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 investigate the impacts of usnea acid(UA)on the proliferation of human ovarian cancer(OC)cells.Methods Ovarian adenocarcinoma cells SKOV3 were randomly divided into control group,L-UA group,M-UA group,H-UA group(with 10,20,and 50 μmol/L UA added respectively),pcDNA3.1-NC group and pcDNA3.1-PD-1 group.RT-qPCR method was applied to detect the expression of programmed cell death 1(PD-1)and programmed cell death ligand 1(PD-L1)in SKOV3 cells.CCK-8 assay and plate method were applied to detect the effect of UA on SKOV3 cell proliferation.The effect of UA on SKOV3 cells apoptosis was examined by flow cytometry.Mouse ovarian epithelial cancer cell line ID8 cells were collected to construct an OC mouse model,and the mass and volume of OC tumors were recorded.Immuno-histochemical microscopy was applied to detect the infiltration of PD-1,PD-L1,and CD8+T cells.Results The PD-1 mRNA,PD-L1 mRNA,colony count,A450 val-ue,PCNA protein,PD-1 protein,and PD-L1 protein in the L-UA,M-UA,and H-UA groups were lower than those in the control group,the apoptosis rate and Bax protein were higher in the control group(P<0.05).Com-pared with the H-UA group and the pcDNA3.1-NC group,the PD-1 mRNA,PD-L1 mRNA,colony count,A450 value,PCNA protein,PD-1 protein,and PD-L1 protein in the pcDNA-3.1-PD-1 group increased and the apoptosis rate and Bax protein decreased(P<0.05).The quality,volume,positivity rate of PD-1and PD-L1 of OC tumors in the UA group was lower than that in the control group,the counting number of CD8+T cell infiltration was higher than control group(P<0.05).Conclusions UA may inhibit progression of OC cell line SKOV3 by regula-ting cell proliferation,apoptosis,and immune escape.

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.

Objective:To compare the difference of tumor control probability (TCP) and normal tissue complication probability (NTCP) between different radiotherapy schemes bases on biological model of non-small cell lung cancer(NSCLC) that used in assessing radiotherapy. Methods:The radiotherapy data of 15 NSCLC patients who admitted to Tianjin Medical University General Hospital from April 2021 to July 2022 were collected. The low resolution Poisson (TCP Poisson LQ) model,Zaider Minerbo (TCP-ZM) model and TCP Logit model were respectively adopted to fit TCP curve for all patients. Lyman-Kutcher-Burman (LKB) model and linear quadratic (LQ) model were adopted to fit NTCP curves for comparing applicability of several models in tumor control rate,radiation pneumonitis and radiation pericarditis,and the differences in TCP and NTCP among conventional radiotherapy regimen (scheme 1),regimen of maximum gain ratio of treatment (scheme 2),and maximum segmentation frequency regimen (scheme 3) as mean lung dose (MLD)<20 Gy. Results:The average TCP of the TCP Poisson LQ model was (87.2±11.92)％ at 60-70 Gy,which met the requirement of clinical dose. The incidence rate of radiation pneumonitis,which was calculated by the NTCP-LQ model,was higher than that by the NTCP-LKB model when the average radiation dose of whole lung was less than 26 Gy. In the comparison of different schemes,the TCP mean of scheme 3 was (81.56±11.20)％,which was respectively higher than that of other two schemes (60.28±8.04)％ and (69.46±18.09)％,and the differences of them were statistically significant (t=-6.196,-1.969,P<0.05). The average incidence of radiation pneumonitis in Scheme 3 was (19.24±0.43)％,which was respectively higher than that in Scheme 1 and Scheme 2[(15.07±3.24)％ and (15.89±4.55)％],respectively,and the differences of them were statistically significant (t=-5.878,-2.386,P<0.05). Conclusion:It is reasonable to use Poisson-LQ model and NTCP-LQ model to calculate TCP,and incidence of radiation pneumonitis in NSCLC patients. The maximum segmentation frequency scheme (Scheme 3) can effectively improve TCP under the premise of ensuring treatment safety when MLD<20 Gy.

Objective:To compare the difference of tumor control probability (TCP) and normal tissue complication probability (NTCP) between different radiotherapy schemes bases on biological model of non-small cell lung cancer(NSCLC) that used in assessing radiotherapy. Methods:The radiotherapy data of 15 NSCLC patients who admitted to Tianjin Medical University General Hospital from April 2021 to July 2022 were collected. The low resolution Poisson (TCP Poisson LQ) model,Zaider Minerbo (TCP-ZM) model and TCP Logit model were respectively adopted to fit TCP curve for all patients. Lyman-Kutcher-Burman (LKB) model and linear quadratic (LQ) model were adopted to fit NTCP curves for comparing applicability of several models in tumor control rate,radiation pneumonitis and radiation pericarditis,and the differences in TCP and NTCP among conventional radiotherapy regimen (scheme 1),regimen of maximum gain ratio of treatment (scheme 2),and maximum segmentation frequency regimen (scheme 3) as mean lung dose (MLD)<20 Gy. Results:The average TCP of the TCP Poisson LQ model was (87.2±11.92)％ at 60-70 Gy,which met the requirement of clinical dose. The incidence rate of radiation pneumonitis,which was calculated by the NTCP-LQ model,was higher than that by the NTCP-LKB model when the average radiation dose of whole lung was less than 26 Gy. In the comparison of different schemes,the TCP mean of scheme 3 was (81.56±11.20)％,which was respectively higher than that of other two schemes (60.28±8.04)％ and (69.46±18.09)％,and the differences of them were statistically significant (t=-6.196,-1.969,P<0.05). The average incidence of radiation pneumonitis in Scheme 3 was (19.24±0.43)％,which was respectively higher than that in Scheme 1 and Scheme 2[(15.07±3.24)％ and (15.89±4.55)％],respectively,and the differences of them were statistically significant (t=-5.878,-2.386,P<0.05). Conclusion:It is reasonable to use Poisson-LQ model and NTCP-LQ model to calculate TCP,and incidence of radiation pneumonitis in NSCLC patients. The maximum segmentation frequency scheme (Scheme 3) can effectively improve TCP under the premise of ensuring treatment safety when MLD<20 Gy.

The temporomandibular joint (TMJ) is surrounded by a joint capsule, the smooth inner layer of which is called the synovial membrane. Synovium is involved in various intraarticular diseases, and it is a key area of joint disease. Synovial type-A cells are located in the lining layer of the synovial membrane, mostly on the side of the membrane close to the joint cavity. They have a strong phagocytic effect, and their main role is to remove the degradation products of the intra-articular and extracellular matrix. Various intra-articular diseases will affect the synovium, which is the key area of joint disease. The method of cell culture in vitro can effectively simulate the growth environment of cells in vivo and can accurately understand the effects of single and multiple factors on synovial cells, which has become a basic research method. In this review paper, the latest research progress in human temporomandibular joint type-A synoviocytes is reviewed from the aspects of cell origin, in vitro culture, cell purification, and cell biological function.

The cross regional loose medical alliance is an important carrier in the current integrated development process of medical services in the Yangtze River Delta region. Smith policy implementation process model was used to analyze the development difficulties of cross regional loose medical alliances from idealized policies, policy implementation institutions, policy target groups, and policy implementation environment. Such medical alliances were formed under the background of integrated development in the Yangtze River Delta, with Shanghai′s tertiary public hospitals as leading units and medical institutions in Jiangsu, Zhejiang, and Anhui provinces as member units. Analysis showed that the policies for such medical alliances development had not yet clearly defined the organizational management mode, operational mechanism, and implementation path, and the corporate governance structure of medical alliance was immature; The policy implementation agencies were relatively lagging behind in the support of special funds and the formulation of related supporting policies; Participation of policy target groups was insufficient and their incentive mechanisms was imperfect; There were problems in the policy implementation environment, namely inconsistent medical and health service regulations and systems in different regions, different health financing capabilities of local governments, insufficient coordination of medical institution management concepts, and a lack of unified standards in information systems. Based on the above difficulties, this study proposed to strengthen the development planning and layout of cross regional loose medical alliances, and improve the corporate governance structure; To strengthen the government′s main responsibility and improving policy implementation capabilities; To improve the internal cooperation and operation mechanism of cross regional loose medical alliances, and enhance the sense of identity of the target group; To optimize the policy implementation environment and implement various support measures, so as to provide references for further promoting the coordinated development of high-quality medical resources in the Yangtze River Delta region.

Tetracycline (TC) natural products possess a variety of remarkable bioactivities and diverse structures. They are an important and fertile source for developing novel drugs. As one of the most successful drug families, TC antibiotics have been in clinical use for over seven decades, and continue to make an important contribution to human health nowadays. To date, studies on TC natural products and their biosynthesis have revealed numerous novel biochemical mechanisms and regulatory elements, which facilitates the rational metabolic engineering studies for generating novel bioactive TC analogs and inspires the development of new synthetic biology tools. In this review, we provide a comprehensive overview on the discovery, biosynthesis, and engineering of the existing TC natural products. These analyses will be of great value for the discovery, design and development of novel TC drugs in the future.
Humans ; Biological Products/metabolism* ; Anti-Bacterial Agents ; Metabolic Engineering ; Synthetic Biology ; Tetracycline