1.Protective effects of exosomes derived from MSCs in radiation-induced lung injury
Lili WANG ; Zien YANG ; Mingyue OUYANG ; Sining XING ; Song ZHAO ; Huiying YU
Chinese Journal of Radiological Health 2025;34(1):13-20
Objective To investigate the role and related mechanisms of exosomes derived from mesenchymal stem cells (MSCs) in radiation-induced lung injury (RILI). Methods Human umbilical cord-derived MSCs were isolated and cultured for the extraction and identification of exosomes. Eighteen male SD rats were randomly divided into Control group, RILI group and RILI + exosomes group (EXO group), with 6 rats in each group. Except for Control group, the other groups received a single X-ray dose of 30 Gy to the right lung. Immediately after irradiation, the EXO group was administered 2 × 109 exosomes/kg via tail vein injection. Control group and RILI group were given the same volume of normal saline. Eight weeks post-irradiation, the rats were sacrificed, lung tissue and peripheral venous blood were collected. HE and Masson staining were employed to observe the pathological and fibrotic changes of lung tissue. The levels of serum inflammatory factors IL-6, IFN-γ, TNF-α, and IL-10 were detected by ELISA. RT-qPCR was used to assess the mRNA levels of IL-1β, IL-6, Cdh1, and Col1a1 in lung tissue. The expression levels of Vimentin and TGF-β1 in lung tissue were measured by immunohistochemical staining. The expression levels of AMPK, p-AMPK, and TGF-β1 in lung tissue were detected by Western blot. Results MSC-derived exosomes were successfully extracted and identified. Compared with RILI group, EXO group showed significantly reduced pathological changes of lung inflammation and collagen deposition. The levels of serum inflammatory factors IL-6, INF-γ, and TNF-α were significantly decreased (P < 0.05), and the level of anti-inflammatory factor IL-10 was significantly increased (P < 0.05). The mRNA levels of IL-1β, IL-6, and Col1a1 in lung tissue were significantly decreased (P < 0.05 or P < 0.01), and the mRNA level of Cdh1 was significantly increased (P < 0.05 or P < 0.01). The levels of Vimentin and TGF-β1 in lung tissue were significantly reduced, while p-AMPK level was significantly up-regulated (P < 0.05). Conclusion Exosomes derived from MSCs may alleviate RILI by inhibiting inflammatory responses and regulating epithelial-mesenchymal transition mediated by AMPK/TGF-β1 signaling pathway.
2.Risk factor research and risk prediction model establishment for early Q-T interval prolongation after acute myocardial infarction
Sifan LI ; Ying XIAO ; Dongbo WANG ; Sining LIU ; Yadong TANG ; Xuefeng TIAN
Chinese Journal of Primary Medicine and Pharmacy 2024;31(2):175-179
Objective:To establish a prediction model of risk factors for early Q-T interval prolongation after acute myocardial infarction (AMI), which helps prevent and reduce the occurrence of acute malignant events.Methods:This is a case-control study. A total of 100 patients with Q-T interval prolongation after AMI who received treatment at Heilongjiang Provincial Hospital from January 2018 to December 2022 were included in this study. An additional 100 patients without Q-T interval prolongation after AMI who concurrently received treatment in the same hospital were also included in this study. Two model groups, including model group 1 (with Q-T interval prolongation, n = 50) and model group 2 (without Q-T interval prolongation, n = 50), and two test groups, including test group 1 (with Q-T interval prolongation, n = 50) and test group 2 (without Q-T interval prolongation, n = 50), were designated. Logistic regression analysis was performed to construct a prediction model of risk factors for Q-T interval prolongation. The area under the receiver operating characteristic curve was determined to evaluate the prediction model. The value of the prediction model was validated in the test groups. Results:Multivariate logistic regression showed that female gender ( OR = 2.307, 95% CI: 0.09-0.91, P = 0.041) and heart failure ( OR = 3.087, 95% CI: 1.15-8.27, P = 0.025) were independent risk factors for early Q-T interval prolongation after AMI. The area under the receiver operating characteristic curve of the prediction model was 0.770, with a sensitivity of 84.0%, a specificity of 66.0%, the Jordan index of 0.44, and the corresponding optimal critical value of 0.43. This indicates good fit of the model. Conclusion:Female gender and heart failure are independent risk factors for early Q-T interval prolongation after AMI. The model constructed based on the above-mentioned risk factors fits well and has a high predictive value, which helps reduce the occurrence of early Q-T interval prolongation after AMI.
3.Research progress and clinical application of thulium fiber laser in urology
Sha ZHU ; Sining LI ; Jian WANG
Clinical Medicine of China 2023;39(6):475-480
Thulium fiber laser (TFL) is a new and potential laser with significant advantages in that the therapeutic range covers the entire urinary system. In the field of lithotripsy, compared with the holmium laser, which not only can dust any urinary stone composition types, but also has a higher ablation rate、smaller retropulsion、thinner fragements and fewer complications. In terms of soft tissue applications, compared with other lasers, it has efficient vaporization、precise incision、remarkable hemostatic ability and safety. Additionally the laser is small in size, high in power conversion efficiency, stable in performance, low noise during operation and ordinary power socket in power supply. Most of the current research on TFL lithotripsy and tissue vaporization is preclinical and few clinical studies. This article reviews the physical properties、advantages、ablation efficiency、vaporization and incision ability、laser safety and clinical application of TFL in order to provide more reference for future clinical applications.
4.Research progress of mesh-related visceral complications after tension-free inguinal hernia repair
Tianhao XIE ; Xiangxiang REN ; Sining HA ; Xinli SUN ; Qiang WANG ; Litao LIU ; Zheng NIU ; Lingyun LIU ; Qian SUN ; Xiaoshi JIN
Chinese Journal of Digestive Surgery 2022;21(9):1240-1246
Mesh-related visceral complications caused by mesh erosion after tension-free inguinal hernia repair are one kind of rare long-term complications, but they are easily neglected. Interval time from initial hernia repair to mesh-related visceral complications by preperitoneal and laparoscopic repair is short. Rutkow and transabdominal preperitoneal repair have the highest reported rate. Lichtenstein has the longest interval time and the lowest reported rate. The most frequently eroded organs are sigmoid colon, bladder and small intestine. The common clinical manifestations of sigmoid colon erosion are hematochezia, abdominal wall fistula and colitis, hematuria and recurrent urinary tract infection in bladder erosion cases, intestinal obstruction and abdominal wall fistula in intestinal erosion case, sigmoid-bladder fistula and intestinal-bladder fistula in multiple organ erosion cases. Resection or repair of corresponding organs with mesh removal have good efficacies in most patients. The authors summarize and analyze researches on mesh-related visceral complications after tension-free inguinal hernia repair from 1994 to 2021, review their advances, in order to raise awareness of such complications in clinicians.
5.Experimental study on α1 adrenergic receptor blocker in reducing portal hypertension in rats
Zhen LI ; Guangchuan WANG ; Sining WANG ; Lianhui ZHAO ; Chunqing ZHANG
Chinese Journal of Digestion 2022;42(5):336-339
Objective:To observe whether α1 adrenergic receptor (α1AR) blocker can reduce and antagonize portal hypertension caused by α1AR activation in rats, and to provide a new approach for the clinical treatment of portal hypertension.Methods:Phenylephrine was chosen as α1AR agonist, and alfuzosin was used as α1AR blocker. The route of administration was portal vein injection, and the pressure was measured by trans-portal vein puncture. According to random number table, 32 male Sprague-Dawley rats were divided into 4 groups: control group, portal hypertension model group, alfuzosin treatment group and alfuzosin prevention group. The portal venous pressure (PVP) was measured in all rats before administration. The rats in the control group were injected with 0.9% sodium chloride solution (1 L/g), and the rats in portal hypertension model group were injected with phenylephrine(1.5 μg/g), and the PVP of the above two groups was measured again at 5 and 10 min after injection. The rats in alfuzosin treatment group were injected with phenylephrine(1.5 μg/g), PVP was measured again at 5 min after administration, and then the rats were given alfuzosin(0.9 μg/g), PVP was measured again at 5 min after administration. The rats in alfuzosin prevention group were injected with alfuzosin(0.9 μg/g), PVP was measured at 1 min after administration, and then the rats were given phenylephrine(1.5 μg/g), PVP was measured again at 1, 5 and 10 min after phenylephrine injection respectively. One way analysis of variance and Dunnett- t test were used for statistical analysis. Results:The portal vein puncture was successfully performed in 4, 6, 8 and 5 rats in the control group, portal hypertension model group, alfuzosin treatment group and alfuzosin prevention group, respectively. The PVP of rats in portal hypertension model group at 5 and 10 min after phenylephrine injection was (18.045±7.636) and (15.515±5.440) mmHg (1 mmHg = 0.133 kPa), respectively, which were both higher than that before administration ((8.452±2.830) mmHg), and the differences were statistically significant ( t=2.89 and 2.82, both P<0.05). At 5 min after alfuzosin injection, the PVP of rats in the alfuzosin treatment group was (10.088±3.743) mmHg, which was lower than that of rats at 5 min after phenylephrine injection ((16.146±4.324) mmHg) and that of portal hypertension model group at 10 min after phenylephrine injection, and the differences were statistically significant ( t=3.00 and 2.22, both P<0.05). There were no significant differences in PVP in the alfuzosin prevention group before administration, at 1 min after injection of alfuzosin, and at 1, 5 and 10 min after injection of phenylephrine (all P > 0.05). Conclusions:α1AR is an important factor involved in the regulation of PVP, and its blockers can reduce and antagonize the portal hypertension caused by α1AR activation, which is of great significance in the prevention and treatment of portal hypertension progression in liver cirrhosis.
6.Effects of human umbilical cord-derived mesenchymal stem cells and their conditioned medium on proliferation, migration and apoptosis of non-small cell lung cancer polyploid A549 cells
Mingyue OUYANG ; Lili WANG ; Sining XING ; Song ZHAO ; Shuo LIU ; Huiying YU
Cancer Research and Clinic 2022;34(1):8-14
Objective:To investigate the effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSC) and their conditioned medium on proliferation, migration and apoptosis of human non-small cell lung cancer (NSCLC) polyploid A549 cells.Methods:A549 cells in logarithmic phase were selected. After induction treatment with 1 μmol/L docetaxel for 24 h, DMEM/F12 medium with 10% fetal bovine serum was used to culture the cells for 3 d, finally the polyploid A549 cells model was successfully established. After finishing the separation and culture of hUC-MSC, hUC-MSC conditioned medium was prepared. Normally cultured polyploid A549 cells were treated as the control group, conditioned medium cultured polyploid A549 cells were treated as the conditioned medium group. hUC-MSC was co-cultured with polyploid A549 cells, and the ratio of the total number of cells was 2:1 and 5:1, respectively, which were recorded as MSC 1 group and MSC 2 group. Cells in each group were continually cultured for 48 h or 72 h. Proliferation and apoptosis of polyploid A549 cells in each group were detected by using flow cytometry, cell migration ability was detected by using Transwell assay, and the expressions of migration and apoptosis-related proteins were detected by using Western blotting.Results:Polyploid A549 cells model was successfully established and hUC-MSC was cultured separately. The result of cell proliferation detected by flow cytometry showed that at 48 h, the mean fluorescence intensity of the control group, conditioned medium group, MSC 1 group and MSC 2 group was 1 695±305, 2 020±85, 1 259±35 and 1 356±33, respectively, and the difference was statistically significant ( F = 14.00, P < 0.05); at 72 h, the mean fluorescence intensity of the control group, conditioned medium group, MSC 1 group and MSC 2 group was 1 052±77, 1 309±24, 864±201 and 1 103±237, respectively, and the difference was statistically significant ( F = 3.90, P > 0.05). The result of Transwell assay showed that at 48 h, the number of cell migration in the control group, conditioned medium group, MSC 1 group and MSC 2 group was 52±9, 57±12, 68±8 and 75±11, respectively, and the difference was statistically significant( F = 32.16, P < 0.05); the number of cell migration in each experimental group was all higher than that in the control group (all P < 0.05). The percentage of apoptotic cells in the control group, conditioned medium group, MSC 1 group and MSC 2 group was (15.53±4.27)%, (13.77±1.75)%, (3.60±0.50)% and (2.33±0.06)%, respectively, and the difference was statistically significant ( F = 182.36, P < 0.05); there was no statistically significant difference between the control group and conditioned medium group ( P > 0.05); there were statistically significant differences between MSC 1 group and the control group, MSC 2 group and the control group (both P < 0.05). Western blotting results showed that compared with the control group, the expression of migration-related protein matrix metallopeptidase 9 (MMP-9) was increased, the expression of pro-apoptotic protein bax was reduced, the expression of anti-apoptotic protein bcl-xL was increased in conditioned medium group, MSC 1 group and MSC 2 group. Conclusions:hUC-MSC can improve the migration and anti-apoptotic ability of polyploid A549 cells, suggesting that hUC-MSC may affect the survival of tumor cells during the process of chemotherapy damage and repair.
7.Status and progress of partial cystectomy in the treatment of myometric invasive bladder cancer
Jiaxi HE ; Dihao DENG ; Zeen HE ; Yi ZHANG ; Sining LI ; Jian WANG
Clinical Medicine of China 2021;37(4):317-322
Bladder cancer is one of the most common malignant tumors in the urinary system, and the current standard treatment for muscle-invasive bladder cancer(MIBC) is radical cystectomy combined with pelvic lymphadenectomy.However, radical cystectomy is a surgical method with serious damege and high incidence of perioperative complications, leading to a low postoperative quality of life for patients.In recent years, with the improvement of chemotherapy regimens and the development of radiotherapy techniques, bladder preservation comprehensive therapy based on partial cystectomy(PC) has attracted the attention of domestic and foreign scholars again.This article reviews the current application and treatment progress of PC.
8.Role of docetaxel induced polyploid tumor cells in tumor recurrence
Lili WANG ; Song ZHAO ; Mingyue OUYANG ; Xiaodong XIE ; Sining XING ; Shuo LIU ; Huiying YU
Journal of International Oncology 2020;47(6):340-345
Objective:To study the migration of polyploid tumor cells induced by docetaxel, the characteristics of epithelial-mesenchymal transition, and the killing effect of immune cells on them, in order to explore the potential role of polyploid tumor cells in tumor recurrence.Methods:The human non-small cell lung cancer A549 cells were treated with 1 μmol/L docetaxel for 24 h, and the cells were collected as Doc 1 d group. After drug removal, the cells were cultured in fresh and complete medium for 3 or 5 days, then the cells were collected as Doc 3 d group or Doc 5 d group respectively. The A549 cells were treated with DMSO for 24 h as control group. Immunofluorescence staining was used to detect cell morphology, flow cytometry was used to analyze cell ploidy, scratch test was used to detect cell migration, Western blotting was used to detect the expression of epithelial-mesenchymal transition related proteins, and lactate dehydrogenase release method was used to evaluate the killing activity of cytokine-induced killer (CIK) cells.Results:Compared with the control group, most of the cells in the Doc 1 d group, Doc 3 d group and Doc 5 d group were apoptotic, a few of the surviving cells were significantly larger, and the nucleus was polynuclear. The proportions of polyploid cell subset (DNA content > 4N) in the control group, Doc 1 d group, Doc 3 d group and Doc 5 d group were (1.93±0.55)%, (22.97±2.37)%, (51.30±12.51)% and (67.87±8.31)% respectively, and the difference among the four groups was statistically significant ( F=26.521, P<0.001). The proportion of polyploid cell subset in Doc 1 d group, Doc 3 d group and Doc 5 d group was significantly higher than that in the control group (all P<0.001). With the prolongation of withdrawal time, the proportion of polyploid cell subset in Doc 3 d group and Doc 5 d group was significantly higher than that in Doc 1 d group ( P=0.009; P=0.004). After 24 h and 48 h culture, the wound healing rates of the control group were both 100%, and the wound healing rates of the Doc 3 d group were (39.10±2.12)% and (46.13±5.32)% respectively, with no significant difference ( t=2.126, P=0.051). Compared with the control group at 24 h and 48 h, the cell migration abilities of Doc 3 d group were significantly lower ( t=49.756, P<0.001; t=30.825, P<0.001). Compared with the control group, the expression of E-cadherin protein decreased gradually in the Doc 1 d group, Doc 3 d group and Doc 5 d group, the expression of Vimentin protein increased gradually, and the expressions of Snail protein and N-cadherin protein did not change significantly. The killing efficiencies of CIK cells against the cells of the control group, Doc 3 d group and Doc 5 d group were (27.27±1.91)%, (17.87±2.35)%, (9.47±0.51)% respectively, and the difference was statistically significant ( F=11.294, P<0.001). The killing efficiency of Doc 3 d group and Doc 5 d group was significantly lower than that of the control group ( P=0.004; P<0.001). The killing efficiency of Doc 5 d group was significantly lower than that of Doc 3 d group ( P=0.003). Conclusion:The migration ability of polyploid tumor cells induced by docetaxel is weakened, but epithelial-mesenchymal transition is likely to occur, and the killing effect of immune cells on them is reduced.
9. Protective effect and mechanism of glucose regulatory protein on atrial fibrillation
Xuefeng TIAN ; Zheng WANG ; Lin CHEN ; Sining LIU ; Yue ZHANG ; Zhihong ZHANG ; Mingyang HONG
Chinese Journal of Primary Medicine and Pharmacy 2019;26(14):1708-1712
Objective:
To investigate the protective effect of glucose regulatory protein 78 (GRP78) on cardiomyocytes in atrial fibrillation and its mechanism.
Methods:
HL-1 cardiomyocyte cell line was cultured from June 2016 to March 2017 at Harbin Medical University Central Laboratory.The cells were randomly divided into 4 groups: control group, pacing group, pacing+ GRP78cDNA group, pacing+ GRP78siRNA group.The following indicators were detected: (1)oxidative stress: flow cytometry was used to detect the content of reactive oxygen species (ROS) in each group; (2)Ca2+ overload and cell electrophysiology: flow cytometry was used to detect Ca2+ content in each group; (3)cell structure reconstruction: cell apoptosis was detected by flow cytometry.
Results:
The ROS production in the pacing group was significantly higher than that in the control group [(28.8±0.5)% vs.(4.5±0.8)%,
10.Efficacy of TIGIT in the cancer immune cycle
Yusheng ZHANG ; Yaoguang CHEN ; Sining LI ; Jian WANG
Clinical Medicine of China 2018;34(1):89-91
Immunotherapy is a therapeutic method that uses the immune system to inhibit tumor activity and kill tumor cells.It has been proved to be effective in the treatment of various malignant tumors.In general, the immune system can recognize and kill the abnormal cells,while the tumor cells can produce a variety of mechanisms to inhibit the immune system,resulting into the incomplete death of the cells.TIGIT is a type of inhibitory receptor containing T cell immunoglobulin and immunoreceptor protein tyrosine inhibitory motif (ITIM)protein domain.This paper discusses the role of TIGIT in limiting antitumor responses and reviews the mechanisms of action during the cancer immunity cycles.

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