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This study aimed to elucidate the resistance trends of P. aeruginosa isolates from 2005 to 2023 in Zhejiang Province, emphasizing the impact of Coronavirus disease 2019 (COVID-19) on antimicrobial resistance patterns and clinical management. We retrospectively analyzed 7326 P. aeruginosa isolates collected from diverse clinical sources in a tertiary hospital in Zhejiang Province from 2005 to 2023. Identification and antibiotic susceptibility testing of each isolate were performed using the VITEK-32 automated system and the disk diffusion method, following Clinical and Laboratory Standards Institute guidelines. We assessed resistance patterns for key antibiotic classes relevant to P. aeruginosa treatment, including carbapenems, β-lactams, aminoglycosides, and quinolones. Statistical analyses, including trend evaluations and resistance determinant assessments, were conducted in R software (version 4.2.2), with visualizations generated through ggplot2 to illustrate resistance trends over time. This study focused on key anti-pseudomonal agents including carbapenems (imipenem and meropenem), β-lactams (piperacillin), and quinolones (ciprofloxacin and levofloxacin). We observed a progressive increase in resistance to imipenem from 6.8% in 2005 to 48.2% in 2023 and meropenem from 25.4% to 44.2% over the same period. Conversely, resistance rates to aminoglycosides declined, with gentamicin resistance dropping from 22.0% in 2005 to 5.0% in 2019. Cephalosporins exhibited variable trends, with cefepime resistance peaking at 40.4% in 2013 before declining to 12.1% in 2023. The findings indicated a progressive increase in resistance rates for these antibiotics, with notable peaks coinciding with changes in clinical practices and the COVID-19 pandemic. The analysis demonstrated that shifts in prescription habits, particularly during the COVID-19 pandemic, influenced resistance patterns, underscoring the need for context-specific antimicrobial stewardship strategies. This study identifies significant, evolving resistance patterns in P. aeruginosa over a 19-year period, with marked increases in resistance to critical antibiotics, including carbapenems (imipenem, meropenem), quinolones (levofloxacin, ciprofloxacin), and certain β-lactams (piperacillin). These findings underscore an urgent need for dynamic, tailored infection control measures, emphasizing the importance of robust antibiotic stewardship programs, localized treatment guidelines, and proactive monitoring of resistance trends. Implementing these strategies is essential to effectively counter the challenges posed by multi-drug resistant P. aeruginosa, improve patient outcomes, and sustain the efficacy of vital antibiotic therapies., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: This study aims to analyze the literature on periocular basal cell carcinoma, identify research trends, and offer insights into future research areas in this field to assist clinicians and researchers., Methods: 903 publications on periocular basal cell carcinoma were collected from the Web of Science Core Collection database. We assessed the contributions from various countries, institutions, journals, and authors, and performed network analysis using Excel, VOSviewer, and R Studio to represent the prominent areas of research visually., Results: The country with the highest number of publications and citations in this study was the United States of America, with 250 publications, 5917 citations, and the highest H-index of 44. Ophthalmic Plastic and Reconstructive Surgery is the leading journal. The UTMD Anderson Cancer Center had the highest number of publications, accounting for 43, or 4.76% of the total. Selva D from the University of Adelaide, Australia, is the top author with 26 publications, and 751 citations. Targeted therapy for PBCC-related pathways has been a hot topic in recent years., Conclusions: This study using bibliometrics seeks to explore the patterns and focal points of research and analyzes publication patterns, key research areas, influential authors, and prominent journals in periocular basal cell carcinoma during the last 2 decades., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Background: Cardiac hypertrophy and its associated remodeling are among the leading causes of heart failure. Lysine crotonylation is a recently discovered posttranslational modification whose role in cardiac hypertrophy remains largely unknown. NAE1 (NEDD8 [neural precursor cell expressed developmentally downregulated protein 8]-activating enzyme E1 regulatory subunit) is mainly involved in the neddylation modification of protein targets. However, the function of crotonylated NAE1 has not been defined. This study aims to elucidate the effects and mechanisms of NAE1 crotonylation on cardiac hypertrophy., Methods: Crotonylation levels were detected in both human and mouse subjects with cardiac hypertrophy through immunoprecipitation and Western blot assays. Tandem mass tag (TMT)-labeled quantitative lysine crotonylome analysis was performed to identify the crotonylated proteins in a mouse cardiac hypertrophic model induced by transverse aortic constriction. We generated NAE1 knock-in mice carrying a crotonylation-defective K238R (lysine to arginine mutation at site 238) mutation (NAE1 K238R) and NAE1 knock-in mice expressing a crotonylation-mimicking K238Q (lysine to glutamine mutation at site 238) mutation (NAE1 K238Q) to assess the functional role of crotonylation of NAE1 at K238 in pathological cardiac hypertrophy. Furthermore, we combined coimmunoprecipitation, mass spectrometry, and dot blot analysis that was followed by multiple molecular biological methodologies to identify the target GSN (gelsolin) and corresponding molecular events contributing to the function of NAE1 K238 (lysine residue at site 238) crotonylation., Results: The crotonylation level of NAE1 was increased in mice and patients with cardiac hypertrophy. Quantitative crotonylomics analysis revealed that K238 was the main crotonylation site of NAE1. Loss of K238 crotonylation in NAE1 K238R knock-in mice attenuated cardiac hypertrophy and restored the heart function, while hypercrotonylation mimic in NAE1 K238Q knock-in mice significantly enhanced transverse aortic constriction-induced pathological hypertrophic response, leading to impaired cardiac structure and function. The recombinant adenoviral vector carrying NAE1 K238R mutant attenuated, while the K238Q mutant aggravated Ang II (angiotensin II)-induced hypertrophy. Mechanistically, we identified GSN as a direct target of NAE1. K238 crotonylation of NAE1 promoted GSN neddylation and, thus, enhanced its protein stability and expression. NAE1 crotonylation-dependent increase of GSN promoted actin-severing activity, which resulted in adverse cytoskeletal remodeling and progression of pathological hypertrophy., Conclusions: Our findings provide new insights into the previously unrecognized role of crotonylation on nonhistone proteins during cardiac hypertrophy. We found that K238 crotonylation of NAE1 plays an essential role in mediating cardiac hypertrophy through GSN neddylation, which provides potential novel therapeutic targets for pathological hypertrophy and cardiac remodeling., Competing Interests: None.

The aim of this study was to evaluate the efficacy of fast-track cardiac anesthesia using target-controlled infusion of sufentanil and propofol in valve replacement surgery. The clinical data of 88 patients with rheumatic heart disease undergoing valve replacement surgery were retrospectively analyzed and grouped based on different treatment methods. Among them, 44 cases received fast-track cardiac anesthesia using target-controlled infusion of fentanyl and propofol from November 2019 to July 2021 were set as the control group, and 44 cases received fast-track cardiac anesthesia using target-controlled infusion of sufentanil and propofol from August 2021 to February 2022 were set as the study group. The study group showed shorter postoperative awakening time, extubation time, and hospital stay duration, and lower dosage of dopamine and nitroglycerin consumption compared to the control group (P < .05). At T5 and T6, both groups exhibited higher ACTH, cortisol (Cor), and C3a than at T0, and the study group showed significantly lower ACTH, Cor, and C3a at T5 and T6 than the control group (P < .05). At T7, the control group showed higher ACTH, Cor, and C3a than at T0, and ACTH, Cor, and C3a were significantly lower in the study group than in the control group at T7 (P < .05). Fast-track cardiac anesthesia using target-controlled infusion of sufentanil and propofol in valve replacement surgery has demonstrated favorable application effects, which stabilizes hemodynamics, alleviates myocardial damage, suppresses endocrine stress responses, and does not increase adverse reactions, thereby exhibiting good safety., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

This study aimed to elucidate the molecular mechanisms underlying the therapeutic effects of Cangzhu Erchen decoction (CZECD) in the treatment of chronic obstructive pulmonary disease (COPD) using microarray analysis, network pharmacology, and molecular docking. The active components and candidate targets of CZECD were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Swiss Target Prediction. COPD-related targets were collected from 5 databases. Access to drug-disease interface targets in the Venny platform. The Cytoscape program and the STRING database were used for protein-protein interaction analysis and subsequent core target screening. The DAVID database was used for Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment pathway analysis, while AutoDockTools was used for molecular docking to confirm binding affinity between drugs and key targets. A total of 140 compounds from CZECD and 5100 COPD-related targets were identified. SRC, PIK3CA, STAT3, PIK3R1, AKT1, HSP90AA1, PIK3CB, GRB2, PIK3CD, and MAPK1 were identified as the major targets of CZECD in its anti-COPD activity. GO and Kyoto Encyclopedia of Genes and Genomes enrichment studies revealed that CZECD mainly affects biological processes such as protein phosphorylation, xenobiotic response, positive regulation of the MAPK cascade, and inflammatory responses. Cancer, PI3K/AKT, and MAPK were the key pathways mediating these effects. The positive association between the core targets and the compounds was further validated by molecular docking. CZECD exerts its therapeutic role in COPD mainly through multiple compounds, targets, and pathways., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: Paraneoplastic neurological syndrome with anti-Hu antibody (Hu-PNS) is a neurological disorder that occur in patients with malignancy. The syndrome has a wide range of presentations and can present before diagnosis of primary malignancy. Familiarity with these paraneoplastic neurological syndromes can help early recognition and take appropriate regimens., Patients Concerns: Diagnosis and treatment of Hu-PNS., Diagnoses: This is retrospective study that analyzed the clinical data of this case. Through retrospective analysis and targeted antibody screening, serum anti-Hu antibody was detected. Subsequent spinal imaging revealed a mass in the paraspinal region, which was confirmed as ganglioneuroblastoma by pathologic examination., Interventions: The child was treated with a course of intravenous immunoglobulin and radical surgical operation without chemotherapy., Outcomes: The neurological symptoms were gradually improved and no signs indicate disease progression or tumor recurrence., Lessons: Hu-PNS has rarely been reported in children with ganglioneuroblastomas. They can mimic non-neoplastic processes, making detection and diagnosis difficult. Serum and/or cerebrospinal fluid onconeural antibody can strongly indicate occult cancers. Early detection of paraneoplastic neurological syndromes can help take appropriate regimens and improve prognosis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To explore the mediating effect of self-efficacy and coping mode between powerlessness and quality of life in patients with a venous leg ulcer (VLU)., Methods: The authors used a convenience sampling method to select 208 patients with a VLU in four tertiary grade A hospitals in Qingdao and Tianjin from June 2021 to August 2022. Instruments included the Powerlessness Assessment Tool, Venous Leg Ulcer Self-efficacy Tool, Medical Coping Modes Questionnaire, and Venous Leg Ulcer Quality of Life Questionnaire. The authors used descriptive statistics, Pearson correlation, and PROCESS macros for data analysis., Results: The powerlessness score was significantly negatively associated with self-efficacy and confrontation coping mode scores and positively associated with patients' quality-of-life scores. In addition, self-efficacy and confrontation coping modes separately and sequentially mediated the relationship between powerlessness and quality of life., Conclusions: Self-efficacy and confrontation coping mode play important mediating roles between powerlessness and quality of life in patients with VLUs. By decreasing patients' sense of powerlessness, boosting their self-efficacy, and encouraging them to adopt confrontation coping mode, health professionals can improve patients' quality of life., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: Acute stent thrombosis (AST) is not uncommon and even catastrophic during intracranial stenting angioplasty in patients with symptomatic high-grade intracranial atherosclerotic stenosis (ICAS). The purpose of this study was to investigate whether adjuvant intravenous tirofiban before stenting could reduce the risk of AST and periprocedural ischemic stroke in patients receiving stent angioplasty for symptomatic ICAS., Methods: A prospective, multicenter, open-label, randomized clinical trial was conducted from September 9, 2020, to February 18, 2022, at 10 medical centers in China. Patients intended to receive stent angioplasty for symptomatic high-grade ICAS were enrolled and randomly assigned to receive intravenous tirofiban or not before stenting in a 1:1 ratio. The primary outcomes included the incidence of AST within 30 minutes after stenting, periprocedural new-onset ischemic stroke, and symptomatic intracranial hemorrhage. The outcomes were analyzed using logistic regression analysis to obtain an odds ratio and 95% confidence interval., Results: A total of 200 participants (122 men [61.0%]; median [interquartile ranges] age, 57 [52-66] years) were included in the analysis, with 100 participants randomly assigned to the tirofiban group and 100 participants to the control (no tirofiban) group. The AST incidence was lower in the tirofiban group than that in the control group (4.0% vs 14.0%; adjusted odds ratio, 0.25; 95% CI 0.08-0.82; p = 0.02). No significant difference was observed in the incidence of periprocedural ischemic stroke (7.0% vs 8.0%; p = 0.98) or symptomatic intracranial hemorrhage between the 2 groups., Discussion: This study suggests that adjuvant intravenous tirofiban before stenting could lower the risk of AST during stent angioplasty in patients with symptomatic high-grade ICAS., Trial Registration Information: URL: chictr.org.cn; Unique identifier: ChiCTR2000031935., Classification of Evidence: This study provides Class II evidence that for patients with symptomatic high-grade ICAS, pretreatment with tirofiban decreases the incidence of acute stent thrombosis. This study is Class II due to the unequal distribution of involved arteries between the 2 groups.

Introduction: Desmoplastic small round cell tumor (DSRCT) is a highly aggressive primitive sarcoma with a 5-year survival rate estimated at only 15% to 30%. Although few curative treatment options exist, patients are most often treated with a combination of aggressive chemotherapy, radiation, and surgery. Targeted therapy inhibitors of platelet-derived growth factor A, insulin-like growth factor receptor 1, and vascular endothelial growth factor receptor-2, which are almost uniformly overexpressed in DSRCT, have largely failed in clinical trials. Anlotinib is a multitarget receptor tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor α/β, c-Kit, and Met. In this study, we presented 3 cases of DSRCT treated effectively with anlotinib combined with chemotherapy., Case Presentation: Three children DSRCT patients were enrolled from September 2020 to December 2021 and monitored until August 30, 2022. The clinical data were prospectively studied. The peritoneal cancer index classified all 3 patients as stage IV. After surgery, all 3 patients received anlotinib in combination with chemotherapy and reacted to the medication. For all 3 patients, clinical symptoms were substantially eased, and the size of the masses was reduced. Patient 1 and patient 3's progression-free survival had been extended, and anlotinib was continued as a maintenance medication in the 2 patients who were in good health at the end of the follow-up. Patient 2 died of postoperative complications 1 month after second-stage surgery. The main side effects of anlotinib were fatigue and hypertension. However, its toxicity was controllable and tolerable in children patients., Conclusions: This is the first report that anlotinib is effective in children with DSRCT. This report may provide an additional option for the treatment of metastatic DSRCT., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study aimed to evaluate the effects of three antioxidants, selenium yeast capsule, vitamin E and vitamin C, alone or in combination, on the salivary glands of patients with differentiated thyroid cancer (DTC) treated with iodine-131 ( 131 I)., Methods: A total of 69 postoperative DTC patients were randomly divided into three groups: vitamin E combined with vitamin C group (21 cases); selenium yeast group (23 cases); and selenium yeast combined with vitamin C group (25 cases). Salivary gland functional changes were assessed by salivary gland dynamic imaging functional parameters in the enrolled patients before and 1 month after 131 I treatment., Results: Comparison of salivary gland function parameters before and after 131 I treatment in the three groups were evaluated. In the vitamin E combined with the vitamin C group, the left parotid gland excretion fraction (EF) value was significantly higher than that before treatment. In the selenium yeast group, the left parotid gland excretion part, bilateral parotid gland excretion ratio (ER), left submandibular gland maximum uptake ratio within 20 min (UR20), and the right submandibular gland ER values were significantly higher than that before treatment, while in the selenium yeast combined with vitamin C group, the bilateral parotid gland EF, bilateral submandibular gland UR20, EF, and left submandibular gland ER values were significantly higher than that before treatment (all P  < 0.05)., Conclusion: During high-dose 131 I treatment, vitamin E combined with vitamin C improved the excretory function of parotid glands in DTC patients; selenium supplementation had a protective effect on salivary glands; and the combination of selenium and vitamin C had a better effect., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Lymphoma can appear in all parts of the body and present with different symptoms. However, bronchial lymphoma is rare and can be misdiagnosed as airway malignancy or lung disease.Patient: An older adult woman with tracheal lymphoma experienced severe breathing difficulties, and chest computed tomography indicated severe narrowing of the airway. She did not respond to repeated antibiotic treatment, and she was eventually diagnosed with lymphoma based on pathology after surgical removal of the tumor., Diagnosis: The patient received a diagnosis of thoracic tracheal stenosis due to intratracheal inflammatory granulomatous lesions or a tumor., Interventions: Treatment involved the use of a high-frequency electrotome, freezing, and argon plasma coagulation., Outcomes: The patient reported improvements in dyspnea, cough, and other symptoms after the operation. The pathological results confirmed follicular lymphoma. Reexamination by fiberbronchoscopy indicated that the degree of stenosis in the middle and upper tracheal segments was significantly reduced following interventional therapy., Conclusion: Endoscopic interventional therapy can be an effective treatment for tracheal lymphoma., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: Intravascular/intravenous leiomyomatosis (IVL) is a peculiar variant of uterine leiomyoma that is classified as a histologically benign smooth muscle tumor with a biological behavior similar to that of a malignant tumor. It is characterized by the proliferation of leiomyomas spreading along the uterine and extrauterine venous circulation., Patient Concerns: Herein, we present 2 cases of IVL who had completely different clinical manifestations to stress the need for constant vigilance of IVL diagnosis and the understanding of uterine leiomyoma heterogenicity. Case 1 was registered for fever without specific triggering factors, irregular menstruation and clinically diagnosed uterine diverticula, while no information about fibroids was mentioned. Case 2 was characterized by an aggressively growing abdominal mass. With a large space-occupying lesion in the right abdominopelvic cavity and no imaging evidence of involvement of the iliac vein or above vein, the patient was initially diagnosed with multiple myomata., Diagnoses: Both patients' diagnoses were confirmed as IVL by histopathology. To our knowledge, the mass of case 1 is the minimum IVL in the English literature., Interventions: Subtotal hysterectomy with bilateral salpingectomy was performed on the former, while total hysterectomy with bilateral salpingectomy was performed on the latter., Outcomes: Both patients were comfortable, and no relapse occurred., Lessons: Two cases in the study showed 2 different proceeding stages of the same disease and corroborated multiple pathogeneses, which have been mentioned in the available literature on IVL. Our work provides both supplement for clinical data to facilitate further research and better understanding of special types of fibroids to clinicians., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Competing Interests: Disclosures J.C. consults for LEXEO Therapeutics and Morphic Therapeutic. J.B. consults for Rocket Pharmaceuticals on image analysis. The other authors report no conflicts.

Background: Fatal massive hemoptysis is a life-threatening emergency in the respiratory system. Currently, the treatment methods and techniques for massive hemoptysis are still limited, and there are often issues of delayed treatment or improper methods in clinical practice, leading to the difficulty of rescuing patients and high mortality rates. When fatal massive hemoptysis occurs, the key to successful treatment lies in whether intrapulmonary blood clots can be effectively cleared and airway patency can be ensured. Our practice of combining fiberoptic bronchoscopy with urokinase treatment to clear intrapulmonary blood clots after fatal massive hemoptysis demonstrates the effectiveness of this method., Case Summary: We report a 32-year-old female who experienced cough, accompanied by fatal massive hemoptysis with extensive blood clot obstruction in the airway. Considering the difficulty of clearing the airway using conventional methods, it was decided to perform fiberoptic bronchoscopy combined with urokinase therapy after reviewing relevant literature. After treatment, the intrapulmonary blood clots were successfully extracted, thereby relieving airway obstruction. Finally, the patient was successfully weaned off extracorporeal membrane oxygenation, extubated, and evacuated from the ventilator. Currently, the patient's condition is stable, and follow-up chest X-ray as well as computed tomography scans have shown improvement compared to previous assessments., Conclusion: Fatal massive hemoptysis is a intractable emergency in clinical practice. In this case, we confirmed that fiberoptic bronchoscopy combined with urokinase therapy may be effective and safe in the treatment of fatal massive hemoptysis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: The aim of this study was to investigate the computed tomography (CT) features of recurrent acute pancreatitis (RAP) in the early phase and late phase., Methods: Recurrent acute pancreatitis data were obtained over the past 5 years. Recurrent acute pancreatitis patients were divided into 2 groups according to the time from RAP onset to performing CT examination: the early phase (first week) and late phase (after the first week) based on the 2012 revised Atlanta classification (RAC). Evaluation and comparison of patients' demographic data, RAC, CT findings, CT severity index (CTSI) score, and extrapancreatic inflammation on CT (EPIC) score were conducted in the 2 groups., Results: Hypertriglyceridemia was the most common cause of RAP in 679 of 686 patients (positive CT rate: 98.98%). Among 679 CT-positive patients, interstitial edematous pancreatitis and necrotizing pancreatitis accounted for 61.71% (419/679) and 38.29% (260/679), respectively. The CTSI and EPIC scores were higher in the late phase than in the early phase (both P 's < 0.05). The proportion of moderately severe and severe RAP patients based on RAC was higher in the late phase than in the early phase ( P < 0.05). Early-stage EPIC score was more accurate than CTSI and Acute Physiology and Chronic Health Evaluation (APACHE) II scores in predicting clinically severe RAP (EPIC vs CTSI; EPIC vs APACHE II, both P 's < 0.05)., Conclusions: Recurrent acute pancreatitis is more severe in the late phase than in the early phase. The EPIC score is more indicative of clinically severe RAP than CTSI and APACHE II scores in the early phase of RAP., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: FLNC (filamin C), a member of the filamin family predominantly expressed in striated muscles, plays a crucial role in bridging the cytoskeleton and ECM (extracellular matrix) in cardiomyocytes, thereby maintaining heart integrity and function. Although genetic variants within the N-terminal ABD (actin-binding domain) of FLNC have been identified in patients with cardiomyopathy, the precise contribution of the actin-binding capability to FLNC's function in mammalian hearts remains poorly understood., Methods: We conducted in silico analysis of the 3-dimensional structure of mouse FLNC to identify key amino acid residues within the ABD that are essential for FLNC's actin-binding capacity. Subsequently, we performed coimmunoprecipitation and immunofluorescent assays to validate the in silico findings and assess the impact of these mutations on the interactions with other binding partners and the subcellular localization of FLNC. Additionally, we generated and analyzed knock-in mouse models in which the FLNC-actin interaction was completely disrupted by these mutations., Results: Our findings revealed that F93A/L98E mutations completely disrupted FLNC-actin interaction while preserving FLNC's ability to interact with other binding partners ITGB1 (β1 integrin) and γ-SAG (γ-sarcoglycan), as well as maintaining FLNC subcellular localization. Loss of FLNC-actin interaction in embryonic cardiomyocytes resulted in embryonic lethality and cardiac developmental defects, including ventricular wall malformation and reduced cardiomyocyte proliferation. Moreover, disruption of FLNC-actin interaction in adult cardiomyocytes led to severe dilated cardiomyopathy, enhanced lethality and dysregulation of key cytoskeleton components., Conclusions: Our data strongly support the crucial role of FLNC as a bridge between actin filaments and ECM through its interactions with actin, ITGB1, γ-SAG, and other associated proteins in cardiomyocytes. Disruption of FLN-actin interaction may result in detachment of actin filaments from the extracellular matrix, ultimately impairing normal cardiac development and function. These findings also provide insights into mechanisms underlying cardiomyopathy associated with genetic variants in FLNC ABD and other regions., Competing Interests: Disclosures J. Chen consults for LEXEO Therapeutics and Morphic Therapeutic. The other authors report no conflicts.

Background: A loss-of-function cardiac ryanodine receptor (RyR2) mutation, I4855M +/- , has recently been linked to a new cardiac disorder termed RyR2 Ca 2+ release deficiency syndrome (CRDS) as well as left ventricular noncompaction (LVNC). The mechanism by which RyR2 loss-of-function causes CRDS has been extensively studied, but the mechanism underlying RyR2 loss-of-function-associated LVNC is unknown. Here, we determined the impact of a CRDS-LVNC-associated RyR2-I4855M +/- loss-of-function mutation on cardiac structure and function., Methods: We generated a mouse model expressing the CRDS-LVNC-associated RyR2-I4855M +/- mutation. Histological analysis, echocardiography, ECG recording, and intact heart Ca 2+ imaging were performed to characterize the structural and functional consequences of the RyR2-I4855M +/- mutation., Results: As in humans, RyR2-I4855M +/- mice displayed LVNC characterized by cardiac hypertrabeculation and noncompaction. RyR2-I4855M +/- mice were highly susceptible to electrical stimulation-induced ventricular arrhythmias but protected from stress-induced ventricular arrhythmias. Unexpectedly, the RyR2-I4855M +/- mutation increased the peak Ca 2+ transient but did not alter the L-type Ca 2+ current, suggesting an increase in Ca 2+ -induced Ca 2+ release gain. The RyR2-I4855M +/- mutation abolished sarcoplasmic reticulum store overload-induced Ca 2+ release or Ca 2+ leak, elevated sarcoplasmic reticulum Ca 2+ load, prolonged Ca 2+ transient decay, and elevated end-diastolic Ca 2+ level upon rapid pacing. Immunoblotting revealed increased level of phosphorylated CaMKII (Ca 2+ -calmodulin dependent protein kinases II) but unchanged levels of CaMKII, calcineurin, and other Ca 2+ handling proteins in the RyR2-I4855M +/- mutant compared with wild type., Conclusions: The RyR2-I4855M +/- mutant mice represent the first RyR2-associated LVNC animal model that recapitulates the CRDS-LVNC overlapping phenotype in humans. The RyR2-I4855M +/- mutation increases the peak Ca 2+ transient by increasing the Ca 2+ -induced Ca 2+ release gain and the end-diastolic Ca 2+ level by prolonging Ca 2+ transient decay. Our data suggest that the increased peak-systolic and end-diastolic Ca 2+ levels may underlie RyR2-associated LVNC., Competing Interests: Disclosures J. Wei and H. Wang, recipients of the Libin Cardiovascular Institute of Alberta and Cumming School of Medicine Postdoctoral Fellowship Award. Z. Song, recipient of the University of Calgary Eyes High Postdoctoral Fellowship Award. J. Yao, recipient of the Alberta Innovates-Health Solutions (AIHS) Fellowship Award. T.M. Roston, supported by the University of British Columbia Clinician Investigator Program, and a UBC Friedman Scholar in Health and CHRS George Mines Travelling Fellow in Cardiac Electrophysiology. S.R.W. Chen, Heart and Stroke Foundation Chair in Cardiovascular Research. The other authors report no conflicts.

Rationale: Multiple system atrophy (MSA) is a group of adult-onset sporadic neurodegenerative diseases, mainly classified as MSA-C and MSA-P types. Due to the diversity of clinical symptoms, diagnosis faces a significant challenge. In the present case, we report a patient with isolated vertigo as the first presentation and abnormalities of the oculomotor system as the characteristic manifestations., Case Concern: A 64-year-old male had dizziness for 1 year, aggravated for 4 months, with accompanying symptoms of unsteady walking. Physical examination revealed spontaneous nystagmus, abnormal ataxic movements, and a broad basal gait. Video nystagmography revealed saccade intrusions and macrosaccadic oscillations, and opsoclonus. Magnetic resonance imaging (MRI) was unremarkable early, and positron emission tomography-computed tomography (PET-CT) announced a reduction in the volume of the cerebellum and brainstem., Diagnosis: The diagnosis of the possibility of MSA type-C, peripheral neuropathy, hypertension, and lacunar cerebral infarction was performed., Conclusion: Atypical early clinical presentation may lead to delays, and identifying the critical problem through the patient simple clinical status requires long-term clinical experience and various ancillary examination tools., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To explore the application potential of continuous nursing training based on a comprehensive virtual platform in patients with colostomy or ileostomy., Methods: A total of 100 patients with colostomy or ileostomy were equally divided into two groups. Patients in the control group received standardized routine care, whereas patients in the experimental group received continuous nursing care through the virtual platform. Both the control group and the experimental group were followed up by regular telephone calls once per week and completed the following questionnaires both 1 week after discharge and 3 months after discharge: Stoma Care Self-efficacy Scale, Exercise of Self-care Agency Scale, State-Trait Anxiety Inventory, Short Form-36 Health Survey Questionnaire, and a questionnaire on postoperative complications., Results: Patients in the experimental group, who received continuous care, exhibited significantly higher scores in self-efficacy (P = .029), self-care responsibility (P = 0.030), state anxiety and trait anxiety (both Ps < .001), and mental health (P < .001) 1 week after discharge in comparison with patients in the control group. At 3 months postdischarge, compared with the control group, the experimental group showed significant advantages in all dimensions of self-efficacy, self-care ability, mental health, and quality-of-life questionnaires (P < .001). In addition, the incidence of complications in the experimental group was significantly lower (P < .0001)., Conclusions: The virtual platform-based continuous nursing model effectively improves the self-care ability and self-efficacy of patients with a colostomy or ileostomy after colorectal cancer, thereby promoting an improved quality of life and psychological state while simultaneously reducing the incidence of complications after discharge., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Studies comparing the detection of clean mucosal areas in capsule endoscopy (CE) using human judgment versus artificial intelligence (AI) are rare. This study statistically analyzed gastroenterologist judgments and AI results. Three hundred CE video clips (100 patients) were prepared. Five gastroenterologists classified the video clips into 3 groups (≥75% [high], 50%-75% [middle], and < 50% [low]) according to their subjective judgment of cleanliness. Visualization scores were calculated using an AI algorithm based on the predicted visible area, and the 5 gastroenterologists' judgments and AI results were compared. The 5 gastroenterologists evaluated CE clip video quality as "high" in 10.7% to 36.7% and as "low" in 28.7% to 60.3% and 29.7% of cases, respectively. The AI evaluated CE clip video quality as "high" in 27.7% and as "low" in 29.7% of cases. Repeated-measures analysis of variance (ANOVA) revealed significant differences in the 6 evaluation indicators (5 gastroenterologists and 1 AI) (P < .001). Among the 300 judgments, 90 (30%) were consistent with 5 gastroenterologists' judgments, and 82 (91.1%) agreed with the AI judgments. The "high" and "low" judgments of the gastroenterologists and AI agreed in 95.0% and 94.9% of cases, respectively. Bonferroni's multiple comparison test showed no significant difference between 3 gastroenterologists and AI (P = .0961, P = 1.0000, and P = .0676, respectively) but a significant difference between the other 2 with AI (P < .0001). When evaluating CE images for cleanliness, the judgments of 5 gastroenterologists were relatively diverse. The AI produced a relatively universal judgment that was consistent with the gastroenterologists' judgements., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: Owing to the anatomical characteristics of the duodenum, gastroduodenal artery (GDA) pseudoaneurysms can be caused by duodenal ulcers, which may rupture and lead to massive or repeated bleeding. Pseudoaneurysms are usually diagnosed using enhanced computerized tomography or angiography, whereas endoscopic signs have rarely been reported., Patient Concerns: Three patients aged 18 to 83 years with bleeding duodenal ulcers and GDA pseudoaneurysms were treated., Diagnosis: All patients had symptoms of gastrointestinal bleeding, and endoscopy revealed duodenal ulcers with visible vessels or adherent clot pulsations. Angiography confirmed the presence of a GDA pseudoaneurysm, which had an adjacent relationship with the duodenum., Interventions: The GDA pseudoaneurysm was embolized in each patient., Outcomes: Through transcatheter arterial embolization, endoscopic treatment, and traditional treatment, hematemesis or melena was gradually stopped and all patients were discharged., Lessons: The pulsation of visible vessels or adherent clots observed during endoscopy in patients with duodenal ulcer may indicate the formation of a gastroduodenal artery pseudoaneurysm. Therefore, we suggest that such patients receive enhanced computerized tomography or angiography to assess whether they need timely endovascular intervention treatment to avoid bleeding caused by a pseudoaneurysm., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Elevated metabolic activity of amygdala is known to be related to atherosclerotic cardiovascular event by increasing inflammatory cell production from bone marrow. We tried to identify the factors of metabolic activity in the amygdala, vertebrae, liver, spleen, and internal carotid artery related to the future vascular events after stroke., Methods: A total of 110 patients with acute stroke were included (72±10 years of age, 39% women) and underwent whole-body 18 F-fluorodeoxyglucose (FDG) positron emission tomography between August 1, 2015 and February 28, 2020. We compared the FDG uptake in the amygdala, vertebrae, liver, spleen, and internal carotid artery between patients with and without recurrent vascular event. Cox proportional hazards model was used to identify factors related to recurrent stroke and vascular event., Results: During the median follow-up period of 18 months, 22 patients experienced vascular events, including 15 stroke recurrence. Patients with recurred vascular event had a significantly higher FDG uptake in the amygdala and vertebrae than those without. The Cox proportional hazard model including diabetes, renal function, and carotid stenosis showed that a higher FDG uptake in the amygdala was independently associated with total vascular events (hazard ratio, 3.11 [95% CI, 1.11-8.70]) and higher FDG uptake in the vertebrae with stroke recurrence (hazard ratio, 4.94 [95% CI, 1.29-18.9])., Conclusions: The increased metabolic activities of the vertebrae and amygdala are related to future vascular event among stroke survivors.

Rationale: Transjugular intrahepatic portosystemic stent-shunt (TIPSS) is a minimally invasive procedure used for the treatment of portal hypertension. Intrahepatic hematoma is the rare complication caused by hepatic arterial injuries from TIPSS procedure., Patient Concerns: This case report illustrated a 77-year-old man with hepatitis B virus-induced cirrhosis who underwent TIPSS., Diagnoses: The patient suffered from intrahepatic hematoma and hepatic pseudoaneurysm because of the hepatic artery injury after TIPSS., Interventions: The hepatic artery laceration began at the level of the branch of the left hepatic artery was embolized., Outcomes: The acute intrahepatic hematoma and hepatic pseudoaneurysm of the patient were cured., Conclusion: In this report, we describe a cirrhosis patient with a large intrahepatic hematoma secondary to TIPSS, and a literature review is also presented. The intrahepatic hematoma and hepatic pseudoaneurysm should be paid more attention after TIPSS while early-stage prevention should be carried out., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The aim of this study was to evaluate the effect of vitamin E and supragingival scaling with vitamin C on the salivary glands of patients with differentiated thyroid carcinoma after 131I treatment., Methods: A total of 89 prospective patients with differentiated thyroid carcinoma were enrolled and randomly divided into the following groups: vitamin E group (n = 30, group A), vitamin C group (n = 30, group B) and supragingival scaling with vitamin C group (n = 29, group C). Using functional indices (e.g. maximum uptake fraction, uptake index, excretion fraction, secretion time and excretion rate), changes in the salivary gland functions before and a month after 131I treatment were assessed by dynamic imaging of salivary gland., Results: We compared the before and after 131I therapy results of the three groups. In group A (P  < 0.05), the excretion fraction and excretion rate of the left parotid gland were significantly higher, and the uptake index of the bilateral submandibular glands was significantly lower. No significant changes in salivary gland functional parameters were observed in group B (P > 0.05). The uptake index of the bilateral parotid glands and the excretion rate of the left parotid gland were significantly higher in group C (P < 0.05). The degree of serum amylase level reduction decreased significantly in group C (P < 0.05)., Conclusion: Vitamin E showed a protective effect on parotid excretion function in patients with differentiated thyroid carcinoma who underwent 131I treatment. Supragingival scaling may be a promising radiation protector because it is associated with a protective effect on the salivary gland functions., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale: Jacobsen syndrome is a rare chromosomal disorder caused by deletions in the long arm of human chromosome 11, resulting in multiple developmental defects including congenital heart defects. Combined studies in humans and genetically engineered mice implicate that loss of ETS1 (E26 transformation specific 1) is the cause of congenital heart defects in Jacobsen syndrome, but the underlying molecular and cellular mechanisms are unknown., Objective: To determine the role of ETS1 in heart development, specifically its roles in coronary endothelium and endocardium and the mechanisms by which loss of ETS1 causes coronary vascular defects and ventricular noncompaction., Methods and Results: ETS1 global and endothelial-specific knockout mice were used. Phenotypic assessments, RNA sequencing, and chromatin immunoprecipitation analysis were performed together with expression analysis, immunofluorescence and RNAscope in situ hybridization to uncover phenotypic and transcriptomic changes in response to loss of ETS1. Loss of ETS1 in endothelial cells causes ventricular noncompaction, reproducing the phenotype arising from global deletion of ETS1. Endothelial-specific deletion of ETS1 decreased the levels of Alk1 (activin receptor-like kinase 1), Cldn5 (claudin 5), Sox18 (SRY-box transcription factor 18), Robo4 (roundabout guidance receptor 4), Esm1 (endothelial cell specific molecule 1) and Kdr (kinase insert domain receptor), 6 important angiogenesis-relevant genes in endothelial cells, causing a coronary vasculature developmental defect in association with decreased compact zone cardiomyocyte proliferation. Downregulation of ALK1 expression in endocardium due to the loss of ETS1, along with the upregulation of TGF (transforming growth factor)-β1 and TGF-β3, occurred with increased TGFBR2/TGFBR1/SMAD2 signaling and increased extracellular matrix expression in the trabecular layer, in association with increased trabecular cardiomyocyte proliferation., Conclusions: These results demonstrate the importance of endothelial and endocardial ETS1 in cardiac development. Delineation of the gene regulatory network involving ETS1 in heart development will enhance our understanding of the molecular mechanisms underlying ventricular and coronary vascular developmental defects and will lead to improved approaches for the treatment of patients with congenital heart disease.

Objective: Hypertensive disorder complicating pregnancy (HDCP) consists of various heterogeneous conditions. Long noncoding RNAs (LncRNA) FAM99A is implicated in HDCP diagnosis. This study discussed the diagnostic efficiency of lncRNA FAM99A in HDCP., Methods: Totally 130 singleton HDCP patients including 50 patients of gestation hypertension (GH), 44 of mild preeclampsia (mPE), and 36 of severe preeclampsia (sPEz) were enrolled, with 70 healthy pregnant women as the control. Serum lncRNA FAM99A expression was detected and its diagnostic efficiency in HDCP was analyzed using the receiver operating characteristic curve. The influencing factors of PE grade were analyzed using the logistic regression model., Results: Serum lncRNA FAM99A was downregulated in HDCP patients. The SBP/DBP, 24-h urinary protein, and serum creatinine (SCr), AST and ALT contents were elevated, and platelet count (PLT) was diminished in HDCP patients. Relative to the high-expression group, SBP/DBP, 24-h urinary protein, SCr, AST, and ALT contents were raised, and PLT was lowered in the low-expression group. The area under curve of lncRNA FAM99A for HDCP diagnosis was 0.9514, and the cutoff value was 0.8450, with 83.85% sensitivity and 94.29% specificity. LncRNA FAM99A expression was downregulated in the GH group, then mPE group, and sPEz group the least. L ncRNA FAM99A had diagnostic efficiency for GH and mPE, and mPE and sPEz. DBP, urinary protein, PLT, and lncRNA FAM99A were independent risk factors for PE severity., Conclusion: LncRNA FAM99A was diminished in HDCP patients and was related to HDCP severity, which might be used as a potential diagnostic marker of HDCP., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Total hip arthroplasty (THA) has been an effective tool of advanced hemophiliac hip arthritis. There are only limited data of bilateral synchronous THA for end-stage arthropathy in hemophilia A patients. The aim of this retrospective study was to analyze clinical outcome and complication rate of bilateral THA for hemophilia A patients with end-stage arthropathy of hip and review the operative strategy. From August 2012 to July 2016, 48 hips of 24 patients with hemophilia A patients underwent THA by a single experienced chief orthopedic surgeon. Clinical and radiological evaluations were included of operation time, blood loss, the quantity of blood transfusion, clotting factor consumption, duration of hospitalization, modified Harris hip score, complication rate, and radiographic assessment. All the 24 patients successfully completed the operation, followed up for 5 to 8 years, and the mean time was 6.5 years. The average operation time was 140 minutes (range, 120-180 minutes). The average total blood loss was 225 mL (range, 150-400 mL). The mean red blood cell transfusion amount was 2.4 U (range, 0-6 U). the mean hospitalization time was 24 days (range, 16-46 days). The mean amount of clotting factor VIII used in the perioperative period for management of hemophilia A was 30,600 U (range, 18,000-52,000 U). Average modified Harris hip score increased from 46.6 (range 28-70) points preoperatively to 90.2 (range 75-98) points at final follow-up, complications were few. With excellent operative techniques and hematological management, bilateral synchronous THA for end-stage arthropathy in hemophilia A patients can provide satisfactory outcomes., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: The nonstructured abstract were supplied as following: Estrogen receptor is involved in the pathogenesis of recurrent spontaneous abortion (RSA). The ESR1 and ESR2 genes can mediate nongenomic estrogen responses. This study aimed to assess the genetic association between the ESR1 and ESR2 genes polymorphisms and RSA susceptibility in a Chinese Han population. A total of 258 women who had experienced RSA and 264 unrelated healthy women were recruited. Genotypes of the 6 polymorphisms in the ESR1 (rs9340799, rs2234693, and rs3798759) and ESR2 genes (rs207764, rs4986938, and rs1256049) were analyzed using Snapshot technology. No association was detected between the alleles and genotypes of ESR1 rs9340799, rs2234693, and rs3798759 polymorphims and RSA risk (P > .05). Subjects carrying the haplotype of rs9340799A-rs2234693C-rs3798759A had a significantly increased RSA risk in the case group compared with the control group (P = .0005, Padj = .003, odds ratios [95% CI] = 0.35 [0.19-0.65]). However, subjects carrying the haplotype of rs9340799G-rs2234693C-rs3798759A had a significantly decreased RSA risk in the case group compared with the control group (P = .0005, Padj = .003, odds ratios [95% CI] = 2.99 [1.57-5.70]). In addition, no association was found between the alleles, genotypes, and haplotypes of ESR2 rs207764, rs4986938, rs1256049 polymorphisms and RSA risk (P > .05). In conclusion, the haplotype rs9340799A-rs2234693C-rs3798759A of ESR1 might be a risk factor. And the haplotype rs9340799G-rs2234693C-rs3798759A of ESR1 might be a protective factor for RSA in a Chinese Han population., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Sepsis remains a highly lethal disease, whereas the precise reasons for death remain poorly understood. Prokineticin2 is a secreted protein that regulates diverse biological processes. Whether prokineticin2 is beneficial or deleterious to sepsis and the underlying mechanisms remain unknown., Design: Prospective randomized animal investigation and in vitro studies., Setting: Research laboratory at a medical university hospital., Subjects: Prokineticin2 deficiency and wild-type C57BL/6 mice were used for in vivo studies; sepsis patients by Sepsis-3 definitions, patient controls, and healthy controls were used to obtain blood for in vitro studies., Interventions: Prokineticin2 concentrations were measured and analyzed in human septic patients, patient controls, and healthy individuals. The effects of prokineticin2 on sepsis-related survival, bacterial burden, organ injury, and inflammation were assessed in an animal model of cecal ligation and puncture-induced polymicrobial sepsis. In vitro cell models were also used to study the role of prokineticin2 on antibacterial response of macrophages., Measurements and Main Results: Prokineticin2 concentration is dramatically decreased in the patients with sepsis and septic shock compared with those of patient controls and healthy controls. Furthermore, the prokineticin2 concentration in these patients died of sepsis or septic shock is significantly lower than those survival patients with sepsis or septic shock, indicating the potential value of prokineticin2 in the diagnosis of sepsis and septic shock, as well as the potential value in predicting mortality in adult patients with sepsis and septic shock. In animal model, recombinant prokineticin2 administration protected against sepsis-related deaths in both heterozygous prokineticin2 deficient mice and wild-type mice and alleviated sepsis-induced multiple organ damage. In in vitro cell models, prokineticin2 enhanced the phagocytic and bactericidal functions of macrophage through signal transducers and activators of transcription 3 pathway which could be abolished by signal transducers and activators of transcription 3 inhibitors S3I-201. Depletion of macrophages reversed prokineticin2-mediated protection against polymicrobial sepsis., Conclusions: This study elucidated a previously unrecognized role of prokineticin2 in clinical diagnosis and treatment of sepsis. The proof-of-concept study determined a central role of prokineticin2 in alleviating sepsis-induced death by regulation of macrophage function, which presents a new strategy for sepsis immunotherapy., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Objective: To analyze the stimulating effect of axial length development on orbital volume development in patients (ages 12-60 years) with congenital microphthalmia., Methods: This retrospective cohort study included 43 patients (86 eyes) with congenital microphthalmia. Three-dimensional images of the orbit were generated from past computed tomography scans, and digital orbital volume and axial length measurements were taken. The patients were divided into four age groups for analyses. Paired t tests and one-way analysis of variance tests were used to compare orbital volume and axial length between the affected and unaffected eyes. Pearson correlation analyses and scatter plots were used to investigate the correlations between age, orbital volume, and axial length in the affected and unaffected eyes. Linear regression analysis was used to determine the association between orbital volume and axial length., Results: The mean orbital volume in the affected and unaffected eyes was 17.08 ± 2.88 and 20.80 ± 2.55 cm3, respectively. The mean axis length in the affected and the unaffected groups was 12.73 ± 3.54 and 23.84 ± 1.43 mm, respectively. Significant differences were observed among orbital (t = 13.538, P < 0.001) volume and axial length (t = 21.339, P < 0.001) in the affected and the unaffected groups. There were no significant differences in affected orbital volume (F = 0.527, P > 0.05), unaffected orbital volume (F = 1.628, P > 0.05), affected axial length (F = 0.946, P > 0.05), and unaffected axial length (F = 2.217, P > 0.05) among the four age groups. According to the Pearson correlations, there were no significant correlations between age and affected volume, unaffected volume, affected axis, and unaffected axis (r = 0.095, 0.097, 0.084, and 0.022, respectively; all P > 0.05). Orbital volume was moderately correlated with axial length in the affected and unaffected groups (r = 0.470 and 0.410, respectively; both P < 0.01). Linear regression analysis revealed that a 1 mm change in axis length was associated with a 0.38 cm3 and 0.73 cm3 change in orbital volume in the affected and unaffected groups, respectively., Conclusions: In individuals ages 12 to 60 years old with congenital microphthalmia, the effect of axis length on the orbital volume growth of the affected eye is only half that of the unaffected eye. The eyeball, orbital tissue, and craniofacial development all play an important role in the growth of orbital volume., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Background: Left ventricular noncompaction cardiomyopathy (LVNC) was discovered half a century ago as a cardiomyopathy with excessive trabeculation and a thin ventricular wall. In the decades since, numerous studies have demonstrated that LVNC primarily has an effect on left ventricles (LVs) and is often associated with LV dilation and dysfunction. However, in part because of the lack of suitable mouse models that faithfully mirror the selective LV vulnerability in patients, mechanisms underlying the susceptibility of LVs to dilation and dysfunction in LVNC remain unknown. Genetic studies have revealed that deletions and mutations in PRDM16 (PR domain-containing 16) cause LVNC, but previous conditional Prdm16 knockout mouse models do not mirror the LVNC phenotype in patients, and the underlying molecular mechanisms by which PRDM16 deficiency causes LVNC are still unclear., Methods: Prdm16 cardiomyocyte-specific knockout ( Prdm16 cKO ) mice were generated and analyzed for cardiac phenotypes. RNA sequencing and chromatin immunoprecipitation deep sequencing were performed to identify direct transcriptional targets of PRDM16 in cardiomyocytes. Single-cell RNA sequencing in combination with spatial transcriptomics was used to determine cardiomyocyte identity at the single-cell level., Results: Cardiomyocyte-specific ablation of Prdm16 in mice caused LV-specific dilation and dysfunction, as well as biventricular noncompaction, which fully recapitulated LVNC in patients. PRDM16 functioned mechanistically as a compact myocardium-enriched transcription factor that activated compact myocardial genes while repressing trabecular myocardial genes in LV compact myocardium. Consequently, Prdm16 cKO LV compact myocardial cardiomyocytes shifted from their normal transcriptomic identity to a transcriptional signature resembling trabecular myocardial cardiomyocytes or neurons. Chamber-specific transcriptional regulation by PRDM16 was attributable in part to its cooperation with LV-enriched transcription factors Tbx5 and Hand1., Conclusions: These results demonstrate that disruption of proper specification of compact cardiomyocytes may play a key role in the pathogenesis of LVNC. They also shed light on underlying mechanisms of the LV-restricted transcriptional program governing LV chamber growth and maturation, providing a tangible explanation for the susceptibility of LV in a subset of LVNC cardiomyopathies.

Purpose: The true impact of postoperative radioiodine therapy on survival has been controversial for patients with poorly differentiated thyroid carcinoma (PDTC). We aimed to determine the impact of postoperative radioiodine on survival in PDTC through a population-based study., Methods: Data on patients with PDTC were collected from the US SEER database (2004 to 2015). Patients were divided into the radioiodine group and nonradioiodine group. Survival comparison between groups was evaluated by Kaplan-Meier curves, log-rank test and multivariate Cox regression analysis. Akaike information criterion was used to select variables in the nomogram. The performance of the nomogram was assessed by discrimination (C-index) and calibration plots., Results: The radioiodine group had more aggressive features, such as advanced tumor node metastasis stage and radical surgery, compared to the nonradioiodine group. PDTC patients receiving radioiodine therapy had a significant survival advantage in terms of overall survival (OS) (P = 0.001) but not in terms of cancer-specific survival (P = 0.083). Multivariate analysis revealed radioiodine therapy was an independent favorable factor for OS in PDTC patients (hazard ratio = 0.57; 95% CI, 0.44-0.75, P < 0.001). Subgroup analysis identified patients' characteristics favoring radioiodine therapy. The nomogram (age, tumor size, extension, neck lymph nodes metastasis and radioiodine therapy) of OS for predicting 3-, 5- and 10-year OS probability showed good discrimination (C-index, 0.797) and calibration power., Conclusion: Postoperative radioiodine therapy can prolong the long-term OS in patients with PDTC, and is an independent favorable prognostic factor for those patients. Further prospective studies are warranted., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Langerhans cell histiocytosis (LCH) is characterized pathologically by langerin-positive (CD207+) dendritic cell proliferation and is considered by some as a myeloid neoplastic disorder. Hemophagocytic lymphohistiocytosis (HLH) is associated with immune dysregulation characterized by the accumulation of activated macrophages and hypercytokinemia. However, these 2 histiocytosis rarely coexist. Currently, the etiology, risk factors, optimal therapy, and outcomes of LCH-HLH remain unclear. We reviewed the medical records of 7 LCH-HLH patients from our hospital and analyzed 50 LCH-HLH patients reported in scientific literature. The median age of LCH onset of these 57 LCH-HLH patients was 1 year, and 91% (52/57) of patients diagnosed as LCH were less than 2 years old. Fifty-six LCH-HLH patients belonged to the multisystem LCH category and 84% (47/56) patients had risk-organ involvement. Twenty-three LCH-HLH patients were complicated with infection and 3 patients had a primary pathogenic mutation of HLH. Overall, 90% of LCH patients developed HLH at the diagnosis or during chemotherapy. Of the 57 LCH-HLH patients, 15 died. Multisystem LCH patients with risk-organ involvement under 2 years old were most likely to develop HLH when complicated with infection at diagnosis or during chemotherapy. Identifying LCH-HLH patients during early stages and treating them with prompt chemotherapy, hematopoietic stem cell transplantation, or supportive therapies are important for better survival., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cancer-related fatigue (CRF) is one of the most common adverse events of anticancer therapies, with an incidence of up to 90%, which seriously affects the quality of life in cancer patients. Complementary and alternative therapies for CRF include acupuncture, Chinese herbal medicine, Tai Chi, Qigong, and massage therapy. Several studies have shown that traditional Chinese medicine (TCM) exercise therapies, such as Tai Chi, Ba Duan Jin, the classics of tendon changing, Six Healing Sounds, and Wu Qin Xi, can improve CRF, anxiety symptoms, and sleep quality in cancer patients. However, their specific efficacy and which TCM exercise therapy is the best remain controversial. In this study, we assess and compare the effects of different TCM exercise therapies on CRF, anxiety, and sleep quality in cancer patients by network meta-analysis (NMA)., Methods: Randomized controlled trials reporting TCM exercise therapies for CRF, anxiety and sleep quality in cancer patients published before October 2021 will be searched in the PubMed, Web of Science, Scopus, Cochrane Library, Embase, China Scientific Journal Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wanfang Data. Two researchers will be independently responsible for literature screening, data extraction and assessment of their quality. Standard pair-wise and NMA will be performed to compare the efficacy of different TCM exercise therapies on CRF, anxiety and sleep quality in cancer patients using Stata 14.0 software., Results: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication., Conclusions: This NMA will contribute to identify the optimal TCM exercise therapy for CRF and provide evidence-based bias for clinical decision-making., Ethics and Dissemination: Ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms., Osf Registration Number: DOI 10.17605/OSF.IO/MJ8DA., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Traditional Chinese medicine injections (TCMJs) combined with FOLFOX4 regimen could achieve favorable effects in the treatment of gastric cancer. However, the efficacy and safety of different TCMJs combined with FOLFOX4 in the treatment of gastric cancer have not been fully clarified. Due to the fact that there are as many as 10 kinds of TCMJs, how to choose an appropriate TCMJ has become an urgent clinical problem. The objective of this network meta-analysis is to explore the optimal options among different TCMJs for gastric cancer., Methods: PubMed, Web of Science, Scopus, Cochrane Library, Embase, China Scientific Journal Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wanfang Data were searched to identify randomized controlled trials which focused on TCMJs combined with FOLFOX4 against gastric cancer from its inception to September 2021. Subsequently, 2 researchers will be independently responsible for literature screening, data extraction, and assessment of their quality. Standard pair-wise and Bayesian network meta-analysis will be performed to compare the efficacy and safety of different TCMJs combined with FOLFOX4 regimen via Stata 14.0 and WinBUGS1.4 software., Results: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication., Conclusions: The conclusion of this systematic review will provide evidence for selecting an optimal TCMJ combined with FOLFOX4 for patients with gastric cancer., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Breast cancer has recently become one of the most common causes of cancer-related deaths, and several studies have suggested that genetic polymorphisms in the folate metabolism pathway may be associated with susceptibility to breast cancer, although their results have been inconsistent or inconclusive. Therefore, the aim of this meta-analysis was to obtain accurate, consistent conclusions regarding the potential associations of genetic polymorphisms in the folate metabolism pathway with the risk of breast cancer, based on case-controlled studies., Methods: From the beginning of database establishment through May 2021, we indexed and searched domestic and foreign databases, including the Chinese National Knowledge Infrastructure, Web of Science, VIP and BioMedical Database of China, PubMed, EMBASE, Wanfang database, and the Cochrane Library. To determine the effects of folate metabolism-related genetic polymorphisms on breast cancer risk, we used Stata version 16.0 to analyze all data and calculated variable odds ratios and 95% confidence intervals., Results: The findings of the current meta-analysis are going to be presented to peer-reviewed journals for publication when the analysis is completed., Conclusion: The meta-analysis will summarize the association of genetic polymorphisms in the folate metabolism pathway with breast cancer., Registration Number: May 26, 2021.osf.io/25r48. (https://osf.io/25r48/)., Competing Interests: The authors have no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: With the popularization of ultrasound, nerve blocks have been widely implemented in current clinical practice. Although, they have seen limited success due to their shorter duration and suboptimal analgesia. Magnesium sulfate as a local anesthetic adjuvant for peripheral nerve blocks could enhance the effects of local anesthetics. However, previous investigations have not thoroughly investigated the analgesic efficacy of magnesium sulfate as an adjunct to local anesthetics for peripheral nerve blocks. Thus, we attempted to fill the gap in the existing literature by conducting a meta-analysis., Materials and Methods: We performed of a quantitative systematic review of randomized controlled trials published between May 30, 2011 and November 1, 2018. Inclusion criteria were: (1) magnesium sulfate used as adjuvant mixed with local anesthetic for nerve blockade, (2) complete articles and published abstracts of randomized controlled trials, (3) English language., Primary and Secondary Outcome Measures: The primary outcome measures were time of onset, total duration of the sensory blockade, and Visual Analog Scale pain scores. The secondary outcomes were postoperative oral and intravenous analgesics consumption and the incidence of nausea and vomiting., Results: The 21 trials analyzed in this study included 1323 patients. Magnesium sulfate effectively prolonged the total duration of sensory blockade (mean difference [MD]=114.59 min, 95% confidence interval [CI]: 89.31-139.88), reducing Visual Analog Scale pain scores at 6 hours (MD=1.36 points, 95% CI: -2.09 to -0.63) and 12 hours (MD=1.54 points, 95% CI: -2.56 to -0.53) postsurgery. Magnesium sulfate also effectively reduced postoperative analgesic use within 24 hours postsurgery (standard MD=-2.06, 95% CI: -2.67 to -1.35). Furthermore, adjuvant magnesium sulfate significantly reduced the incidence of nausea and vomiting after transversus abdominis plane blockade (odds ratio: 0.39, 95% CI: 0.18-0.81)., Conclusion: Adjuvant magnesium sulfate enhanced the anesthetic effects of local anesthetics and improved postoperative analgesia following the perineural blockade., Competing Interests: Supported by the Foundation of National Cancer Center in China (NCC2017A06 to B.Y.) Chongqing/China, Foundation of Chongqing Science and Technology Commission (cstc2016jcyjA0158 to B.Y.), Chongqing/China, and Foundation and Frontier Research Projects of Chongqing Science and Technology Commission (cstc2018jxjl0052 to B.Y.), Chongqing/China. The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Lacunar infarction (LI) is the mild type in the classification of ischemic stroke, mostly occurs in the middle-aged and elderly, with mild hemiplegia and partial sensory disorder as the main manifestations. In the treatment of LI, acupuncture is often regarded as dominant therapy in the convalescence period. However, acupuncture for treatment of LI in the recovery period lacks high-quality reports and evidence-based medical evidence. Thus, we aim to evaluate the curative effect and safety of acupuncture for LI objectively., Methods: Pubmed, Cochrane Library, Web of Science, EBSCO, Springer, China National Knowledge Infrastructure, Chinese Scientific and Technical Journals Database (VIP), Wan-fang Database, Chinese Biomedical Literature Database, Chinese Science Citation Database, and other electronic databases will be retrieved from the inception to May, 2021. Randomized controlled trials related to this subject will be searched. The inclusion criteria are established and a detailed literature search strategy is designed through discussion. Article retrieval, screening, excluding repetitive studies, assessment of quality, and data processing will be conducted by 2 reviewers independently using EndNote (X9) and Review Manager (5.3.5). The outcome measures include primary outcome measures (total effective rate, National Institute of Health Stroke Scale score, and Fugl-Meyer Assessment score), secondary outcome measures (blood pressure, plasma glucose, and blood lipid), and safety outcome measures. We will perform a meta-analysis, descriptive analysis, and subgroup analysis based on data conditions., Results: The study of total effective rate, National Institute of Health Stroke Scale score, Fugl-Meyer Assessment score, blood pressure, plasma glucose, blood lipid, and adverse effects will provide evidenced outcome for high-quality synthesis and descriptive analysis., Conclusion: This systematic review will kindly provide evidence of whether acupuncture is an effective and safe intervention for LI in the recovery period., Inplasy Registration Number: INPLASY202150060 (DOI:10.37766/inplasy2021.5.0060)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: Mosaicism can be observed in karyotype analyses of amniotic fluid cells. Differentiating between true mosaicism and pseudomosaicism and determining mosaic proportions can help avoid misjudgments by doctors and effectively reduce mental and physical harm to pregnant women. However, the detection of mosaicism and mosaic proportions via karyotype analysis and fluorescence in situ hybridization (FISH) is extremely complex. We have developed a novel approach, "segmental duplication quantitative fluorescent PCR" (SD-QF-PCR), to detect mosaicism and mosaic proportions.In this study, twenty control samples and fourteen mosaic samples were tested by first-line karyotype analysis; by second-line karyotype analysis, SD-QF-PCR and FISH were used to reassess fetal sex chromosome mosaicism and mosaic proportions.Detection of the 20 control samples by second-line karyotype analysis via FISH and SD-QF-PCR showed normal and consistent results. Among the 14 mosaic samples, the numbers of samples showing true mosaicism and pseudomosaicism detected by the three methods were 6 and 8, respectively.Our study demonstrates that SD-QF-PCR can be used as a complementary method to traditional cytogenetic analysis of amniotic fluid mosaics and has clinical application value., Competing Interests: The authors report no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Our previous research has shown that monocytic leukemia-associated antigen-34 (MLAA-34) was a novel antiapoptotic molecule with unique expression in acute monocytic leukemia (M5), making it an ideal target for T-cell-based immunotherapy. Here, we sought to identify HLA-A*0201-restricted cytotoxic T-lymphocyte (CTL) epitope of MLAA-34 by reverse immunology. In all, 10 HLA-A*0201 restricted epitopes of MLAA-34 were predicted by bioinformatics. MLAA-34324-332, MLAA-34293-301, and MLAA-34236-244 showed the strongest HLA-A*0201-binding affinity. The percentages of HLA-A*0201-MLAA-34236-244 tetramer+ CD8+ T cells in MLAA-34236-244-induced CTLs were raised apparently. Enzyme-linked immunospot showed that MLAA-34236-244 and MLAA-34324-332-specific CTLs produced a higher amount of interferon-γ. MLAA-34236-244-induced CTLs presented a stronger cytotoxic effect on THP-1 cells (HLA-A*0201+MLAA-34+) at various effector to target ratios. MLAA-34236-244 peptide vaccine could inhibit the tumor growth and improve mean survival time of leukemia-bearing human peripheral blood lymphocyte reconstituting severe combined immunodeficient mice. Mice immunized with MLAA-34236-244 vaccine had increased percentages of MLAA-34236-244 tetramer+ CD8+ T cells in the spleen after each round of immunization. High-purity CD8+ and CD4+ T cells were sorted by Dynabeads as effector cells. The killing activity of CD8+ T cells was higher than that of CD4+ T cells. CTLs derived from the MLAA-34 peptide vaccine group were significantly higher than other therapeutic groups and showed specific cytotoxicity to THP-1 cells. Increased interferon-γ and interleukin (IL)-2 and decreased IL-10 and IL-4 were seen in the MLAA-34236-244 peptide vaccine group. MLAA-34236-244 peptide (ILDRHNFAI) is an effective HLA-A*0201-restricted CTL epitope and that it may serve as a promising strategy in designing antigen-specific immunotherapy against MLAA-34-positive acute monocytic leukemia., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: The study aimed to explore the reliability and validity of the Sub-Health Measurement Scale version 1.0 (SHMS v1.0) for the assessment of the suboptimal health status (SHS) of Tianjin residents.This was a cross-sectional study that surveyed 2640 urban residents in Tianjin from June 2016 to January 2018. Demographic and clinical characteristics were collected. Each subject completed the SHMS v1.0 and Short Form-36 (SF-36) scale assessments.The retest coefficient was 0.675. The overall Cronbach's α coefficient was 0.921. The correlation between SHMS v1.0 and SF-36 was 0.781 (P < .01). The SHS frequency increased with age, from 62.4% in participants ≤25 years of age to 72.8% in those ≥ 56 years of age. The multivariable analysis showed that female sex (P < .001), age >25 years old (P = .009), bachelor degree or above (P < .001), obesity (P < .0), regular smoking (P = .043), frequent drinking (P = .045), sleep time < 6 hours (P = .006), working time >10 hours (P < .001), physical exercise <5 times/mo (P < .001), and adverse events >9 (P < .001) were associated with SHS.The prevalence of SHS is high among urban residents in Tianjin., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: COVID-19 has strong transmission power, and people are generally susceptible to it. Patients with weak constitution and low immunity function are more likely to be infected. Aromatic therapy of traditional Chinese medicine has the effect of inhibiting virus and sterilization, especially the external treatment of traditional Chinese medicine has played an important role in the fight against the epidemic situation., Methods: Nine databases will be searched under the guideline of research strategy, from their inception to March 31, 2021, for relevant randomized controlled trial (RCTs) published. These databases are Cochrane Library, PubMed, EMBASE, Web of Science, ScienceDirect, China National Knowledge Infrastructure, Wan-fang Data, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database. The types on Language of literature are English and Chinese. Researchers will independently operate the literature research, screening, quality evaluation, data collection, and data analysis with same research strategy and selection criteria. Methodological quality will be evaluated under the guideline of the Cochrane Collaboration's tool. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) will be used to determine confidence in the effect estimates. Meta-analysis or subgroup analysis will be performed according to the including data type. Meta-analysis will be performed with Stata 13.0 software., Results: Outcome will be displayed by effective rates, quality of life score, adverse effect., Conclusion: This systematic review will provide evidence whether Chinese herbal sachets are effective and safe intervention of COVID-19 Pandemic., Registration Number in Prospero: CRD42021238580., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: Glomerular capillaries are lined with a highly specialized fenestrated endothelium and contribute to the glomerular filtration barrier. The Notch signaling pathway is involved in regulation of glomerular filtration barrier, but its role in glomerular endothelium has not been investigated due to the embryonic lethality of animal models with genetic modification of Notch pathway components in the endothelium., Objective: To determine the effects of aberrant activation of the Notch signaling in glomerular endothelium and the underlying molecular mechanisms., Methods and Results: We established the ZEG-NICD1 (notch1 intracellular domain)/Tie2-tTA/Tet-O-Cre transgenic mouse model to constitutively activate Notch1 signaling in endothelial cells of adult mice. The triple transgenic mice developed severe albuminuria with significantly decreased VE-cadherin (vascular endothelial cadherin) expression in the glomerular endothelium. In vitro studies showed that either NICD1 (Notch1 intracellular domain) lentiviral infection or treatment with Notch ligand DLL4 (delta-like ligand 4) markedly reduced VE-cadherin expression and increased monolayer permeability of human renal glomerular endothelial cells. In addition, Notch1 activation or gene knockdown of VE-cadherin reduced the glomerular endothelial glycocalyx. Further investigation demonstrated that activated Notch1 suppression of VE-cadherin was through the transcription factors SNAI1 (snail family transcriptional repressor 1) and ERG (Ets related gene), which bind to the -373 E-box and the -134/-118 ETS (E26 transformation-specific) element of the VE-cadherin promoter, respectively., Conclusions: Our results reveal novel regulatory mechanisms whereby endothelial Notch1 signaling dictates the level of VE-cadherin through the transcription factors SNAI1 and ERG, leading to dysfunction of glomerular filtration barrier and induction of albuminuria. Graphic Abstract: A graphic abstract is available for this article.

Rationale: Clitoris swelling as the initial clinical presentation of acute lymphoblastic leukemia (ALL) is extremely rare. These patients may be misdiagnosed with acute myeloid leukemia or solid tumor, and the main treatment can also be delayed., Patient Concerns: A 2.10-year-old girl was referred to the pediatric surgery clinic with a worsening onset of clitoris swellings. The patient was afebrile and well appearing. Multiple retroperitoneal mass were confirmed by computed tomography (CT) and high serum neuron-specific enolase level was high. She was scheduled for an abdominal biopsy from the retroperitoneal mass suspicious of neuroblastoma., Diagnoses: The child was eventually diagnosed as having precursor B cell ALL with central nervous system involved, with TCF3-PBX1 fusion gene and additional chromosomal aberrations, based on examinations of the bone marrow and brain magnetic resonance imaging., Interventions: Before the diagnosis of leukemia, the patient was given symptomatic treatment for 1 week. She was treated with chemotherapy in accordance with the Chinese Children's Cancer Group protocol 2015 after confirmed diagnosis., Outcomes: After induction chemotherapy for ALL, although the girl had transiently clinical remission, the bone marrow aspirate indicated a poor outcome. Our patient discontinued treatment and discharged. From literature review, there was only 1 case of in acute myeloid leukemia with clitoris swelling as the initial symptom., Lessons: The clinical symptoms of ALL with clitoris swelling are not typical, with a high rate of misdiagnosis. When the cause of clitoris swelling is unknown, ALL should be considered. Bone marrow aspiration must be done before doing a more invasive investigation like biopsy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)