1.SOX7 inhibits colorectal cancer proliferation,invasion and migration through the SHP-2/Wnt/β-catenin/ROS pathway
Xueliang WU ; Likun WANG ; Hongqing MA ; Shaodong LI ; Yan LIANG ; Zhilong HUI ; Lei HAN ; Jun XUE
Acta Universitatis Medicinalis Anhui 2024;59(7):1237-1243
Objective To investigate the molecular mechanisms by which SOX7 regulates the SHP-2/Wnt/β-cate-nin/ROS pathway,affecting the proliferation,invasion,and migration of colorectal cancer cells.Methods Twenty nude mice with subcutaneously transplanted tumor models were randomly divided into four groups:SOX7 NC(n=5),SOX mimic(n=5),SOX7 NC+PHPS1(n=5),and SOX7 mimic+PHPS1(n=5)to observe tumor growth.Human colorectal cancer cell line SW480 cells were transfected via lipofection and divided into six groups:SOX7 NC,SOX7 mimic,SOX7 NC+H2 O2,SOX7 mimic+H2O2,SOX7 NC+PHPS1,and SOX7 mimic+PHPS1.The ex-pression of SHP-2/Wnt/β-catenin/ROS pathway-related proteins in SW480 cells of each group was detected by Western blot.The invasion and migration capabilities of SW480 cells were assessed through scratch and Transwell invasion assays,while cell proliferation was evaluated using CCK-8.Results In vivo experiments demonstrated that tumors in the SOX7 mimic group were significantly smaller than those in the SOX7 NC group(P<0.01).Tumors treated with PHPS1 intervention exhibited a significant increase in volume.There was no statistical significance in the difference in tumor volume between the SOX7 mimic+PHPS1 group and the SOX7 NC+PHPS1 group.In vitro experiments revealed that SOX7 mimic inhibited the expression of Wnt,β-catenin,NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins(P<0.01),and promoted the expression of p-SHP-2 protein(P<0.01).The addition of hydrogen peroxide and SHP-2 inhibitor reversed the effects of SOX7 on SW480 cells(P<0.05),and significantly promoted the expression levels of Wnt,β-catenin,NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins,with no sig-nificant difference,while significantly reducing the expression levels of SHP-2,p-SHP-2 proteins,with no significant difference.PHPS1 inhibited the expression of SHP-2,p-SHP-2 proteins(P<0.05)and upregulated the expression of Wnt,β-catenin,NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins(P<0.05).Scratch,Transwell invasion and migration assays,and CCK-8 experiments indicated that SOX7 suppressed the migration,invasion,and proliferation of SW480 cells through oxidative stress and the SHP-2 pathway(P<0.01),while H2O2 and PHPS1 intervention promoted the migration,invasion,and proliferation of SW480 cells(P<0.05).Conclusion SOX7 can suppress the proliferation,invasion,and migration of colorectal cancer by targeting the SHP-2/Wnt/β-catenin/ROS pathway.
2.Analysis of VSIG4 expression in clear cell renal cell carcinoma and its correlation with tumor infiltrating immune cells
Hangfeng LIU ; Shenglu LIU ; Lianrui DUAN ; Likun ZAN ; Yanjie MA ; Lijun YANG
Chinese Journal of Immunology 2024;40(5):918-924
Objective:To explore expression of VSIG4 in clear cell renal cell carcinoma(ccRCC)and its correlation with immune cells infiltration and prognosis.Methods:RNA-seq data of ccRCC and corresponding clinical data of patients were downloaded from The Cancer Genome Atlas(TCGA)database.Wilcoxon rank-sum test was used to analyze VSIG4 mRNA expression in ccRCC and normal renal tissues.Correlation between VSIG4 expression and clinicopathological parameters was analyzed by Wilcoxon rank-sum or Kruskal-Wallis rank-sum test.Kaplan-Meier method was used to analyze the correlation between VSIG4 expression and progno-sis of patients.Gene set enrichment analysis(GSEA)was used to explore the signaling pathway of VSIG4 in ccRCC.Correlation between VSIG4 level and tumor infiltrating immune cells was analyzed via CIBERSORT in R software.Western blotting was used to detect VSIG4 protein level in human renal epithelial cell line 293T,and human renal carcinoma cell line ACHN,A498,786-O and OS-RC-2.Results:Expression level of VSIG4 in ccRCC was significantly higher than that in normal tissues(P<0.05).VSIG4 expression was significantly correlated with the stages of distant metastasis and lymph node metastasis(P<0.05).Overall survival rate of patients with high VSIG4 expression was significantly lower than that of patients with low expression(P<0.05).GSEA enrichment analysis showed that VSIG4 was mainly enriched in apoptosis,chemokine signaling pathway,cell adhesion molecules and other signaling path-ways.VSIG4 expression was negatively correlated with M1 macrophages(r<0,P<0.05),while positively correlated with M2 macro-phages(r>0,P<0.05).Western blotting results showed that expression of VSIG4 in renal cell carcinoma cells was higher than that in normal renal cells.Conclusion:VSIG4 is highly expressed in ccRCC,and is negatively associated with prognosis,which may become a prognostic biomarker for ccRCC patients.
3.Comparison of internal fixation and total hip replacement in elderly patients with femoral neck fractures
Likun ZHAO ; Shuangshuang CUI ; Jianxiong MA ; Qiang DONG ; Yumin WANG ; Xinlong MA
Chinese Journal of Geriatrics 2023;42(11):1320-1325
Objective:To compare the clinical results and costs of treatment between internal fixation and total hip replacement in patients aged 60 to 75 years with femoral neck fractures, in order to provide a reference basis for choosing the appropriate surgical procedure for patients in this age group.Methods:According to the inclusion and exclusion criteria, we selected 69 patients treated with internal fixation and 88 patients treated with total hip replacement for femoral neck fractures, and collected relevant data to analyze the differences in clinical characteristics and prognosis between the two groups.Results:The total hip replacement group was older than the internal fixation group[68(64, 72) vs.63(61, 68), Z=-4.536, P<0.001]. There were 20 men(29.0%)and 49 women(71.0%)in the internal fixation group, and 13 men(14.8%)and 75 women(85.2%)in the total hip replacement group.Both groups had more women than men( χ2=4.706, P=0.030). The ratio of the displaced type to the non-displaced type was higher in the total hip replacement group than in the internal fixation group(90.9% vs.46.4%, χ2=37.510, P<0.001). Postoperative serum albumin levels were lower than preoperative levels in both groups, with greater decreases in the total hip replacement group than in the internal fixation group[(9.06±3.45)g/L vs.(7.07±3.37)g/L, t=-3.393, P=0.001]. The total hip replacement group had a higher intraoperative bleeding volume and blood transfusion volume than the internal fixation group( P<0.05), and the days of hospitalization[12(9, 14)d]and hospitalization costs[¥89222.1(84826.8, 93040.0)]were higher than those in the internal fixation group[9(8, 10)d; ¥51158.9(47816.5, 54098.4), Z=-5.138, -10.737, P<0.001 for both]. Weight-bearing after total hip replacement occurred earlier than the internal fixation group[32.0(28.0, 36.5)d vs.92.0(89.3, 95.5)d, Z=-10.228, P<0.001]. There were no significant differences between the two types of surgery for non-displaced femoral neck fractures at 1 year after surgery in the Harris hip score and the quality of life score EQ-5D.For patients with displacement, the rates of excellent and good outcomes based on the Harris score for the total hip replacement group were significantly higher than those for the internal fixation group at 1 year after surgery(97.5% vs.81.3%, χ2=6.697, P=0.010); the postoperative quality of life score EQ-5D was also better than that of the internal fixation group[0.9(0.7, 1.0) vs.1.0(1.0, 1.0), Z=-4.785, P<0.001], and the incidence of postoperative pain and anxiety was lower than that in the internal fixation group(6.3% vs.28.1%, 1.3%, vs.50.0%, χ2=7.928, 38.032, all P<0.01). Conclusions:The mortality and short-term postoperative complications between internal fixation and total hip replacement have no significant differences.There is no significant difference in postoperative function between the two surgical methods for patients with non-displaced femoral neck fractures.For patients with displacement, total hip arthroplasty is superior to internal fixation.The cost of initial hospitalization for internal fixation is significantly lower than for total hip replacement.
4.Hepatocyte-specific TM6SF2 knockout aggravates hepatic steatosis in mice with nonalcoholic fatty liver disease
Jie ZHANG ; Xuefeng MA ; Yifen WANG ; Mengke WANG ; Likun ZHUANG ; Shousheng LIU ; Yongning XIN
Journal of Clinical Hepatology 2021;37(11):2612-2616
Objective To establish a mouse model of hepatocyte-specific TM6SF2 knockout, and to investigate the role of TM6SF2 in the development of nonalcoholic fatty liver disease (NAFLD). Methods The CRISPR/Cas9 technique and the Cre/LoxP strategy were used to establish a stable mouse model of hepatocyte-specific TM6SF2 knockout. The mice with hepatocyte-specific TM6SF2 knockout and the control mice were given a normal diet or a high-fat diet (HFD) for 16 weeks, and related indices were measured, including general status (body weight and liver weight), glucose metabolic indices (fasting blood glucose and insulin), and lipid metabolism (plasma triglyceride, cholesterol, and liver triglyceride). The t -test was used for comparison of normally distributed continuous data between two groups. Results Under the condition of HFD, compared with the control mice, the mice with hepatocyte-specific TM6SF2 knockout had significantly higher liver weight (2.235±0.175 g vs 1.258±0.106 g, t =4.789, P < 0.01) and liver index (4.970%±0.298% vs 3.210%±0.094%, t =5.630, P < 0.01), and the loss of the TM6SF2 gene in hepatocytes aggravated the abnormal level of alanine aminotransferase induced by HFD (62.517±1.526 U/L vs 25.991±5.947 U/L, t =5.949, P < 0.01). Compared with the control mice under the condition of normal diet or HFD, the mice with TM6SF2 knockout had a significant increase in plasma insulin level (normal diet: 37.203±0.836 mIU/L vs 34.835±0.426 mIU/L, t =2.520, P =0.025; HFD: 41.093±1.226 mIU/L vs 35.817±0.500 mIU/L, t =3.985, P =0.007), while there were no significant differences in the other indices associated with glucose metabolism (all P > 0.05). Under the condition of HFD, there were no significant differences in the levels of plasma triglyceride and cholesterol between the mice with hepatocyte-specific TM6SF2 knockout and the control group ( P > 0.05), while the mice with hepatocyte-specific TM6SF2 knockout had a significant increase in the level of liver triglyceride compared with the control mice (23.969±0.978 mg/g vs 18.229±1.633 mg/g, t =3.015, P =0.024). Conclusion Hepatocyte-specific knockout of TM6SF2 can aggravate liver lipid accumulation and liver injury in mice with NAFLD.
5.The application of "internet +" disease management based on the AISAS model on young and middle-aged patients after PCI therapy
Jiaoyu CAO ; Panpan SUN ; Lixiang ZHANG ; Xia CHEN ; Anping OU ; Wenjuan GUI ; Likun MA
Chinese Journal of Practical Nursing 2021;37(15):1121-1127
Objective:To investigate the effect of the application of "internet +" disease management based on the AISAS model on the young and middle-aged patients after PCI therapy.Method:A total of 90 young and middle-aged patients hospitalized in cardiological department of the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) were enrolled between June 2018 to October 2019, and they were randomly divided into observation group and control group with 45 cases in each group. Patients in the control group received telephone follow-up while "internet +" disease management based on the AISAS model was applied in the observation group. The drug therapy compliance, acquisition of the disease knowledge, quality of life, anxiety and depression levels, return to workand incidence of cardiovascular events.Results:One year after the intervention, the drug therapy compliance score, disease-related knowledge score, quality of life score, SAS and SDS scores of the observation group were 7.55±1.21, 7.29±1.27, 701.17±74.86, 32.55± 4.31, 34.74±4.16, the scores of patients in the control group were 6.48±1.56, 6.12±1.94, 670.58±65.29, 41.72±4.33, 40.79±4.17. The difference was statistically significant ( t value was 2.066-11.203, P<0.05). The comparison between the return of the patients and the incidence of cardiovascular events in the two groups was statistically significant ( χ2 value was 5.031, 11.275, P<0.05). Conclusion:This management model can increase the knowledge of disease PCI postoperative patients, improve their quality of life, make patients return to society earlier, and promote the improvement of the quality of continuous nursing service.
6.Clinical characteristics analysis of adult femoral neck fracture: a retrospective hospital-based study
Likun ZHAO ; Shuangshuang CUI ; Jianxiong MA ; Yumin WANG ; Qiang DONG ; Xinlong MA
Chinese Journal of Orthopaedics 2021;41(3):157-164
Objective:To analyze the clinical characteristics of patients with femoral neck fracture in Tianjin Hospital.Methods:Data of femoral neck fracture patients discharged from Tianjin Hospital from January 1, 2016 to December 31, 2017 were retrospectively analyzed. The gender, age, fracture type, injury mechanism and treatment method were collected.Results:Total of 2,150 eligible patients including 736 males and 1414 females were selected. There were significant differences in the gender distribution in different age groups ( χ2=91.63, P<0.001). Among young patients, males were more than females, while among middle-aged and elderly patients, females were more than males. The main type of fracture was displaced type (75.56%, 1,646/2,150), the displaced rate was the lowest in young patients (55.17%, 64/116), while it was the highest in old patients (81.91%, 1,159/1,415). The main injury mechanism of the three age groups were falls [young 61.21% (71/116), middle 80.29% (497/619), eldly 91.24% (1,291/1,415)]. There was a significant difference in the treatment methods between different age groups ( χ2=1,057.11, P<0.001). The main treatment method for young and middle-aged patients was internal fixation, no matter whether the fracture was displaced or not. The proportion of undisplaced patients with internal fixation (86.22%, 169/196) was higher than that of displaced patients with internal fixation (62.88%, 266/423) in middle-aged group ( χ2=34.93, P<0.001). In the elderly, more patients used internal fixation in undisplaced group, while more patients used hemiarthroplasty in displaced group. The age of old femoral neck fracture (median age was 74) was older than that of fresh fracture (median age was 70) ( Z=-2.777, P=0.005). And the displaced rate of patients with old femoral neck fracture (92.41%, 73/79) was higher than that of the fresh ones (75.95%, 1,573/2,071)( χ2=11.48, P=0.001). The patients with old femoral neck fracture usually adopt total hip replacement, while the proportion of three kinds of operation (internal fixation, hemiarthroplasty, total hip replacement) were similar among the fresh ones, and the internal fixation was the most. Conclusion:Femoral neck fracture is the most common in elderly women. The patients with displaced fracture are more than that with undisplaced fracture. Falling is the main injury mechanism in both young and old people. Internal fixation is commonly used in young and middle-aged patients, while arthroplasty is often used in elderly patients.
7.COVID-ONE-hi:The One-stop Database for COVID-19-specific Humoral Immunity and Clinical Parameters
Xu ZHAOWEI ; Li YANG ; Lei QING ; Huang LIKUN ; Lai DAN-YUN ; Guo SHU-JUAN ; Jiang HE-WEI ; Hou HONGYAN ; Zheng YUN-XIAO ; Wang XUE-NING ; Wu JIAOXIANG ; Ma MING-LIANG ; Zhang BO ; Chen HONG ; Yu CAIZHENG ; Xue JUN-BIAO ; Zhang HAI-NAN ; Qi HUAN ; Yu SIQI ; Lin MINGXI ; Zhang YANDI ; Lin XIAOSONG ; Yao ZONGJIE ; Sheng HUIMING ; Sun ZIYONG ; Wang FENG ; Fan XIONGLIN ; Tao SHENG-CE
Genomics, Proteomics & Bioinformatics 2021;19(5):669-678
Coronavirus disease 2019(COVID-19),which is caused by SARS-CoV-2,varies with regard to symptoms and mortality rates among populations.Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19.However,differences in immune responses and clinical features among COVID-19 patients remain largely unknown.Here,we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters(named COVID-ONE-hi).COVID-ONE-hi is based on the data that contain the IgG/IgM responses to 24 full-length/truncated proteins corresponding to 20 of 28 known SARS-CoV-2 proteins and 199 spike protein peptides against 2360 serum samples collected from 783 COVID-19 patients.In addition,96 clinical parameters for the 2360 serum samples and basic information for the 783 patients are integrated into the database.Furthermore,COVID-ONE-hi provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups.A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters.After the"START"button is clicked,one can readily obtain a comprehensive analysis report for further interpretation.COVID-ONE-hi is freely available at www.COVID-ONE.cn.
8.The effects of optimizing the timeliness of emergency care of patients with ST-elevation myocardial infarction in hospital
Jiaoyu CAO ; Xia CHEN ; Dandan YIN ; Hua YU ; Hongzhi JI ; Cuihong ZHU ; Likun MA
Chinese Journal of Practical Nursing 2018;34(23):1782-1787
Objective To investigate the effect of optimizing rescue time for patients with acute st-elevation myocardial infarction (STEMI) in the hospital. Methods A retrospective analysis of the clinical data of 133 patients with ST-elevation myocardial infarction who were hospitalized in the first affiliated hospital of university of science and technology of china during July,2016 to June,2017 was performed. Timeline in the rescue, the result of coronary reperfusion and satisfaction degree of patients were analyzed. Results The rapid evaluation time (F=2.609, P=0.046),emergency handling time(F=7.581, P=0.032), login and logout time (F=5.667, P=0.017)and visit-ballon time (F=8.942, P=0.007) were shortened quarter by quarter . The average time of each project in the four quarters showed a statistically significant difference. The difference of TIMI classification of coronary flow reperfusion among the four quarters was statistically significant (H=8.402, P=0.038). The satisfaction degree of each quarter showed a statistically significant difference (the third quarter of 2016:94.68±2.38, the fourth quarter of 2016:96.72± 5.10, the first quarter of 2017:97.23 ± 7.64,the second quarter of 2017:98.36 ± 4.86;F=7.891,P=0.048). Conclusions Enhancing timeliness of emergency care can remarkably shorten rescue time, improve satisfaction degree of patients and help to improve the success rate of emergency treatment for patients with STEMI.
9.Determination of Triptolide in Shenshe Ointment by LC-MS/MS
Zhiqiang MENG ; Shanbo MA ; Likun DING ; Shan MIAO ; Yin WU ; Jinyi CAO ; Long LI ; Biyan DANG ; Xiaopeng SHI
China Pharmacist 2017;20(4):745-748
Objective:To establish an LC-MS/MS method for the content determination of triptolide in Shenshe ointment.Methods:The chromatographic separation was performed on an Agilent TC-C18 (250 mm×4.6 mm,5 μm)column with the mobile phase consisting of methanol-0.1% formic acid solution (73∶27,v/v).The flow rate was 0.5 ml·min-1 and the column temperature was maintained at 35℃.An electrospray ionization (ESI) source was applied with multiple reaction monitoring (MRM) combined with a positive mode.Metronidazole was used as the internal standard.The mass transitions were 361.4→43.2 for triptolide and 172.1→128.0 for metronidazole,respectively.Results:The linear range was 10-500 ng·ml-1 with good correlation coefficient (r=0.999 9).The limit of quantification (LOQ) was 9.5 ng·ml-1.The intra-and inter-day RSDs of peak areas were all less than 3% and the average recovery was 96.87%(RSD=2.79,n=6).Conclusion:The established LC-MS/MS method is simple,efficient,sensitive and accurate in the quality control of Shenshe ointment.
10.Preparation of silk fibroin/chitosan/nano-hydroxyapatite scaffold for sustained release of bone morphogenetic protein-2
Wenliang HUANG ; Peng YE ; Gang MO ; Renyuan TIAN ; Likun MA ; Shiqiang RUAN ; Lin XU ; Jiang DENG
Chinese Journal of Tissue Engineering Research 2017;21(22):3488-3493
BACKGROUND:Bone morphogenetic protein-2 (BMP-2) is a key to bone formation and repair.However,it has some disadvantages such as easy to lose and degrade and difficult to sustain continuous effect.OBJECTIVE:To study the preparation and properties of silk fibroin/chitosan/nano-hydroxyapatite (SF/CS/nHA) scaffold loading BMP-2.METHODS:After silk degumming,dissolution and purification,2% SF solution was obtained.BMP-2 was dissolved in 2% CS solution,and then fully mixed with equal volume of SF solution and proper amount of nHA.At last,the SF/CS/nHA scaffold loading BMP-2 was prepared using freeze-drying method as experimental group.The SF/CS/nHA scaffold was soaked in the BMP-2 solution as control group.The scaffold porosity was measured by Archimedes method,the surface morphology of the scaffold was observed by scanning electron microscope,the compressive strength was measured by universal testing machine.Scaffolds in the two groups were soaked in PBS,and the release of BMP-2 was measured by ELISA method at different time points.RESULTS AND CONCLUSION:(1) The scaffolds in the two groups had irregular porous structure,interconnected pores and uneven pore wall.There was no significant difference between the two groups in mean pore diameter,porosity and maximum compressive strength.(2) On the 1st day,the release rate of BMP-2 was 4.63% in the experimental group,and the release curve increased slowly.After 28 days,the release curve of BMP-2 was transferred to the plateau stage.But in the control group,the release rate of BMP-2 on the 1stday was 58.84%,and it was a significant initial burst release.The release curve increased rapidly,and was transferred to the platform stage on the 10th day.The release rate of BMP-2 release was significantly different between the two groups at days 1,2,4,10 (P < 0.05).These results show that the SF/CS/nHA scaffold loading BMP-2 could sustainably and slowly release BMP-2.


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