Objective To investigate the heterogeneous lineage of cancer-associated fibroblast(CAF)in clear cell renal cell carcinoma(ccRCC),and explore the relationship between antigen-presentation carcinoma-associated fibroblast(apCAF)and the spatial distribution and formation potential of tertiary lymphoid structure(TLS).Methods Seven single-cell transcriptomic cohorts(n=88)were integrated,and batch effects were corrected using the Harmony algorithm to identify consistent CAF subpopulations across samples.The spatial transcriptomics(GSE175540,n=24)were combined to analyze the spatial interactions between CAF and TLS.Functional annotation was performed using AUCell,and Wilcoxon test was employed to compare the differences in CAF abundance between the immune-sensitive group and the resistant group.The co-localization of TLS with different chemokines was assessed.Results Nine conserved CAF clusters were defined,which were reproducible across different cohorts.Among them,Fibro 4 served as an antigen-presenting type of apCAF,characterized by high expression of HLA-DRA/CD74,and abundance in the immune-sensitive group;its functions were enriched in T cell activation pathways;it was strongly correlated with TLS,and positioned at the periphery of TLS.Cell co-localization analysis revealed that apCAF could recruit lymphocytes to aggregate and form TLS structures via the CXCL13-CXCR5 and CCL19-CCR7 axes.Conclusion This study first reveals that apCAF drives the formation of TLS in ccRCC through a chemokine network,thereby correlating with the response to immunotherapy.The apCAF-TLS axis provides a new strategy for targeting stromal remodeling in the immune microenvironment,and its combined scoring is expected to serve as a biomarker for predicting the efficacy of immune checkpoint blockade therapy.

Objective To investigate the heterogeneous lineage of cancer-associated fibroblast(CAF)in clear cell renal cell carcinoma(ccRCC),and explore the relationship between antigen-presentation carcinoma-associated fibroblast(apCAF)and the spatial distribution and formation potential of tertiary lymphoid structure(TLS).Methods Seven single-cell transcriptomic cohorts(n=88)were integrated,and batch effects were corrected using the Harmony algorithm to identify consistent CAF subpopulations across samples.The spatial transcriptomics(GSE175540,n=24)were combined to analyze the spatial interactions between CAF and TLS.Functional annotation was performed using AUCell,and Wilcoxon test was employed to compare the differences in CAF abundance between the immune-sensitive group and the resistant group.The co-localization of TLS with different chemokines was assessed.Results Nine conserved CAF clusters were defined,which were reproducible across different cohorts.Among them,Fibro 4 served as an antigen-presenting type of apCAF,characterized by high expression of HLA-DRA/CD74,and abundance in the immune-sensitive group;its functions were enriched in T cell activation pathways;it was strongly correlated with TLS,and positioned at the periphery of TLS.Cell co-localization analysis revealed that apCAF could recruit lymphocytes to aggregate and form TLS structures via the CXCL13-CXCR5 and CCL19-CCR7 axes.Conclusion This study first reveals that apCAF drives the formation of TLS in ccRCC through a chemokine network,thereby correlating with the response to immunotherapy.The apCAF-TLS axis provides a new strategy for targeting stromal remodeling in the immune microenvironment,and its combined scoring is expected to serve as a biomarker for predicting the efficacy of immune checkpoint blockade therapy.

Objective:To analyze the imaging features of primary leiomyosarcoma of the inferior vena cava (PLV).Methods:This study was a case series analysis. The clinical and imaging data of 17 patients with PLV confirmed by pathology who underwent CT, MRI and/or PET-CT examinations in the Second Affiliated Hospital of Zhejiang University School of Medicine from June 2012 to September 2022 were retrospectively collected. The CT or MRI findings, including the number, location, size, shape, margin, density (signal), enhancement characteristics, surrounding invasion, and metastasis of the lesion were analyzed.Results:Among the 17 cases there were 7 males and 10 females, aged 32 to 78 years. All patients had single tumors, the maximum diameter of the mass was 3.8 to 19.0 cm, and in 12 cases it was consistent with the inferior venacava.There were 11 cases of "petal-like" necrosis cystic lesion, and 6 cases of "fissure" necrosis cystic lesion. Collateral circulation was found around the mass in 15 cases. There were 3 cases of intraluminal type, 2 cases of extraluminal type, and 12 cases of junctional type. The tumors of intraluminal type presented as "worm-like" appearance, while the extraluminal and junctional type tumors presented as lobulated shape, with local "umbilical depression sign". The margins were clear in 3 cases and unclear in 14 cases. Vascular invasion by the mass was observed in 7 cases. On CT plain scan, the solid component of PLV presented as isodense or slightly hypodense. On MRI T1-weighted images, the solid component presented as isodense or slightly hypodense, and on fat-suppressed T2-weighted images, it presented as isodense or slightly hyperdense. On MRI diffusion-weighted imaging, 12 cases showed high signal intensity, and the corresponding apparent diffusion coefficient map showed low signal intensity. On CT enhanced scan, 8 cases showed mild to moderate enhancement of the solid part of PLV in the arterial phase and 9 cases showed obvious enhancement. In the venous phase and delayed phase, 10 cases showed continuous enhancement and 7 cases showed progressive enhancement. On MRI enhanced scan, 8 cases showed moderate enhancement and 6 cases showed obvious enhancement of the solid part of PLV in the arterial phase. In the venous phase and delayed phase, continuous progressive enhancement was observed; no enhancement was seen in the necrotic and cystic areas.Conclusion:The imaging characteristics of PLV show that the maximum diameter of the masses are consistent with the direction of inferior vena cava, most masses exhibit a "petal-like" necrotic cyst morphology with collateral circulation, and a localized "umbilical concave sign", and some cases possess hemophilic tube features.

Objective:To analyze the imaging features of primary leiomyosarcoma of the inferior vena cava (PLV).Methods:This study was a case series analysis. The clinical and imaging data of 17 patients with PLV confirmed by pathology who underwent CT, MRI and/or PET-CT examinations in the Second Affiliated Hospital of Zhejiang University School of Medicine from June 2012 to September 2022 were retrospectively collected. The CT or MRI findings, including the number, location, size, shape, margin, density (signal), enhancement characteristics, surrounding invasion, and metastasis of the lesion were analyzed.Results:Among the 17 cases there were 7 males and 10 females, aged 32 to 78 years. All patients had single tumors, the maximum diameter of the mass was 3.8 to 19.0 cm, and in 12 cases it was consistent with the inferior venacava.There were 11 cases of "petal-like" necrosis cystic lesion, and 6 cases of "fissure" necrosis cystic lesion. Collateral circulation was found around the mass in 15 cases. There were 3 cases of intraluminal type, 2 cases of extraluminal type, and 12 cases of junctional type. The tumors of intraluminal type presented as "worm-like" appearance, while the extraluminal and junctional type tumors presented as lobulated shape, with local "umbilical depression sign". The margins were clear in 3 cases and unclear in 14 cases. Vascular invasion by the mass was observed in 7 cases. On CT plain scan, the solid component of PLV presented as isodense or slightly hypodense. On MRI T1-weighted images, the solid component presented as isodense or slightly hypodense, and on fat-suppressed T2-weighted images, it presented as isodense or slightly hyperdense. On MRI diffusion-weighted imaging, 12 cases showed high signal intensity, and the corresponding apparent diffusion coefficient map showed low signal intensity. On CT enhanced scan, 8 cases showed mild to moderate enhancement of the solid part of PLV in the arterial phase and 9 cases showed obvious enhancement. In the venous phase and delayed phase, 10 cases showed continuous enhancement and 7 cases showed progressive enhancement. On MRI enhanced scan, 8 cases showed moderate enhancement and 6 cases showed obvious enhancement of the solid part of PLV in the arterial phase. In the venous phase and delayed phase, continuous progressive enhancement was observed; no enhancement was seen in the necrotic and cystic areas.Conclusion:The imaging characteristics of PLV show that the maximum diameter of the masses are consistent with the direction of inferior vena cava, most masses exhibit a "petal-like" necrotic cyst morphology with collateral circulation, and a localized "umbilical concave sign", and some cases possess hemophilic tube features.

Objective:To explore the causes of the crosstalk in the gross α and gross β measurement using an MPC 9604 low background α/β counter.Methods:With the A4 copy paper (70 g/m 2), polyethylene (PE) films (8.7 g/m 2), and 304 stainless steel seperately as shielding materials, the gross α and gross β experiments, gamma spectrometry experiments and solid state nuclear track detection (SSNTD) experiments were conducted by using 241Am and 40K standard materials. A comprehensive analysis encompassing statistical analysis and nuclear physics analysis was performed to reveal the impact of contributing factors on the crosstalk in the gross α and gross β measurement with an MPC 9604 low background α/β counter. Results:241Am powder source experimental result: when two sheets of copy paper were used in the experiment, α-rays did not generate one count in the β channel of the low background α/β counter. The same test with the shielding material of two layers of PE films showed that the α count rate further decreased by about 36.5%, while the β count rate hardly changed. The gross α and gross β experiments and γ spectrometry with the shielding material of stainless steel demonstrated that the characteristic γ ray peaking at 59.5 keV of the 241Am powder source did not generate one count in the β channel. 40K powder source experimental result: when the source was covered with steel of total thickness of 0.965 mm in the gross α and gross β experiments, the γ rays of 40K did not generate one count in the β channel. Compared with naked 40K powder source, when source was covered with one and two sheets of copy paper, the gross α count rate decreased approximately from 3.30 × 10 -3 to 1.50 × 10 -3 and 1.75 × 10 -3, respectively. The SSNTD indicated the presence of other α nuclides in 40K powder source. Conclusions:The β counting in the β channel with the 241Am powder source using MPC 9604 low background α/β counter was, instead of α-rays, caused by the internal conversion electrons and the characteristic X rays of 11.870-22.402 keV emitted from the 241Am powder source, thus this is not a true α/β crosstalk. The α counting in α channel with the 40K powder source, except the contribution of impurity α nuclides, was mainly attributed to the α signals arising from β particles when the amplitude of the piled-up β pules exceeded the discrimination threshold of the detector, therefore it is a true crosstalk.

Objective To screen the pharmacodynamic material basic components of Artemisiae Annuae Herba and study its antioxidant activity in vitro by investigating the spectrum-effect relationship between the HPLC fingerprints of 11 batches of Artemisiae Annuae Herba(dried aerial part of Artemisia annua L.).Methods The determination was performed on Aglient C18 column(250 mm×4.6 mm,5 μm)with mobile phase consisted of 0.2%phosphoric acid solution-Methanol(gradient elution)at the flow rate of 1.0 ml/min.The column temperature was indoor temperature,and detection wavelength was 220 nm,with sample size of 10 μl.Using isochlorogenic acid A as reference,HPLC fingerprints of 11 batches of samples were determined.The common peaks of 11 batches of samples were identified and recorded through TCM chromatographic fingerprint similarity evaluation system(2012 edition).Using scavenging rate of DPPH and ABTS free radical as pharmacodynamic indicators of antioxidant effects,SIMCA 14.1 analysis software was used for PLSR to establish the spectra-effect relationship.Results There were 48 common peaks on 11 batches of sample,11 components were identified as scopoletin,scoparone,isochlorogenic acid B,A,C,luteolin,apigenin,chrysosplenetin,artemisinin,artemisetin and artemisinic acid.The scavenging activity of 11 batches of samples to DPPH and ABTS free radicals was detected.The spectrum-effect relationship showed that isochlorogenic acid A,B,C and scoparone were positively associated with its antioxidant capacity,and variable projection value was greater than 1.It was suggested that these components were the material basis of antioxidant effect in Artemisiae Annuae Herba.Conclusion This study investigates the antioxidant capacity of different substances in Artemisiae Annuae Herba in vitro,and proves that isochlorogenic acid A,B,C and scoparone play a major role for the antioxidant capacity.

Objective To explore the effect of Bajitianwan(BJTW)formula on bone formation of Aβ-injured osteoblasts and its mechanism.Methods Osteoblasts isolated from neonatal 24-hour Wistar rats were used for the study,and osteoblasts were subjected to damage with Aβ1-42 oligomers,and pharmacological intervention was performed with the aqueous extract of BJTW formula.The MTT assay,alkaline phosphatase(ALP)activity assay,catalase(CAT)activity assay,superoxide dismutase(SOD)activity assay,glutathione(GSH)activity assay and malondialdehyde(MDA)activity assay were carried out respectively.The expression levels of bone morphogenetic protein 2(BMP2),osteogenic specific transcription factor(RUNX-2)and osteoprotective protein(OPG)were detected by Western blotting.After confirming the effect of BJTW formula on Aβ-injured osteoblasts,the network pharmacology method was used to predict the potential pathways.Results The BJTW formula significantly promoted the proliferation of Aβ-injured osteoblasts,increased ALP,SOD and GSH activity,inhibited MDA activity,and promoted the expression of bone formation-related proteins BMP2,RUNX-2 and OPG.Network pharmacological analysis showed that the effect of ameliorating of Aβ-injured osteoblasts by BJTW formula was mainly mediated by AGE-RAGE,PI3K-Akt,MAPK and neuroactive ligand-receptor interaction signaling pathways.Conclusion In this study,the effect of BJTW formula on improving the osteoblasts damaged by Aβ was confirmed for the first time,and its related mechanism was explored based on network pharmacology method.The results lay a strong foundation for the clinical application of traditional formula BJTW against osteoporosis.

kV X-ray radiotherapy was the primary mode of radiotherapy widely used to treat many types of cancer, including deep tumors, before the invention of the Co-60 therapy machine and the electron linear accelerator, which gradually replaced kV X-ray radiotherapy. kV X-ray radiotherapy equipment requires less space and shielding, and still has application value in the treatment of skin lesions and superficial tumors. Especially in recent years, kV X-ray has been used in the treatment of keloid, and electronic brachytherapy equipment has been used in intracavitary, intraoperative, and superficial radiotherapy. Therefore, kV X-ray radiotherapy has seen renewed application. The quality control of kV X-ray radiotherapy equipment is the key to ensure the treatment effect and safety of patients. This paper reviews the current status of quality control of kV X-ray radiotherapy equipment and provides a reference for the formulation of quality control assessment standards for kV X-ray radiotherapy equipment.

Objective To explore the effect and mechanism of Bajitianwan on preventing D-galactose (D-gal)-induced osteoblast bone loss. Methods Osteoblasts isolated from 24 h old Wistar rats were injured by D-gal and intervened with Bajitianwan extract. The osteoblastic proliferation and differentiation were determined by MTT and alkaline phosphatase (ALP), respectively. The cell reactive oxygen species (ROS) levels were detected by DCFH-DA fluorescent probes. The expression of cellular oxidation-related protein nuclear factor erythroid 2-related factor 2 (Nrf2), phosphorylated protein kinase B (p-AKT), protein kinase B (AKT), heme oxygenase-1 (HO-1), and NADPH quinone oxidoreductase 1 (NQO1) were detected by Western blotting. The intranuclear expression of Nrf2 protein was measured by immunofluorescence. Results Bajitianwan extract had significantly increased the osteoblastic proliferation and differentiation, and significantly reduced the intracellular ROS level. Bajitianwan extract had activated the PI3K/AKT pathway via activating the phosphorylation of AKT in osteoblasts, and promoted NQO1 and HO-1 expression. In addition, Bajitianwan had significantly promoted the expression of Nrf2 in the nucleus of osteoblasts, activating Nrf2 signaling pathway, and further promoted bone formation. Conclusion This study confirmed that Bajitianwan could prevent D-gal injured osteoblastic bone loss for the first time. The mechanism might be related to the regulation of oxidative stress associated PI3K/AKT and Nrf2 signaling pathway.

Objective:To evaluate the effectiveness of enhanced CT texture feature analysis in predicting pseudoprogression in patients with metastatic clear cell renal cell carcinoma (mccRCC) undergoing programmed cell death protein 1 (PD-1) inhibitor therapy.Methods:A cross-sectional study. Data from 32 patients with mccRCC were retrospectively collected who received monotherapy with PD-1 inhibitors after standard treatment failure at Henan Cancer Hospital, from June 2015 to January 2021. Clinical information and enhanced CT images were analyzed to assess target lesion response. The lesions were divided into pseudoprogression and non-pseudoprogression groups. Manual segmentation of target lesions was performed using ITK-Snap software on baseline enhanced CT, and texture analysis was conducted using A.K. software to extract feature parameters. Differences in texture features between the pseudoprogression and non-pseudoprogression groups were analyzed using univariate and multivariate logistic regression. A predictive model for pseudoprogression was constructed, and its performance was evaluated using ROC curve analysis.Results:A total of 32 patients with 89 lesions were included in the study. Statistical analysis revealed significant differences in seven texture features between the pseudoprogression and non-pseudoprogression groups. These features included“original_ngtdm_Strength”(0.49 vs. -0.61, P=0.006), “wavelet-HLH_glszm_ZonePercentage”(0.67 vs. -0.22, P=0.024),“wavelet-LHL_ngtdm_Strength”(1.20 vs. -0.51, P=0.002), “wavelet-HLL_gldm_LargeDependenceEmphasis”(-0.84 vs. 0.19, P=0.002), “wavelet-HLH_glcm_Id” (-0.30 vs. 0.43, P=0.037),“wavelet- HLH_glrlm_RunPercentage”(0.45 vs. -0.01, P=0.032),“wavelet-LHH_firstorder_Skewness”(0.25 vs. -0.27, P=0.011). Based on these features, a pseudoprogression prediction model was developed with a P-value of 0.000 2 and an odds ratio of 0.045 (95% CI 0.009-0.227). The model exhibited a high predictive performance with an AUC of 0.907 (95% CI 0.817-0.997) according to ROC curve analysis. Conclusions:Enhanced CT texture feature analysis shows promise in predicting lesion pseudoprogression in patients with metastatic ccRCC undergoing PD-1 inhibitor therapy. The developed predictive model based on texture features demonstrates good performance and may assist in evaluating treatment response in these patients.