Polo-like kinase 1(PLK1)is a serine/threonine kinase which is highly conserved, and its activity is elevated in many human tumor cell lines.Lots of reports have shown that PLK1 is critical for all stages of mitosis.The newest report finds that PLK1 is required for DNA synthesis, maintenance of DNA integrity, and prevention of cell death.PLK1 physically binds to the tumor suppressor p53 in mammalian cultured cells, and inhibits its transactivation activity as well as its function in activate checkpoint protein and its pro-apoptotic function.Also PLK1 is involved in the development of tumors, and Polo-like kinase1(PLK1)regulates IFN induction by MAVS, breakdown the innate immunity. Various of inhibitors of PLK1 show the feature of high performance and low toxicity, suggesting that PLK1 may be a feasible target for cancer therapy and immunity therapy.

Objective To evaluate the effect of concomitantdifferent regimens chemotherapy and radiotherapy for inoperable stage Ⅲ non small cell lung cancer (NSCLC). Methods From September 1995 to December 1998, 62 patients with inoperable stage Ⅲ NSCLC were randomized into two groups. Twenty nine patients received paclitaxel 30 mg and cisplatin 30 mg weekly for 5～6 weeks (paclitaxel group), and 33 patients received etoposide (Vp 16) 100 mg and cisplatin 30 mg weekly for 5～6 weeks (VP 16 group). All patients received concomitant radiotherapy as well. Radiotherapy was given with conventional fraction in 2Gy per fraction and five fractions per week. The total tumor doses were 60～70 Gy. Treatment fields covered clinical tumor and lymph node involved. Results The overall response (CR+PR) rate in paclitaxel group was 82.8% with a complete response (CR) rate of 10.3%. The overall response rate in the VP 16 group was 54.6% with a CR rate of 18%. The difference of overall response rate between the two groups was statistically significant (P0.05). The major toxic effects of chemotherapy were gastrointestinal tract reaction and myelosuppression. Conclusions Concomitant chemotherapy of paclitaxel plus cisplatin and radiotherapy for inoperable stage Ⅲ NSCLC is acceptable, and its efficacy is superior to cisplatin plus etoposide combined with radiotherapy.

Objective To investigate the changes of thrombomodulin and matrix metalloproteinase-9 in sepsis and determine their significance in the early diagnosis and prognosis of multiple organ dysfunction syndrome. Methods The plasma levels of thrombomodulin and matrix metalloproteinase-9 in 32 ICU patients with sepsis were measured by immunofluorescence. Results Compared with control group,the levels of TM and MMP-9 were significantly higher on the day of the diagnosis of sepsis(P

Objective To investigate the changes in the serum MMP-9 (matrix metalloproteinase-9) and the expressions of MMP-9 in lung, kidney and intestine in rats with multiple organ dysfunction syndrome (MODS) and confirm extracellular matrix injuries being the mechanism in MODS in order to propose a novel theoretical basis for cfinical treatment of MODS. Method Forty wister rats were randomly divided into two groups: control group (n=8) and MODS model group (n=32). The rats of model group were further divided into four subgroups ac-cordingto the time elapsed after modelling: 12 h (n=8), 24 h(n=8) ,48 h(n=8) and 72 h (n=8), and were modelled by celiac injection of mixed liquid of zymosan-paraffin (4 mL/100 g) after blood loss (1mL/100 g) by extirpating their left eyes. Blood,lung, kidney and intestine were sampled 12,24,48 and 72 hours after models were established. The histological changes in the lung, kidney and intestine of the rats were observed by light mi-croscope. The serum MMP-9 were measured by enzyme-linked immunosorbent assay (ELISA). The immunohisto-chemistry was used to observe the expression of MMP-9 in lung,kidney and intestine during different phases of MODS. The data were processed by one-way ANOVA and Bivariate analysis. Results Compared with control group, the organs were injured by congestion, edema and inflammatory cells infiltration to a certain extent in model groups. The serum MMP-9 increased markedly 12 hours after modelling (P<0.01 ) and peaked 48 hours later. The expressions of MMP-9 in lung, kidney and small intestine significantly increased from 12 h to 72 h after mod-elling (P<0.01 or 0.05). Conclusions The MMP-9 increased both in serum and tissue are closely associated with the pathological process of MODS. The mechanism of organ damage probably attributes to the damage of extra-celluar matrix and tissue construction.

Objective To evaluate the clinical effects and experiences of short stem ceramic-on-ceramic total hip arthroplasty in the treatment of young and middle-aged patients with femoral head necrosis.Methods From December 2009 to March 2011,40 patients with femoral head necrosis were treated primarily with short stem ceramic-on-ceramic hip arthroplasty (43 hips) through posterior-lateral or anterior-lateral approach.There were 23 males,17 females； with the mean age of 40.5 years (range,27-55 years).All cases were stage Ⅳ or more according Steinberg stage.The patients were followed up at the 3,6,12 months after operation,and then once each year.Standard X-ray films were taken at the follow-ups.Femoral prosthesis subsidence was assessed through X-ray films.Harris scores system and WOMAC Osteoarthritis Index were recorded before and after operation to evaluate clinical effects of surgery.Results Thirty-eight patients (41 hips) were followed up for 21-36 months,with an average of 31.3 months.The femoral stem subsided 0.68±2.90 mm at the last follow-up.After operation,hip pain of patients was relieved obviously.The Harris score improved from 38.7±12.1 (15-66) preoperatively to 95.2±4.49 (83-100) postoperatively,WOMAC Index from 66.7±12.0 (49-94) to 12.8±5.6 (0-24).During follow-up period,there was no serious complication such as femoral neck fracture,infection of wound,pulmonary embolism,et al.No dislocation,implant prosthesis failure and infection were observed.Conclusion The short stem hip arthroplasty preserves bone stock to a great extent.The short stem implant showed a good stability and osseous integration.The wear rate of ceramic-on-ceramic bearing surface is extremely low.Short stem hip arthroplasty plus ceramic-on-ceramic bearing surface might be a good option for the young and middle-aged patients with femoral head necrosis.

Objective To evaluate the clinical indications and outcomes of dynesys neutralization system in the treatment of degenerative lumbar diseases.Methods From January 2007 to December 2011,102 consecutive patients with degenerative lumbar spine diseases underwent posterior decompression and internal fixation with the Dynesys dynamic neutralization system.Among them,69 patients were followed up,including 39 males and 30 females,aged from 30 to 62 years (average,44 years).The series of cases were composed of 24 cases of lumber disc herniation,35 cases of degenerative spinal stenosis,10 cases of degenerative changes of lumbar discs.Results The mean follow-up period was 35 months (range,6-44 months).The visual analogue scale (VAS) score decreased from preoperative 8.6 (range,6-9) to postoperative 2.8 (range,0-5),and the Oswestry disability index (ODI) improved from preoperative 73％ (range,30％-91％) to postoperative 30％ (range,0-61％).There were no implant failure or infection.According to the evaluation criteria of surgical treatment for low back pain,which was established by the Chinese Orthopaedic Association,the result was excellent in 53 patients,good in 12 patients,fair in 4 patients and poor in 1 patient.Conclusion The Dynesys dynamic neutralization system is effective in the treatment of degenerative lumbar spine disease,which can reserve the range of motion of stabilized segments,prevent degeneration of adjacent segments and improve clinical outcomes.

Objective To retrospectively analyze the methods and clinical outcome to treat Crowe type Ⅳ developmental dysplasia of the hip (DDH) in young adults with total hip arthroplasty (THA) after limb-lengthing with external fixator.Methods From October 2007 to January 2012,12 patients with unilateral Crowe type Ⅳ DDH were treated with two-staged surgical method in our department.There were 2 males and 10 females with an average age of 25.7 years (range,18-35 years).In the first stage,the patients underwent soft tissue relaxation and iliofemoral distraction with use of an external fixator for 10-17 days.There were 1-2 cm distraction at the first time and 3-5 mm daily distraction.When the femoral head was distracted to the level of anatomical position,the second stage-THA was performed.All patients underwent uncemented prosthesis with bulk femoral head autograft for acetabular reconstruction.The acetabular cup was placed in the anatomical position in every patient.Shortening femoral osteotomies were not required.Results The mean time of first operation was 35.2±3.6 min,and hospital stay was 13.3±1.6 days.The mean time of second operation was 77.3±12.4 min,and hospital stay was 9.2±2.5 days.The average follow-up was 13.6±3.2 months,limb-length discrepancy was 5.6±1.5 cm on average preoperatively and 0.5±0.2 cm on average postoperatively.The Harris hip score was increased from 45.7±2.6 preoperatively to 92.3±3.3 postoperatively.All of the cases had acquired good hip and knee function.No patient suffered pin-site infection,hip joint infection,prosthesis loosening or deep vein thrombosis in our research.Transient nerve palsy occurred during the leg limb lengthening in 3 cases; calf skin numbness after THA occurred in 5 cases.Conclusion For the Crowe type Ⅳ DDH in young adults,normal limb length can be restored nearly and avoid nerve injury via continuously limb-lengthing with external fixator before THA.This method can get precise results,improve limb function significantly and have fewer complications.

Osteoarthritis is a common cause of functional deterioration in older adults and is an immense burden on the aging population. Altered chondrogenesis is the most important pathophysiological process involved in the development of osteoarthritis. However, the molecular mechanism underlying the regulation of chondrogenesis in patients with osteoarthritis requires further elucidation, particularly with respect to the role of microRNAs. MiR-21 expression in cartilage specimens was examined in 10 patients with knee osteoarthritis and 10 traumatic amputees. The effect of miR-21 on chondrogenesis was also investigated in a chondrocyte cell line. The effect of miR-21 on the expression of growth differentiation factor 5 (GDF-5) was further assessed by luciferase reporter assay and western blot. We found that endogenous miR-21 is upregulated in osteoarthritis patients, and overexpression of miR-21 could attenuate the process of chondrogenesis. Furthermore, we identified GDF-5 as the direct target of miR-21 during the regulation of chondrogenesis. Our data suggest that miR-21 has an important role in the pathogenesis of osteoarthritis and is a potential therapeutic target.
Cartilage/metabolism/pathology ; Case-Control Studies ; Cell Line ; Chondrocytes/*metabolism/pathology ; Growth Differentiation Factor 5/genetics/*metabolism ; Humans ; MicroRNAs/genetics/*metabolism ; Osteoarthritis/*metabolism/pathology ; Up-Regulation

BACKGROUND:Nanocomposite hydrogel has great research prospects and application potential in the treatment of osteoarthritis. OBJECTIVE:To review the research progress of nanocomposite hydrogel in osteoarthritis and cartilage repair. METHODS:Databases such as CNKI and PubMed were searched.The English key words were"nanocomposite hydrogel,nanogel,osteoarthritis,cartage,physical encapsulation,electrostatic interaction,covalent crosslinking",and the Chinese key words were"nanocomposite hydrogel,nanogel,osteoarthritis,cartage,physical encapsulation,physical encapsulation,electrostatic effect,covalent cross-linking".After an initial screening of all articles based on inclusion and exclusion criteria,71 articles with high correlation were retained for review. RESULTS AND CONCLUSION:In cell or animal experiments,nanocomposite hydrogel has the effect of improving osteoarthritis.Nanocomposite hydrogel can promote cartilage repair,improve the internal environment of osteoarthritis,and achieve the therapeutic purpose of osteoarthritis by improving the mechanical environment between joints,carrying targeted drugs,and promoting the chondrogenesis of seed cells.At present,the research of nanocomposite hydrogel in osteoarthritis disease still has a huge space to play.It is expected to open up a new way for the clinical treatment of osteoarthritis by continuing to deepen the research of material preparation and actively carrying out cell and animal experiments.

MicroRNAs (miRNAs) have recently been recognized to have a role in human orthopedic disorders. The objective of our study was to explore the expression profile and biological function of miRNA-17-5p (miR-17-5p), which is well known to be related to cancer cell proliferation and invasion, in osteoblastic differentiation and in cell proliferation. The expression levels of miR-17-5p in the femoral head mesenchymal stem cells of 20 patients with non-traumatic osteonecrosis (ON) and 10 patients with osteoarthritis (OA) were examined by quantitative reverse transcription-PCR (qRT-PCR). Furthermore, the interaction between miR-17-5p and SMAD7 was observed. We found that in non-traumatic ON samples the level of mature miR-17-5p was significantly lower than that of OA samples (P=0.0002). By targeting SMAD7, miR-17-5p promoted nuclear translocation of beta-catenin, enhanced expression of COL1A1 and finally facilitated the proliferation and differentiation of HMSC-bm cells. We also demonstrated that restoring expression of SMAD7 in HMSC-bm cells partially reversed the function of miR-17-5p. Together, our data suggested a theory that dysfunction of a network containing miR-17-5p, SMAD7 and beta-catenin could contribute to ON pathogenesis. The present study prompts the potential clinical value of miR-17-5p in non-traumatic ON.
Adult ; Base Sequence ; Bone Morphogenetic Protein 2/metabolism ; Cell Differentiation ; Cell Line ; Cell Proliferation ; Female ; *Gene Expression Regulation ; Humans ; Male ; MicroRNAs/genetics/*metabolism ; Middle Aged ; Osteoarthritis/genetics/metabolism/pathology ; Osteoblasts/*cytology/metabolism/*pathology ; Osteogenesis ; Osteonecrosis/*genetics/metabolism/pathology ; Signal Transduction ; Smad7 Protein/*genetics/metabolism ; beta Catenin/metabolism