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Guanyu Ruan,1,* Yiyi Song,2,* Binhua Dong,1 Xiaodan Mao,1 Fen Lin,1 Yafang Kang,1 Shuxia Xu,3 Xianjing Chen,2 Qibin Wu,2 Pengming Sun1,2 1Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China; 2Department of Gynecology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China; 3Department of Pathology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China *These authors have contributed equally to this work Objectives: The Cervista® high-risk human papillomavirus (HR-HPV) test was evaluated as a primary screening method for cervical cancer in women aged ≥21 years and was compared with different screening and triage combinations.Materials and methods: A nested case–control study within the Fujian provincial Cervical Lesion Screening Cohorts was used to evaluate the Cervista test as the primary cervical screening method in a hospital-based population. Strategy 1 primarily screened using a cytology screen with HR-HPV testing used for triage. Strategy 2 primarily screened using cytology and HR-HPV co-testing. Strategy 3 primarily screened using HR-HPV testing and triaged HPV-positive women based on cytology. Strategy 4 primarily screened using HR-HPV testing and referred A9 pool HPV-positive women to colposcopy directly, whereas non-A9 HPV-positive women were triaged using cytology.Results: There were 10,183 women included in this study; 16.49% (1677/10,183) were HR-HPV‑positive, 9.52% had abnormal cytology, and 9907 women were normal during follow-up. A total of 276 women were diagnosed with cervical intraepithelial neoplasia 2 or worse (CIN2+), 197 with CIN3 or worse (CIN3+), and 70 with cervical cancer. Moreover, 10.15% (20/197) women who were CIN3+ were identified as cytology-negative, while 8.63% (17/197) were HR-HPV negative (P>0.05). The cumulative risk rate for HPV–/cytology– was 0.836 (95% CI, 0.424–1.648) in CIN3+ cases. Strategy 4 yielded the highest sensitivity for CIN2+ or CIN3+ and the lowest positive predictive value for CIN2+ or CIN3+ among the four screening strategies.Conclusion: The Cervista HR-HPV test can provide a reliable and sensitive clinical reference for the cervical cancer primary screen. Keywords: human papillomavirus, primary screen, A9 pool, liquid-based cytology, histology

Background: The early diagnosis of laryngeal cancer (LCA) is crucial for prognosis, driving our search for an accurate, precise, and sensitive deep learning model to assist in LCA detection., Methods: We collected 5768 laryngoscopic images from 1462 patients and created the intelligent laryngeal cancer detection system (ILCDS) based on Swin-Transformer. Following training and validation, we assessed the ILCDS performance on the internal and external test sets and compared it with previous convolutional neural network (CNN) models and three professional laryngologists., Results: The ILCDS outperformed the six CNNs, with the highest accuracy of 92.78% and an area under the curve (AUC) of 0.9732. Despite a slight drop in performance on external sets, the ILCDS maintained the best superiority, with 85.79% accuracy and an AUC of 0.9550. Surpassing professional laryngologists, the ILCDS achieved 92.00% accuracy., Conclusions: The ILCDS offers high accuracy and stability for LCA detection, reducing the burden on laryngologists., (© 2024 Wiley Periodicals LLC.)

Prostate cancer is a significant cause of cancer-related deaths in men. Poly (ADP-ribose) polymerase inhibitors (PARPi) have been shown to improve progression-free survival, especially in patients with BRCA1/2 mutations and deficiencies in homologous recombination repair (HRR). We conducted systematic reviews and meta-analyses and found that PARPi, combined with androgen receptor inhibitors, significantly improved overall survival (OS) and progression-free survival (PFS) in BRCA1/2-mutant and HRR-deficient patients. PARPi therapies increased the incidence of adverse events (AEs), including fatigue, nausea, anemia, neutropenia, and thrombocytopenia. Among different PARP inhibitors, Olaparib, Talazoparib, and Rucaparib demonstrated the strongest efficacy in improving OS and PFS but were also linked to higher rates of AEs. Combination therapies with PARPi and hormonal treatments proved more effective than monotherapy, especially in genetically targeted subgroups like BRCA1/2-mutant patients. This umbrella review demonstrates that PARPi treatment significantly improves clinical outcomes, particularly in BRCA1/2-mutant and HRR-deficient mCRPC patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Previous studies have reported that alterations in gut microbiota composition are associated with male fertility. However, it is unclear and difficult to establish whether these associations reflect a causal relationship. We assessed genome-wide association study summary statistics for gut microbiota and male fertility to perform MR analysis. Independent single nucleotide polymorphisms closely associated with 211 gut bacterial taxa (N = 122,110) were identified as instrumental variables. The summary statistic data for male infertility (N = 733,479), abnormal spermatozoa (N = 209,921) and erectile dysfunction (N = 223,805) were obtained from the latest release from the FinnGen consortium as the outcome of interest. Two-sample MR was performed to evaluate the causal effect of gut microbiota on male fertility, including inverse-variance-weighted (IVW) method, weighted median method, MR-Egger, mode-based estimation and MR-PRESSO. A series of sensitivity analyses was performed to validate the robustness of the results. The robustness of the estimation was tested by a series of sensitivity analyses including Cochran's Q test, MR-Egger intercept analysis, leave-one-out analysis and funnel plot were used to assess the causal association. Combining the results from the discovery and replication stages, we identified 3 causal bacterial genus. Ruminiclostridm6 (OR = 0.537, 95%CI = 0.292-0.987, P = .045, PFDR = 0.234) was found to be closely associated with male infertility, and the decrease in its quantity increased the risk of male infertility. Decreased Prevotella9 (OR = 0.670, 95% CI = 0.452-0.992, P = .046, PFDR = 0.175) was found to be closely related to abnormal sperm. Lachnospiraceae NC2004 group (OR = 1.173, 95% CI = 1.008-1.366, P = .078, PFDR = 0.530) was found to be closely related to male erectile dysfunction, and there was a positive correlation between them. No heterogeneity and pleiotropy were detected. This study implied a causal relationship between the Ruminiclostridm6 genus, Prevotella9 genus, Lachnospiraceae NC2004 group genus and male fertility, thus providing novel insights into the gut microbiota-mediated development mechanism of ADs. Nevertheless, future studies are warranted to dissect the underlying mechanisms of specific bacterial taxa's role in the pathophysiology of male fertility., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.)

BACKGROUNDEBV is associated with nasopharyngeal carcinoma (NPC), but the existence of a NPC protective antibody against EBV-associated antigens remains unclear.METHODSPatients with NPC and matched controls were identified from prospective cohorts comprising 75,481 participants in southern China. ELISA and conditional logistic regression were applied to assess the effects of gp42-IgG on NPC. The expression of HLA-II, the gp42 receptor, in nasopharyngeal atypical dysplasia and its effect on EBV infection of epithelial cells were evaluated.FINDINGSgp42-IgG titers were significantly lower in patients with NPC compared with controls across various follow-up years before NPC diagnosis (P < 0.05). Individuals in the highest quartile for gp42-IgG titers had a 71% NPC risk reduction compared with those in the lowest quartile (ORsQ4vsQ1= 0.29, 95% CIs = 0·15 to 0.55, P < 0.001). Each unit antibody titer increase was associated with a 34% lower risk of NPC (OR = 0.66, 95% CI = 0.54-0.81, Ptrend< 0.001). The protective effect of of gp42-IgG was observed in patients diagnosed 5 years or more, 1-5 years, and less than 1 year after blood collection (P < 0.05). HLA-II expression was detected in 13 of 27 specimens of nasopharyngeal atypical dysplasia, and its overexpression substantially promoted epithelial cell-origin EBV infection.CONCLUSIONElevated EBV gp42-IgG titers can reduce NPC risk, indicating that gp42 is a potential EBV prophylactic vaccine target.TRIAL REGISTRATIONNCT00941538, NCT02501980, ChiCTR2000028776, ChiCTR2100041628.FUNDINGNoncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0501003), National Natural Science Foundation of China (82030046, 82073625, 81860601, 82373655), Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2019BT02Y198), and Central Financial Transfer Payment Projects of the Chinese Government, Cancer Research Grant of Zhongshan City.

Objective: Early diagnosis of laryngeal cancer (LC) is crucial, particularly in rural areas. Despite existing studies on deep learning models for LC identification, challenges remain in selecting suitable models for rural areas with shortages of laryngologists and limited computer resources. We present the intelligent laryngeal cancer detection system (ILCDS), a deep learning-based solution tailored for effective LC screening in resource-constrained rural areas., Methods: We compiled a dataset comprised of 2023 laryngoscopic images and applied data augmentation techniques for dataset expansion. Subsequently, we utilized eight deep learning models-AlexNet, VGG, ResNet, DenseNet, MobileNet, ShuffleNet, Vision Transformer, and Swin Transformer-for LC identification. A comprehensive evaluation of their performances and efficiencies was conducted, and the most suitable model was selected to assemble the ILCDS., Results: Regarding performance, all models attained an average accuracy exceeding 90 % on the test set. Particularly noteworthy are VGG, DenseNet, and MobileNet, which exceeded an accuracy of 95 %, with scores of 95.32 %, 95.75 %, and 95.99 %, respectively. Regarding efficiency, MobileNet excels owing to its compact size and fast inference speed, making it an ideal model for integration into ILCDS., Conclusion: The ILCDS demonstrated promising accuracy in LC detection while maintaining modest computational resource requirements, indicating its potential to enhance LC screening accuracy and alleviate the workload on otolaryngologists in rural areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Although enrofloxacin (ENR) is a widely used broad-spectrum antibiotic in veterinary medicine, its residues in animals can pose a risk to human health. Thus, we developed a new method for detecting ENR based on aptamers and AuNPs. In the absence of ENR, the aptamers attached to the surface of the AuNPs via electrostatic interactions to protect the AuNPs from NaCl, and the solution remained red. Conversely, the aptamer bonded with ENR, leading the aptamer to detach from the AuNP surface, and the color of the solution changed from red to blue. Based on this principle, ENR can be qualitatively detected by the naked eye and quantitatively detected by measuring the absorbance ratio at 650 nm and 530 nm. The experimental results showed a good linear relationship within the ENR concentration range of 0-400 nM, with a limit of detection (LOD) of 1.72 nM, which is satisfactory for detection in food safety. Additionally, this method has also been successfully applied to the detection of ENR in tap water, river water, milk, serum and urine, with good recovery rates and RSD values of less than 7%, indicating its great potential for ENR detection in environmental water samples. More importantly, the combination of this method with a smartphone platform provided great convenience for on-site and visual detection of ENR, offering promising applicability prospects.

Colorectal cancer (CRC) is challenging to treat due to its high metastatic rate. Recent strategies have focused on combining immune checkpoint inhibitors (ICIs) with other treatments. The aim of the present study was to conduct a network meta-analysis of randomized controlled trials (RCTs) to assess the efficacy and adverse effects of different ICI treatments for CRC. A literature search for RCTs was conducted using PubMed, the Cochrane Library, Embase, ClinicalTrials.gov and Web of Science databases, covering the period from the inception of each database until April 2024. A total of 12 RCTs involving 2,050 participants were selected for inclusion in the analysis. The network meta-analysis employed the MetaInsight tool to assess multiple endpoints. The criteria for study selection were based on the Population, Intervention, Comparison, Outcome and Studies framework as follows: i) Population, patients with CRC; ii) intervention, studies using ICI to treat CRC; iii) comparison, active comparators, including placebo; iv) outcome, overall survival, progression-free survival, objective response rate and adverse events; and v) study design, RCTs. The results of the analysis revealed that programmed cell death-ligand 1 (PD-L1) inhibitors significantly improved overall survival time [mean difference (MD), 2.28 months; 95% confidence interval (CI), 0.44 to 4.11], while programmed cell death protein 1 (PD-1) inhibitors exhibited a superior progression-free survival time (MD, 4.79 months; 95% CI, 3.18 to 6.40) compared with active comparators. However, none of the ICI treatments had significant differences in odds ratios for the objective response rate and adverse events compared with active comparators. These findings indicate that treatment with PD-L1 and PD-1 inhibitors improved the overall survival time and delayed disease progression in patients with CRC. These findings offer valuable insights for future research aimed at improving CRC patient outcomes., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Tzang et al.)

Ethnopharmacological Relevance: Zhilong Huoxue Tongyu Capsule (ZL) is clinically prescribed for acute ischemic stroke (AIS). However, only a few studies have addressed the mechanisms of ZL in treating AIS., Aim of the Study: To explore the underlying mechanism of macrophage polarization and inflammation mediated by ZL, and to provide a reference for AIS treatment., Materials and Methods: Sixteen SD rats were fed with different dose of ZL (0, 0.4, 0.8, and 1.6 g/kg/d) for 4 days to prepare ZL serum. After 500 ng/mL lipopolysaccharide (LPS) stimulation, RAW264.7 cells were administrated with ZL serum. Then, experiments including ELISA, flow cytometry, real-time quantitative PCR and Western blot were performed to verify the effects of ZL on macrophage polarization and inflammation. Next, let-7i inhibitor was transfected in RAW264.7 cells when treated with LPS and ZL serum to verify the regulation of ZL on the let-7i/TLR9/MyD88 signaling pathway. Moreover, the interaction between let-7i and TLR9 was confirmed by the dual-luciferase assay., Results: ZL serum significantly decreased the expression of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), and increased the expression of IL-10 and transforming growth factor β1 (TGF-β1) of LPS stimulated-macrophages. Furthermore, ZL serum polarized macrophages toward M2, decreased the expressions of TLR9, MyD88, and iNOS, as well as increased the expressions of let-7i, CHIL3, and Arginase-1. It is worth mentioning that the effect of ZL serum is dose-dependent. However, let-7i inhibitor restored all the above effects in LPS stimulated-macrophages. In addition, TLR9 was the target of let-7i., Conclusions: ZL targeted let-7i to inhibit TLR9 expression, thereby inhibiting the activation of the TLR9/MyD88 pathway, promoting the M2 polarization, and inhibiting the development of inflammation in AIS., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We designed and developed the probe W-3 for detection of Cu 2+ . The results showed probe can selectively detect Cu 2+ , accompanied by noticeable color change. The probe can detect the Cu 2+ in water samples and drinks based on absorption detection. In addition, the combination of portable test paper and the smartphone platform obtained great convenience for on-site and visual detection of Cu 2+ , with satisfactory sensitivity and reliability. More importantly, the fluorescence probe W-3 can be used for the detection of Cu 2+ in cells and mice. Therefore, the W-3 provided potential chemical tools for detecting Cu 2+ in vitro and vivo., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Diabetes has become one of the most common endocrine and metabolic diseases threatening human health, which can induce mitochondrial dysfunction and exacerbate the excessive production of reactive oxygen species (ROS). Among them, ONOO - level fluctuation was closely related to diabetes. Hence, it is of great significance to develop a near-infrared fluorescence probe for visualizing ONOO - level fluctuations in diabetes. In this paper, we constructed a fluorescence probe YBL with dicyano-isophorone derivative as fluorophore and diphenyl phosphate as ONOO - response site, which can detect ONOO - with the low detection limit (39.8 nM) and exhibit excellent selectivity and sensitivity. The probe YBL has been applied to monitor intracellular ONOO - level fluctuations. Meanwhile, the image results showed that high sugar promoted the increase of ONOO - level in cells. More important, the probe YBL can be used for imaging in mice, and the results showed that content of ONOO - was increased in diabetic mice. Therefore, the probe YBL provided a tool for understanding diabetes progression by imaging ONOO - ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: The deep circumflex iliac artery flap (DCIA) and vascularized fibular free flap (FFF) are mainstay flaps for maxillary defect reconstruction. This study compared the functional outcomes and success rates of these flaps to provide midface reconstruction strategies., Materials and Methods: Maxillary defects reconstructed with DCIA or FFF at the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology between May 2016 and May 2023 were retrospectively analyzed. The length, width, and height of the grafted bone segments; intermaxillary distance; buttress reconstruction rate (BRR); dental arch reconstruction rate (DAR); success rate; and dental implantation rate were compared., Results: The DCIA and FFF groups had 33 and 27 patients, respectively. Success rate in the DCIA group was 93.94 % and 100 % in the FFF group. The DCIA length was less than that of FFF; however, the width and height were significantly larger. 87.10 % of cases in the DCIA group were classified as Brown class b and c, 51.85 % of cases in the FFF group were classified as Brown class d. The average BRR in the DCIA group was 69.89 % ± 16.05 %, which was significantly higher than that in the FFF group. A total of 38.7 % and 11.1 % patients in the DCIA and FFF groups, respectively, had completed implantation., Conclusion: DCIA has a greater width and height, and is more suitable for repairing Brown class b and c defects, providing sufficient bone for implantation, while the FFF is longer and more suitable for Brown class d defect reconstruction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

We designed and prepared probe W-1 for the detection of H 2 O 2 . W-1 showed excellent selectivity for H 2 O 2 and was accompanied by colorimetric signal changes. The excellent linear relationship between fluorescence intensity and H 2 O 2 concentration (0-100 μM) provided favorable conditions for its quantitative detection. In addition, the combination of portable test strips with a smartphone platform provided great convenience for on-site visual detection of H 2 O 2 . Moreover, W-1 possessed targeting mitochondria property and could be applied to image the exogenous and endogenous H 2 O 2 in cells to distinguish normal cells and cancer cells. Lastly, W-1 was used for monitoring the H 2 O 2 fluctuation of the diabetic process in mice, and the results showed an increase in H 2 O 2 levels in diabetes. Therefore, the probe provided a tool for understanding the pathological and physiological mechanisms of diabetes by imaging H 2 O 2 .

Intracellular microenvironment (viscosity and polarity) and peroxynitrite ions (ONOO - ) are involved in maintaining cell morphology, cell function, and signaling so that it is crucial to explore their level changes in vitro and vivo. In this work, we designed and synthesized a mitochondria-targeted fluorescence probe XBL for monitoring the dynamic changes of viscosity, polarity, and ONOO - based on TICT and ICT mechanism. The fluorescence spectra showed obvious changes for polarity at 500 nm as well as ONOO - and viscosity at 660 nm, respectively. The XBL can image simultaneously viscosity, polarity, and ONOO - in cells, and the results showed excess ONOO - leaded to the increase of viscosity in mitochondrial. The ferroptosis process was accompanied by increase of intracellular viscosity and ONOO - levels (or decrease of polarity), which allowed us to better understand the relevant physiological and pathological processes. The XBL can distinguish normal cells and cancerous cells by the fluorescence intensity changes in green and red channels, and image viscosity in inflamed mice. Thus, XBL can provided the chemical tool to understand the physiological and pathological mechanisms of disease by simultaneous detection of viscosity, polarity and ONOO - ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To analyze the occurrence of concomitant gene mutations in cytogenetically normal acute myeloid leukemia (CN-AML) patients with CEBPA mutation and its impact on the clinical characteristics and prognosis of the patients., Methods: 151 newly diagnosed patients with CN-AML in the Second Hospital of Shanxi Medical University from June 2013 to June 2020 were analyzed retrospectively. 34 common genetic mutations associated with hematologic malignancies were detected by next-generation sequencing technology. The occurrence of concomitant gene mutations in patients with CEBPA positive and negative groups was compared, and the correlation between concomitant mutations in different functional groups and the clinical characteristics and prognosis of CN-AML patients with CEBPA mutation was analyzed., Results: In 151 patients with CN-AML, 55 (36.42%) were positive for CEBPA mutation (including 36 cases of CEBPA dm and 19 cases of CEBPA sm ), of which 41 (74.55%) had co-mutations with other genes. The main mutated genes were GATA2 (25.45%, 14/55), TET2 (21.82%, 12/55), FLT3 (20.00%, 11/55), NRAS (12.73%, 7/55) and WT1 (9.09%, 9/55), etc. Some cases had two or more concomitant gene mutations. Grouping the mutant genes according to their functions showed that CEBPA + group had lower mutation rates of histone methylation ( P =0.002) and chromatin modification genes ( P =0.002, P =0.033), and higher mutation rates of transcription factors ( P =0.037) than CEBPA - group. In 55 patients with CEBPA + CN-AML, the platelet count at diagnosis in signaling pathway gene mutation-positive group was lower than that in the mutation-negative group ( P =0.005), the proportion of bone marrow blasts in transcription factor mutation-positive group was higher than that in the mutation-negative group ( P =0.003), and the onset age in DNA methylation gene mutation-positive group and chromatin modifier mutation-positive group was older than that in the mutation-negative group, respectively ( P =0.002, P =0.008). DFS of CEBPA + CN-AML patients in signaling pathway gene mutation group was shorter than that in signaling pathway gene mutation-negative group (median DFS: 12 months vs not reached) ( P =0.034). Compared with DNA methylation gene mutation-negative group, CEBPA + CN-AML patients with DNA methylation gene mutation had lower CR rate ( P =0.025) significantly shorter OS and DFS (median OS: 20 months vs not reached, P =0.006; median DFS: 15 months vs not reached, P =0.049). OS in patients with histone methylation gene mutation was significantly shorter than that in the histone methylation gene mutation-negative group (median OS: 12 months vs 40 months) ( P =0.008). Multivariate analysis of prognostic factors showed that the proportion of bone marrow blasts ( P =0.046), concomitant DNA methylation gene mutation ( P =0.006) and histone methylation gene mutation ( P =0.036) were independent risk factors affecting the prognosis., Conclusion: CN-AML patients with CEBPA mutation have specific concomitant gene profile, and the concomitant mutations of different functional genes have a certain impact on the clinical characteristics and prognosis of the patients.

Systemic autoimmune diseases (SADs) are a growing spectrum of autoimmune disorders that commonly affect multiple organs. The role of Epstein-Barr virus (EBV) infection or reactivation as a trigger for the initiation and progression of SADs has been established, while the relationship between EBV envelope glycoproteins and SADs remains unclear. Here, we assessed the levels of IgG, IgA, and IgM against EBV glycoproteins (including gp350, gp42, gHgL, and gB) in serum samples obtained from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and found that RA and SLE patients exhibited a statistically significant increase in the levels of 8 and 11 glycoprotein antibodies, respectively, compared to healthy controls (p < 0.05). The LASSO model identified four factors as significant diagnostic markers for RA: gp350 IgG, gp350 IgA, gHgL IgM, and gp42 IgA; whereas for SLE it included gp350 IgG, gp350 IgA, gHgL IgA, and gp42 IgM. Combining these selected biomarkers yielded an area under the curve (AUC) of 0.749 for RA and 0.843 for SLE. We subsequently quantified the levels of autoantibodies associated with SADs in mouse sera following immunization with gp350. Remarkably, none of the tested autoantibody levels exhibited statistically significant alterations. Elevation of glycoprotein antibody concentration suggests that Epstein-Barr virus reactivation and replication occurred in SADs patients, potentially serving as a promising biomarker for diagnosing SADs. Moreover, the absence of cross-reactivity between gp350 antibodies and SADs-associated autoantigens indicates the safety profile of a vaccine based on gp350 antigen., (© 2024 Wiley Periodicals LLC.)

Objective: Secreted phospholipase A2 Group IB (sPLA2GIB) regulates the release of arachidonic acid, prostaglandins, and other inflammatory lipid mediators. Although it has been well involved in extensive inflammatory diseases, its specific mechanism in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. In this study, we investigated the role of sPLA2GIB in the pathophysiology of CRSwNP., Methods: Quantitative PCR, immunofluorescence staining, western blotting, and enzyme-linked immunosorbent assay (ELISA) were used to analyze the expression of sPLA2s, phospholipase A2 receptor (PLA2R), and prostaglandin D2 (PGD2) in nasal samples. Human nasal epithelial cells (HNECs) were cultured at an air-liquid interface (ALI) and stimulated with various cytokines. The human mast cell line HMC-1 was stimulated with sPLA2GIB, and the expression of PGD2 and cytokines in the culture supernatant was detected by ELISA., Results: The mRNA and protein levels of sPLA2GIB were significantly higher in eosinophilic CRSwNP than in control tissues. sPLA2GIB was predominantly expressed in the nasal epithelial cells. PLA2R mRNA and protein levels were upregulated in both eosinophilic and non-eosinophilic CRSwNP compared with the control groups. IL-4, IL-13, TNF-α, and IL-1β upregulated the expression of sPLA2GIB in ALI-cultured HNECs. sPLA2GIB induced PGD2 and IL-13 production in HMC-1 cells in a hydrolytic activity-independent manner. PGD2 protein expression was elevated in tissue homogenates of eosinophilic CRSwNP, and PGD2 upregulated the expression of IL-13 in HMC-1 cells., Conclusion: Increased secretion of sPLA2GIB by epithelial cells may promote eosinophilic inflammation in CRSwNP by enhancing PGD2 and IL-13 production in mast cells via binding to PLA2R., Level of Evidence: N/A Laryngoscope, 134:1107-1117, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: This study aimed to evaluate the differences in the accuracy of immediate intraoral, immediate extraoral, and delayed dental implant placement with surgical guides (static computer-aided implant surgery) in patients treated with mandibular reconstruction., Methods: This was a retrospective study. The patients were divided into three groups: immediate intraoral placement (IIO), immediate extraoral placement (IEO), and delayed placement (DEL). Four variables were used to compare the planned and actual implant positions: angular deviation, three-dimensional (3D) deviation at the entry point of the implant, 3D deviation at the apical point of the implant, and depth deviation., Results: The angular deviation was significantly higher in the IIO group than in the IEO (p < .05) and DEL (p < .05) groups. The 3D deviation at the entry point was significantly higher in the IIO group than in the IEO (p < .05) and DEL (p < .01) groups. The 3D deviation at the apical point was significantly higher in the IIO group than in the IEO (p < .01) and DEL (p < .01) groups. The depth deviation was significantly higher in the IIO group than in the IEO (p < .05) and DEL (p < .05) groups. There was no statistical difference between the IEO and DEL group in angular and 3D deviation., Conclusion: With surgical guides, among the different approaches for implant placement, delayed implant placement remains the most accurate approach for patients treated with mandibular reconstruction., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Microsurgical bone reconstruction is challenging in cases of anterior maxillary defects because of the presence of residual teeth. The study analyzed the method and feasibility of using vascularized bone flaps to reconstruct anterior maxillary defects., Methods: We retrospectively analyzed 15 patients treated at the Department of Oral and Maxillofacial Surgery, Peking University School, and Hospital of Stomatology between November 2017 and January 2023., Results: A total of 14 patients were successfully reconstructed using the digital technique: 6 deep circumflex iliac artery (DCIA) flaps and 8 fibular free flaps. Palatal and buccal pedicle paths were used in 4 and 10 cases, respectively, for vascular anastomosis. The implant coverage rates of the DCIA and fibular free flaps were 87.2% and 92.6%, respectively (p > 0.05)., Conclusion: Anterior maxillary defects reconstructed with the DCIA and fibular free flaps are reliable methods. Furthermore, the palatal and buccal paths are recommended for vascular anastomosis., (© 2023 Wiley Periodicals LLC.)

Background: One-stage jaw reconstruction with fibular flap and prosthetic rehabilitation restores bony and dental continuity simultaneously. It was also called as "jaw-in-a-day (JIAD)" technique. However, bone volume and height of fibular flap may be insufficient for dental implant insertion. The provision of a considerable amount of bone makes an iliac flap the ideal choice in these cases. We present the first case report to document the use of one-stage jaw reconstruction and prosthetic rehabilitation with the iliac flap., Case Presentation: We modified the conventional JIAD workflow to make it suitable for iliac flap. Two cases were presented who both underwent segmental mandibulectomy for ameloblastoma. Virtual surgical planning was performed in all cases. The iliac crest was positioned upward to provide cortical bone for achieving primary stability of dental implants. Similar to the "all-on-4" procedure, the iliac bone was placed 12 to 15 mm below the occlusal plane to create adequate space for the implant-retained prosthesis. Immediate implant-based dental rehabilitation was performed at same stage. The surgery was successful in all cases without any short-term complications. In the first postoperative week, patients were given a liquid diet through a nasal feeding tube. The liquid diet is advised until 1 month after the surgery. Thereafter, a soft diet is recommended. Patients were advised to resume routine mastication and normal diet 3 months after the surgery. Peri-implantitis occurred in one patient, and additional gingival graft was required. Postoperative function and esthetics were satisfactory at the last follow-up visit., Conclusions: One-stage jaw reconstruction and prosthetic rehabilitation with the iliac flap are safe and useful for restoring postoperative function and esthetics. It should be used in more cases with a longer follow-up in further studies., (© 2024. The Author(s).)

Epstein-Barr virus (EBV) is associated with various malignancies and infects >90% of the global population. EBV latent proteins are expressed in numerous EBV-associated cancers and contribute to carcinogenesis, making them critical therapeutic targets for these cancers. Thus, this study aims to develop mRNA-based therapeutic vaccines that express the T-cell-epitope-rich domain of truncated latent proteins of EBV, including truncatedlatent membrane protein 2A (Trunc-LMP2A), truncated EBV nuclear antigen 1 (Trunc-EBNA1), and Trunc-EBNA3A. The vaccines effectively activate both cellular and humoral immunity in mice and show promising results in suppressing tumor progression and improving survival time in tumor-bearing mice. Furthermore, it is observed that the truncated forms of the antigens, Trunc-LMP2A, Trunc-EBNA1, and Trunc-EBNA3A, are more effective than full-length antigens in activating antigen-specific immune responses. In summary, the findings demonstrate the effectiveness of mRNA-based therapeutic vaccines targeting the T-cell-epitope-rich domain of EBV latent proteins and providing new treatment options for EBV-associated cancers., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Epstein-Barr virus (EBV) is closely associated with cancer, multiple sclerosis, and post-acute coronavirus disease 2019 (COVID-19) sequelae. There are currently no approved therapeutics or vaccines against EBV. It is noteworthy that combining multiple EBV glycoproteins can elicit potent neutralizing antibodies (nAbs) against viral infection, suggesting possible synergistic effects. Here, we characterize three nAbs (anti-gp42 5E3, anti-gHgL 6H2, and anti-gHgL 10E4) targeting different glycoproteins of the gHgL-gp42 complex. Two antibody cocktails synergistically neutralize infection in B cells (5E3+6H2+10E4) and epithelial cells (6H2+10E4) in vitro. Moreover, 5E3 alone and the 5E3+6H2+10E4 cocktail confer potent in vivo protection against lethal EBV challenge in humanized mice. The cryo-EM structure of a heptatomic gHgL-gp42 immune complex reveals non-overlapping epitopes of 5E3, 6H2, and 10E4 on the gHgL-gp42 complex. Structural and functional analyses highlight different neutralization mechanisms for each of the three nAbs. In summary, our results provide insight for the rational design of therapeutics or vaccines against EBV infection., Competing Interests: Declaration of interests Xiao Zhang and Yixin Chen have filed two provisional patents (CN116284348A and CN116253795A) and hold one patent (CN113372440B) related to this work., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Epstein-Barr virus (EBV) is a global public health concern, as it is known to cause multiple diseases while also being etiologically associated with a wide range of epithelial and lymphoid malignancies. Currently, there is no available prophylactic vaccine against EBV. gB is the EBV fusion protein that mediates viral membrane fusion and participates in host recognition, making it critical for EBV infection in both B cells and epithelial cells. Here, we present a gB nanoparticle, gB-I53-50 NP, that displays multiple copies of gB. Compared with the gB trimer, gB-I53-50 NP shows improved structural integrity and stability, as well as enhanced immunogenicity in mice and non-human primate (NHP) preclinical models. Immunization and passive transfer demonstrate a robust and durable protective antibody response that protects humanized mice against lethal EBV challenge. This vaccine candidate demonstrates significant potential in preventing EBV infection, providing a possible platform for developing prophylactic vaccines for EBV., Competing Interests: Declaration of interests The authors declare a potential conflict of interest related to the research presented in this article. Associated authors M.-S.Z., C.S., Y.-X.Z., G.-K.F., Y.-F.K., X.-C.C., X.Z., Q.Z., and X.-W.K. hold a patent (ZL202011417091.0) entitled as “Self-assembled nano-particles containing EB virus gB protein and preparation method and application thereof,” which is related to the technology/methods discussed in this study. This patent is held with the Sun Yat-sen University and Sun Yat-sen University Cancer Center. The authors affirm that this conflict of interest did not influence the design, execution, or reporting of the research and that they have adhered to the journal’s policies on transparency and disclosure., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The aim of this study is to assess the relationship between somatosensory functional changes and inferior alveolar nerve (IAN) exposure after impacted mandibular third molars (M3M) removal. We recruited 35 patients who underwent impacted M3M extraction near the IAN. The M3Ms were extracted by combined endoscopy, piezosurgery, and contra-angle high-speed turbine handpiece. All IAN canal perforations and exposed regions were recorded and measured by endoscopy after extraction and on cone-beam computed tomography (CBCT) images before extraction. The patients were followed up 1, 7, and 35 days after surgery. A standardized quantitative sensory testing (QST) battery was performed on the lower lip skin. All of 35 cases had exposed IAN on CBCT images, 5 of which had no exposed IAN under endoscopy. For the other 30 cases, the endoscopy-measured IAN length and width were shorter than the CBCT measurements (P < 0.001). The warm and mechanical detection thresholds (MDT) on the operation side were significantly higher than the contralateral side after surgery (P < 0.05). Thermal sensory limen, MDT, and cold pain threshold were strongly correlated with the exposed IAN length and MDT also with the exposed IAN width one day after surgery. In conclusion, it was found that not all exposed IAN in CBCT images were real exposure after surgery. The intraoperative exposed IAN endoscopic measurements were smaller than by CBCT and strongly correlated with some QST parameters., (© 2023. The Author(s).)

Background: The purpose of this study was to investigate the effect of anterior superior iliac spine (ASIS) preservation on donor site morbidity and function after harvesting a vascularized iliac bone flap (VIBF)., Methods: Patients who underwent jaws reconstruction with VIBF were divided into a maintaining the anterior superior iliac spine (MASIS) group and a not maintaining the anterior superior iliac spine (NMASIS) group. Pain, tenderness, sensory deficit, gait disturbance, and function of the donor site were evaluated before and after the operation., Results: Thirty-three patients were included in this study, of which 18 were in the MASIS group. The incidence of sensory deficit in the MASIS group was significantly lower than that in the NMASIS group (50.0% vs. 86.7%, p = 0.010). Pain, tenderness, gait disturbance, and function did not differ statistically between the two groups., Conclusion: Except for sensory deficit, ASIS preservation has minimal impact on donor site morbidity and function., (© 2023 Wiley Periodicals LLC.)

Objective: To explore the concentration range and penetration depth of methylene blue near-infrared fluorescence imaging, and to clarify the role of methylene blue in oral lymphatic drainage and sentinel lymph node localization, so as to lay a foundation for the potential research and application of sentinel lymph node in oral cancer., Methods: 10% (mass fraction) methylene blue injection was diluted into 29 different concentrations with 0.9% (mass fraction) normal saline, and the concentration range of methylene blue near-infrared fluorescence imaging was determined by near-infrared fluorescence imager. The maximum penetration depth of methylene blue near-infrared fluorescence was determined by covering pigskin with different thicknesses (1, 2, 3, 4 and 5 mm) in methylene blue solution. 0.2 mL methylene blue solution was injected into the submucosal 0.5 cm at the lateral margin of tongue on one side of the rats. The near-infrared fluorescence imager was used for continuously monitoring for 3 hours. The first near-infrared fluorescence hotspot was identified as sentinel lymph node and labeled by percutaneous observation. The rats were then sacrificed and dissected in the head and neck. Near-infrared fluorescence imaging was performed again to observe whether the fluorescent tissue was consistent with the labeled fluorescent hotspot in vitro , and the presence of lymphoid tissue was confirmed by pathological examination after resection., Results: Except that no fluorescence signals were detected in the blank control groups, the fluorescence intensity of methylene blue increased first and then decreased with its solution concentration decreased. When the concentration of methylene blue was diluted to the picomole level, the fluorescence signal could still be detected. The maximum penetration depth of methylene blue fluorescence was 4 mm. Methylene blue near-infrared fluorescence could be localized in oral lymphatic drainage and sentinel lymph node. The fluorescence was sustained for more than 3 hours after methylene blue injection. Methylene blue solution concentrations of 3.34 mmol/L, 6.68 mmol/L, 13.37 mmol/L and 26.74 mmol/L were selected in the rats to map sentinel lymph node by near-infrared fluorescence., Conclusion: Methylene blue near-infrared fluorescence has a certain penetrating ability and can transcuta-neously map the sentinel lymph node and their associated lymphatic vessels in rats, which is expected to be further applied in the study of sentinel lymph node in oral cancer.

Ethnopharmacological Relevance: Hemorrhagic transformation after acute ischemic stroke is a life-threatening disease that currently has no effective chemotherapy. Zhilong Huoxue Tongyu Capsule (ZL) is an empirical prescription of traditional Chinese medicine that is used to prevent and treat cardiovascular and cerebrovascular diseases in China. However, only a few studies have addressed the mechanisms of ZL in treating hemorrhagic transformation., Aim of the Study: To evaluate the anti-inflammatory effects of ZL on hemorrhagic transformation model rats and lipopolysaccharide (LPS)-induced RAW264.7 macrophages and to explore the underlying molecular mechanisms., Materials and Methods: Murine RAW264.7 cells were treated with ZL and LPS (1 μg/mL), and cell viability was detected by cell counting kit-8 assay. RT-qPCR was used to detect the expression of inflammatory chemokines, microRNA let-7a/e/i/f, toll like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa-B (NF-κB) p65. The protein expression levels of TLR4, MyD88, NF-κB p65, and apoptosis related molecules were determined by Western blotting. The apoptosis rate of RAW264.7 macrophages was detected by Annexin V-FITC/PI double staining. A hemorrhagic transformation model in rats was established by intraperitoneal injection of high glucose solution combined with thread embolization. Then, the model rats were observed behaviourally, pathologically, and molecularly. The gene expression of TLR4, MyD88, and NF-κB p65 was measured by RT-qPCR and used to evaluate the protective effect of ZL against hemorrhagic transformation in rats., Results: ZL (5, 20, 40 μg/mL) was beneficial in cell proliferation. LPS (1 μg/mL) stimulated the production of inflammatory chemokines and inhibited the production of let-7a/e/i/f, with let-7f being influenced most strongly. Moreover, overexpression of let-7f decreased the gene and protein levels of TLR4, MyD88, and NF-κB p65, downregulated TLR4, and inhibited its transcriptional activity. ZL (5, 20, and 40 μg·mL-1) inhibited the production of TLR4, MyD88, and NF-κB p65 and promoted the production of let-7f in a concentration-dependent manner. Furthermore, the blockade of TLR4 antagonized the promoting effects of TLR4 pathway activation in cell inflammation and apoptosis by downregulating let-7f. Critically, it was confirmed in vivo and in vitro that ZL upregulated the expression of let-7f and inhibited the gene expression of TLR4, MyD88, and NF-κB p65 to reduce inflammatory cell infiltration, which determined the occurrence of hemorrhagic transformation., Conclusions: ZL can reduce inflammatory response by upregulating let-7f and subsequently inhibiting the TLR4 signaling pathway, thereby decreasing the occurrence of hemorrhagic transformation., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The aim of this study was to evaluate the feasibility and accuracy of occlusion-driven maxillary reconstruction with the deep circumflex iliac artery (DCIA) flap, using computer-assisted design and manufacturing (CAD/CAM) technology and intraoral anastomosis. The data of 11 patients who underwent occlusion-driven maxillary reconstruction with this method between December 2018 and December 2020 in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology were reviewed retrospectively. Postoperative complications and functional and aesthetic outcomes were recorded. The accuracy of the postoperative restoration was assessed using Geomagic Control 2014. Reconstruction was successful in nine patients; all were satisfied with their aesthetic and functional outcomes. One patient underwent extraoral anastomosis after failure of intraoral anastomosis. In another patient, the DCIA flap had to be removed after the operation because of flap failure. Among the 10 patients with DCIA flap success, colour map analysis showed a mean deviation of 0.40 ± 0.08 mm between the preoperative and postoperative craniomaxillary models. Thus, occlusion-driven maxillary reconstruction with the DCIA flap, using CAD/CAM technology and intraoral anastomosis, appears to be a feasible and accurate method for the repair of maxillary defects., (Copyright © 2022. Published by Elsevier Inc.)

Background: This retrospective study reviewed all patients who underwent oral and maxillofacial reconstruction with fibular flaps in the last 2 decades at a single hospital., Materials and Methods: We reviewed all patients with fibular flaps from 1999 to 2018. The following data were collected: sex; age; reconstruction region; diagnosis; the number of days spent in the hospital after surgery; time spent using a tourniquet for harvesting a fibula flap; vessels at the recipient site; the prevalence of unplanned reoperations; the prevalence of flap failure; history of preoperative radiotherapy; virtual surgical planning; segments of the fibula., Results: In total, 2640 patients were included. The mean age was 45.5 years. The most prevalent region of reconstruction was the mandible (n=2347, 88.9%). The most common diagnosis was squamous cell carcinoma (n=1057, 40.0%). The mean number of days spent in the hospital after surgery decreased year-by-year from 18.3 days to 10.4 days. The first choice of recipient artery was the facial artery (n=1643, 62.2%) and that of the recipient vein was the external jugular vein (n=1196, 45.3%). The prevalence of surgical success was 97.6%. Prevalence of unplanned reoperations was 7.5%., Conclusions: The fibular flap was a good choice for oral and maxillofacial bony reconstruction in most cases., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Purpose: To investigate the clinical characteristics of oral and maxillofacial tumors in children and adolescents., Methods: This is a retrospective study of patients who had oral and maxillofacial tumors under the age of 18 years and were treated at the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from January 1990 to July 2021 (31 y). Their general conditions, pathological diagnosis, gender, age, and anatomical location were counted to analyze their morbidity and composition characteristics., Results: This study contained 5405 cases, including 2903 male patients and 2502 female patients, with a median age of 9 years. Peak incidence was observed in the 14 to 18 years age group. The mandible (22.15%), maxilla (11.75%), and tongue (9.25%) were the most common sites of incidence. Malignant and intermediate type tumors accounted for 13.04%, benign tumors and tumor-like lesions for 55.67%, most often occurs in the maxillofacial bone, of which fibro-osseous lesions constitute an important part. Cysts accounted for 31.29%. Among the tumors occurring in the jaws, the most common malignant type was sarcoma, and ameloblastoma was the most common benign tumor. Malignant jaw tumors were mostly treated by resection, 10.64% by fibular flap reconstruction. While benign jaw tumors and tumor-like lesions were mostly treated by resection or curettage., Conclusions: The distribution of anatomical location and pathological types of oral and maxillofacial tumors in children has certain characteristics, so that the selection of their treatment options is different from that of adults due to the consideration of the growth and developmental characteristics of children., Competing Interests: The author reports no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Background: Glucose concentrations are increased in nasal secretions in chronic rhinosinusitis (CRS). However, the glucose metabolism and its contribution to disease pathogenesis in CRS remain unexplored., Objectives: We sought to explore the glucose metabolism and its effect on the function of nasal epithelial cells in CRS with and without nasal polyps (CRSwNP and CRSsNP)., Methods: Glucose metabolites were detected with mass spectrometry. The mRNA levels of glucose transporters (GLUTs), metabolic enzymes, and inflammatory mediators were detected by quantitative RT-PCR. The protein expression of GLUTs was studied by immunofluorescence staining, Western blotting, and flow cytometry. Glucose uptake was measured by using fluorescent glucose analog. Human nasal epithelial cells (HNECs) were cultured. Bioenergetic analysis was performed with Seahorse XF analyzer. Gene expression in HNECs was profiled by RNA sequencing., Results: Increased glucose concentrations in nasal secretions was confirmed in both CRSsNP and CRSwNP. GLUT4, GLUT10, and GLUT11 were abundantly expressed in HNECs, whose expression was upregulated by inflammatory cytokines and D-glucose and was increased in CRS. Glucose uptake, glycolysis and tricarboxylic acid cycle metabolites, metabolic enzymes, and extracellular acidification rate and oxygen consumption rates were increased in HNECs in CRSsNP and CRSwNP, with a predominant shift to glycolysis. HNECs treated with high-level apical D-glucose showed enhanced glucose uptake, predominant glycolysis, and upregulated production of IL-1α, IL-1β, TNF-α, CCL20, and CXCL8, which was suppressed by 2-deoxy-D-glucose, an inhibitor of glycolysis., Conclusions: Increased glucose in nasal secretions promotes glucose uptake and predominant glycolysis in epithelial cells, augmenting the proinflammatory function of epithelial cells in CRS., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the resorption of the iliac bone after maxillary reconstruction with a vascularized free iliac flap. Twenty-seven patients with maxillary defects who underwent maxillary reconstruction with the vascularized free iliac flap between January 2017 and January 2021 were included. Computed tomography (CT) images taken at 1 week, approximately 6 months, and 1 year after the surgery were used for evaluation. The total iliac bone thickness and height, cortical bone thickness, and cancellous bone density were measured in the CT images. Compared with 1 week after the surgery, the total thickness and height of the iliac bone were reduced significantly 1 year after the surgery, and the cortical bone thickness and cancellous bone density were reduced significantly at 6 months and 1 year after the surgery. Compared with 6 months after the surgery, cancellous bone density was reduced significantly 1 year after the surgery. In conclusion, during the first year after maxillary reconstruction with a vascularized free iliac flap, there was significant resorption of iliac bone, including the total iliac bone thickness and height, the cortical bone thickness, and the cancellous bone density., (Copyright © 2022 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: The study aims to compare differences among iliac bone flaps with different iliac crest orientations for the repair of mandibular defects with an aim to analyze their advantages, disadvantages, and effects., Material and Methods: Clinical data and computed tomography scans of all patients who underwent iliac bone flap repair of the mandible in Peking University School and Hospital of Stomatology from January 2016 to April 2021 were collected. Patients were divided into the iliac crest towards alveolar process (Group A) and the iliac crest towards mandibular inferior margin (Group B). Software was used to measure corresponding indicators. The results obtained for the groups were statistically analyzed., Results: The study included 78 patients (25 and 53 in groups A and B, respectively). The symmetry of the LC-type defect was better in group A (p < 0.05). The all-bone width of the alveolar process side in group A was greater than 6 mm; in 15 cases of group B, the width was less than 6 mm (p < 0.05). The intermaxillary distance of two sites were higher in group B (p < 0.05). The bone cortical thickness was significantly thicker in group A (p < 0.05)., Conclusion: One year after the mandibular body defect was reconstructed with a vascularized iliac bone flap, the iliac crest towards alveolar process group showed better bone symmetry, width, intermaxillary distance, and cortical thickness to meet the planting requirements., Clinical Relevance: The use of an iliac crest towards alveolar process may be a better approach for mandible reconstruction., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Peroxynitrite (ONOO - ) as an active substance, is produced during normal physiological process, which plays an important role in maintaining cell REDOX balance and cell function. Moreover, the peroxynitrite is involved in many diseases and especially can be used as a biomarker of drug-induced liver injury (DILI). Therefore, in this work, we synthesized a fluorescent probe JQ-3 for detecting ONOO - . The results showed the probe JQ-3 possessed excellent selectivity, fast response time (10 min) and low detection limit (32 nM). The probe JQ-3 is almost unaffected by pH, showing the potential application in biological systems. Moreover, the probe JQ-3 can be successfully used for the detection of exogenous and endogenous ONOO - in living cells and zebrafish. At the same time, the DILI was successfully recognized by visualizing ONOO - with JQ-3 in living cells and zebrafish. Therefore, the probe JQ-3 provides a potential tool for detecting ONOO - to understand physiological and pathology processes of disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In this study, we constructed and displayed a ratiometric fluorescent probe JQ-2 for detecting ONOO - . The probe JQ-2 showed a ratiometric signal for visualizing ONOO - with a rapid response and high selectivity over a panel of biological analytes. Moreover, the JQ-2 has near-infrared emission (657 nm), which provides an excellent basis for the practical application in biological systems. The probe JQ-2 possessed low cytotoxicity and excellent cell membrane permeability, which can specifically visualize the exogenous and endogenous ONOO - in vitro and vivo by emission in two channels. Meanwhile, JQ-2 can be used for diagnosing drug-induced liver injury by visualizing and monitoring the fluctuations of endogenous ONOO - . Therefore, JQ-2 provided a potential tool for precisely detecting the fluctuation of ONOO - in biological systems to understand physiological and pathological process., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: The current standard for mandibular reconstruction is a contour-based approach using a fibular flap offering good cosmetic results but challenging to reconstruct using dental implants. An iliac flap is more amenable to implant placement and better suited for occlusion-driven reconstruction. We aimed to describe an occlusion-driven workflow that involves the use of digital surgical guides to perform mandibular reconstruction using an iliac flap; we also aimed to compare our results to those we achieved with conventional contour-based reconstruction., Methods: This was a retrospective cohort study. All patients who underwent mandibular reconstruction with an iliac flap at our university hospital between September 2017 and December 2019 were considered eligible for the study. The inclusion criteria included mandibular defects after tumor ablation and stable preoperative occlusal relationship. The exclusion criteria were as follows: defects involving the condyle and ramus, temporomandibular joint disease, and obvious preoperative nontumor-related facial asymmetry. To evaluate surgical outcomes, patients were assigned to 2 groups based on the implemented surgical workflow: the occlusion-driven and traditional contour-driven groups. The intermaxillary distance, intermaxillary angle, surface deviation, and implantation rates were compared between the 2 groups. The operating time, length, and number of iliac bone segments were recorded. Intergroup differences were investigated using an independent samples t test and Fisher exact test., Results: Overall, 24 patients were included (13 in the occlusion-driven group and 11 in the contour-driven group). Implantation rate was higher in the occlusion-driven group (61.5%) compared with the contour-driven group (18.2%; P = .047). The average acceptable intermaxillary distance was greater in the occlusion-driven group (92.3 ± 27.7%) than in the contour-driven group (47.0 ± 47.6%; P = .01). The average intermaxillary angle was 88.2 ± 8.4° in the occlusion-driven group and 76.4 ± 10.3° in the contour-driven group (P < .01)., Conclusions: Digital surgical guides can precisely transfer virtual surgical planning to real-world mandibular surgery. An occlusion-driven workflow might provide a better intermaxillary jaw relationship than traditional contour-driven surgical procedures, resulting in improved mastication., (Copyright © 2022 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

The Epstein-Barr virus (EBV) is associated with a variety of human malignancies, including Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma and gastric cancers. EBV infection is crucial for the oncogenesis of its host cells. The prerequisite for the establishment of infection is the virus entry. Interactions of viral membrane glycoproteins and host membrane receptors play important roles in the process of virus entry into host cells. Current studies have shown that the main tropism for EBV are B cells and epithelial cells and that EBV is also found in the tumor cells derived from NK/T cells and leiomyosarcoma. However, the process of EBV infecting B cells and epithelial cells significantly differs, relying on heterogenous glycoprotein-receptor interactions. This review focuses on the tropism and molecular mechanism of EBV infection. We systematically summarize the key molecular events that mediate EBV cell tropism and its entry into target cells and provide a comprehensive overview.

This study aimed to demonstrate the feasibility of near-infrared (NIR) fluorescence imaging using methylene blue (MB) for detecting oral sentinel lymph nodes (SLNs) in rats and compared MB’s tracer effects with those of indocyanine green (ICG) in SLN mapping. Different concentrations of MB were injected into the rats’ left lingual submucosa to determine the optimal concentration by using a continuous (1 h) MI-1 fluorescence imaging system. To compare the tracer effects of the optimal MB concentration with ICG in oral SLN mapping, MI-1 imaging was continuously monitored for 12 h. The mean signal-to-background ratio (SBR) of the SLNs and SLN fluorescence area fraction were analyzed. SLNs and lymphatic vessels were clearly visible in all rats. The optimal injection dose of MB infected into lingual submucosa for NIR fluorescence imaging was 0.2 mL of 6.68 mM MB. During continuous monitoring for 12 h, the mean SBR of the SLNs was significantly higher in the ICG groups than in the MB groups (p < 0.001). However, the area fraction of SLN fluorescence in the ICG groups increased continuously, owing to strong fluorescent contamination. This study examined the feasibility of detection of draining lymph nodes in the oral cavity of rats using MB NIR fluorescence imaging. MB causes less fluorescent contamination than does ICG, which shows promise for clinical research and application.

Background: The epithelial barrier plays an important role in the regulation of immune homeostasis. The effect of the immune environment on E-cadherin has been demonstrated in previous studies. This discovery prompted new research on the targeting mechanism of E-cadherin in chronic rhinosinusitis (CRS)., Methods: E-cadherin and p120 expression was determined by quantitative RT-PCR, and western blot. The interaction between E-cadherin and p120 was assessed by immunofluorescence staining and coimmunoprecipitation assays. Human nasal epithelial cells (HNECs) were cultured with submerged methods and transfected with p120-specific small interfering RNA. In other experiments, HNECs differentiated with the air-liquid interface (ALI) method were stimulated with various cytokines and Toll-like receptor (TLR) agonists. The barrier properties of differentiated HNECs were determined by assessing fluorescent dextran permeability., Results: E-cadherin and p120 expression was decreased in HNECs from patients with CRS, and the p120 protein expression level was positively correlated with that of E-cadherin. Two isoforms of p120 (p120-1 and p120-3) were expressed in HNECs, with p120-3 being the main isoform. Knocking down p120 in HNECs cultured under submerged conditions significantly reduced the E-cadherin protein expression. The Rac1 inhibitor NSC23766 reversed the protein expression of E-cadherin in p120 knockdown experiments. Inflammatory mediators, including IL-4, TNF-α, TGF- β, LPS and IFN-Î, reduced E-cadherin and p120 protein expression and increased paracellular permeability. Dexamethasone abolished the downregulation of E-cadherin and p120 caused by inflammatory mediators., Conclusions: p120 is involved in regulating E-cadherin protein expression in CRS. Dexamethasone may alleviate the reduction in E-cadherin and p120 protein expression caused by inflammatory mediators.

Despite the rapid deployment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, the emergence of SARS-CoV-2 variants and reports of their immune evasion characteristics have led to an urgent need for novel vaccines that confer potent cross-protective immunity. In this study, we constructed three different SARS-CoV-2 spike S1-conjugated nanoparticle vaccine candidates that exhibited high structural homogeneity and stability. Notably, these vaccines elicited up to 50-times-higher neutralizing antibody titers than the S1 monomer in mice. Crucially, it was found that the S1-conjugated nanoparticle vaccine could elicit comparable levels of neutralizing antibodies against wild-type or emerging variant SARS-CoV-2, with cross-reactivity to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), the effect of which could be further enhanced using our designed nanoparticles. Our results indicate that the S1-conjugated nanoparticles are promising vaccine candidates with the potential to elicit potent and cross-reactive immunity against not only wild-type SARS-CoV-2, but also its variants of concern, variants of interest, and even other pathogenic betacoronaviruses. IMPORTANCE The emergence of SARS-CoV-2 variants led to an urgent demand for a broadly effective vaccine against the threat of variant infection. The spike protein S1-based nanoparticle designed in our study could elicit a comprehensive humoral response toward different SARS-CoV-2 variants of concern and variants of interest and will be helpful to combat COVID-19 globally.

Radiation-induced functional and structural brain alterations are well documented in patients with nasopharyngeal carcinoma (NPC), followed by radiotherapy (RT); however, alterations in structure-function coupling remain largely unknown. Herein, we aimed to assess radiation-induced structure-function decoupling and its importance in predicting radiation encephalopathy (RE). We included 62 patients with NPC (22 patients in the pre-RT cohort, 18 patients in the post-RT-RE +ve cohort, and 22 patients in the post-RT-RE -ve cohort). A metric of regional homogeneity (ReHo)/voxel-based morphometry (VBM) was used to detect radiation-induced structure-function decoupling, which was then used as a feature to construct a predictive model for RE. Compared with the pre-RT group, patients in the post-RT group (which included post-RT-RE +ve and post-RT-RE -ve ) showed higher ReHo/VBM coupling values in the substantia nigra (SN), the putamen, and the bilateral thalamus and lower values in the brain stem, the cerebellum, the bilateral medial temporal lobes (MTLs), the bilateral insula, the right precentral and postcentral gyri, the medial prefrontal cortex (MPFC), and the left inferior parietal lobule (IPL). In the post-RT group, negative correlations were observed between maximum dosage of RT (MDRT) to the ipsilateral temporal lobe and ReHo/VBM values in the ipsilateral middle temporal gyrus (MTG). Moreover, structure-function decoupling in the bilateral superior temporal gyrus (STG), the bilateral precentral and postcentral gyri, the paracentral lobules, the right precuneus and IPL, and the right MPFC exhibited excellent predictive performance (accuracy = 88.0%) in identifying patients likely to develop RE. These findings show that ReHo/VBM may be a novel effective imaging metric that reflects the neural mechanism underlying RE in patients with NPC., 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 Kang, Chen, Ding, Li, Gao, Liu and Zhang.)

Emerging SARS-CoV-2 variants of concern (VOCs) harboring multiple mutations in the spike protein raise concerns on effectiveness of current vaccines that rely on the ancestral spike protein. Here, we design a quadrivalent mosaic nanoparticle vaccine displaying spike proteins from the SARS-CoV-2 prototype and 3 different VOCs. The mosaic nanoparticle elicits equivalent or superior neutralizing antibodies against variant strains in mice and non-human primates with only small reduction in neutralization titers against the ancestral strain. Notably, it provides protection against infection with prototype and B.1.351 strains in mice. These results provide a proof of principle for the development of multivalent vaccines against pandemic and potential pre-emergent SARS-CoV-2 variants., (© 2022. The Author(s).)

Epstein-Barr virus (EBV), the first identified human tumor virus, is etiologically associated with various kinds of malignant and benign diseases, accounting for 265,000 cancer incident cases and 164,000 cancer deaths in 2017. EBV prophylactic vaccine development has been gp350 centered for several decades. However, clinical studies show that gp350-centered vaccines fail to prevent EBV infection. Advances in the EBV infection mechanisms shed light on gB and gHgL, the two key components of the infection apparatus. In this study, for the first time, we utilized recombinant vesicular stomatitis virus (VSV) to display EBV gB (VSV-ΔG-gB/gB-G) or gHgL (VSV-ΔG-gHgL). In vitro studies confirmed successful virion production and glycoprotein presentation on the virion surface. In mouse models, VSV-ΔG-gB/gB-G or VSV-ΔG-gHgL elicited potent humoral responses. Neutralizing antibodies elicited by VSV-ΔG-gB/gB-G were prone to prevent B cell infection, while those elicited by VSV-ΔG-gHgL were prone to prevent epithelial cell infection. Combinatorial vaccination yields an additive effect. The ratio of endpoint neutralizing antibody titers to the endpoint total IgG titers immunized with VSV-ΔG-gHgL was approximately 1. The ratio of IgG1/IgG2a after VSV-ΔG-gB/gB-G immunization was approximately 1 in a dose-dependent, adjuvant-independent manner. Taken together, VSV-based EBV vaccines can elicit a high ratio of epithelial and B lymphocyte neutralizing antibodies, implying their unique potential as EBV prophylactic vaccine candidates. IMPORTANCE Epstein-Barr virus (EBV), one of the most common human viruses and the first identified human oncogenic virus, accounted for 265,000 cancer incident cases and 164,000 cancer deaths in 2017 as well as millions of nonmalignant disease cases. So far, no prophylactic vaccine is available to prevent EBV infection. In this study, for the first time, we reported the VSV-based EBV vaccines presenting two key components of the EBV infection apparatus, gB and gHgL. We confirmed potent antigen-specific antibody generation; these antibodies prevented EBV from infecting epithelial cells and B cells, and the IgG1/IgG2a ratio indicated balanced humoral-cellular responses. Taken together, we suggest VSV-based EBV vaccines are potent prophylactic candidates for clinical studies and help eradicate numerous EBV-associated malignant and benign diseases.

Background: Oseltamivir resistance in influenza virus (IFV) has been of widespread concern. An increase in the frequency of viruses with reduced inhibition was observed. Whether oseltamivir is effective is uncertain. We conducted this study to understand the real-world situation in northern China and the clinical efficacy for patients with IFV infection after the use of oseltamivir., Methods: The longitudinal study was performed on influenza-like illness (ILI) cases in a tertiary general hospital in Beijing, China during the flu season of 2018-2019. All ILI cases (≥18 years) were recruited into the study. We analyzed the effect of the oseltamivir therapy on the number of clinic visits, hospitalization frequency, and the duration of fever and cough., Results: A total of 689 ILI patients were recruited in this study with 355 in the oseltamivir therapy group and 334 in the supportive therapy group. Among the ILI patients, 388 patients were detected for IFV infection (364 IFV-A and 24 IFV-B) and divided into two groups with or without the oseltamivir therapy (302 vs. 86). There were no significant differences in the basic characteristics between the oseltamivir and supportive therapy groups in the ILI patients or in the IFV positive patients (all p  < 0.05). After adjusting for the potential confounders, oseltamivir therapy reduced the times of clinic visits in the ILI and IFV positive patients ( p  = 0.043 and p  = 0.011). No effectiveness with oseltamivir therapy was observed in the outcomes of hospitalization frequency, and the duration of fever and cough., Conclusion: Oseltamivir use may reduce the times of clinic visits. However, we did not observe the differences in the duration of fever, cough, and the frequency of hospitalization between oseltamivir therapy and supportive therapy., 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 Li, Chen, Wang, Lin, Li, Liang, Deng, Zhang, Jia, Su, Kang, Du, Liu, Xu and Lu.)

Mex-3 RNA Binding Family Member A (MEX3A) is an RNA-binding protein that plays complex and diverse roles in the development of various malignancies. However, its role and mechanism in nasopharyngeal carcinoma (NPC) remain undefined and were therefore evaluated in this study. By analyzing Gene Expression Omnibus data and using tissue microarrays, we found that MEX3A is significantly upregulated in NPC and negatively associated with prognosis. Notably, MEX3A depletion led to decreased cell proliferation, invasion, and migration, but increased apoptosis in NPC cells in vitro, while inhibiting tumor growth in vivo. Using whole-transcript expression arrays and bioinformatic analysis, we identified scinderin (SCIN) and miR-3163 as potential downstream targets of MEX3A in NPC. The regulatory mechanisms of MEX3A, SCIN and miR-3163 were further investigated using rescue experiments. Importantly, SCIN depletion and miR-3163 inhibition reversed and rescued the oncogenic effects of MEX3A, respectively. Moreover, NF-κB signaling inhibition reversed the oncogenic effects of both SCIN and MEX3A. In summary, our results demonstrate that MEX3A may promote NPC development and progression via the miR-3163/SCIN axis by regulating NF-κB signaling, thus providing a potential target for NPC treatment., (© 2022. The Author(s).)

Thrombin is a potent platelet activator and a key mediator of blood coagulation, thereby playing a crucial role in cardiovascular disease. Recently, protease-activated receptor 4 (PAR4), one of thrombin receptors in human platelets, is emerging as a promising target for antiplatelet therapy. 3,5,2',4'-Tetramethoxystilbene (TMS), a resveratrol analog, have demonstrated promising effects on preventing atherosclerosis and hypertension, whereas its antiplatelet effect has never been investigated. Herein we show that TMS at concentrations of a few micromolar selectively inhibits PAR4-mediated human platelet aggregation, ATP secretion, integrin αIIbβ3 activation, and signaling pathways. In a whole-blood model of arterial flow, TMS also significantly reduced in vitro thrombus formation. Analysis of the structure-activity relationships of TMS and a panel of stilbene analogs reveal that full methylation of hydroxy groups of the stilbenes is the critical structural determinant for the anti-PAR4 activity. Our results suggest that fully methylated resveratrol analogs with anti-PAR4 activity are potential candidates for development of novel antiplatelet agents., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Influenza A virus (IAV) is a global health threat. The cellular endocytic machineries harnessed by IAV remain elusive. Here, by tracking single IAV particles and quantifying the internalized IAV, we found that sphingomyelin (SM)-sequestered cholesterol, but not accessible cholesterol, is essential for the clathrin-mediated endocytosis (CME) of IAV. The clathrin-independent endocytosis of IAV is cholesterol independent, whereas the CME of transferrin depends on SM-sequestered cholesterol and accessible cholesterol. Furthermore, three-color single-virus tracking and electron microscopy showed that the SM-cholesterol complex nanodomain is recruited to the IAV-containing clathrin-coated structure (CCS) and facilitates neck constriction of the IAV-containing CCS. Meanwhile, formin-binding protein 17 (FBP17), a membrane-bending protein that activates actin nucleation, is recruited to the IAV-CCS complex in a manner dependent on the SM-cholesterol complex. We propose that the SM-cholesterol nanodomain at the neck of the CCS recruits FBP17 to induce neck constriction by activating actin assembly. These results unequivocally show the physiological importance of the SM-cholesterol complex in IAV entry. IMPORTANCE IAV infects cells by harnessing cellular endocytic machineries. A better understanding of the cellular machineries used for its entry might lead to the development of antiviral strategies and would also provide important insights into physiological endocytic processes. This work demonstrated that a special pool of cholesterol in the plasma membrane, SM-sequestered cholesterol, recruits FBP17 for the constriction of clathrin-coated pits in IAV entry. Meanwhile, the clathrin-independent cell entry of IAV is cholesterol independent. The internalization of transferrin, the gold-standard cargo endocytosed solely via CME, is much less dependent on the SM-cholesterol complex. These results provide new insights into IAV infection and the pathway/cargo-specific involvement of the cholesterol pool(s).

SARS-CoV-2 variants have evolved a variety of critical mutations, leading to antigenicity changes and immune escape. The recent emerging SARS-CoV-2 Omicron variant attracted global attention due to its significant resistance to current antibody therapies and vaccines. Here, we profiled the mutations of Omicron and other various circulating SARS-CoV-2 variants in parallel by computational interface analysis and in vitro experimental assays. We identified critical mutations that lead to antigenicity changes and diminished neutralization efficiency of a panel of 14 antibodies due to diverse molecular mechanisms influencing the antigen-antibody interaction. Our study identified that Omicron exhibited extraordinary potency in immune escape compared to the other variants of concern, and explores the application of computational interface analysis in SARS-CoV-2 mutation surveillance and demonstrates its potential for the early identification of concerning variants, providing preliminary guidance for neutralizing antibody therapy., (© 2022. The Author(s).)