Purpose To explore the key molecules mechanisms underlying the selective activation of macrophage and the regulation of Dicer expression induced by glioblastoma(GBM)cells,as well as its prognostic significance.Methods Glioblastoma conditional medium(GCM)was fractionated by molecular weight using ultrafiltration.Specif-ic molecular weight components of GCM that upregulate Dicer expression in mouse bone marrow derived macrophages(BMDMs)were identified.Secreted proteins were identified by mass spectrometry(MS).The correlation between candidate proteins and GBM prognosis was analyzed using the TCGA and CGGA database.In vitro experiments of the candidate proteins on Dicer expression in BMDMs were further carried out.Results GCM components with a molecu-lar weight of＞50 kDa significantly upregulated Dicer expression in BMDMs.MS identified five key secreted proteins:Prg4,Psap,Hexa,Aebp1,and Itih2.High expression of Prg4 was significantly positively correlated with poor progno-sis in GBM patients(P＜0.001)and was associated with the expression of selective macrophage activation markers.Recombinant Prg4 protein stimulated BMDMs and induced Dicer expression in mouse BMDMs.Conclusion This study reveals that glioma cells induce Dicer expression in macrophages by secreting Prg4,providing a theoretical basis for GBM therapeutic strategies targeting the Prg4-Dicer axis.

Purpose To explore the key molecules mechanisms underlying the selective activation of macrophage and the regulation of Dicer expression induced by glioblastoma(GBM)cells,as well as its prognostic significance.Methods Glioblastoma conditional medium(GCM)was fractionated by molecular weight using ultrafiltration.Specif-ic molecular weight components of GCM that upregulate Dicer expression in mouse bone marrow derived macrophages(BMDMs)were identified.Secreted proteins were identified by mass spectrometry(MS).The correlation between candidate proteins and GBM prognosis was analyzed using the TCGA and CGGA database.In vitro experiments of the candidate proteins on Dicer expression in BMDMs were further carried out.Results GCM components with a molecu-lar weight of＞50 kDa significantly upregulated Dicer expression in BMDMs.MS identified five key secreted proteins:Prg4,Psap,Hexa,Aebp1,and Itih2.High expression of Prg4 was significantly positively correlated with poor progno-sis in GBM patients(P＜0.001)and was associated with the expression of selective macrophage activation markers.Recombinant Prg4 protein stimulated BMDMs and induced Dicer expression in mouse BMDMs.Conclusion This study reveals that glioma cells induce Dicer expression in macrophages by secreting Prg4,providing a theoretical basis for GBM therapeutic strategies targeting the Prg4-Dicer axis.

Objective:To investigate the impact of different target sites, number of treatments, and age on setup errors in dual-isocenter radiotherapy for breast cancer, and to provide a basis for planning target volume (PTV) margin expansion.Methods:A retrospective analysis was conducted on data from 15 patients with left-sided breast cancer who underwent dual-isocenter breath-hold radiotherapy in the Department of Radiotherapy Oncology at the Second Hospital of Hebei Medical University from May 2021 to May 2023. Setup errors were acquired using a Varian TrueBeam STX linear accelerator. Patients were grouped by target site (supraclavicular/chest wall), treatment phase (early/late), and age (younger/older). Non-parametric tests were used to analyze differences in setup errors in : vertical (Vrt), longitudinal (Lng), lateral (Lat) directions, and pitch, roll, and rotation (Rtn) angles. The formula proposed by van Herk was applied to calculate PTV margins.Results:The Vrt direction setup error in the supraclavicular region (0.2 cm) was smaller than that in the chest wall region (0.26 cm), but errors and margin expansions in other directions were larger ( P<0.05 for Lng and Lat directions). No significant correlation was observed in Vrt direction errors between the two sites ( P=0.062), while significant correlations were found in the other directions and angles (all P<0.05). As treatment progressed, setup errors increased in the Vrt and Rtn directions for the supraclavicular region, and in the Vrt, Lng, Lat directions and Rtn angle for the chest wall region. Among these, only the increase in Lat direction error for the chest wall region was statistically significant ( P=0.028). The PTV margins in the late phase group (except for the Lat direction of the supraclavicular region) were greater than or equal to those in the early phase group. Elderly patients had significantly larger setup errors than younger patients in Vrt, Lng, and Lat directions for the supraclavicular region, as well as in Vrt and Lat directions for the chest wall region (all P<0.05). Conclusions:In dual-isocenter radiotherapy for breast cancer, the supraclavicular region requires larger PTV margins than the chest wall region, and elderly patients require greater margins overall. Mid-course rescanning is recommended. If cone-beam CT guidance cannot be ensured for every session, expansion of PTV margins should be considered for the supraclavicular region and elderly patients to reduce the risk of geographic miss.

Anaplastic lymphoma kinase (ALK) rearranged renal cell carcinoma (ALK-RCC) is an exceedingly rare malignancy, recently classified as a distinct molecular entity in the 5th edition of the WHO classification for urinary and male genital tumors. Due to its non-specific clinical symptoms and diverse histopathological patterns, accurate diagnosis is difficult. This paper reports a case of ALK-RCC with morphology and immunophenotype resembling papillary renal cell carcinoma. After second-generation sequencing, EML4-ALK gene fusion was found, and positive staining for ALK was confirmed by immunohistochemistry subsequently. Following informed consent from the patient, targeted therapy with crizotinib was initiated. During a 17-month follow-up period, no recurrence or metastasis was observed.

Objective:To investigate the causal relationships between multiple obesity indices, including body mass index (BMI), body fat percentage, whole-body fat mass, trunk fat mass, leg fat percentage, arm fat percentage, waist circumference, and hip circumference, and preeclampsia (PE) using Mendelian randomization (MR), and to evaluate the mediating effect of triglycerides.Methods:Genome-wide association studies (GWAS) summary statistics from European populations were utilized. Independent genetic loci associated with obesity indices and PE served as instrumental variables of exposure and outcomes. Obesity data (approximately 191 000 female samples) came from UK Biobank; PE data ( n=242 852) from FinnGen Biobank. Causal effects were assessed primarily via inverse variance weighted (IVW), supplemented by MR-Egger, weighted median, MR-pleiotropy residual sum and outlier (MR-PRESSO), and Bayesian weighted MR. Bonferroni correction was applied. Cochran's Q test evaluated heterogeneity; MR-Egger intercept test assessed horizontal pleiotropy; leave-one-out, funnel, and scatter plots conducted sensitivity analyses. Odds ratio ( OR) measured effect sizes. Two-step MR explored triglyceride mediation. Results:Eighty-two to 112 single nucleotide polymorphisms were included as instrumental variables. After Bonferroni correction, significant positive causal associations with PE were observed for: BMI (IVW: OR=1.703, 95% CI: 1.469-1.974, P<0.001), body fat percentage (IVW: OR=1.595, 95% CI: 1.321-1.925, P<0.001), whole-body fat mass (IVW: OR=1.639, 95% CI: 1.389-1.934, P<0.001), right leg fat percentage (IVW: OR=1.610, 95% CI: 1.360-1.905, P<0.001), left leg fat percentage (IVW: OR=1.622, 95% CI: 1.363-1.930, P<0.001), right arm fat percentage (IVW: OR=1.591, 95% CI: 1.351-1.872, P<0.001), left arm fat percentage (IVW: OR=1.710, 95% CI: 1.444-2.024, P<0.001), and waist circumference (IVW: OR=1.815, 95% CI: 1.534-2.148, P<0.001). Sensitivity analyses confirmed robustness. Triglycerides mediated 4.6%-8.2% of these effects. Trunk fat mass and hip circumference showed potential positive associations (IVW: OR>1, 0.005≤ P<0.05). Conclusions:Higher BMI, body fat percentage, whole-body fat mass, leg/arm fat percentages, and waist circumference may increase PE risk, with waist circumference showing the strongest association. These effects may be partially mediated by triglycerides.

Objective:To investigate the impact of different target sites, number of treatments, and age on setup errors in dual-isocenter radiotherapy for breast cancer, and to provide a basis for planning target volume (PTV) margin expansion.Methods:A retrospective analysis was conducted on data from 15 patients with left-sided breast cancer who underwent dual-isocenter breath-hold radiotherapy in the Department of Radiotherapy Oncology at the Second Hospital of Hebei Medical University from May 2021 to May 2023. Setup errors were acquired using a Varian TrueBeam STX linear accelerator. Patients were grouped by target site (supraclavicular/chest wall), treatment phase (early/late), and age (younger/older). Non-parametric tests were used to analyze differences in setup errors in : vertical (Vrt), longitudinal (Lng), lateral (Lat) directions, and pitch, roll, and rotation (Rtn) angles. The formula proposed by van Herk was applied to calculate PTV margins.Results:The Vrt direction setup error in the supraclavicular region (0.2 cm) was smaller than that in the chest wall region (0.26 cm), but errors and margin expansions in other directions were larger ( P<0.05 for Lng and Lat directions). No significant correlation was observed in Vrt direction errors between the two sites ( P=0.062), while significant correlations were found in the other directions and angles (all P<0.05). As treatment progressed, setup errors increased in the Vrt and Rtn directions for the supraclavicular region, and in the Vrt, Lng, Lat directions and Rtn angle for the chest wall region. Among these, only the increase in Lat direction error for the chest wall region was statistically significant ( P=0.028). The PTV margins in the late phase group (except for the Lat direction of the supraclavicular region) were greater than or equal to those in the early phase group. Elderly patients had significantly larger setup errors than younger patients in Vrt, Lng, and Lat directions for the supraclavicular region, as well as in Vrt and Lat directions for the chest wall region (all P<0.05). Conclusions:In dual-isocenter radiotherapy for breast cancer, the supraclavicular region requires larger PTV margins than the chest wall region, and elderly patients require greater margins overall. Mid-course rescanning is recommended. If cone-beam CT guidance cannot be ensured for every session, expansion of PTV margins should be considered for the supraclavicular region and elderly patients to reduce the risk of geographic miss.

Anaplastic lymphoma kinase (ALK) rearranged renal cell carcinoma (ALK-RCC) is an exceedingly rare malignancy, recently classified as a distinct molecular entity in the 5th edition of the WHO classification for urinary and male genital tumors. Due to its non-specific clinical symptoms and diverse histopathological patterns, accurate diagnosis is difficult. This paper reports a case of ALK-RCC with morphology and immunophenotype resembling papillary renal cell carcinoma. After second-generation sequencing, EML4-ALK gene fusion was found, and positive staining for ALK was confirmed by immunohistochemistry subsequently. Following informed consent from the patient, targeted therapy with crizotinib was initiated. During a 17-month follow-up period, no recurrence or metastasis was observed.

Objective:To investigate the causal relationships between multiple obesity indices, including body mass index (BMI), body fat percentage, whole-body fat mass, trunk fat mass, leg fat percentage, arm fat percentage, waist circumference, and hip circumference, and preeclampsia (PE) using Mendelian randomization (MR), and to evaluate the mediating effect of triglycerides.Methods:Genome-wide association studies (GWAS) summary statistics from European populations were utilized. Independent genetic loci associated with obesity indices and PE served as instrumental variables of exposure and outcomes. Obesity data (approximately 191 000 female samples) came from UK Biobank; PE data ( n=242 852) from FinnGen Biobank. Causal effects were assessed primarily via inverse variance weighted (IVW), supplemented by MR-Egger, weighted median, MR-pleiotropy residual sum and outlier (MR-PRESSO), and Bayesian weighted MR. Bonferroni correction was applied. Cochran's Q test evaluated heterogeneity; MR-Egger intercept test assessed horizontal pleiotropy; leave-one-out, funnel, and scatter plots conducted sensitivity analyses. Odds ratio ( OR) measured effect sizes. Two-step MR explored triglyceride mediation. Results:Eighty-two to 112 single nucleotide polymorphisms were included as instrumental variables. After Bonferroni correction, significant positive causal associations with PE were observed for: BMI (IVW: OR=1.703, 95% CI: 1.469-1.974, P<0.001), body fat percentage (IVW: OR=1.595, 95% CI: 1.321-1.925, P<0.001), whole-body fat mass (IVW: OR=1.639, 95% CI: 1.389-1.934, P<0.001), right leg fat percentage (IVW: OR=1.610, 95% CI: 1.360-1.905, P<0.001), left leg fat percentage (IVW: OR=1.622, 95% CI: 1.363-1.930, P<0.001), right arm fat percentage (IVW: OR=1.591, 95% CI: 1.351-1.872, P<0.001), left arm fat percentage (IVW: OR=1.710, 95% CI: 1.444-2.024, P<0.001), and waist circumference (IVW: OR=1.815, 95% CI: 1.534-2.148, P<0.001). Sensitivity analyses confirmed robustness. Triglycerides mediated 4.6%-8.2% of these effects. Trunk fat mass and hip circumference showed potential positive associations (IVW: OR>1, 0.005≤ P<0.05). Conclusions:Higher BMI, body fat percentage, whole-body fat mass, leg/arm fat percentages, and waist circumference may increase PE risk, with waist circumference showing the strongest association. These effects may be partially mediated by triglycerides.

Pathological specimen sampling is not only the prerequisite of a good pathological diagnosis, but also the primary clinical skill that must be mastered by the standardized residency training trainees (resident trainees) in clinical pathology department. In view of the problems and difficulties encountered in the teaching of specimen sampling, through five years of exploration and attempt, this paper has gradually established a new model with five basic elements, including theory teaching, practice teaching, promoting teaching effect by examination, learning from senior students, and review teaching. The results of evaluation analysis and questionnaire survey show that the teaching mode can make the trainees master the methods of specimen sampling quickly and efficiently, learn and improve clinical skills in practice, and lay a solid foundation for the subsequent standardized training of histopathological diagnosis.

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.