indicated that neuronal apoptosis was accompanied by inhibiting of the PI3K-AKT pathway. Then, the activation of microglia IL-17 pathway and NLRP3 inflammasome effectuated the neuroinflammation, and astrogliosis was ascribed to the activation of TGF-β and the inhibition of the Hippo pathway in the chronic cervical cord of compression. Therefore, therapeutic methods targeting these pathways in nerve cells could be promising CSM treatments., Competing Interests: Declaration of competing interest The author states that there is no conflict of interest., (Copyright © 2023 Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The purpose of this study was to construct an animal model of Graves' ophthalmopathy (GO) by comparing recombinant adenovirus expressing human thyrotropin receptor A subunit (Ad-TSHR A) gene immunization and dendritic cell (DC) immunization. We evaluated the animal models that are closer to the pathology of human GO, and laid the foundation for the study of GO., Materials and Methods: Ad-TSHR A was injected intramuscularly into female BALB/c mice to induce the GO animal model. A GO animal model was constructed using TSHR combined with IFN-γ-modified primary DC immunized female BALB/c. The animal models constructed by the above two methods were evaluated in terms of ocular appearance, serology, pathology, and imaging to assess the modeling rate of the animal models, respectively., Results: Both modeled mice exhibited increased serological indexes of free thyroxine (FT4) and TSH receptor antibodies (TRAbs) levels and decreased TSH (P < 0.01). Thyroid pathology analysis revealed the number of thyroid follicles increases, the size varies, and the follicular epithelial cells proliferate to varying degrees in a cuboidal or tall columnar pattern, with a small amount of lymphocytic infiltration visible. Adipose tissue behind the eyeball was accumulated, the muscle outside the eyeball was broken and fibrotic, and hyaluronic acid (HA) behind the eyeball was increased. The animal model of GO constructed by immunization of TSHR with IFN-γ-modified DC had a modeling rate of 60%, whereas that of Ad-TSHR A gene immunization was 72%., Conclusions: Both gene immunization and cellular immunization can be used to construct GO models, and the modeling rate of gene immunization is higher than that of cellular immunization., Translational Relevance: In this study, two innovative methods, cellular immunity and gene immunity, were used to establish GO animal models, which improved the success rate to a certain extent. To our knowledge, this study presents the first cellular immunity modeling idea of TSHR combined with IFN-γ for the GO animal model, which provides an animal model basis for understanding the pathogenesis of GO and developing new treatment methods.

Cervical spondylotic myelopathy (CSM) refers to a chronic injury of the cervical cord caused by cervical intervertebral disc degeneration. Endoplasmic reticulum (ER) homeostasis is essential to counteract neuronal apoptosis. ER stress, an integral part of ER homeostasis, was observed in a rat model of chronic cervical cord compression in our previous study. However, the correlation between ER homeostasis and CSM remains unknown. The antioxidant melatonin is known to exert therapeutic effects in acute spinal cord injury, but the specific effects and their potential mechanisms in the pathological processes of CSM require further exploration. The present study hypothesized that ER homeostasis is essential for neuronal apoptosis in the CSM and that melatonin maintains this homeostasis. The results showed that ER stress led to neuronal apoptosis in rats with chronic cervical cord compression. Conversely, melatonin attenuates protein kinase R-like ER kinase-eukaryotic initiation factor 2α-C/EBP-homologous protein, inositol-requiring enzyme 1, and transcription factor 6 signaling pathways to release ER stress and prevents Bax translocation to the mitochondrion, thereby promoting motor recovery and protecting neurons in vivo. It also rescued primary rat cortical neurons from ER stress-induced glutamate toxicity in vitro. Moreover, melatonin remodels the ER morphology and restores homeostasis via ER-phagy in injured neurons. FAM134B, CCPG1, RTN3, and Sec. 62 are four known ER-phagy receptors. In this study, Sec. 62 was identified as a key melatonin factor in promoting ER-phagy and restoring ER homeostasis in damaged neurons in vivo and in vitro. In conclusion, melatonin suppresses neuronal apoptosis by reducing ER stress and promoting ER-phagy to restore ER morphology and homeostasis. The current results suggested that melatonin is a promising treatment for CSM owing to its restorative effect on ER homeostasis; however, well-designed randomized controlled trials must be carried out to further investigate its clinical effects., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Autoimmune thyroid diseases (ATDs) are potentially connected to lacrimal gland dysfunction and ocular surface disruption. This study aimed to evaluate the relationships between ATD, dry eye disease (DED), and corneal surface damage. In a matched nationwide cohort study, we used Taiwan's National Health Insurance research database to compare the incidences of DED and corneal surface damage between subjects with and without ATD. Multivariable Cox proportional hazards regression models were used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for the ophthalmological outcomes. A total of 50,251 matched pairs with 748,961 person-years of follow-up were included for analysis. The incidence of DED was 16.37 and 8.36 per 1000 person-years in the ATD and non-ATD groups, respectively. ATDs were significantly associated with increased DED (aHR: 1.81, 95% CI: 1.73-1.89, p < 0.0001). This association was generally consistent across the subgroups of age, sex, different comorbidity levels, and use of systemic corticosteroids or not. Furthermore, patients with ATD had a higher risk of corneal surface damage compared with non-ATD subjects (aHR: 1.31, 95% CI: 1.19-1.44, p < 0.0001), including recurrent corneal erosions (aHR: 2.00, 95% CI: 1.66-2.41, p < 0.0001) and corneal scars (aHR: 1.26, 95% CI: 1.01-1.59, p = 0.0432). Other independent factors for corneal surface damage were age, sex, diabetes mellitus, Charlson Comorbidity Index scores, and use of systemic corticosteroids. Our results suggested that ATDs were associated with higher risks of DED and corneal surface damage. Considering the high prevalence of ATD, prophylactic and therapeutic strategies should be further developed to prevent irreversible vision loss in this susceptible population.

Systemic lupus erythematosus (SLE) potentially involves multiple parts of the ocular system, including the lacrimal glands and the cornea. The present study sought to assess the risk of aqueous-deficient dry eye disease (DED) and corneal surface damage in patients with SLE. We conducted a population-based cohort study using Taiwan's National Health Insurance research database to compare the risks of DED and corneal surface damage between subjects with and without SLE. Proportional hazard regression analyses were used to calculate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for the study outcomes. The propensity score matching procedure generated 5083 matched pairs with 78,817 person-years of follow-up for analyses. The incidence of DED was 31.90 and 7.66 per 1000 person-years in patients with and without SLE, respectively. After adjusting for covariates, SLE was significantly associated with DED (aHR: 3.30, 95% CI: 2.88-3.78, p < 0.0001) and secondary Sjögren's syndrome (aHR: 9.03, 95% CI: 6.86-11.88, p < 0.0001). Subgroup analyses demonstrated that the increased risk of DED was augmented among patients with age < 65 years and female sex. In addition, patients with SLE had a higher risk of corneal surface damage (aHR: 1.81, 95% CI: 1.35-2.41, p < 0.0001) compared to control subjects, including recurrent corneal erosion (aHR: 2.98, 95% CI: 1.63-5.46, p = 0.0004) and corneal scar (aHR: 2.23, 95% CI: 1.08-4.61, p = 0.0302). In this 12-year nationwide cohort study, we found that SLE was associated with increased risks of DED and corneal surface damage. Regular ophthalmology surveillance should be considered to prevent sight-threatening sequelae among patients with SLE.

Background: The treatment of bone defects remains a clinical challenge. The effect of negative pressure wound therapy (NPWT) on osteogenesis in bone defects has been recognized; however, bone marrow fluid dynamics under negative pressure (NP) remain unknown. In this study, we aimed to examine the marrow fluid mechanics within trabeculae by computational fluid dynamics (CFD), and to verify osteogenic gene expression, osteogenic differentiation to investigate the osteogenic depth under NP. Methods: The human femoral head is scanned using micro-CT to segment the volume of interest (VOI) trabeculae. The VOI trabeculae CFD model simulating the bone marrow cavity is developed by combining the Hypermesh and ANSYS software. The effect of trabecular anisotropy is investigated, and bone regeneration effects are simulated under NP scales of -80, -120, -160, and -200 mmHg. The working distance (WD) is proposed to describe the suction depth of the NP. Finally, gene sequence analysis, cytological experiments including bone mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation are conducted after the BMSCs are cultured under the same NP scale. Results: The pressure, shear stress on trabeculae, and marrow fluid velocity decrease exponentially with an increase in WD. The hydromechanics of fluid at any WD inside the marrow cavity can be theoretically quantified. The NP scale significantly affects the fluid properties, especially those fluid close to the NP source; however, the effect of the NP scale become marginal as WD deepens. Anisotropy of trabecular structure coupled with the anisotropic hydrodynamic behavior of bone marrow; An NP of -120 mmHg demonstrates the majority of bone formation-related genes, as well as the most effective proliferation and osteogenic differentiation of BMSCs compared to the other NP scales. Conclusion: An NP of -120 mmHg may have the optimal activated ability to promote osteogenesis, but the effective WD may be limited to a certain depth. These findings help improve the understanding of fluid mechanisms behind NPWT in treating bone defects., 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. The handling editor, AP, declared a past co-authorship with the author CF., (Copyright © 2023 Huang, Zheng, Dai, Hu, Ning, Li, Fan, Lin and Huang.)

Exploring the depolymerization strategy of liposoluble luminophores in the aqueous phase is vital for the development of electrochemiluminescence (ECL). In this work, tetraoctylammonium bromide (TOAB) with four long hydrophobic chains and short hydrophilic ends is used as a template to limit the aggregation of benzimidazole (BIM). By adjusting the loading of BIM on the hydrophobic chains of TOAB, a two-dimensional lamellar BIM/TOAB is formed, the ECL intensity of which is 6.4 times higher than that of the aggregated BIM (H 2 O 2 as the coreactant). In terms of ECL spectroscopies, cyclic voltammetry , ECL transients, and the adjustment of the scanning potential range, the ECL mechanism is thoroughly studied. This work provides a new way to depolymerize organic luminophores and reveals a possible pathway in the annihilation ECL mechanism.

Rheumatoid arthritis is potentially connected to ocular disorders, such as corneal inflammation and lacrimal gland destruction. This study aimed to evaluate the risk of dry eye disease (DED) and corneal surface damage among patients with rheumatoid arthritis. In a nationwide cohort study, we utilized Taiwan’s National Health Insurance research database and conducted propensity score matching to compare the risks of DED and corneal surface damage between patients with and without rheumatoid arthritis. Proportional hazards regression analyses were used to calculate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for the outcomes of interest. The matching procedure generated 33,398 matched pairs with 501,377 person-years of follow-up for analyses. The incidence of DED was 23.14 and 10.25 per 1000 person-years in patients with and without rheumatoid arthritis, respectively. After adjusting for covariates, rheumatoid arthritis was significantly associated with DED (aHR: 2.03, 95% CI: 1.93−2.13, p < 0.0001). The association was generally consistent across the subgroups of age, sex, use of systemic corticosteroids, and different comorbidity levels. In addition, patients with rheumatoid arthritis had a higher risk of corneal surface damage (aHR: 1.36, 95% CI: 1.21−1.51, p < 0.0001) compared to control subjects. Other independent factors for corneal surface damage were age and sleeping disorders. Rheumatoid arthritis was associated with an increased risk of DED and corneal surface damage. Ophthalmological surveillance is required to prevent vision-threatening complications in this susceptible population.

Dupilumab interferes with the signaling pathways of IL-4 and IL-13 and is effective in treating atopic dermatitis. Specific genodermatoses, including Netherton syndrome, epidermolysis bullosa pruriginosa, and hyper-IgE syndrome, are Th2 skewed diseases with activation of type 2 inflammation. We performed this systematic review to investigate the therapeutic role of dupilumab in the treatment of genodermatosis. A systematic search was conducted of the PubMed, Embase, Web of Science, and Cochrane databases from inception to December 13, 2021. The review included studies with relevant terms including "dupilumab," "genodermatosis", "Netherton syndrome", "ichthyosis", "epidermolysis bullosa" and "hyper-IgE syndrome". The initial search yielded 2,888 results, of which 28 studies and 37 patients with genodermatosis were enrolled. The assessed genodermatoses included Netherton syndrome, epidermolysis bullosa pruriginosa, hyper-IgE syndrome, Hailey-Hailey disease, and severe eczema associated with genetic disorders. Most of the reported cases showed significant clinical improvement after the initiation of dupilumab treatment without major adverse events. Decreased immunoglobulin E levels and cytokine normalization have also been documented. In conclusion, Dupilumab may have a potential therapeutic role in certain genodermatoses skewed towards T helper 2 (Th2) immunity, including Netherton syndrome, epidermolysis bullosa pruriginosa, hyper-IgE syndrome, Hailey-Hailey disease, and severe eczema associated with some genetic disorders., (© 2023 Deutsche Dermatologische Gesellschaft (DDG).)

Background: There is growing evidence that patients with alopecia areata (AA) have an increased risk of developing psychiatric comorbidities. However, the relationship between AA and suicidal behaviors remains unclear., Objective: The objective of this study was to investigate the association between AA and suicidal behaviors., Methods: Participants were recruited from the National Health Insurance Research Database in Taiwan, including 10,515 patients with AA and 10,5150 matched controls, to assess the risk of suicide attempts. A Cox regression model was used for all analyses., Results: Compared with the controls, an increased risk of suicide attempts was observed in patients with AA, with an adjusted hazard ratio of 6.28 (95% confidence interval, 4.47-8.81). Suicide risk remained significantly elevated in AA patients when stratified by underlying psychiatric disorders. The mean age of initial suicidal behaviors was also lower in patients with AA., Conclusions: Patients with AA had a significantly higher incidence of suicidal attempts than controls, regardless of concurrent psychiatric illness. Further studies are needed to elucidate the pathophysiology of the association between AA and suicidality. In addition, dermatologists should be aware of the increased suicidality of patients with AA., (© 2023 S. Karger AG, Basel.)

Vaccinated or not? This is an attitude survey for 'approach-avoidance conflict' under uncertainty. Therefore, measuring people's attitude toward COVID-19 vaccination is relatively distinctive from an attitude over a general conflict. An online survey of 3123 respondents from 30 provincial-level regions - out of 31 - on the Chinese mainland was conducted from January 22 to 27, 2021 to measure their willingness to be vaccinated. We found that over half of the respondents chose the options 'not to be vaccinated now' and 'wait and see before making a vaccination decision,' thereby indicating that people's willingness to be vaccinated is not as optimistic as anticipated in the early stage of vaccination in China. Hence, investigators should carefully select the measuring method to assess the 'true' levels of willingness to accept COVID-19 vaccines. Lastly, the relevant departments should fully predict obstacles to achieve immunity coverage and prepare for the 'vaccine hesitancy' of people in need.

Background: Growing evidence has revealed abnormalities in the retinal structures of patients with alopecia areata (AA). However, the relationship between AA and retinopathy remains unclear., Objective: To investigate the association between AA and retinal diseases., Methods: The study participants were recruited from the National Health Insurance Research Database in Taiwan. We included 9909 patients with AA and 99,090 matched controls to assess the risk of retinal diseases. A Cox regression model was used for all analyses., Results: Compared with the controls, patients with AA had an adjusted hazard ratio (aHR) of 3.10 (95% confidence interval [CI] 2.26-4.26) for retinal diseases. With respect to individual retinal diseases, Patients with AA had significantly higher risks of developing retinal detachment (aHR 3.98; 95% CI 2.00-7.95), retinal vascular occlusion (aHR 2.45; 95% CI 1.22-4.92), and retinopathy (aHR 3.24; 95% CI 2.19-4.81) than controls., Limitations: This was a retrospective cohort study. Meanwhile, almost all the participating individuals were residents of Taiwan; therefore, the validity of our findings in other demographics remains unclear., Conclusion: Patients with AA had a significantly higher risk of retinal disease than controls. Further studies are needed to clarify the pathophysiology of AA and retinal diseases., Competing Interests: Conflict of interest None disclosed., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the related factors and early predictors of persistent ectopic pregnancy (PEP) in patients with interstitial pregnancy after operation. Methods: The clinical data of patients with interstitial pregnancy who underwent surgery in the Department of Obstetrics and Gynecology of Peking Union Medical College Hospital from January 2013 to August 2021 were collected. Patients were divided into two groups according to whether PEP occurred (8 patients in PEP group and 124 patients in non-PEP group). Using propensity score matching (PSM) analysis, the basic data, surgical methods, the ratio of postoperative to preoperative serum β-human chorionic gonadotropin (β-hCG), the duration of when the serum β-hCG had decreased to normal after the operation were compared and analyzed to find the related factors of PEP after interstitial pregnancy surgery. The sensitivity and specificity of the ratio of 24-48 hours postoperative β-hCG to preoperative β-hCG in predicting postoperative PEP were evaluated by drawing receiver operating characteristic (ROC) curve. Results: Before PSM, the ages of patients in PEP group and non-PEP group were (30.0±4.0) and (32.4±5.0) years old, respectively, P >0.05. After PSM, 8 PEP patients in the study group and 29 patients in the control group were matched successfully, and the ages of the two groups were (30.0±4.0) and (30.1±3.2) years old, respectively, P >0.05. After PSM, there was no significant difference in gravidity, parity, menopausal days, preoperative β-hCG level and maximum diameter of lesions, all P >0.05. After PSM, the proportion of patients with maximum diameter ≤ 2.6 cm in PEP group (6/8) was significantly higher than that in control group (31.0%, 9/29), P =0.025. The median ( Q 1 , Q 3 ) of the ratio of 24-48 hours postoperative β-hCG to preoperative β-hCG ratio was 52.9% (49.9%, 59.7%) in the PEP group, which was significantly higher than 31.5% (23.8%, 39.0%) in the control group ( P =0.001); The median ( Q 1 , Q 3 ) of duration of when the serum β-hCG had decreased to normal after the operation in PEP group was 52.0 (34.8, 92.0) d, which was significantly higher than 24.0 (20.5, 31.0) d in control group ( P <0.001). The ROC-Area Under Curve of the ratio of 24-48 hours postoperative β-hCG to preoperative β-hCG ratio for predicting postoperative PEP in the two groups was 0.892 (95% CI : 0.725-1.000, P =0.001). The cut-off value for predicting PEP was 48.5%, where the diagnostic sensitivity was 87.5%, the specificity was 93.1%. Conclusions: In the operation of interstitial pregnancy, the maximum diameter of lesion ≤ 2.6 cm is a related factor for postoperative PEP. There was no significant difference in the risk of PEP between cornuotomy and cornectomy. The ratio that 24-48 hours postoperative β-hCG/preoperative β-hCG ratio greater than 48.5% was a reference index for predicting postoperative PEP and guiding treatment.

G-quadruplexes (G4s) are unusual stable DNA structures that cause genomic instability. To overcome the potential barriers formed by G4s, cells have evolved different families of proteins that unfold G4s. Pif1 is a DNA helicase from superfamily 1 (SF1) conserved from bacteria to humans with high G4-unwinding activity. Here, we present the first X-ray crystal structure of the Thermus oshimai Pif1 (ToPif1) complexed with a G4. Our structure reveals that ToPif1 recognizes the entire native G4 via a cluster of amino acids at domains 1B/2B which constitute a G4-Recognizing Surface (GRS). The overall structure of the G4 maintains its three-layered propeller-type G4 topology, without significant reorganization of G-tetrads upon protein binding. The three G-tetrads in G4 are recognized by GRS residues mainly through electrostatic, ionic interactions, and hydrogen bonds formed between the GRS residues and the ribose-phosphate backbone. Compared with previously solved structures of SF2 helicases in complex with G4, our structure reveals how helicases from distinct superfamilies adopt different strategies for recognizing and unfolding G4s., (© 2022 The Authors.)

Sedative−hypnotic misuse is associated with psychiatric diseases and overdose deaths. It remains uncertain whether types of anesthesia affect the occurrence of new postoperative uses of sedative−hypnotics (NPUSH). We used reimbursement claims data of Taiwan’s National Health Insurance and conducted propensity score matching to compare the risk of NPUSH between general and neuraxial anesthesia among surgical patients who had no prescription of oral sedative−hypnotics or diagnosis of sleep disorders within the 12 months before surgery. The primary outcome was NPUSH within 180 days after surgery. Multivariable logistic regression models were used to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI). A total of 92,222 patients were evaluated after matching. Among them, 15,016 (16.3%) had NPUSH, and 2183 (4.7%) were made a concomitant diagnosis of sleep disorders. General anesthesia was significantly associated both with NPUSH (aOR: 1.17, 95% CI: 1.13−1.22, p < 0.0001) and NPUSH with sleep disorders (aOR: 1.11, 95% CI: 1.02−1.21, p = 0.0212) compared with neuraxial anesthesia. General anesthesia was also linked to NPUSH that occurred 90−180 days after surgery (aOR: 1.12, 95% CI: 1.06−1.19, p = 0.0002). Other risk factors for NPUSH were older age, female, lower insurance premium, orthopedic surgery, specific coexisting diseases (e.g., anxiety disorder), concurrent medications (e.g., systemic steroids), postoperative complications, perioperative blood transfusions, and admission to an intensive care unit. Patients undergoing general anesthesia had an increased risk of NPUSH compared with neuraxial anesthesia. This finding may provide an implication in risk stratification and prevention for sedative−hypnotic dependence after surgery.

Background: In neck pain treatment, many therapies are focused on etiology, while it is well-known that placebo analgesia is also present in these therapies. The specific efficacy for etiology may be underestimated by ignoring their actual placebo effect. In this study, a logistic regression analysis is used to explore the risk factors causing different placebo responses in patients with neck pain among two RCTs. The probability of the placebo effect is predicted based on these risk factors. Methods: Trial A and Trial B were similarly designed, randomized, double-/single-blind, placebo-controlled trials in patients treating neck pain with Qishe pill or Shi-style manipulation. Both studies set a placebo pill twice a day or traction for every other day as control. For further analyses on the placebo effect in neck pain management, logistic regression was used to assess subgroup-placebo interactions. The odds ratio assessed a significant influence on the placebo effect. Results: In this pooled analysis, the total number of patients recruited for these two studies was 284, of which 162 patients received placebo treatment (placebo drug or traction for every other day). No statistically significant differences are found at baseline between the participants with placebo effect and non-placebo effect in the gender, age, and disease duration except in VAS and NDI at the initial time. There are numerically more patients with placebo effect in the shorter disease duration subgroup (< 4 months [76%]), higher initial VAS subgroup (>60 mm [90%]), and worse initial NDI subgroup (>24 [72%]) compared with the gender and age subgroup. An ROC curve is established to assess the model-data fit, which shows an area under the curve of 0.755 and a 95% confidence interval of 0.677-0.830. Participants who show placebo effect after 2 weeks have significantly lower VAS scores after 4 weeks, while there is no significant difference in NDI improvement between the two groups after 4 weeks. Conclusion: Neck pain patients with shorter disease duration are more likely to overscore their pain severity, because of their less experience in pain perception, tolerance, and analgesia expectation., 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 Sun, Yao, Zhu, Yin, Liu, Chen, Huang, Dai, Wang, Ma, Wang and Cui.)

Purpose: Vaginal cuff dehiscence (and evisceration) (VCD(E)) is an extremely rare and late-onset complication of total hysterectomy (TH). Limited evidence is available to guide clinicians in managing VCD(E). This study aimed to summarize the clinical characteristics of patients with VCD(E) treated in our center and share our experience in managing VCD(E)., Patients and Methods: From 1983 to 2020, a total of 14 cases of VCD(E), including 10 cases in our hospital and 4 cases in other hospitals, were included. Medical records were reviewed to summarize the clinical features and management of VCD(E)., Results: The incidence of VCD(E) in our hospital was 10/46,993 (0.02%), and all 10 patients underwent laparoscopic hysterectomy. The median TH-to-VCD(E) interval was 3.13 months (8 days-27.43 months), and 11/14 (78.57%) patients experienced VCD(E) after coitus. The 3 major symptoms included abdominal pain in 11 patients, irregular vaginal bleeding in 8, and sensation of bulging or prolapsed organs in 4. Except for 2, most patients presented to our hospital within 72 h since the onset of the discomfort. All 14 cases were diagnosed through speculum examination: 3 had simple VCD, and 11 had VCDE. The protruding bowels of 4 patients were immediately manually repositioned in the emergency department without anesthesia. Regarding the surgical approach, 11 patients underwent simple transvaginal, 2 patients underwent laparoscopic-vaginal combined (transvaginal cuff closures), and 1 patient underwent laparoscopic. All but 1 patient did not undergo resection of the eviscerated organs. The median follow-up period was 39.33 (7.9-159.33) months. No patients showed any evidence of recurrence to date., Conclusions: Laparoscopic hysterectomy is a risk factor for VCD(E), and early initiation of sexual intercourse is the most common trigger of VCD(E). Clinicians should educate patients to postpone sexual intercourse for at least 3-6 months after TH. Immediate medical attention and patient-specific surgical management are crucial to avoid serious complications., 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 Ma, Cao and Dai.)

Background: Alopecia areata (AA) and irritable bowel syndrome (IBS) are two distinct diseases that share a similar pathophysiology; however, the relationship between these two diseases is unknown. This study aimed to investigate the bidirectional relationship between AA and IBS., Methods: Participants were recruited from the National Health Insurance Research Database in Taiwan. We included 5446 patients with AA and 21 784 matched controls to assess the risk of IBS, and 56 429 patients with IBS and 225 716 matched controls to assess the risk of AA. The Cox proportional-hazards regression model was used to calculate the adjusted hazard ratio (aHR)., Results: After adjustment for potential confounders, patients with AA had an aHR of 5.20 [95% confidence interval (CI) 3.97-6.82] for IBS in comparison with the controls. Furthermore, compared with the controls, IBS patients had an aHR of 5.38 (95% CI 3.95-7.34) for AA., Conclusion: AA is bidirectionally associated with IBS. Further investigation is needed to elucidate the shared pathogenesis underlying these two diseases., (© 2022 Australasian College of Dermatologists.)

In order to reveal the dissolution behavior of iron tailings in blast furnace slag, the main component of iron tailings, SiO 2 , was used for research. Aiming at the problem of information loss and inaccurate extraction of tracking molten SiO 2 particles in high temperature, a method based on the improved DeepLab v 3+ network was proposed to track, segment, and extract small object particles in real time. First, by improving the decoding layer of the DeepLab v 3+ network, construct dense ASPP (atrous spatial pyramid pooling) modules with different dilation rates to optimize feature extraction, increase the shallow convolution of the backbone network, and merge it into the upper convolution decoding part to increase detailed capture. Secondly, integrate the lightweight network MobileNet v3 to reduce network parameters, further speed up image detection, and reduce the memory usage to achieve real-time image segmentation and adapt to low-level configuration hardware. Finally, improve the expression of the loss function for the binary classification model of small object in this paper, combining the advantages of the Dice Loss binary classification segmentation and the Focal Loss balance of positive and negative samples, solving the problem of unbalanced dataset caused by the small proportion of positive samples. Experimental results show that MIoU (mean intersection over union) of the proposed model for small object segmentation is 6% higher than that of the original model, the overall MIoU is increased by 3%, and the execution time and memory consumption are only half of the original model, which can be well applied to real-time tracking and segmentation of small particles., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Tian-yu Jiang et al.)

We designed a study to compare the newly developed 5-mg flunarizine hydrochloride capsules (test) to that of its marketed counterpart (5-mg; reference) among healthy adult Chinese volunteers. We performed an open-label, single-center study that consisted of 2 randomized, crossover trials, including a fasting trial and a fed trial. In each part of the study, the subjects were randomly assigned to either receive the test or reference products (5-mg flunarizine) in a 1:1 ratio. Subjects then received the alternative products, following a 14-day washout period. Concentrations of plasma flunarizine were analyzed using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters (noncompartmental model) were evaluated using the WinNonlin software. The analysis of variance and Food and Drug Administration bioequivalence statistical criterion of 90% confidence interval for 80% to 125% range (set at P ≤ .05) of geometric means ratios of test: reference product for peak plasma concentration, area under the plasma concentration-time curve (AUC) from time 0 to time t, and AUC from time 0 to infinity were determined. Tolerability was evaluated during the entire study period. Overall, 23 volunteers completed the fasting study, while 40 volunteers completed the fed study. The test formulation was found to be bioequivalent to the marketed formulation, as the 90% confidence interval for the ratio of geometric means of peak plasma concentration (fasting: 87.61%-101.67%; fed: 87.38%-104.06%), AUC from time 0 to time t (fasting: 89.44%-99.92%; fed: 92.65%-98.28%), and AUC from time 0 to infinity (fasting: 95.02%-104.33%; fed: 90.41%-96.96%) were within equivalence limits (80-125%) under both the fasting and fed conditions. When flunarizine was given alongside high-fat meals, time to maximum concentration was delayed ≈3.5 hours compared to fasting conditions. Meantime, high-fat meals increased its exposure by nearly 50%. Furthermore, there were no serious adverse events found among the subjects. This study confirmed that test and reference flunarizine hydrochloride capsules were bioequivalent under fasting and postprandial conditions., (© 2021, The American College of Clinical Pharmacology.)

Background: The concurrent incidence of autoimmune comorbidities in obsessive-compulsive disorder (OCD) is known. However, the association between OCD and related autoimmune skin diseases (ASDs) has not been well studied., Objective: This study aimed to investigate the association between OCD and the risk of ASDs., Methods: To assess the risk of developing ASDs, we recruited 44 324 patients with OCD and 177 296 matched controls from the National Health Insurance Research Database in Taiwan. A Cox regression model was used for the analyses., Results: After adjusting for confounders, an increased risk of ASDs among the patients with OCD (adjusted hazard ratio [aHR]: 6.36; 95% confidence interval [CI]: 5.43-7.45) was found when compared to the controls. Statistically significant associations were found between OCD and seven individual ASDs, including psoriasis (aHR: 12.52; 95% CI: 8.78-17.85), lichen planus (aHR: 27.22; 95% CI: 13.09-56.60), alopecia areata (aHR: 13.69; 95% CI: 9.38-19.98), autoimmune bullous diseases (aHR: 4.30; 95% CI: 2.03-9.11), hidradenitis suppurativa (aHR: 29.95; 95% CI: 3.35-267.62), vitiligo (aHR: 9.35; 95% CI: 5.35-16.32), and lupus erythematosus (aHR: 2.10; 95% CI: 1.52-2.91)., Conclusions: Patients with OCD had an increased risk of developing ASDs compared to matched controls. Further studies are required to clarify the underlying mechanisms.

Migraine headaches can be provoked by surgical stress and vasoactive effects of anesthetics of general anesthesia in the perioperative period. However, it is unclear whether general anesthesia increases the migraine risk after major surgery. Incidence and risk factors of postoperative migraine are also largely unknown. We utilized reimbursement claims data of Taiwan's National Health Insurance and performed propensity score matching analyses to compare the risk of postoperative migraine in patients without migraine initially who underwent general or neuraxial anesthesia. Multivariable logistic regressions were applied to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) for migraine risk. A total of 68,131 matched pairs were analyzed. The overall incidence of migraine was 9.82 per 1000 person-years. General anesthesia was not associated with a greater risk of migraine compared with neuraxial anesthesia (aORs: 0.93, 95% CI: 0.80-1.09). This finding was consistent across subgroups of different migraine subtypes, uses of migraine medications, and varying postoperative periods. Influential factors for postoperative migraine were age (aOR: 0.99), sex (male vs. female, aOR: 0.50), pre-existing anxiety disorder (aOR: 2.43) or depressive disorder (aOR: 2.29), concurrent uses of systemic corticosteroids (aOR: 1.45), ephedrine (aOR: 1.45), and theophylline (aOR: 1.40), and number of emergency room visits before surgery. There was no difference in the risk of postoperative migraine between surgical patients undergoing general and neuraxial anesthesia. This study identified the risk factors for postoperative migraine headaches, which may provide an implication in facilitating early diagnoses and treatment.

Hepatitis C virus (HCV) infection is associated with several cutaneous manifestations, including lichen planus and psoriasis. However, its association with other chronic inflammatory skin diseases (CISD) remains largely unknown. The aim of this study was to investigate the association between HCV infection and CISD. Participants were recruited from the National Health Insurance Research Database in Taiwan. Altogether 23 509 patients with HCV infection and 94 036 matched controls were included to assess the risk of CISD. A Cox regression model was used for the analyses. Compared with controls, patients with HCV infection had an adjusted hazard ratio (aHR) of 6.34 (95% confidence interval [CI], 5.30-7.58) for CISD after adjustment for potential confounders. Regarding individual CISD, patients with HCV infection had a significantly increased risk of developing lichen planus, psoriasis, vitiligo, alopecia areata, and cutaneous lupus erythematosus. Interferon-based antiviral therapy (IFN-based AVT) was significantly associated with a decreased risk of CISD (aHR = 0.42; 95% CI, 0.28-0.64). Patients with HCV infection had a significantly increased risk of CISD, while IFN-based AVT was associated with a decreased risk. These findings suggest monitoring of CISD in patients with HCV infection., (© 2021 Japanese Dermatological Association.)

Background: Vitiligo is a common depigmenting disorder caused by the autoimmune destruction of melanocytes. Some evidence suggests the involvement of melanocytes in the auditory system in the disease process. However, the relationship between vitiligo and sensorineural hearing loss (SNHL) remains uncertain., Objective: We investigated the association between vitiligo and SNHL., Methods: In this systematic review and meta-analysis, EMBASE, MEDLINE, PubMed, and the Cochrane database were searched for studies examining the association between SNHL and vitiligo from inception to June 28, 2020., Results: A total of 14 case-control studies with 938 patients with vitiligo were included. The meta-analysis showed a significant association of SNHL with vitiligo (odds ratio [OR] 6.02 [95% confidence interval {CI} 3.41-10.62]). The association remained significant after adjustment of study quality and publication bias, with ORs of 5.30 (95% CI 1.53-18.35), and 3.45 (95% CI 1.75-6.81), respectively., Limitations: Heterogenous definition and measurement of hearing loss and racial differences are potential sources of bias., Conclusion: The evidence to date supports an association of SNHL with vitiligo. These results suggest audiologic assessment for early recognition and management of hearing loss in patients with vitiligo., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To study the clinical characteristics of cornual pregnancy and compare the effects of various surgical methods on the outcomes. Methods: This was a single-center retrospective study. The clinical records of patients with cornual pregnancy who underwent surgery in Peking Union Medical College Hospital from June 2012 to December 2020 were collected. Surgical interventions included curettage (guided by ultrasound or monitored by laparoscope), and cornuostomy/cornectomy (the surgical approach by laparoscopy or laparotomy). The baseline data, perioperative treatment and whether persistent ectopic pregnancy (PEP) occurred after surgery were collected and analyzed statistically. Results: A total of 109 patients with cornual pregnancy diagnosed by surgical treatment were included in this study, whose average age was (32.9±4.8) years. Among them, the incidence of postoperative PEP was 16.5% (18/109). The risk of PEP in multipara was significantly higher than that in nulliparous women ( OR =7.639, 95% CI : 2.063-28.279, P =0.001). The risk of PEP in patients with the maximum diameter of lesion<1.5 cm was significantly higher than that in patients with the maximum diameter of lesion≥1.5 cm ( OR =8.600, 95% CI : 2.271-32.571, P =0.002). Among all surgical approaches for cornual pregnancy, the proportion of PEP in curettage under ultrasound monitoring was the highest (56.0%, 14/25), which was higher than that in curettage under laparoscope monitoring (1/10; χ 2 =6.172， P =0.013); the proportion of PEP in curettage group (42.9%, 15/35) was higher than that in cornuostomy/cornectomy group (4.1%, 3/74; χ 2 =25.950， P <0.01). Neither salpingectomy in the operation nor the routine use of methotrexate (MTX) in perioperative period could significantly reduce the incidence of PEP (all P >0.05). Conclusions: Among the patients with cornual pregnancy, multipara, the maximum diameter of lesion<1.5 cm and ultrasound-guided curettage are the risk factors of PEP after operation. Cornuostomy or cornectomy is recommended for patients with cornual pregnancy. If the patients would perform the curettage operation, laparoscopic monitoring is recommended. For patients with possible satisfactory operation outcome, it is not recommended to use MTX as a routine preventing measure.

Objectives: Periodontal disease is prevalent in patients with chronic kidney disease (CKD) and potentially associated with kidney function decline. However, it is uncertain whether periodontal disease affects the risk of mortality and morbidity in patients with advanced CKD., Materials and Methods: Taiwan's National Health Insurance Research Database was used to conduct a nationwide population-based cohort study. Propensity score matching procedures were performed to select people with stage 5 CKD and to compare the long-term risk of mortality, end-stage renal disease, and major adverse cardiovascular events (MACE) between people with and without periodontal disease. Multivariable Cox regression analyses were conducted to calculate the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for the outcome of interest., Results: A total of 8119 subjects with stage 5 CKD were initially included. After matching to demographic and clinical covariates, 1254 subjects with 7099 person-years of follow-up were selected for analyses. Periodontal disease was not associated with long-term risks of all-cause mortality (aHR: 0.77, 95% CI: 0.49-1.22), progression to end-stage renal disease (aHR: 0.91, 95% CI: 0.75-1.10), or MACE (aHR: 1.18, 95% CI: 0.91-1.53). These findings were generally consistent across subgroups of age, sex, comorbid diabetes, uses of systemic antibiotic, and different dental procedures., Conclusions: Periodontal disease is not a predictor for long-term mortality or morbidity in patients with advanced CKD., Clinical Relevance: These results provide important evidence to elucidate the relationship between periodontitis and critical clinical outcomes of advanced CKD., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Alopecia areata (AA) is associated with multiple comorbidities and shares a similar inflammatory signature with dementia. The great negative psychosocial impact of AA may result in poor social engagement, a typical risk factor for dementia. However, little is known about the association between AA and dementia., Methods: Via the Taiwan National Health Insurance Research Database, 2,534 patients with AA ( International Classification of Diseases, 9th Revision, Clinical Modification code: 704.01) aged ≥ 45 years and 25,340 controls matched for age, sex, residence, income, dementia-related comorbidities, systemic steroid use, and annual outpatient visit were included between 1998 and 2011 for investigation of subsequent dementia from enrollment to the end of 2013. After controlling for potential confounders, stratified Cox regression analysis on each matched pair was applied to assess the dementia risk between the AA and control groups., Results: Patients with AA were more likely to develop any dementia (adjusted hazard ratio [aHR]  = 3.24; 95% CI, 2.14-4.90), Alzheimer's disease (aHR = 4.34; 95% CI, 1.45-12.97), and unspecified dementia (aHR = 3.36; 95% CI, 2.06-5.48) than the control cohort. Stratification analysis by age and sex revealed increased risks of any dementia and unspecified dementia in both age groups (ie, < 65 and ≥ 65 years) and both sex groups and increased risks of AD in male patients and in those with age at dementia onset ≥ 65 years. Sensitivity analyses after exclusion of the first year or first 3 years of observation showed consistent findings., Conclusions: Patients with AA had a higher risk of developing dementia. Further studies are needed to elucidate the underlying pathophysiology between AA and dementia risk., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

This study aimed to develop an LC-MS/MS method for determining sildenafil and its metabolites N-desmethylsildenafil and N1,N4-desmethylsildenafil in human plasma and applying it to a pharmacokinetic study of sildenafil in healthy volunteers. Sildenafil-d8 was used as the internal standard. Plasma samples were pretreated via protein precipitation with acetonitrile. The extractives were then separated on an ACQUITY UPLC BEH C18 (50-mm × 2.1-mm, 1.7-μm) column using gradient elution. The aqueous and organic mobile phases were ammonium formate 2 mM supplemented with 0.1% formic acid in water and acetonitrile, respectively, and the flow rate was 0.3 mL/min. An electrospray ionization source was applied, and multiple reaction monitoring was operated in the positive mode with selective channels at m/z 475.30 → 100.10, 461.20 → 283.30, 483.30 → 108.10, and 449.00 → 283.00 for sildenafil, sildenafil-d8, N-desmethylsildenafil, and N1,N4-desmethylsildenafil, respectively. The linear calibration curves of sildenafil and its metabolites spanned 1.0-1000 ng/mL. The lower limit of quantification was 1.0 ng/mL. The extractive recovery of analytes from the biological matrix was more than 90% and the matrix effect complied with relevant provisions. The intra- and inter-day precisions of sildenafil and its metabolite were <10%. The intra- and inter-day accuracy of sildenafil, N-desmethylsildenafil, and N1,N4-desmethylsildenafil was more than 99%. The method is highly sensitive and selective, and it was successfully applied to the bioequivalence studies of 100-mg sildenafil citrate tablets in 40 healthy Chinese volunteers., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The effects of cigarette smoking on the risk of herpes zoster (HZ) infection remain unclear. This study aimed to examine the association between cigarette smoking and HZ. Participants were collected from four rounds (2001, 2005, 2009 and 2013) of the Taiwan National Health Interview Survey. Incident cases of HZ were identified from the Taiwanese National Health Insurance database. Of the 57 641 participants, 3346 developed HZ during the observation period. After controlling for confounders, current smokers had a lower risk of incident HZ than never-smokers (adjusted hazard ratio 0.69; 95% CI 0.62-0.77). There was a trend toward a decreased risk of HZ with increasing numbers of cigarettes per day, years of smoking and cumulative pack-years of smoking among current smokers (P trend < 0.001). Former smoking was not associated with risk of HZ. In conclusion, current smoking was significantly associated with a decreased risk of developing HZ., (© 2021 British Association of Dermatologists.)

Psoriasis has been associated with the risk of several ocular complications; however, its relationship with retinal diseases remains unknown. This study aimed to investigate the risk of developing retinal diseases in patients with psoriasis. Study participants were recruited from the National Health Insurance Research Database in Taiwan. A total of 11 729 psoriasis patients and 117 290 matched controls were included, showing an incidence rate of 121.15 and 28.34 cases of retinal diseases per 100 000 person-years, respectively. Compared with controls, patients with psoriasis had an adjusted hazard ratio (aHR) of 3.40 (95% confidence interval [CI], 2.63-4.39) for retinal diseases after adjustment for potential confounders. Regarding the individual retinal disease, psoriasis patients had a significantly higher risk of developing retinal detachment (aHR, 5.07; 95% CI, 2.92-8.79), retinal vascular occlusion (aHR, 3.75; 95% CI 2.42-5.82), and retinopathy (aHR, 2.84; 95% CI, 1.99-4.05) than controls. In conclusion, patients with psoriasis had a significantly higher risk of retinal diseases than controls. Further studies are necessary to investigate the pathophysiology underlying the relationship between psoriasis and retinal diseases., (© 2021 Japanese Dermatological Association.)

There is broad consensus that RecQ family helicase is a high-order oligomer that dissociates into a dimer upon ATP binding. This conclusion is based mainly on studies of highly purified recombinant proteins, and the oligomeric states of RecQ helicases in living cells remain unknown. We show here that, in contrast to current models, monomeric RECQL helicase is more abundant than oligomer/dimer forms in living cells. Further characterization of endogenous BtRECQL and isolated monomeric BtRECQL using various approaches demonstrates that both endogenous and recombinant monomeric BtRECQL effectively function as monomers, displaying higher helicase and ATPase activities than dimers and oligomers. Furthermore, monomeric BtRECQL unfolds intramolecular G-quadruplex DNA as efficiently as human RECQL and BLM helicases. These discoveries have implications for understanding endogenous RECQL oligomeric structures and their regulation. It is worth revisiting oligomeric states of the other members of the RecQ family helicases in living cells., Competing Interests: Declaration of interests The authors declare no competing interests, (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Periodontitis is prevalent in patients with chronic kidney disease (CKD) and is also associated with kidney function decline. It is unclear whether dental scaling treatment prevents the progression of CKD. In a nationwide cohort study, Taiwan's National Health Insurance Research Database was used to select people with CKD. Propensity score-matching procedures were performed to compare the long-term risk of end-stage renal disease (ESRD) between CKD patients with and without the receipt of dental scaling. A total of 33,637 matched pairs with CKD were included, with 503,373 person-years of follow-up for analyses. Dental scaling was significantly associated with a lower risk of ESRD (adjusted hazard ratio (aHR): 0.83, 95% confidence interval (CI): 0.77-0.90). In addition, there was a dose-dependent relationship between the frequency of dental scaling and a reduced risk of ESRD. Dental scaling was also linked to reduced risks of major adverse cardiovascular events (aHR: 0.91, 95% CI: 0.87-0.95), sepsis (aHR: 0.81, 95% CI: 0.77-0.85), and all-cause mortality (aHR: 0.81, 95% CI: 0.76-0.87). Dental scaling was significantly associated with lower risks of progression to ESRD in patients with CKD. Regular dental scaling may serve as a prophylactic measure for kidney function decline.

Metal-organic frameworks (MOFs) act as versatile coordinators for the subsequent synthesis of high-performance catalysts by providing dispersed metal-ion distribution, initial coordination condition, dopant atom ratios, and so on. In this work, a crystalline MOF trans -[Cu(NO 3 ) 2 (Him) 4 ] was synthesized as the novel precursor of a redox-alternating Cu x O electrochemical catalyst. Through simple temperature modulation, the gradual transformation toward a highly active nanocomposite was characterized to ascertain the signal enhancing mechanism in H 2 O 2 reduction. Owing to the proprietary structure of the transducer material and its ensuing high activity, a proof-of-principle sensor was able to provide an amplified sensitivity of 2330 μA mM -1 cm -2 . The facile one-pot preparation and intrinsic nonenzymatic nature also suggests its wide potentials in medical settings.