To review the structure and function of the calcified cartilage zone and its role in the pathogenesis of osteoarthritis (OA). Methods Recent l iterature about calcified zone was reviewed and analyzed in terms of architecture, composition, biomechanics, and biological function. Results Calcified zone has particular structure and material properties, and functions as a semi permeable membrane; chondrocytes in the calcified zone retain some characteristics of growth plate cells, which play a crucial role in cartilage function maintenance and pathogenesis of OA. Therefore, reconstructionof the calcified zone at osteochondral conjunction has become one of the hot research in the fields of interface tissue engineering. Conclusion It is necessary to pay more attention to calcified cartilage zone, which is important for both the treatment of OA and the preparation of tissue engineered osteochondral composite.
To investigate the pathologic characteristics of the articular cartilage and subchondral bone from osteoarthritic knees, and to compare the structural parameters of articular cartilage and subchondral bone between the medial and lateral tibial plateau, so as to determine the role of calcified zone and subchondral bone in the pathogenesis of osteoarthritis (OA). Methods The tibial plateaus were taken from 30 patients undergoing total knee arthroplasty between October 2009 and May 2011. The subjects included 11 males and 19 females with an average age of 65.1 years (range, 55-78years). The mean disease duration was 16.6 years (range, 10-25 years); the mean varus angle of the diseased knee was 9.3° (range, 1-23°). After gross observation, the cartilage-bone samples were taken out from the most weight-bearing regions in the internal areas of the medial and lateral plateaus. The decalcified paraffin-embedded sections were prepared and stained with HE and Safranin O/fast green for cartilage assessment (Mankin score), staging, and bone histomorphometry; the pathologic features of the cartilage and subchondral bone were also observed. The thickness of total articular cartilage (TAC), articular calcified cartilage (ACC), subchondral bone plate (SCP), and the trabecular bone volume (BV/TV) were measured by Image Pro Plus 6.0 imaging system, then the ratio of ACC/TAC was calculated. Results Macroscopic results showed that articular cartilage degeneration was more severe in the medial plateau than in the lateral plateau; Mankin score of the medial plateau (12.4 ± 1.1) was significantly higher than that of the lateral plateau (8.3 ± 1.6) (t=12.173, P=0.000). In the 60 samples, 14 samples were at stage I, characterisd by fissures within the superficial zone, dupl icated tidemark, and thickend subchondral bone; 19 samples were at stage II, characterisd by fissures extending into the deep zone, multiple subchondral bone resorption pits, and obviously thickend subchondral bone; and 27 samples were at stage III, characterisd by full-thickness cartilage defects, endochondral ossification, and eburnated subchondral bone. The bone histomorphometric study showed that TAC thickness of the medial plateau was significantly lower than that of the lateral plateau (P lt; 0.05); the ratios of ACC/TAC, BV/TV, and SCP thickness of the medial plateau were significantly higher than those of the lateral plateau (P lt; 0.05). However, there was no significantdifference in the ACC thickness between the medial and lateral plateaus (P gt; 0.05). Conclusion The calcified zone andsubchondral bone may play an important role in the initiation and progression of OA.
Objective To analyze the methodological quality of clinical trails on butylphthalide for cerebral ischemic stroke. Methods We collected all of the published clinical studies on butylphthalide for cerebral ischemic stroke in the world, and evaluated the methodological quality of the included studies according to clinical epidemiologic standard. The search time was from the establishment of each database to December, 2009. Results A total of 62 studies involving 5 762 patients were included. In all included studies, there were 56 randomized controlled trials (RCTs). A total of 8 studies described the method of random assignments. There were 4 multi-center randomized double-blind placebo-control trials. A total of 55 reported diagnosis criteria, 40 reported included criteria, 28 reported excluded criteria; 36 reported the curative efficacy at the end of the treatment, 51 assessed the neurological deficit score of patients before and after the treatment, 27 evaluated the ADL scores; 32 studies reported the side effects; 6 trials did not conduct intention-to-treat analysis even though some people withdrew the treatment because of the side effects or poor tolerance, etc. Conclusion Except for several high quality RCTs, current quality of some clinical trials on butylphthalide for ischemic stroke should be improved. We recommend that researchers should use internationally accepted consolidate standards of reporting trials (CONSORT) in future studies.
【摘要】 目的 研究不同亚型多系统萎缩（multiple system atrophy，MSA）患者的临床特点。 方法 回顾分析2009年1月—2011年1月收治的105例“很可能的”MSA患者的临床资料，包括发病年龄、首发症状、临床表现、治疗反应性等。 结果 105例MSA患者中，男57例，女48例，发病年龄58岁。以小脑性共济失调为主要特点的MSA（MSA with predominant cerebellar ataxia，MSA-C）患者76例，以帕金森综合征为主要特点的多系统萎缩（MSA with predominant parkinsonism，MSA-P）患者29例。39例患者仅以小脑功能障碍为首发症状；29例患者仅以帕金森综合征为首发症状，23例患者仅以自主神经功能障碍为首发症状，其余14例患者的首发表现至少包括2种症状组合。至最后一次随访时，54例患者同时存在小脑功能障碍、帕金森综合征、自主神经功能障碍和锥体束征，51例患者表现为自主神经功能障碍与小脑功能障碍和（或）帕金森综合征的不同形式的组合。 结论 MSA患者以MSA-C为主。由于在病程早期，MSA与其他帕金森综合征或小脑性共济失调疾病的鉴别较为困难，因此，仔细动态观察患者临床特点的演变情况，对MSA的诊断至关重要。【Abstract】 Objective To investigate subtypes and clinical features of multiple system atrophy (MSA). Methods The clinical data of 105 probable MSA patients treated in our hospital from January 2009 to January 2011 were analyzed, including the age at onset, initial symptoms, clinical manifestations and responsivity to levodopa. Results The 105 probable MSA patients consisted of 57 males and 48 females, including 76 patients (72.4%) of MSA with predominant cerebellar ataxia (MSA-C) and 29 patients (27.6%) of MSA with predominant parkinsonism (MSA-P). The mean age at onset was 58 years. The initial symptom of 39 patients was pure cerebellar dysfunction. Twenty-nine patients presented pure parkinsonism as the initial symptom. The initial symptom of 23 patients was pure dysautonomia. By the last clinical visit, 54 patients had cerebellar dysfunction, parkinsonism, autonomic failure and pyramidal signs. Conclusion The study revealed a predominance of MSA-C patients. The differentiation of MSA and other forms of parkinsonism or cerebellar ataxia may be difficult at the early stage. For more accurate diagnosis, it is important to carefully observe the clinical progression.
目的通过改良Robicsek法胸骨固定及双侧胸大肌内侧头转移在非体外循环冠状动脉旁路移植术（OPCAB）患者胸骨固定中的应用，探讨此技术在预防OPCAB术后胸骨并发症的作用。 方法回顾性分析2011年2月至2013年4月北京安贞医院46例符合高危人群指征的心脏病患者行改良Robicsek法胸骨固定及双侧胸大肌内侧头转移手术的临床资料。男17例，女29例；年龄63～82（68.6±4.6）岁。 结果46例患者手术过程顺利，无1例发生胸骨并发症。1例死于围手术期心肌梗死、左心力衰竭，其余患者术后肌瓣存活良好。45例术后14 d拆线，伤口愈合良好。所有患者出院后1个月、6个月进行随访，皮肤切口愈合良好，胸骨固定良好，无窦道形成，未见反常呼吸运动，胸廓外形良好。 结论相对于传统闭合切口的方法，对可能发生胸骨合并症的高危人群，采用改良Robicsek法胸骨固定及双侧胸大肌内侧头转移术有一定的优势，能降低胸骨裂开及切口感染的概率，从而降低全身感染的概率，缩短患者康复时间，减轻心理压力。
Objective To assess the changes in depression symptoms in patients with Parkinson’s disease (PD) receiving combined treatment of deep brain stimulation (DBS) and antiparkinsonian drug therapy (DT) compared with under DT alone. Methods Related literature was retrieved from electronic databases, including PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang Data, and VIP databases. Stata 14.0 software was used for statistical analysis. Network meta-analysis was performed using frequentist model to compare different interventions with each other. Results Five cohort studies and seven randomized controlled trials (RCTs) were included. The total number of participants was 1241. Assessed by the Beck Depression Inventory (BDI) score as the primary outcome, patients who received DT alone showed worse outcome in depression as compared to those who received subthalamic nucleus (STN)-DBS plus DT [standardized mean difference (SMD)=0.30, 95% confidence interval (CI) (0.01, 0.59), P<0.05], and there was no significant difference between the patients receiving globus pallidus interna (GPi)-DBS plus DT and those receiving STN-DBS plus DT [SMD=–0.12, 95%CI (–0.41, 0.16), P>0.05] or those receiving DT alone [SMD=–0.42, 95%CI (–0.84, 0.00), P>0.05]. Assessed by BDI-Ⅱ as the primary outcome, patients who received DT alone showed worse outcome in depression than those who received STN-DBS plus DT [SMD=0.29, 95%CI (0.05, 0.54), P<0.05]; compared with STN-DBS plus DT and DT alone, GPi-DBS plus DT was associated with better improvement in depression [SMD=–0.26, 95%CI (–0.46, –0.06), P<0.05; SMD=–0.55, 95%CI (–0.88, –0.23), P<0.05]. The ranking results of surface under the cumulative ranking curves showed that DBS plus DT had a better superiority in depression symptoms, and GPi-DBS was better than STN-DBS. Conclusion Compared with DT, STN-DBS plus DT is more likely to improve the depressive symptoms of PD patients, and GPi-DBS may be better than STN-DBS.
ObjectiveTo investigate the effect of phosphorylatable short peptide (pSP) conjugated chitosan (CS) (pSP-CS) mediated insul in-l ike growth factor 1 (IGF-1) gene and human interleukin 1 receptor antagonist (IL-1Ra) gene local transfection on the repair of articular cartilage defect. MethodsCo-expression plasmid pBudCE4.1-IL-1Ra+IGF-1, single gene expression plasmid pBudCE4.1-IL-1Ra and pBudCE4.1-IGF-1 were constructed and combined with pSP-CS to form pSP-CS/ pDNA complexes. Thirty 3-month-old healthy male New Zealand white rabbits, weighing 2.0-2.5 kg, double legs were randomly divided into 5 groups (n=12). Lateral femoral condyle articular surface was only exposed in sham-operated group (group A); full-thickness cartilage defects were created in the articular surface of the lateral femoral condyle of the knee in 4 intervention groups: pSP-CS/pBudCE4.1 (group B), pSP-CS/pBudCE4.1-IL-1Ra (group C), pSP-CS/pBudCE4.1-IGF-1(group D), and pSPCS/ pBudCE4.1-IL-1Ra+IGF-1 (group E). At 1 week after operation, intra-articular injection of pSP-CS/pDNA complexes was administrated 2 times a week for 7 weeks in each intervention group, the same volume normal sal ine in group A. The general condition of animal was observed after operation, and rabbits were sacrificed at 8 weeks. Knee joint synovial fluid was collected to measure the concentrations of the IL-1Ra and IGF-1 by ELISA; mRNA expressions of Aggrecan, matrix metalloproteinase 3 (MMP-3), and MMP inhibitor 1 (TIMP-1) were detected by real-time fluorescent quantitative PCR; the chondrogenic phenotype of nascent cells in the damage zone was identified by alcian blue-periodic acid/schiff (AB-PAS) histochemistry and Aggrecan immunohistochemistry staining. ResultsThirty experimental rabbits all survived to the end of experiment, without infection and death. Large amounts of exogenous proteins of IGF-1 and IL-1Ra were detected in the synovial fluid of 4 intervention groups. There were significant differences between groups D, E and group A in IGF-1 protein expression, and between goups C, E and group A in IL-1Ra protein expression (P < 0.05). Aggrecan and TIMP-1 mRNA expressions were significantly up-regulated in group E, simultaneously MMP-3 mRNA expression was significantly down-regulated when compared with groups C and D (P < 0.05). Varying degrees of cartilage repair appeared in groups C, D, and E, showing positive staining of AB-PAS and Aggrecan, and group E had better results than groups C and D (P < 0.05); inflammatory cell infiltration and fibrous tissue prol iferation were seen in the defect region of group B, without significant cartilage repairing. ConclusionpSP-CS is an ideal gene del ivery system for cartilage defect gene therapy; IL-1Ra and IGF-1 double gene transfection has better biologic effect on cartilage defect repair.
【摘要】 目的 探讨佛波酯激活的蛋白激酶C与扭转蛋白A在亚细胞成分中的表达之间的关系。 方法 采用免疫荧光法观察扭转蛋白A在原代培养的神经元和小鼠胚胎成纤维细胞（NIH 3T3细胞）中的分布。运用蛋白质印迹法分析蛋白激酶C和扭转蛋白A在细亚细胞成分中的表达。 结果 扭转蛋白A在NIH 3T3细胞中的表达类似于神经元。扭转蛋白A在细胞质溶质、膜成分中均有分布。佛波酯活化蛋白激酶C后并不引起扭转蛋白A在细胞质成分和膜成分中表达含量的变化。 结论 扭转蛋白A可能是膜相关蛋白，细胞氧化应激中扭转蛋白A表达上调和重分布变化不是由佛波酯诱导的蛋白激酶C活化途径来实现的。鉴于扭转蛋白A表达上调具有潜在的治疗原发性早发扭转性肌张力障碍的前景，影响其分布和表达的分子机制需要进一步研究。【Abstract】 Objective To investigate the relationship between the phorbol 12-myristate 13-acetate (PMA) activated protein kinase C (PKC) and the subcellular expression of TorsinA protein. Methods The expression of TorsinA in the primary cultured neurons and the NIH 3T3 cells was detected by immunofluorescence. The expression of PKC and TorsinA in subcellular fraction was analyzed by the western blotting. Results The expression pattern of TorsinA in NIH 3T3 cells was similar to neuron. PMA, an activator of PKC, did not promote the up-expression of TorsinA or redistribution in the subcellular fraction of NIH 3T3 cells. Conclusions TorsinA may be a membrane-associated protein. The up-regulation and redistribution of TorsinA is not caused by the pathway of the PMA activating PKC after cells insulted by oxidative stress. We should pay more attention on the mechanisms of the expression of TorsinA protein for the potential therapies to early-onset primary torsion dystonia (DYT1).
ObjectiveTo evaluate the effectiveness of anatomic femoral component prosthesis for severe development dysplasia of the hip (DDH) in total hip arthroplasty (THA). MethodsBetween September 2009 and September 2013, 48 patients (51 hips) with severe DDH underwent THA with cementless anatomic femoral component prosthesis. There were 5 males (5 hips) and 43 females (46 hips) with an average age of 51 years (range, 28-67 years). The left hip was involved in 25 cases, the right hip in 20 cases, and bilateral hips in 3 cases. There were 39 cases (44 hips) of Crowe type Ⅲ and 9 cases (7 hips) of Crowe type ⅠV. The visual analogue scale (VAS) score was 5.72±1.84, and Harris score was 41.66±4.87 at preoperation. All patients had leg discrepancy with a length difference of (4.31±0.84) cm. ResultsThe duration of surgery was 59-110 minutes (mean, 78.6 minutes), and the hospitalization days were 6-20 days (mean, 12.3 days). All patients obtained primary healing of incision without wound related complications of swelling, effusion, and infection. Two patients were found to have intramuscular venous thrombosis. All patients were followed up 10-54 months (mean, 29 months). Limp was observed at the early stage after operation in 9 patients and disappeared after 1 year, the other patients had normal gait. The VAS score 1.46±0.47, Harris score 88.66±3.48, and the leg length difference (1.15±0.33) cm at last follow-up all showed significant differences when compared with the preoperative values (P<0.05). No prosthesis loosening or subsidence, heterotopic ossification, dislocation, and infection occurred. ConclusionAnatomic femoral component prosthesis for severe DDH in THA can relieve pain, and improve the hip joint function and limb discrepancy. Short-term effectiveness was satisfactory, but the long-term effectiveness should still be observed in future.
Objective To investigate the effects of nucleus localization signal linked nucleic kinase substrate short peptide (NNS) conjugated chitosan (CS) (NNSCS) mediated the transfection of microRNA-140 (miR-140) in rabbit articular chondrocytes in vitro. Methods Recombinant plasmid GV268-miR-140 and empty plasmid GV268 were combined with NNSCS to form NNSCS/pDNA complexes, respectively. Chondrocytes were isolated and cultured through trypsin and collagenase digestion from articular cartilage of newborn New Zealand white rabbits. The second generation chondrocytes were divided into 3 intervention groups: normal cell control group (group A), NNSCS/GV268 empty plasmid transfection group (group B), and NNSCS/GV268-miR-140 transfection group (group C). NNSCS/GV268 and NNSCS/GV268-miR- 140 complexes were transiently transfected into cells of groups B and C. After transfection, real-time fluorescent quantitative PCR (RT-qPCR) was used to detect the expressions of exogenous miR-140; Annexin Ⅴ-FITC/PI double staining and MTT assay were used to detect the effect of exogenous miR-140 on apoptosis and proliferation of transfected chondrocytes; the expressions of Sox9, Aggrecan, and histone deacetylase 4 (Hdac4) were detected by RT-qPCR. Results RT-qPCR showed that the expression of miR-140 in group C was significantly higher than that in groups A and B (P<0.05). Compared with groups A and B, the apoptosis rate in group C was decreased and the proliferation activity was improved, Sox9 and Aggrecan gene expressions were significantly up-regulated, and Hdac4 gene expression was significantly down-regulated (P<0.05). There was no significant difference in above indexes between groups A and B (P>0.05). Conclusion Exogenous gene can be carried into the chondrocytes by NNSCS and expressed efficiently, the high expression of miR-140 can improve the biological activity of chondrocytes cultured in vitro, which provides important experimental basis for the treatment of cartilage damage diseases.