ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride（CRPV）， and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts， as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards， databases， and relevant literature were utilized for compound annotation， with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups， including the blank group， model group， diazepam group（2.5 mg·kg^-1）， raw CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， and vinegar-processed CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， with 10 mice per group. Except for the blank group， all other groups underwent chronic restraint stress（2 h·d^-1） for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling， with a total treatment duration of 10 d. Following model-based drug administration， mice underwent open-field， forced swimming， and elevated plus maze tests. After anesthesia with isoflurane， whole brains were collected from each group of mice， and hippocampi were dissected. Reactive oxygen species（ROS） level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay（ELISA）. Hematoxylin-eosin（HE） staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei（NeuN） and peroxisome proliferator-activated receptor alpha（PPARα） expressions in hippocampal tissue. Then， pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders， exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV， with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds， including 20 flavonoids， 20 flavonoid glycosides， 3 triterpenes， 3 phenolic acids， 1 alkaloid， and 6 other compounds. Twenty-one components were detected in blood（15 methoxyflavones， 4 flavonoid glycosides， and 2 phenolic acids）， with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues（all common to both forms）. In regulating emotional disorders， Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology， particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS（P<0.05）. ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing， but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway， thereby negatively regulating ROS generation in the hippocampus， reducing oxidative stress， and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards， pharmacodynamic material research， and active drug development of raw and vinegar-processed CRPV.

OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory disease around the world, and pharmacotherapy is the foremost treatment method currently. In recent decades, with the rapid development of bronchoscopic interventional therapy, endoscopic physical ablation technology presents a therapeutic effect in treating COPD, with few treatment-related side effects, showing excellent application prospects in treating COPD. Since ablation techniques in this field are emerging technologies with low patient acceptance, they are not widely used in the clinical treatment of COPD. This article reviews the development process of physical ablation techniques. Moreover, their current application status and the prospects in the field of COPD treatment are also summarized and analyzed. We hope to promote the application of physical ablation in the clinical treatment of COPD and provide practical references and a theoretical basis for the clinical treatment of COPD.

ObjectiveIn traditional Chinese medicine (TCM), the foundational doctrine that the eyes reflect the essence of the internal viscera establishes ocular observation as a cornerstone of diagnostic practice. Specifically, the morphological characteristics and coloration variations of the scleral microvasculature serve as critical clinical indicators for assessing the dynamic balance of Qi and Blood, as well as the pathological status of internal organs. Historically, however, TCM eye diagnosis has relied predominantly on the subjective clinical experience and visual acuity of individual practitioners, leading to inherent challenges in standardization and reproducibility. While automated computer-aided diagnostic systems offer a promising solution, existing vessel segmentation algorithms encounter significant domain-specific bottlenecks when applied to scleral imagery. These challenges primarily stem from the highly reflective and moist nature of the ocular surface, which generates severe reflective interference. Furthermore, the inherent low contrast of fine capillary networks against complex background textures, compounded by non-uniform illumination, frequently results in high false-positive rates, misdetections, and severe vessel fragmentation. To address these critical limitations and advance the objective quantification of TCM diagnostics, this paper proposes a novel, highly robust sclera vessel segmentation framework that innovatively integrates Frangi-Sato dual-filter adaptive enhancement with pixel-level reflection detection. MethodsThe proposed methodology systematically addresses the segmentation pipeline through three synergistic stages. First, to overcome the structural limitations of single-filter approaches, a multi-scale weighted fusion strategy is meticulously designed to harness the complementary extraction capabilities of both Frangi and Sato filters. This adaptive enhancement optimally balances the preservation of main vessel trunk continuity with the heightened sensitivity required for delineating delicate, low-contrast peripheral capillaries. Second, to tackle the persistent issue of reflective highlights, a sophisticated multi-feature synergistic reflection detection module is introduced. By jointly analyzing local information entropy, gradient field variations, and intensity statistical distributions, this module achieves precise, pixel-level identification and elimination of reflective artifacts without compromising the underlying vascular structures. Finally, a dual-level adaptive thresholding strategy, featuring an innovative “core protection” mechanism, is implemented. This critical step effectively suppresses complex background noise while rigorously preserving the structural and topological integrity of the intricate vessel network, preventing the structural breaks often seen in conventional binarization methods. ResultsThe efficacy of the proposed framework was rigorously evaluated using both self-constructed clinical datasets specifically acquired for TCM research and standardized public datasets. Extensive experimental results demonstrate that the proposed method consistently outperforms state-of-the-art traditional approaches and contemporary deep learning models. Specifically, the proposed method achieves a Dice similarity coefficient of approximately 0.71 on the private clinical dataset, and secures the best performance across the majority of quantitative metrics on both datasets. Notably, the framework exhibits exceptional robustness and generalization capabilities in highly challenging scenarios characterized by intense reflective interference, low signal-to-noise ratios, and cross-domain image variations. ConclusionThis study successfully realizes the high-integrity, automated segmentation of scleral vessel networks under complex clinical imaging conditions. By overcoming the fundamental algorithmic challenges of reflection interference and micro-vessel loss, the proposed methodology provides potential support for the digitization, objective standardization, and intelligent advancement of modern TCM eye diagnosis systems.

ObjectiveIn traditional Chinese medicine (TCM), the foundational doctrine that the eyes reflect the essence of the internal viscera establishes ocular observation as a cornerstone of diagnostic practice. Specifically, the morphological characteristics and coloration variations of the scleral microvasculature serve as critical clinical indicators for assessing the dynamic balance of Qi and Blood, as well as the pathological status of internal organs. Historically, however, TCM eye diagnosis has relied predominantly on the subjective clinical experience and visual acuity of individual practitioners, leading to inherent challenges in standardization and reproducibility. While automated computer-aided diagnostic systems offer a promising solution, existing vessel segmentation algorithms encounter significant domain-specific bottlenecks when applied to scleral imagery. These challenges primarily stem from the highly reflective and moist nature of the ocular surface, which generates severe reflective interference. Furthermore, the inherent low contrast of fine capillary networks against complex background textures, compounded by non-uniform illumination, frequently results in high false-positive rates, misdetections, and severe vessel fragmentation. To address these critical limitations and advance the objective quantification of TCM diagnostics, this paper proposes a novel, highly robust sclera vessel segmentation framework that innovatively integrates Frangi-Sato dual-filter adaptive enhancement with pixel-level reflection detection. MethodsThe proposed methodology systematically addresses the segmentation pipeline through three synergistic stages. First, to overcome the structural limitations of single-filter approaches, a multi-scale weighted fusion strategy is meticulously designed to harness the complementary extraction capabilities of both Frangi and Sato filters. This adaptive enhancement optimally balances the preservation of main vessel trunk continuity with the heightened sensitivity required for delineating delicate, low-contrast peripheral capillaries. Second, to tackle the persistent issue of reflective highlights, a sophisticated multi-feature synergistic reflection detection module is introduced. By jointly analyzing local information entropy, gradient field variations, and intensity statistical distributions, this module achieves precise, pixel-level identification and elimination of reflective artifacts without compromising the underlying vascular structures. Finally, a dual-level adaptive thresholding strategy, featuring an innovative “core protection” mechanism, is implemented. This critical step effectively suppresses complex background noise while rigorously preserving the structural and topological integrity of the intricate vessel network, preventing the structural breaks often seen in conventional binarization methods. ResultsThe efficacy of the proposed framework was rigorously evaluated using both self-constructed clinical datasets specifically acquired for TCM research and standardized public datasets. Extensive experimental results demonstrate that the proposed method consistently outperforms state-of-the-art traditional approaches and contemporary deep learning models. Specifically, the proposed method achieves a Dice similarity coefficient of approximately 0.71 on the private clinical dataset, and secures the best performance across the majority of quantitative metrics on both datasets. Notably, the framework exhibits exceptional robustness and generalization capabilities in highly challenging scenarios characterized by intense reflective interference, low signal-to-noise ratios, and cross-domain image variations. ConclusionThis study successfully realizes the high-integrity, automated segmentation of scleral vessel networks under complex clinical imaging conditions. By overcoming the fundamental algorithmic challenges of reflection interference and micro-vessel loss, the proposed methodology provides potential support for the digitization, objective standardization, and intelligent advancement of modern TCM eye diagnosis systems.

Background and Aims:Patients with end-stage liver disease(ESLD)frequently experience persistent pruritus,which significantly impairs their quality of life.Although relief of pruritus after liver transplantation is often attributed to the normalization of bilirubin levels,the role of skin microbiota in developing pruritus remains unclear.This study aimed to investigate the dynamic changes in skin microbiota during the perioperative period of liver transplantation in ESLD patients and to explore their association with pruritic symptoms.Methods:Fifteen ESLD patients treated in the Third Xiangya Hospital between 2022 and 2023 were enrolled and skin swabs were collected from the anterior tibial region at three time points:before liver transplantation and on postoperative days 7 and 30.Skin samples from 15 age-matched healthy controls were collected at the same anatomical site.Microbial composition was analyzed using 16S rRNA sequencing.Meanwhile,pruritus severity was assessed using a visual analogue scale(VAS),and multiple serological indicators were measured to evaluate correlations between microbiota changes,pruritus severity,and liver function parameters.Results:Compared with healthy controls,ESLD patients exhibited significantly altered β-diversity in skin microbiota and an increased relative abundance of Staphylococcus(LDA>4),which was strongly correlated with VAS scores for pruritus(r=0.93,Padj=3.08×10?1?).On postoperative day 7,α-diversity decreased,and Staphylococcus abundance peaked,then gradually normalized by day 30 as pruritus improved.Further analysis revealed that Staphylococcus abundance was positively correlated with alanine aminotransferase,aspartate aminotransferase,total bilirubin,direct bilirubin,total bile acids,and international normalized ratio,and negatively correlated with albumin(all Padj<0.05).Notably,Staphylococcus levels were significantly higher in patients with moderate to severe pruritus(VAS score>5).Conclusion:ESLD patients demonstrate marked dysbiosis of the skin microbiota during the perioperative period of liver transplantation,characterized by an abnormal proliferation of Staphylococcus,which may contribute to the development and exacerbation of pruritus.Targeting the skin microbiome,particularly interventions against Staphylococcus,may offer a novel therapeutic strategy for alleviating pruritus in ESLD patients.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8⁺ to CD4⁺ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8⁺ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).