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.

Photothermal therapy,as a novel anti-tumor treatment strategy,faces many challenges such as insufficient targeting,limited penetration ability,and inability to achieve long-term inhibition when used alone for anti-tumor treatment.Based on this,in this study,macrophage extracellular vesicles(MEVs)were modified onto the surface of a vector carrying CSF1R-siRNA and photothermal agents to form a multifunctional gene delivery vector MEVs@RNPs.It could induce the macrophages to reprogram from M2 type to M1 type,so as to achieve efficient photothermal and immunotherapy for triple negative breast cancer(TNBC).The basic physicochemical properties of each nanocarrier were characterized using nanoparticle size analyzer,UV-vis spectrometer,fluorescence spectrometer,thermal imaging instrument,etc.TNBC cells 4T1,endothelial cells Bend3,and macrophages 264.7 were used as in vitro experimental subjects for measurement of MEVs@RNPs.The ability to target tumor cells,kill tumor cells,and induce macrophage reprogramming in vitro was investigated.With Balb/c mice as the in vivo research object,a subcutaneous transplant tumor model was established in mice,and the changes in tumor volume and body weight of mice in different treatment groups were measured.In addition,further isolation of mouse blood and tumor tissue was performed,and hematoxylin-eosin(HE)staining,terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)method,and enzyme-linked immunosorbent assay(ELISA)method were used to determine the apoptosis and cytokine secretion of tumor cells for comprehensive evaluation of MEVs@RNPs.The results showed that the MEVs@RNPs could preferentially target tumor cells and induce stronger TNBC cell killing effect under photothermal conditions.Meanwhile,the results of flow cytometry and ELISA analysis showed that the MEVs@RNPs could promote the transformation of macrophages from M2 type to anti-tumor M1 type,significantly enhancing the secretion levels of anti-tumor cytokines tumor necrosis factor-α(TNF-α)and interleukin-12(IL-12).The in vivo anti-tumor treatment effect assessment of the MEVs@RNPs showed that under laser processing conditions,the MEVs@RNPs could significantly induce pathological necrosis and apoptosis of tumor cells,promote macrophage reprogramming and infiltration of CD4+/CD8+T cells into the tumor site,and enhance the secretion levels of TNF-α and IL-12,thereby comprehensively improving the therapeutic effect of TNBC.

Accurate analysis of metal nanoparticles(MNPs)in sediments is a prerequisite for assessing the ecological risks of MNPs in aquatic environmental sediments.In this study,an analytical method for quantitative detection of concentration and particle size distribution of silver-containing nanoparticles(Ag-NPs),zinc-containing nanoparticles(Zn-NPs),cerium-containing nanoparticles(Ce-NPs),and titanium-containing nanoparticles(Ti-NPs)in sediments was established based on ultrasonic extraction-single particle inductively coupled plasma mass spectrometry(SP-ICP-MS).The effects of sample preparation conditions such as extraction solvent type,solid-liquid ratio,ultrasonic time,and settling time on the recovery of MNPs were investigated.The results showed that the extraction of MNPs from sediment by distilled water could effectively eliminate the high background signal interference introduced by the extractant under the conditions of solid-liquid ratio of 1∶400(g∶mL),ultrasonic extraction time of 1 h and settling time of 3 h.The detection limits for particle size of Ag-NPs,Zn-NPs,Ce-NPs and Ti-NPs in sediments were 31,35,26 and 85 nm,respectively,while the detection limits of particle concentrations were 1.21×104,1.90×104,5.26×107 and 1.48×107 particles/g,respectively.The spiking recoveries of Ag-NPs,Zn-NPs,Ce-NPs and Ti-NPs in sediments were 62.1％-108.7％,with relative standard deviations below 10％.This method could rapidly,accurately and simultaneously determine the concentration and particle size distribution of various MNPs in sediments,and was successfully applied to analysis of Ag-NPs,Zn-NPs,Ce-NPs,and Ti-NPs in authentic marine sediments.

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

OBJECTIVE: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351). METHODS: K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot. RESULTS: Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks. CONCLUSION These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals ; COVID-19/genetics* ; Mice ; Brain/metabolism* ; Apoptosis ; Mice, Inbred C57BL ; SARS-CoV-2/physiology* ; Pyroptosis ; Gene Expression Profiling ; Transcriptome ; Male ; Female

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.

[Purpose]To analyze the trends of cancer incidence and mortality in cancer registration areas of Guizhou Province in 2019 and change trend from 2015 to 2019.[Methods]The incidence and mortality data of malignant tumors in 54 cancer registries in Guizhou Province that met the quality standards in 2019 were included.The incidence and mortality rate,age-standardized in-cidence/mortality rates by Chinese standard population(ASIRC,ASMRC)and world standard pop-ulation(ASIRW,ASMRW)as well as cumulative rates(0～74 years old)were calculated for urban and rural areas,as well as for men and women.Joinpoint software was used to calculate the an-nual percentage change(APC)and 95％confidence interval for trend anaylsis.[Results]In 2019,the crude incidence of cancers in Guizhou cancer registration areas was 246.72/105,ASIRC was 189.45/105,ASMRC was 181.85/105 and the cumulative incidence rate(0～74 years old)was 19.43％.Among the rankings of cancer incidence,lung cancer ranked the first,followed by liver cancer,female breast cancer,cervical cancer and colorectal cancer.In the same year,the crude mortality rate of cancers was 158.57/105,the ASMRC was 114.08/105,ASMRW was 111.94/105,with the cumulative mortality rate(0～74 years old)of 11.99％.Among the rankings of cancer mor-tality,lung cancer ranked the first,followed by liver cancer,colorectal cancer,stomach cancer and cervical cancer.In 2019,the incidence and mortality of cancers in the cancer registration areas of Guizhou Province showed an increasing trend with age.From 2015 to 2019,the ASIRC in Guizhou showed a decreased trend(APC=-1.13％)and the ASMRC showed an increasing trend(APC=2.48％),but they were not statistically significant(both P＞0.05).[Conclusion]From 2015 to 2019,the mortality rate of malignant tumors in the cancer registered areas of Guizhou Province increased and was higher than the national average level,and the disease burden was heavy.Lung cancer,malignant tumors of the digestive system,female breast cancer,and cervical cancer were malignant tumors with high incidence and mortality rates,and should be given priority for preven-tion and control.

Objective:To explore the construction method of a resistant multiple myeloma(MM)patient-derived xenotransplantation(PDX)model.Methods:1.0 × 107 MM patient-derived mononuclear cells(MNCs),2.0 × 106 MM.1S cells and 2.0 × 106 NCI-H929 cells were respectively subcutaneously inoculated into NOD.CB17-Prkdcscid Il2rgtml/Bcgen(B-NDG)mice with a volume of 100 p1 per mouse to establish mouse model.The morphologic,phenotypic,proliferative and genetic characteristics of PDX tumor were studied by hematoxylin-eosin staining,immunohistochemical staining(IHC),cell cycle analysis,flow cytometry and fluorescence in situ hybridization(FISH).The sensitivity of PDX tumor to bortezomib and anlotinib monotherapy or in combination was investigated through cell proliferation,apoptosis and in vitro and in vivo experiments.The effects of anlotinib therapy on tumor blood vessel and cell apoptosis were analyzed by IHC,TUNEL staining and confocal fluorescence microscope.Results:MM PDX model was successfully established by subcutaneously inoculating primary MNCs.The morphologic features of tumor cells from MM PDX model were similar to those of mature plasma cells.MM PDX tumor cells positively expressed CD138 and CD38,which presented 1q21 amplification,deletion of Rb1 and IgH rearrangement,and had a lower proliferative activity than MM cell lines.In vitro,PDX,MM.1S and NCI-H929 cells were treated by bortezomib and anlotinib for 24 hours,respectively.Cell viability assay showed that the IC50 value of bortezomib were 5 716.486,1.025 and 2.775 nmol/L,and IC50 value of anlotinib were 5 5107.337,0.706 and 5.13 μmol/L,respectively.Anlotinib treatment increased the apoptosis of MM.1S cells(P＜0.01),but did not affect PDX tumor cells(P＞0.05).In vivo,there was no significant difference in PDX tumor growth between bortezomib monotherapy group and control group(P＞0.05),while both anlotinib monotherapy and anlotinib combined with bortezomib effectively inhibited PDX tumor growth(both P＜0.05).The vascular perfusion and vascular density of PDX tumor were decreased in anlotinib treatment group(both P＜0.01).The apoptotic cells in anlotinib treatment group were increased compared with those in control group(P＜0.05).Conclusion:Bortezomib-resistant MM PDX model can be successfully established by subcutaneous inoculation of MNCs from MM patients in B-NDG mice.This PDX model,which retains the basic biological characteristics of MM cells,can be used to study the novel therapies.

Nuclear factor-erythroid 2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4)signaling pathway plays a key role in the occurrence and development of tumors,and is involved in tumor cell proliferation,apoptosis,ferroptosis,invasion,migration,and drug resistance.Based on the Nrf2/GPX4 signaling pathway,this paper summarizes the research progress of the anti-tumor effects of traditional Chinese medicine.It is found that flavonoids(ginkgetin,luteolin,etc.),terpenoids(atractylenolide,cucurbitacin B,etc.),saponins(polyphyllin Ⅰ,polyphyllin Ⅶ),ester(brusatol)and other effective components,and traditional Chinese medicine extracts(total coumarins in Pileostegia tomentella and total flavonoids of Pterocarya hupehensis Skan),traditional Chinese medicine compounds(Fushao diqin fang,Xiaoai jiedu fang,etc.)can promote ferroptosis in tumor cells by inhibiting Nrf2/GPX4 signaling pathway and the expressions of its upstream and downstream factor proteins,as well as by increasing Fe2+levels and lipid peroxidation,thereby exerting an antitumor effect.