1.Effects of IGF-1 on Proliferation of Human Non-small Cell Lung Cancer Cells
Xiuhua SUN ; Haiyang HU ; Hongkai ZHANG ; Zhihui XIE ; Aiming YU
Journal of China Medical University 2010;(9):727-729,736
Objective To investigate the effects of insulin-like growth factor-1(IGF-1)on the cell proliferation of human non-small-cell lung cancer(NSCLC) and the possible molecular mechanism.Methods MTT assay was used to examine the effects of IGF-1 (0.1,1,10,100 ng/mL)on the cell proliferation of NSCLC cell lines(A549,LK2,H460),Flow cytometry(FCM)and Western blot to ana-lyze the cell cycles and the protein expression of S-Phase Kinase-Associated Proteins 2(Skp2)and CDC20 homolog 1(CDH1),respectively.Results The cell proliferation of NSCLC cell lines(A549,LK2,H460)could be promoted by the IGF-1 at different concentrations and the proliferation rate peaked when the cells were treated with 1 ng/mL IGF-1.Compared with control,the percentage of the S-phase cell population was significantly increased after the treatment of IGF-I(P 〈 0.01)and the protein expression of SKP2 also increased obviously(P 〈0.05).However,there was no change in the CDH1 protein expression(P 〉 0.05).Conclusion IGF-1 may accelerate the cell-cycle pro-gression of NSCLC cells by negatively modulating p27 protein via the up-regulation of SKP2 protein expression.
2.Imaging findings of posterior reversible encephalopathy syndrome caused by pregnancy-induced hypertension
Duocheng SUN ; Zhong XIAO ; Fuzhang LI ; Hongkai QIU ; Lingling TAN
International Journal of Cerebrovascular Diseases 2009;17(1):16-19
Objective To investigate the computer tomography (CT) and magnetic res-onance imaging (MRI) features of posterior reversible encephalopathy syndrome (PRES) caused by pregnancy-indueed hypertension (PIH). Methods CT scan and MRI scan + diffusion-weighted imaging (DWI) were used in 31 patients with PIH. Results CT scan found low density lesions in parietal-occipital lobe of watershed regions in 31 patients with PIH. CT value was 19 to 23Hu. Among them, MRI showed slight hypointensity lesions on T1-weighted images and slight hyperintensity lesions on T2-weight images in 11 patients, fluid-attenuated inversion recovery (FLAIR) sequence showed hyperintensity lesions, DWI revealed isointense, and apparent diffusion coefficient- did not decrease. The recovery time of clinical symptoms was earlier than that of MRI. Conclusions The lesion sites on cr and MRI had certain characteristics in PIH occurred PRES at late pregnancy, combining clinical history a clear diagnosis could be made.
3.Effectiveness of percutaneous iliosacral screwing versus reconstruction plating for treatment of pelvic posterior ring fractures of Tile C: a Meta analysis
Changmeng ZHANG ; Haoyun LI ; Zhi ZHU ; Kai YANG ; Hongkai LIAN ; Tiansheng SUN
Chinese Journal of Orthopaedic Trauma 2017;19(6):476-483
Objective To assess the clinical efficacy of percutaneous iliosacral screwing versus reconstruction plating in the treatment of pelvic posterior ring fractures of Tile C.Methods The authors retrieved the randomized controlled trials (RCTs) and clinical controlled trials (CCTs) comparing percutaneous iliosacral screwing versus reconstruction plating for Tile C pelvic posterior ring fractures from the Cochrane library,Medline,Embase,CNKI,Wanfang Data and Chinese Biomedical Database by computer and from major Chinese orthopedic journals by hand.Qualified data were extracted by statistical software Revman 5.2 for meta-analysis.Results 334 cases were included in this Meta-analysis from one RCT and 3 CCTs.Of them,162 underwent percutaneous iliosacral screwing and 172 reconstruction plating (including 66 cases of percutaneous reconstruction plating and 106 ones of anterior reconstruction plating).There was no significant difference between percutaneous iliosacral screwing and reconstruction plating in operation time (P =0.16).Percutaneous reconstruction plating consumed significantly less operation time than anterior reconstruction plating (P < 0.001).Percutaneous iliosacral screwing decreased significantly incision length and intraoperative blood loss than both methods of reconstruction plating (P < 0.001),but significantly increased times of X-ray exposure than percutaneous reconstruction plating (P < 0.001).There were no significantly differences in the good to excellence rates by Matta scores and Majeed scores between percutaneous iliosacral screwing and percutaneous reconstruction plating (P > 0.05),but percutaneous iliosacral screwing performed significantly better than anterior reconstruction plating (P < 0.001).Percutaneous reconstruction plating led to significantly fewer postoperative complications than anterior reconstruction plating (P < 0.001) but similar incidence of postoperative pain at the sacroiliac joint compared with percutaneous reconstruction plating (P =0.30).Conclusion Compared with anterior reconstruction plating,pereutaneous iliosacral screwing and percutaneous reconstruction plating may lead to better clinical efficacy and fewer complications.Percutaneous iliosacral screwing may be superior in incision length and intraoperative blood loss,but it requires more intraoperative X-ray exposure and more demanding technical skills.
4.Quantization Methodology of Autolfuorescence Bronchoscopy Image in the YUV System
ZHENG XIAOXUAN ; XIONG HONGKAI ; LI YONG ; HAN BAOHUI ; SUN JIAYUAN
Chinese Journal of Lung Cancer 2014;(11):797-803
Background and objective hTe aim of this study is to determine the best reference values of the opti-mal evaluation indexes that identify different disease types. Disease identiifcation was conducted using the YUV quantitative analysis of autolfuorescence bronchoscopy (AFB) images in the target areas. Furthermore, this study discusses the signiifcance of AFB in the diagnosis of the central-type lung cancer. Methods A biopsy was conducted for cases that showed pathologic changes under either autolfuorescence or white-light bronchoscopy. Moreover, MATLAB was used to carry out the quantita-tive analyses of lesion in multi-color spaces from AFB images. hTe cases were divided into different groups according to the pathological diagnosis of normal bronchial mucosa, inlfammation, low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive cancer. SPSS 11.5 was used to process the data for statistical analysis. Results hTe Y values were different and statistically different between invasive cancer and LGD (P<0.001) and invasive cancer and inlfammation (P=0.040), respec-tively. hTe U values between invasive cancer and the other groups were statistically different (P<0.050). Similarly, the V values between invasive cancer and LGD and inlfammation and normal bronchial mucosa were different. Lastly, the V values between normal bronchial mucosa and HGD and inlfammation and normal bronchial mucosa were different. Conclusion hTe YUV values in the AFB effectively identiifed benign and malignant diseases and were proven to be effective scientiifc bases for the ac-curate AFB diagnosis of lung cancer.
5.Central neurocytoma:MRI manifestation and clinicopathological findings
Jing LI ; Hongkai ZHANG ; Lina JIANG ; Miaomiao SUN ; Pan LIANG ; Dandan ZHANG ; Xin LI ; Jianbo GAO ; Hailiang LI
Journal of Practical Radiology 2018;34(4):501-504,525
Objective To explore the clinical and MRI features of central neurocytoma(CNC).Methods The clinical and MRI data of the pathologically confirmed CNC were retrospectively collected and compared,all the patients had undergone pre-surgery MRI plain and contrast enhanced scans.Patients were divided according to the location of the tumor as intra-lateral ventricle and ex-lateral ventricle group.Results Forty patients were finally enrolled,all tumors were solitary,39 of which were located in the ventricular system,including 2 7 cases located in lateral ventricle and 1 2 in the lateral ventricle,2 in third ventricle,5 in both lateral and third ventricle and 5 involving the whole ventricles;and 1 located in ex-ventricle(left temporal lobe).The tumors showed iso-intense on T1WI and T2WI with varying degrees of cystic degeneration.Hemorrhage was shown in 5 cases,calcification in 2 cases,markedly hyper-vascular enhancements were shown in 36 cases with 26 cases presented visible enhanced vessel sign.The comparison analysis between intra-and ex-lateral ventricle groups revealed that,the patients age,tumor size and Ki-67 expression were higher in ex-lateral ventricle group(P<0.05);hypervascular enhancement (P<0.05),gender ratio,cystic/cystic-solid appearance and vessel sigh(P>0.05)were lower than those in intra-lateral ventricle group.Conclusion CNC is typically located in lateral ventricle,with cystic and necrotic degeneration areas,hypervascular enhancement with visible vessels in solid portion on enhanced MR images;The ex-lateral ventricle CNC is rare,it commonly presents a larger tumor with high Ki-67 expression,and moderate enhancement with less visible vessels on enhanced MRI.
6.Lipids, Anthropometric Measures, Smoking and Physical Activity Mediate the Causal Pathway From Education to Breast Cancer in Women: A Mendelian Randomization Study
Hongkai LI ; Lei HOU ; Yuanyuan YU ; Xiaoru SUN ; Xinhui LIU ; Yifan YU ; Sijia WU ; Yina HE ; Yutong WU ; Li HE ; Fuzhong XUE
Journal of Breast Cancer 2021;24(6):504-519
Purpose:
We aimed to investigate whether obtaining a higher level of education was causally associated with lower breast cancer risk and to identify the causal mechanism linking them.
Methods:
The main data analysis used publicly available summary-level data from 2 large genome-wide association study consortia. Mendelian randomization (MR) analysis used 65 genetic variants derived from the Social Science Genetic Association Consortium as instrumental variables for years of schooling. The outcomes from the Breast Cancer Association Consortium (BCAC) were the overall breast cancer risk (122,977 cases/105,974 controls in women) and the two subtypes: estrogen receptor (ER)-positive breast cancer and ER-negative breast cancer. Fixed and random effects inverse variance weighted methods were used to estimate the causal effects, along with other additional MR methods for sensitivity analyses.
Results:
Results showed that each additional standard deviation of 4.2 years of education was causally associated with a 27% lower risk of ER-negative breast cancer (odds ratio, 0.73; 95% confidence interval, 0.64–0.84; p-value < 0.001). This finding was consistent with the results of the sensitivity analyses. Physical activities can help improve the protective effect of education against breast cancer, with relatively large mediation proportions. Education increases the risk of ER-positive breast cancer due to alterations in high-density lipoprotein level, triglyceride level, height, waist-to-hip ratio, body mass index, and smoking status, with relative medium mediation proportions. Other mediators including low-density lipoprotein, hip circumference, number of cigarettes smoked per day, time spent performing light physical activity, and performing vigorous physical activity for > 10 minutes explain a small part of the causal effect of education on the risk of developing breast cancer, and their mediation proportion is approximately 1%.
Conclusion
A low level of education is a causal risk factor in the development of breast cancer as it is associated with poor lipid profile, obesity, smoking, and types of physical activity.
7.Hemostatic effects of preperitoneal balloon tamponade with different volumes on hemodynamically unstable pelvic fracture-associated arterial and venous hemorrhage in a swine model
Hailong BING ; Chenxi ZHANG ; Liwei SUN ; Fang LI ; Lin LIN ; Liumei LI ; Qinjun CHU ; Xiaogao JIN ; Hongkai LIAN
Chinese Journal of Orthopaedic Trauma 2023;25(6):537-543
Objective:To determine the effects of preperitoneal balloon (PPB) tamponade with different volumes of fluid on hemodynamically unstable pelvic fracture-associated arterial and venous hemorrhage in a swine model.Methods:A model of open-book pelvic fracture with injuries to external iliac vessels was established in 18 female 12-month old Bama miniature pigs. After the successful establishment of hemodynamically unstable pelvic fracture with vascular injury was confirmed by contrast agent imaging, the animals were randomized into 3 even groups ( n=6): a control group (group C) subjected to PPB tamponade with 0 mL fluid injected, group T1 subjected to PPB tamponade with 500-mL fluid injected, and group T2 subjected to PPB tamponade with 1,000-mL fluid injected. The 3 groups were compared in terms of 60-min survival rate, balloon pressure, peritoneal pressure, bladder pressure, 70-min survival rate, blood loss, and infusion volume. Results:There was no statistically significant difference in the basic hemodynamic or other experimental indicators among the 3 groups before experiment, indicating comparability ( P>0.05). The 60-min survival rate in group T2 was 100.0% (6/6), significantly higher than those in group C and group T1 [0.0% (0/6), 0.0% (0/6)] ( P<0.05). After fluid injection, the balloon pressure and preperitoneal pressure in group T2 were respectively (127.2±4.7) mmHg and (34.5±3.6) mmHg, significantly higher than those in group T1 [(78.7±3.8) mmHg and (13.7±2.8) mmHg] and in group C [0 mmHg and (9.0±1.4) mmHg], and the 2 indicators in group T1 were significantly higher than those in group C (all P<0.05). After fluid injection, there was no statistically significant difference among groups C, T1, and T2 in bladder pressure [(6.7±1.0) mmHg, (5.8±1.9) mmHg, and (6.0±1.1) mmHg] or in bleeding volume [(1,163.0±191.3) mL, (1,212.0±148.4) mL, and (975.0±133.2) mL] (all P≥ 0.05). The infusion volume in group T1 [(1,250.0±225.8) mL] was significantly larger than that in group C [(951.7±177.8) mL] ( P<0.05). No colorectal or bladder injuries were found by the anatomy of the experimental animals in 3 groups. Conclusions:PPB tamponade with 1,000-mL fluid injected in a swine model can efficiently control pelvic fracture-associated arterial and venous hemorrhage, and increase the 60-min survival rate with no colorectal or bladder injuries.
8.Effects of different anesthesia methods on inflammatory factors and pain after total knee arthroplasty in patients with osteoarthritis
Zifei CHENG ; Xinying LI ; He YANG ; Yanhui YU ; Hongkai SUN ; Lihui ZHANG
Chinese Journal of Endemiology 2022;41(11):918-923
Objective:To explore the effects of general anesthesia and combined spinal and epidural anesthesia on inflammatory factors and pain in patients with osteoarthritis after total knee arthroplasty.Methods:A total of 84 patients with osteoarthritis who underwent unilateral total knee arthroplasty in Hulunbuir People's Hospital from January 2020 to May 2021 were selected as the research subjects. They were randomly divided into general anesthesia group (40 cases) and combined spinal and epidural anesthesia group (44 cases). Venous blood samples of 5 ml were collected before operation and 6, 24, 48 hours after operation, and the contents of inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6] in serum were determined by enzyme-linked immunosorbent assay (ELISA). The visual analogue pain scale (VAS) of the two groups at 30 min, 6, 24 and 48 hours after operation was compared.Results:At 6 and 24 hours after operation, TNF-α, IL-1β and IL-6 levels in the combined spinal and epidural anesthesia group were lower than those in the general anesthesia group ( t = 4.17, 3.85, 8.95, 10.98, 10.04, 9.87, P < 0.05). There were significant differences in the levels of TNF-α, IL-1β and IL-6 at different time points between the general anesthesia group and combined spinal and epidural anesthesia group ( F = 271.67, 149.26, 81.70, 189.36, 102.44, 157.32, P < 0.001). At 6 and 24 hours after operation, the VAS scores of patients in the combined spinal and epidural anesthesia group were significantly lower than those in the general anesthesia group ( t = 6.60, 3.66, P < 0.05). There were statistically significant differences in VSA scores between the two groups at different time points ( F = 67.47, 52.37, P < 0.05). Conclusion:The effect of combined spinal and epidural anesthesia is significantly higher than general anesthesia in inhibiting the expression of TNF-α, IL-1β and IL-6 in patients with osteoarthritis after operation, and the effect of analgesia is obvious.
9.Sodium butyrate activates HMGCS2 to promote ketone body production through SIRT5-mediated desuccinylation.
Yanhong XU ; Xiaotong YE ; Yang ZHOU ; Xinyu CAO ; Shiqiao PENG ; Yue PENG ; Xiaoying ZHANG ; Yili SUN ; Haowen JIANG ; Wenying HUANG ; Hongkai LIAN ; Jiajun YANG ; Jia LI ; Jianping YE
Frontiers of Medicine 2023;17(2):339-351
Ketone bodies have beneficial metabolic activities, and the induction of plasma ketone bodies is a health promotion strategy. Dietary supplementation of sodium butyrate (SB) is an effective approach in the induction of plasma ketone bodies. However, the cellular and molecular mechanisms are unknown. In this study, SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting enzyme in ketogenesis, to promote ketone body production in hepatocytes. SB administrated by gavage or intraperitoneal injection significantly induced blood ß-hydroxybutyrate (BHB) in mice. BHB production was induced in the primary hepatocytes by SB. Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis. However, the alteration was mostly observed in mitochondrial proteins with 41% down- and 65% up-regulation, respectively. Succinylation status of HMGCS2 protein was altered by a reduction at two sites (K221 and K358) without a change in the protein level. The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice. The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver. The effect was not associated with an elevation in NAD+/NADH ratio according to our metabolomics analysis. The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.
Mice
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Animals
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Butyric Acid/metabolism*
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Ketone Bodies/metabolism*
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Liver/metabolism*
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Hydroxybutyrates/metabolism*
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Down-Regulation
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Sirtuins/metabolism*
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Hydroxymethylglutaryl-CoA Synthase/metabolism*
10.PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism.
Mingming SUN ; Leilei LI ; Yujia NIU ; Yingzhi WANG ; Qi YAN ; Fei XIE ; Yaya QIAO ; Jiaqi SONG ; Huanran SUN ; Zhen LI ; Sizhen LAI ; Hongkai CHANG ; Han ZHANG ; Jiyan WANG ; Chenxin YANG ; Huifang ZHAO ; Junzhen TAN ; Yanping LI ; Shuangping LIU ; Bin LU ; Min LIU ; Guangyao KONG ; Yujun ZHAO ; Chunze ZHANG ; Shu-Hai LIN ; Cheng LUO ; Shuai ZHANG ; Changliang SHAN
Acta Pharmaceutica Sinica B 2023;13(1):157-173
Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.