Objective:To explore the time variations of the influence of the ultra-high dose rate irradiation (FLASH irradiation, FLASH-IR) and conventional dose rate irradiation (CONV-IR) of electron beams under different doses on the energy metabolism of triple-negative breast cancer cells MDA-MB-231.Methods:The basal metabolism of the MDA-MB-231 cells and normal breast epithelial cells MCF-10A was compared using a Seahorse XF Pro Metabolic Analyzer. Based on an irradiation platform with a thermionic cathode electron accelerator (6 MeV), the MDA-MB-231 cells were exposed to FLASH-IR (106 Gy/s) and CONV-IR (0.1 Gy/s) at 2 and 14 Gy, respectively. Meanwhile, a sham irradiation group was established under identical culture conditions. The mitochondrial metabolism and glycolytic metabolism of the cells at 4, 24, and 48 h post-irradiation were analyzed.Results:Compared to the MCF-10A cells, the MDA-MB-231 cells exhibited a greater reliance on glycolytic metabolism. Compared to those of the sham irradiation group, MDA-MB-231 cells in the 2 Gy CONV-IR group showed up-regulated ATP-linked respiration at 4, 24, and 48 h post-irradiation ( t = 2.69-3.70, P < 0.05). Their glycolytic level and glycolytic capacity were up-regulated only at 4 h post-irradiation and were down-regulated at 48 h ( t = 2.79, -4.44, P < 0.05). In contrast, there was no statistically significant difference in these indicators between the FLASH-IR and CONV-IR groups ( P > 0.05). However, the proton leak of the MDA-MB-231 cells in the FLASH-IR group was relatively down-regulated at 4 h post-irradiation and was significantly up-regulated at 24 h and 48 h post-irradiation compared with the CONV-IR group ( t = -2.45, 3.19, 6.51, P < 0.05). At 14 Gy, the MDA-MB-231 cells in the CONV-IR group showed progressively increased mitochondrial and glycolytic metabolism across all time points ( t = 2.48-12.14, P < 0.05). Notably, compared with the CONV-IR group, the MDA-MB-231 cells in the FLASH-IR group exhibited more significantly up-regulated basal respiration, ATP-linked respiration, and non-mitochondrial oxygen consumption ( t = 2.56-6.51, P < 0.05), as well as a higher glycolytic capacity at 24 h post-irradiation ( t = 2.86, P < 0.05). Conclusions:Low-dose (2 Gy) FLASH-IR induces relatively up-regulated proton leak in breast cancer cells MDA-MB-231 at 24 h post-irradiation. In contrast, under high-dose (14 Gy) FLASH-IR, the MDA-MB-231 cells show more pronounced mitochondrial metabolic stress and a higher demand for energy metabolism.

Objective:This study systematically summarized the construction experience of the immunology platform at the Institute of Basic Medical Sciences, Peking University Third Hospital, aiming to provide theoretical references and practical guidance for research-oriented hospitals in building high-quality research platforms.Methods:This study employed case study analysis to elaborate on the platform development initiatives, integrating literature analysis and in-depth interviews to conduct a horizontal comparison of management models among peer research platforms.Results:Through five years of development, the platform had achieved remarkable outcomes via a model integrating ″Talent cultivation-Technological innovation-Equipment procurement″ Research talents had demonstrated breakthroughs in securing national-level research grants, publishing high-impact papers, and obtaining scientific awards. The technical service system had achieved enhancement in both service scope and professional depth, fostering robust interdisciplinary synergy. The platform had effectively expanded its societal engagement capacity.Conclusions:The sustainable advancement of research-oriented hospital immunology platform necessitates establishing standardized flow cytometry databases and implementing high-dimensional data integration. Building upon multidisciplinary convergence, it is imperative to pioneer innovative operational mechanisms characterized by efficiency, open-access, and shared frameworks.

Objective:This study systematically summarized the construction experience of the immunology platform at the Institute of Basic Medical Sciences, Peking University Third Hospital, aiming to provide theoretical references and practical guidance for research-oriented hospitals in building high-quality research platforms.Methods:This study employed case study analysis to elaborate on the platform development initiatives, integrating literature analysis and in-depth interviews to conduct a horizontal comparison of management models among peer research platforms.Results:Through five years of development, the platform had achieved remarkable outcomes via a model integrating ″Talent cultivation-Technological innovation-Equipment procurement″ Research talents had demonstrated breakthroughs in securing national-level research grants, publishing high-impact papers, and obtaining scientific awards. The technical service system had achieved enhancement in both service scope and professional depth, fostering robust interdisciplinary synergy. The platform had effectively expanded its societal engagement capacity.Conclusions:The sustainable advancement of research-oriented hospital immunology platform necessitates establishing standardized flow cytometry databases and implementing high-dimensional data integration. Building upon multidisciplinary convergence, it is imperative to pioneer innovative operational mechanisms characterized by efficiency, open-access, and shared frameworks.

Objective:To explore the time variations of the influence of the ultra-high dose rate irradiation (FLASH irradiation, FLASH-IR) and conventional dose rate irradiation (CONV-IR) of electron beams under different doses on the energy metabolism of triple-negative breast cancer cells MDA-MB-231.Methods:The basal metabolism of the MDA-MB-231 cells and normal breast epithelial cells MCF-10A was compared using a Seahorse XF Pro Metabolic Analyzer. Based on an irradiation platform with a thermionic cathode electron accelerator (6 MeV), the MDA-MB-231 cells were exposed to FLASH-IR (106 Gy/s) and CONV-IR (0.1 Gy/s) at 2 and 14 Gy, respectively. Meanwhile, a sham irradiation group was established under identical culture conditions. The mitochondrial metabolism and glycolytic metabolism of the cells at 4, 24, and 48 h post-irradiation were analyzed.Results:Compared to the MCF-10A cells, the MDA-MB-231 cells exhibited a greater reliance on glycolytic metabolism. Compared to those of the sham irradiation group, MDA-MB-231 cells in the 2 Gy CONV-IR group showed up-regulated ATP-linked respiration at 4, 24, and 48 h post-irradiation ( t = 2.69-3.70, P < 0.05). Their glycolytic level and glycolytic capacity were up-regulated only at 4 h post-irradiation and were down-regulated at 48 h ( t = 2.79, -4.44, P < 0.05). In contrast, there was no statistically significant difference in these indicators between the FLASH-IR and CONV-IR groups ( P > 0.05). However, the proton leak of the MDA-MB-231 cells in the FLASH-IR group was relatively down-regulated at 4 h post-irradiation and was significantly up-regulated at 24 h and 48 h post-irradiation compared with the CONV-IR group ( t = -2.45, 3.19, 6.51, P < 0.05). At 14 Gy, the MDA-MB-231 cells in the CONV-IR group showed progressively increased mitochondrial and glycolytic metabolism across all time points ( t = 2.48-12.14, P < 0.05). Notably, compared with the CONV-IR group, the MDA-MB-231 cells in the FLASH-IR group exhibited more significantly up-regulated basal respiration, ATP-linked respiration, and non-mitochondrial oxygen consumption ( t = 2.56-6.51, P < 0.05), as well as a higher glycolytic capacity at 24 h post-irradiation ( t = 2.86, P < 0.05). Conclusions:Low-dose (2 Gy) FLASH-IR induces relatively up-regulated proton leak in breast cancer cells MDA-MB-231 at 24 h post-irradiation. In contrast, under high-dose (14 Gy) FLASH-IR, the MDA-MB-231 cells show more pronounced mitochondrial metabolic stress and a higher demand for energy metabolism.

Objective:To explore the paths and goals of organized construction for scientific research platforms in large-scale hospitals under the background of organized scientific research in China.Methods:By reviewing the relevant literature, and analyzing the construction of existing international and domestic research platforms for organized scientific research, this article elaborated on the importance and necessity of building a research platform for clinical hospitals under the background of organized scientific research and made suggestions for the platform construction.Results:Organized scientific research requires the organized construction of scientific research platforms. The construction of organized scientific research platforms should always focus on the major national needs, serve major scientific plans, carry out organized talent training, and internal efficient and orderly organization and operation, under the principle of interdisciplinary and multi-level collaborative innovation and development.Conclusions:In response to the strategic needs of national science and technology in the 14-Five Year Plan, the hospital scientific research platforms should be upgraded, integrated, expanded, and improved in an organized way, to form a multi-disciplinary and cross-dimensional platform structure to ensure the smooth development of organized scientific research.

Objective:To analyze the expression of human leukocyte antigen G (HLA-G) in human T-cell leukemia virus type 1 (HTLV-1)-positive T cells, and to investigate its role in the occurrence and development of HTLV-1 infection.Methods:The expression of HLA-G in HTLV-1-positive T cell lines (MT2 and MT4) was detected by Western blot and real-time PCR. HLA-G gene in MT2 and MT4 cells was knocked down by siRNA, and the effects of HLA-G on the expression of HTLV-1 Tax and P19 at mRNA and protein levels were detected by Western blot and real-time PCR. Moreover, the changes in cytokine expression in MT2 and MT4 cells were monitored at RNA level after HLA-G gene silencing. The proliferation ability of MT2 and MT4 cells was analyzed by CCK8. Signal transducer and activator of transcription 3 (STAT3) pathway-related proteins were detected by Western blot.Results:Compared with HTLV-1-negative T cells (Jurkat and MOLT4), the expression of HLA-G increased significantly in MT2 and MT4 cells. After knocking down the HLA-G gene with siRNA in MT2 and MT4 cells, the expression of HTLV-1 Tax and P19 at mRNA and protein levels was decreased, and the expression of antiviral cytokines IFN-γ and TNF-α was increased. The proliferation of MT2 and MT4 cells and STAT3 phosphorylation in these cells were decreased.Conclusions:HTLV-1 could induce T cells to overexpress the immune tolerance molecule HLA-G. Silencing HLA-G gene in HTLV-1-positive T cells could promote the production of antiviral cytokines and reduce IL-6 expression and STAT3 phosphorylation, thereby effectively inhibiting the replication of HTLV-1.

Objective:To observe the mRNA and protein expression levels of thyroid stimulating hormone receptor (TSHR), protein kinase A (PKA) and sodium iodine transporter (NIS) in mammary gland tissue of lactating rats with different iodine nutrition levels, and to explore the role of thyroid stimulating hormone (TSH)-THSR-cyclic adenosine monophosphate (cAMP)-PKA signal pathway in the process of mammary iodine uptake during lactation.Methods:Using a group design, according to body weight (80 - 100 g), 110 Wistar female rats were randomly divided into normal iodine (NI) group, severe iodine deficiency (SID) group, moderately iodine deficiency (MID) group, moderately iodine excess (MIE) group and severe iodine excess (SIE) group, with 22 rats in each group. Another 22 Wistar male rats were selected, and the feeding situation was consistent with that of NI group. After 3 months of feeding, 24-hour urine samples of female rats were collected, and the female rats were caged with the male rats (5 ∶ 1). After mating, each female rat was fed separately. At 10 days of childbirth, the lactating rats were sacrificed and thyroid and mammary gland tissues were taken. The urinary iodine was determined by arsenic cerium catalytic spectrophotometry. The morphological changes of thyroid and mammary gland tissues were observed by HE staining. The mRNA expression levels of TSHR, PKA and NIS in thyroid and mammary gland tissues were measured by real-time PCR; the protein expression levels of TSHR, PKA, phosphorylated PKA (p-PKA), and NIS in mammary gland tissue were measured by Western blotting.Results:Compared with NI group (162.59 μg/L), the median urinary iodine of female rats in SID and MID groups (3.16, 6.36 μg/L) was lower, and the median urinary iodine of female rats in MIE and SIE groups (2 356.27, 11 507.29 μg/L) was higher ( P < 0.01). HE staining showed that different levels of iodine uptake had different effects on thyroid follicles: most of the follicles in NI group were uniform round or oval; in MID group, the number of small follicles increased, the epithelial cells were monolayer columnar or cubic, the follicular cavity became smaller, and the glia decreased; the follicles in SID group became smaller, and the epithelial cells were columnar or high columnar, with reduced or absent glia in the follicular cavity; pleomorphic changes were found in thyroid follicles in SIE and MIE groups, with some follicles significantly enlarged and some small follicles hyperplasia. Different levels of iodine intake had different effects on mammary duct: compared with NI group, the connective tissue around the mammary duct in SID and MID groups showed obvious fibrosis, while the fibrosis in MIE and SIE groups was significantly reduced. The results of real-time PCR showed that there were significant differences in the mRNA expression levels of TSHR, PKA and NIS in thyroid tissues of lactating rats with different levels of iodine nutrition ( F = 10.73, 92.37, 115.75, P < 0.01). There were statistically differences in the mRNA expression levels of TSHR, PKA and NIS in mammary gland tissues of lactating rats with different levels of iodine nutrition ( F = 40.25, 39.63, 14.92, P < 0.05). Western blotting results showed that there were significant differences in the protein expression levels of TSHR, PKA, p-PKA and NIS in mammary gland tissues of lactating rats with different levels of iodine nutrition ( F = 4.14, 6.73, 8.48, 4.51, P < 0.05). Among them, the protein expression level of TSHR in MIE and SIE groups was lower than that in NI group ( P < 0.05); the protein expression level of PKA in SID and MID groups was higher than that in NI group ( P < 0.05); the protein expression level of p-PKA in SID group was higher than that in NI group, but that in SIE group was lower than that in NI group ( P < 0.05), the protein expression level of NIS in SID group was higher than that in NI group ( P < 0.05). Conclusions:The mRNA and protein expression levels of TSHR are decreased in mammary gland tissues of lactating rats with high iodine intake, while the mRNA and protein expression levels of PKA and NIS are increased in low iodine intake. TSH-TSHR-cAMP-PKA signal pathway may be involved in the regulation of iodine intake in mammary gland tissue of lactating rats, which may protect itself and its offspring.

Microbial ecosystem comprises a complex community in which bacteria interact with each other. The potential roles of the intestinal microbiome play in human health have gained considerable attention. The imbalance of gut microbial community has been looked to multiple chronic diseases. Cardiovascular diseases (CVDs) are leading causes of morbidity worldwide and are influenced by genetic and environmental factors. Recent advances have provided scientific evidence that CVD may also be attributed to gut microbiome. In this review, we highlight the complex interplay between microbes, their metabolites, and the potential influence on the generation and development of CVDs. The therapeutic potential of using intestinal microbiomes to treat CVD is also discussed. It is quite possible that gut microbes may be used for clinical treatments of CVD in the near future.

Objective To explore the diagnosis and treatment of Castleman's disease (CD) of the abdomen and pelvis.Methods The clinical data of 51 cases of abdomen and pelvis CD were analyzed retrospectively from Jan 2007 to Oct 2017 in the First Affiliated Hospital of Zhengzhou University.Patients were divided into two groups according to the different clinical classifications:Localized CD (n =42) and Multicentric CD (n =9).Results 32 cases of LCD were asymptomatic (76％),others accompanied by abdominal or waist pain,abdominal distention.The main pathological type was hyaline vascular (93％),which can be cured by surgical treatment (41/42).MCD always accompanied by multiple superficial and deep lymph node enlargement in the whole body.Most of them suffered from anemia,fever,weight loss and dyspnea.CRP increased,hypoproteinemia,globulin increased,neutropenia were found.The main pathological type was plasma cell type (56％).There were no progress in 3 cases,and 6 cases were on remission after operation.Conclusion The diagnosis of abdomen and pelvis CD depends on pathological examination.LCD clinical symptoms are mild and good prognosis after surgery.However,MCD clinical manifestations are complex,and relatively poor prognosis after comprehensive treatment.

Objective To explore the effect of oral-muscle biofeedback system training on the rehabilitation of cognitive dysfunction in patients with obstructive sleep apnea (OSA) after ischemic stroke.Methods A total of 60 cases of poststroke OSA patients with cognitive dysfunction admitted to the rehabilitation center of deAn hospital in changzhou city from June 2017 to March 2018 were selected.On the basis of routine rehabilitation treatment,the control group was given positive pressure ventilation treatment,and the observation group was given oral muscle biofeedback system training.The changes of polysomnography (PSG) parameters,Montreal cognitive assessment (MoCA) score,serum matrix metalloproteinase-9 (MMP-9) and plasma homcysteinemia (Hcy) expression levels in the two groups before and after treatment were compared.Results Apnea hypopnea index and maximum apnea time of the two groups were significantly decreased after treatment compared with those before treatment,and the lowest SpO2 and average SpO2 were significantly higher than those before treatment(P＜0.05).After treatment,MoCA total score and the dimensions score of patients in the observation group were significantly higher than those in the control group at the same time (P＜0.05).After treatment,the levels of Hcy((12.38±4.54) μmol/L) and MMP-9((124.52± 12.94) μg/L) in the observation group were significantly lower than those in the control group at the same time(Hcy(17.52±6.27) μmol/L,MMP-9(268.25±20.5 7)μg/L),and the difference was statistically significant (Hcy:t=3.637,P＜0.05;MMP-9:t =32.395,P＜0.05).Conclusions Positive pressure ventilation and oral muscle biofeedback system training have the same effect on OSA after stroke,but oral muscle biofeedback system training can also effectively improve patients' cognitive function.