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 squa-mous cell carcinoma organoid bank,ZL202311378598.3).Through groundbreaking optimization of cul-ture media,enzymatic digestion kinetics,and stepwise cryopreservation,we achieved a biobanking suc-cess 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 as-says;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 transi-tion(pEMT).This"holographic patient-mirroring"platform provided unprecedented resolution for OSCC precision therapy and had been formally incorporated into the Chinese Stomatological Association Techni-cal Guidelines(Technical guideline for establishing patient-derived oral squamous cell carcinoma or-ganoid banks,CHSA 2024-08).Future integration of immune-competent organoids,3D-bioprinted vas-culature,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.

Corneal neovascularization(CNV)is a pathological condition characterized by the invasion of new blood vessels into the normally avascular corneal area from the corneal periphery,leading to severe vision loss and potentially blindness.Currently,surgical,physical,and pharmacological therapies are the main clinical approaches for treating CNV.Surgical treatment aims to remove abnormal vascular tissue or perform corneal trans-plantation to inhibit angiogenesis;however,it carries a risk of postoperative rejection.Physical therapy involves the direct application of non-invasive modalities,such as laser treatment,to the neovascularized area to suppress vascular growth.Nevertheless,this approach may cause damage to surrounding healthy tissues.Pharmacotherapy has recently become a research hotspot in CNV treatment due to its convenient administration.Clinically,the drugs used for CNV treatment mainly include anti-inflammatory agents,anti-VEGF drugs,and immunosuppressants,which inhibit CNV progression by targeting angiogenesis-related signaling pathways.However,these drugs often lead to drug resistance and toxic side effects.Therefore,there is an urgent need to develop more effective and safer therapeutic agents for CNV.This article reviews the current clinical treatment status of CNV and highlights recent advances in the use of small molecule extracts from traditional Chinese medicine for CNV therapy,aiming to provide potential candidate drugs and a scientific theoretical basis for clinical management of CNV.

Objective:To explore the application value of deep learning reconstruction(DLR)of magnetic resonance(MR)on the image quality and lesion diagnostic efficacy of three-dimensional liver acceleration volume acquisition(3D-LAVA)sequences.Methods:A retrospective analysis was conducted on the image data of magnetic resonance imaging(MRI)of 45 patients who underwent MR contrast-enhanced examinations on abdomen at West China Hospital of Sichuan University from June 2023 to September 2023.For the venous phase of the LAVA sequence,conventional reconstruction and DLR were performed respectively to obtain conventional LAVA images and DLR-LAVA images at the venous phase.Two radiologists conducted subjective evaluation for the overall image quality,image clarity,artifacts,and diagnostic confidence of the two groups of images by using a 5-point scale.And then,the signal-to-noise ratio(SNR)of the images of liver,spleen,and lesion,as well as the contrast-to-noise ratio(CNR)of the liver,spleen to fat,muscle,and lesions were objectively evaluated.The two radiologists measured respectively the maximum and minimum diameters of the largest layer of the largest lesion,and compared the diagnostic efficacy of conventional LAVA and DLR-LAVA for lesions.The diagnostic efficacies of conventional LAVA and DLR-LAVA were respectively assessed by using the receiver operating characteristic(ROC)curve.Results:The consistency of the two radiologists'subjective evaluations for the image quality of the conventional LAVA and DLR-LAVA sequences was moderate and above moderate,with Kappa values ranging from 0.553 to 0.902,and P<0.001.Both radiologists found that the subjective image quality,image clarity,artifacts,and diagnostic confidence of the DLR-LAVA sequence were higher than those of the conventional LAVA sequence(Z Physician 1=4.24,5.49,3.50,4.47,Z Physician 2=4.15,3.12,3.77,4.26,P<0.05).The SNR values of the liver,spleen,and lesions in the DLR-LAVA images were all higher than those in the conventional LAVA sequence(t=-20.45,-18.58,-5.51,P<0.001).The CNR values between liver and fat,between liver and muscle,between liver and spleen,between spleen and fat,between spleen and muscle,and between lesion and liver in DLR-LAVA sequence were higher than those in the conventional LAVA sequence(t=-20.49,-19.94,-18.05,-16.74,P<0.001).There were no statistically significant differences in the measured values of the maximum and minimum diameters of the largest lesions between the conventional LAVA and DLR-LAVA sequences(P>0.05).The area under curve(AUC)values of physician 1 who used respectively the conventional LAVA and DLR-LAVA sequences were 0.897 and 0.916 in diagnosing lesions,while those of physician 2 were respectively 0.851 and 0.890.Conclusion:DLR can improve the image quality of the LAVA sequence for liver,and has a higher diagnostic value for lesions.

Objective:To explore the application value of deep learning reconstruction(DLR)of magnetic resonance(MR)on the image quality and lesion diagnostic efficacy of three-dimensional liver acceleration volume acquisition(3D-LAVA)sequences.Methods:A retrospective analysis was conducted on the image data of magnetic resonance imaging(MRI)of 45 patients who underwent MR contrast-enhanced examinations on abdomen at West China Hospital of Sichuan University from June 2023 to September 2023.For the venous phase of the LAVA sequence,conventional reconstruction and DLR were performed respectively to obtain conventional LAVA images and DLR-LAVA images at the venous phase.Two radiologists conducted subjective evaluation for the overall image quality,image clarity,artifacts,and diagnostic confidence of the two groups of images by using a 5-point scale.And then,the signal-to-noise ratio(SNR)of the images of liver,spleen,and lesion,as well as the contrast-to-noise ratio(CNR)of the liver,spleen to fat,muscle,and lesions were objectively evaluated.The two radiologists measured respectively the maximum and minimum diameters of the largest layer of the largest lesion,and compared the diagnostic efficacy of conventional LAVA and DLR-LAVA for lesions.The diagnostic efficacies of conventional LAVA and DLR-LAVA were respectively assessed by using the receiver operating characteristic(ROC)curve.Results:The consistency of the two radiologists'subjective evaluations for the image quality of the conventional LAVA and DLR-LAVA sequences was moderate and above moderate,with Kappa values ranging from 0.553 to 0.902,and P<0.001.Both radiologists found that the subjective image quality,image clarity,artifacts,and diagnostic confidence of the DLR-LAVA sequence were higher than those of the conventional LAVA sequence(Z Physician 1=4.24,5.49,3.50,4.47,Z Physician 2=4.15,3.12,3.77,4.26,P<0.05).The SNR values of the liver,spleen,and lesions in the DLR-LAVA images were all higher than those in the conventional LAVA sequence(t=-20.45,-18.58,-5.51,P<0.001).The CNR values between liver and fat,between liver and muscle,between liver and spleen,between spleen and fat,between spleen and muscle,and between lesion and liver in DLR-LAVA sequence were higher than those in the conventional LAVA sequence(t=-20.49,-19.94,-18.05,-16.74,P<0.001).There were no statistically significant differences in the measured values of the maximum and minimum diameters of the largest lesions between the conventional LAVA and DLR-LAVA sequences(P>0.05).The area under curve(AUC)values of physician 1 who used respectively the conventional LAVA and DLR-LAVA sequences were 0.897 and 0.916 in diagnosing lesions,while those of physician 2 were respectively 0.851 and 0.890.Conclusion:DLR can improve the image quality of the LAVA sequence for liver,and has a higher diagnostic value for lesions.

Objective:To investigate the influence of prealbumin on cerebral infarction severity, hemorrhage transformation and 1-year prognosis.Methods:A retrospective study was conducted to select 752 patients with cerebral infarction who were treated in Beijing Tiantan Hospital,Capital Medical University from December 2018 to December 2019 as the study objects. Personal information and laboratory indicators of the patients were collected including prealbumin, hemoglobin, white blood cell count, etc.Patients were divided into group B1 (<238 mg/L) and group B2 (≥238 mg/L) based on median prealbumin. By inquiry patient's case, NIHSS score (<16 was classified as mild, ≥16 as moderate and severe)and cerebral infarction volume (<20 cm 3 as small infarct, >20 cm 3 as large infarct) were recorded to evaluate the severity of the disease, and whether hemorrhage transformation occurred during hospitalization was recorded. Patients were followed up 1 year after discharge, and prognostic information of patients was recorded, including neurological function recovery (mRS score <3 was classified as good recovery, ≥3 as poor recovery),all-cause case fatality rate, and recurrence of cardio-cerebrovascular events. Normally distributed measurement data were expressed as xˉ±s, non-normally distributed measurement data were expressed as median and quartiles[ M( Q1, Q3)], categorical variable were expressed as ratio and percent(%). Comparison between groups of measurement data were performed by independent sample t test and Mann-Whitney U test. Chi-square test were used on comparison between groups of categorical variable. Single-factor comparison, Spearman correlation analysis and multiple Logistic regression were used to analyze the correlation between prealbumin and other laboratory indicators, cerebral infarction severity, hemorrhage transformation and 1-year prognosis, respectively. Results:The NIHSS score and infarct volume of patients in group B1 were 5(2,10) and 3.18(0.72,18.00) cm 3, and those in group B2 were 3(2,7) and 2.0(0.5,10.0) cm 3, respectively, which were higher in group B1 than in group B2, the differences were statistically significant ( Z=3.85, P<0.001, Z=2.81, P=0.005). The proportion of mRS Score ≥3 in group B1 was 28.8%(107/371), and the all-cause case fatality rate was 7.5%(28/371), both higher than 20.5%(78/381) and 3.1%(12/381) in group B2, with statistical significance ( χ2=7.10, P=0.008, χ2=7.22, P=0.007). Hemorrhage transformation and recurrence of cardio-cerebrovascular events were 13.5%(50/371) and 11.6%(43/371) in group B1 and 9.2% (35/381) and 8.7%(33/381) in group B2, respectively, with no significant difference between the two groups ( χ2=3.45, P=0.063, χ2=1.78, P=0.183). Multivariate logistic regression analysis showed that, after adjusted for potential confounding factors, prealbumin was protective factor of NIHSS ( OR and 95% CI: 0.990(0.984-0.997), P=0.035), poor neurological recovery(mRS≥3) ( OR and 95% CI:0.992(0.988-0.997), P<0.001) and all-cause case fatality rate ( OR and 95% CI:0.991(0.983-0.999), while prealbumin had no significant influence on cardiocerebrovascular recurrence events ( OR and 95% CI: 0.999(0.993-1.005), P=0.729). Conclusion:Prealbumin is significantly associated with the severity of cerebral infarction and poor prognosis 1 year after discharge, and low prealbumin was an independent risk factor for NIHSS score(≥16), poor neurological recovery (mRS≥3) and all-cause case fatality rate.

Objectives:To explore the effects of infarct volume, infarct type, inflammation, and coagulation indicators on hemorrhagic transformation in patients with acute cerebral infarction.Methods:711 patients with cerebral infarction admitted to Beijing Tiantan Hospital were retrospectively included as the study objects from December 2018 to December 2019 [535 males and 176 females, age 22-95 years, mean age (59.6±12.1) years]. Clinical data, laboratory indicators such as inflammation and coagulation function of patients were collected, and information such as location, volume and type of infarction were recorded. The patients were divided into hemorrhage transformation group and non-hemorrhage transformation group according to whether hemorrhage transformation occurred during hospitalization. Normally distributed measurement data were expressed as xˉ± s, non-normally distributed measurement data were expressed as median and quartiles [ M( Q1, Q3)], categorical variable were expressed as ratio and percent (%). Comparison between groups of measurement data were performed by independent sample t test and Mann-Whitney U test. χ2 test were used on comparison between groups of categorical variable. Univariate comparison and multivariate Logistic regression were used to analyze the correlation between hemorrhage transformation and infarct volume, infarction type and laboratory indicators, respectively, to explore the risk factors of hemorrhage transformation. ROC curve analysis was used to evaluate the diagnostic value of indicators. Results:The rates of coronary heart disease and atrial fibrillation history in the hemorrhage transformation group were 23.5% (20/85) and 22.4% (19/85), respectively, which were significantly higher than those in the non-hemorrhage transformation group (13.9% (87/626) and 5.8% (36/626), respectively), and the difference between the two groups was statistically significant ( χ2=5.43, χ2=28.90, P=0.020, P<0.001, respectively). The NIHSS score [10(4,17) points] and infarct volume [46.50 (14.21,118.42) mL] in the hemorrhage transformation group were significantly higher than those in the non-hemorrhage transformation group [4(2,7) points, 2.00(0.51,8.94) mL]. The difference between the two groups was statistically significant ( Z values were 6.69 and 10.69, respectively, P<0.001). The results of multivariate Logistic regression analysis showed that atrial fibrillation (OR=2.604, 95% CI: 1.186-5.716, P=0.107), infarct volume (OR=1.009, 95% CI: 1.004-1.015, P=0.001), infarct type of Chinese ischemic stroke subclassfication (OR=1.371, 95% CI: 1.085-1.731, P=0.008) and neutrophil/lymphocyte ratio (OR=1.047, 95% CI: 1.006-1.090, P=0.023) were independent risk factors for hemorrhage transformation. ROC curve analysis showed that the area under curve (AUC) of infarct volume and neutrophil/lymphocyte ratio were 0.861 (0.821-0.901) and 0.684 (0.626-0.741), respectively, which were effective in predicting hemorrhage transformation after cerebral infarction. The prediction of infarct volume was more efficient. Conclusion:History of atrial fibrillation, classification of cardioembolic stroke, infarct volume, and neutrophil/lymphocyte ratio are all risk factors for hemorrhagic transformation after acute cerebral infarction.

Objective:To optimize the image quality of PET/CT following 90Y-selective internal radiation therapy ( 90Y-SIRT) using block-sequential regularized expectation maximization (BSREM) reconstruction algorithm, and to evaluate its impact of different β values on image quality and quantitative analysis. Methods:A retrospective study was conducted on 8 male patients with hepatic tumors (age: 62(52, 71) years) treated at Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine Tsinghua University, between June 2024 and January 2025. All patients were treated with 90Y resin microspheres (2.6(0.9, 3.6)GBq) and underwent post-treatment 90Y PET/CT liver imaging. Imaging data were reconstructed using BSREM with different noise penalty weighting factors ( β values: 0, 300, 1000, 1500, 2500, 3500, 4000, 6000, 8000, 10000). Visual assessment was independently performed by two nuclear medicine physicians, using a 4-point scale (1=worst, 4=best). The mean score was considered as the final score. The consistency of the 2 reviewers was calculated and analyzed by Kappa test. Visual scores of different β value groups were compared by Friedman test. The β value demonstrating highest mean score and optimal consistency was selected as the optimal. Quantitative analysis was performed using MIM software to calculate the maximum absorbed dose ( Dmax) and the mean absorbed dose ( Dmean) for tumor, normal liver, and whole liver regions, and the CV was used to evaluate the impact of β values. Results:The visual assessment consistency of reviewers in 3 β value groups (0, 3500, 6000) were the highest (7/8) (all kappa=0.88, all P<0.05). Visual scores of the 10 β value groups were significantly different ( χ2=28.74, P<0.001), and the visual scores of 2 β value groups (3500, 4000) were the highest, both of which were 4.0(4.0, 4.0). Overall, visual assessment identified β=3500 as the optimal. Quantitative analysis revealed that, (1) Dmax in all regions (tumor, normal liver, whole liver) decreased with the increasing β values, stabilizing when β>1000 ( CV 56%-67%); (2) Dmean remained stable across different β values ( CV 0.04%-5.00%). Conclusions:In BSREM reconstruction, β=3500 is the optimal parameter for improving 90Y-PET image quality. β values significantly affect Dmax (stabilizing at β > 1000), but have no significant impact on Dmean, suggesting that reconstruction parameters primarily influence dose distribution morphology rather than average dose assessments.

The peripheral blood of healthy or ketosis dairy cows was collected,and CD4+T cells were isolated.The expressions of lipid synthesis related proteins fatty acid synthase(FASN),acetyl coenzyme A carboxylase 1(ACC1),cluster of differentiation 36(CD36)and store-operated calcium entry(SOCE)related proteins ORAIl,ORAI2,ORAI3,STIM1,STIM2 were detected by Western blot.IL-17 cells were detected by flow cytometry.CD4+T cells were isolated from the spleen of 1-day-old calves and cultured in vitro.Cells were treated and divided into control(Ctrl)group,si-lenced CD36(siCD36)group,stearic acid(SA)group,and SA+siCD36 group.Cells in the Ctrl and SA groups were transfected with 75 pmol/L negative control siRNA for 48 h,and then stimulated with 200 μmol/L SA for 24 h;Cells in the siCD36 group and SA+siCD36 group were transfected with 75 pmol/L CD36 siRNA for 48 h,and then stimulated with 200 μmol/L SA for 24 h in the SA+siCD36 group.The protein expression of FASN,CD36,ACC1,ORAI1,ORAI2,ORAI3,STIM1 and STIM2 was detected by Western blot,and IL-17 cells were detected by flow cytometry.The results showed that the expression of IL-17 in peripheral blood CD4+T cells of ketosis dairy cows was significantly increased compared to that of healthy cows(P＜0.01).Additionally,the protein level of FASN,CD36,STIM1(P＜0.05),and ACC1,ORAI2,ORAI3,STIM2(P＜0.01)were up-regulated.Compared with the Ctrl group,the protein expression levels of CD36,ACC1 and ORAI3(P＜0.05)were up-regulated in the SA group,as well as the protein expression of FASN and STIM1(P＜0.01).Additionally,the expression of IL-17 was significantly increased(P＜0.05).Compared with the SA group,there was a decrease in the protein expression of STIM1,ORAI1(P＜0.05)and CD36,ACC1,FASN,ORAI2(P＜0.01)in the siCD36+SA group,as well as IL-17(P＜0.05).These results suggest that SA can promote the expression of IL-17 in CD4+T cells in ketosis cows by regulating fatty acid synthesis and activating SOCE channels through CD36.

Objective This study aimed to investigate the relationship between multiple inflammatory markers and poor outcome in patients with intracerebral hemorrhage,and to compare their predictive abilities.Methods We retrospectively analyzed the patients with intracerebral hemorrhage admitted to the Department of Neurology of the First Affiliated Hospital of Nanchang University from January 1,2015 to March 31,2023.According to the Modified Rankin Scale at 90 days after onset,the patients were divided into good outcome(mRS≤2 points)and poor outcome(mRS score≥3 points).Clinical information,laboratory examinations and follow-up data were compared between the two groups.Inflammatory markers include neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),monocyte to high-density lipoprotein ratio(MHR),systemic inflammatory response index(SIRI),systemic immune-inflammation index(SII),white blood cell count to mean platelet volume ratio(WMR),lymphocyte to monocyte ratio(LMR),and systemic coagulation-inflammation index(SCI).Univariate and multivariate logistic regression analysis were used to analyze the predictors of poor prognosis after intracerebral hemorrhage,and receiver operating characteristic curve(ROC)was constructed to compare their predictive ability.Results A total of 510 patients with intracerebral hemorrhage were included.Of those,297(58.2%)had good outcome,and 213(41.8%)had poor outcome.Comparison of baseline characteristics demonstrated that patients with poor prognosis had higher levels of white blood cells,neutrophils,high-density lipoprotein,fibrinogen,NLR,PLR,SIRI,SII,WMR at admission,larger baseline hematoma volume and baseline perihematomal edema volume,a higher proportion of lobar hemorrhage,older age,and lower levels of platelets,lymphocytes,LMR,and SCI(P<0.05).Multivariate regression analysis showed that NLR(OR:1.081,95%CI:1.032～1.1131,P=0.001),SIRI(OR:1.089,95%CI:1.014～1.169,P=0.019),SII(OR:1.000,95%CI:1.000～1.001,P=0.011),WMR(OR:2.627,95%CI:1.267～5.445,P=0.009)were independently associated with poor prognosis in patients with ICH.In ROC analysis,the area under the curve of NLR(0.729,95%CI:0.685～0.774)was higher than SIRI(0.692,95%CI:0.645～0.738),SII(0.688,95%CI:0.641～0.735)and WMR(0.65,95%CI:0.602～0.698)for predicting poor outcomes.Conclusion NLR,SIRI,SII and WMR at admission are independently associated with poor outcomes in patients with intracerebral hemorrhage,and NLR has the strongest predictive ability.

To understand the pathogenicity and drug resistance of swine-derived E.coli and its bio-logical characteristics in some areas in Hebei,E.coli was isolated and identified from diarrheal fe-ces of piglets collected from swine farms,and the isolated strains were subjected to drug sensitivity test,detection of the ability to form biofilm,pathogenicity test,virulence gene test,drug resistance gene test,and identification of phylogenetic subgroups.The results showed that a total of 35 patho-genic E.coli strains were isolated from the feces of diarrheic piglets,and most of the isolates were multidrug-resistant,and were resistant to at least three antibiotics,including amoxicillin(88.57％),ampicillin(88.57％),doxycycline(88.75％),sulfisoxazole(77.17％),lincomycin(100％),and chloramphenicol(100％);the isolates were severely resistant.The isolates all carried virulence genes,with a total of five virulence genes detected,namely,EAST1(77.14％),eaeA(17.14％),stx2e(5.71％),LT(2.86％),and STb(2.86％),and the isolates also carried multi-re-sistance genes,with a total of five virulence genes detected,namely,bla TEM-1(65.71％),bla CTX-M(20.00％),tetA(82.86％),tetB(14.29％),aadA2(17.14％),aac(6')-Ib(14.29％),qnrS(17.14％),sul 1(40.00％),sul2(34.29％),and floR(60.00％);the phylogenetic grouping showed that the isolates had a high proportion of group B1 and group A;and all 35 isolates showed differ-ent pathogenicity after infection of mice.This study provides a reference for the selection of effec-tive therapeutic drugs and the development of prevention and control programs for swine-origin pathogenic E.coli in Hebei Province.