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Junpeng Chen, Qiuyun Yao, Xirui Wang, Jinpeng Jiang, Huiyong Zhu, Dan Yu Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Dan Yu, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Shangcheng District, Hangzhou City, Zhejiang Province, 310003, People’s Republic of China, Tel/Fax, Email yudang85@zju.edu.cnObjective: The multidisciplinary team (MDT) approach is increasingly being utilized in the management of complex head and neck diseases. This study analyzed the benefits of MDT for patients with head and neck diseases as primary or secondary conditions and categorized MDT meetings into two types: head and neck surgery initiation (HNI) and head and neck surgery participation (HNP). The study further explored the characteristics of these MDT meetings and the factors influencing patient compliance, aiming to optimize MDT treatment models to maximize patient benefits.Design: Retrospective analysis.Methods: MDT meetings from January 2021 to December 2023 were reviewed. The meetings and patients were classified into the HNI group and the HNP group. Various factors, including general patient conditions, disease characteristics et al were analyzed using chi-square tests and point biserial correlation tests. P-values < 0.05 were considered statistically significant.Results: A total of 292 MDT cases were analyzed, comprising 127 cases in the HNI group and 165 cases in the HNP group. In the HNI group, the initial diagnosis was modified in 11 cases (8.7%), with 92 patients (72.4%) receiving major recommendations for their treatment plans. In the HNP group, the initial diagnosis was modified in 28 cases (17.0%). The head and neck surgeons had a major impact on treatment plans in 47 cases (28.5%). Notably, patients with head and neck tumors received more major recommendations (p

Yantao Yu,1– 3,&ast; Chenkai Zhang,2,3,&ast; Qiannan Sun,2– 4 Shantanu Baral,2,3 Jianyue Ding,2,3 Fanyu Zhao,2,3 Qing Yao,2,3 Shuyang Gao,2,3 Bin Liu,2– 4 Daorong Wang1– 4 1The Yangzhou School of Clinical Medicine of Dalian Medical University, Yangzhou, 225001, People’s Republic of China; 2General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou, 225001, People’s Republic of China; 3Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou, 225001, People’s Republic of China; 4Northern Jiangsu People’s Hospital, Yangzhou, 225001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Daorong Wang; Bin Liu, Email 18051062590@yzu.edu.cn; liubin2006cool@126.comBackground: Gastric cancer (GC) is a highly phenotypically heterogeneous disease and is caused by a combination of factors. Retinol binding protein 4 (RBP4) is a member of a family of lipid transport proteins that are involved in the transport of substances between cells and play a crucial role in a variety of cancers. However, the expression and role of RBP4 in GC remain unknown.Methods: In this study, we explored the expression, prognostic significance, immune microenvironment, drug responsiveness and function of associated signaling pathways of RBP4 in GC using web-based bioinformatics tools. Immunohistochemistry and real-time quantitative PCR were utilized to analyze the tissue and cell expression levels of RBP4. CCK-8, colony formation, EDU incorporation, wound healing and transwell assays were applied to demonstrate the effect of RBP4 on GC cell function. Flow cytometric detection of apoptosis after RBP4 knockdown. Nude mice xenograft model elucidates the role of RBP4 for GC in vivo. Related proteins of the RAS signaling pathway were analyzed by employing Western blot assays.Results: RBP4 is highly expressed in GC. RBP4 is closely associated with patient survival and sensitivity to a wide range of antitumor agents. Knockdown of RBP4 promoted apoptosis and inhibited cell proliferation, invasion and migration. RBP4 promotes GC tumorigenesis in vivo. Finally, RBP4 modulates the RAS/RAF/ERK axis.Conclusion: RBP4 may promote gastric carcinogenesis and development through the RAS/RAF/ERK axis and is expected to be a novel target for GC treatment.Keywords: RBP4, gastric cancer, invasion, migration, RAS/RAF/ERK axis

The interactions between electrons and antiferromagnetic magnons (AFMMs) are important for a large class of correlated materials. For example, they are the most plausible pairing glues in high-temperature superconductors, such as cuprates and iron-based superconductors. However, unlike electron-phonon interactions (EPIs), clear-cut observations regarding how electron-AFMM interactions (EAIs) affect the band structure are still lacking. Consequently, critical information on the EAIs, such as its strength and doping dependence, remains elusive. Here we directly observe that EAIs induce a kink structure in the band dispersion of Ba1-xKxMn2As2, and subsequently unveil several key characteristics of EAIs. We found that the coupling constant of EAIs can be as large as 5.4, and it shows strong doping dependence and temperature dependence, all in stark contrast to the behaviors of EPIs. The colossal renormalization of electron bands by EAIs enhances the density of states at Fermi energy, which is likely driving the emergent ferromagnetic state in Ba1-xKxMn2As2 through a Stoner-like mechanism with mixed itinerant-local character. Our results expand the current knowledge of EAIs, which may facilitate the further understanding of many correlated materials where EAIs play a critical role.

Qingyuan Huang,1– 3,&ast; Hang Cao,1– 3,&ast; Qianlan Yao,3– 5,&ast; Xiaoyan Zhou,3– 5 Hang Li,1– 3 Qianming Bai,3– 5 Hong Hu1– 3 1Departments of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China; 2Institute of Thoracic Oncology, Fudan University, Shanghai, 200032, People’s Republic of China; 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China; 4Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China; 5Institute of Pathology, Fudan University, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Hu; Qianming Bai, Email huhong0997@163.com; baiqianming@163.comBackground: NOTCH1 is frequently mutated in non-small cell lung cancer (NSCLC), and also is a poor therapeutic target. It is of clinical importance to investigate the effects of NOTCH1 mutations on anti-tumor immunity and response to immune checkpoint blockade (ICB).Methods: An observational study with targeted sequencing in 963 NSCLC patients at our center were performed (FUSCC cohort). Data of the Cancer Genome Atlas Pan-Lung Cancer study (TCGA cohort) were analyzed, and gene set enrichment analysis (GSEA) was performed. The Samstein et al cohort included 350 patients with advanced NSCLC undergoing genomic profiling with the MSK-IMPACT assay, and receiving at least one dose of ICB therapy.Results: NOTCH1 mutations were more common in smokers and patients with squamous-cell carcinoma (SCC) (all P value < 0.05). For patients who did not receive ICB therapy (TCGA cohort), the overall survival (OS) of NOTCH1-mutant and -WT patients were comparable (log-rank P = 0.72), while for patients who received ICB therapy in the Samstein et al cohort, NOTCH1-mutant patients had significantly superior OS than WT patients (log-rank P = 0.041). On multivariate Cox analysis, the predictive value of NOTCH1 mutations reached marginal statistical significance (HR, 0.42; 95% CI, 0.17– 1.04; P = 0.059). The median of TMB for NOTCH1-mutant tumors was significantly higher than that for NOTCH1-WT tumors, and GSEA revealed that NOTCH1 mutations manifested various defects in the repair of DNA damage. NOTCH1-mutant tumors displayed an inflamed tumor microenvironment (TME), manifesting as increased PD-L1 expression and tumor-infiltrating CD8+ T cells.Conclusion: NOTCH1 mutations define a molecular subtype of NSCLC, which are more common in smokers and patients with SCC, are characterized with higher TMB, inflamed TME, and display improved survival of ICB therapy for NSCLC patients.Keywords: NOTCH1, non-small cell lung cancer, immunotherapy, survival, tumor mutational burden, tumor microenvironment

Qianqian Yao,1,&ast; Kexin Jiang,1,&ast; Fei Lin,2 Tao Zhu,3 Nazeer Hussain Khan,1,4 Enshe Jiang1,4 1Institute of Nursing and Health, Henan University, Kaifeng, People’s Republic of China; 2School of Medicine, Shangqiu Institute of Technology, Shangqiu, People’s Republic of China; 3Department of Geriatrics, Kaifeng Traditional Chinese Medicine Hospital, Kaifeng, People’s Republic of China; 4Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Enshe Jiang, Email esjiang@gmail.comAbstract: Alzheimer’s disease (AD), the most common cause of dementia and the fifth leading cause of death in the adult population has a complex pathophysiological link with hypertension (HTN). A growing volume of published literature on a parallel elevation of blood pressure (BP), amyloid plaques, and neurofibrillary tangles formation in post-middle of human brain cells has developed new, widely accepting foundations on this association. In particular, HTN in elderly life mediates cerebral blood flow dysfunction, neuronal dysfunction, and significant decline in cognitive impairment, primarily in the late-life populace, governing the onset of AD. Thus, HTN is an established risk factor for AD. Considering the impact of AD, 1.89 million deaths annually, and the failure of palliative therapies to cure AD, the scientific research community is looking to adopt integrated approaches to target early modified risk factors like HTN to reduce AD burden. The current review highlights the significance and impact of HTN-based prevention in lowering the AD burden in the elderly by providing a comprehensive overview of the physiological relationship between AD and HTN with an in-detail explanation of the role and applications of pathological biomarkers in this clinical association. The review will gain worth in presenting new insights and providing inclusive discussion on the correlation between HTN and cognitive impairment. It will increase across a wider scientific audience to expand understanding of this pathophysiological association.Keywords: Alzheimer’s disease, hypertension, elderly population, clinical biomarkers

Yingli Wu,1– 3,&ast; Yu Yang,1– 3,&ast; Xiaolin Lv,1– 3 Menghan Gao,1 Xujin Gong,1– 3 Qingqiang Yao,1– 4 Yanna Liu1– 3 1School of Pharmacy and Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China; 2NHC Key Laboratory of Biotechnology Drugs (Shandong Academy of Medical Sciences), Jinan, Shandong, 250117, People’s Republic of China; 3Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Jinan, Shandong, 250117, People’s Republic of China; 4Jining Medical University, Jining, Shandong, 272067, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingqiang Yao, Jining Medical University, No. 133 HeHua Road, Jinan, Shandong, 272067, People’s Republic of China, Email qqyao@sdfmu.edu.cn Yanna Liu, Shandong First Medical University, No. 6699 Qingdao Road, HuaiYin District, Jinan, Shandong, 250117, People’s Republic of China, Email liuyanna@sdfmu.edu.cnAbstract: Ovarian cancer is one of the most common malignant tumors in gynecology with a high incidence. Combination therapy, eg, administration of paclitaxel followed by a platinum anticancer drug is recommended to treat ovarian cancer due to its advantages in, eg, reducing side effects and reversing (multi)drug-resistance compared to single treatment. However, the benefits of combination therapy are often compromised. In chemo and chemo/gene combinations, co-deposition of the combined therapeutics in the tumor cells is required, which is difficult to achieve due to dramatic pharmacokinetic differences between combinational agents in free forms. Moreover, some undesired properties such as the low-water solubility of chemodrugs and the difficulty of cellular internalization of gene therapeutics also hinder the therapeutic potential. Delivery of dual or multiple agents by nanoparticles provides opportunities to tackle these limits. Nanoparticles encapsulate hydrophobic drug(s) to yield aqueous dispersions facilitating its administration and/or to accommodate hydrophilic genes facilitating its access to cells. Moreover, nanoparticle-based therapeutics can not only improve drug properties (eg, in vivo stability) and ensure the same drug disposition behavior with controlled drug ratios but also can minimize drug exposure of the normal tissues and increase drug co-accumulation at targeted tissues via passive and/or active targeting strategies. Herein, this work summarizes nanoparticle-based combination therapies, mainly including anticancer drug-based combinations and chemo/gene combinations, and emphasizes the advantageous outcomes of nanocarriers in the combination treatment of ovarian cancer. In addition, we also review mechanisms of synergetic effects resulting from different combinations.Keywords: ovarian cancer, nanoparticles, combination therapy, chemotherapy, gene therapy

Ying Shi1– 3&ast;, Wenming Kong1 &ast;, Haiqin Jiang,2,3 Wenyue Zhang,2,3 Chen Wang,2– 4 Limei Wu,1 Yunliang Shen,1 Qiang Yao,1 Hongsheng Wang1– 3,5 1Department of Leprosy Control, Zhejiang Provincial Institute of Dermatology, Huzhou, People’s Republic of China; 2Hospital of Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, People’s Republic of China; 3National Centre for STD and Leprosy Control, China CDC, Nanjing, People’s Republic of China; 4Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 5Centre for Global health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China&ast; These authors contributed equally to this workCorrespondence: Qiang Yao, Department of Leprosy Control, Zhejiang Provincial Institute of Dermatology, St 61, Zhejiang, People’s Republic of China, Email 7793908@qq.com Hongsheng Wang, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 12 Jiangwangmiao Street, Nanjing, People’s Republic of China, Tel: +86 025 8547 8953, Email whs33@vip.sina.comPurpose: Reports on antimicrobial resistance (AMR) of Mycobacterium leprae (M. leprae) in Zhejiang Province are limited. Thus, this study aimed to investigate the drug resistance of new leprosy cases within several years and analyse the emergence of AMR mutations from Zhejiang Province.Methods: This study enrolled 34 leprosy cases in Zhejiang Province, China, from 2018 to 2021. Gene mutation of WHO-recommended DRDRs (folP1, rpoB and gyrA) and genes of compensatory AMR-associated DRDRs, including nth, rpoA, rpoC, gyrB and 23S rRNA, were detected by amplification. Clinical data analysis was performed to investigate the epidemiological association of leprosy.Results: Of the 34 samples, 2 (5.9%) strains showed drug resistance, which were mutated to dapsone and ofloxacin, separately. Two single mutations in gyrB were detected in different strains (5.9%), whereas one of the rpoC mutation was also detected in one strain each (2.9%), which were proved to be polymorphs. No correlation of drug resistance proportion was identified in male vs female, nerve vs no nerve involvement, deformity vs no deformity and reaction vs non-reaction cases.Conclusion: Results showed well control of leprosy patients in Zhejiang Province. Gene mutations of WHO-recommended DRDRs folP1 and gyrA confirmed the resistance to dapsone and ofloxacin. Compensatory AMR-associated mutations confirmed to be polymorphs still require further study to determine their phenotypic outcomes in M. leprae. The results demonstrated that drug-resistant strains are not epidemic in this area. Given the few cases of leprosy, analysing the AMR of M. leprae in Zhejiang Province more comprehensively is difficult. However, regular MDT treatment and population management in the early stage may contribute to the low prevalence of leprosy.Keywords: M. leprae, antimicrobial resistance, gene mutation

Xiaoming Li,1,2,&ast; Qiandong Yao,3,&ast; Chen Liu,1,&ast; Jian Wang,1 Huarong Zhang,4 Shiguang Li,2,5 Ping Cai1 1Department of Radiology, Southwest Hospital, Third Military Medical University (Army Military Medical University), Chongqing, People’s Republic of China; 2Department of Radiology, The First People’s Hospital of Zunyi, The Third Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of China; 3Department of Radiology, Sichuan Science City Hospital, Mianyang, People’s Republic of China; 4Institute of Pathology and Southwest Cancer Center, Third Military Medical University (Army Military Medical University), Chongqing, People’s Republic of China; 5The Second People’s Hospital of Guiyang (Jinyang Hospital), Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiguang Li; Ping Cai, Email imaging_sgli@163.com; 530305942@qq.comAbstract: Hepatocellular carcinoma is one of the most common malignancies globally. Recently, a newly identified histological subtype, designated as “macrotrabecular-massive hepatocellular carcinoma” (MTM-HCC), has been associated with an aggressive phenotype and has received extensive attention. MTM-HCC was a strong independent prognostic predictor of early and overall recurrence because it is closely related to tumor molecular subclass, gene mutation, carcinogenesis pathways, and immunohistochemical markers. In addition, preoperative imaging examination can potentially provide an essential clue for diagnosing MTM-HCC, intratumor necrosis or ischemia is an independent predictor for MTM-HCC on Gd-EOB-DTPA enhanced MRI or CT. Early diagnosis and appropriate treatment of MTM-HCC could prove beneficial for preventing early recurrence and could improve outcomes.Keywords: hepatocellular carcinoma, macrotrabecular-massive, molecular subclass, gene mutation, magnetic resonance imaging

Background There are currently three strategies for the duration of low molecular weight heparin (LMWH) lead-in before direct oral anticoagulants (DOACs) in patients with acute pulmonary embolism (PE): one is at least 5 days, the other is at least 3 days and the last one is less than 3 days. Which one is the best is yet unknown. Aim To explore optimal initial duration of LMWH lead-in before DOACs for short-term outcomes of hospitalized patients with non-high-risk acute PE. Design Retrospective observational cohort study using propensity score matching. Methods We divided non-high-risk PE patients into short-LMWH (LMWH <3 days), intermediate-LMWH (LMWH 3-5 days) and long-LMWH (LMWH >5 days) groups, in a 1:1:2 ratio by using propensity score matching. Primary outcomes were a composite of mortality including all-cause and PE-related mortality, VTE recurrence and major bleeding, as well as each one of them, at 3-month after PE diagnosis. Results The short-LMWH group (N  = 504) had higher 3-month composite primary outcome (129 [25.6%] vs. 67 [13.3%], P  < 0.001), all-cause mortality (112 [22.2%] vs. 39 [7.7%], P  < 0.001) and PE-related mortality (48 [9.5%] vs. 17 [3.4%], P  < 0.001), than the intermediate-LMWH group (N  = 504). The short-LMWH group also had higher 3-month composite primary outcome (129 [25.6%] vs. 151 [15.0%], P  < 0.001), all-cause mortality (112 [22.2%] vs. 90 [8.9%], P  < 0.001) and PE-related mortality (48 [9.5%] vs. 41 [4.1%], P  < 0.001) than the long-LMWH group (N  = 1008). The VTE recurrence and major bleeding rates were similar between the short-LMWH and intermediate-LMWH groups, and between the short-LMWH and long-LMWH groups. The intermediate-LMWH and long-LMWH groups had similar 3-month primary outcomes rates in whole or in part with each other. Conclusions For patients with non-high-risk acute PE, the optimal duration of initial LMWH lead-in before switching to DOACs could be 3–5 days. [ABSTRACT FROM AUTHOR]

A dual-jet collecting device is highly efficient at picking up small-sized polymetallic nodules; however, its performance is not as effective for large nodules in deep-sea mining. To address this problem, numerical simulations have been conducted to thoroughly investigate the flow characteristics and particle motions during the collection of larger nodules. The collection performance of the enhanced device is analyzed across varying front jet velocities (Vf), suction pressures (Pout), and nozzle heights (h/d). The results reveal that increasing Vf improves the drag force and particle velocity in the jet impingement and upwelling zones, facilitating nodule lifting movement and transport. However, increasing Pout reduces the drag forces in these zones while increasing the particle velocity in the upwelling zone. A large Pout is not conducive to nodule initiation but has benefits for transport. Increasing h/d reduces the drag force in the anti-gravity direction in the jet impingement zone. The improved collecting device attains a pick-up efficiency that exceeds 80% for large-sized nodules when h/d < 1.3. The pick-up efficiency with suction pressure, which remains 40%, is higher than that without suction pressure when h/d > 1.3. The research findings may shed light on the design of more efficient dual-jet collection systems. [ABSTRACT FROM AUTHOR]

Hydrodynamic approaches that treat granular materials as a continuum via the homogenization of discrete flow properties have become viable options for efficient predictions of bulk flow behaviours. However, simplified boundary conditions in computational fluid dynamics are often adopted, which have difficulty in describing the complex stick-slip phenomenon at the boundaries. This paper extends the lattice Boltzmann method for granular flow simulations by incorporating a novel frictional boundary condition. The wall slip velocity is first calculated based on the shear rate limited by the Coulomb friction, followed by the reconstruction of unknown density distribution functions through a modified bounce-back scheme. Validation is performed against a unique plane Couette flow configuration, and the analytical solutions for the flow velocity profile and the wall slip velocity, as functions of the friction coefficient, are reproduced by the numerical model. The transition between no-slip and partial-slip regimes is captured well, but the convergence rate drops from second order to first order when slip occurs. The rheological parameters and the basal friction coefficient are calibrated further against the discrete element simulation of a square granular column collapsing over a horizontal bottom plane. It is found that the calibrated continuum model can predict other granular column collapses with different initial aspect ratios and slope inclination angles, including the basal slip and the complex internal flow structures, without any further adjustments to the model parameters. This highlights the generalization ability of the numerical model, which has a wide range of application in granular flow predictions and controls. [ABSTRACT FROM AUTHOR]