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.

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

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.

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.

Objective:To explore the differences in bacterial community structure between proximal colon cancer (PC), distal colon cancer (DC), and rectal cancer (RC), and the values of featured microbiota in differentiating PC with tumor markers.Methods:This case-control study enrolled 85 newly diagnosed colorectal cancer patients, including 22 PC, 15 DC and 48 RC patients, and 8 colorectal adenoma patients from May 2019 to July 2022 at the Department of General Surgery, Anyang Oncology Hospital. The blood and fecal samples were collected before surgery and then subjected to biochemical tests for tumor markers and 16S rDNA tests, respectively. SPSS (27.0.1) was applied to perform the t-test, one-way ANOVA, Mann-Whitney U test, Kruskal-Wallis H test, and Chi-Squared Test. Also, the receiver operating characteristic curve (ROC) was plotted on tumor markers and/or f_Bacteroidaceae with SPSS software .Results:All groups had significant differences in the CA125 ( F=3.543, P<0.05), CA72-4 ( F=3.596, P<0.05), and serum tumor-associated materials (TAM) levels ( F=5.787, P<0.01). In PC group, the levels of CA125 [PC vs RC, (36.84±6.30) kU/L vs (12.73±4.21) kU/L, P<0.01] and CA72-4 [PC vs RC, (45.56±10.86) kU/L vs (3.30±7.63) kU/L, P<0.01] were significantly higher than that of the RC group, while the level of TAM was remarkably elevated in PC group than in RC group [PC vs RC, (124.84±5.19) U/ml vs (102.44±3.63) U/ml, P<0.001] and CRA group [PC vs CRA, (124.84±5.19) U/ml vs (95.39±8.42) U/ml, P<0.01]. The LEfSe analysis showed that the featured microbiota in the PC group included f_Bacteroidaceae, f_Neisseriaceae, f_Clostridiaceae_1, f_Spirochaetaceae, and so on. The largest area under the ROC belonged to the combination of TAM and f_Bacteroidaceae, which reached 0.845 (95% CI 0.747-0.944), with sensitivity being 0.857 and specificity being 0.815. Conclusions:There is heterogeneity in gut microbiota composition among PC, DC, RC, and CRA. The combination of gut microbiota and tumor biomarkers demonstrated good differentiating effects in proximal colon cancers.

OBJECTIVE: To explore the effectiveness of Nice knot technique for wound closure in Gustilo type ⅢA and ⅢB open tibial fractures. METHODS: A retrospective study was performed on 22 patients with Gustilo type ⅢA and ⅢB open tibial fractures, who underwent wound closure using the Nice knot technique and were admitted between June 2021 and June 2022. There were 15 males and 7 females. The age ranged from 18 to 67 years, with an average of 41.9 years. The causes of injury included traffic accident in 11 cases, falling from height in 7 cases, and heavy object injuries in 4 cases. Fractures were located on the left side in 9 cases and on the right side in 13 cases. And 9 cases were type ⅢA fractures and 13 were type ⅢB fractures according to Gustilo classification. All patients had extensive soft tissue injuries, and no vascular or neurological damage was observed. The time from injury to debridement was 3-8 hours (mean, 6.5 hours). The sizes of wounds before operation and at 2 weeks after operation were measured and wound healing rate at 2 weeks after operation were calculated. The wound healing time and wound healing grading were recorded. The Vancouver Scar Scale (VSS) score was used to assess the wound scar after wound healed and the excellent and good rate was calculated. RESULTS: The wound area was 21.0-180.0 cm ² (mean, 57.82 cm ²) before operation, and it was 1.2-27.0 cm ² (mean, 6.57 cm ²) at 2 weeks after operation. The wound healing rate at 2 weeks after operation was 76%-98% (mean, 88.6%). After operation, 2 cases needed to adjust Nice knot due to skin cutting and 1 case occurred soft tissue infection on the wound. The other patient's wounds healed. The average wound healing time was 27.8 days (range, 18-44 days). And the wound healing were grade A in 13 cases and grade B in 9 cases. VSS score was 2-9, with an average of 4.1; 10 cases were rated as excellent, 10 as good, and 2 as poor, with an excellent and good rate of 90.9%. All patients were followed up 9-24 months (mean, 14.6 months). During follow-up, no deep infection or osteomyelitis occurred. Two cases experienced fracture non-union, and were treated with compression fixation and bone grafting. The fractures of the other patients all healed, with a healing time of 85-190 days (mean, 148.2 days). CONCLUSION Nice knot technique can be used in wound closure of Gustilo type ⅢA and ⅢB open tibial fractures effectively, which is easy to operate.
Male ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Cicatrix ; Retrospective Studies ; Treatment Outcome ; Tibial Fractures/surgery* ; Wound Healing ; Fracture Fixation, Internal/methods* ; Fractures, Open/surgery*

Objective:To compare demographic characteristics,clinical characteristics,therapeutic characteris-tics and physiological indicators of patients with bipolar Ⅰ disorder and bipolar Ⅱ disorder.Methods:A total of 381 patients with bipolar disorder(BD)diagnosed by the Diagnostic and Statistical Manual of Mental Disorders 5 th Edi-tion(DSM-5)were selected,including 302 patients with BD-Ⅰ(79.27％),74 patients with BD-Ⅱ(19.42％)and 5 patients with other specific and related disorders(1.31％).Demographic and clinical characteristics were collected with self-designed clinical information questionnaire.Multivariate logistic regression and multivariate linear regres-sion analysis were used for analysis.Results:Compared with patients with BD-Ⅱ,patients with BD-Ⅰ had more risk to have psychotic features(OR=5.75,95％CI:2.82-11.76),longer disease duration,and more repeated transcra-nial magnetic therapy(OR=3.09,95％CI:1.02-9.35),higher uric acid,total cholesterol and high-density lipo-protein.BD-Ⅰ in Han nationality was more common(OR=11.50,95％CI:1.76-75.30),and had lower education level(OR=10.22,95％CI:1.16-89.77),and less family history of psychosis(OR=2.34,95％CI:1.01-5.42).Conclusion:There are significant differences between BD-Ⅰ and BD-Ⅱ in demographic and clinical charac-teristics,treatment status,and physiological indicators,which could provide clues for exploring the pathogenesis of bipolar disorder.

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.