BACKGROUND:Laser therapy is a non-invasive and painless treatment that is considered to be an effective method suitable for the treatment of osteoarthritis due to its simplicity and non-invasive nature.Currently,the mechanism of action of laser therapy is unclear and the results of studies on its clinical application are controversial. OBJECTIVE:To review and summarize the latest research progress of laser therapy on chondrocytes,animal experiments and clinical efficacy,and to explore the possible mechanism of laser-mediated multi-pathway biological effects,so as to provide a theoretical basis for further research on the laser treatment of osteoarthritis of the knee joint. METHODS:A literature search was performed in CNKI,WanFang Data,VIP and PubMed databases for relevant literature published from 2018 to 2023,with"laser therapy,low level laser therapy,high level laser therapy,photobiomodulation,knee osteoarthritis,chondrocytes"as the search terms in Chinese and English,respectively.Together with 14 articles searched manually,70 articles were finally included for review. RESULTS AND CONCLUSION:Laser therapy in the treatment of knee osteoarthritis is mainly categorized into two types:low-level laser therapy and high-level laser therapy.Differences in laser parameters and treatment protocols have a direct impact on laser efficacy.When appropriate parameters are used,low-level lasers show positive effects in cellular experiments,animal models,and clinical efficacy.High-level lasers have been less studied in the treatment of knee osteoarthritis,but some preliminary clinical studies have shown positive results.Cell experiments have shown that low-level laser promotes chondrocyte proliferation and cartilage matrix synthesis,thereby reducing inflammatory response.Animal experiments have shown that low-level laser can reduce the release of pro-inflammatory factors,promote cartilage matrix synthesis,inhibit matrix degradation,and effectively improve the repair process of cartilage tissue.Low-level laser is also able to reduce oxidative stress damage and relieve pain in knee osteoarthritis.In clinical trials,both low-and high-level laser can reduce patients'pain and improve functional activities.The combination of laser therapy and exercise therapy modalities may improve the therapeutic effect.Lasers may affect intracellular signaling and cellular functions through photobiological or thermodynamic effects.This provides direct evidence that laser promotes articular cartilage regeneration.

Objective:To investigate the differences in gene expression levels in knee chondrocytes and chondrons in vitro.Methods:The chondrocytes and chondrons were isolated from full thickness of the 8-months ( n=5) rabbit knees cartilage. Chondrons from right knee were enzymatically isolated using 0.3% dispase and 0.2% collagenase-2 with shaking for 3 hours. Chondrocytes were isolated by 0.4% Pronase and 0.025% collagenase-2 from left knee. The mRNA levels in chondrocytes and chondrons were analyzed by quantitative real-time PCR, including matrix proteins [aggrecan(Agg), collagen(Col-2), Col-6A6, Col-10, Col-11], MMPs and inhibitors (MMP-1, MMP-3, MMP-9, MMP-13, TIMP-1, TIMP-2, TIMP-3), cytoskeletal proteins (Sox-9, vinculin, tubulin, actin), cytokines (IL-β, TNF-α). Analysis was performed using SPSS 16.0 statistical software, and the two-group comparisons were considered as significant by t-test at P<0.05. Results:Compared to the chondrocytes, the Agg [(5.78±0.90) vs (1.89±0.27), t=9.26, P<0.001], Col-2 [(6.29±0.76) vs (3.06±0.60), t=7.46, P<0.001], Col-6A6 [(0.89±0.18) vs (0.22±0.06), t=7.90, P<0.001], Col-10 [(3.83±0.76) vs (1.00±0.26), t=7.88, P<0.001] and TIMP-1 [(1.98±0.85) vs (1.03±0.34), t=2.32, P=0.049], TIMP-2[(3.46±1.50) vs (1.52±1.06), t=2.36, P=0.046], TIMP-3 [(3.96±0.50) vs (1.36±0.18), t=10.94, P<0.001], Sox-9 [(7.09±2.93) vs (3.24±0.77), t=2.84, P=0.022], vinculin [(3.42±1.69) vs (1.46±0.68), t=2.41, P=0.043], tubulin[(9.34±0.71) vs (2.35±0.80), t=14.61, P<0.001] showed higher expression in the chondrons. Compared to the chondrocytes, the MMP-1 [(1.02±0.30) vs (2.67±0.45), t=6.91, P<0.001], MMP-3 [(1.21±0.32) vs (2.52±0.79), t=3.44, P=0.009], MMP-13 [(1.23±0.34) vs (3.42±0.86), t=5.30, P=0.007], IL-1β [(1.02±0.14) vs (2.70±0.49), t=7.37, P<0.001], TNF-α [(0.99±0.08) vs (3.15±0.54), t=8.85, P<0.001] showed lower expression in the chondrons. There were no difference between chondrons and chondrocytes for Col-11, MMP-9, actin ( P>0.05). Conclusion:The gene expression of extracellular matrix components are higher and the gene expression levels of inflammatory factors and MMPs are decreased in chondrons compared with the chondrocytes, suggesting the chondrons have more multiplication potential as seeding cells for tissue-engineered cartilage.

Objective:To explore the effects of Alpha-2-macroglobulin-rich serum (A2MRS) on knee post-traumatic osteoarthritis (PTOA).Methods:The knee PTOA models were constructed by transection of the anterior cruciate ligament (ACL) in 80 SD male rats, aged 2 months and weighing from 250 to 300 g, which were randomized into 4 groups ( n=20): a high dose group (A2MRS containing 20 μg/μL A2M administered), a low dose group (A2MRS containing 10 μg/μL A2M administered), a positive control group (normal saline administered), and a blank control group (the knee joint cut pseudooperatively and normal saline administered). HE, toluidine blue staining, safranine O staining, modified Mankin scoring and Osteoarthritis Research Society International (OARSI) scoring were conducted to evaluate and compare the therapeutic effects of A2MRS on the knee PTOA among the 4 groups. Results:The rat cartilage was thinner with patchy and cracked surface, and the chondrocytes were reduced and distributed unevenly in the positive control group, compared with the blank control group. The modified Mankin score (3.89±0.93) and OARSI score (10.05±0.72) in the positive control group were significantly higher than those in the blank control group (0.67±0.07 and 3.10±0.29) ( P<0.05). The rat cartilage was thicker with basically complete and crack-free surface, and the chondrocytes were increased and distributed more evenly in the high dose group and the low dose group, compared with the positive control group. The modified Mankin scores (1.33±0.50 and 1.56±0.53) and OARSI scores (6.30±0.64 and 4.75±0.66) in the high dose group and the low dose group were significantly lower than those in the positive control group ( P<0.05). However, there were no such differences between the high dose group and the low dose group ( P>0.05). Conclusion:A2MRS effectively delays the pathological process of knee PTOA.

Objective:To compare the efficacy of augmentation suture and direct suture in treatment of acute Achilles tendon ruptures so as to provide evidences for the selection of surgical methods.Methods:A systematic search was conducted in PubMed, Web of Science, EMBASE, CNKI and Wanfang database for studies of augmentation suture versus direct suture of acute Achilles tendon ruptures. Literatures were retrieved from January 1990 to January 2019. Literatures were screened according to the pre-set inclusion and exclusion criteria, and the rating of included literature was strictly evaluated by the Cochrane System Evaluation Manual and Newcastle-Ottawa scale (NOS). The relevant data were analyzed using RevMan 5.3 to compare patient satisfaction, rerupture rate, infection rate, ankle's range of motion and other complications (postoperative calf atrophy, plantar flexion, plantar flexion strength).Results:Eight articles involving 558 patients were identified including 273 patients in augmentation suture group and 285 patients in direct suture group. There were no significant differences between two groups in aspects of patient satisfaction ( OR=1.00, 95% CI 0.54-1.84, P>0.05), rerupture rate ( OR=0.75, 95% CI 0.34-1.66, P>0.05), infection rate ( OR=1.73, 95% CI 0.76-3.94, P>0.05), ankle's range of motion ( OR=0.97, 95% CI 0.33-2.87, P>0.05) and other complications rate ( OR=1.93, 95% CI 0.91-4.09, P>0.05). Meantime, the two groups showed similar effect on postoperative calf atrophy and average isokinetic calf muscle strength ( P>0.05). There was a significant difference in plantar flexion of injured limbs after augmentation suture( P<0.05). Conclusion:Compared with direct suture, augmentation suture cannot improve patient satisfaction or reduce complication rate in repair of acute Achilles tendon ruptures.

Objective:To investigate the short-term effects of articular injection of hyaluronic acid combined with glucocorticoid in patients with knee osteoarthritis.Methods:From October 2017 to June 2018, a total of 188 patients diagnosed with knee osteoarthritis received parallel articular injection. There were 60 cases with mild knee osteoarthritis, 72 with moderate and 56 with severe according to the WOMAC knee functional score. There patients were divided into group rank Ⅰ48 cases, Ⅱ 49 cases, Ⅲ 45 cases, Ⅳ 46 cases according to the knee joint X-ray Kellgren-Lawrence classification. The unified treatment regimen was 2.5 ml Sodium Hyaluronate (SHA) injection for the first time, SHA 2.5 ml and compound betamethasone injection (CBI) 1 ml for the second week, and 2.5 ml of SHA for the third week. WOMAC score and Lequesne index were used to evaluate joint function before the first injection and after SHA and SHA+CBI injection. The improvement rate of Lequesne index ≥30% or improvement rate of WOMAC score ≥25% was regarded as effective treatment.Results:Lequesne index and WOMAC score decreased gradually in the mild, moderate and severe groups after 3 weeks of injection. Among these patients, the improvement rates of Lequesne index after SHA injection and SHA+CBI injection were 36.44%±8.46% and 49.26%±13.75% in the mild group, 23.09%±12.61% and 30.66%±14.95% in the moderate group, and 10.50%±8.78% and 11.07%±6.52% in the severe group. The improvement rate of WOMAC score in the mild group after SHA injection and after SHA+CBI injection was greater than 25%. After SHA injection, the improvement rate of WOMAC score was 13.06%±10.21% in the moderate group, and 27.49%±13.61% after SHA+CBI injection. Those in severe group were all less than 25%. Kendall's staub correlation analysis results showed that there was a strong positive correlation between WOMAC function score and X-ray Kellgren-Lawrence classification ( r=0.744, P<0.001). The Lequesne index and WOMAC scores of the Kellgren-Lawrence X-ray classification decreased gradually after 3 weeks of injection. The improvement rate of Lequesne index period in group rank Ⅰ after SHA and SHA+CBI injection was 36.64%±10.05% and 52.00%±8.19%, respectively. That for group rank Ⅱ was 32.05%±8.09% and 41.95%±10.53%, group rank Ⅲ 16.93%±10.34% and 27.77%±10.25%, group rank Ⅳ 7.52%±5.53% and 7.60%±6.66%. The improvement rate of WOMAC score period in group rank Ⅰ after SHA and SHA+CBI injection was 29.48%±11.77% and 42.59%±13.55%, respectively. That for group rank Ⅱ was 26.72%±10.21% and 30.49%±16.90%, group rank Ⅲ 13.78%±5.96% and 23.05%±9.52%, group rank Ⅳ 4.77%±3.80% and 4.27%±4.23%. Conclusion:For mild or X-ray classification Ⅰ, Ⅱ knee osteoarthritis patients, articular injection SHA or SHA+CBI are effective. Further, SHA+CBI is better than single injection of SHA. SHA+CBI injection was effective for moderate knee osteoarthritis patients. For severe or X-ray classification Ⅲ, Ⅳ patients, SHA or SHA+CBI injection at interval are invalid.

Objective To compare the efficacy and safety between minimally invasive plate osteosynthesis (MIPO) and open reduction and internal fixation (ORIF) in the treatment of humeral shaft fracture.Methods Case-control studies and randomized clinical trials comparing MIPO with ORIF in the treatment of humeral shaft fracture from January 2010 to June 2018 were retrieved from PubMed Library,Cochrane Library,Embase Library,China National Knowledge Internet and Wanfang Data.Methodological quality of the studies and trials was critically assessed.REVMANS.3 was used for data analysis.The 2 groups of patients were compared in terms of University of California,Los Angeles shoulder rating scale (UCLA),Mayo Elbow Performance Score (MEPS),union time,nonunion rate and complications.Results A total of 452 patients from 9 articles were included.There were 216 cases in the MIPO group and 236 ones in the ORIF group.The Meta analyses showed that the MIPO group had a significantly higher UCLA score (WMD =0.36,P=0.03),significantly lower incidences of complications (OR =-0.15,P ＜ 0.05) and iatrogenie radial nerve palsy (OR =0.24,P ＜ 0.05),and significantly shorter union time (SMD =-0.36,P =0.02) than the ORIF group.There were no significant differences between the 2 groups in MEPS (WMD =-0.48,P =0.43) or nonunion rate (OR =0.45,P =0.11).Conclusion MIPO may be a better choice for humeral shaft fracture than ORIF in regards to postoperative shoulder functions,union time,and incidences of complications and iatrogenic radial nerve palsy.

Objective To identify the risk factors for the fractures secondary to percutaneous vertebroplasty for osteoporotic vertebral compression fractures.Methods A comprehensive search was conducted for the studies from January 2006 to September 2016 on the risk factors for secondary fractures after percutaneous vertebroplasty in the Cochrane Library,PubMed Data,CNKI,Chinese Biomedical Database,Wanfang Data and manually as well.After retrieval of the eligible data,software Revman5.0 was used to perform the heterogeneity test and calculate the pooled odds ratio (OR),weighted mean difference(WMD) value and 95％ confidence interval (CI).Results Twenty studies involving 3,602 patients,627 of whom had fracture secondary to the surgery,were included in this meta-analysis.Meta-analyses showed the secondary fracture after percutaneous vertebroplasty for osteoporotic vertebral compression fracture was related to bone mineral density [WMD =-0.66,95％ CI (-0.97,-0.36),P ＜ 0.05] and kyphosis after primary operation [WMD =4.51,95％ CI (3.02,6.00),P ＜ 0.05],but not to gender [OR =0.98,95％ CI (0.77,1.25),P＞ 0.05],age [WMD=1.48,95％CI (-0.13,3.09),P＞ 0.05],body mass index [WMD=-0.76,95％ CI(-1.61,0.08),P＞ 0.05],cement volume [WMD=-0.15,95％CI (-0.60,0.30),P＞0.05],intradiscal cement [0R=1.11,95％CI (0.56,2.22),P＞0.05],number of vertebrae primarily treated [OR=0.74,95％ CI (0.09,6.45),P ＞ 0.05],thoracolumbar spine [OR =0.86,95％ CI (0.63,1.18),-P ＞ 0.05],or cement injection approach [OR =1.58,95％ CI (0.74,3.37),P ＞ 0.05].Conclusions Bone mineral density and kyphosis after primary operation may be the risk factors closely correlative to the secondary fracture after percutaneous vertebroplasty.There has not been enough evidence to support the associations between the secondary fracture and gender,age,body mass index,cement volume,intradiscal cement,number of vertebrae primarily treated,thoracolumbar spine,or cement injection approach.

Objective We performed comprehensive proteomic analyses of synovial fluid by using the isobaric tags for relative and absolute quantitation (iTRAQ) method and LC-MS/MS, and searched for candidate biomarkers for osteoarthritis. Methods Synovial fluid was collected from patients with late-stage OA, earlystage OA and the control group. Molecular variations were detected by the iTRAQ method. T test was used for statistical analysis. Results Using the iTRAQ method, we identified 1 283 proteins from synovial fluid of patients with osteoarthritis, of which 268 proteins were not reported previously. There were 72 proteins upregulated and 249 proteins down-regulated between moderate OA group and controls. One hundred and twentyeight proteins were up-regulated and 141 proteins were down-regulated between severe OA group and controls.One hundred and ninety-two proteins were up-regulated and 76 proteins were down-regulated between severe OA group and moderate OA group. Eight proteins were found to be up-regulated in the three groups.Conclusion This is an in-depth analysis of the synovial fluid proteome from patients with osteoarthritis by iTRAQ method. The catalog of proteins generated in this study will further expand our knowledge regarding the pathophysiology of osteoarthritis and help us in identifying good biomarkers for early diagnosis.

Objective To analyze the effect of the fracture healing by using selective sensory radicotomy before and after the ganglion.Methods From September,2014 to August,2015,120 rats were averagely divided into 3 groups,which was the sham operate group(SO),the anterior injury of ganglion rhizotomy group (AGR) and the posterior injury of ganglion rhizotomy group (PGR).Tibial transverse fracture was performed on right or left randomly and the fracture was fixed with intramedullary.In coordination with the fractured-side,the selective radicotomy from L4 to L6 was made.The mRNA level of collagen-Ⅰ and collagen-Ⅱ in bony callus was quantified at 3,7 days and 2 weeks after the operation by RT-PCR(n=5).The histological examination,X-ray,biomechanical testing were performed at 4 and 8 weeks.The quantitative data of iconography and biomechanics was acquired by using the relative ration which resulted from fractured-side data dividing the unfractured-side one for every pair tibia in same rat.Results At 3 days after surgery,the mRNA of collagen-Ⅰ were 81.3±11.1,37.5±8.2 and 24.7±9.2,the mRNA of collagen-Ⅱ were 2.4±0.5,2.1±1.0 and 2.9±1.2 in SO,AGR and PGR group respectively;At 7 days after surgery,the mRNA of collagen-Ⅰ were 17.9±5.8,7.2±1.8 and 6.7±2.4,the mRNA of collagen-Ⅱ were 12.5±3.4,2.8±1.3 and 1.2±0.4 in SO,AGR and PGR group respectively.The SO group had significantly upregulation of collagen-Ⅰ and collagen-Ⅱ mRNA compared with the AGR and PGR groups at 3 days and 7 days respectively after surgery(P＜0.05).There was a significant difference of the collagen-Ⅱ between AGR group (2.8±1.3) and PGR group (1.2±0.4) at 7 days after injury(P＜ 0.05).The fracture bony callus in PGR group was a significantly larger and less ossified than that in the AGR group.The mechanical load of fracture in SO group was larger than that of the other 2 groups (P＜0.05).Conclusion Sensory denervation negatively affects fracture-healing.The ganglion of sensory nerve plays an important role in bone fracture healing and normal innervation is essential for the fracture repair.

BACKGROUND:Such methods as transplanting autologous periosteum or autologous bone marrow mesenchymal stem cells (BMSCs) can promote the repair of articular cartilage defects for sure. But they all have their own limits in chondrogenic abilities,which results in an unsatisfactory curative effect.OBJECTIVE:To study the effect of transplanting BMSCs (which were induced into chondrocytes) combined with autogenous periosteum on repairing articular cartilage defects in rabbits.MATERIALS:A total of 18 New Zealand rabbits,aged 6-8 months,were divided with random digits table method into 3 groups,namely,periosteum+BMSCs group,periosteum group and blank control group,with 6 ones (12 knee joint samples) in each group. METHODS:In periosteum+BMSCs group,BMSCs were harvested and adherently cultured with trypsin digestion method. Then they were induced by transforming growth factor 81 into chondrocytes. At the same time,immunofluorescence labeling was performed to BMSCs membranes with PKH-26. Full-thickness articular cartilage defects (diameter:3mm,depth:3mm) were made to bilateral condylus medialis femoris of all rabbits. In periosteum+BMSCs group and periosteum group,defects were covered by homolateral autogenous proximal tibia periosteums,with germinal layer facing to cavitas medullaris. After that,the periosteum+BMSCs group received 3 sutures,followed by injection of 20 μL BMSCs suspension (1×109/L) into the defects,after which the last suture was taken. The periosteum group underwent coverage with periosteum on defects only. The blank control group underwent perforate only.MAIN OUTCOME MEASURES:General observation,histological observation,Wakitani's score,immunohistochemical and in situ hybridization detection of collagen type Ⅱ were performed to defects at 6 and 12 weeks following operation.RESULTS:No sutured periosteums were found desquamate. In periosteum+BMSCs group,defects were filled with hyaline cartilage-like repairing tissues at week 6 following operation;Week 12 following operation saw remodeled tissues whose cells were mainly the implanted cells labeled with PKH-26. In periosteum group,repairing tissues in defect areas were ivory white,smooth with light introcession and distinctively different from the surrounding normal cartilage tissue. In the blank control group,clearer introcession or irregular appearance,even broken surrounding cartilage tissues could be seen in the defect area. Both Wakitani's score and histological score were highest in periosteum+BMSCs group at week 6 and 12 following operation (P＜0.05),with higher ones in periosteum group than in the control group (P＜0.05). What'more,matrix around cells in the repairing tissues showed positive results to both immunohistochemical and in situ hybridization staining of collagen typeⅡ,which proved that cells in repairing tissues were the implanted ones.CONCLUSION:Transplanted BMSCs (which were induced into chondrocytes) combined with autogenous periosteum can form hyaline cartilage-like repairing tissues through which articular cartilage defects are repaired.