Abstract:Objective To investigate the epidemiological characteristics of cervical cancer and precancerous lesions among women in Baoding area,and to explore the clinical significance of combined ThinPrep cytologic test(TCT)and human papillomavirus(HPV)genotyping in screening for cervical cancer and precancerous lesions.Methods A total of 9,867 women who were screened for cervical lesions at the Gynecology Clinic of Maternal and Child Health Hospital of Baoding City were selected.All patients underwent both TCT and HPV genotyping testing.The patients with positive results of TCT and/or HPV genotyping were subject to colposcopy and histopathological examination,with histopathological results as the diagnostic criteria.The diagnostic values of TCT alone,HPV genotyping alone,and their combination in screening for cervical cancer and precancerous lesions were compared and analyzed.Results Among the 9,867 subjects,the number of positive cases for TCT and HPV genotyping was 741(7.5%)and 1,771(17.9%),respectively.A total of 717 cases with positive TCT and/or HPV genotyping underwent colposcopy and histopathological examination.among whom 602 cases(83.96%)were histopathologically positive.Specifically,there were 455 cases(63.46%)of low-grade squamous intraepithelial lesion(LSIL/CINⅠ),130 cases(18.13%)of high-grade squamous intraepithelial lesion(HSIL/CIN Ⅱ-Ⅲ),13 cases(1.81%)of cervical squamous cell carcinoma,and 4 cases(0.56%)of cervical adenocarcinoma.With histopathological results as the diagnostic criteria,the number of cervical cancer and precancerous lesions detected by TCT alone,HPV genotyping alone,and their combination was 401,565,and 602 cases,accounting for 55.93%(401/717),78.80%(565/717),and 83.96%(602/717)among the total screened cases,respectively.The histopathological positivity rate of TCT and HPV genotyping combined screening was significantly higher than that of TCT alone or HPV typing alone,with a statistically significant difference(P<0.05).Conclusion Combined screening with TCT and HPV genotyping can improve the detection rate of cervical cancer and precancerous lesions,reduce missed diagnoses,and is a relatively accurate and reliable screening method.

Abstract:Objective To evaluate the predictive value of tumor-infiltrating lymphocytes(TILs)in HE-stained slides of triple-negative breast cancer(TNBC)patients using artificial intelligence(AI)-assisted quantification before neoadjuvant therapy.Methods Clinical and pathological data from 123 TNBC patients who received neoadjuvant therapy were collected from three hospitals.Semi-automated annotation of HE-stained biopsy slides was performed to train a random forest model.Three spatially stratified TILs variables were constructed:intratumoral TILs(eTILs),stromal TILs(esTILs),and global TILs(etTILs),to assess the value of TILs from a spatial perspective.Results In the discovery cohort,esTILs demonstrated the best predictive performance for disease-free survival(DFS)(AUC=0.90),which was significantly superior to that of etTILs(AUC=0.78)and eTILs(AUC=0.61).Patients with high esTILs exhibited significantly prolonged DFS.For pathological complete response(pCR)prediction,etTILs emerged as the sole independent predictor in multivariate analysis(OR=16.58,95%CI:4.28-64.22,P＜0.01),and higher etTILs was associated with a higher likelihood of achieving pCR.These findings were robustly validated in an independent cohort.Conclusion This study reveal the differential predictive value of the spatial heterogeneity of TILs in TNBC:esTILs serves as an independent predictor for DFS,likely reflecting sustained immune surveillance function,while etTILs is specifically associated with pCR rate.

Abstract:Objective To investigate the expression of forkhead box protein P1(FOXP1),estrogen receptor(ER),and GATA binding protein 3(GATA-3)in breast invasive lobular carcinoma(ILC)and their clinical significance.Methods A retrospective analysis was conducted on the clinicopathological data of 46 patients with breast ILC treated at Dongying People's Hospital from April 2020 to February 2025.The expression levels of FOXP1,ER,and GATA-3 in breast ILC tissues and adjacent tissues were compared,and their relationships with clinicopathological characteristics were analyzed.Correlation analysis was performed using Spearman's rank correlation.Results The positive expression rates of FOXP1,ER,and GATA-3 in breast ILC tissues were significantly lower than those in adjacent tissues(P＜0.05).The positive expression of FOXP1,ER,and GATA-3 was negatively correlated with TNM stage and lymph node metastasis,and positively correlated with the degree of differentiation(P＜0.05).In breast ILC,the expression of both FOXP1 and GATA-3 was positively correlated with the expression of ER(P＜0.05).Conclusion FOXP1,ER,and GATA-3 all exhibit low expression in breast ILC tissues,and the reduction in their positive expression rates is associated with patient's TNM stage,lymph node metastasis,and degree of differentiation.

Abstract:Objective To analyze the expression levels of Glypican-3,HepPar-1,Arginase-1,and Ki-67 in hepatocellular carcinoma(HCC)tissues,and explore the predictive value of their combined detection for the pathological differentiation of HCC.Methods The pathological tissues of 98 patients with HCC admitted to our hospital were collected from July 2023 to June 2024,and the adjacent tissues of 70 cases were randomly collected.The expression levels of Glypican-3,HepPar-1,Arginase-1,and Ki-67 were detected by immunohistochemical staining,and the associations between these expressions and clinicopathological features were analyzed.The predictive value of Glypican-3,HepPar-1,Arginase-1,Ki-67 and combined detection of the four markers on pathological differentiation of HCC was analyzed by receiver operating characteristic curve(ROC).Results The positive expression rates of Glypican-3,HepPar-1,Arginase-1,and Ki-67 in HCC cancer tissues were higher than those in adjacent tissues(P＜0.05).There was no significant correlation between the positive expression of these markers and age,gender,tumor size,or differentiation grade(P＞0.05).The positive expressions of Glypican-3,HepPar-1,Arginase-1,and Ki-67 were significantly higher in patients with poorly differentiated or undifferentiated HCC than in those with moderate-to-high differentiated HCC(P＜0.05).ROC results indicated that the area under the curve(AUC)for the combined detection of Glypican-3,HepPar-1,Arginase-1,and Ki-67 in predicting HCC pathological differentiation was 0.677,which was higher than that of individual detection(Glypican-3:0.625;HepPar-1:0.600;Arginase-1:0.542;Ki-67:0.578).The specificity of combined detection was 98.70%,which was superior to that of each individual marker.Conclusion The pathological differentiation of HCC patients is related to the expressions of Glypican-3,HepPar-1,Arginase-1,and Ki-67,and the combined detection of these four markers provides higher predictive value for identifying HCC with pathological differentiation gradeⅢ～Ⅳ than individual marker detection.

Abstract:Objective To evaluate the effects of four red blood cell lysates on the DNA extraction quality from tumor cells in bloody pleural effusion obtained by image-guided puncture,and to analyze their impacts on DNA integrity and subsequent detection efficacy.Methods Four groups(a-d)of red blood cell lysates were selected for testing.Pleural effusion samples from 30 patients with histopathologically diagnosed lung adenocarcinoma were collected,processed with the four lysates respectively,followed by DNA extraction for quality comparison.Additionally,eight samples with matched surgical tissue with genetic testing results were selected for next-generation sequencing to observe the effects of these four red blood cell lysates on tumor cell DNA quality while lysing red blood cells.Results The experimental results revealed that the four red blood cell lysates exhibited differences in their ability to remove red blood cells while preserving DNA quality,but the differences were not statistically significant.The DNA quality ratings across the four groups were predominantly Grade a,with no significant differences among groups.Group A demonstrated the highest stability in DNA quality,with the highest proportion of Grade a samples.The DNA concentration(QB)values in Group a were significantly higher than those in other groups,while Group D generally showed lower concentration values.Spearman rank correlation analysis indicated a strongly positive correlation between quality rating and concentration(QB)values(P=0.644,P＜0.000 1),meaning that higher quality ratings corresponded to significantly increasing median concentration(QB)values.Among the eight cases with next-generation sequencing results from matched surgical tissue samples,the current data showed no statistically significant differences compared to previous results.Conclusion The red blood cell lysate in Group A of this study demonstrates superior preservation effects on preserving the quality of nucleated cell DNA,while the processing conditions of Group D may have reduced the DNA concentration of tumor cells.However,given that the differences are not statistically significant,these results should be interpreted with caution.Subsequent experiments should increase the sample size and conduct detailed investigations into other potential influencing factors.

Abstract:Objective To investigate the expression patterns and correlation between GLUT-1 and PD-L1 in colorectal cancer.Methods Clinical data and surgical specimens were collected from 113 patients who underwent radical resection for colorectal cancer at the Department of General Surgery,Beijing Chaoyang Hospital,Capital Medical University,from January 2024 to December 2024.Immunohistochemistry was performed to detect the expression of GLUT-1 and PD-L1 in tumor tissues,and their associations with clinicopathological features were analyzed.Liposome-mediated transfection was employed to silence GLUT-1 gene expression in HCT-116 cells,and the mRNA and protein expression levels of PD-L1 were subsequently assessed.Results The positive expression rates of GLUT-1 and PD-L1 in colorectal cancer tissues were 60.2%and 38.1%,respectively.A significant positive correlation was observed between the expression levels of GLUT-1 and PD-L1(r=0.235,P=0.012).GLUT-1 expression was significantly associated with vascular tumor thrombus(P=0.002)and TNM stage(P=0.001),whereas PD-L1 expression was only associated with postoperative TNM stage(P=0.018).Silencing the GLUT-1 gene in HCT-116 cells resulted in significantly lower mRNA and protein expression levels of PD-L1 compared to the control group(P<0.05).Conclusion There is a positive correlation between GLUT-1 and PD-L1 expression in colorectal cancer,and silencing the GLUT-1 gene inhibits PD-L1 expression.

Abstract:Objective Weakly Supervised Semantic Segmentation(WSSS)leverages image-level labels instead of pixel-level annotations,significantly improving annotation efficiency.To further reduce the burden on pathologists'annotation,this study proposes a novel Single Positive Multi-Label Weakly Supervised Semantic Segmentation(SP-WSSS)framework,which requires only one positive label per image indicating the presence of any tissue type.Methods To mitigate the impact of extensive noise in pseudo-labels,we introduce an early-learning strategy to prevent the model from overfitting to noisy signals.The tissue segmentation performance is evaluated on two public datasets,LUAD-HistoSeg and BCSS-WSSS.Additionally,three pathologists are invited to assess the annotation efficiency.Results Experiments demonstrate that SP-WSSS achieves outstanding tissue segmentation performance on two public datasets,LUAD-HistoSeg and BCSS-WSSS.Three board-certified pathologists were invited to evaluate annotation efficiency:for a task involving 100 images,pixel-level annotation took approximately 200 minutes on average,while single-positive multi-label annotation required less than 2 minutes.Furthermore,compared to conventional annotation methods,single-positive multi-label annotation achieved higher consistency(consistency scores:pixel-wise annotation 85.64%;image-level multi-label 92.25%;single-positive multi-label 98%).Conclusion The proposed novel annotation paradigm for segmentation SP-WSSS shows strong potential to replace traditional annotation approaches,substantially alleviating the annotation burden on pathologists.

Abstract:Objective To analyze the relationship between the expressions of hypoxia-inducible factor-1 α(HIF-1α),glutathione peroxidase 1(GPX1),and phosphatidylinositol 3-kinase catalytic subunit β(PI3KCB)in colorectal cancer tissues and pathological characteristics,as well as their predictive value for prognosis one year after treatment.Methods A total of 111 patients with colorectal cancer admitted to our hospital from June 2021 to May 2024 were followed up for 1 year(by phone or in-person review)after treatment,in this study,3 cases were lost to follow-up,and ultimately 108 patients with colorectal cancer were included.They were divided into a good prognosis group(82 cases,defined as survival without recurrence or metastasis after 1 year of follow-up)and a poor prognosis group(26 cases,defined as death or recurrence/metastasis within 1 year of follow-up).The expression of HIF-1α,GPX1,and PI3KCB in cancer tissues,adjacent tissues,and different pathological features was compared.Patients with poor prognosis were considered positive cases,and those with good prognosis were considered negative controls.The predictive value of HIF-1α,GPX1,and PI3KCB expression in cancer tissues for the prognosis of colorectal cancer patients was analyzed using the receiver operating characteristic curve(ROC).Results The expression positive rate of HIF-1α,GPX1,and PI3KCB in cancer tissues were higher than those in adjacent tissues(P＜0.05).The expression of HIF-1α,GPX1,and PI3KCB in poorly and moderately differentiated colorectal cancer tissues was higher than that in well-differentiated tissues(P＜0.05);the expression of HIF-1α,GPX1,and PI3KCB in stage Ⅲ colorectal cancer tissues was higher than that in stage Ⅰ～Ⅱ(P＜0.05).The expression levels of HIF-1α,GPX1,and PI3KCB in the poor prognosis group were higher than those in the good prognosis group(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of HIF-1α,GPX1,and PI3KCB expression in cancer tissues for predicting the prognosis of colorectal cancer patients was 0.894,which was higher than that of individual detection(0.651,0.696,0.701,P＜0.05),with a sensitivity of 88.46%and a specificity of 90.24%.Conclusion The expression levels of HIF-1α,GPX1 and PI3KCB could promote the occurrence of colorectal cancer and facilitate the malignant progression of the degree of differentiation and tumor stage in patients,the combined detection had high predictive value for the prognosis of patients after 1 year of treatment.

Abstract:Objective To explore the application value of artificial intelligence(AI)-assisted diagnosis in cervical liquid-based cytology screening.Methods A total of 97,201 cervical cytology samples were collected from the cervical cancer screening program conducted at Changzhou Maternal and Child Health Hospital from January 2024 to August 2025.After preparing liquid-based thin-layer cytology slides,the slides were digitally scanned and analyzed using an AI-assisted diagnostic system.The 2022 version of The Bethesda System(TBS)for cervical cytology reporting was adopted as the diagnostic standard.Atypical squamous cells of undetermined significance(ASC-US)and higher-grade lesions were defined as positive.The sensitivity,specificity,false-negative rate,and false-positive rate of AI-assisted diagnosis and manual screening were evaluated.Results The success rate of AI-assisted diagnosis in this large-scale cervical cancer screening was 99.91%(97,114/97,201).Compared with manual screening,AI demonstrated strong diagnostic agreement across categories:98.99%(8,913/9,004)in NILM,84.32%(3,751/4,449)in ASCUS,87.58%(213/244)in ASC-H,80.58%(1,282/1,591)in LSIL,97.06%(324/334)in HISL,100%(6/6)in SCC,and 68.59%(142/207)in glandular abnormalities.The overall concordance was excellent(Kappa coefficient>0.800).For cervical cancer screening,AI-assisted diagnosis achieved a sensitivity of 94.51%,specificity of 99.10%,positive predictive value(PPV)of 87.42%,and negative predictive value(NPV)of 99.63%,indicating good performance as a screening tool.Conclusion AI-assisted diagnosis demonstrates strong concordance with manual screening in cervical cancer detection.The combination of AI-assisted diagnosis and manual review significantly improves the sensitivity and specificity of cervical liquid-based cytology screening,reduces the risk of missed diagnoses,and greatly enhances diagnostic efficiency.In large-scale cervical cancer screening programs,the combination of AI-assisted diagnostic system and manual review has improved slide-reading efficiency by 3 to 6 times,demonstrating significant advantages in workflow optimization.

Abstract:Objective To investigate the clinicopathological characteristics and prognosis of SMARCA4/BRG1-deficient non-small cell lung cancer(NSCLC).Methods A total of 96 pathologically confirmed BRG1-intact or BRG1-deficient advanced NSCLC cases were analyzed.Additionally,NSCLC data containing SMARCA4 mutational profiles,mRNA expression levels and corresponding survival data were retrieved from TCGA and MSKCC databases.Results The main mutation types of SMARCA4 gene included missense mutation(52%),nonsense mutation(23%),frameshift deletion(12%),frameshift insertion(3%),and splice site mutation(10%).BRG1-deficient NSCLC was predominantly found in male(68.8%)with a history of tobacco exposure(65.6%)and a poor prognosis(median OS of 12.0 months).The histopathological types were diverse,with poorly differentiated adenocarcinomas being the most prevalent.The tumors were often accompanied by significant necrosis,brisk mitotic figures,and obvious inflammatory cell infiltration in the stroma.Additionally,TTF-1 was negatively expressed in 76.1%of cases and the median proliferative index of Ki-67 was 70%.While SMARCA4 mutational status lacked prognostic significance(P>0.05),both low SMARCA4 mRNA expression(P=0.03)and BRG1 protein deficiency(P<0.001)predicted a worse clinical prognosis.Conclusions SMARCA4/BRG1-deficient NSCLC exhibits highly aggressive clinicopathological phenotypes.The loss of BRG1 protein serves as a superior prognostic stratification factor compared to SMARCA4 gene alterations.

Abstract:Objective To explore the clinical and pathological features of intravascular large B-cell lymphoma(IVLBCL)and the status of MYD88 and CD79B gene mutations.Methods The clinical and pathological data of 10 patients with IVLBCL diagnosed at China-Japan Friendship Hospital from 2018 to 2021 were collected and analyzed by HE staining,immunohistochemistry and next-generation sequencing.Results The median age of the patients was 58.7 years,with a majority being female(7 cases).The involved sites included the lung,skin,bone marrow and liver.Pathological examination showed that tumor cells mainly aggregated in small blood vessels.Immunohistochemistry revealed diffuse positivity for CD20 and CD79a,and a high Ki-67 proliferation index.Gene testing found MYD88 mutations in 20%of cases and CD79B mutations in 60%,with one case having both mutations.Five patients were Lugano stage Ⅳ,and one died during hospitalization.Three patients received R-CHOP plus intrathecal methotrexate,one received R-CHOP,one received R-miniCHOP,and one received rituximab once.During follow-up,four patients survived and two died.Conclusion IVLBCL is an aggressive B-cell lymphoma with non-specific and insidious clinical manifestations,which is prone to misdiagnosis.The pathological morphology is diverse.MYD88 and CD79B mutations may be related to its pathogenesis.Treatment regimen BTK inhibitors deserve further exploration.Early multi-site biopsy(such as random skin biopsy)is crucial for improving the diagnos rate.Imaging studies can provide for biopsy sites.Advances in molecular pathology and treatment regimens improve survival rates.

Abstract:Objective To investigate the expressions of programmed death ligand 1(PD-L1)and astrocyte elevated gene-1(AEG-1)in gastric cancer tissues with Helicobacter pylori(Hp)infection,and to analyze their relationships with clinicopathological features and prognosis.Methods A total of 93 patients with Hp-infected gastric cancer who underwent surgical treatment in Tianmen First People's Hospital from January 2020 to June 2022 were enrolled.Cancer tissues and adjacent tissues were collected,and after specimen preparation,immunohistochemistry was used to detect the expression levels of PD-L1 and AEG-1.The expression levels of PD-L1 and AEG-1 in cancer tissues and adjacent tissues were compared,and the expressions of PD-L1 and AEG-1 in cancer tissues of patients with different clinicopathological features and prognoses were analyzed.Results The positive rate of PD-L1 in cancer tissues was 63.44%,which was higher than 11.83%in adjacent tissues;the positive rate of AEG-1 in cancer tissues was 76.34%,which was higher than 17.20%in adjacent tissues(P＜0.05).The positive expression rates of PD-L1 and AEG-1 in patients with high-stage gastric cancer,poor differentiation,lymph node metastasis,and invasion depth reaching the muscular layer/serosa were higher than those in patients with low-stage,well-differentiated,no lymph node metastasis,and invasion depth limited to the mucosal layer/submucosal layer(P＜0.05).The 3-year survival rate of PD-L1-positive patients was 67.80%,which was lower than 88.24%of PD-L1-negative patients;the 3-year survival rate of AEG-1-positive patients was 70.00%,which was lower than 91.30%of AEG-1-negative patients(P＜0.05).Conclusion The expression levels of PD-L1 and AEG-1 in cancer tissues of patients with Hp-infected gastric cancer are relatively high,and they are correlated with tumor clinical stage,differentiation degree,lymph node metastasis,invasion depth,and prognosis.

Abstract:Objective Objective To systematically explore the association between thyroid calcification and papillary thyroid carcinoma(PTC),its impact on the expression of immunohistochemical markers,and to evaluate the value and optimization schemes of surface decalcification techniques in addressing diagnostic challenges of intraoperative frozen section.Methods A retrospective analysis of 451 thyroid surgery cases was conducted.The correlation between calcification and PTC was analyzed using the χ² test.The expression differences of Galectin-3,CD56,and Ki-67 were examined.A surface decalcification experiment was performed on fresh calcified tissues to assess the impact of decalcification time on frozen section quality and cellular morphology.Results Association analysis between calcification and malignancy showed that the proportion of PTC in the calcification group was significantly higher than in the non-calcification group.Immunohistochemically,the absence of CD56 showed 100%specificity for PTC with calcification;Galectin-3 had high sensitivity but low specificity;Ki-67>5%was more commonly detected in PTC without calcification.Decalcification experiment revealed that prolonged decalcification time improved section quality,but morphological features of most tumor cells were lost.Decalcification did not affect paraffin sectioning or immunohistochemical results.Conclusion Thyroid calcification is an important indicator of PTC.The'time-gradient decalcification and twice frozen sections'can effectively balance section quality and cell morphology preservation,providing a systematic solution to improve the accuracy of intraoperative frozen diagnosis of calcified thyroid lesions.

Abstract:Objective To explore the diagnostic value of apparent diffusion coefficient(ADC)from diffusion-weighted imaging(DWI)of 3.0T magnetic resonance imaging(MRI)in pathological grading of stage T1b clear cell renal cell carcinoma(CCRCC).Methods A total of 120 patients with stage T1b CCRCC admitted to our hospital between January 2020 and November 2024 were enrolled.All patients underwent pathological examination and 3.0T MRI examination.According to the results of pathological examination,patients were divided into the low-grade group(71 cases,ISUP grading:grades I-II)and the high-grade group(49 cases,ISUP grading:grades Ⅲ-Ⅳ).The basic data and imaging characteristics of patients with different pathological grades were compared.ADC values in the regions of interest(tumor ADC value,peritumoral ADC value,and rADC)and positive expression of Ki-67 were recorded.The correlation between tumor ADC value,rADC value and positive expression of Ki-67 was analyzed.The diagnostic value of 3.0T MRI ADC value and rADC value in pathological grading of stage T1b CCRCC was analyzed by receiver operating characteristic(ROC)curves.Results There was no significant difference in basic data among patients with different pathological grades(P＞0.05).The lesion diameter,boundary definition,significant enhancement,bleeding,calcification and cystic necrosis rate in the high-grade group were significantly higher than those in the low-grade group(P＜0.05).The tumor ADC value and rADC value in the high-grade group were significantly higher than those in the low-grade group(P＜0.05),but there was no significant difference in peritumoral ADC value between the two groups(P＞0.05).The tumor ADC value and rADC value were negatively correlated with positive expression of Ki-67(P＜0.05).Through ROC curve analysis,for the diagnosis of pathological grading of stage T1b CCRCC,the area under the curve(AUC)of ADC value and rADC value was 0.863 and 0.811,the sensitivity was 89.80%and 70.42%,and the specificity was 77.55%and 76.06%,respectively(P＜0.05).Conclusion 3.0T MRI examination can effectively distinguish pathological characteristics of stage T1b CCRCC with different pathological grades and analyze the degree of tumor malignancy.The ADC value has high diagnostic value in pathological grading,which can be applied as an auxiliary diagnostic method for clinical evaluation.