1.Role and mechanism of cysteine and glycine-rich protein 2 in the malignant progres-sion of neuroblastoma
Yao ZHANG ; Jinxin GUO ; Shijia ZHAN ; Enyu HONG ; Hui YANG ; Anna JIA ; Yan CHANG ; Yongli GUO ; Xuan ZHANG
Journal of Peking University(Health Sciences) 2024;56(3):495-504
Objective:To investigate the function and underlying mechanism of cysteine and glycine-rich protein 2(CSRP2)in neuroblastoma(NB).Methods:The correlation between the expression level of CSRP2 mRNA and the prognosis of NB children in NB clinical samples was analyzed in R2 Genomics Analysis and Visualization Platform.The small interfering RNA(siRNA)targeting CSRP2 or CSRP2 plasmid were transfected to NB cell lines SK-N-BE(2)and SH-SY5Y.Cell proliferation was observed by crystal violet staining and real-time cellular analysis.The ability of colony formation of NB cells was ob-served by colony-forming unit assay.Immunofluorescence assay was used to detect the expression of the proliferation marker Ki-67.Flow cytometry analysis for cell cycle proportion was used with cells stained by propidium iodide(PI).Annexin V/7AAD was used to stain cells and analyze the percentage of cell apoptosis.The ability of cell migration was determined by cell wound-healing assay.The level of protein and mRNA expression of CSRP2 in NB primary tumor and NB cell lines were detected by Western blot and quantitative real-time PCR(RT-qPCR).Results:By analyzing the NB clinical sample databases,it was found that the expression levels of CSRP2 in high-risk NB with 3/4 stages in international neuroblas-toma staging system(INSS)were significantly higher than that in low-risk NB with 1/2 INSS stages.The NB patients with high expression levels of CSRP2 were shown lower overall survival rate than those with low expression levels of CSRP2.We detected the protein levels of CSRP2 in the NB samples by Western blot,and found that the protein level of CSRP2 in 3/4 INSS stages was significantly higher than that in 1/2 INSS stages.Knockdown of CSRP2 inhibited cell viability and proliferation of NB cells.Overexpression of CSRP2 increased the proliferation of NB cells.Flow cytometry showed that the proportion of sub-G1,G0/G1 and S phase cells and Annexin V positive cells were increased after CSRP2 deficiency.In the cell wound-healing assay,the healing rate of NB cells was significantly attenuated after knockdown of CSRP2.Further mechanism studies showed that the proportion of the proliferation marker Ki-67 and the phospho-rylation levels of extracellular signal-regulated kinases 1/2(ERK1/2)were significantly decreased after CSRP2 knockdown.Conclusion:CSRP2 is highly expressed in high-risk NB with 3/4 INSS stages,and the expression levels of CSRP2 are negatively correlated with the overall survival of NB patients.CSRP2 significantly increased the proliferation and cell migration of NB cells and inhibited cell apoptosis via the activation of ERK1/2.All these results indicate that CSRP2 promotes the progression of NB by activating ERK1/2,and this study will provide a potential target for high-risk NB therapy.
2.Impact of soy protein and whey protein on body composition in hospitalized lung cancer patients with cancer-related sarcopenia
Yu ZHANG ; Shijia WANG ; Xiaoyan LIU ; Yang DU ; Kang YU
Chinese Journal of Clinical Nutrition 2024;32(5):270-278
Objective:This study aims to assess the effects of soy and whey protein on body composition and muscle function in hospitalized lung cancer patients with cancer-related sarcopenia.Methods:Paired comparison method was adopted for data collected before and after intervention. All enrolled non-small cell lung cancer patients with cancer-related sarcopenia were assigned to either the soy protein (30 g/d) or the whey protein (30 g/d) group to receive the 12-week intervention. Changes in muscle mass (MM) and muscle function before and after intervention were observed to assess intra-group and inter-group differences.Results:The study included 48 patients, 32 of whom completed the intervention and follow-up (16 from the whey protein group and 16 from the soy protein group). After 12 weeks of intervention with whey protein, significant increases were observed in trunk muscle mass (TMM, P=0.014) and TMM adjusted for height (TMM/Ht 2, P=0.011). After 12 weeks of intervention with soy protein, significant increases were noted in appendicular muscle mass (AMM, P=0.049), AMM adjusted for body mass index (AMM/BMI, P=0.044), fat free mass (FFM, P=0.041), and MM ( P=0.038). After adjustment using generalized estimating equations, only TMM/Ht 2 ( P=0.049) showed a significant increase in the whey protein group, while TMM ( P=0.040) and TMM/Ht 2 ( P=0.005) significantly increased in the soy protein group. Despite that all MM-related indices increased in both groups, there were no significant inter-group differences after adjusted by covariate analysis. Conclusions:Interventions with soy protein and whey protein can help maintain and improve muscle mass and muscle function in patients with lung cancer-related sarcopenia. Soy protein and whey protein may have comparable benefits in patients with lung cancer-related sarcopenia.
3.Visualization of research trends and hotspots in the field of end tuberculosis based on VOSviewer
Shijia GE ; Jibin XIN ; Yang LI ; Jun YING ; Wenhong ZHANG
Chinese Journal of Infectious Diseases 2024;42(7):409-415
Objective:To analyze the research literature related to end tuberculosis (TB) using bibliometric methods, so as to provide researchers with insights into current research trends and hotspots in this field.Methods:A search was conducted using the Web of Science core collection data base on March 5, 2024. The research was limited to articles and reviews published between 2014 and 2023. The results were visualized with VOSviewer, and an analysis was performed on the involved national, international research cooperation networks and keyword clustering.Results:A total of 1 092 articles related to end TB research were retrieved and screened, with a total citation counts of 14 871 and an average citation counts of 13.62 per article. The United States of America had the highest number of publications (328 articles, 30.04%), while China ranked seventh (100 articles, 9.16%). International scientific collaboration network analysis indicated that countries primarily included the United Kindom, the United States of America, Switzerland, South Africa, the Netherlands, Australia, and India, which had formed close cooperation in the field of end TB research. Keyword clustering analysis suggested that current research hotspots in end TB field included cost analysis related to TB, management of latent TB individuals, strategies for TB prevention and control, key technologies in TB elimination, and TB epidemiology and associated risk factors.Conclusions:Over the past decade, the number of publications and citations in the field of end TB is relatively high. International research collaboration has been extensive, and the research content covers multiple dimensions, including the management and cost analysis of different disease stages, technological innovations, considerations for comprehensive control strategy, and epidemiology.
4.Prevalence and risk factors of cancer related muscle disorder in lung cancer patients
Yu ZHANG ; Shijia WANG ; Xiaoyan LIU ; Yang DU ; Kang YU
Chinese Journal of Health Management 2024;18(5):370-377
Objective:To Investigate the prevalence of cancer related muscle disorder (CRMD) in hospitalized lung cancer patients, and to identify the possible risk factors.Methods:This study was a cross-sectional study. The study enrolled 259 patients without missing data who met the inclusion and exclusion criteria from 347 lung cancer patients who were non-repeated hospitalized in the Department of Respiratory and Critical Care Medicine of Peking Union Medical College Hospital from March 2023 to August 2023. Bioimpedance analysis was used to measure muscle mass in patients, and dietary information was collected using the food frequency questionnaire. Disease information and laboratory test results were obtained by consulting Hospital Information System. According to AWGS 2019, patients were divided into five groups: possible sarcopenia (PS), sarcopenia (S), severe sarcopenia (SS), low muscle mass (LMM), and non-muscle disorder (non-MD). The analysis of variance, Kruskal-Wallis test, and χ 2 test were used to compare differences in baseline data, energy and macronutrient intake, and laboratory test indicators among different groups, and ordered logistic regression analysis was applied for multivariate analysis to identify the influencing factors of CRMD in lung cancer patients. Results:This study included 259 hospitalized lung cancer patients who met the inclusion and exclusion criteria. The prevalence of CRMD among 259 patients was 64.5%, PS was 27.4%, S was 13.5%, SS was 14.3%, and LMM was 5.4%. plant protein intake ( OR=0.969, 95% CI: 0.942-0.996) and regular exercise ( OR=0.485, 95% CI: 0.269-0.869) were found to be protective factors for CRMD in hospitalized lung cancer patients, while age ( OR=1.056, 95% CI: 1.013-1.101), weight loss of more than 5% in the last six months ( OR=4.546, 95% CI: 1.363-15.563), and diabetes ( OR=2.342, 95% CI: 1.137-4.866) were identified as risk factors. Conclusion:The prevalence of CRMD in hospitalized lung cancer patients is relatively high, and is closely related to age, weight changes, exercise, comorbidities, and dietary intake.
5.Research progress on pharmacological mechanism of polygona-polysaccharose
Di WANG ; Jian ZHAO ; Tian ZHOU ; Shijia ZHENG ; Yuanyuan YANG ; Zengxin HAN ; Zhongguang ZHOU
International Journal of Traditional Chinese Medicine 2023;45(1):122-125
Polygona-polysaccharose is an important indicator to measure the quality of Polygonati Rhizoma. The polygona-polysaccharose has the effect of lowering blood sugar, regulating blood lipid, anti-fatigue, improving learning and memory ability. The Polygonati Rhizoma, as a Chinese herbal medicine with homology of medicine and food, has a good prospect and application value in the development of food and health products.
6.A novel inhibitor of ARfl and ARv7 induces protein degradation to overcome enzalutamide resistance in advanced prostate cancer.
Yan LI ; Ya CHU ; Guangjiang SHI ; Xiaobin WANG ; Wanli YE ; Chun SHAN ; Dajia WANG ; Di ZHANG ; Wei HE ; Jingwei JIANG ; Shuqian MA ; Yuhong HAN ; Zhili ZHAO ; Shijia DU ; Zhen CHEN ; Zhiyu LI ; Yong YANG ; Chen WANG ; Xi XU ; Hongxi WU
Acta Pharmaceutica Sinica B 2022;12(11):4165-4179
Enzalutamide (ENZ) is a second-generation androgen receptor (AR) antagonist used for the treatment of castration-resistant prostate cancer (CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance (ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR (ARfl) or dominantly active androgen receptor splice variant 7 (ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood-brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.
7.Fingerprint Establishment ,Content Determination and α-glucosidase Inhibitory Activity Study of Polysaccharide from Desmodium styracifolium
Xuanxuan CHENG ; Liangyuan CHEN ; Shijia ZHENG ; Xiaomin TANG ; Quan YANG
China Pharmacy 2020;31(2):183-189
OBJECTIVE:To estab lish the fingerprint ,analyze the monosaccharide composition and content ,investigate the inhibitory effects of the polysaccharide from Desmodium styracifolium on α-glucosidase in vitro . METHODS :Polysaccharide from D. styracifolium was prepared by water extraction and ethanol precipitation. After hydrolyzed by TFA and derived by PMP ,HPLC method was adopted to establish the fingerprint (using glucose peak as reference ),and analyze the constituent and content of monosaccharide. The content determination was performed on Phenomenex Luna C 18 column with mobile phase consisted of acetonitrile-0.05 mol/L potassium phosphate (pH adjusted to 6.8 with sodium hydroxide )in gradient elution at the flow rate of 0.8 mL/min. The detection wavelength was set at 250 nm,and column temperature was set at 30 ℃. The sample size was 10 μL. Using acarbose as control ,PNPG assay was used to investigate the α-glucosidase inhibitory activity of polysaccharide from D. styracifolium. RESULTS :There were 9 common peaks in HPLC fingerprints of 18 batches of samples ,and the similarity of 15 batches of samples was higher than 0.90. Totally 7 peaks were identified as mannose ,rhamnose,galacturonic acid ,glucose, galactose,xylose and arabinose. The contents of rhamnose ,galacturonic acid ,glucose,galactose and arabinose were 0.471-2.092, 1.379-8.919,2.560-35.679,1.194-6.905,0.566-4.158 mg/g,respectively. Based on rhamnose ,the molar ratios of the other four monosaccharides were 1.58-4.07,2.26-19.95,2.20-4.21 and 1.31-2.86,respectively. The inhibitory activity of polysaccharide from D. styracifolium on α-glucosidase increased with the increase of dose ,and the half inhibitory concentrations of it was 0.70 mg/mL, lower than 7.76 mg/mL of acarbose (positive control ). CONCLUSIONS :Glucose is the main component of D. styracifolium polysaccharide in different batches ,and the contents of monosaccharides are different. The polysaccharide from D. styracifolium have significant inhibitory activity on α-glucosidase,which is better than that of acarbose.
8.Evaluation of left ventricular systolic function in patients with hypertension by layer‐specific strain and transmural gradient
Shijia LYU ; Jianjun YUAN ; Haohui ZHU ; Xijun ZHANG ; Jiyun CHEN ; Yang LI ; Shuai LI ; Ming WU ; Changhua WEI
Chinese Journal of Ultrasonography 2019;28(5):392-396
Objective To investigate the value of ultrasonic two‐dimensional speckle tracking imaging ( 2D‐ST I) layer‐specific strain and transmural gradient in evaluating the changes of hypertensive patients′left ventricular three layers myocardial function . Methods Thirty‐five hypertensive patients without renal insufficiency were selected as group A ,and 25 hypertensive patients with renal insufficiency as group B .For comparison ,40 healthy volunteers were gathered as control group . T hen ,the systolic peak longitudinal strain of the left ventricle( LPS) ,endocardium( LPS Endo ) ,mid‐cardium ( LPSMid ) and epicardium ( LPSEpi ) were collected .After that ,features of transmural gradient ( ΔLS ) and its percentage ( ΔLS% ) were analyzed . Results For each group ,gradient features exist in each layer of left ventricular myocardium :LPS Endo >LPSMid>LPSEpi . For each group ,the differences between LPSEndo and LPSMid ,and that between LPSEndo and LPSEpi were both statistically significant( P <0 .05) . When it came to the differences between LPS Mid and LPSEpi ,those of group A and control group were both statistically significant ( P <0 .05 ) . Compared with control group ,the LPSEndo of group A ,and LPSEndo ,LPSMid and LPSEpi of group B declined ,all the differences were statistically significant ( P <0 .05 ) . Compared with group A ,LPS Endo ,LPSMid and LPSEpi of group B declined ,the differences were statistically significant ( all P <0 .05) . For ΔLS′s differences among all three groups ,there was no statistical significance( P >0 .05) . Compared with control group ,the ΔLS% Endo‐Mid of group A rised , and the ΔLS% Endo‐Mid , ΔLS% Mid‐Epi of group B rised , the differences were statistically siginificant ( all P < 0 .05 ) . Compared with group A ,the ΔLS% Endo‐Mid ,ΔLS% Mid‐Epi of group B rised ,the differences were statistically siginificant( all P <0 .05) . Conclusions T he layer‐specific strain technique can quantitatively evaluate the changes of systolic function of the left ventricular myocardium in hypertensive patients . ΔLS% may have better sensitivity than ΔLS in dection of systolic function damage of the left ventricular myocardium and can provide more reference for the evaluation of left ventricular systolic function .
9.Real-time virtual navigation system combined with CEUS guided radiofrequency ablation therapy of neonatal or recurrent hepatocellular carcinoma lesions
Qian XU ; Shuzhi LIN ; Shijia DONG ; Jinyu WU ; Wei YANG ; Wei WU ; Kun YAN ; Minhua CHEN
Chinese Journal of Medical Imaging Technology 2018;34(5):701-704
Objective To investigate the value of real-time virtual navigation system (RVS) combined with CEUS in guiding radiofrequency ablation (RFA) therapy of neonatal or recurrent lesions of hepatocellular carcinoma (HCC).Methods Totally 111 patients with neonatal or recurrent lesions of HCC after RFA therapy were enrolled.Seventy-eight patients with 86 lesions (77 neonatal lesions and 9 recurrent lesions) underwent RFA guided by RVS combined with CEUS (RVS combined with CEUS group),and 33 patients with 38 lesions (26 neonatal lesions and 12 recurrent lesions) underwent RFA guided by CEUS alone (control group).The precise localization,inactivation rate and local recurrence rate between the two groups were compared.Results Eighty-four lesions (84/86,97.67%) in RVS combined with CEUS group and 25 lesions (25/38,65.79%) in control group were clearly showed and localized (P<0.001).One month after RFA therapy,the tumor inactivation rate in RVS combined with CEUS group and control group was 95.35 % (82/86) and 76.31% (29/38),respectively (P=0.003).The local recurrence rate in RVS combined with CEUS group was 8.14% (7/86),while was 36.84% (14/38) in control group (x2 =15.434,P<0.001).Conclusion RVS combined with CEUS guidance can improve the accurate position rate and early inactivation rate of RFA therapy for neonatal or recurrent lesions of HCC.
10.Clinical Features and Prognosis of t(8;21) AML Patients in China: A Multicenter Retrospective Study.
Dan GONG ; Wei LI ; Liang-Ding HU ; Jian-Min LUO ; Jian-Liang SHEN ; Mei-Yun FANG ; Qing-Ming YANG ; Heng-Xiang WANG ; Xiao-Yan KE ; Hui-Ren CHEN ; Zhao WANG ; Hui LIU ; Feng LIU ; Yi-Gai MA ; Jing-Wen WANG ; Hong-Hua LI ; Quan-Shun WANG ; Yu JING ; Xiao-Ning GAO ; Li-Ping DOU ; Yong-Hui LI ; Li YU
Journal of Experimental Hematology 2017;25(4):980-986
OBJECTIVETo summarize the clinical characteristics of peripheral blood, immune phenotypes, fusion genes and cytogenetics of patients with t(8;21) acute myeloid leukemia(AML) through the retrospective analysis of 586 patients with t(8;21) AML from 15 blood disease research centers in Northern area of China.
METHODSThe factors affecting prognosis of patients with t(8;21) AML were investigated by using univariate and multivariate COX regression.
RESULTSThe immune type of t(8;21) AML patients was mainly with HLA-DR, CD117, CD34, MPO, CD38, CD13and CD33(>95%), part of them with CD19and CD56; the most common accompanied mutation of t(8;21) AML patients was C-KIT mutation (37.8%); in addition to t(8;21) ectopic, the most common chromosomal abnormality was sex chromosome deletions (38.9%). The univariate analysis revealed a significant survival superiority of OS and PFS in t(8;21) AML patients of WBC≤3.5×10/L without C-KIT mutation, the newly diagnosed ones achieved HSCT(P<0.05), only survival superiority on OS in t(8;21) AML patients with extramedullary infiltration and CD19 positive; the results of multivariate analysis showed a significant survival superiority on OS and PFS in t(8;21) AML patients with WBC≤3.5×10/L(P<0.05).
CONCLUSIONThe clinical features of t(8;21) AML patients in China are similar to those in other countries, WBC≤3.5×10/L is a good prognostic factor while the C-KIT mutation is a poor one in t(8;21) AML patients.

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