1.Effects of Tuina on cartilage degradation and chondrocyte terminal differentiation in rats with knee osteoarthritis (KOA) via the Wnt/β-catenin signaling pathway
Yinan YU ; Youhong XIE ; Chenglin TANG ; Xiao GUO
Journal of Acupuncture and Tuina Science 2023;21(1):18-26
Objective: To investigate the therapeutic effects of Tuina (Chinese therapeutic massage) in a knee osteoarthritis (KOA) rat model and its influence on proteins associated with the Wnt/β-catenin signaling pathway. Methods: A total of 32 specific-pathogen-free grade Sprague-Dawley rats were used. Eight rats were randomly selected as the control group (CG). The remaining 24 rats underwent intra-articular injections with 0.2 mL of 4% papain to prepare the KOA rat models. After the model was established, the 24 rats were randomly and equally assigned to 3 groups, including a model group (MG), a Tuina group (TG), and a positive medicine group (PMG), with 8 rats in each group. The Lequesne score was applied to evaluate the success of model development. After the model was successfully established, the CG did not receive any intervention, and the TG was treated with local, clockwise annular Rou-Kneading around the knee joint with the thumbs. The pressure in the longitudinal direction was 3 N, and the frequency was designed to be 120-140 times/min for 15 min, followed by flexing the joint 10 times. The PMG was intragastrically administered with celecoxib [24 mg/(kg·bw)] every day. These interventions were performed once a day, 6 d per week, for a total of 4 weeks. After treatment, the Lequesne score was applied again to assess the severity of the KOA in the rats; hematoxylin-eosin (HE) staining and a mixture of equal volumes of aqueous solutions of safranin O-fast green were used to stain and observe the cartilage morphology and structure; the modified Mankin score was applied to evaluate the pathology; enzyme-linked immunosorbent assay method was used to quantify the C-telopeptide fragments of type Ⅱ collagen (CTX-Ⅱ) and cartilage oligomeric matrix protein (COMP); Western blotting was then applied to quantify Wnt4, β-catenin, matrix metalloproteinase 13 (MMP-13), and bone morphogenetic protein 2 (BMP-2) protein expression; immunohistochemistry was conducted to determine the percentage of collagen type X (ColX)-positive cells. Results: The Lequesne score of the TG and PMG was both lower than that of the MG (P<0.01); the HE staining, safranin O-fast green stained morphology and structure, and modified Mankin scores of the TG and the PMG were also better than those in the MG (P<0.01). Compared with the CG, the amounts of CTX-Ⅱ and COMP in the serum were significantly increased (P<0.01); the expression of Wnt4, β-catenin, MMP-13, and BMP-2 proteins in the cartilage tissue was significantly increased (P<0.01), and the percentage of ColX-positive chondrocytes was significantly increased (P<0.01) in the MG. In comparison with those in the MG, the amounts of CTX-Ⅱ and COMP were significantly decreased (P<0.01), the expression of Wnt4, β-catenin, MMP-13, and BMP-2 proteins was significantly decreased (P<0.01), and the percentage of ColX-positive chondrocytes was significantly decreased (P<0.01) in the TG and PMG. Compared with the PMG, the contents of CTX-Ⅱ and COMP and the expression of Wnt4, β-catenin, MMP-13, and BMP-2 proteins were decreased (P<0.05 or P<0.01); the percentage of ColX-positive chondrocytes was significantly decreased (P<0.01) in the TG. Conclusion: Tuina can relieve the degeneration of KOA, and the mechanism may be related to the down-regulation of the Wnt/β-catenin signaling pathway, the decrease in MMP-13 and BMP-2 protein expression, the reduction in chondrocyte extracellular matrix degradation, and slowing down the terminal cell differentiation.
2.Discovery of novel heteroaryl alkynes for highly potent KITD816V cells inhibition to treat gastrointestinal stromal tumors.
Zhicheng XIE ; Lin LI ; Yihao GUO ; Mi ZHANG ; Taiwen CHEN ; Yongpeng LI ; Xin LI ; Xi ZHU ; Yu ZHANG ; Liguang LOU ; Youhong HU
Acta Pharmaceutica Sinica B 2022;12(10):4004-4007
3.Effect of shear wave elastography in predicting pathological responses to neoadjuvant chemotherapy in patients with breast cancer
Danfeng HUANG ; Lina TANG ; Youhong SHEN ; Yaoqin WANG ; Yijie CHEN ; Wanping CHEN ; Wenrong LIN ; Wenting XIE
Chinese Journal of Ultrasonography 2021;30(8):715-720
Objective:To investigate the clinical value of shear wave elastography (SWE) in predicting pathological responses to neoadjuvant chemotherapy in breast cancer.Methods:According to the postoperative pathological responses, 56 patients who received neoadjuvant chemotherapy followed by surgical excision in the Fujian Cancer Hospital from August 2019 to September 2020 were divided into responders and non-responders. The relative change rates of tumor maximum diameter(ΔD2, ΔD4) and SWE stiffness (ΔEmax2, ΔEmax4, ΔEmean2, ΔEmean4) were assessed before NAC and after different NAC cycles (t2, t4). Clinical information, including age, T, N stages, ER, PR, HER2, Ki67, and molecular subtype were also considered as the variables. The independent influencing factors of pathological responses after neoadjuvant chemotherapy were obtained by logistic regression analysis and diagnostic test was carried out.Results:There were 23 cases as responders (41.0%, 23/56), and 33 cases as non-responders (58.9%, 33/56). Results of multivariate analysis showed ΔEmax4 and HER2 index were independent influencing factors of pathological responses ( OR=1.11, P<0.001; OR=31.81, P=0.002). Area under curve of the ΔEmax4 (AUC: 0.869, 95% CI: 0.746-0.941) was higher than that of HER2 (AUC: 0.690, 95% CI: 0.545-0.834). The combination of ΔEmax4 and HER2 gave the best prediction of pathological responses (AUC 0.930, 95% CI: 0.829-0.981). the sensitivity, specificity, diagnostic accuracy, postive predictive value, and negative predictive value were 78.26%, 96.97%, 75.23%, 94.73%, and 86.49%, respectively. Conclusions:ΔEmax4 and HER2 are independent predictors of pathological responses after neoadjuvant chemotherapy for breast cancer. Combined ΔEmax4 and HER2 can improve the predictive diagnostic efficacy of pathological responses to chemotherapy for breast cancer.
4.Pregnancy-preserving and maternal-fetal management in a patient with rare large cell neuroendocrine carcinoma of the uterine cervix.
Geyang DAI ; Gaowen CHEN ; Li XIAOXUAN ; Youhong ZHENG ; Yuan WANG ; Xingsong LI ; Li JING ; Jing ZHOU ; Yu XIE ; Yifeng WANG
Journal of Southern Medical University 2021;41(1):1-9
OBJECTIVE:
To explore the strategy of pregnancy-preserving and maternal- fetal management in patients with primary gynecologic neuroendocrine tumors (gNETs) during pregnancy.
METHODS:
We performed whole genome sequencing (WGS) for analyzing maternal and fetal somatic and germline single nucleotide variations (SNVs) and small insertions and deletions (InDels) for a 29-year-old pregnant woman diagnosed with stage IB2 large cell neuroendocrine carcinoma (LCNEC) and adenocarcinoma in the cervix. A systematic literature review was performed to explore the strategies for treatment of such rare histological type while maintaining pregnancy.
RESULTS:
Global case analysis of cervical NETs during pregnancy suggested that negative lymph node metastasis and an early FIGO stage were potentially associated with a good prognosis of the patients. In the case presented herein, a pregnancy-preserving strategy was adopted and favorable maternal-fetal outcomes were achieved after neoadjuvant chemotherapy, radical surgery and postoperative systemic chemotherapy. At 35
CONCLUSIONS
Although gNETs in pregnancy are rare and highly risky, pregnancy-preserving managements of gNETs can still be considered and favorable maternalfetal outcomes are possible with proper assessment of the clinical indications and implementation of multimodal treatments. Precise treatment and follow-up strategies based on the results of WGS for risk-reducing intervention of cancer recurrence or occurrence can potentially benefit the patient and the neonate.
Adenocarcinoma
;
Adult
;
Carcinoma, Neuroendocrine/genetics*
;
Child
;
Female
;
Humans
;
Infant, Newborn
;
Neoplasm Recurrence, Local
;
Pregnancy
;
Uterine Cervical Neoplasms/genetics*
5.Evaluation of common inspection techniques for acute atlantoaxial trauma
Shiming WANG ; Rui JIN ; Xie HE ; Youhong CAO ; Yunfeng LU
Chinese Journal of Orthopaedic Trauma 2019;21(4):353-357
Objective To evaluate and compare the 3 common inspection techniques for acute atlantoaxial trauma:tomosynthesis(DTS),digital radiology(DR) and computed tomography(CT).Methods The imaging data from March 2013 through December 2017 were retrieved from the Picture Archiving and Communication Systems(PACS) of The First Affiliated Hospital of Chongqing Medical University concerning the patients with acute atlantoaxial trauma.Selected for this study were 50 DTS images(DTS group),50 CT images(CT group) and 50 DR images(DR group).The image diagnoses for the 3 groups were conducted by 2 senior radiologists and their judgments were compared with the definite clinical diagnoses.The 3 groups were compared in terms of diagnostic accuracy,diagnostic rate of acute atlantoaxial trauma,image quality and effective radiation dosage.Results DR was insignificantly different from DTS or CT in diagnostic accuracy for the acute atlantoaxial Irauma which had been caused by mild violence like spraining and falling(P>0.05),but significantly inferior to both DTS and CT in diagnostic accuracy and diagnostic rate of the acute atlantoaxial trauma which had been caused by severe violence like traffic accident(P<0.05).In detection of atlas/axial fracture and atlantoaxial dislocation,DTS was slightly weaker than CT but significantly better than DR(P<0.05).The image quality scores for CT group(4.60±0.11) and DTS group(4.16±0.15) were significantly higher than that for DR group(2.80±0.18)(P<0.05).In average effective radiation dosage,CT group(2.33±0.020 mSv/time) was the highest,followed by DTS group(0.61±0.076 mSv/time) and DR group(0.025±0.003 mSv/time),showing significant differences between any two(P<0.05).Conclusions DR technique may be used for inspection of the atlantoaxial acute trauma caused by mild violence like spraining and falling,but has little value for inspection of most cases of atlantoaxial acute trauma.DTS technique may be the first choice for inspection of most atlantoaxial acute trauma.CT should be applied as a further inspection for complex cases because of its highest diagnostic accuracy and highest effective radiation dosage.
6.Regulatory Effects of Ionotropic and GroupⅠ Metabotropic Glutamate Receptors on Temperature Hypersensitivity in Rats
Liping XIE ; Youhong JIN ; Fang YE ; Yu LUO ; Juanxia YANG ; Xia CHEN
Journal of China Medical University 2018;47(2):145-150
Objective To study the effects of ionic and group Ⅰ metabotropic glutamate receptors on rats' thermal hypersensitivity by intraplantar administration of drugs. Methods After intraplantar administration of glutamate receptor agonists,L-glutamic acid (Glu), N-methyl-D-aspartic-acid (NMDA),and (RS)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid hydrobromide (AMPA);a Group Ⅰ mGluR agonist, (S) 3,5-dihydroxyphenylglycine [(S)-DHPG];a noncompetitive NMDA receptor antagonist, (+)-MK801 maleate (MK-801);a competitive AMPA/kainate receptor antagonist,6-cyano-7-nitroquinoxaline-2,3-dione (CNQX);and a selective GroupⅠ mGluR antagonist,7-hydroxyiminocyclo propan[b]chromen-1a- carboxylic acid ethyl ester (cpccoEt) into the left hind paws of rats whose L5-6 nerves were sham-operated or ligated,we examined the response of the rats to thermal stimuli provided by radiant heat. Results In sham-operated rats,glutamate,NMDA,AMPA,and (S)-DHPG reduced paw withdrawal latency (PWL) but did not have any effect on SNL rats. However,in SNL rats,MK-801,CNQX,and cpccoEt increased PWL but exerted no effect on sham-operated rats. Conclusion These results suggest that changes in sensitivity of peripheral ionic and group Ⅰ metabotropic glutamate receptors can lead to changes in peripheral nerve plasticity;the generation and maintenance of neuropathic pain caused by nerve injury is based on this plasticity.
7.Protective effects of Jinqi Jiangtang tablets on diabetic complications of cardiovascular diseases in Drosophila
Youhong ZHAO ; Yang YANG ; Zhishen XIE ; Xiaojun XU ; Li LIU
Journal of China Pharmaceutical University 2016;47(3):348-352
This study was to investigate the protective effects of Jinqi Jiangtang tablets on diabetic complications of cardiovascular disease in Drosophila. The effects of Jinqi Jiangtang tablets on hypolipidemia and hypoglycemia by high fat diet(HFD)induced model organism Drosophila with the content of triglyceride and trehalose in Drosophila as indexes, were investigated. And the Drosophila heart function was detected by high speed EM-CCD; cell signaling pathways were detected by Western blot and RT-PCR. The results showed that high fat diet could induce the appearance of hyperglycemia and hyperlipidemia on Drosophila model. Jinqi Jiangtang tablets could significantly reduce triglyceride and trehalose and protect heart function of Drosophila induced by high fat diet. Jinqi Jiangtang tablets could also increase the expression of 4ebp mRNA, while decreasing p-4EBP protein and pepck mRNA expression. This study demonstrated that Jinqi Jiangtang tablets have a protective effect on HFD-induced dyslipidemic-diabetic and cardiac dysfunction, which may be related to mTOR/4EBP pathway.
8.Analysis of disease and health risk factors among teachers in one university of Chongqing
Xiaohong YANG ; Shanbi ZHOU ; Youhong XIE ; Qiongwu YU ; Hao LIU ; Zongliang LU ; Yu QIN ; Qingli HE ; Mantian MI
Chongqing Medicine 2014;(25):3325-3328
Objective To understand the teachers′health status of one university in Chongqing to provide the basis for the healthcare of this group.Methods The teachers′health examination information in1 303 cases of physical healthy examination was retrospectively analyzed.The data were analyzed by the SPSS17.0 statistical software.Results The main detected diseases were conj unctivitis,fatty liver,cataract,refractive error,eyeground arteriosclerosis and hypertension.The top-5 health risk factors includ-ed dyslipidemia,overweight,hyperpiesia,increased uric acid and fasting blood glucose abnormality.The detection rates of conj uncti-vitis,fatty liver,eyeground arteriosclerosis,overweight,hyperpiesia,increased uric acid,fasting blood glucose abnormality examined in males were obviously higher than those in females(P<0.05),while which of cataracts,refractive errors,hypertension and dyslip-idimia were not relevant to gender(P>0.05).Apart from the increased uric acid(P=0.740),the morbidity and risk factors in dif-ferent ages were markedly different(P<0.01).The case rate of diabetes and hypertension was lower than the national average. Conclusion The eye health status of teachers in this university is not optimistic;there were many health risk factors.The health knowledge education of overweight,dyslipidemia,pathoglycemia and hyperpiesia should be carried out aiming at this group.
9.Effect of TUBB3, TS and ERCC1 mRNA expression on chemoresponse and clinical outcome of advanced gastric cancer by multiplex branched-DNA liquid chip technology.
Jin HUANG ; Huabin HU ; Yangchun XIE ; Youhong TANG ; Wei LIU ; Meizuo ZHONG
Journal of Central South University(Medical Sciences) 2013;38(6):582-589
OBJECTIVE:
To analyze the impact of β-tubulin-III (TUBB3), thymidylate synthase (TS) and excision repair cross complementation group 1 (ERCC1) mRNA expression on chemoresponse and clinical outcome of patients with advanced gastric cancer treated with TXT/CDDP/FU (DCF) regimen chemotherapy.
METHODS:
The study population consisted of 48 patients with advanced gastric cancer. All patients were treated with DCF regimen palliative chemotherapy. The mRNA expressions of TUBB3, TS and ERCC1 of primary tumors were examined by multiplex branched-DNA liquid chip technology.
RESULTS:
The patients with low TUBB3 mRNA expression had higher response rate to chemotherapy than patients with high TUBB3 expression (P=0.011). There were no significant differences between response rate and TS or ERCC1 expression pattern. Median overall survival (OS) and median time to progression (TTP) were significantly longer in patients with low TUBB3 mRNA expression (P=0.002, P<0.001). TS or ERCC1 expression was not correlated with TTP and OS. In the combined analysis including TUBB3, TS and ERCC1, the patients with 0 or 1 high expression gene had better response rate, TTP and OS than the remaining patients (all P<0.001). Multivariate analysis revealed that ECOG (Eastern Cooperative Oncology Group)≥2 (HR=2.42, P=0.009) and TUBB3 (HR=2.34, P=0.036) mRNA expression significantly impacted on OS.
CONCLUSION
High TUBB3 mRNA expression is correlated with resistance to DCF regimen chemotherapy. TUBB3 might be a predictive and prognostic factor in patients with advanced gastric cancer treated with TXT-based chemotherapy. The combined evaluation of TUBB3, TS and ERCC1 expression can promote the individual treatment in advanced gastric cancer.
Antineoplastic Combined Chemotherapy Protocols
;
therapeutic use
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Biomarkers, Tumor
;
metabolism
;
DNA-Binding Proteins
;
genetics
;
metabolism
;
Drug Resistance, Neoplasm
;
Endonucleases
;
genetics
;
metabolism
;
Humans
;
RNA, Messenger
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genetics
;
metabolism
;
Stomach Neoplasms
;
drug therapy
;
genetics
;
Thymidylate Synthase
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genetics
;
metabolism
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Treatment Outcome
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Tubulin
;
genetics
;
metabolism
10.Autophagy Induced by NGAL Protein in Esophageal Carcinoma Cells
Pixian ZHANG ; Wangkai FANG ; Liyan XU ; Jikai JIANG ; Zhongying SHEN ; Zepeng DU ; Xiaofeng LU ; Fei ZHOU ; Jianjun XIE ; Bingli WU ; Youhong CUI ; Dong XIE ; Enmin LI
Progress in Biochemistry and Biophysics 2006;0(08):-
Previous studies suggest that NGAL (neutro phil gelatinase-associated lipocalin) is involved in the transformation and development of esophageal carcinoma. Alteration of NGAL expression can trigger the change of cellular morphology in esophageal carcinoma cells. However, the mechanisms remain unclear. To get a better understanding of NGAL function in esophageal carcinoma, NGAL protein was expressed in methylotrophic yeast, Pichia pastoris, and purified by chromatography. EC1.71 cells expressed high levels of NGALR (NGAL receptor) and EC109 cells expressed low levels of NGALR were used as cells model. The trafficking and the possible function of NGAL protein were then analyzed in the esophageal carcinoma cells. The results showed that 5-FAM-labeled recombinant NGAL protein could internalize into the EC1.71 and EC109 cells. Furthermore, the internalized NGAL protein could induce the alteration of cellular morphology, resulting in generation of autophagosome, transcriptional up-regulation of genes associated with autophagy and increase of phospho-ERK1/2 (p-ERK1/2). Interestingly, the treatment with the NGAL protein did not affect the intracellular iron level. These data indicate that induced autophagy by exogenous NGAL protein is a mechanism that internalized NGAL plays important roles in esophageal carcinoma cells, independent with NGAL-mediated iron transport process, while ERK1/2 signal pathway is involved in activation of autophagy by exogenous NGAL protein.

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