Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral malignancies, with more than 370 000 new cases and approximately 188 000 deaths annually worldwide. In China, there are roughly 65 000 new cases and 35 000 deaths each year, showing a significant upward trend compared with 2015 statistics. Despite continuous advancements in treatment modalities, the 5-year survival rate remains stagnant at 50%-60%, where tumor heterogeneity and therapy resistance persist as fundamental barriers to precision oncology. To address these critical challenges, this study established a standardized bioban-king protocol for OSCC patient-derived organoids (PDOs) (Patent: Method for constructing an oral squamous cell carcinoma organoid bank, ZL202311378598.3). Through groundbreaking optimization of culture media, enzymatic digestion kinetics, and stepwise cryopreservation, we achieved a biobanking success rate exceeding 95% and pioneered synchronous cultivation of matched primary tumors, lymph node metastases, and adjacent normal mucosa from individual patients, preserving spatial heterogeneity and stromal interactions. Leveraging this platform, we developed high-throughput drug screening: Quantified heterogeneity-driven differential chemoresponse using adenosine triphosphate (ATP)-based viability assays; We discovered resistance mechanisms: Identified sialylated cancer IgG (SIA-cIgG)-mediated cis-platin resistance (primary/secondary) through PTPN13 suppression, with anti-SIA-cIgG combination therapy demonstrating synergistic efficacy. Besides, we elucidated metastatic drivers: CRISPR-Cas9-edited organoids revealed WDR54 promoted metastasis via H3K4me3/H4K16ac epigenetic reprogramming, activating epithelial-mesenchymal plasticity (EMP) and inducing partial epithelial-mesenchymal transition (pEMT). This "holographic patient-mirroring" platform provided unprecedented resolution for OSCC precision therapy and had been formally incorporated into the Chinese Stomatological Association Technical Guidelines (Technical guideline for establishing patient-derived oral squamous cell carcinoma organoid banks, CHSA 2024-08). Future integration of immune-competent organoids, 3D-bioprinted vasculature, and multi-omics-AI systems will accelerate personalized oncology. These innovations will accelerate clinical translation of personalized therapeutic regimens, ultimately bridging the gap between bench research and bedside application.
Humans ; Organoids/pathology* ; Mouth Neoplasms/genetics* ; Carcinoma, Squamous Cell/pathology* ; Tissue Banks ; Biological Specimen Banks

Objective To analyze the interactions between different structural types of volatile oil compo-nents(VOCs)and skin lipid molecules,and investigate the mechanism of volatile oil in Chi-nese materia medica(VOCMM)as penetration enhancers. Methods In this study,210 different structural types of VOCs were selected from the VOCMM penetration enhancer database,and the molecular docking experiments were conducted with three main lipid molecules of skin:ceramide 2(CER2),cholesterol(CHL),and free fatty acid(FFA).Each VOC was docked individually with each lipid molecule.Cluster analysis was used to explore the relationship between the binding energy of VOCs and their molecular struc-tures.Nine specific pathogen-free(SPF)Sprague Dawley(SD)rats were randomly divided in-to Control,Nootkatone,and 3-Butylidenephthalide groups for in vitro percutaneous experi-ments,with three rats in each group.The donor pool solutions were 3%gastrodin,3%gas-trodin+3%nootkatone,and 3%gastrodin+3%3-butylidenephthalide,respectively.The pen-etration enhancing effects of VOCs with higher binding energy were evaluated by comparing the 12-hour cumulative percutaneous absorption of gastrodin(Q12,μg/cm2). Results(i)Most of the VOCs were non-hydrogen bonded to the hydrophobic parts of CHL and FFA,and hydrogen bonded to the head group of CER2.Among them,sesquiterpene ox-ides showed the most pronounced binding affinity to CER2.The VOCs with 2-4 rings(in-cluding carbon rings,benzene rings,and heterocycles)demonstrated stronger binding affini-ty for three skin lipid molecules compared with the VOCs without intramolecular rings(P<0.01).(ii)According to the cluster analysis,most of the VOCs that bond well to CER2 had 2-3 intramolecular rings.The non-oxygenated VOCs were bonded to CER2 in a hydrophobic manner.The oxygenated VOCs were mostly bonded to CER2 by hydrogen bonding.(iii)The results of Franz diffusion cell experiment showed that the Q12 of Control group was 260.60±25.09 μg/cm2,and the transdermal absorption of gastrodin was significantly increased in Nootkatone group(Q12=5 503.00±1 080.00 μg/cm2,P<0.01).The transdermal absorption of gastrodin was also increased in 3-Butylidenephthalide group(Q12=495.40±56.98 μg/cm2,P>0.05).(iv)The type of oxygen-containing functional groups in VOCs was also an influencing factor of binding affinity to CER2. Conclusion The interactions between different types of VOCs with different structures in the VOCMM and three skin lipid molecules in the stratum corneum were investigated at the molecular level in this paper.This research provided theoretical guidance and data support for the screening of volatile oil-based penetration enhancers,and a simple and rapid method for studying the penetration-enhancing mechanism of volatile oils.

Subthreshold depression belongs to the category of psychological sub-health.Because it does not meet the diagnostic criteria of depression,it may cause misdiagnosis,missed diagnosis,excessive medical treatment,violation of patient autonomy,poor effect or unclear adverse reactions.The ethical problems in clin-ical diagnosis and treatment are worthy of attention.This article aimed to explore the ethical issues that may exist in the clinical diagnosis and treatment of subthreshold depression,a sub-depression state,and propose so-lutions.

OBJECTIVE: To propose a diffusion tensor field estimation network based on 3D U-Net and diffusion tensor imaging (DTI) model constraint (3D DTI-Unet) to accurately estimate DTI quantification parameters from a small number of diffusion-weighted (DW) images with a low signal-to-noise ratio. METHODS: The input of 3D DTI-Unet was noisy diffusion magnetic resonance imaging (dMRI) data containing one non-DW image and 6 DW images with different diffusion coding directions. The noise-reduced non-DW image and accurate diffusion tensor field were predicted through 3D U-Net. The dMRI data were reconstructed using the DTI model and compared with the true value of dMRI data to optimize the network and ensure the consistency of the dMRI data with the physical model of the diffusion tensor field. We compared 3D DTI-Unet with two DW image denoising algorithms (MP-PCA and GL-HOSVD) to verify the effect of the proposed method. RESULTS: The proposed method was better than MP-PCA and GL-HOSVD in terms of quantitative results and visual evaluation of DW images, diffusion tensor field and DTI quantification parameters. CONCLUSION The proposed method can obtain accurate DTI quantification parameters from one non-DW image and 6 DW images to reduce image acquisition time and improve the reliability of quantitative diagnosis.
Diffusion Tensor Imaging ; Reproducibility of Results ; Diffusion Magnetic Resonance Imaging ; Algorithms ; Signal-To-Noise Ratio

Objective : To study the effect of lipopolysaccharide ( LPS) -induced immune system activation on syn- aptic structure and DISC1. Methods : 40 rats were divided into 4 groups，which were PBS group，PBS + MK-801 group，LPS group and LPS + MK-801 group．The rats in LPS group and LPS + MK-801 group were administrated with LPS solution (0. 2 mg / kg，i．p．BIW) for 6 times in total， the rats in PBS group and PBS + MK801 group were administrated with PBS．At the third time when the rats were administrated with LPS solution，the rats in PBS + MK-801 group and LPS + MK-801 group were administrated with MK-801 solution (0. 5 mg / kg，i．p．BIW) for a total of 4 times，the rats in PBS group and LPS group were adminis- trated with saline．The head shaking and the open field tests were then evaluated in the rats．Immediately，the rats were sacrificed，and their brain were saved for testing. RT-qPCR , Golgi staining，immunohistochemistry and ELISA kits were used to detect DISC1 gene expression，dendritic spine status，microglia activation and inflammatory cytokine content in cortex，respectively. gene expression in the cortex of rats with schizophrenia． Results : Compared with the PBS group，the expression of DISC1 gene of the rats in the PBS + MK-801 group increased (P ＜0. 01) ，the score of head shaking increased (P ＜0. 01) ，and the distance of the open field increased (P ＜0. 000 1) ; As well as the LPS + MK-801 group，compared with the LPS group，the expression of DISC1 gene increased (P＜0. 000 1) ，the head shaking score and the distance of the open field increased (P＜0. 000 1) . In addition，compared with the PBS + MK-801 group，the expression of DISC1 gene， the shaking head score and the open field distance of the LPS + MK-801 group further improved (P ＜0. 000 1) . Furthermore，compared with PBS group and PBS + MK-801 group，the content of iba1 in the cortex of LPS group and LPS + MK-801 group significantly increased (P ＜0. 05 ) ，the content of inflammatory cytokines significantly increased (P＜0. 05) ，and the length and density of dendritic spines significantly decreased (P＜0. 05) ． Conclusion The activation of the immune system induced by LPS can contribute to the susceptibility of schizophrenia model， and the possible mechanism is that it cooperates with MK-801 to increase the expression of DISC1 gene，which ulti- mately leads to abnormal mental behavior in rats.

Objective To investigate the association between single nucleotide polymorphisms(SNPs)of YTHDF1 rs6011668,HNRNPA2B1 rs2070601 and rs76558212 with the risk of gastric cancer.Methods A total of 457 cases with gastric cancer and 525 healthy controls were collected.The candidate SNPs were genotyped using Hi-SNP genotyping methods by multiplex rounds of PCR and high-throughput sequencing;the association between the three SNPs with the risk of gastric cancer was analyzed by test and Logistic regression.Multifactorial logistic regression and Risk Score(RS)model was used to analyze the influence of environmental and genetic factors on the risk of gastric cancer.Results YTHDF1rs6011668 TT genotype carriers had 3.075 times higher risk of gastric cancer than CC genotype carriers(95%CI:1.128～8.382,P = 0.028),and 2.961 times higher risk than CC/TC genotypes carriers(95%CI:1.091～8.033,P = 0.033).Subgroups-analysis revealed that TT genotype mainly increased the risk of gastric cancer in non-tea drinkers,pickled food eaters and fried food eaters(P<0.05).In addition,TT genotype carriers had the increased risk of gastric cancer infiltration,lymph node metastasis,distal metastasis and intermediate to advanced stages(P<0.05).The RS of the case and control groups were calculated by combining environmental and genetic factors.The higher the RS score,the higher the risk of gastric cancer was found in the RS quartile groups.Compared with the RS

For diabetes patients, especially elderly diabetes patients, insulin is widely used as an important treatment to control hyperglycemia.However, since a high percentage of elderly diabetes patients use high doses of insulin, it is common to incur issues such as increased insulin resistance and inappropriate treatment.Exogenous insulin-induced autoantibody production is associated with severe insulin resistance and refractory hyperglycemia and hypoglycemia and is referred to as exogenous insulin antibody syndrome.With hypoglycemia, high insulin levels may be inconsistent with C-peptide levels.Increasing the dose of insulin to control blood glucose may be counterproductive.It is necessary to quickly and accurately make a diagnosis and make personalized adjustments to the glucose-lowering regimen to avoid serious consequences.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the fourth-leading cause of cancer-related deaths worldwide. HCC is refractory to many standard cancer treatments and the prognosis is often poor, highlighting a pressing need to identify biomarkers of aggressiveness and potential targets for future treatments. Kinesin family member 2C (KIF2C) is reported to be highly expressed in several human tumors. Nevertheless, the molecular mechanisms underlying the role of KIF2C in tumor development and progression have not been investigated. In this study, we found that KIF2C expression was significantly upregulated in HCC, and that KIF2C up-regulation was associated with a poor prognosis. Utilizing both gain and loss of function assays, we showed that KIF2C promoted HCC cell proliferation, migration, invasion, and metastasis both in vitro and in vivo. Mechanistically, we identified TBC1D7 as a binding partner of KIF2C, and this interaction disrupts the formation of the TSC complex, resulting in the enhancement of mammalian target of rapamycin complex1 (mTORC1) signal transduction. Additionally, we found that KIF2C is a direct target of the Wnt/β-catenin pathway, and acts as a key factor in mediating the crosstalk between Wnt/β-catenin and mTORC1 signaling. Thus, the results of our study establish a link between Wnt/β-catenin and mTORC1 signaling, which highlights the potential of KIF2C as a therapeutic target for the treatment of HCC.
Adult ; Aged ; Animals ; Carcinoma, Hepatocellular/pathology* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition/genetics* ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism* ; Kinesins/metabolism* ; Liver Neoplasms/pathology* ; Male ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Neoplasm Staging ; Prognosis ; Protein Binding ; RNA, Small Interfering/metabolism* ; Survival Analysis ; Tumor Burden ; Wnt Signaling Pathway ; Xenograft Model Antitumor Assays ; beta Catenin/metabolism*

Nuclear bodies are membrane-free nuclear substructures that are localized in the mammalian nuclear matrix region. They are multiprotein complexes that recruit other proteins to participate in various cellular activities, such as transcription, RNA splicing, epigenetic regulation, tumorigenesis and antiviral defense. It is of great significance to clarify the functions and regulatory mechanisms of nuclear bodies to probe related diseases and virus-host interactions. This review takes several nuclear bodies associated proteins as examples, summarizes the formation process, structure and functions of nuclear bodies, and focuses on their important roles in antiviral infection. It is expected to provide new insight into host antiviral mechanisms.
Animals ; Cell Nucleus ; Epigenesis, Genetic ; Intranuclear Inclusion Bodies/metabolism* ; Nuclear Proteins/metabolism*

Blepharokeratoconjunctivitis (BKC) is a chronic inflammatory disorder and can be defined as lid margin blepharitis accompanied by conjunctivitis and keratopathy.Typical clinical characteristics of BKC consisted of conjunctival hyperemia,papillary hyperplasia follicles,punctate keratitis,marginal keratitis,corneal punctuate epithelial erosion,corneal ulcer,corneal scar and vascularization,corneal perforation.The clinical symptoms and signs of BKC are complicated,which can lead to misdiagnose.The physiotherapy of BKC includes eyelid hygiene,meibomian glands massage and warm compresses;the drug treatment of BKC includes artificial tear,topical antibiotics,corticosteroids,nonsteroidal anti-inflammatory drugs (NSAIDs),immunosuppressants and so on.Corneal transplantation is required for the severe BKC patients.The etiology,pathogenesis,diagnosis and management of BKC was reviewed in this artcle.