1.Role of IL-22/IL-22RA1 pathway in the malignant progression of oral squamous carcinoma and its mechanism
Chinese Journal of Cancer Biotherapy 2024;31(1):19-26
[摘 要] 目的:探讨IL-22/IL-22受体A1(IL-22RA1)通路在口腔鳞状细胞癌(OSCC)恶性进展中的作用及其机制。方法:利用GEO数据库和免疫组化法分析IL-22RA1在OSCC组织及配对癌旁组织中的表达水平,采用组织芯片免疫组化法检测并分析IL-22RA1表达水平与OSCC患者临床病理特征的关系,通过EBI ArrayExpress数据库分析IL-22RA1表达水平与患者预后的关系。采用免疫荧光法检测IL-22和IL-22RA1在OSCC组织中表达水平并分析两者间的相关性。用RNA干扰技术敲减OSCC细胞WSU-HN4和CAL27的IL-22RA1表达,用qPCR法验证敲减效率。采用克隆形成实验、Transwell小室法分别检测IL-22对阴性对照(siNC)组和IL-22RA1敲减(siIL-22RA1)组OSCC细胞克隆形成及迁移能力的影响,WB法检测IL-22对OSCC细胞IL-22RA1表达水平及STAT1、STAT3和ERK1/2磷酸化水平的影响。结果:OSCC组织中IL-22RA1 mRNA的表达水平显著高于癌旁组织(P<0.05)。IL-22RA1表达水平与OSCC患者的肿瘤大小(P<0.05)、淋巴结转移(P<0.01)及预后不良(P<0.05)有关联。OSCC组织中的IL-22和IL-22RA1表达水平无明显关联,IL-22对OSCC细胞IL-22RA1表达无影响(均P>0.05)。IL-22可显著增强OSCC细胞的克隆形成和迁移能力(均P<0.01),并可激活OSCC细胞的STAT1、STAT3及ERK1/2信号分子;敲减OSCC细胞的IL-22RA1后,IL-22则无法发挥上述作用。结论:IL-22/IL-22RA1可通过调控细胞增殖和迁移促进OSCC的生长和转移,其下游机制可能是激活ERK1/2-STAT1/3信号通路。
2.The exploration of the significance of proactive healthy living index for the elderly based on the functional capacity of Chinese older people
Guifang ZHANG ; Yiwen HAN ; Chi ZHANG ; Jing PANG ; Huan GONG ; Jian LI ; Tiemei ZHANG ; Ping ZENG
Chinese Journal of Geriatrics 2022;41(6):714-719
Objective:To explore the significance of proactive healthy living index(PHLI)to provide a reference for the elderly to maintain function through healthy daily life.Methods:The functional status of the elderly was defined based on gait speed and cognitive function.Logistic regression model was used to select the daily life indicators which could be the risk factors for the functional status, and a nomogram was graphed for its visualization.PHLI was formed according to the result of the nomogram.Receiver operating characteristic curve(ROC)was plotted according to the functional status of the elderly, and the cut-off value of PHLI was determined based on the principle of the maximum sum of sensitivity and specificity.Results:A total of 4 971 participants with an average age of (70.9±7.5)years were included in the cross-sectional study, of whom 2 649 cases(53.3%)maintained normal function.The Logistic regression analysis showed that the housework had the most significant effect on the functional status of the elderly, followed by positive psychology( OR=2.04, 1.92; both P<0.001), increasing the likelihood of maintaining normal function by 104% and 92%, respectively.Regular life patterns, adequate protein intake, sleep quality and so on also influenced functional status of the elderly(all P<0.05). The PHLI median score of the elderly was 7.3(5.9, 8.3)points.The area under the curve(AUC)was 0.70(95% CI: 0.68-0.71), and the cut off value of PHLI was 6.8 points. Conclusions:The PHLI is associated with the maintenance of functional capacity in the elderly, which can be applied as a simple tool to provide reference for old people to keep functional health through living a proactive healthy daily life.
3.Effect of lncRNA SNHG15 targeting miR-153 on apoptotic of mitochondrial pathway in breast cancer cells
WU Chao ; WANG Caixing ; HAN Yujiao ; NIU Guifang
Chinese Journal of Cancer Biotherapy 2020;27(10):1087-1092
[Abstract] Objective: To investigate the effect of lncRNA SNHG15 targeting miR-153 on cell viability and apoptosis of breast cancer cells and its apoptotic mechanism. Methods:The expression of SNHG15 in breast cancer cell lines(MDA-MB-231, BT-549 and MCF-7)
were detected by Real-time fluorescent quantitative PCR (qPCR). MDA-MB-231 cells were divided into control (Ctrl) group, si-NC group, si-SNHG15 group, si-SNHG15+anti-NC group and si-SNHG15+anti-miR-153 group. Cell viability and apoptosis rate were detected by MTT and Flow cytometry, respectively. The targeting relationship between SNHG15 and miR-153 was verified by Dual luciferase report gene system. Mitochondrial membrane potential fluorescent probe (JC-1) staining method was used to detect cell mitochondrial membrane potential. The expressions of mitochondrial apoptosis-related proteins (Bcl-2, Bax, caspase3, cleaved caspase3
[c-caspase3] and Cyt-C)were detected by Western blotting. Results: The expression of SNHG15 in breast cancer cells was significantly
higher than that in human normal mammary epithelial MCF10A cells (P<0.01). There was a targeting relationship between SNHG15
and miR-153. Compared with the control group, the cell viability and mitochondrial membrane potential of MDA-MB-231 cells in si-SNHG15 group were decreased, while apoptosis rate was increased (all P<0.01); the expressions of Bcl-2 and caspase3 were
decreased while expressions of Bax, c-caspase3 and Cyt-C were increased (all P<0.01). However, co-transfection of si-SNHG15 and
anti-miR-153 significantly attenuated the effects of si-SNHG15 on cell viability, apoptosis, mitochondrial membrane potential and
expressions of Bcl-2, Bax, caspase3, c-caspase3 and Cyt-C (all P<0.01). Conclusion: lncRNA SNHG15 can target miR-153 to induce
apoptosis of MDA-MB-231 cells, and the mechanism may be related to the regulation of apoptosis of mitochondrial pathway.
4.Results of thalassemia screening and genetic diagnosis for 13 738 pregnant women.
Yuanyuan HAN ; Wei DAI ; Xingmei LIU ; Guifang LI ; Yin XU ; Xingwei MA ; Yuanyuan LI ; Wenping HAN ; Nannan YANG ; Qin XU ; Ling HUANG ; Shengwen HUANG
Chinese Journal of Medical Genetics 2017;34(4):588-591
OBJECTIVETo report on the result of thalassemia screening and genetic diagnosis for pregnant women from Guiyang region.
METHODSPrenatal screening for thalassemia was carried out based on erythrocyte parameters and hemoglobin electrophoresis. Single-tube multiplex GAP-PCR and PCR-reverse dot blot hybridization were performed on suspected cases to identify common alpha- and beta- thalassemia mutations, and direct sequencing was used for identifying rare mutations.
RESULTSAmong 13 738 pregnant women, 1745 (12.70%) were suspected as thalassemia. In terms of native place, the provinces with highest screening-positive rates were Guangxi, Guangdong, Jiangxi and Guizhou. And the ethnic groups with highest screening-positive rates were Zhuang, Li, and Buyi. Among 801 women subjected to genetic testing, 457 (57.05%) were diagnosed with thalassemia. In total 9 genotypes of alpha- thalassemia were detected, with the most common genotypes being --/alpha alpha (63.35%), - alpha/alpha alpha (19.37%) and - alpha/alpha alpha (8.90%). Eleven genotypes of beta- thalassemia were detected, with the most common genotypes being CD17/N (42.91%), CD41-42/N (32.46%) and IVS-II-654/N (11.94%). Two cases were detected with rare beta-thalassemia mutations (CD54-58/N and IVS-I-130/N).
CONCLUSIONThe screening-positive rate of thalassemia among pregnant women in Guiyang region is relatively high. The rates have shown substantial difference in terms of native place and ethnic group. Thalassemia-related mutations in Guizhou region have a diverse spectrum, which showed certain difference from those of other regions.
Adolescent ; Adult ; Female ; Genotype ; Humans ; Middle Aged ; Pregnancy ; Prenatal Diagnosis ; methods ; Thalassemia ; genetics ; Young Adult
5.Effect of Ganoderma Lucidum Preparation on the Behavior,Biochemistry,and Autoimmune Parameters of Mouse Models of APP/PS1 Double Transgenic Alzheimer's Disease.
Chuan QIN ; Shanqiu WU ; Baosheng CHEN ; Xiaoxian WU ; Kunyao QU ; Junmin LIU ; Guifang ZHANG ; Yanfeng XU ; Shunli SHU ; Lihua SUN ; Yanhong LI ; Hua ZHU ; Lan HUANG ; Chunmei MA ; Yuhuan XU ; Yunlin HAN ; Yaozeng LU
Acta Academiae Medicinae Sinicae 2017;39(3):330-335
Objective To evaluate the efficacy of Ganoderma lucidum preparation on the behaviors,biochemistry,and autoimmunity parameters of mouse models of APP/PS-1 double transgenic Alzheimer's disease(AD).Methods A total of 44 4-month-old APP/PS-1 double transgenic AD mice were randomly divided into AD model group,Aricept group,Ganoderma lucidum middle-dose(LZ-M)group,and Ganoderma lucidum high-dose(LZ-H)group,with 11 mice in each group.In addition,10 4-month-old C57BL/6 mice were used as the control group.Water maze test was conducted to observe the behavior changes,and the protein expressions in brain tissues were detected by Western blot analysis.The autoimmune indicators were detected by indirect immunofluorescence method.Results In the navigation experiment,the time of finding the platform was gradually shortened since the 2day in the control,LZ-H,and LZ-M groups,and the time of searching the platform in the AD model group gradually increased.On the 5day,the time of finding platform was significantly shorter in control group (t=5.607,P=0.000) and LZ-H group(t=2.750,P=0.010)than AD model group.In the space exploration experiment,the number of crossing the target platform(t=2.452,P=0.025)and the residence time in the target quadrant(t=2.530,P=0.020)in AD model group mice was significantly smaller/shorter than those in control group;in addition,the number of crossing the target platform in the AD model group was significantly smaller than that in LZ-H group(t=2.317,P=0.030)and LZ-M group(t=2.443,P=0.030),while the residence time in target quadrant decreased significantly(t=2.770,P=0.020)compared with LZ-H group;the number of crossing through the target platform quadrant(t=2.493,P=0.022)and residence time in the target quadrant(t=2.683,P=0.015)in LZ-H group were significantly higher than in Aricept group.Western blot analysis showed that the expression of ApoA1 in the brain tissues of mice in LZ-H and LZ-M groups were significantly higher than those in AD model group(P<0.01,P<0.05);Aβ-40 expression in LZ-H group was significantly lower than that in AD model group(P<0.05);the expressions of Syt1,ApoE,and ABCA1 in brain tissues of mice in LZ-H group were significantly higher than those in model group(P<0.01,P<0.05).The plasma IgG level in Aricept group(t=30.945,P=0.000),LZ-M group(t=25.639,P=0.000)and LZ-H group(t=4.689,P=0.001)were significantly higher than that in the control group.Conclusion Ganoderma lucidum preparation can improve behavior disorders of AD model mice,promote the expressions of ApoA1,ApoE and Syt1,inhibit the expression of Aβ-40 protein,and improve the autoimmune function.
6.Application of liner-accelerator two-degrade collimator in the treatment of breast cancer after radical mastectomy with intensity-modulated radiotherapy
Guifang ZHANG ; Jie LU ; Changsheng MA ; Tao SUN ; Dali HAN ; Yong YIN
Chinese Journal of Radiological Medicine and Protection 2017;37(8):594-598
Objective To evaluate the dosimetric imnpact of the fixed position of two-degrade collimator in the treatment of breast cancer after radical mastectomy using intensity-modulated radiotherapy (IMRT) technique.Methods A total of ten patients with breast cancer were treated with radical mastectomy and radiotherapy sequaciously involving the supraclavicular region and the chest wall.Two different IMRT treatment plans were designed for each patient:0°,40° and two tangential field.There was no restriction on the position of two-degrade collimator(IMRT-1) (P > 0.05).The beam angles and the parameters were as same as IMRT-1,but fixed the position of the two-degrade collimator of 0° and 40° at the inferior border of the supraclavicular (IMRT-2).The dose distribution of target volume and normal tissues,conformal index (CI),and heterogeneous index (HI) were estimated with the dose volume histogram (DVH) for the two intensity modulated modes.Results The CI were 0.79 and 0.73 (Z =-2.316,P<0.05),and the HI of the IMRT-2 plans was not different from IMRT-1 (P > 0.05).Considering the dose volunes of the ipsilateral lung in two plans,the values of V5,V10,D of IMRT-2 were significantly less than those of IMRT-1 (Z =-2.805,-2.812,-2.521,P < 0.05).Meanwhile,the D of the contralateral lung,D of heart and D of the contralateral breast from the IMRT-2 were all lower than those oflMRT-1 (Z=-2.666,-2.701,-2.310,P<0.05).There was no significant difference in the values of V20,V30 of the ipsilateral lung,V30 of heart and between IMRT-1 and IMRT-2 (P >0.05).Conclusions Compared with IMRT-1,IMRT-2 with fixed position of the two-degrade collimator could significantly reduce the low dose region of the lung and heart.It may be used as an effective alternative for breast cancer after radical mastectomy irradiation.
7.Analysis of Plantar Pressure Differences in Patients with Adolescent Idiopathic Scoliosis and Influence of Insoles on Patients
Xiulan HAN ; Yi XU ; Xiaojin LI ; Chuhuai WANG ; Guifang ZHANG ; Dan LI ; Zijing ZHANG ; Zhenfa ZHANG
Journal of Sun Yat-sen University(Medical Sciences) 2017;38(4):582-589
[Objective] To explore the characteristics of the plantar pressure data of the patients with adolescent idiopathic scoliosis (AIS).[Methods] 56 AIS patients who were diagnosed from October 2015 to March 2017 in the East branch of the First Affiliated Hospital of Sun Yat-sen University divided into 3 groups,18 cases in spinal lateral bending to right,18 cases in spinal lateral bending to left,20 cases in type S who were thoracolumbar scoliosis.Another 19 healthy persons were as the control group.The left and right foot pressure,half foot pressure and other biomechanical data were compared.The changes of the plantar pressure and the Cobb angle were analyzed with the patients who wore orthopedic insoles.[Results] Compared with the control group,the mean pressure of the left foot and the pressure of the left anterior half of the right bending group were less than those of the control group,and the right half foot pressure were greater than those of the control group (P < 0.017).To the left bending group,the mean pressure of right anterior half foot were less than those of the control group,and the right rear half foot pressure was greater than that of the control group (P < 0.017).The pressure of the left anterior half foot of the S type scoliosis group was less than that of the control group.To the right bending group,the left foot average pressure (44.7%±6.0%) was significantly less than the average pressure of right foot (55.4% ± 6.0%).There was no difference in bilateral plantar pressure of the left bending group,S type group and control group.There was difference with the plantar pressure distribution in patients with only one curve after they wore orthotic insoles,but there was no difference in patients with type S.There was no significant difference in the Cobb angle after the patients wearing the orthotic insoles (P =0.102).[Conclusions] The right and left foot pressure symmetry of the right bending patients is poor,but the left and right plantar pressure in the patients with type S is symmetrical.The orthotic insole can be used to adjust the plantar pressure distribution in patients with a single curved scoliosis (left or right),but their effect on the patient's spinal lateral curvature should be further observed.
8.Total flavonoids of Epimedium attenuate aging-related inflammation in rat brain by inhibiting MAPK/NF-κB signaling pathway
Laixin SONG ; Changcheng ZHANG ; Ting WANG ; Zhencai LIU ; Guifang HAN ; Ding YUAN ; Haixia ZHAO
Chinese Pharmacological Bulletin 2017;33(1):84-89,90
Aim To investigate the effect of the total flavonoids of Epimedium (TFE)on MAPK/NF-κB sig-naling pathway and the inflammatory reaction in the hippocampus of natural aging male rats.Methods The morphological changes of the hippocampus com-posed of three areas (CA1 ,CA3 and DG)were ob-served using haematoxylin-eoin (HE ) staining.The protein expression levels of senescence-associated pro-tein p21,apoptosis-related proteins Bax and Bcl-2, nuclear transcription factor-κB p65 (NF-κB p65 )and its downstream inflammatory factors TNF-α,IL-1βand COX-2,and MAPK signaling pathway-related proteins (ERK1/2,p-ERK1/2,JNK,p-JNK,p38MAPK,p-p38MAPK)in hippocampal were detected by Western blot.Results Compared with natural aging group, TFE obviously improved the morphology and structure of hippocampal neurons,and the nerve cells arranged neatly and closely. Furthermore, TFE significantly downregulated the protein expression levels of p2 1 and Bax,upregulated the protein expression levels of Bcl-2 and the ratio of Bcl-2/Bax,and reduced the expression of NF-κB p65 and of its downstream inflammatory fac-tors TNF-α, IL-1β, COX-2, and MAPK signaling pathway-related proteins (p-ERK1/2,p-JNK and p-p38 MAPK ) in hippocampus of natural aging rats. Conclusions TFE effectively protects against inflam-matory reaction in brain aging of SD male rats.The mechanism is related with inhibition of NF-κB nuclear translocation and reduction of its downstream inflamma-tory cytokines expression by inhibiting MAPK signaling pathway activation.
9.Biomechanical analysis of lower limbs in adolescents patients with idiopathic scoliosis
Xiulan HAN ; Yi XU ; Xiaojing LI ; Chuhuai WANG ; Guifang ZHANG ; Dan LI
Chinese Journal of Physical Medicine and Rehabilitation 2016;38(6):440-443
Objective To analyze the biomechanical properties of the lower limb in patients with adolescent idiopathic scoliosis (AIS),and to explore the relationship between the biomechanical anomaly of lower limbs and AIS.Methods A total of 116 AIS patients were recruited as the observation group,and another 116 healthy counterparts were selected as the control group.The biomechanical properties of the lower limbs including the torsion angle of the tibia,forefoot-rearfoot angle,rotation angle of the hip joint,leg length difference,and pronation of the ankle were measured and compared between the 2 groups.Then multiple factors regression analysis was conducted to reveal the risking factors for AIS.Results Significant differences were observed between the AIS group and the control group in the leg length difference [(5.94±6.07) mm vs (0.74±2.20)mm] and forefoot-rearfoot angle [(0.17±4.72) ° vs (-0.46±3.60)°] (P<0.01).In the AIS group,significant differences were found in the rotation amplitude of the left and right ankle,with a difference of-1.27° at standard deviation of 3.28 (P<0.01).Multi-factor regression analysis indicated that the leg length difference and forefootrearfoot angle were risk factors for AIS.The odds ratio of the leg length difference and forefoot-rearfoot angle were 1.45 and 0.97,respectively.Conclusions The leg length difference and forefoot-rearfoot angle are risk factors for AIS.
10.Effects of Chaihu Shugan powder on hepatic lipid metabolism and AMPK/SIRT1 pathway in rats with non-alcoholic fatty liver disease
Yupei ZHANG ; Yuanjun DENG ; Chaofeng HU ; Li HAN ; Qinhe YANG ; Yinji LIANG ; Yilin KONG ; Yifang HE ; Ling JIN ; Yuanyuan LI ; Guanlong WANG ; Shaobing CHENG ; Guifang TU
Chinese Journal of Pathophysiology 2016;32(2):307-313
[ ABSTRACT] AIM:To investigate the effects of Chaihu Shugan powder ( CSP) on lipid metabolism and the pro-teins involved in adenosine 5’-monophosphate-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver tissues of the rats with non-alcoholic fatty liver disease (NAFLD).METHODS: Sprague-Dawley rats were randomly di-vided into normal control ( NC) group, with HFD ( HFD) group and CSP group.The NAFLD models were established by feeding with HFD for 16 weeks in the rats.The rats in CSP group were intragastrically administered with CSP extracts (9.6 g· kg-1 · d-1 ) , and blood and liver samples were collected 16 weeks later.Serum and liver levels of total cholesterol ( TC) and triglyceride ( TG) , and serum levels of alanine aminotransferase ( ALT) and aspartate aminotransferase ( AST) were measured using an automatic biochemical analyzer.The histological changes of liver tissues were observed with HE staining, while the lipid deposition was observed with Oil Red O staining.The ultrastructural changes of the liver tissues were observed under transmission electron microscope.Moreover, the protein levels of AMPK, phosphorylated AMPK (pAMPK), SIRT1 and uncoupling protein 2 (UCP2) in the liver were detected by Western blot.RESULTS:The results of HE staining, Oil Red O staining and electron microscopy demonstrated that NAFLD rat model was successfully estab-lished.Compared with NC group, the serum and liver levels of TC and TG, and serum level of AST in model group were markedly elevated ( P<0.01) .Moreover, the protein levels of pAMPK and SIRT1 in HFD group were markedly reduced (P<0.01), whereas UCP2 level was elevated (P<0.01).Furthermore, liver levels of TC and TG, and serum level of AST in GSP group were markedly reduced as compared with HFD group ( P<0.05 ) .The protein levels of pAMPK and SIRT1 were elevated ( P<0.05 ) , whereas the UCP2 level was reduced as compared with HFD group ( P<0.01 ) .The protein level of AMPK between the 3 groups had no significant difference.CONCLUSION: CSP attenuates hepatic lipid disorder and hepatic lipid deposition in NAFLD rats induced by feeding with HFD for 16 weeks, which is associated with the activation of AMPK/SIRT1 pathway.

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