γδ T cells are a distinct subset of T lymphocytes that demonstrate anti-tumor activity that is not contingent upon conventional major histocompatibility complex-restricted antigen presentation. These cells demonstrate extensive reactivity to anti-breast cancer cells and are capable of exerting anti-breast cancer through mechanisms such as direct cell killing and immune regulation. γδ T cells are a promising type of effector cell that is being developed for the treatment of breast cancer through immunotherapy. Immunotherapy has emerged as a critical treatment modality for patients with postoperative or advanced breast cancer. The activation of γδ T cells in vivo or their use in adoptive cell therapy has emerged as a potential strategy for breast cancer immunotherapy. In this review, research progress on the characteristics of γδ T cells in breast cancer patients and their anti-breast cancer mechanism were summarized.

Objective:To explore the efficacy and safety of endovascular intervention combined with preoperative laparoscopic exploration in the treatment of patients with acute mesenteric artery ischemia.Methods:This was a prospective cohort study (NCT04686981). The study enrolled 31 patients with acute mesenteric artery ischemia from Oct 1, 2020 to Oct 1, 2022. Among them, 26 patients (84%) were male, with a mean age of (67±13) years and a mean time to onset of (21±8) hours. All patients underwent laparoscopic exploration in the hybrid operating room. If the presence of intestinal necrosis or suspected necrosis was clearly determined, the patient would undergo open surgery (mesenteric artery embolization, intestinal resection and intestinal double stoma) as the treatment by gastrointestinal surgeon. If intestinal necrosis or suspected necrosis was not found by laparoscopy, the patient would undergo endovascular intervention by vascular surgeon. The primary observational endpoints of this study were the proportion of patients who were not dependent on total parenteral nutrition and all-cause mortality within 30 days after operation. The secondary observational endpoints were the rate of mesenteric vascular patency within 30 days and the proportion of interventions that were converted to open surgery.Results:Six patients underwent open surgery and 25 patients underwent endovascular intervention, including 13 cases of thrombus reduction alone, 3 cases of stent implantation during the same period after reduction, and 9 cases of stent implantation alone. Twenty-four patients (77%) were completely weaned from the TPN within 30 days after the procedure, and all-cause mortality was observed in 3 cases (9.7%). The patency rate of the mesenteric artery within 30 days after the procedure was 82.1%. The rate of conversion to open surgery after intervention was 16%.Conclusions:Endovascular intervention combined with preoperative laparoscopic exploration can clarify intestinal ischemia in acute mesenteric patients as early as possible, and individualized treatment strategies for each patient by multidisciplinary care team can potentially improve the prognosis of such patients.

Objective To observe the value of dual domain(projection domain and image domain)joint learning reconstruction network(DDRNet)for reconstructing chest limited angle CT images.Methods Totally 4 300 chest enhanced CT images of 65 patients with chest tumors were retrospectively enrolled and reconstructed with DDRNet,and 3D and 2D projection information fusion were performed.The reconstruction effect of DDRNet was evaluated and compared with that of single domain reconstruction and filtered back projection(FBP),residual encoder-decoder convolutional neural network(RED-CNN),Resnet and deconvolution network(RDN),as well as of generative adversarial network(GAN).Results The peak signal to noise ratio(PSNR)of DDRNet reconstructed images tended to stabilize after approximately 60 iterations,while the projection domain and image domain learning networks tended to stabilize after approximately 90 and 80 iterations.After stable training,compared to the projection domain learning network,the fluctuation of output results of DDRNet and image domain learning networks were less.After 200 rounds of training,PSNR of DDRNet reconstructed images was significantly higher than that of projection domain and image domain learning networks.The quality of DDRNet reconstructed image was significantly better than that of FBP,RED-CNN,RDN and GAN.Conclusion DDRNet could be used to effectively reconstruct high-quality chest limited angle CT images.

Objective:To investigate the dosimetric impact of tumor treating fields (TTF) transducer arrays on concurrent radiotherapy for patients with glioblastoma (GBM).Methods:A strategy was developed to accurately simulate the dosimetric impact of TTF arrays on radiotherapy, including the establishment of accurate auto-segmentation technique for TTF arrays, determination of the relative electron density (RED) of the transducer arrays and validation of the dose calculation accuracy in the treatment planning system (TPS) for TTF arrays. Based on this strategy, the dosimetric impact of TTF arrays on clinical treatment plans of 10 patients with GBM was evaluated. Furthermore, the dosimetric comparison between the clinical plans with different beam energies were investigated when TTF arrays were used. The methods of analysis of variance were paired t-test or Wilcoxon signed-rank test based on whether the differences followed a normal distribution. Results:The auto-segmentation technique for TTF arrays was established by designing a workflow in Mim software and achieved a Dice coefficient of 0.93 and a Jaccard index of 0.87 compared to the standard contours. The RED of TTF arrays was 3.3 which was derived from the comparison between the measured and simulated percentage depth dose (PDD) with and without TTF arrays on phantom. Measured and calculated dose distributions were compared using the 2D gamma analysis. The gamma passing rates on the coronal plane of 4 mm and 5.1 cm depth were 96.64% and 94.55% at the criteria of 3% /3 mm, indicating that the calculation accuracy of algorithm in TPS for TTF arrays could meet clinical requirements. In the clinical treatment plans of patients with GBM, the presence of TTF arrays caused a mean reduction of planning target volume (PTV) dose of approximately 1%, and an increase in scalp dose of approximately 5%, with minimal impact on other organs at risk (OAR). The 10 MV plans resulted in a higher dose of PTV by 0.3% and lower dose of scalp by approximately 3% compared to the 6 MV plans, when considering TTF arrays.Conclusions:The accurate simulation strategy for the dosimetric impact of TTF arrays on radiotherapy established in this study ensures the accuracy and precision of the calculations. In TTF therapy combined with concurrent radiotherapy for GBM, TTF arrays have slight effect on PTV dose, but significantly increase scalp dose. High-energy beam can reduce the impact of TTF arrays.

Objective:To compare the plan quality between coplanar and non-coplanar volumetric modulated arc therapy (co-VMAT and nco-VMAT) techniques for the whole brain radiotherapy with hippocampus and hypothalamic-pituitary (HT-P) axis sparing.Methods:A total of 15 patients who underwent prophylactic cranial irradiation in Tianjin Medical University General Hospital from November 2021 to August 2023 were retrospectively selected. The hippocampus and HT-P axis were delineated according to Radiation Therapy Oncology Group (RTOG) 0933 and contouring guidelines for hypothalamus. Co-VMAT and nco-VMAT plans were generated for each patient with a prescription dose of 30 Gy in 10 fractions. Then, dosimetric parameters, plan robustness, plan complexity, and delivery efficiency for both plans were compared using paired t-test. Results:Both co-VMAT and nco-VMAT plans could achieve dosimetric objectives. There were no significant differences in D 2%, D 95% and conformity index (CI) of planning target volume (PTV) between the two plans. The D 98% and homogeneity index (HI) of PTV in co-VMAT showed a slight inferiority compared to that in nco-VMAT (D 98%: 26.37 Gy vs. 26.96 Gy, P=0.001; HI: 0.25 vs. 0.24, P=0.002). The D min of bilateral hippocampus in co-VMAT were 8.55 Gy (left) and 8.32 Gy (right), which were lower than 9.31 Gy (left) and 9.26 Gy (right) in nco-VMAT. In addition, the D mean of the hypothalamus and pituitary in the co-VMAT plan were lower than those in the nco-VMAT plan (hypothalamus: 11.54 Gy vs. 12.27 Gy; pituitary: 11.72 Gy vs.12.1 Gy, both P<0.001). The doses to the hippocampus and HT-P axis were highly sensitive to errors in both co-VMAT and nco-VMAT plans, while the sensitivity of dose to errors in the PTV and other organs at risk was low. The co-VMAT plan had lower complexity compared to the nco-VMAT plan, with γ passing rate at 3%/3 mm criteria of 99.06%±0.60% and 98.05%±2.89%, respectively. The average beam-on time of the co-VMAT plan was 4.8 min, approximately 2/3 of the time for nco-VMAT, while the average treatment time was 6.3 min, approximately half of the treatment time for nco-VMAT. Conclusions:Both co-VMAT and nco-VMAT can achieve hippocampus and HT-P axis sparing in the whole brain radiotherapy. In the co-VMAT plan, the D 98% of the PTV is slightly smaller, but it provides better protection for the hippocampus and HT-P axis. The doses to the hippocampus and HT-P axis are sensitive to errors in both plans. However, the co-VMAT plan has lower complexity, higher delivery efficiency, and is more suitable for clinical treatment.

Alzheimer's disease (AD) is the most common type of dementia. Almost two-thirds of patients with AD are female. The reason for the higher susceptibility to AD onset in women is unclear. However, hormone changes during the menopausal transition are known to be associated with AD. Most recently, we reported that follicle-stimulating hormone (FSH) promotes AD pathology and enhances cognitive dysfunctions via activating the CCAAT-enhancer-binding protein (C/EBPβ)/asparagine endopeptidase (AEP) pathway. This review summarizes our current understanding of the crucial role of the C/EBPβ/AEP pathway in driving AD pathogenesis by cleaving multiple critical AD players, including APP and Tau, explaining the roles and the mechanisms of FSH in increasing the susceptibility to AD in postmenopausal females. The FSH-C/EBPβ/AEP pathway may serve as a novel therapeutic target for the treatment of AD.
Female ; Humans ; Male ; Alzheimer Disease/pathology* ; CCAAT-Enhancer-Binding Protein-beta/metabolism* ; Cognitive Dysfunction/metabolism* ; Signal Transduction ; Follicle Stimulating Hormone

Cystic fibrosis (CF) is a rare autosomal recessive disease with only one pathogenic gene cystic fibrosis transmembrane conductance regulator (CFTR). To identify the potential pathogenic mutations in a Chinese patient with CF, we conducted Sanger sequencing on the genomic DNA of the patient and his parents and detected all 27 coding exons of CFTR and their flanking intronic regions. The patient is a compound heterozygote of c.2909G > A, p.Gly970Asp in exon 18 and c.1210-3C > G in cis with a poly-T of 5T (T5) sequence, 3 bp upstream in intron 9. The splicing effect of c.1210-3C > G was verified via minigene assay in vitro, indicating that wild-type plasmid containing c.1210-3C together with T7 sequence produced a normal transcript and partial exon 10-skipping-transcript, whereas mutant plasmid containing c.1210-3G in cis with T5 sequence caused almost all mRNA to skip exon 10. Overall, c.1210-3C > G, the newly identified pathogenic mutation in our patient, in combination with T5 sequence in cis, affects the CFTR gene splicing and produces nearly no normal transcript in vitro. Moreover, this patient carries a p.Gly970Asp mutation, thus confirming the high-frequency of this mutation in Chinese patients with CF.
China ; Cystic Fibrosis/genetics* ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics* ; Humans ; Mutation ; Poly T ; RNA, Messenger/genetics*

Objective:Due to the low contrast between tumors and surrounding tissues in CBCT images, this study was designed to propose an automatic segmentation method for central lung cancer in CBCT images.Methods:There are 221 patients with central lung cancer were recruited. Among them, 176 patients underwent CT localization and 45 patients underwent enhanced CT localization. The enhanced CT images were set as the lung window and mediastinal window, and elastic registration was performed with the first CBCT validation images to obtain the paired data set. The CBCT images could be transformed into" enhanced CT" under the lung window and mediastinal window by loading the paired data sets into cycleGAN network for style transformation. Finally, the transformed images were loaded into the UNET-attention network for deep learning of GTV. The results of segmentation were evaluated by Dice similarity coefficient (DSC), Hausdorff distance (HD) and the area under the receiver operating characteristic curve (AUC).Results:The contrast between tumors and surrounding tissues was significantly improved after style transformation. The DSC value of cycleGAN+ UNET-attention network was 0.78±0.05, HD value was 9.22±3.42 and AUC value was 0.864, respectively.Conclusion:The cycleGAN+ UNET-attention network can effectively segment central lung cancer in CBCT images.

Objective:To analyze the effect of endovascular therapy (including balloon dilation, debulking and anti-restenosis technique) for below-the-ankle atherosclerotic lesions in chronic limb threatening ischemic patients.Methods:A retrospective analysis was performed on the clinical data of 465 patients (570 limbs) with below-the-ankle atherosclerosis who were consecutively admitted to Beijing Tsinghua Changgung Hospital Affiliated to Tsinghua University from April 2018 to December 2021. All patients received balloon dilatation below the ankle artery as basic treatment, including 67 patients in debulking subgroup, 82 patients in anti-restenosis subgroup and 11 patients in the triple therapy subgroup. The reocclusion rate, target lesion reintervention rate at 1, 3, 6 and 12 months after surgery were compared; The wound healing rate at 3 months, limb salvage rate at 6 and 12 months and mortality at 12 months in the Global Limb Anatomic Staging System (GLASS) grading groups P0, P1 and P2 were compared.Results:The technical success rate of this group was 76.0%(433 limbs/570 limbs). The follow-up rates of 6 and 12 months after operation were 85.4%(370 limbs/433 limbs) and 75.3%(326 limbs/433 limbs), respectively. The length of treated lesions was (3.6±1.3)cm; The reocclusion rates were 5.5%(23 limbs/420 limbs), 8.2%(33 limbs/403 limbs), 14.9%(55 limbs/370 limbs) and 23.6%(77 limbs/326 limbs) at 1, 3, 6 and 12 months after operation; The reintervention rate of target lesions in 6, 12 months was 7.6%(28 limbs/370 limbs) and 12.0%(39 limbs/326 limbs) respectively; The wound healing rate in groups P0, P1 and P2 within 3 months was 87.3%(192 limbs), 70.5%(62 limbs) and 10.5%(2 limbs) respectively ( P<0.001), the limb salvage rate in 6 months was 96.2%(200 limbs), 84.7%(127 limbs) and 33.3%(4 limbs) respectively ( P<0.001), and the limb salvage rate in 12 months was 78.7%(170 limbs), 54.5%(55 limbs) and 22.2%(2 limbs) respectively ( P<0.001). The mortality was 6.9%(32/465) 12 months after operation. Conclusions:Endovascular therapy below-the-ankle is feasible and has high technical success rate. The constitute integrity of pedal-plantar loop in limb- threatening phase is related to 3-month wound healing rate and limb salvage rate.