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Ye Zhou,1,&ast; Ming-Jun Liu,2,&ast; Xiu-Yu Liao,1 Yu-Ting Chen,3 Qiu-Xia Liao,1 Jian-Dong Lin,1 Hai-Rong Lin,4 Ying-Hong Huang1 1Department of Intensive Care Unit, First Affiliated Hospital of Fujian Medical University, Fuzhou, 350000, People’s Republic of China; 2Department of Infection, People’s Hospital of YangJiang, YangJiang, 529500, People’s Republic of China; 3Department of Gastroenterology, Fuzhou NO. 1 Hospital, Fuzhou, 350000, People’s Republic of China; 4Department of Intensive Care Unit, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiu-Yu Liao; Ying-Hong Huang, Department of Intensive Care Unit, First Affiliated Hospital of Fujian Medical University, No. 20 of Chazhong Road, TaiJiang District, Fuzhou, 350000, People’s Republic of China, Tel +86 15959021313 ; +86 13306901596, Fax +86 591-87982028, Email liaoxiuyullxuiyu@126.com; huangyinghonghyh@126.comObjective: To investigate the antibacterial impact of daptomycin and azithromycin in vitro on methicillin-resistant Staphylococcus aureus (MRSA) biofilm.Methods: (1) Measure the strain growth curve and the biofilm formation curve. (2) Determine the minimum inhibitory concentrations (MICs) of daptomycin and azithromycin. (3) Investigate the antibacterial impact of the combination of daptomycin and azithromycin. (4) Perform the evaluation of the intervention impact of antimicrobial agents on MRSA biofilm. (5) Observe the biofilm after intervention with the antibacterial agent.Results: (1) MRSA exhibited three phases: lag phase (0– 4 h), logarithmic growth (4– 8 h) and stationary phase after 18 h; its biofilm began to form at 6 h, semi-matured at 24 h, and reached maturity after 48 h. (2) The MICs of daptomycin and azithromycin were 8 μg/mL and greater than 256 μg/mL, respectively. (3) The combination of daptomycin and azithromycin has an additive effect on MRSA (Fractional Inhibitory Concentration Index [FICI] 0.625) (FICI = MIC of drug A in combination/MIC of drug A alone + MIC of drug B in combination/MIC of drug B alone). Evaluation criteria: Synergistic effect is considered when FICI ≤ 0.5; additive effect is considered when 0.5 < FICI ≤ 1; irrelevant effect is considered when 1 < FICI ≤ 2; antagonistic effect is considered when FICI > 2). (4) Daptomycin or azithromycin at MICs inhibited not only the growth of planktonic bacteria but also the formation of biofilm. (5) The combination of both, in which group the ratio of live/dead bacteria is low and the biofilm morphology was incomplete, was more productive than monotherapy in against biofilm.Conclusion: Both daptomycin and azithromycin have anti-MRSA biofilm activity, and daptomycin is dominant. The fact that the combination of both can significantly inhibit the further maturation of MRSA biofilm and destroy already formed biofilm demonstrates the superiority of the combination over the monotherapy.Keywords: azithromycin, bacterial resistance, biofilm, daptomycin, MRSA

Xin-Yu Liao,1,* Yang Lei,2,* Song-Feng Chen,2 Jing Cheng,3 Dan Zhao,4 Zhi-Feng Zhang,2 Xin Han,5 Ya Zhang,2 Hua-Bao Liao,2 Yang Zhuang,2 Juan Chen,6 Hai-Bing Zhou,5 Qi Wan,7 Ying-Ying Zou,11Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming 650500, People’s Republic of China; 2Department of Physiology, School of Basic Medical Sciences, Wuhan University School of Medicine, Wuhan 430071, People’s Republic of China; 3Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, People’s Republic of China; 4Department of Physiology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, People’s Republic of China; 5School of Pharmacy, Wuhan University, Wuhan 430071, People’s Republic of China; 6Department of Neurology, The Central Hospital of Wuhan, Tongji Medical College of Huazhong University of Science & Technology, Wuhan 430013, People’s Republic of China; 7Institute of Neuroregeneration & Neurorehabilitation, Collaborative Innovation Center for Brain Science, Department of Neurosurgery of the Affiliated Hospital, Qingdao University, Qingdao 266071, People’s Republic of China*These authors contributed equally to this work Background: The authors have recently designed a new compound bisperoxovandium (pyridin-2-squaramide) [bpV(pis)] and verified that bpV(pis) confers neuroprotection through suppressing PTEN and activating ERK1/2, respectively. Intracerebral hemorrhage (ICH) is the second most common cause of stroke and has severe clinical outcome. In this study, we investigate the effect of bpV(pis) in ICH model both in vivo and in vitro.Materials and methods: The novel drug bpV(pis) was synthesized in the Faculty of Pharmacy, Wuhan University School of Medicine. An ICH model was generated on both SD rats and cells. bpV(pis) was injected into intracerebroventricular or culture media. Western blotting was applied to test the signal pathway. To determine the effect of bpV(pis) on PTEN inhibition and ERK1/2 activation, we measured the phosphorylation level of AKT (a direct downstream target of PTEN that negatively regulates AKT) and ERK1/2. FJC, MTT, and LDH were applied to measure the cell viability. Neurobehavioral tests were performed to measure the effect of bpV(pis).Results: The in vivo results showed that intracerebroventricular administration of bpV(pis) significantly alleviates hematoma, the damage of brain–blood barrier and brain edema. The in vitro results demonstrated that bpV(pis) treatment reduces ICH-induced neuronal injury. Western blotting results identified that bpV(pis) exerts a neuroprotective effect by significantly increasing the phosphorylation level of AKT and ERK1/2 after experimental ICH. Neurobehavioral tests indicate that bpV(pis) promotes functional recovery in ICH animals.Conclusion: This study provides first and direct evidence for a potential role of bpV(pis) in ICH therapy.Keywords: bpV(pis), intracerebral hemorrhage, PTEN, AKT, ERK1/2, neuroprotection

Alveolar bone defects pose a significant challenge in oral clinical treatments, impacting procedures such as dental implants, orthodontics, and oral restoration. Despite their frequent occurrence due to various causes, the effective restoration and reconstruction of alveolar bone defects remain a significant clinical challenge in dentistry. Existing treatments often rely on intrinsic blood coagulation to stabilize bone grafts, but they present limitations such as gradual clotting and reduced effectiveness in patients with coagulation dysfunction. Injectable gel holds promise as an alternative to coagulation-dependent bone graft matrices, but it also faces challenges, including low initial viscosity and dependence on the natural formation of the defect area during the curing process. Here, we present a ceramic-craft-inspired osteogenic (CIO) hydrogel, designed to achieve moldable and curable properties for bone defect regeneration. This injectable paste, composed of gelatin methacrylate (GelMA), nanoclay, and bone grafts, allows for local injection and manual shaping without the need for molds. The shaped hydrogel rapidly crosslinks within 15 s under UV irradiation, providing malleability, strength, and coagulation-independent bone graft stabilization. This approach offers a potential breakthrough in addressing the persistent clinical challenge of alveolar bone defect restoration., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Abstract: This umbrella review aimed to summarize and provide a general evaluation of the effectiveness of current treatments for male infertility and assess the quality of evidence and possible biases. An umbrella review of systematic reviews and meta-analyses available in PubMed, Web of Science, and Scopus, covering studies published up to October 2023, was conducted. Sperm concentration, morphology, and motility were used as endpoints to evaluate the effectiveness of the treatments. Of 2998 studies, 18 published meta-analyses were extracted, yielding 90 summary effects on sperm concentration ( n = 36), sperm morphology ( n = 26), and sperm motility ( n = 28) on 28 interventions. None of the meta-analyses were classified as having low methodological quality, whereas 12 (66.7%) and 6 (33.3%) had high and moderate quality, respectively. Of the 90 summary effects, none were rated high-evidence quality, whereas 53.3% ( n = 48), 25.6% ( n = 23), and 21.1% ( n = 19) were rated moderate, low, and very low, respectively. Significant improvements in sperm concentration, morphology, and motility were observed with pharmacological interventions (N-acetyl-cysteine, antioxidant therapy, aromatase inhibitors, selective estrogen receptor modulators, hormones, supplements, and alpha-lipoic acid) and nonpharmacological interventions (varicocele repair and redo varicocelectomy). In addition, vitamin supplementation had no significant positive effects on sperm concentration, motility, or morphology. Treatments for male infertility are increasingly diverse; however, the current evidence is poor because of the limited number of patients. Further well-designed studies on single treatment and high-quality meta-analysis of intertreatment comparisons are recommended., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

Abstract: Objective: The objective of this study is to assess and compare the efficacy of oXiris with conventional continuous renal replacement therapy (CRRT) in managing severe abdominal infections. Methods: A retrospective analysis encompassing cases from 2017 to 2023 was conducted at the Department of Critical Care Medicine within the First Affiliated Hospital of Fujian Medical University. Parameters including heart rate (HR), mean arterial pressure (MAP), oxygenation index, lactate (Lac), platelet count, neutrophil ratio, procalcitonin, C-reactive protein (CRP), interleukin 6 (IL-6), norepinephrine dosage, Acute Physiology and Chronic Health Evaluation II (APACHE II), and Sequential Organ Failure Assessment (SOFA) were recorded prior to treatment initiation, at 24 h, and 72 h after treatment for both the oXiris and conventional CRRT groups. In addition, the duration of respiratory support, CRRT treatment, length of stay in the intensive care unit (ICU), total hospitalization period, and mortality rates at 14 and 28 days for both groups were recorded. Results: 1) Within the conventional CRRT group, notable enhancement was observed solely in Lac levels at 24 h after treatment compared with pretreatment levels. In addition, at 72 h after treatment, improvements were evident in HR, Lac, CRP, and IL-6 levels. 2) Conversely, the oXiris group exhibited improvements in HR, MAP, Lac, oxygenation index, neutrophil ratio, and IL-6 at 24 h after treatment when compared with baseline values. In addition, reductions were observed in APACHE II and SOFA scores. At 72 h after treatment, all parameters demonstrated enhancement except for platelet count. 3) Analysis of the changes in the indexes (Δ) between the two groups at 24 h after treatment revealed variances in HR, MAP, Lac, norepinephrine dosage, CRP levels, IL-6 levels, APACHE II scores, and SOFA scores. 4) The Δ indexes at 72 h after treatment indicated more significant improvements following oXiris treatment for both groups, except for procalcitonin. 5) The 14-day mortality rate (24.4%) exhibited a significant reduction in the oXiris group when compared with the conventional group (43.6%). However, no significant difference was observed in the 28-day mortality rate between the two groups. 6) Subsequent to multifactorial logistic regression analysis, the results indicated that oXiris treatment correlated with a noteworthy decrease in the 14-day and 28-day mortality rates associated with severe abdominal infections, by 71.3% and 67.6%, respectively. Conclusion: oXiris demonstrates clear advantages over conventional CRRT in the management of severe abdominal infections. Notably, it reduces the fatality rates, thereby establishing itself as a promising and potent therapeutic option., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Purpose: The current study aims to investigate the significance of N6-methyladenosine (m 6 A) methylationrelated genes in the clinical prognosis of childhood relapsed B-cell acute lymphoblastic leukemia (B-ALLL) patient., Methods: Transcriptome data and corresponding clinical data on m 6 A methylation-related genes (including 20 genes) were obtained from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET) database., Results: The bone marrow (BM) samples of 134 newly diagnosed (naive) and 116 relapsed B-ALL from TARGET were enrolled in the current study. Three genes (FTO, HNRNPC, RBM15B) showed significant up-regulation in relapsed B-ALL compared with that in naive B-ALL.The three genes had a significantly worse survival (P < 0.05). The LASSO Cox regression model was used to select the most predictive genes as prognostic indicators, and YTHDC1 and FTO were identified as prognostic factors for relapsed B-ALL. Finally, the results of multivariate regression analysis showed that the risk score of m 6 A methylation-related genes was an independent prognostic factor in relapsed B-ALL (P < 0.05)., Conclusion: We found that the expression levels of m 6 A methylation-related genes were different in naive and relapsed patients with B-ALL and correlated with survival and prognosis.This implies that m 6 A methylation-related genes may be promising prognostic indicators or therapeutic targets for relapsed B-ALL., (© 2024. The Author(s).)

Sodium-glucose co-transporter 2 (SGLT2) inhibitor (SGLT2i) is a novel class of anti-diabetic drug, which has displayed a promising benefit for non-alcoholic fatty liver disease (NAFLD). In this study, we investigated the protective effects of SGLT2i against NAFLD and the underlying mechanisms. The db/db mice and western diet-induced NAFLD mice were treated with dapagliflozin (1 mg·kg -1 ·d -1 , i.g.) or canagliflozin (10 mg·kg -1 ·d -1 , i.g.) for 8 weeks. We showed that the SGLT2i significantly improved NAFLD-associated metabolic indexes, and attenuated hepatic steatosis and fibrosis. Notably, SGLT2i reduced the levels of pro-inflammatory cytokines and chemokines, downregulated M1 macrophage marker expression and upregulated M2 macrophage marker expression in liver tissues. In cultured mouse bone marrow-derived macrophages and human peripheral blood mononuclear cell-derived macrophages, the SGLT2i (10, 20 and 40 μmol/L) significantly promoted macrophage polarization from M1 to M2 phenotype. RNA sequencing, Seahorse analysis and liquid chromatography-tandem mass spectrometry analysis revealed that the SGLT2i suppressed glycolysis and triggered metabolic reprogramming in macrophages. By using genetic manipulation and pharmacological inhibition, we identified that the SGLT2i targeted PFKFB3, a key enzyme of glycolysis, to modulate the macrophage polarization of M1 to M2 phenotype. Using a co-culture of macrophages with hepatocytes, we demonstrated that the SGLT2i inhibited lipogenesis in hepatocytes via crosstalk with macrophages. In conclusion, this study highlights a potential therapeutic application for repurposing SGLT2i and identifying a potential target PFKFB3 for NAFLD treatment., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Platelet-rich plasma (PRP) holds promise as a therapeutic modality for wound healing; however, immediate utilization encounters challenges related to volume, concentration, and consistency. Cryopreservation emerges as a viable solution, preserving PRP's bioactive components and extending its shelf life. This study explores the practicality and efficacy of cryopreserved platelet-rich plasma (cPRP) in wound healing, scrutinizing both cellular mechanisms and clinical implications. Fresh PRP and cPRP post freeze-thaw underwent assessment in macrophage, fibroblast, and endothelial cell cultures. The impact of cPRP on active component release and cell behavior pertinent to wound healing was evaluated. Varied concentrations of cPRP (1%, 5%, 10%) were examined for their influence on cell polarization, migration, and proliferation. The results showed minimal changes in cPRP's IL-1β levels, a slight decrease in PDGF-BB, and superior effects on macrophage M2 polarization and fibroblast migration, while no statistical significance was observed in endothelial cell angiogenesis and proliferation. Remarkably, 5% PRP exhibited the most significant stimulation among all cPRP concentrations, notably impacting cell proliferation, angiogenesis, and migration. The discussion underscores that cPRP maintains platelet phenotype and function over extended periods, with 5% cPRP offering the most favorable outcomes, providing a pragmatic approach for cold storage to extend post-thaw viability and amplify therapeutic effects.

Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder affecting millions globally. It encompasses both motor and non-motor symptoms, with a notable impact on patients' quality of life. Electroencephalogram (EEG) is a non-invasive tool that is increasingly utilized to investigate neural mechanisms in PD, identify early diagnostic markers, and assess therapeutic responses., Methods: The data were sourced from the Science Citation Index Expanded within the Web of Science Core Collection database, focusing on publications related to EEG research in PD from 2004 to 2023. A comprehensive bibliometric analysis was conducted using CiteSpace and VOSviewer software. The analysis began with an evaluation of the selected publications, identifying leading countries, institutions, authors, and journals, as well as co-cited references, to summarize the current state of EEG research in PD. Keywords are employed to identify research topics that are currently of interest in this field through the analysis of high-frequency keyword co-occurrence and cluster analysis. Finally, burst keywords were identified to uncover emerging trends and research frontiers in the field, highlighting shifts in interest and identifying future research directions., Results: A total of 1,559 publications on EEG research in PD were identified. The United States, Germany, and England have made notable contributions to the field. The University of London is the leading institution in terms of publication output, with the University of California closely following. The most prolific authors are Brown P, Fuhr P, and Stam C In terms of total citations and per-article citations, Stam C has the highest number of citations, while Brown P has the highest H-index. In terms of the total number of publications, Clinical Neurophysiology is the leading journal, while Brain is the most highly cited. The most frequently cited articles pertain to software toolboxes for EEG analysis, neural oscillations, and PD pathophysiology. Through analyzing the keywords, four research hotspots were identified: research on the neural oscillations and connectivity, research on the innovations in EEG Analysis, impact of therapies on EEG, and research on cognitive and emotional assessments., Conclusion: This bibliometric analysis demonstrates a growing global interest in EEG research in PD. The investigation of neural oscillations and connectivity remains a primary focus of research. The application of machine learning, deep learning, and task analysis techniques offers promising avenues for future research in EEG and PD, suggesting the potential for advancements in this field. This study offers valuable insights into the major research trends, influential contributors, and evolving themes in this field, providing a roadmap for future exploration., 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 Liao, Gao, Qian, Zhou, Li, Gong and Ye.)

To explore the effect of K33 only mutant ubiquitin (K33O) on bone marrow-derived dendritic cells' (BMDCs') maturity, antigen uptake capability, surface molecule expressions and BMDC-mediated CTL priming, and further investigate the role of PI3K-Akt engaged in K33O-increased BMDC maturation, antigen uptake and presentation, surface molecule expressions and BMDC-based CTL priming. BMDCs were conferred K33O and other ubiquitin mutants (K33R, K48R, K63R-mutant ubiquitin) incubation or LY294002 and wortmannin pretreatment. PI3K-Akt phosphorylation, antigen uptake, antigenic presentation and CD86/MHC class I expression in BMDC were determined by western blot or flow cytometry. BMDC-based CTL proliferation and priming were determined by in vitro mixed lymphocyte reaction (MLR), ex vivo enzyme-linked immunospot assay (Elispot) and flow cytometry with intracellular staining, respectively. The treatment with K33O effectively augmented PI3K-Akt phosphorylation, BMDCs' antigen uptake, antigenic presentation, CD86/MHC class I and CD11c expressions. MLR, Elispot and flow cytometry revealed that K33O treatment obviously enhanced CTL proliferation, CTL priming and perforin/granzyme B expression. The pretreatment with PI3K-Akt inhibitors efficiently abrogated K33O's effects on BMDC. The replenishment of K33 only mutant ubiquitin augments BMDC-mediated CTL priming in bone marrow-derived dendritic cells via PI3K-Akt signalling., (© 2024 John Wiley & Sons Ltd.)

Chronic obstructive pulmonary disease (COPD) is now considered among the top three contributors to mortality globally. There is limited understanding surrounding the contribution of magnesium to the progression of COPD. This survey aims to evaluate the connection between dietary magnesium intake and both lung function and COPD prevalence among the US population. The research comprised 4865 participants in the National Health and Nutrition Examination Survey (NHANES) program conducted from 2007 to 2012. To evaluate the association between dietary magnesium intake and lung function as well as COPD, the study conducted multiple regression analyses, stratified analyses, and smoothed curves. In this study, we explored the relationship between higher magnesium intake and higher FEV 1 [β = 0.21 (95% CI 0.12, 0.30)] and FVC [β = 0.25 (95% CI 0.14, 0.36)] after accounting for all potential confounding factors. We demonstrated a relationship between increased magnesium intake and reduced odds of developing COPD [OR = 0.9993 (95% CI 0.9987, 1.0000)]. The results of stratified analyses further indicated that the relationship between magnesium intake and the risk of COPD is more pronounced in the 40-60 age group and males. The study demonstrated positive associations between the intake of dietary magnesium and both FEV 1 and FVC. Additionally, an adverse relationship between magnesium intake and the prevalence of COPD was also observed, suggesting that supplementation with magnesium may be a practical approach to preventing and managing COPD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Myocardial infarction (MI) is a significant global health issue and the leading cause of death. Myocardial infarction (MI) is characterized by events such as damage to heart cells and stress generated by inflammation. Punicalagin (PCN), a naturally occurring bioactive compound found in pomegranates, exhibits a diverse array of pharmacological effects against many disorders. This study aimed to assess the preventive impact of PCN, with its potential anti-inflammatory and antioxidant properties, on myocardial injury caused by isoproterenol (ISO) in rats and elucidate the possible underlying mechanisms. Experimental rats were randomly categorized into four groups: control group (fed a regular diet for 15 days), PCN group (orally administered PCN at 50 mg/kg body weight (b.w.) for 15 days), ISO group (subcutaneously administered ISO (85 mg/kg b.w.) on days 14 and 15 to induce MI), and PCN+ISO group (orally preadministered PCN (50 mg/kg b.w.) for 15 days and administered ISO (85 mg/kg b.w.) on days 14 and 15). The rat cardiac tissue was then investigated for cardiac marker, oxidative stress marker, and inflammatory marker expression levels. PCN prevented ISO-induced myocardial injury, suppressing the levels of creatine kinase-myocardial band, C-reactive protein, homocysteine, cardiac troponin T, and cardiac troponin I in the rats. Moreover, PCN treatment reversed (P<0.01) the ISO-induced increase in blood pressure, attenuated lipid peroxidation markers, and depleted both enzymatic and nonenzymatic markers in the rats. Additionally, PCN inhibited (P<0.01) ISO-induced overexpression of oxidative stress markers (p-38, p-c-Jun N-terminal kinase, and p-extracellular signal-regulated kinase 1), inflammatory markers (nuclear factor-kappa B, tumor necrosis factor-alpha, and interleukin-6), and matrix metalloproteinases and decreased the levels (P<0.01) of apoptosis proteins in the rats. Nuclear factor erythroid 2-related factor 2/silent information regulator transcript-1 (Nrf2/Sirt1) is a major cellular defense protein that regulates and scavenges oxidative toxic substances through apoptosis. Therefore, overexpression of Nrf2/Sirt1 to inhibit inflammation and oxidative stress is considered a novel target for preventing MI. PCN also significantly enhanced the expression of Nrf2/Sirt1 in ISO-induced rats. Histopathological analyses of cardiac tissue revealed that PCN treatment exhibited a protective effect on the heart tissue, mitigating damage. These findings show that by activating the Nrf2/Sirt1 pathway, PCN regulates oxidative stress, inflammation, and apoptosis, hence providing protection against ISO-induced myocardial ischemia.

The surgical outcomes of robot-assisted radical prostatectomy have shown remarkable improvement over the last two decades since its advent, due to advances in surgical concepts, techniques, and equipment. Today, ongoing research aims to compare the benefits and drawbacks of various surgical approaches, such as anterior, posterior, lateral, transvesical, and transperineal approaches, in terms of tumor control, functional recovery, and complication reduction in order to achieve the goal of pentafecta (no postoperative complications and negative surgical margins in addition to trifecta) to the maximum extent. It is imperative to explore and integrate novel technologies such as 5G remote surgery and artificial intelligence into the clinical practice of robot-assisted radical prostatectomy while ensuring patient safety, which has immense potential for substantial benefits to patients with prostate cancer.

Objectives: To examine the functional outcomes of robot-assisted radical prostatectomy (RARP) with preservation of pelvic floor stabilized structure and early elevated retrograde liberation of the neurovascular bundle (PEEL). Methods: This study was a retrospective cohort study. Between June 1, 2022, and March 20, 2023, 27 cases of RARP with PEEL and 153 cases of RARP with preservation of pelvic floor stabilized structure (PPSS) were included in this study. All patients were males, aged (62.5±5.2) years (range: 50 to 73 years). There were 18 cases of ≤T2b stage and 9 cases of T2c stage. After 1∶1 propensity score matching, the postoperative functional outcomes of 27 cases of RARP with PEEL and 27 cases of RARP with PPSS were compared. All surgeries were performed by a single surgeon and included patients were clinically staged as cT1-2N0M0 without preoperative urinary incontinence or erectile dysfunction. In RARP with PEEL, the prostate was cut near the midline at the front when dissecting the neurovascular bundle, dissection was performed between the visceral layer of the pelvic fascia and the prostatic fascia, preserving the parietal layer and the visceral layer of the pelvic fascia, and the neurovascular bundle was retrogradely released from the apex. The cumulative probability curve was plotted using the Kaplan-Meier method and the Log-rank test was used to compare the differences in functional outcomes between the two groups. Univariate and multivariate analysis with the Cox proportional hazards model was used to compare postoperative urinary continence and sexual function. Results: The recovery time of continence and potency was significantly longer in the PPSS group than in the PEEL group (all P <0.05). The continence rate of the PEEL group was significantly higher than that of the PPSS group (92.59% vs. 68.10%, P =0.026) at 3 months after surgery. The potency rate of the PEEL group was also significantly higher than that of the PPSS group (40.70% vs. 15.10%, P =0.037) at 3 months after surgery. In the univariate analysis, compared to the PPSS technique, the PEEL technique was associated with a shorter recovery time of continence ( HR =1.94, 95% CI : 1.08 to 3.48, P =0.027) and a shorter recovery time of potency ( HR =2.06, 95% CI : 1.03 to 4.13, P =0.042). In the multivariate analysis, the PEEL technique was an independent prognosis factor for postoperative recovery of continence ( HR =2.05, 95% CI : 1.01 to 4.17, P =0.047) and potency ( HR =3.57, 95% CI : 1.43 to 8.92, P =0.007). All the cases of the PPSS group and the PEEL group were performed successfully with negative surgical margins. Conclusion: Compared with PPSS, PEEL may be more conducive to the recovery of urinary continence and sexual function after RARP.

Aims: This study aimed to identify gray/white matter volume (GMV/WMV) alterations in Internet Gaming Disorder (IGD), with a special focus on the subregions of the mesocorticolimbic dopaminergic system and their clinical association., Results: Compared with healthy controls, IGDs showed bigger GMV in the bilateral caudate and the left nucleus accumbens (NAc), and bigger WMV in the inferior parietal lobule. The comparison of regions of interest (ROI) confirmed increased GMV in the bilateral caudate (including the dorsal anterior, body, and tail) and the left core of NAc in IGD, but no significant WMV alterations in the mesocorticolimbic dopaminergic system. GMVs in the left lateral orbital gyrus of orbitofrontal cortex (OFC) were associated with craving for games, while GMVs in the left anterior insula, right NAc, right caudate, and right OFC were associated with self-control in IGD., Conclusions: IGD was accompanied by changed GMV, but not WMV, in the mesocorticolimbic dopaminergic system. GMV in the mesocorticolimbic dopaminergic system may contribute to impaired self-control and craving in IGD., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Inflammatory bowel disease (IBD) is a global health concern with varying levels and trends across countries and regions. Understanding these differences is crucial for effective prevention and treatment strategies., Methods: Using data from the 2019 Global Burden of Disease study, we examine IBD incidence, mortality, and disability-adjusted life years (DALYs) rates in 198 countries from 1990 to 2019. To assess changes in the burden of IBD, estimated annual percentage changes (EAPC) were calculated, and a Bayesian age-period-cohort model was used to predict the future 30-year trends of IBD., Results: In 2019, there were 405,000 new IBD cases globally (95% uncertainty interval (UI) 361,000 to 457,000), with 41,000 deaths (95% UI 35,000 to 45,000) and 1.62million DALYs (95% UI 1.36-1.92million). The global age-standardized incidence rate in 2019 was 4.97 per 100,000 person-years (95% UI 4.43 to 5.59), with a mortality rate of 0.54 (95% UI 0.46 to 0.59) and DALYs rate of 20.15 (95% UI 16.86 to 23.71). From 1990 to 2019, EAPC values for incidence, mortality, and DALYs rates were - 0.60 (95% UI - 0.73 to - 0.48), - 0.69 (95% UI - 0.81 to - 0.57), and - 1.04 (95% UI - 1.06 to - 1.01), respectively. Overall, the burden of IBD has shown a slow decline in recent years. In SDI stratification, regions with higher initial SDI (high-income North America and Central Europe) witnessed decreasing incidence and mortality rates with increasing SDI, while regions with lower initial SDI (South Asia, Oceania, and Latin America) experienced a rapid rise in incidence but a decrease in mortality with increasing SDI. Predictions using a Bayesian model showed lower new cases and deaths from 2020 to 2050 than reference values, while the slope of the predicted incidence-time curve closely paralleled that of the 2019 data., Conclusion: Increasing cases, deaths, and DALYs highlight the sustained burden of IBD on public health. Developed countries have stabilized or declining incidence rates but face high prevalence and societal burden. Emerging and developing countries experience rising incidence. Understanding these changes aids policymakers in effectively addressing IBD challenges in different regions and economic contexts., (© 2023. The Author(s).)

Background: Patients with anomic aphasia experience difficulties in narrative processing. General discourse measures are time consuming and require necessary skills. Core lexicon analysis has been proposed as an effort-saving approach but has not been developed in Mandarin discourse., Aims: This exploratory study was aimed (1) to apply core lexicon analysis in Mandarin patients with anomic aphasia at the discourse level and (2) to verify the problems with core words among people with anomic aphasia., Methods & Procedure: The core nouns and verbs were extracted from narrative language samples from 88 healthy participants. The production of core words for 12 anomic aphasia and 12 age- and education-matched controls were then calculated and compared. The correlation between the percentages and the Aphasia Quotients of the revised Western Aphasia Battery was analyzed as well., Outcomes & Results: The core nouns and verbs were successfully extracted. Patients with anomic aphasia produced fewer core words than healthy people, and the percentages differed significantly in different tasks as well as word classes. There was no correlation between the core lexicon use and the severity of aphasia in patients with anomic aphasia., Conclusions & Implications: Core lexicon analysis may potentially serve as a clinician-friendly manner of quantifying core words produced at the discourse level in Mandarin patients with anomic aphasia., What This Paper Adds: What is already known on the subject Discourse analyses in aphasia assessment and treatment have increasingly garnered attention. Core lexicon analysis based on English AphasiaBank has been reported in recent years. It is correlated with microlinguistic and macrolinguistic measures in aphasia narratives. Nevertheless, the application based on Mandarin AphasiaBank is still under development in healthy individuals and patients with anomic aphasia. What this paper adds to existing knowledge A Mandarin core lexicon set was developed for different tasks. The feasibility of core lexicon analysis to evaluate the corpus of patients with anomic aphasia was preliminarily discussed and the speech performance of patients and healthy people was then compared to provide a reference for the evaluation and treatment of clinical aphasia corpus. What are the potential or actual clinical implications of this work? The purpose of this exploratory study was to consider the potential use of core lexicon analysis to evaluate core word production in narrative discourse. Moreover, normative and aphasia data were provided for comparison to develop clinical use for Mandarin patients with anomic aphasia., (© 2023 The Authors. International Journal of Language & Communication Disorders published by John Wiley & Sons Ltd on behalf of Royal College of Speech and Language Therapists.)

Background: The childhood patients with mixed-lineage leukemia rearrangement (MLL-r) gene have worse outcome than non-MLL, and thus often treated with high-risk chemotherapy regimens, so targeted therapy is important for this type of leukemia. This purpose of study was to explore the effects of ruxolitinib on the proliferation, apoptosis, and cell cycle of Nalm-6 cells., Methods: In this study, human acute lymphoblastic leukemia (ALL) cell line Nalm-6 was used as the research object. By constructing an MLL overexpression vector to transfect Nalm-6 cells, exogenous JAK2/STAT3 signal pathway inhibitor ruxolitinib was applied to observe the proliferation, apoptosis, and cell cycle changes of the transfected Nalm-6 cells. Western blot was performed to determine the proteins (MLL-BP, JAK, STAT) involved in the mechanism of action of MLL-r leukemia. CCK8 assay and flow cytometry (FCM) were used for testing the proliferation and apoptosis among MLL-BP transfected Nalm-6 cells., Results: Firstly, we determine the IC50 of ruxolitinib on Nalm-6 cells. Secondly, FCM and CCK8 showed that ruxolitinib dosedependentlyinhibits proliferation of Nalm-6 cells by blocking the cell cycle at G 0 /G 1 phase. In addition, FCM showed that ruxolitinib promoted the apoptosis of MLL-BP transfected Nalm-6 cells. Mechanistically, ruxolitinib inactivated JAK/STAT signaling pathway in MLL-BP transfected Nalm-6 cells, mediating ruxolitinib's inhibition of cell proliferation, and inducing apoptosis. Finally, ruxolitinib significantly inhibited the proliferation of MLL-r ALL cells and promoted their apoptosis., Conclusions: These data provide compelling evidence that ruxolitinib is a promising agent against MLL-r leukemia cell line. However, it needs going through multiple more steps to confirm before it can be an option in clinical practice., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-23-16/coif). The authors have no conflicts of interest to declare., (2023 Translational Pediatrics. All rights reserved.)

Background: Immune checkpoint inhibitors (ICIs) have become a standard care in non-small-cell lung cancer (NSCLC). However, its application to epidermal growth factor receptor (EGFR)-mutant NSCLC patients is confronted with drug resistance. This study aimed to clarify the potential role of Yes1-associated transcriptional regulator (YAP1) in ICIs treatment for EGFR-mutant NSCLC population., Methods: All the clinical data of NSCLC were downloaded from Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) for GSE11969 and GSE72094. Based on YAP1 expression, all the NSCLC patients including the EGFR-mutant and EGFR-wildtype (WT) patients were divided into two groups, YAP1&#95;High and YAP1&#95;Low. Using cBioPortal, genetic alterations were analyzed for identification of immunogenicity in EGFR-mutant NSCLC. MR analysis was used to analyze the hub gene of EGFR. The infiltration of immune cells and the expression of the identified tumor-associated antigens were identified with TIMER. By graph learning-based dimensionality reduction analysis, the immune landscape was visualized. Moreover, survival analysis was performed to verify the predictive value of YAP1 in ICIs treatment for EGFR-mutant NSCLC population using Ren's research data (NCT03513666)., Results: YAP1 was a poor prognostic factor of EGFR-mutant NSCLC population rather than lung adenocarcinoma (LUAD) patients. MR analysis revealed that the EGFR gene regulated YAP1 expression. YAP1 was identified as a hub gene closely associated with immunosuppressive microenvironment and poor prognosis in EGFR-mutant NSCLC population in TCGA LUAD. Tumors with YAP1&#95;High showed an immune-"cold" and immunosuppressive phenotype, whereas those with YAP1&#95;Low demonstrated an immune-"hot" and immunoactive phenotype. More importantly, it was verified that YAP1&#95;High subpopulation had a significantly shorter progression-free survival (PFS) and overall survival (OS) after ICIs treatment in EGFR-mutant NSCLC patients in the clinical trial., Conclusions: YAP1 mediates immunosuppressive microenvironment and poor prognosis in EGFR-mutant NSCLC population. YAP1 is a novel negative biomarker of ICIs treatment in EGFR-mutant NSCLC population. Clinical Trials . This trial is registered with NCT03513666., Competing Interests: The authors declare that they have no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023 Ling-Chen Li et al.)

Monocots are a major taxon within flowering plants, have unique morphological traits, and show an extraordinary diversity in lifestyle. To improve our understanding of monocot origin and evolution, we generate chromosome-level reference genomes of the diploid Acorus gramineus and the tetraploid Ac. calamus, the only two accepted species from the family Acoraceae, which form a sister lineage to all other monocots. Comparing the genomes of Ac. gramineus and Ac. calamus, we suggest that Ac. gramineus is not a potential diploid progenitor of Ac. calamus, and Ac. calamus is an allotetraploid with two subgenomes A, and B, presenting asymmetric evolution and B subgenome dominance. Both the diploid genome of Ac. gramineus and the subgenomes A and B of Ac. calamus show clear evidence of whole-genome duplication (WGD), but Acoraceae does not seem to share an older WGD that is shared by most other monocots. We reconstruct an ancestral monocot karyotype and gene toolkit, and discuss scenarios that explain the complex history of the Acorus genome. Our analyses show that the ancestors of monocots exhibit mosaic genomic features, likely important for that appeared in early monocot evolution, providing fundamental insights into the origin, evolution, and diversification of monocots., (© 2023. The Author(s).)

The trigeminal root entry zone is the zone at which the myelination switches from peripheral Schwann cells to central oligodendrocytes. Its special anatomical and physiological structure renders it susceptible to nerve injury. The etiology of most primary trigeminal neuralgia is closely related to microvascular compression of the trigeminal root entry zone. This study aimed to develop an efficient in vitro model mimicking the glial environment of trigeminal root entry zone as a tool to investigate the effects of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor on the structural and functional integrity of trigeminal root entry zone and modulation of cellular interactions. Primary astrocytes and Schwann cells isolated from trigeminal root entry zone of postnatal rats were inoculated into a two-well silicon culture insert to mimic the trigeminal root entry zone microenvironment and treated with glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor. In monoculture, glial cell line-derived neurotrophic factor promoted the migration of Schwann cells, but it did not have effects on the migration of astrocytes. In the co-culture system, glial cell line-derived neurotrophic factor promoted the bidirectional migration of astrocytes and Schwann cells. Brain-derived neurotrophic factor markedly promoted the activation and migration of astrocytes. However, in the co-culture system, brain-derived neurotrophic factor inhibited the migration of astrocytes and Schwann cells to a certain degree. These findings suggest that glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor are involved in the regulation of the astrocyte-Schwann cell interaction in the co-culture system derived from the trigeminal root entry zone. This system can be used as a cell model to study the mechanism of glial dysregulation associated with trigeminal nerve injury and possible therapeutic interventions., Competing Interests: None

Purpose: To explore the outcome and prognostic factors between inv(16) and t(8;21) disrupt core binding factor (CBF) in acute myeloid leukemia (AML)., Methods: The clinical characteristic, probability of achieving complete remission (CR), overall survival (OS) and cumulative incidence of relapse (CIR) were compared between inv(16) and (8;21)., Results: The CR rate was 95.2%, 10-year OS was 84.4% and CIR was 29.4%. Subgroup analysis showed that patients with t(8;21) had significant lower 10-year OS and CIR than patients with inv(16). Unexpectedly, there was a trend for pediatric AML receiving five courses cytarabine to have a lower CIR than four courses cytarabine (19.8% vs 29.3%, P = 0.06). Among the cohort of no-gemtuzumab ozogamicin(GO) treatment, inv (16) patients showed a similar 10-year OS (78.9% vs 83.5%; P = 0.69) and an inferior outcome on 10-year CIR (58.6% vs 28.9%, P = 0.01) than those patients with t(8;21). In contrast, inv (16) and t(8;21) patients receiving GO treatment had comparable OS (OS: 90.5% vs. 86.5%, P = 0.66) as well as CIR (40.4% vs. 21.4%, P = 0.13)., Conclusion: Our data demonstrated that more cumulative cytarabine exposure could improve the outcome of childhood patients with t(8;21), while GO treatment was beneficial to the pediatric patients with inv(16)., (© 2023. The Author(s).)

Objective: Common bile duct stone (CBDS) is one of the common diseases in the digestive system, for which endoscopic retrograde cholangiopancreatography (ERCP) is a treatment procedure. However, the risk factors for CBDS recurrence after ERCP remains unclear. This study aims to compare the risk factors of CBDS recurrence after ERCP, and to set up a nomogram model to predict the long-term risk., Patients and Methods: A retrospective analysis of 355 patients was reviewed. Univariate and multivariate analyses were performed to identify the risk factors for recurrence. The R packages were used for the model building. The validation set contained 100 patients., Results: The patients were divided into three subgroups: treated by cholecystectomy after ERCP (11.76% recurrence rate), treated without surgery after ERCP (19.70%), and with a prior history of cholecystectomy (43.64%). Each of them has different independent risk factors, and high body mass index (BMI) is correlated with an increased risk among all the subgroups. A prior history of cholecystectomy is a candidate factor that increases the risk of CBDS recurrence in patients older than 60 years, with a greater BMI, or receiving ERCP combined with EPBD. We built a nomogram model to predict the risk of long-term CBDS recurrence based on the risk factors including age, BMI, CBD diameter, the number of CBDS, and the gallbladder- or biliary tract-related events., Conclusions: CBDS recurrence is related to congenital and anatomical factors. Cholecystectomy would not be helpful to prevent CBDS recurrence, and a prior history of cholecystectomy may indicate a high risk of recurrence.

Student populations are susceptible to the COVID-19 pandemic and may easy develop mental health problems related to their immaturity of psychological development and fluctuation of mood. However, little has been known about the effects of the pandemic on college students and the associated influencing factors. This study aimed to explore the role of psychological resilience as a mediator between general self-efficacy and mental health. A cross-sectional survey was conducted with 480 Chinese college students from 12 universities in Hunan province of China. The participants responded anonymously to the Generalized Self-Efficacy Scale (GSES), the Chinese version of the Resilience Scale for College Students (RSCS), and the 12-item General Health Questionnaire (GHQ-12). Hierarchical linear regression and structural equation modeling were used in this study. The average of GSES and RSCS scores of college students were 25.00 ± 4.68 and 137.97 ± 15.50, which were at a medium level. The average score for the GHQ-12 was 1.59 ± 1.59, and 22.03% of the college students scored ≥ 3 on the GHQ-12, indicating that they were at risk of developing mental disorders. According to the analyses of mediation effect, psychological resilience played a fully mediating role in the relationship between general self-efficacy and mental health. In conclusion, Chinese college students were at high risk of developing mental disorders during the COVID-19 period. General self-efficacy was positively associated with psychological resilience, and psychological resilience played a fully mediating role in the relationship between general self-efficacy and mental health. Future studies and interventions should aim to promote psychological resilience and general self-efficacy.

Purpose: To evaluate the prognostic factors and outcome for acute lymphoblastic leukemia (ALL) in children with MLL rearrangement (MLL-r)., Methods: A total of 124 pediatric patients who were diagnosed with ALL were classified into two groups based on the MLL-r status by using a retrospective case-control study method from June 2008 to June 2020., Results: The prevalence of MLL-r positive in the whole cohort was 4.9%. The complete remission (CR) rate on Day 33 in the MLL-r positive group was not statistically different from the negative group (96.8% vs 97.8%, P = 0.736). Multivariate analysis showed that T-cell, white blood cell counts (WBC) ≥ 50 × 10 9 /L, MLL-AF4, and D15 minimal residual disease (MRD) positive were independent risk factors affecting the prognosis of MLL-r positive children. Stem cell transplantation (SCT) was a favorable independent prognostic factor affecting event-free survival (EFS) in MLL-r positive patients (P = 0.027), and there was a trend toward an independent prognostic effect on overall survival (OS) (P = 0.065). The 10-year predicted EFS for patients with MLL-AF4, MLL-PTD, MLL-ENL, other MLL partner genes, and MLL-r negative cases were 46.67 ± 28.61%, 85.71 ± 22.37%, 75 ± 32.41%, 75 ± 32.41%, and 77.33 ± 10.81%, respectively (P = 0.048). The 10-year predicted OS were 46.67 ± 28.61%, 85.71 ± 22.37%, 75 ± 32.41%, 75 ± 32.41%, and 85.2 ± 9.77%, respectively (P = 0.049). The 124 patients with ALL were followed up and eventually 5 (4%) cases relapsed, with a median relapse time of 3.9 years., Conclusion: Patients with MLL-r positive ALL have moderate remission rates, but are prone to relapse with low overall survival. The outcome of MLL-r positive ALL was closely related to the partner genes, and clinical attention should be paid to screening for MLL partner genes and combining them with other prognostic factors for accurate risk stratification., (© 2022. The Author(s).)

Purpose Our aim is to analyze the clinical characteristics and prognostic factors of Epstein-Barr (EB) virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in children. Methods Children with newly diagnosed HLH were retrospectively analyzed. Results Finally, a total of 95 children with HLH were enrolled in this study, including 43 (45.3%) with EBV-HLH and 52 (54.7%) with non-EBV-HLH. Laboratory tests showed that the levels of absolute neutrophil count (ANC) decrease ( P  = 0.031) and triglycerides (TG) increase ( P  = 0.036) in the EBV-HLH group were statistically significant compared with those in the non-EBV-HLH group, respectively. We found that the remission rate during induction period in the EBV-HLH group and non-EBV-HLH group was 75.8% and 89.3%, respectively. The correlation analysis showed that the elevated degree of total bilirubin (TBIL) ( P  = 0.042), triglyceride (TG) ( P  = 0.009), serum ferritin (SF) ( P  = 0.008) and interleukin-8 (IL-8) ( P  = 0.004) were related with the remission rate during induction in the EBV-HLH group. Further univariate analysis showed that the elevated degree of TBIL ( P  = 0.048) and TG ( P  = 0.019) were significant risk factors for the remission rate during induction in the EBV-HLH group. In the multivariate analysis, we observed that there was statistical significance for the degree of TG elevation ( P  = 0.015) between the two groups. The correlation analysis showed that the elevated degree of TBIL ( P  = 0.030), the elevated degree of SF ( P  = 0.020) and the elevated degree of interleukin-6 ( P  = 0.010) were related to the induction mortality of children with EBV-HLH. Conclusion TBIL and TG are valid indicators to assess the efficacy and prognosis of EVBHLH among children in induction period.

Objectives: Mental health resources are an important basis for coping with mental health services. The equity is an important index of a reasonable allocation of health resources. This study aims to evaluate the mental health resources and its equity allocation in Hunan Province, which is one of the typical central south areas of China, so as to provide reference for the development of mental health in China and other areas., Methods: Data related to mental health resources was obtained from the Project of Mental Health Resources in Hunan Province, which was conducted by the Department of Hunan Mental Health Center in 2019. The Gini coefficient, the Theil index and other indicators were employed to quantitatively evaluate the equity of mental health resources' allocation., Results: By the end of 2018, there were a total of 141 mental health institutions in Hunan Province of China, the bed density was 5.31 beds per 10,000 people, the ratio of doctors to nurses was 2.20, the number of outpatients of mental health institutions was 1288,047 per year. The mental health resources' allocation in terms of demographic dimension were in a preferred status with the Gini values all less than 0.3, and the Gini values for mental health resources`allocation in terms of geographical dimension ranged from 0.24 to 0.35. The Theil index for mental health allocation in terms of demographic dimension was lower than 0.05, and the Theil index for mental health allocation in terms of geographical dimension ranged from 0.04 to 0.11., Conclusions: The shortage of mental health resources is still the priority issue to be increased and optimized by policy-makers in Hunan in the future, especially the human resources. Moreover, the utilization of mental health resources was low though its equity was fair. Policy-makers need to consider the high utilization and geographical accessibility of health resources among different regions to ensure people in different regions could get access to available health services., Competing Interests: The authors have declared that no competing interests exist.

Atrial fibrillation (AF) is a common arrhythmia. Radiofrequency ablation (RFA) is the major AF treatment. Long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is related to AF diagnosis. This study explored the clinical roles of PVT1 in AF. Totally, 168 AF patients and 100 healthy controls were selected. Plasma lncRNA PVT1 in AF patients before/after RFA was detected and the diagnostic efficacy and postoperative recurrence prediction value in AF were analyzed. Effects of plasma PVT1 expression on AF recurrence and its correlation with transforming growth factor beta 1 (TGF-β1) in the recurrence and non-recurrence groups were analyzed by Pearson coefficient. The risk factors of AF recurrence were evaluated. Plasma PVT1 was highly expressed in AF patients and diminished after RFA. PVT1 level >1.255 assisted AF diagnosis. The plasma PVT1 level in the recurrence group was higher than that of the non-recurrence group. PVT1 level >1.525 assisted the prediction for postoperative recurrence. AF postoperative recurrence incidence in high PVT1 expression group was clearly higher than that in low PVT1 expression group, and plasma PVT1 expression in patients of the recurrence and non-recurrence groups was positively correlated with TGF-β1 content. High PVT1 expression was an independent risk factor for postoperative recurrence. Briefly, high PVT1 level assisted AF diagnosis and recurrence evaluation after RFA and was an independent risk factor for AF postoperative recurrence., (© 2022 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Objective: To explore the safety and feasibility of posterior pars interarticularis screw fixation on axis by CT measurement., Methods: The CT data of 137 patients with complete upper cervical spine who underwent full cervical spine CT examination from January 2016 to December 2019 were collected, including 71 males and 66 females, aged from 22 to 65 years old with an average of (41.8±17.4) years old. Mimics 19.0 software was used to measure anatomical data related to the pars interarticularis screw, including the pars width, pars vertical length, pars vertical height, length of pars screw trajectory, upward inclination angle of pars screw trajectory. And the correlation between each index was analyzed., Results: The axis pars has an average width of (9.05±1.63) mm, an average vertical length of (11.21±1.43) mm, and an average vertical height of (17.53±2.93) mm. The mean length of pars screw trajectory was(19.07±3.20) mm. Regarding to the length of pars screw trajectory, 94.53% of pars measured more than 14 mm, 82.12% of pars measured at 14-16 mm, 63.14% of pars measured at 16-18 mm, 39.78% of pars measured at 18-20 mm. The upward inclination angle of pars screw was 30°-68° with an average of (46.06±8.06) °. There was a highly positive correlation between the length of screw trajectory and upward inclination angle( r =0.965, P =0.000). The vertical length of pars was weakly positively correlated with length of screw trajectory and upward inclination angle( r =0.240, P =0.000; r =0.163, P =0.007). Pars width was moderately negative correlated with length of scrwe trajectory and upward inclination angle(r =-0.333, P =0.000; r =-0.380, P =0.000)., Conclusion: The posterior pars interarticularis screw fixation is safe and reliable. It has a more wider applicability than pedicle screw fixation and can be used as an alternative to pedicle screws.

The recovery of spinal cord injury (SCI) is closely associated with the obstruction of oligodendrocyte progenitor cell (OPC) differentiation, which ultimately induces the inability to generate newly formed myelin. To address the concern, drug-based methods may be the most practical and feasible way, possibly applying to clinical therapies for patients with SCI. In our previous study, we found that clemastine treatment preserves myelin integrity, decreases the loss of axons, and improves functional recovery in the SCI model. Clemastine acts as an antagonist of the muscarinic acetylcholine receptor (muscarinic receptor, MR) identified from a string of anti-muscarinic drugs that can enhance oligodendrocyte differentiation and myelin wrapping. However, the effects of clemastine on OPC differentiation through MRs in SCI and the underlying mechanism remain unclear. To explore the possibility, a rat model of SCI was established. To investigate if clemastine could promote the differentiation of OPCs in SCI via MR, the expressions of OPC and mature OL were detected at 7 days post injury (dpi) or at 14 dpi. The significant effect of clemastine on encouraging OPC differentiation was revealed at 14 dpi rather than 7 dpi. Under pre-treatment with the MR agonist cevimeline, the positive role of clemastine on OPC differentiation was partially disrupted. Further studies indicated that clemastine increased the phosphorylation level of extracellular signal-regulated kinase 1/2 (p-ERK1/2) and the expressions of transcription factors, Myrf and Olig2. To determine the relationship among clemastine, ERK1/2 signaling, specified transcription factors, and OPC differentiation, the ERK1/2 signaling was disturbed by U0126. The inhibition of ERK1/2 in SCI rats treated with clemastine decreased the expressions of p-ERK 1/2, Myrf, Olig2, and mature OLs, suggesting that ERK1/2 is required for clemastine on promoting OPC differentiation and that specified transcription factors may be affected by the activity of ERK1/2. Moreover, the impact of clemastine on modulating the level of p-ERK 1/2 was restricted following cevimeline pre-injecting, which provides further evidence that the role of clemastine was mediated by MRs. Altogether, our data demonstrated that clemastine, mediated by MRs, promotes OPC differentiation under the enhancement of Myrf and Olig2 by activating ERK1/2 signaling and suggests a novel therapeutic prospect for SCI recovery., 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 Tong, Deng, Du, Zhou, Liao and Jiang.)

Introduction and Hypothesis: Hysteropreservation and hysterectomy for uterine prolapse have been compared in several randomized controlled trials (RCTs), as the best treatment has not been definitively determined. This study aimed to summarize the available evidence in RCTs of hysteropreservation versus hysterectomy., Methods: We performed electronic searches in the PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure databases for eligible RCTs from inception to June 2020. The relative risks (RRs) and weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) were calculated for categorical and continuous variables using random-effects models., Results: Twelve RCTs involving 1177 patients were selected for meta-analysis. There were no significant differences between hysteropreservation and hysterectomy for the incidences of recurrence (RR, 0.55; 95% CI, 0.26-1.19; P = 0.130) and reoperation (RR, 1.15; 95% CI, 0.56-2.37; P = 0.705). Moreover, neither hysteropreservation nor hysterectomy had any significant effect on the risk of constipation (RR, 0.72; 95% CI, 0.15-3.46; P = 0.681), voiding dysfunction (RR, 0.99; 95% CI, 0.54-1.84; P = 0.981), intraoperative bleeding (RR, 0.35; 95% CI, 0.05-2.26; P = 0.271), upper leg dullness (RR, 0.70; 95% CI, 0.15-3.17; P = 0.643), dyspareunia (RR, 1.47; 95% CI, 0.69-3.13; P = 0.317), and wound infection (RR, 1.38; 95% CI, 0.24-7.80; P = 0.714). Furthermore, hysteropreservation was associated with less intraoperative blood loss (WMD, -25.68; 95% CI, -44.39 to -6.96; P = 0.007), shorter duration of surgery (WMD, -11.30; 95% CI, -19.04 to -3.55; P = 0.004), and shorter duration of hospitalization (WMD, -0.63; 95% CI, -1.10 to -0.16; P = 0.009) compared with hysterectomy., Conclusion: This study found that both hysteropreservation and hysterectomy have similar effects on recurrence and reoperation rates, while hysteropreservation was superior to hysterectomy in reducing intraoperative blood loss and shortening the duration of surgery and hospitalization., (© 2021. The International Urogynecological Association.)

K48-linked ubiquitination determines antigen degradation and plays vital roles in the process of cross-presentation of bone marrow precursor cell (BMPC)-derived dendritic cells (DCs). Although previous studies revealed that K48 and K27-linked ubiquitination regulates innate immunity, the exact roles of K48 and K27-linked ubiquitination in cross-presentation and BMPC-based adaptive immunity are still uncertain. In this study, we investigated the effects of K48- and K27-mutant ubiquitin (Ub) on BMPC-based adaptive immune response by observing the effects of MG132, Ub deficiency, and K48/K27-mutant Ub on cross-presentation, T cell proliferation, IFN-γ secretion, BMPC-based CTL priming, and thereby the efficiency of cytolytic capacity of BMPC-activate T cells. We demonstrated that MG132, Ub deficiency, and K48-mutant Ub impair cross-presentation, T cell proliferation, IFN-γ secretion, BMPC-based CTL priming, and the cytolytic capacity of BMPC-activated T cells. Moreover, although K27-only Ub decreases cross-presentation, the replenishment of K27-mutant Ub restores Ub deficiency impaireds the abilities of T cell proliferation, IFN-γ secretion, CTL priming, and the cytolytic capacity of BMPC-activated T cells. Thus, these data suggest that K48- and K27-linked ubiquitination contributes to BMPC-mediated adaptive immune response by affecting BMPC cross-presentation and the cytolytic capacity by up-regulating both perforin and granzyme B in BMPC-activated T cells. K48- and K27-mutant Ub might have potential clinical therapeutic function in adaptive immune response-associated diseases., (©2022 Society for Leukocyte Biology.)

Activating FLT3 mutations are the most common mutations in acute myeloid leukemia (AML), but the optimal threshold of FLT3/ITD allelic ratio (AR) among pediatric AML patients remains controversial. Here, we present the outcome and prognostic significance of FLT3/ITD AR analysis among pediatric patients with AML from the TARGET dataset. Applying fitting curve models and threshold effect analysis using the restrictive cubic spline function following Cox proportional hazards models identifies the cut-off value of 0.5 on FLT3/ITD AR. Moreover, we observe that high FLT3/ITD AR patients have an inferior outcome when compared to low AR patients. Our study also demonstrates that stem cell transplantation may improve the outcome in pediatric AML patients with high FLT3/ITD AR and may be further improved when combined with additional therapies such as Gemtuzumab Ozogamicin. These findings underline the importance of individualized treatment of pediatric AML., (© 2022. The Author(s).)

To evaluate the outcome and prognostic significance of CEBPA mutations among pediatric acute myeloid leukemia (AML) from TARGET dataset. A total of 1803 pediatric patients who were diagnosed with AML were classified into two groups based on the CEBPA status by using a retrospective cohort study method from September 1996 to December 2016. The incidence of CEBPA mutations was 18%. CEBPA mutations were significantly associated with elder age (p < 0.001), higher WBC (p = 0.004), higher proportion of peripheral blood blast (p < 0.001), normal karyotype (p < 0.001), low risk (p < 0.001) and higher complete remission induction rates (p < 0.05). Overall, CEBPA mutations patients had a significantly better 5-year EFS (p < 0.001) and OS (p < 0.001) compared to CEBPA wild-type patients, and this favorable impact was maintained even in the presence of FLT3/ITD mutations. Stem cell transplantation had no significant impact on the survival of patients with coexistence of CEBPA and FLT3/ITD mutations. Multivariate analysis demonstrated that mutated CEBPA were an independent favorable indicators of better outcome in terms of EFS (p = 0.007) and OS (p = 0.039). Our study demonstrate mutated CEBPA have an excellent outcome in pediatric AML patients. Furthermore, pediatric AML patients with coexistence of CEBPA and FLT3/ITD mutation appear to have favorable prognoses and might not required stem cell transplantation., (© 2022 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

To improve our understanding of the origin and evolution of mycoheterotrophic plants, we here present the chromosome-scale genome assemblies of two sibling orchid species: partially mycoheterotrophic Platanthera zijinensis and holomycoheterotrophic Platanthera guangdongensis. Comparative analysis shows that mycoheterotrophy is associated with increased substitution rates and gene loss, and the deletion of most photoreceptor genes and auxin transporter genes might be linked to the unique phenotypes of fully mycoheterotrophic orchids. Conversely, trehalase genes that catalyse the conversion of trehalose into glucose have expanded in most sequenced orchids, in line with the fact that the germination of orchid non-endosperm seeds needs carbohydrates from fungi during the protocorm stage. We further show that the mature plant of P. guangdongensis, different from photosynthetic orchids, keeps expressing trehalase genes to hijack trehalose from fungi. Therefore, we propose that mycoheterotrophy in mature orchids is a continuation of the protocorm stage by sustaining the expression of trehalase genes. Our results shed light on the molecular mechanism underlying initial, partial and full mycoheterotrophy., (© 2022. The Author(s).)

The aim of this study was to observe the effects of remifentanil on organ damage and energy metabolism in lipopolysaccharide (LPS)-induced septic rats. A total of 45 clean-grade male Wistar rats (weight 270-320 g) were randomly divided into three groups: a control group, an LPS group, and an LPS with remifentanil treatment (LPS+REM) group. After 6 hours of modeling, the levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in lung and kidney tissues of rats in each group were detected by ELISA. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in lung and kidney tissues were determined, and the content of lactic acid, pyruvate and epinephrine in heart and kidney tissues were detected. Reverse transcription polymerase chain reaction and the Western blot test were used to detect the expression of pyruvate dehydrogenase kinase 4 (PDK4) in the myocardial tissue. We found that remifentanil treatment inhibited the levels of IL-6, TNF-α, and MDA in the lung and kidneys 6 h after the administration of LPS and increased the level of SOD activity. Treatment with remifentanil reduced the expression of lactic acid, pyruvate, and epinephrine in the heart and kidney tissues and attenuated the expression of PDK4 messenger RNA and PDK4 protein in the myocardial tissue. We concluded that remifentanil might inhibit the release of tissue inflammatory factors, regulate the body's energy metabolism, and ultimately protect the sepsis tissue damage caused by LPS.

The marvelously diverse Orchidaceae constitutes the largest family of angiosperms. The genus Cymbidium in Orchidaceae is well known for its unique vegetation, floral morphology, and flower scent traits. Here, a chromosome-scale assembly of the genome of Cymbidium ensifolium (Jianlan) is presented. Comparative genomic analysis showed that C. ensifolium has experienced two whole-genome duplication (WGD) events, the most recent of which was shared by all orchids, while the older event was the τ event shared by most monocots. The results of MADS-box genes analysis provided support for establishing a unique gene model of orchid flower development regulation, and flower shape mutations in C. ensifolium were shown to be associated with the abnormal expression of MADS-box genes. The most abundant floral scent components identified included methyl jasmonate, acacia alcohol and linalool, and the genes involved in the floral scent component network of C. ensifolium were determined. Furthermore, the decreased expression of photosynthesis-antennae and photosynthesis metabolic pathway genes in leaves was shown to result in colorful striped leaves, while the increased expression of MADS-box genes in leaves led to perianth-like leaves. Our results provide fundamental insights into orchid evolution and diversification., (© 2021. The Author(s).)

Malvids is one of the largest clades of rosids, includes 58 families and exhibits remarkable morphological and ecological diversity. Here, we report a high-quality chromosome-level genome assembly for Euscaphis japonica, an early-diverging species within malvids. Genome-based phylogenetic analysis suggests that the unstable phylogenetic position of E. japonica may result from incomplete lineage sorting and hybridization event during the diversification of the ancestral population of malvids. Euscaphis japonica experienced two polyploidization events: the ancient whole genome triplication event shared with most eudicots (commonly known as the γ event) and a more recent whole genome duplication event, unique to E. japonica. By resequencing 101 samples from 11 populations, we speculate that the temperature has led to the differentiation of the evergreen and deciduous of E. japonica and the completely different population histories of these two groups. In total, 1012 candidate positively selected genes in the evergreen were detected, some of which are involved in flower and fruit development. We found that reddening and dehiscence of the E. japonica pericarp and long fruit-hanging time promoted the reproduction of E. japonica populations, and revealed the expression patterns of genes related to fruit reddening, dehiscence and abscission. The key genes involved in pentacyclic triterpene synthesis in E. japonica were identified, and different expression patterns of these genes may contribute to pentacyclic triterpene diversification. Our work sheds light on the evolution of E. japonica and malvids, particularly on the diversification of E. japonica and the genetic basis for their fruit dehiscence and abscission., (© 2021 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

Transcranial direct-current stimulation (tDCS) is proved safe and shows therapeutic effect in cerebral ischemic stroke in clinical trials. But the underlying molecular mechanisms remain unclear. Here we show that tDCS treatment reduces the infarct volume after rat cerebral ischemia-reperfusion (I/R) injury and results in functional improvement of stroke animals. At the cellular and molecular level, tDCS suppresses I/R-induced upregulation of Cezanne in the ischemic neurons. Cezanne inhibition confers neuroprotection after rat I/R and oxygen glucose deprivation (OGD) in the cortical neuronal cultures. Inhibiting Cezanne increases the level of SIRT6 that is downregulated in the ischemic neurons. Suppressing SIRT6 blocks Cezanne inhibition-induced neuroprotective effect and overexpressing SIRT6 attenuates OGD-induced neuronal death. We further show that downregulating Cezanne reduces DNA double-strand break (DSB) through upregulation of SIRT6 in OGD-insulted neurons. Together, this study suggests that Cezanne-dependent SIRT6-DNA DSB signaling pathway may mediate the neuroprotective effect of tDCS in ischemic neurons., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The effects of phloridzin (PHL), main component of Malus hupehensis (MH) tea leaves, on blood glucose (BG) and glucose-6-phosphatase (G-6-Pase) were investigated to provide a basis for finding a scheme of stabilizing BG. Glucose uptake of insulin resistant HepG2 cells was measured by glucose oxidase method. Glucose tolerance, fasting BG (FBG) and postprandial BG (PBG) were determined by BG test strips. The expression of G-6-Pase was detected by Western blot. The results showed that glucose uptake was enhanced and the expression of G-6-Pase was inhibited by PHL in insulin resistant HepG2 cells. Glucose tolerance was enhanced, FBG level was increased and PBG level was decreased by PHL in mice. The expression of G-6-Pase in the liver was enhanced under fasting state, and was inhibited by the low and medium dose under postprandial state. It indicated that PHL has a positive effect on stabilizing BG in mice, which is related to bidirectional regulation of G-6-Pase activity. PRACTICAL APPLICATIONS: Malus hupehensis, edible and medicinal plant, which has been proved by long-term application and experiments that it has a good effect on stabilizing blood glucose, preventing diabetes and adjuvant treatment. Its effect is closely related to its main component PHL. Thus, MH can be used as a dietary regulating drink for daily life to maintain blood glucose. Its main ingredient is PHL, which can be developed as a candidate drug for diabetes treatment., (© 2021 Wiley Periodicals LLC.)

Interactive effects of inorganic arsenic (As) species and polycyclic aromatic hydrocarbons (PAHs) on their uptake, accumulation and translocation in the hyperaccumulator Pteris vittata L. (P. vittata) were studied hydroponically. The presence of PAHs hindered As uptake and acropetal translocation by P. vittata, decreasing As concentrations by 29.8%-54.5% in pinnae, regardless of the initial As speciation. The inhibitive effect of PAHs was 1.6-8.7 times greater for arsenite [As(III)] than for arsenate [As(V)]. Similarly, inorganic As inhibited the uptake of fluorene (FLU) and benzo[a]pyrene (BaP) by P. vittata roots by 0.4%-21.7% and by 33.1%-69.7%, respectively. Interestingly, coexposure to As and PAHs slightly enhanced the translocation of PAHs by P. vittata with their concentrations increased 0.3 to 0.8 times in shoots, except for the As(III)+BaP treatment. The antagonistic interaction between As and PAHs uptake is likely caused by competitive inhibition or oxidative stress injury. By using synchrotron radiation micro X-ray fluorescence imaging, high concentrations of As were found distributed throughout the microstructures far from main vein of the pinnae when coexposed with PAHs, the opposite of what was observed with exposure to As only. PAHs could also significantly inhibit the accumulation and distribution of As in vascular bundles in rachis treated with As(III). The results of two-photon laser scanning confocal microscopy revealed that PAHs were mainly distributed in the vascular cylinder, epidermal cells, vascular bundles, epidermis and vein tissues, and this was independent of As speciation and treatment. This work offers new positive evidence for the interaction between As and PAHs in P. vittata, presents new information on the underlying mechanisms for interactions of As and PAHs affecting their uptake and translocation within P. vittata L., and provides direction for future research on the mechanisms of PAHs uptake by plants., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: This study was aimed to evaluate the value of DNA index(DI) among pediatric acute lymphoblastic leukemia (ALL) treated on Children's Oncology Group (COG) protocols between 2000 and 2015., Methods: Retrospective study were analysis among pediatric ALL patients from the TARGET dataset., Result: Totally, 1668 eligible pediatric patients were enrolled in this study. Of them, 993 are male and 675 are female with a median age of 7.6 years old. The median follow-up for those patients was 7.7 years (range 0.1-15.7 years). The probability of 15-year EFS and OS were reported to be 67.5 ± 3.1% and 78.3 ± 2.5%, respectively. BCR/ABL1 fusion gene affected the early treatment response and the survival of childhood ALL. Moreover, those patients with ETV6/RUNX1 fusion gene were also significantly associated with better EFS (HR = 0.6, 95% CI 0.4-0.8, P = 0.003) and OS (HR = 0.3, 95%CI 0.2-0.5, P < 0.001) compared to patients with no ETV6/RUNX1. On the contrary, BM NR on Day+ 29 showed a significant decrease in EFS (HR = 3.1, 95%CI 2.1-4.5, P < 0.001) and OS (HR = 1.7, 95%CI 1.1-2.8, P = 0.026). Multivariate analysis showed that DI was significantly associated with better EFS and OS. The threshold effect of DI on poor outcome was significant after adjusting for potential confounders. The adjusted regression coefficient (Log RR) was 0.7 (95%CI 0.1-3.2, P = 0.597) for DI < 1.1 while 8.8 (95%CI 1.4-56.0, P = 0.021) for DI ≥ 1.2 and 0.0 (95%CI 0.0-0.8, P = 0.041) for 1.1 ≤ DI < 1.2. Generalized additive models revealed that the lowest rates of the adverse outcomes estimated to occur among DI between 1.1 and 1.2., Conclusion: For those childhood ALL treated on COG protocols between 2000 and 2015, ETV6/RUNX1 and BM NR were closely related to the prognosis. Moreover, the DI between 1.1 and 1.2 can serve as a significant cut-point discriminating the risk group, which indicated a favourable prognostic factor., (© 2021. The Author(s).)

The proteasome has been validated as an anticancer drug target, while the role of a subunit of proteasome, PSMC6, in lung adenocarcinoma (LUAD) has not been fully unveiled. In this study, we observed that both the RNA and protein of PSMC6 were highly upregulated in LUAD compared with the adjacent normal tissues. Moreover, a high PSMC6 expression was associated with poor prognosis. In accordance with this finding, PSMC6 was associated with poor tumor differentiation. Furthermore, the silence of PSMC6 by small interference RNAs (siRNAs) could significantly inhibit cell growth, migration, and invasion in lung cancer cell lines, suggesting that PSMC6 might serve as a promising therapeutic target in LUAD. To further explore the molecular mechanism of PSMC6 in LUAD, we observed that the proteasome subunits, such as PSMD10, PSMD6, PSMD9, PSMD13, PSMB3, PSMB1, PSMA4, PSMC1, PSMC2, PSMD7, and PSMD14, were highly correlated with PSMC6 expression. Based on the gene set enrichment analysis, we observed that these proteasome subunits were involved in the degradation of AXIN protein. The correlation analysis revealed that the positively correlated genes with PSMC6 were highly enriched in WNT signaling-related pathways, demonstrating that the PSMC6 overexpression may activate WNT signaling via degrading the AXIN protein, thereby promoting tumor progression. In summary, we systematically evaluated the differential expression levels and prognostic values of PSMC6 and predicted its biological function in LUAD, which suggested that PSMC6 might act as a promising therapeutic target in LUAD., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021 Jian-Yu Zhang et al.)

Parapteronemobius contains 7 species or subspecies distributed in East Asia with only one species recorded from China. In this study, we reported the second species, P. chenggong He sp. nov., from Zhejiang. The new species differs from P. dibrachiatus in body size, male genitalia and COI gene. The phylogeny of this genus in subfamily Nemobiinae are discussed based on COI, 18S and 28S genes. The type specimens are deposited in the Museum of Biology, East China Normal University (ECNU).