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.

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.

Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

Currently, the drug delivery system (DDS) based on nanomaterials has become a hot interdisciplinary research topic. One of the core issues is drug loading and controlled release, in which the key lever is carriers. Vaterite, as an inorganic porous nano-material, is one metastable structure of calcium carbonate, full of micro or nano porous. Recently, vaterite has attracted more and more attention, due to its significant advantages, such as rich resources, easy preparations, low cost, simple loading procedures, good biocompatibility and many other good points. Vaterite, gained from suitable preparation strategies, can not only possess the good drug carrying performance, like high loading capacity and stable loading efficiency, but also improve the drug release ability, showing the better drug delivery effects, such as targeting release, pH sensitive release, photothermal controlled release, magnetic assistant release, optothermal controlled release. At the same time, the vaterite carriers, with good safety itself, can protect proteins, enzymes, or other drugs from degradation or inactivation, help imaging or visualization with loading fluorescent drugs in vitro and in vivo, and play synergistic effects with other therapy approaches, like photodynamic therapy, sonodynamic therapy, and thermochemotherapy. Latterly, some renewed reports in drug loading and controlled release have led to their widespread applications in diverse fields, from cell level to clinical studies. This review introduces the basic characteristics of vaterite and briefly summarizes its research history, followed by synthesis strategies. We subsequently highlight recent developments in drug loading and controlled release, with an emphasis on the advantages, quantity capacity, and comparations. Furthermore, new opportunities for using vaterite in cell level and animal level are detailed. Finally, the possible problems and development trends are discussed.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Objectives:To investigate the association between cardiac magnetic resonance(CMR)structural parameters and myocardial fibrosis in patients with hypertrophic cardiomyopathy(HCM),and to assess their predictive value for major adverse cardiovascular events(MACE).Methods:A total of 120 patients with HCM who underwent CMR examination at Affiliated Hospital of Guangdong Medical University between December 2021 and December 2023 were retrospectively enrolled.Patients were divided into the MACE group and the non-MACE group.MACE included acute myocardial infarction,angina pectoris,stroke,heart failure,severe arrhythmia.The CMR parameters were compared between the two groups.The correlation between CMR structural parameters and the myocardial fibrosis index(number of myocardial fibrotic segments/total segment number×100%)was evaluated using the locally weighted scatterplot smoothing method(LOWESS).Multivariate Cox regression was performed to identify the influencing factors of MACE.Threshold effect analysis of CMR structural parameters was conducted,and receiver operating characteristic(ROC)curves were generated to evaluate the diagnostic performance of CMR structural parameters for MACE.Results:During a follow-up period of 12(5,30)months,a total of 78(65.0%)patients developed MACE(the MACE group),and the remaining 42(35.0%)patients were assigned to the non-MACE group.Compared with the non-MACE group,patients in the MACE group had significantly larger left atrial diameter,left ventricular end-diastolic maximum diameter,maximal interventricular septal thickness,maximal left ventricular wall thickness,and higher myocardial fibrosis index(all P<0.05).The LOWESS analysis showed significant positive correlations between the above CMR structural parameters and the myocardial fibrosis index(all Poverall<0.05).The multivariate Cox regression showed that the echocardiographic interventricular septal thickness OR=2.622,95%CI:1.537-3.033),left ventricular posterior wall thickness(OR=1.597,95%CI:1.353-2.420),as well as CMR-derived left atrial diameter(OR=1.623,95%CI:1.314-2.595),left ventricular end-diastolic maximum diameter(OR=1.927,95%CI:1.594-2.981),maximal interventricular septal thickness(OR=2.085,95%CI:1.426-2.563),and maximal left ventricular wall thickness(OR=2.306,95%CI:1.760-2.805)were independent predictors of MACE(all P<0.05).The threshold effect analysis revealed that the left atrial diameter,left ventricular end-diastolic maximum diameter,maximal interventricular septal thickness,and maximal left ventricular wall thickness were all positively associated with the risk of MACE(all Poverall<0.05).The ROC curve analysis demonstrated that among individual CMR parameters,maximal interventricular septal thickness had the highest predictive performance(AUC=0.86,95%CI:0.74-0.95;sensitivity was 83.67%,specificity was 78.87%).Combined structural parameters(left atrial diameter,left ventricular end-diastolic maximum diameter,maximal interventricular septal thickness,and maximal left ventricular wall thickness)provided superior predictive accuracy(AUC=0.91,95%CI:0.84-0.99;sensitivity was 86.22%,specificity was 76.26%).Conclusions:HCM patients with MACE exhibit distinct clinical and imaging features compared with those without MACE.CMR structural parameters,including left atrial diameter,left ventricular end-diastolic maximum diameter,maximal interventricular septal thickness,and maximal left ventricular wall thickness,are closely related to myocardial fibrosis and strongly associated with MACE risk.A composite index integrating these parameters shows high predictive value for MACE.

Objective:To investigate the inhibitory effect and mechanism of puerarin(Pue)on hydrogen peroxide(H2 O2)induced ferroptosis in the rat Schwann cell derived cell line RSC96.Methods:The RSC96 cells were incuba-ted with H2 O2 to establish a cellular injury model,while a subset of cells were co-incubated with H2 O2 and Pue.The vi-ability of cells was examined using the CCK-8 assay.The intracellular levels of glutathione(GSH),total superoxide dismutase(T-SOD),reactive oxygen species(ROS),malondialdehyde(MDA),and ferrous ions(Fe2+)levels were quantified using commercial kits.Western blot was employed to detect the protein expression level of glutathione peroxi-dase 4(GPX4),cyclooxygenase-2(COX-2),solute carrier family 7 member 11(SLC7A11),nuclear factor erythroid 2-related factor 2(Nrf2),and heme oxygenase-1(HO-1).Immunofluorescence assay was performed to examine the expression and nuclear distribution of Nrf2.Results:Pue pretreatment significantly increased the survival rate of H2 O2-treated RSC96 cells,increased the intracellular content of GSH and T-SOD,and inhibited the concentration of ROS and MDA.It also activated the nuclear translocation of Nrf2 and upregulated GPX4,SLC7A11,HO-1,and Nrf2 proteins in RSC96 cells;This effect was abolished by the Nrf2 inhibitor ML385.Conclusion:Pue treatment alleviated the H2 O2-induced ferroptosis of RSC96 cells via the Nrf2/SLC7A11/GPX4 signaling pathway.

Objective:To investigate the inhibitory effect and mechanism of puerarin(Pue)on hydrogen peroxide(H2 O2)induced ferroptosis in the rat Schwann cell derived cell line RSC96.Methods:The RSC96 cells were incuba-ted with H2 O2 to establish a cellular injury model,while a subset of cells were co-incubated with H2 O2 and Pue.The vi-ability of cells was examined using the CCK-8 assay.The intracellular levels of glutathione(GSH),total superoxide dismutase(T-SOD),reactive oxygen species(ROS),malondialdehyde(MDA),and ferrous ions(Fe2+)levels were quantified using commercial kits.Western blot was employed to detect the protein expression level of glutathione peroxi-dase 4(GPX4),cyclooxygenase-2(COX-2),solute carrier family 7 member 11(SLC7A11),nuclear factor erythroid 2-related factor 2(Nrf2),and heme oxygenase-1(HO-1).Immunofluorescence assay was performed to examine the expression and nuclear distribution of Nrf2.Results:Pue pretreatment significantly increased the survival rate of H2 O2-treated RSC96 cells,increased the intracellular content of GSH and T-SOD,and inhibited the concentration of ROS and MDA.It also activated the nuclear translocation of Nrf2 and upregulated GPX4,SLC7A11,HO-1,and Nrf2 proteins in RSC96 cells;This effect was abolished by the Nrf2 inhibitor ML385.Conclusion:Pue treatment alleviated the H2 O2-induced ferroptosis of RSC96 cells via the Nrf2/SLC7A11/GPX4 signaling pathway.

TAFRO syndrome is a systemic inflammatory disease with unknown etiology.It has low incidence rate and progresses rapidly,which poses a significant challenge for clinicians to make a timely diagnosis and provide reasonable treatment.This article retrospectively analyzed a 65-year-old male patient with iMCD-TAFRO admitted to Minhang Hospital,Fudan University,and visited the Department of Nephrology due to bilateral lower limb edema.The patient exhibited systemic edema,fever,and multiple enlarged lymph nodes.A comprehensive examination showed thrombocytopenia,renal dysfunction,elevated CRP levels,multiple serosal fluid accumulations,and bone marrow reticulin fibrosis.For further diagnosis and treatment,he visited the Hematology Clinic of Zhongshan Hospital,Fudan University.Based on the clinical manifestations,the diagnosis of TAFRO syndrome was considered.After further lymph node pathological consultation,the diagnosis was confirmed as idiopathic multicentric Castleman disease(iMCD)-TAFRO syndrome.Later,the patient was transferred to the hematology department of Minhang Hospital,Fudan University.After 15 days of treatment with methylprednisolone,cyclosporine A,rituximab,and thrombopoietin,there was no significant improvement in the condition.Due to personal reasons,the patient discontinued further treatment and passed away 2 weeks later.

Objective To conduct a bibliometric analysis of relevant literature on liver failure caused by viral hepatitis from the past five years,and to help researchers understand the current status and hotspots in this field,and to provide insights into future research trends.Methods Based on the Science Citation Index Expanded(SCI-Expanded)data from Web of Science Core Collection,visualization analysis and mapping were conducted through VOSviewer and CiteSpace software to generate visual representations of international research collaboration networks,keyword co-occurrence clustering,and keyword bursts.Results From 2019 to 2023,a total of 873 relevant literature were included,with a total citation frequency of 7 364 and an average citation frequency of 8.44.Among them,China had the highest number of publications(458 articles,52.46%)and had the most cooperation with the United States.The research hotspots of viral hepatitis induced liver failure were mainly divided into three categories:basic and clinical research on liver failure caused by non-hepatitis B virus(HBV),the pathogenesis of HBV related liver failure,and treatment and prediction models of liver failure.The keyword time overlay map and burst map showed that the research hotspots had gradually shifted from the prevention and control of new infections to the treatment and prognosis assessment of patients with chronic infection.Conclusion China is a major international research entity in liver failure caused by viral hepatitis and actively participates in international scientific collaborations.The research hotspots on liver failure caused by viral hepatitis have gradually shifted from preventing viral hepatitis infections and expanding treatment options to the treatment of chronic infection patients and prognostic prediction.