1.Effects of forsythinol on apoptosis of hepatocellular carcinoma cells through the JAK2-STAT3 signaling pathway
Xin ZHANG ; Dong-Xiang HUANG ; Can-Hui TANG ; Zhi-Piao HUANG
The Chinese Journal of Clinical Pharmacology 2024;40(19):2837-2841
Objective To investigate the effects of forsythinol(Fo)on the expression of matrix metalloproteinase-2(MMP2)in hepatoma cells through Janus kinase 2/signal transduction and transcriptional activator 3(JAK2/STAT3)signaling pathway.Methods SMMC-7721 cells were divided into experimental-L,-M,-H groups,control group,inhibitor group and activator group.The control group was added with equal volume dimethyl sulfoxide(DMSO);the experimental-L,-M,-H groups were treated with 50,200,500 μg·mL-1 Fo;and the inhibitor group was added with 50 μmol·L-1 JAK2/STAT3 inhibitor AG490 based on the experimental-M group.In the activator group,10 μmol·L-1 JAK2/STAT3 activator Broussonin E was added to the experimental-M group.Apoptosis was detected by deoxynucleotide terminal transferase-mediated dUTP notch end labeling(TUNEL);protein expression was detected by Western blot;real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect mRNA levels.Results The apoptosis rates of control group,experimental-M group,inhibitor group and activator group were(19.94±4.88)%,(27.04±5.27)%,(15.36±3.40)%and(46.66±7.89)%,respectively;the relative expression levels of phosphorylated JAK2 protein were 1.00±0.13,0.73±0.11,1.33±0.17 and 0.26±0.07,respectively;the relative expression levels of phosphorylated STAT3 protein were 1.00±0.12,0.27±0.04,0.88±0.13 and 0.12±0.04,respectively;the mRNA relative expression levels of MMP2 were 1.00±0.14,0.68±0.08,1.17±0.17 and 0.51±0.09,respectively.Compared with experimental-M group and control group,inhibitor group and activator group,there were statistically significant differences(P<0.05,P<0.001).Conclusion Fo promotes apoptosis of hepatocellular carcinoma cells,and its mechanism may be related to the effect of Fo on the expression of MMP2 by regulating JAK2-STAT3 signaling pathway.
2.Prediction and analysis of Q-markers of Elephantopus scaber based on its UPLC fingerprint, content determination of components, and in vitro a nti-tumor activity.
Can-Chao JIA ; Ling-Jie LI ; Zhi-Hao ZENG ; Rui-Yin TANG ; De-Zheng JIA ; Min-Juan YANG ; Jin-Yan QIU ; Dong-Mei LI ; Can-Hui XIE ; Guang-Ying WU ; Yang-Xue LI ; Jie-Yi JIANG ; Hong HUANG ; Guan-Lin XIAO ; Da-Ke CAI ; Xiao-Li BI
China Journal of Chinese Materia Medica 2023;48(16):4421-4428
This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 μm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 μL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 μmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.
Humans
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Chromatography, High Pressure Liquid
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Drugs, Chinese Herbal/chemistry*
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Asteraceae/chemistry*
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Lung Neoplasms/drug therapy*
3.Histone deacetylase 3 promotes innate antiviral immunity through deacetylation of TBK1.
Jie-Lin TANG ; Qi YANG ; Chong-Hui XU ; He ZHAO ; Ya-Ling LIU ; Can-Yu LIU ; Yuan ZHOU ; Dong-Wei GAI ; Rong-Juan PEI ; Yun WANG ; Xue HU ; Bo ZHONG ; Yan-Yi WANG ; Xin-Wen CHEN ; Ji-Zheng CHEN
Protein & Cell 2021;12(4):261-278
TANK-binding kinase 1 (TBK1), a core kinase of antiviral pathways, activates the production of interferons (IFNs). It has been reported that deacetylation activates TBK1; however, the precise mechanism still remains to be uncovered. We show here that during the early stage of viral infection, the acetylation of TBK1 was increased, and the acetylation of TBK1 at Lys241 enhanced the recruitment of IRF3 to TBK1. HDAC3 directly deacetylated TBK1 at Lys241 and Lys692, which resulted in the activation of TBK1. Deacetylation at Lys241 and Lys692 was critical for the kinase activity and dimerization of TBK1 respectively. Using knockout cell lines and transgenic mice, we confirmed that a HDAC3 null mutant exhibited enhanced susceptibility to viral challenge via impaired production of type I IFNs. Furthermore, activated TBK1 phosphorylated HDAC3, which promoted the deacetylation activity of HDAC3 and formed a feedback loop. In this study, we illustrated the roles the acetylated and deacetylated forms of TBK1 play in antiviral innate responses and clarified the post-translational modulations involved in the interaction between TBK1 and HDAC3.
4.A Single-center Study on Mortality and Risk Factors in Maintenance Hemodialysis Patients
Ming LI ; Can-ming LI ; Zeng-chun YE ; Wen-bo ZHAO ; Hua TANG ; Xun LIU ; Hui PENG ; Tan-qi LOU
Journal of Sun Yat-sen University(Medical Sciences) 2020;41(4):620-626
【Objective】 To explore the main causes of death and the risk factors for death in maintenance hemodialysis (MHD) patients. 【Methods】 A retrospective study was carried out in 210 MHD patients in The Third Affiliated Hospital of Sun Yat-sen University. Of the 210 patients, 68 dead were designated as the experimental group and the other 142 survivals as the control. Single factor and binary logistic regression analyses were used to investigate the effects of clinical indicators on the prognosis of patients. We further performed subgroup analysis in experimental group, examined the patients died of cardiovascular diseases and those died of non-cardiovascular diseases, and then compared their results of color Doppler echocardiography. 【Results】 The age of the patients was(56.6±16.6) years and 125 of them were male. Compared with those in the control group, the patients in the death group had elder average age, higher rates of complications such as hypertension, diabetes, cardio-cerebro-vascular diseases, lower levels of hemoglobin, albumin, creatinine and uric acid and significantly elevated level of hypersensitive C-reactive protein(P < 0.05). The top three causes of death were cardiocerebro-vascular disease(33 cases, 48.5%), infection(16 cases, 23.5%), malnutrition(8 cases, 11.8%). Logistic regression analysis showed that age, cardio-cerebro-vascular diseases, diabetes mellitus, hypersensitive C-reactive protein and serum creatinine were independent risk factors for death in MHD patients. Subgroup analysis revealed the patients died of CVD diseases had higher incidences of left ventricular hypertrophy and cardiac valve calcification than those died of non-CVD diseases.【Conclusion】Cardio-cerebro-vascular diseases, infection and malnutrition are the main causes of death in MHD patients. Patients died of CVD diseases exhibit significantly higher incidences of left ventricular hypertrophy and cardiac valve calcification compared with those died of non-CVD diseases.
5.Expert consensus on prescription comment of Chinese traditional patent medicine for promoting the rational use of drugs in Beijing.
Rui JIN ; Kui-Jun ZHAO ; Gui-Ming GUO ; Bing ZHANG ; Yu-Guang WANG ; Chun-Miao XUE ; Yi-Heng YANG ; Li-Xia WANG ; Guo-Hui LI ; Jin-Fa TANG ; Li-Xing NIE ; Xiang-Lin ZHANG ; Ting-Ting ZHAO ; Yi ZHANG ; Can YAN ; Suo-Zhong YUAN ; Lu-Lu SUN ; Xing-Zhong FENG ; Dan YAN ; Null
China Journal of Chinese Materia Medica 2018;43(5):1049-1053
With the growth of number of Chinese patent medicines and clinical use, the rational use of Chinese medicine is becoming more and more serious. Due to the complexity of Chinese medicine theory and the uncertainty of clinical application, the prescription review of Chinese patent medicine always relied on experience in their respective, leading to the uncontrolled of clinical rational use. According to the traditional Chinese medicine (TCM) theory and characteristics of the unique clinical therapeutics, based on the practice experience and expertise comments, our paper formed the expert consensus on the prescription review of Chinese traditional patent medicine for promoting the rational use of drugs in Beijing. The objective, methods and key points of prescription review of Chinese patent medicine, were included in this expert consensus, in order to regulate the behavior of prescription and promote rational drug use.
6.Design of ABC damage variable and positioning system for acetabular fractures and 1122 cases multi-center statistic analysis.
Chun-cai ZHANG ; Shuo-gui XU ; Bao-qing YU ; Fang JI ; Qing-ge FU ; Xin-wei LIU ; Yun-tong ZHANG ; Yun-fei NIU ; Pan-feng WANG ; Jia-can SU ; Lie-hu CAO ; Yong-qing XU ; Mo RUAN ; Zhuang-hong CHEN ; Ji-feng HUANG ; Xian-hua CAI ; Hui-liang SHEN ; Li-min LIU ; Ji-fang WANG ; Yan WANG ; Pei-fu TANG ; Yu-tian LIANG ; Jia-rang WANG ; Yu-ri WANG ; Zhen-hao WANG ; Wen-di LIU ; Wen-rui LI ; Wen-hu LI ; Xu-quan WANG ; Dong-sheng ZHOU ; Peng ZHANG ; Ren WANG ; Gang WANG ; Yu-yue CHEN ; Yong-jian CONG
China Journal of Orthopaedics and Traumatology 2011;24(2):102-108
OBJECTIVETo design ABC damage variable and positioning system for acetabular fracture and explore the feasibility and clinical practical value of the system through the multi-center analysis of 1122 acetabular fractures.
METHODSAccording to acetabular three-column conception, and pelvic ring lesions damage direction caused by acetabular fracture domino effect and injury degree of proximal femur joint, it defined class A as any column acetabular fracture; class B as any two-column acetabular fracture; class C as front, dome and posterior mixture acetabular fracture. Lower case English letters a, m, p represented front, dome, posterior fracture, respectively. Acetabular damage variables: 1 was simple displaced fractures; 2 was comminuted fractures; 3 was compression fractures. Pelvic ring lesions damage variables: alpha was sacroiliac joints or sacroiliac fracture horizontal separation deflection; beta was sacroiliac joints or sacroiliac fracture vertical separation deflection; gamma was pubic symphysis separation/superior and inferior ramus of pubis fracture deflection; alpha beta gamma delta was compound floating damage. Proximal humerus joint damage variables: I was femoral head fracture; II was femoral neck fracture; II was intertrochanteric fractures of femur; IV was I to III compound fracture. The ABC damage variable positioning system for acetabular fracture was made up by the above-mentioned variables. The statistics from March 1997 to February 2010 showed 1122 cases acetabular fractures with 18 cases of double side acetabular fracture and 1140 cases of acetabular fractures. The pelvics anterior-posterior view, ilium and obturator oblique view, and 2/3D-CT materials were analyzed and researched.
RESULTSEach damage variables distribution situation in 1140 cases of acetabular fracture involved A in 237 cases (20.8%), B in 605 cases (53.1%), C in 298 cases (26.1%);front column fracture in 808 cases(70.9%), dome fracture in 507 cases (44.5%), posterior fracture in 1026 cases (90%). Acetabular variables: variabe 1 in 203 cases of simple displaced fracture (17.8%); variabe 2 in 516 cases of comminuted fracture(45.3%); variabe 3 in 421 cases of compression fracture (36.9%); 249 cases of pelvic ring lesions damage (21.8%), 75 cases femoral head fracture (6.6%); 18 cases of double side acetabular fracture and relative pelvic ring and proximal humerus joint variables (1.58%). Key part and curative effect elements of 1140 cases acetabular fracture: 507 cases of dome or posterior acetabular fracture (44.5%); 421 cases of compression fracture (36.9%); 249 cases of pelvic ring variables (21.8%); 75 cases of proximal humerus joint variables (6.6%); 486 cases of simple Aa/pl/2,Bapl/2 acetabular fracture (42.6% ).
CONCLUSIONCompression fracture, especially defected compression fracture, takes important part in acetabular damage variables, and also presents that acetabular fracture with pelvic ring and proximal femoral damage variables are not rare at all. The relationship of the acetabular fracture damage variables, and its percentage shows the key points and elements in clinical treatment: weight-bearing to dome accounts for 44.5%; compression to defects account for 36.9%, pelvic ring to float accounts for 21.8%; dome fracture to double side fracture account for 6.6%. The system has significant guiding effects on clinic in terms of evaluation of injury severity, anatomic localization, difficulty index, alternative strategy, operative approach, effect of treatment,and prognosis. And the most important thing is that the system creates the comparison of damage variables in same type of fracture and the communication of homo-language and explores a new method.
Acetabulum ; injuries ; Adolescent ; Adult ; Aged ; Child ; Female ; Fractures, Bone ; classification ; diagnostic imaging ; Humans ; Male ; Medical Informatics ; methods ; Middle Aged ; Tomography, X-Ray Computed ; Young Adult
7.Narcotrend for monitoring the anesthetic depth during endotracheal intubation in sevoflurane anesthesia.
Zhao-hui TANG ; Song-hua LIU ; Zhi-gang CHENG ; Qiong-can LI ; Yun-jiao WANG ; Qu-lian GUO
Journal of Southern Medical University 2010;30(7):1654-1662
OBJECTIVETo study the feasibility of using Narcotrend (NCT) in monitoring the anesthetic depth during endotracheal intubation in sevoflurane anesthesia.
METHODSThirty ASA I-II patients (aged 20-49 years) undergoing gynecologic surgery under general anesthesia with tracheal intubation were randomized into sevoflurane group (n=15) and sevoflurane plus rocuronium group (n=15). In the former group, anesthesia was induced with sevoflurane at the primary concentration of 8% till the final end expiratory concentration reaching 2 MAC(minimum alveolar concentration) for 3 min, followed then by tracheal intubation and further observation of the indicators for another 3 min. The patients in sevoflurane plus rocuronium group received identical anesthesia procedures except for the administration of intravenous injection of rocuronium (0.6 mg/kg) after the loss of eyelash reflex. The NCT, BIS and hemodynamics were recorded during the process.
RESULTSNo significant differences were noted in NCT, bispectral index (BIS), MAP and heart rate before tracheal intubation between the two groups (P>0.05). The NCT and BIS increased significantly after tracheal intubation in sevoflurane group (P<0.05), but remained below 60. No significant changes in NCT and BIS occurred during intubation in sevoflurane plus rocuronium group (P>0.05). The mean arterial pressure (MAP) and heart rate were significantly increased in both groups after tracheal intubation in comparison with those before tracheal intubation (P<0.05), but the increment in sevoflurane group was significantly greater (P<0.05).
CONCLUSIONNCT may reflect the changes of the anesthetic depth resulting from the nociceptive stimulus of tracheal intubation in sevoflurane- induced anesthesia. NCT and BIS can not serve such a purpose in combined anesthesia with sevoflurane and rocuronium.
Adult ; Androstanols ; administration & dosage ; Anesthesia ; Anesthetics, Intravenous ; administration & dosage ; Hemodynamics ; Humans ; Intubation, Intratracheal ; methods ; Methyl Ethers ; administration & dosage ; Middle Aged ; Monitoring, Intraoperative ; methods ; Young Adult
8.Strategy and analysis of early management on ninety multiple trauma patients.
Bao-qing YU ; Hai-bo HU ; Ming LI ; Yu WANG ; Kai-wei HAN ; Jia-can SU ; Hui LIU ; Chun-cai ZHANG ; Yu-shu BAI ; Xiao-bing CAI ; Hao TANG ; Jing-feng LI
Chinese Journal of Surgery 2009;47(20):1550-1552
OBJECTIVETo explore the therapeutical effects through investigating the results of multiple traumas treated by means of damage control surgery (DCS) or early total care (ETC).
METHODSThe clinical data of 90 patients with severe multiple traumas admitted from June 2001 to June 2007 were analyzed retrospectively. Forty-five patients were classified to the DCS group, 45 patients to the ETC group as a control. These severely injured patients were selected with an ISS > 25 points.
RESULTSBetween the two groups, the recovery time of clearance of lactic acid, body temperature, prothrombin time (PT) and activated partial thromboplastin time (APTT) of DCS group was significantly shorter than that of ETC group (P < 0.05). Incidence of complications and mortality in DCS group was significant less than that in ETC group (P < 0.05). No significant differences existed in the volume of bleeding and duration of surgery (P > 0.05).
CONCLUSIONSThe concept of DCS could reduce multiple traumas patients' mortality rate and incidence of complications. The indication of DCS should be the combination of physical feature, mechanism and severity of injuries.
Female ; Humans ; Injury Severity Score ; Male ; Multiple Trauma ; therapy ; Treatment Outcome
9.Effects of hypoxia on human placental decidua basalis-mesenchymal stem cells proliferation, apoptosis and VEGF expression..
Yong-Can HUANG ; Xiao-He CHEN ; Jia WANG ; Xiu-Qun LI ; Hui-Qi XIE ; Li TANG ; Li DENG
Acta Physiologica Sinica 2008;60(6):783-789
Human placental decidua basalis-mesenchymal stem cells (PDB-MSCs) are multipotent cells from the human term placenta, which are ethically conducive, easily accessible and high-yielding source. PDB-MSCs can differentiate into adipogenic, osteogenic and neurogenic cells under appropriate conditions, which may be an attractive and alternative source of seed cells for tissue engineering. To investigate the effect of hypoxia (1% O2) on human PDB-MSCs and the expression of cytokine, PDB-MSCs were isolated from human placenta by density gradient centrifugation and cultured in the Dulbecco's modified Eagle's medium-high glucose (DMEM-HG) containing 10% fetal bovine serum (FBS), and the fifth passage of PDB-MSCs were taken. PDB-MSCs were divided into 4 groups according to the concentrations of O2 and FBS: 20% O2, 10% FBS; 20% O2, 0% FBS; 1% O2, 10% FBS; 1% O2, 0% FBS. The proliferation and apoptosis of PDB-MSCs were detected by MTT and flow cytometric analysis at the time points of 6 h, 12 h, 24 h, 48 h, 72 h, and 96 h, respectively. Vascular endothelial growth factor (VEGF) released from PDB-MSCs was detected by enzyme-linked immunosorbent assay (ELISA) at the same time points. The results showed that hypoxia enhanced the proliferation of PDB-MSCs at 12 h under the condition of 10% FBS, while at 24 h under the condition of 0% FBS (P<0.01, n=3). In normoxia, the cells cultured in 10% FBS displayed a significant proliferation compared to those cultured in 0% FBS. However, in hypoxia, the number of cells cultured in 0% FBS (serum deprivation) increased significantly compared to that cultured in 10% FBS at 24 h and 96 h respectively (P<0.05, P<0.01, n=3). With the flow cytometric analysis of cell apoptosis under the condition of hypoxia and serum deprivation, we found that hypoxia and serum deprivation did not induce PDB-MSCs apoptosis (P>0.05, n=3). This conclusion may relate to the expression of VEGF which needs further research. In conclusion, the results obtained indicate that PDB-MSCs are able to bear hypoxia and serum deprivation, suggesting that PDB-MSCs can be used as seed cells for ischemia related tissue engineering.
Apoptosis
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Cell Hypoxia
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Cell Proliferation
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Cells, Cultured
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Decidua
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cytology
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Female
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Humans
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Mesenchymal Stromal Cells
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cytology
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Placenta
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cytology
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Pregnancy
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Tissue Engineering
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Vascular Endothelial Growth Factor A
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metabolism
10.Effect of basic fibroblast growth factor and hyaluronic acid on proliferation of rabbit chondrocytes in vitro.
Yan SHEN ; Si-ming LI ; Yi TANG ; Can-can ZHONG ; Pei-hong LIANG ; Hong-hui CHEN
Chinese Journal of Traumatology 2004;7(1):42-44
OBJECTIVETo investigate the effect of basic fibroblast growth factor (bFGF) and hyaluronic acid (HA) on the proliferation of rabbit chondrocytes in vitro.
METHODSChondrocytes from the knee joints of New Zealand white rabbits were cultured. bFGF or HA or both were added into the culture medium respectively, and the proliferation of the chondrocytes was measured with MTT 3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyl-tetra-zolium bromide. (MTT, Sigma, M2128).
RESULTSBasic fibroblast growth factor (10 ng/ml) with low concentration of fetal bovine serum in the culture medium promoted the proliferation of chondrocytes significantly, and this effect reached its maximum when concentration of bFGF reached 50 ng/ml. HA itself had no effect on the proliferation of chondrocytes. However, when bFGF was used in combination with HA, especially when the concentration of bFGF was 50-500 ng/ml and that of HA was 10-50 ng/ml, the effect on the proliferation of chondrocytes was much more than when bFGF or HA was used alone.
CONCLUSIONSbFGF can promote the proliferation of chondrocytes. HA, which has no effect on the proliferation of the cells, can maintain a normal growth of chondrocytes. When bFGF is used in combination with HA, more proliferation is obtained.
Analysis of Variance ; Animals ; Cell Division ; drug effects ; physiology ; Cells, Cultured ; Chondrocytes ; drug effects ; physiology ; Female ; Fibroblast Growth Factor 2 ; pharmacology ; Hyaluronic Acid ; pharmacology ; In Vitro Techniques ; Knee Joint ; cytology ; Male ; Probability ; Rabbits ; Sensitivity and Specificity

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