ObjectiveTo investigate the effect of icariin （ICA） on steroid-induced ferroptosis in bone microvascular endothelial cells （BMECs）. MethodsRat BMECs were selected and treated with 500 mg·L^-1 hydrocortisone for 1.5 h to establish a ferroptosis model of BMECs. The experimental cells were divided into a blank group， hormone group （500 mg·L^-1 hydrocortisone）， ICA group （500 mg·L^-1 hydrocortisone + 34 mg·L^-1 ICA）， and ferroptosis agonist group （500 mg·L^-1 hydrocortisone + 34 mg·L^-1 ICA + 2.7 mg·L^-1 erastin）. Cell viability was detected by CCK-8. The levels of ferrous ion， glutathione （GSH）， malondialdehyde （MDA）， superoxide dismutase （SOD）， and reactive oxygen species （ROS） were detected by related kit species. The ferroptosis-related proteins， such as glutathione peroxidase 4（GPX4）， ferritin light chain （FTL）， and transferrin receptor protein1 （sTfR） were detected by Western blot， as well as autophagy-related proteins including microtubule-associated protein 1 light chain 3B （LC3B）， Beclin1， B-cell lymphoma-2 （Bcl-2）， and Caspase-3. Results500 mg·L^-1 hydrocortisone intervention for 1.5 h could effectively induce ferroptosis in BMECs， and ferroptosis levels could reach a peak as the intervention continued. In terms of cellular antioxidant capacity， compared with those in the blank group， the cell vitality， GSH in the hormone group decreased significantly， and the levels of ROS， SOD， MDA， and ferrous ions were significantly increased （P<0.01）. Compared with those in the hormone group， the cell viability， GSH were significantly increased， and the levels of ROS， SOD， MDA， and ferrous ions were decreased in the ICA group （P<0.01）. Compared with those in the ICA group， the cell vitality， GSH in the ferroptosis agonist group decreased significantly， and the levels of ROS， SOD， MDA， and ferrous ions increased significantly （P<0.01）. In terms of the relationship between ferroptosis and autophagy， compared with the blank group， the hormone group had significantly increased expression levels of LC3B， sTfR， Beclin1， and FTL and significantly decreased expression levels of GPX4 （P<0.01）. Compared with the hormone group， The ICA group had significantly decreased expression levels of LC3B， sTfR， and FTL and significantly increased expression levels of Beclin 1 and GPX4 （P<0.01）. Compared with those in the ICA group， the expression levels of LC3B， sTfR， and FTL increased in the rapamycin group， and those of Beclin 1 and GPX4 decreased （P<0.01）. In terms of cell ferroptosis and apoptosis，compared with the blank group， the hormone group had significantly increased expression levels of FTL， sTfR and Caspase-3 and significantly decreased expression levels of GPX4， and Bcl-2 （P<0.01）. Compared with the hormone group， the ICA group had significantly decreased expression levels of FTL， sTfR and Caspase-3 and significantly increased expression levels of GPX4， and Bcl-2 （P<0.01）. Compared with those in the ICA group， the expression levels of FTL， sTfR and Caspase-3 in the ferroptosis agonist group were increased， and the expression levels of GPX4， and Bcl-2 were decreased （P<0.01）. In terms of cell function，compared with that in the blank group， the ability of cell migration and tube formation was significantly decreased in the hormone group （P<0.01）. Compared with that in the hormone group， the cell migration and tube formation ability in the ICA group were significantly increased （P<0.01）. ConclusionFerroptosis is involved in steroid-induced damage in BMECs. ICA can inhibit steroid-induced ferroptosis in BMECs， and the mechanism may be associated with the inhibition of ferroptosis by regulating autophagy.

Abnormal amino acid metabolism promotes tumor progression by inducing malignant behaviors in tumor cells and altering the immune landscape within the tumor microenvironment. However, the underlying mechanisms remain unclear. In this study, we constructed colorectal cancer (CRC) organoids and patient-derived tumor xenograft (PDX) models, performing multifaceted validation to confirm that T-complex protein 1 subunit epsilon (CCT5), mediates the biosynthesis of aspartate and enhances sensitivity to anti-PD-L1 immunotherapy. Mechanistically, CCT5 directly binds to asparagine synthetase (ASNS) and promotes the synthesis of aspartate (Asn). The Asn-mTORC1 axis facilitates tumor cell proliferation while upregulating PD-L1 expression, which leads to a reduction in the number of effector CD8⁺ T cells. Treatment with l-asparaginase (ASNase) combined with anti-PD-L1 therapy effectively reverses the growth of CRC characterized by high CCT5 expression. In summary, we identify CCT5 as a potential biomarker to guide the combined use of ASNase and anti-PD-L1 antibodies in CRC treatment.

Objective:Object To evaluate the therapeutic effectiveness of postoperative adjuvant mitotane therapy in the context of adrenocortical carcinoma (ACC) by using a meta-analysis methodology.Methods:A comprehensive literature review was conducted by systematically searching the PubMed, EMBASE, Web of Science, and Cochrane Library databases. The search spanned from the establishment of each database to October 2023. Search terms, "mitotane", "adrenocortical carcinoma" or synonyms. Inclusion criteria, Studies comparing outcomes (overall survival (OS) and/or recurrence-free survival (RFS)) in ACC patients with or without mitotane, reporting adjusted hazard ratios (HR) in multivariate Cox regression. Exclusion criteria, Patients with distant metastases, RI(Microscopic residual tumor) rection of ACC, or adjuvant chemotherapy. Data extracted on mitotane treatment concentration, duration, and tumor stage. A meta-analysis was conducted utilizing R4.2.2 software to assess the impact of ACC on OS or RFS through the calculation of HR and 95% confidence intervals (CI). Subgroup analysis of RFS was conducted based on the use of mitotane to reach effective levels or adequate duration, as well as tumor stage ≤T 3. Results:A meta-analysis was conducted, including a total of 15 studies and involving 2084 patients with ACC. Of these patients, 991 received post-surgical treatment with mitotane, while 753 had ACC classified as stages ≤T 3. The results showed that adjuvant mitotane therapy in the ACC group after surgery led to significantly improved OS ( HR=0.45, 95% CI 0.34-0.58, I2=0, P=0.79) and RFS ( HR=0.65, 95% CI 0.51-0.83, I2=76%, P<0.01) compared to non-adjuvant mitotane therapy. Subgroup analysis further revealed that patients with effective mitotane concentration or sufficient time after surgery[Subgroup a(Median follow-up duration < 45 months): HR=0.59, 95% CI 0.44-0.79, I2=0, P=0.38; Subgroup b(Median follow-up duration ≥ 45 months): HR=0.93, 95% CI 0.90-0.96, I2=0, P=1.00 ]and with ≤T 3 stage ACC ( HR=0.61, 95% CI 0.47-0.79, I2=0, P=0.62)had better RFS compared to those who did not achieve the requisite mitotane concentration or postoperative interval, as well as patients with stage T 4 ACC. Conclusions:The administration of adjuvant mitotane therapy following ACC resection has been shown to significantly extend patients' OS and RFS, particularly when the therapy achieves optimal concentration or is administered for an adequate duration. Furthermore, in patients with ACC classified as stage ≤T 3, the effect of adjuvant mitotane therapy on prolonging RFS appears to be more consistent and reliable.

Objective To explore the feasibility and diagnostic value of ultra-fast scanning scheme based on deep learning-based reconstruction(DLR)for cervical MR examination.Methods Thirty-six subjects were prospectively enrolled and underwent both conventional scheme(scan time:6 min 14 s)and ultra-fast scheme(2 min)cervical spine MR scanning to acquire encompassing sagittal T1WI,sagittal adipose suppression T2WI and axial T2WI.The ultra-fast MRI were reconstructed using DLR method.The subjective and objective evaluations on imaging qualities of different MRIs were compared,along with the inter-observer agreement for diagnosing intervertebral disc degeneration and herniation.Results Compared with conventional MRI,artifacts in ultra-fast DLR images significantly reduced(P＜0.05).The subjective evaluation results of MRI had good agreement(all Kappa≥0.60).Compared with conventional MRI,the sagittal T1WI,T2WI and axial T2WI obtained with ultra-fast DLR showed significantly improved signal-to-noise ratio(SNR)of the spinal cord,cerebrospinal fluid(CSF)and vertebral body,as well as the spinal cord/CSF contrast(all P＜0.001).The Kappa value of 2 physicians for diagnosing intervertebral disc degeneration based on ultra-fast DLR and conventional scheme images was 0.94 and 1.00,respectively,of intervertebral disc herniation was 0.96 and 0.98,respectively.Conclusion Compared with conventional scanning scheme,using ultra-fast DLR scheme in cervical MR examination could shorten scanning time while achieve similar image quality and diagnostic accuracy.

【Objective】 To study the effects of platelets donation frequency on iron, copper, zinc content and superoxide dismutase(SOD) activity in plasma of blood donors. 【Methods】 128 apheresis platelet donors from August 25, 2020 to August 25, 2021 in our center were divided into 4 groups according to the frequency of platelet donation: first-time donors(n=30) were enrolled as group 1, and donors with 2 to 7 donations(n=23), 8 to 14 donations(n=29), 15 to 24 donations(n=46) within the previous period were group 2, group 3 and group 4. All these donors were males, with the average age of 42 ± 8.3, and had not donated whole blood in the past two years. Inductively coupled plasma mass spectrometry(ICP-MS) was used to detect the content of copper, iron and zinc in plasma of different groups of platelet donors. The SOD activity was detected by WST colorimetric kit. All data were statistically analyzed by SPSS 19.0 software. 【Results】 Significant differences in the content of iron and copper, but no in zinc, were noticed in donors of different groups(P<0.05). Multiple comparison showed that first-time blood donors presented significantly higher iron content but significantly lower copper content than those of donors with 15 to 24 blood donations per year(P<0.05), and no significant difference was found in iron and copper content among other groups(P>0.05). There was no significant difference in zinc content between every two groups(P>0.05). The SOD inhibition rate of blood donors in different groups was not significantly different. 【Conclusion】 The content of plasma iron, copper, and zinc and the SOD activity were not significantly affected if platelet donations were less than 15 times within a year. For those donated platelets more than 15 times within a year, the content of iron was found to decrease and copper to increase. It is suggested that platelet donations more than 15 times is correlated with the content of iron and copper in plasma of blood donors. Therefore, the proportion of iron-rich food should be appropriately increased in the daily diet for high-frequency(≥15 times per year) apheresis platelet donors after blood donation.

Objective: To study the distribution and pharmacokinetics of cefuroxime in rabbit eyes after intravenous administration. Methods: Thirty-five rabbits were randomly divided into 7 groups by random number table method, with 5 rabbits in each group.The rabbits in blank control group were feed without any treatment, the rest rabbits were injected with 40.63 mg/kg cefuroxime intravenously.The rabbits were sacrificed at 0.5 hour, 1.0 hour, 1.5, 2.0, 2.5 and 3.0 hours after injection, and the eyeballs were immediately dissected.The concentration of drug in different ocular tissues was detected by high performance liquid chromatography, and the pharmacokinetic parameters in eyes were computed by the DAS software.This study was approved by the Experimental Animal Ethics Committee of Shanxi Provincial Eye Hospital (201802b). Results: The peak concentrations (Cmax) of cefuroxime were (11.63±0.20), (1.59±0.05), (1.51±0.08), (0.99±0.07), (1.55±0.08) and (8.57±0.17)μg/ml in aqueous humor, iris-ciliary body, vitreous body, retinal-choroid, cornea and sclera, respectively.The times to peak (Tmax) were 1.5 hours, 1.0, 1.0, 0.5, 1.0 and 0.5 hour in aqueous humor, iris-ciliary body, vitreous body, retinal-choroid, cornea and sclera, respectively.The areas under drug time curve (AUC_0-t) were (26.60±0.62), (6.22±0.84), (5.86±0.16), (3.75±0.45), (5.50±0.15) and (26.48±0.73)(μg·h)/ml in aqueous humor, iris-ciliary body, vitreous body, retinal-choroid, cornea and sclera, respectively.Cefuroxime was not detected in the lens at different time points after injection.The parameters of pharmacokinetics were fitted to two compartment model. Conclusions Cefuroxime shows good penetration in aqueous humor, iris-ciliary body, vitreous body, retinal-choroid, cornea and sclera when administrated by intravenous injection in rabbits and cefuroxime has no distribution in lens.Cefuroxime can reach an effective concentration in ocular tissues 0.5 to 1.5 hours after intravenous injection.

The traditional biological principle for developing bone biomaterials is to directly stimulate the osteogenic differentiation of osteoblastic lineage cells, the direct effector cells for osteogenesis. This strategy has been successful for the development of bone biomaterials. However, recent progress in bone biology has revealed the vital role of the local bone microenvironment, especially the immune environment, in controlling osteogenesis. Interdisciplinary osteoimmunology has found that the osteoimmune and skeletal systems are closely related, sharing numerous cytokines and regulators. In addition, immune cells play an important role in the physiological and pathological processes of the skeletal system, suggesting that neglecting the importance of the immune response is a major shortcoming of the traditional strategy. Based on this principle, we propose a novel “osteoimmunomodulation”-based strategy to meet the strict requirements of new-generation bone biomaterials: instead of directly regulating the osteogenic differentiation of osteoblastic lineage cells, we should focus more on manipulating the responses of immune cells and developing biomaterials to induce an immune environment that provides conditions that balance osteogenesis and osteoclastogenesis for optimal osseointegration. This article reviews the recent progress on osteoimmunology and immunomodulatory biomaterials for the generation of the “osteoimmunomodulation” concept. Additionally, the outcomes of “osteoimmunomodulation”-related studies have been summarized to guide the development of advanced “osteoimmune-smart” bone substitute materials.

Objective To investigate the effects of autophagy on breast cancer cells to tamoxifen resist-ance.Methods Immunofluorescence was used to count the proportion of the cells with autophagy in MCF -7 and MCF-7/TAMR,as well as ,the average of autophagosome in each cells .Western blotting was used to detect the different expressions of p38,c-jun and LC3 in MCF-7 and MCF-7/TAMR.Stepwise selection was used to detect the duration of resistance to different doses of tamoxifen when upregulating or downregulating of LC 3.West-ern blot was facilitated to investigate changes of activity of p 38/c-jun.Rusults Compared with MCF -7,the proportion of the cells with autophagosome in MCF -7/TAMR was markedly increased ,the same as the average of autophagosome in each cells .Compared with MCF-7,LC3,especially LC3IIprotein expressive levels in MCF -7/TAMR was significantly increased .The expressive level of LC3 during the induction process of TAM resistance was negative correlated with resistant cell lines .The expressions of phosphorylated p 38 and c-Jun in MCF-7/TAMR were significantly increased .Conclusion Autophagy promotes breast cancer cells to resistant to tamox-ifen,due to downregulation of the expression of autophagy related proteins which may inhibit the generation of re -sistant breast cancer cells .This may be a viable treatment strategy for refractory breast cancer .

Breast cancer is one of the most common malignant tumors in women.Early diagnosis plays a very important role in the treatment of breast cancer.Recently,with the development of epigenetics,it gives us a new orientation for early detection for cancers.The most understood mechanism of epigenetics is DNA methyla-tion.Ras associated domain family 1A gene(RASSFlA)promoter methylation occurres in tumor′s early stage,and have a statistically concern with tumor′s TNM stage,invasiveness and outcomes.Moreover,DNA methylation can be reversed,so RASSF1A can be a promising candidate for early breast cancer detection biomarker,and can be a potential orientation for breast cancer treatment.

OBJECTIVE:To establish a method for determination of dextran70 in Compound dextran70 eye drop. METHODS:HPLC-RID was performed on the column of Phenomenex PolySep-GFC-P 4000 with the mobile phase of 0.7% Na2SO4 solution. The flow rate was 0.5 ml/min,column temperature was 35 ℃ and injection volume was 50 μl,and the inner temperature of refrac-tive index detector was 40 ℃. RESULTS:The linear range of dextran70 was 0.1-5.0 mg/ml(r=0.999 5);RSDs of precision,sta-bility and reproducibility tests were lower than 2%;average recovery was 97.45%-101.76%(RSD=0.57%,n=9). CONCLU-SIONS:The method is simple,fast and reliable with high separation and short analysis time,and can be used for the content deter-mination of dextran70 in Compound dextran70 eye drop.