Radiation-induced intestinal injury (RIII) is identified as a common complication of radiotherapy. However, there exists a lack of safe and effective treatment method. To address this issue, researchers have made great efforts to explore the mechanisms underlying RIII, revealing that mitochondria contribute to the pathological changes of RIII, with the mitochondria-mediated generation of reactive oxygen species (ROS), the regulation of apoptosis, and mitochondrial autophagy representing key processes. This review aims to elucidate the role of mitochondria in pathological changes of RIII and to introduce the progress of research on mitochondria as potential targets for RIII prevention and treatment.

Radiation-induced intestinal injury (RIII) is identified as a common complication of radiotherapy. However, there exists a lack of safe and effective treatment method. To address this issue, researchers have made great efforts to explore the mechanisms underlying RIII, revealing that mitochondria contribute to the pathological changes of RIII, with the mitochondria-mediated generation of reactive oxygen species (ROS), the regulation of apoptosis, and mitochondrial autophagy representing key processes. This review aims to elucidate the role of mitochondria in pathological changes of RIII and to introduce the progress of research on mitochondria as potential targets for RIII prevention and treatment.

Objective:To investigate the relationship between the radioresistance of anaplastic thyroid cancer (ATC) and the induction of epithelial-mesenchymal transition (EMT).Methods:Firstly, the radiotherapy sensitivity of differentiated thyroid cancer cells (TPC-1, FTC-133) and ATC cells (CAL-62, 8305C), and the protein levels of E-cadherin, N-cadherin and vimentin proteins after 6 Gy irradiation were detected. The changes in transcriptional levels before and after 4 Gy X-ray radiation of ATC cells were analyzed using mRNA sequencing. Then, the ATC radio-resistant cell models were constructed and validated, and the cell line with the highest radio-resistance was selected for subsequent experiments. Radio-resistant cells were classified into the control group (no treatment), EMT-inhibitor group (EMT-inhibitor-1 pre-treatment), Vactosertib group [transforming growth factor-β(TGF-β) inhibitor Vactosertib pre-treatment), and si-Snail group (knockdown of Snail gene by siRNA transfection), respectively. The expression level of EMT related proteins and TGF-β/Smad signaling pathway related proteins, the cloning efficiency, and the phosphorylated-histone H2A family member X (γH2AX) positive cells rate in the treatment groups and the control group were detected by Western blotting, clone formation assay, immunofluorescence, respectively, reflecting the changes in EMT level and DNA repair ability. Comparison between two groups was performed by Dunnett t-test. Comparison among multiple groups was conducted by one-way ANOVA. Results:The radiosensitivity of ATC cells were lower than that of differentiated thyroid cancer cells. After irradiation, the expression level of E-cadherin was low, those of N-cadherin and vimentin were high, EMT level was increased, and the expression levels of TGF-β/Smad signaling pathway-associated proteins were up-regulated in ATC cells. After use of EMT inhibitor, Vactosertib and Snail knockdown, the expression levels of EMT-associated proteins were down-regulated, cell survival fraction was declined, γH2AX positive cell rate was increased, DNA damage repair ability was weakened and the radiosensitivity was enhanced in radiotherapy-resistant ATC strains. Conclusions:The level of radiotherapy resistance in ATC cells is positively correlated with the EMT level, and the mechanism of radiotherapy resistance is related to the activation of the TGF-β/Smad/Snail pathway after irradiation.

Objective·To investigate the immunotherapeutic effects of exosomes derived from leukemia cells with high expression of B7 molecules(co-stimulatory molecules CD80 and CD86)in tumor-bearing mice.Methods·L1210 leukemia cells were transfected with lentiviral vectors containing the CD80 and CD86 genes,and thereby the leukemia cells with high expression of CD80 and CD86 molecules were obtained.Exosomes LEX-8086 with high expression of CD80 and CD86 molecules were then isolated from the culture supernatant.The biological characteristics of LEX-8086 were analyzed by using transmission electron microscopy(TEM)and Western blotting.A DBA/2-leukemia tumor-bearing mouse model was established.The tumor-bearing mice were divided into LEX-8086 group and PBS group.The LEX-8086 group received intravenous injections of 500 μL LEX-8086(150 μg/mL)via the tail vein 7 d and 12 d after tumor cell inoculation,while the PBS group received injections of equal volumes of PBS at the same time points.Differences in body weight,tumor volume,tumor mass,and survival of the mice between the two groups were observed.Flow cytometry was used to analyze the changes in the immune cells in spleens and lymph nodes of the mice in both groups.Western blotting and real-time fluorescent quantitative PCR(qPCR)were used to detect the expression of markers for M1 and M2 macrophages in the spleens of the mice in both groups.Results·The exosomes LEX-8086 were isolated from the supernatant of L1210 cells overexpressing CD80 and CD86 molecules.TEM revealed that LEX-8086 exhibited a disc-shaped vesicular structure with a diameter of approximately 100 nm.Western blotting demonstrated the expression of exosome-specific markers.In the animal experiments,compared with the PBS group,the body weight of the LEX-8086 group showed no significant change,while both the tumor volume and the relative tumor mass ratio decreased significantly,and the survival was significantly prolonged(all P<0.05).Flow cytometry results indicated that the proportions of natural killer(NK)cells and CD4+T cells in the lymph nodes and spleens of the LEX-8086 group significantly increased(all P<0.05);as for CD8+T cells,they only increased in the lymph modes(P=0.012).Moreover,flow cytometry results showed that the proportion of M1 macrophages in the spleens of mice in the LEX-8086 group was significantly elevated(P=0.003),while the proportion of M2 macrophages remained unchanged.Western blotting and qPCR also revealed that the mRNA and protein expression levels of M1 macrophage markers interleukin-6 and tumor necrosis factor-α in the spleens of mice in the LEX-8086 group increased significantly(all P<0.05).Conclusion·Exosomes derived from leukemia cells with high expression of co-stimulatory molecules CD80 and CD86 can induce a therapeutic anti-leukemic effect,which may be achieved by increasing the proportions of NK cells,M1 macrophages,CD4+T cells,and CD8+T cells.

Objective·To investigate the immunotherapeutic effects of exosomes derived from leukemia cells with high expression of B7 molecules(co-stimulatory molecules CD80 and CD86)in tumor-bearing mice.Methods·L1210 leukemia cells were transfected with lentiviral vectors containing the CD80 and CD86 genes,and thereby the leukemia cells with high expression of CD80 and CD86 molecules were obtained.Exosomes LEX-8086 with high expression of CD80 and CD86 molecules were then isolated from the culture supernatant.The biological characteristics of LEX-8086 were analyzed by using transmission electron microscopy(TEM)and Western blotting.A DBA/2-leukemia tumor-bearing mouse model was established.The tumor-bearing mice were divided into LEX-8086 group and PBS group.The LEX-8086 group received intravenous injections of 500 μL LEX-8086(150 μg/mL)via the tail vein 7 d and 12 d after tumor cell inoculation,while the PBS group received injections of equal volumes of PBS at the same time points.Differences in body weight,tumor volume,tumor mass,and survival of the mice between the two groups were observed.Flow cytometry was used to analyze the changes in the immune cells in spleens and lymph nodes of the mice in both groups.Western blotting and real-time fluorescent quantitative PCR(qPCR)were used to detect the expression of markers for M1 and M2 macrophages in the spleens of the mice in both groups.Results·The exosomes LEX-8086 were isolated from the supernatant of L1210 cells overexpressing CD80 and CD86 molecules.TEM revealed that LEX-8086 exhibited a disc-shaped vesicular structure with a diameter of approximately 100 nm.Western blotting demonstrated the expression of exosome-specific markers.In the animal experiments,compared with the PBS group,the body weight of the LEX-8086 group showed no significant change,while both the tumor volume and the relative tumor mass ratio decreased significantly,and the survival was significantly prolonged(all P<0.05).Flow cytometry results indicated that the proportions of natural killer(NK)cells and CD4+T cells in the lymph nodes and spleens of the LEX-8086 group significantly increased(all P<0.05);as for CD8+T cells,they only increased in the lymph modes(P=0.012).Moreover,flow cytometry results showed that the proportion of M1 macrophages in the spleens of mice in the LEX-8086 group was significantly elevated(P=0.003),while the proportion of M2 macrophages remained unchanged.Western blotting and qPCR also revealed that the mRNA and protein expression levels of M1 macrophage markers interleukin-6 and tumor necrosis factor-α in the spleens of mice in the LEX-8086 group increased significantly(all P<0.05).Conclusion·Exosomes derived from leukemia cells with high expression of co-stimulatory molecules CD80 and CD86 can induce a therapeutic anti-leukemic effect,which may be achieved by increasing the proportions of NK cells,M1 macrophages,CD4+T cells,and CD8+T cells.

Objective:To investigate the relationship between the radioresistance of anaplastic thyroid cancer (ATC) and the induction of epithelial-mesenchymal transition (EMT).Methods:Firstly, the radiotherapy sensitivity of differentiated thyroid cancer cells (TPC-1, FTC-133) and ATC cells (CAL-62, 8305C), and the protein levels of E-cadherin, N-cadherin and vimentin proteins after 6 Gy irradiation were detected. The changes in transcriptional levels before and after 4 Gy X-ray radiation of ATC cells were analyzed using mRNA sequencing. Then, the ATC radio-resistant cell models were constructed and validated, and the cell line with the highest radio-resistance was selected for subsequent experiments. Radio-resistant cells were classified into the control group (no treatment), EMT-inhibitor group (EMT-inhibitor-1 pre-treatment), Vactosertib group [transforming growth factor-β(TGF-β) inhibitor Vactosertib pre-treatment), and si-Snail group (knockdown of Snail gene by siRNA transfection), respectively. The expression level of EMT related proteins and TGF-β/Smad signaling pathway related proteins, the cloning efficiency, and the phosphorylated-histone H2A family member X (γH2AX) positive cells rate in the treatment groups and the control group were detected by Western blotting, clone formation assay, immunofluorescence, respectively, reflecting the changes in EMT level and DNA repair ability. Comparison between two groups was performed by Dunnett t-test. Comparison among multiple groups was conducted by one-way ANOVA. Results:The radiosensitivity of ATC cells were lower than that of differentiated thyroid cancer cells. After irradiation, the expression level of E-cadherin was low, those of N-cadherin and vimentin were high, EMT level was increased, and the expression levels of TGF-β/Smad signaling pathway-associated proteins were up-regulated in ATC cells. After use of EMT inhibitor, Vactosertib and Snail knockdown, the expression levels of EMT-associated proteins were down-regulated, cell survival fraction was declined, γH2AX positive cell rate was increased, DNA damage repair ability was weakened and the radiosensitivity was enhanced in radiotherapy-resistant ATC strains. Conclusions:The level of radiotherapy resistance in ATC cells is positively correlated with the EMT level, and the mechanism of radiotherapy resistance is related to the activation of the TGF-β/Smad/Snail pathway after irradiation.

Hypothyroidism (HT) can arise as a complication of radiotherapy for breast cancer. Despite having a significant impact on patients′ quality of life, HT had always been overlooked by radiotherapists in the past. In recent years, many studies highlighting the protection of the thyroid in the process of radiotherapy for breast cancer have been conducted, achieving valuable conclusion. These studies can serve as a guide for radiotherapists to limit the dose to the thyroid during radiotherapy, thus reducing the incidence of HT.

Liver is the most common metastatic site for colorectal cancer (CRC), there is no satisfied approach to treat CRC liver metastasis (CRCLM). Here, we investigated the role of a polycomb protein BMI-1 in CRCLM. Immunohistochemical analysis showed that BMI-1 expression in liver metastases was upregulated and associated with T4 stage, invasion depth and right-sided primary tumor. Knockdown

Objective To evaluate the short-term clinical efficacy of three dimension printed titanium augments for the reconstruction of acetabular bone defects in revision total hip arthroplasty.Methods The retrospective study was conducted.To retrospectively analyze clinical data of 21 patients who were underwent revision total hip arthroplasty with severe acetabular bone defects reconstructed by three dimension printed titanium augment from March 2016 to September 2017 from Department of Orthopaedics,Beijing Friendship Hospital,Capital Medical University.There were 9 males and 12 females,age (58.9 ± 6.3) years,51-67 years,body mass index (23.8 ± 2.9) kg/m2.According preoperative CT scan of hip joints,three dimension printed titanium augments were designed for acetabular defects personality.The data including the vertical distance from centre of rotation to the interteardrop line in X-ray examination,preoperative Harris score,final follow-up Harris score of hip postoperatively,and complications were recorded.Outpatient visits ranged from 11.8 to 19.6 months.Measurement data were expressed as (Mean ± SD),and t test was used before and after surgery.Results For X-ray examination,the average vertical distance from centre of rotation to the interteardrop line was (6.1 ± 1.2) cm preoperatively and (2.8 ± 0.7) cm postoperatively,and the difference was statistically significant (P ＜ 0.01).The hip Harris score increased from preoperative (47.5 ± 6.4) scores to the last follow-up (84.6 ± 5.9) scores,and the difference was statistically significant (P ＜ 0.01).The final follow-up data showed the acetabular prosthesis and augments were stable,while there were no hip joint dislocation,periprosthetic joint infection,loosening of acetabular components and other complications.Conclusion Three dimension printed augments can reconstruct severe acetabular bone defects and restore the hip rotation centre.

Objective To explore the validity of two-staged revision for hip periprosthetic joint injection and intermediate-term clinical effects.Methods The clinical data of 31 cases who were underwent two-staged revision for unilateral hip periprosthetic joint infection in Department of Orthopaedics,Beijing Friendship Hospital,Capital Medical University from March 2014 to September 2016 were analyzed retrospectively.There were 13 males and 18 females,aged (67.5 ±7.8) years,with an age range of 52-79 years.All patients underwent two-staged revision,taking preoperative and intraoperative joint puncture fluid,intraoperative infection of soft tissue for bacterial culture was to clear medication.In first stage,prosthesis removed,debridement performed and antibiotic spacer implanted were performed.Antibiotics were used for 8 to 12 weeks for infection.In second stage,total hip arthroplasty revision was performed while infection was controlled.Harris hip scores,Short form 36 health status scores (SF-36),white blood cell counts,C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)were compared between preoperative and postoperative follow-up in all patients,and postoperative complications were recorded.Postoperative outpatient follow-up was 30.1 to 59.3 months,and reviewed every 12 months after 3 months,6 months,and 12 months.The follow-up deadline was April 2019.Measurement data were expressed as mean ± standard deviation (Mean ± SD).The t test was used to compare the preoperative and postoperative follow-up.Results All 29 patients were followed up for follow-up except 2 patients were lost to follow-up.Preoperative Harris hip score,SF-36,white blood cell count,CRP and ESR were (39.4 ± 5.6) scores,(398.8 ± 39.2) scores,(12.5 ± 0.6) × 109/L,(63.3 ± 10.1) mg/L and (83.7 ± 12.5) mm/h,respectively.The last follow-up oftbe above indicators were (76.9 ±9.3) scores,(649.3 ±67.5) scores,(9.1 ±0.5) × 109/L,(5.3 ± 1.7) mg/L and (10.2 ± 1.6) mm/h,respectively.The results of final followed-up were much better than the preoperative results and there were significant differences between postoperation and preoperation for all indexes.One patient developed postoperative hip dislocation and was treated with manual reduction under general anesthesia.The two patients were diagnosed hip periprosthetic joint infection of joint at 8 months and 15 months respectively after two-staged revision and treated by removing the hip prosthesis.One patient was performed revision again and the other was not performed any operation for poor health condition.The remaining 26 patients had no complications.Conclusions Two-staged revision for periprosthetic joint infection of hip joint can not only treat infection effectively but also can recover hip function significantly.The early and intermediate-term clinical effects of the surgical treatment is satisfied.