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 investigate the interventional effect of Rhizoma Corydalis on mice with ulcerative colitis(UC)induced by dextran sulfate sodium(DSS),as well as the potential mechanism of Rhizoma Corydalis in the treatment of UC based on metabolomics and inflammation biomarkers.Methods:A mouse model of UC was established,and then the mice were divided into model group,high-dose group(1.517 g/kg crude drug),middle-dose group(0.986 g/kg crude drug),low-dose group(0.455 g/kg crude drug),and positive drug group(5-aminosalicylic acid at a dose of 718.8 mg/kg),while the mice without modeling were selected as normal group(0.9%NaCl by gavage).The mice in each group were administered for 7 consecutive days,and phenotypic parameters were dynamically moni-tored,such as body weight change,disease activity index(DAI),mean daily food intake,and daily water intake.The mice were sacri-ficed after 7 days to collect serum and colon tissue samples;ELISA was used to measure the serum levels of the proinflammatory fac-tors interleukin-6(IL-6),interleukin-17A(IL-17A),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α),and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was used to perform the non-targeted metabolomics analysis and compare the differences in se-rum metabolite profiles between groups.The mice were selected for modeling and validation with the same method,and glutathione(GSH)was selected as the positive drug.Colon length and mucosal damage were assessed,and quantitative real-time PCR was used to measure the relative mRNA expression levels of the key genes in the glutathione synthesis pathway(γ-glutamylcysteine synthetase[γ-GCS]and oxidative stress regulators yap1p and skn7)and mito-chondrial GSH transporter protein(Slc25a39)in colonic tissue.Results:Rhizoma Corydalis significantly improved weight loss,DAI,and colon length in a dose-dependent manner in the model animals,and there were reductions in the serum levels of IL-6,CRP,and TNF-α,while it had no significant effect on IL-17A.The metabolomics analysis revealed 21 potential biomarkers associated with amino acid and lipid metabolism,which were significantly regulated by Rhizoma Corydalis.In the verification experiment,both Rhi-zoma Corydalis and GSH exerted a significant protective effect against colonic mucosal damage without affecting colon length.Rhizoma Corydalis upregulated the expression of genes associated with glutathione synthesis,especially γ-GCS,suggesting that Rhizoma Co-rydalis could enhance intestinal antioxidant defenses.Conclusion:Rhizoma Corydalis has a therapeutic potential in a mouse model of DSS-induced UC and can alleviate symptoms,reduce the serum levels of inflammatory markers,and regulate metabolic pathways,and upregulation of the genes associated with glutathione synthesis suggests that the drug can enhance intestinal antioxidant defenses.

Objective To investigate the effects of miR-126 on myocardial remodeling and macrophage polarization after acute myocardial infarction(AMI).Methods(1)Twenty-one rats were divided into a sham operation group and an AMI group.The AMI group was further divided into postoperative days 1,3,5,7,9,and 11 days(AMI-1,AMI-3,AMI-5,AMI-7,AMI-9,AMI-11),with 3 rats in each group,and postoperative day 3 was selected for subsequent study.(2)Thirty rats were randomly divided into three groups:sham operation group,AMI group and miR-126 overexpression group,with 10 rats in each group.RT-qPCR was used to detect the expression levels of miR-126 mRNA.2,3,5-Triphenyltetrazole chloride(TTC)staining was used to detect the infarct size.Myocardial fibrosis was detected by Masson staining.The cross-sectional area of the myocardium was determined by H&E staining.Immunofluorescence staining was used to detect the protein levels of CD86 and CD206 in myocardial tissue.Western blotting was used to detect the protein levels of CD86 and CD206 in myocardial tissue.The levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in serum were detected by ELISA kit.Results Compared with the sham operation group,the expression level of miR-126 mRNA in myocardial tissue of rats in the AMI group was significantly decreased on postoperative day 1(P<0.05),reached the lowest level on postoperative day 3.And then although it rose to a certain extent,it remained lower than that of the sham operation group on postoperative day 11(P<0.05),and postoperative day 3 was selected for further study.Compared with the sham operation group,the expression of miR-126 mRNA in myocardial tissue of the AMI group was decreased(P<0.05),and the myocardial fibrosis,infarct size and myocardial cross-sectional area were increased(P<0.05).The expression of CD86 protein in myocardial tissue was increased and the expression of CD206 protein was decreased(P<0.05).The serum levels of TNF-α,IL-6 and IL-1β were increased(P<0.05).Compared with the AMI group,the rats in the miR-126 overexpression group had a significant increase in the mRNA expression of miR-126 in myocardial tissue(P<0.05),a significant reduction in myocardial fibrosis,infarct size,and myocardial cross-sectional area(P<0.05),a significant reduction in the expression of CD86 protein in myocardial tissue,and a significant increase in the expression of CD206 protein(P<0.05).The serum levels of TNF-α,IL-6 and IL-1β were significantly decreased(P<0.05).Conclusion Over-expression of miR-126 can improve myocardial remodeling and promote M2 macrophage polarization in AMI rats.

Objective:To explore the effects of dual task training assisted by a lower limb rehabilitation robot on lower extremity mobility and the walking ability of stroke survivors.Methods:Sixty-one stroke survivors were randomly divided into a control group and an experimental group with 30 in the control group and 31 in the experimental group. In addition to routine exercise training and physical therapy, both groups were given cognitive-motor dual task training 5 times a week for 3 weeks. But only in the experimental group was the dual task training assisted by a lower limb rehabilitation robot. Both groups′ lower limb motor function, walking ability, cognition, balance and ability in the activities of daily living were evaluated before and after the experiment using the Fugl-Meyer lower extremity assessment (FMA-LE), functional ambulation categories (FAC), the digital span test (DST), the Berg Balance Scale (BBS) and the Modified Barthel Index (MBI). Additionally, 6 survivors of a right hemisphere stroke from the experimental group received cognitive-motor dual task training both with and without the robotic assistance alternately. Near-infrared functional brain imaging was applied before and after the intervention, and the functional network connectivity of the resting brains was analyzed.Results:After the intervention the average FMA-LE, FAC, BBS and MBI scores had improved in both groups, with the improvement in the experimental group significantly better than in the control group on average. In terms of cognition there was no significant difference in the DST forward and backward assessment results between the two groups. The analysis of brain network functional connectivity showed that the intensity of functional connectivity between the left prefrontal cortex (PFC) and the left premotor cortex and supplementary motor cortex (PMC/SMA) increased significantly more, on average, after training assisted by the robot.Conclusion:Dual task training with the assistance of a lower limb rehabilitation robot can effectively improve the lower limb motor function, walking, balance and ability in the activities of daily living of stroke survivors. Enhanced functional connection of the PFC and the PMC/SMA in the healthy hemisphere induced by the robot may be the cause.

Urine is produced from the urinary system, and urinary cell-free DNA (cfDNA) carries genomic DNA directly secreted from urinary system.Urine samples are non-invasive, unlimited in quantity and easy to obtain, making urinary cfDNA a promising biomarker for urologic diseases.This article reviews the progress of clinical application of urinary cfDNA in urologic diseases.

Purpose To analyze the correlation between quantitative parameters of spectral CT and the mutation status of epidermal growth factor receptor(EGFR)and anaplastic lymphoma kinase(ALK)genes in solid lung adenocarcinoma,in order to predict the expression of gene mutation in solid lung adenocarcinoma by combining spectral parameters with clinical indicators.Materials and Methods The imaging and clinical data of 86 patients in the First Affiliated Hospital of Xinxiang Medical College pathologically confirmed with lung adenocarcinoma who underwent energy spectral CT plain and enhanced scans from May 2020 to May 2022 were retrospectively collected.According to the mutation status of EGFR and ALK genes,all patietns were divided into mutation group(43 cases)and wild group(43 cases).The single-energy CT values(including 40 keV,70 keV and 100 keV),slope of energy spectrum curve,effective atomic number during plain scan,iodine concentration in arterial and venous phases,water concentration and iodine concentration in arteries at the same level were obtained,and standardized iodine base value was also calculated.Statistically significant parameters were used to construct the prediction model,and the receiver operating characteristic curve was performed to evaluate the prediction efficiency of the model.Results There were statistically significant differences in gender and smoking status between the EGFR mutation group and the wild-type group(χ2=5.628,P=0.018;χ2=4.214,P=0.040).There were statistically significant differences in plain scan effective atomic number and energy spectrum slope,arterial phase 40 keV,70 keV and 100 keV single-energy CT values,40 keV single-energy CT values in the venous phase,the slope of the arteriovenous dual-phase energy spectrum and the standardized iodine base value between the two groups(t=2.067-4.394,all P<0.05).Logistic regression analysis showed that normalized iodine base value and energy spectrum slope in venous phase were the independent predictors of EGFR gene mutation status.There were no significant differences in quantitative parameters of plain scan and arterial phase energy spectrum CT between the ALK mutant group and the wild-type group(P>0.05).There was statistically significant difference in water base value of venous phase between the two groups(t=2.058,P=0.043).Conclusion The quantitative features of spectral CT may be correlated with the mutation status of EGFR and ALK genes in solid lung adenocarcinoma,and the Logistic regression model based on the combination of quantitative features of spectral CT and clinical features has certain value in predicting EGFR gene mutation.

Objective:To explore the clinical characteristics and prognoses of severe autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A).Methods:A retrospective analysis was performed. The clinical data of 12 patients with severe GFAP-A admitted to Department of Neurology, Guangdong 999 Brain Hospital from January 2018 to June 2023 were collected, including demography, clinical manifestations, MRI features, laboratory examination results (such as antibodies), treatments and prognoses.Results:Among the 12 patients, 9 were male and 3 were female, with an average onset age of (46.58±17.53) years. Primary symptoms included headache, limb weakness, limb numbness, mental disorder, epileptic seizure, and urinary and defecation disorder; 9 patients had fever before onset. With aggravated severe GFAP-A, 12 patients had impaired consciousness, 12 had respiratory failure, 6 had unstable blood pressure and heart rate, and 2 had status epilepticus. Cranial MRI indicated abnormal lesions in all 12 patients, including 10 with brainstem involvement (7 had involved medulla oblongata); 10 showed soft meningeal enhancement. In 8 patients received MRI of the whole spinal cord, 7 had abnormal spinal cord lesions; point-like enhancement of the whole spinal meninges was observed in 6 of the 7 patients. All 12 patients had positive cerebrospinal fluid GFAP-IgG, and 3 patients also had positive serum GFAP-IgG. All patients accepted glucocorticoids and immunoglobulin immunotherapy, and 1 patient was supplemented with mycophenolate mofetil; 8 patients had good prognosis, and 4 patients died. Pulmonary infection, hyponatremia, hypoproteinemia, and deep vein thrombosis were the common complications.Conclusion:Patients with severe GFAP-A mainly manifest as meningoencephalitis and meningoencephalomyelitis, and are likely involved medulla oblongata, enjoying rapid clinical progression; even with early immunotherapy, high mortality rate is still noted.

Malnutrition, as an independent predictor of incidence and mortality in patients with chronic heart failure (CHF), has a serious impact on the treatment effect of patients. Conducting nutritional risk assessment and providing nutritional interventions for CHF patients can effectively improve their quality of life. On the basis of elaborating on the risk factors for malnutrition in CHF patients, this paper reviews the assessment tools for malnutrition in CHF patients, aiming to promote the localization of malnutrition assessment tools and the research and clinical application of malnutrition specific assessment tools, making nutrition assessment a routine part of overall health assessment for CHF patients.

OBJECTIVE: To analyze the clinical characteristics and spectrum of SPTB gene variants among 16 Chinese children with Hereditary spherocytosis (HS) and explore their genotype-phenotype correlation. METHODS: Sixteen children who were diagnosed with HS at the Affiliated Hospital of Capital Institute of Pediatrics from November 2018 to July 2022 were selected as the research subjects. Genetic testing was carried out by whole exome sequencing. Candidate variants were verified by Sanger sequencing and subjected to bioinformatic analysis and prediction of 3D structure of the protein. Correlation between the SPTB genotypes and clinical phenotypes was analyzed using Chi-squared test. RESULTS: The male-to-female ratio of the HS patients was 6 : 10, with the median age being 7-year-and-10-month. Clinical features of the patients have included anemia, reticulocytosis and gradual onset of splenomegaly. Mild, moderate and severe anemia have respectively occurred in 56.25% (9/16), 31.25% (5/16) and 12.50% (2/16) of the patients. SPTB gene variants were detected in all patients, among which 10 were unreported previously and 7 were de novo in origin. Loss of function (LOF) variants accounted for 93.75% (15/16). Only one missense variant was detected. Eleven, 4 and 1 of the variants had occurred in the repeat domain, CH1 domain, and dimerization domain, respectively. There was no significant correlation between the type or domain of the SPTB gene variants with the clinical features such as severity of anemia (x² = 3.345, P > 0.05). All of the variants were predicted to be pathogenic or likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics. CONCLUSION Mild to moderate anemia are predominant clinical features of the HS children harboring a SPTB gene variant, for which LOF variants are the main mutational type. The clinical feature of HS is unaffected by the type of the variants.
Child ; Female ; Humans ; Male ; Computational Biology ; Genetic Testing ; Genomics ; Genotype ; Spherocytosis, Hereditary/genetics* ; East Asian People/genetics* ; Spectrin/genetics*

Astragalosides are the main active constituents of traditional Chinese medicine Huang-Qi, of which cycloastragenol-type glycosides are the most typical and major bioactive compounds. This kind of compounds exhibit various biological functions including cardiovascular protective, neuroprotective, etc. Owing to the limitations of natural sources and the difficulties encountered in chemical synthesis, re-engineering of biosynthetic machinery will offer an alternative and promising approach to producing astragalosides. However, the biosynthetic pathway for astragalosides remains elusive due to their complex structures and numerous reaction types and steps. Herein, guided by transcriptome and phylogenetic analyses, a cycloartenol synthase and four glycosyltransferases catalyzing the committed steps in the biosynthesis of such bioactive astragalosides were functionally characterized from Astragalus membranaceus. AmCAS1, the first reported cycloartenol synthase from Astragalus genus, is capable of catalyzing the formation of cycloartenol; AmUGT15, AmUGT14, AmUGT13, and AmUGT7 are four glycosyltransferases biochemically characterized to catalyze 3-O-xylosylation, 3-O-glucosylation, 25-O-glucosylation/O-xylosylation and 2'-O-glucosylation of cycloastragenol glycosides, respectively. These findings not only clarified the crucial enzymes for the biosynthesis and the molecular basis for the structural diversity of astragalosides in Astragalus plants, also paved the way for further completely deciphering the biosynthetic pathway and constructing an artificial pathway for their efficient production.