The presence of magnetic fields in a magnetic resonance accelerator (MR-linac) can affect the reference dosimetry, and thus the existing Code of Practices (CoPs) are inadequate for MR-linac. In this article, the characteristics of adsorbed dose to water and ionization chamber response in the presence of magnetic fields were introduced and a formalism for reference dosimetry in MR-linac was developed based on the existing CoPs, aiming to provide reference for dosimetric quality control and research work of MR-linac in China.

Prostate cancer is the most prevalent malignant tumor among men, ranking first in incidence and second in mortality globally. Novel hormone therapies (NHT) targeting the androgen receptor (AR) pathway have become the standard of care for metastatic prostate cancer. This review offers a comprehensive overview of NHT, including abiraterone, enzalutamide, apalutamide, darolutamide, and rezvilutamide, which have demonstrated efficacy in delaying disease progression and improving patient survival and quality of life. Nevertheless, resistance to NHT remains a critical challenge. The mechanisms underlying resistance are complex, involving AR gene amplification, mutations, splice variants, increased intratumoral androgens, and AR-independent pathways such as the glucocorticoid receptor, neuroendocrine differentiation, DNA repair defects, autophagy, immune evasion, and activation of alternative signaling pathways. This review discusses these resistance mechanisms and examines strategies to counteract them, including sequential treatment with novel AR-targeted drugs, chemotherapy, poly ADP-ribose polymerase inhibitors, radionuclide therapy, bipolar androgen therapy, and approaches targeting specific resistance pathways. Future research should prioritize elucidating the molecular basis of NHT resistance, optimizing existing therapeutic strategies, and developing more effective combination regimens. Additionally, advanced sequencing technologies and resistance research models should be leveraged to identify novel therapeutic targets and improve drug delivery efficiencies. These advancements hold the potential to overcome NHT resistance and significantly enhance the management and prognosis of patients with advanced prostate cancer.

OBJECTIVES: To identify immunosuppressive neutrophil subsets in patients with prostate cancer (PCa) and construct a risk prediction model for prognosis and immunotherapy response of the patients based on these neutrophil subsets. METHODS: Single-cell and transcriptome data from PCa patients were collected from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Neutrophil subsets in PCa were identified through unsupervised clustering, and their biological functions and effects on immune regulation were analyzed by functional enrichment, cell interaction, and pseudo-time series analyses. Lasso-Cox regression was utilized to construct a prognostic risk model based on the immunosuppressive neutrophil subsets, and survival analysis and ROC curve analysis were used to compare the prognosis of PCa patients with high and low risks stratified using this model. The relationship of the prognostic risk model with PCa immune infiltration and immune response was evaluated using CIBERSORT and TIDE scores. RESULTS: PCa tissues showed a significantly greater proportion of infiltrating neutrophils than the adjacent normal tissues (P<0.05). PCa-associated neutrophils could be clustered into two independent cell subsets: Neu_1 and Neu_2. Neu_2 cells exhibited highly enriched immunoregulatory functions and were highly differentiated and mature, with upregulated immunosuppressive cytokines such as TGFB1, ITGB2, and LGALS3. Based on the genetic characteristics of Neu_2 cell subsets, the prognostic risk model was constructed. The patients in the high-risk group identified by the model had a shorter biochemical recurrence time (P<0.05) and a higher proportion of Tregs and M2-TAMs cell infiltration (P<0.05) with a higher risk of immune rejection and poorer immune response scores. CONCLUSIONS PCa-associated neutrophils are highly heterogeneous. The prognostic risk model constructed based on the immunosuppressive neutrophil Neu_2 subset can effectively predict both the survival outcomes and immune response of PCa patients.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Prognosis ; Neutrophils/immunology* ; Immunotherapy

Objective To explore the regulatory mechanism of angiopoietin 1(ANGPT1)on proliferation,invasion and angiogenesis of prostate cancer cells.Methods Mouse prostate cancer cell line(RM-1)was divided into control group,NC-oe group,ANGPT1-oe group,NC-sh group and ANGPT1-sh group.NC-oe,ANGPT1-oe,NC-sh and ANGPT1-sh were transfected into RM-1 cells by Lipofectamine3000 reagent.The transfection efficiency was verified by RT-qPCR and Western blot,cell proliferation was detected by MTT assay and EdU stai-ning and cell invasion was detected by Transwell assay.The cells were divided into the following groups:control group,Tie2-expressing monocytes/macrophages(TEMs)group,NC-oe+TEM group,ANGPT1-oe+TEM group,NC-sh+TEM group and ANGPT1-sh+TEM groups.RM-1 and TEM were co-cultured.RM-1 cells were collected after 72 hours and subjected to MTT proliferation assay,EdU staining assay and Transwell invasion assay.The co-cultured cell supernatant from each group mouse umbilical vein endothelial cells(MUVECs)were co-incubated with cell supernatant collected from each group cells and then to detect the number of tubules formed.The co-cul-tured cell supernatant of each group was collected,and the level of MMP-9,VEGFA and COX-2 were detected by ELISA.Results 1)Compared with control group and NC-oe group,the level of ANGPT1 mRNA and protein in ANGPT1-oe group was increased(P＜0.05).Compared with control group and NC-sh group,the level of ANGPT1 mRNA and protein in ANGPT1-sh group was decreased(P＜0.05).2)Compared with control group,the cell viability,EdU positive rate,counting of invasive cells and of tubules formed in TEM group significantly increased(P＜0.05),the level of MMP-9,VEGFA and COX-2 in the supernatant was increased(P＜0.05).Compared with TEM group and NC-oe+TEM group,the cell viability,EdU positive rate,counting of invasive cells and of tubules formed in ANGPT1-oe+TEM group decreased(P＜0.05).The level of MMP-9,VEGFA and COX-2 in the supernatant was significantly decreased(P＜0.05).Compared with TEM group and NC-sh+TEM group,the cell viability,EdU positive rate,counting of invasive cell and of tubules formed in ANGPT1-sh+TEM group all increased(P＜0.05).The level of MMP-9,VEGFA and COX-2 in the supernatant were increased(P＜0.05).Conclusions The decreased expression of ANGPT1 in prostate cancer significantly enhances the promotion effect of TEMs on the proliferation,invasion and angiogenesis of prostate cancer cells,thus promoting the progression of prostate cancer.

Objective To explore the regulatory mechanism of angiopoietin 1(ANGPT1)on proliferation,invasion and angiogenesis of prostate cancer cells.Methods Mouse prostate cancer cell line(RM-1)was divided into control group,NC-oe group,ANGPT1-oe group,NC-sh group and ANGPT1-sh group.NC-oe,ANGPT1-oe,NC-sh and ANGPT1-sh were transfected into RM-1 cells by Lipofectamine3000 reagent.The transfection efficiency was verified by RT-qPCR and Western blot,cell proliferation was detected by MTT assay and EdU stai-ning and cell invasion was detected by Transwell assay.The cells were divided into the following groups:control group,Tie2-expressing monocytes/macrophages(TEMs)group,NC-oe+TEM group,ANGPT1-oe+TEM group,NC-sh+TEM group and ANGPT1-sh+TEM groups.RM-1 and TEM were co-cultured.RM-1 cells were collected after 72 hours and subjected to MTT proliferation assay,EdU staining assay and Transwell invasion assay.The co-cultured cell supernatant from each group mouse umbilical vein endothelial cells(MUVECs)were co-incubated with cell supernatant collected from each group cells and then to detect the number of tubules formed.The co-cul-tured cell supernatant of each group was collected,and the level of MMP-9,VEGFA and COX-2 were detected by ELISA.Results 1)Compared with control group and NC-oe group,the level of ANGPT1 mRNA and protein in ANGPT1-oe group was increased(P＜0.05).Compared with control group and NC-sh group,the level of ANGPT1 mRNA and protein in ANGPT1-sh group was decreased(P＜0.05).2)Compared with control group,the cell viability,EdU positive rate,counting of invasive cells and of tubules formed in TEM group significantly increased(P＜0.05),the level of MMP-9,VEGFA and COX-2 in the supernatant was increased(P＜0.05).Compared with TEM group and NC-oe+TEM group,the cell viability,EdU positive rate,counting of invasive cells and of tubules formed in ANGPT1-oe+TEM group decreased(P＜0.05).The level of MMP-9,VEGFA and COX-2 in the supernatant was significantly decreased(P＜0.05).Compared with TEM group and NC-sh+TEM group,the cell viability,EdU positive rate,counting of invasive cell and of tubules formed in ANGPT1-sh+TEM group all increased(P＜0.05).The level of MMP-9,VEGFA and COX-2 in the supernatant were increased(P＜0.05).Conclusions The decreased expression of ANGPT1 in prostate cancer significantly enhances the promotion effect of TEMs on the proliferation,invasion and angiogenesis of prostate cancer cells,thus promoting the progression of prostate cancer.

The presence of magnetic fields in a magnetic resonance accelerator (MR-linac) can affect the reference dosimetry, and thus the existing Code of Practices (CoPs) are inadequate for MR-linac. In this article, the characteristics of adsorbed dose to water and ionization chamber response in the presence of magnetic fields were introduced and a formalism for reference dosimetry in MR-linac was developed based on the existing CoPs, aiming to provide reference for dosimetric quality control and research work of MR-linac in China.

Background and aims Adeno-associated virus (AAV) is becoming an attractive vector due to its low toxicity and minimal immunogenicity. However, liver-targeted AAV gene therapy still faces challenges, such as low delivery efficiency and safety risks associated with high vector doses. Isolated hepatic perfusion (IHP) has been explored as a localized drug delivery method, yet its full potential in gene therapy remains under investigation. Here, we investigated the efficiency of AAV8 delivery via the IHP route and its preference for hepatic transduction. Methods The IHP route was established through surgery in rats and cynomolgus monkey, and the AAV8-dTomato solution was injected into the entire liver through the inflow tract and maintained for 10 min. One week later, liver tissues were obtained, and the dTomato fluorescence expression area fraction and intensity were analyzed. Results AAV8-dTomato delivery via the IHP resulted in over 60% dTomato-positive areas in rat liver and showed higher efficiency than the portal vein (PV) and inferior vena cava (IVC) routes at equivalent doses. In rats, AAV8-dTomato expression was primarily periportal across IHP, PV, and IVC routes, while in cynomolgus monkey, IHP delivery showed a pericentral pattern. Conclusions In this study, we found that IHP is an effective strategy for AAV8 delivery. In addition, the distribution characteristics of AAV8, when delivered in cynomolgus monkey via IHP, provide candidate vector delivery schemes for gene therapy for different types of genetic liver diseases.

OBJECTIVE To optimize the water extraction process of Flos Lonicerae-Fructus Forsythuae and determine the range of water extraction process parameters.METHODS The active components were screened by network pharmacology,and the indica-tor ingredients were determined in combination with the quality markers under the relevant terms of Chinese Pharmacopoeia 2020 edition and the literature.Take extraction yield and the extraction rate of the indicative component as the critical quality attributes of the water extraction process to screen critical process parameters.The mathematical model was established by Box-Behnken experimental design to investigate the interaction between CQAs and CPPs and build the design space of the water extraction process of Flos Lonicerae-Fruc-tus Forsythuae.RESULTS The extraction percentages of phenolic acids,forsythoside A and forsythin were screened as the index components;specifications of medicinal slices,extraction time and water addition were the key process parameters.Based on the estab-lishment and optimization of the design space,the optimum water extraction process was obtained as follows:the medicinal slice of Lian-Qiao was broken into 0.8-1.2 cm,adding 12 times the amount of water in the first and extract for 30-50 min,10 times the a-mount of water in the second and extract for 25-30 min.CONCLUSION The verification results show that the measured value ob-tained by using the design space method to optimize the water extraction process is close to the predicted value,indicating that the method is stable and reliable,which can provide ideas for its further process development and quality control for the couple medicines of Flos Lonicerae-Fructus Forsythuae.

Objective:To investigate the effects of ultrasound-guided serratus plane block (US-SPB) on stress response, serum cancer antigen 153 (CA153) and neuron-specific enolase (NSE) levels in patients undergoing radical mastectomy.Methods:A total of 110 patients with radical mastectomy who were admitted to our hospital from Feb. 2022 to Feb. 2024 were chosen and separated into US-SPB group ( n=55, US-SPB) and control group ( n=55, conventional anesthesia) by the principle of random number table. The differences of stress index, tumor index, pain, sedation, and operation related index were observed between the two groups. Results:24h after operation, serum cortisol (Cor), epinephrine (EPI) and noradrenaline (NE) in US-SPB group were significantly lower than those in control group ( t=4.69, 5.07, 5.38, P<0.05) ; The levels of serum CA153 and NSE in US-SPB group were significantly lower ( t=2.15, 2.04, P<0.05) ; The visual analogue scales (VAS) scores and Ramsay sedation score (RSS) scores in US-SPB group were significantly lower at 6h, 12h and 24h after surgery (VAS: Finter-group =17.67, Pinter-group <0.05; Ftime =15.58, Ptime <0.05; Finteraction =0.96, Pinteraction > 0.05; RSS: Finter-group =12.77, Pinter-group <0.05; Ftime =10.88, Ptime <0.05; Finteraction =0.32, Pinteraction > 0.05) ; The intraoperative dosage of remifentanil and the postoperative dosage of sufentanil in US-SPB group were significantly lower ( t=1.99, P<0.05) . Conclusion:US-SPB can not only reduce the stress response of patients undergoing radical mastectomy, but also have a positive effect on the reduction of tumor marker levels, and the pain management effect is better.

Objective:To establish the ultra high performance liquid chromatography (UPLC) fingerprints of Mume flos at different flowering stages; To provide reference for the quality research of Mume flos.Methods:The fingerprints of Mume flos were established by UPLC method, and the common peaks were identified by high performance liquid chromatography high resolution mass spectrometry (LC-MS). Chemometrics analysis was carried out with the fingerprints' common peak area of plum blossom at different flowering stages as a variable. Semiquantitative analysis of changes in flavonoids and phenolic acids in Mume flos at different flowering stages was conduct using peak area calculation method.Results:Totally 31 common peaks were identified in the fingerprints of plum blossom medicinal materials at different flowering stages and 9 components were identified. Clustering analysis (HCA) and principal component analysis (PCA) both classified plum blossom medicinal herbs at different flowering stages into three categories. Among them, there were significant differences between the groups at the bud stage, blooming period, and final flowering period, while the differences between the groups at blooming period and final flowering period were relatively small. The orthogonal partial least squares discriminant analysis (OPLS-DA) screened 16 different components with VIP>1.0. The contents of phenolic acids in different flowering stages were as follows: bud stage>blooming period>final flowering period, while the contents of flavonoids were as follows: blooming period>final flowering period>bud stage.Conclusions:This method is simple and reliable, and can provide reference for the quality evaluation of plum blossom medicinal materials at different flowering stages.