A pH-responsive novel delivery system utilizing carbon quantum dots loaded with PT2385 for targeted inhibition of HIF-2α in the treatment of osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a progressive joint disorder marked by the degradation of cartilage. Elevated concentrations of hypoxia-inducible factor-2α (HIF-2α) are intricately linked to the pathological development of OA. PT2385 has demonstrated effective inhibition of HIF-2α, thereby potentially impeding the initial advancement of OA. Nevertheless, challenges persist, including limited penetration into the deeper layers of cartilage, issues related to charge rejection, and a heightened rate of clearance from the joint. These constraints necessitate further consideration and exploration. METHODS: It has been demonstrated that PT2385 exhibits efficient inhibition of HIF-2α expression, thereby contributing to the delay in the progression of osteoarthritis. The pH-responsive attributes of carbon quantum dots, specifically those employing m-phenylenediamine (m-CQDs) coated with bovine serum albumin (BSA), have been systematically evaluated. In both in vitro settings involving cartilage explants and in vivo experiments, the efficacy of BSA-m-CQDs-PT2385 (BCP) has been confirmed in facilitating the transport of PT2385 to the middle and deep layers of cartilage. Furthermore, the BCP system demonstrates controlled drug release contingent upon alterations in environmental pH. RESULTS: While the use of PT2385 alone provides protective effects on chondrocytes within an inflamed environment, there exists an opportunity for further enhancement in its efficacy when administered via intra-articular injection. The BCP formulation, characterized by appropriate particle size and charge, facilitates seamless penetration into cartilage tissue. Additionally, BCP demonstrates the capability to release drugs in response to changes in environmental pH. In vitro experiments reveal that BCP effectively inhibits Hif-2α expression and catabolic factors in chondrocytes. Notably, cartilage explants and in vivo experiments indicate that BCP surpasses PT2385 alone in inhibiting the expression of HIF-2α and matrix metalloproteinase 13, particularly in the middle and deep layers. CONCLUSIONS: The BCP drug delivery system exhibits selective release of PT2385 in response to pH changes occurring during the progression of osteoarthritis (OA), thereby inhibiting HIF-2α expression deep within the cartilage. The use of BCP significantly augments the capacity of PT2385 to retard both cartilage degeneration and the progression of osteoarthritis. Consequently, BCP as an innovative approach utilizing m-CQDs to deliver PT2385 into articular cartilage, shows potential for treating osteoarthritis.This strategy opens new avenues for osteoarthritis treatment.

[Kinematic gait analysis for patients with meniscus injury].

OBJECTIVE: To investigate application of the Codamotion 2CX1 three-dimensional dynamic joint motion capture system to analyze the kinematic characteristics of patients with different degrees of meniscus injury. METHODS: From December 2020 to June 2022, 135 patients with meniscus injury and recruited normal people were collected, including 82 males and 53 females, aged 14 to 29 years old, with disease duration of 1 to 3 months. Combined with clinical symptoms and MRI examination, the diagnosis of meniscus injury was confirmed, and the patients were divided into stages, including 37 cases of grade 0(normal), 30 cases of gradeⅠ, 33 cases of gradeⅡ, 35 cases of grade Ⅲ according to Stoller grading standard. Subjects in each group were tested walking by using Codamotion 2CX1 three-dimensional dynamic joint motion capture system. Quantitative indexes of walking and kinematics were collected, including knee flexion and extension, internal and external rotation and internal and external turning, and their kinematics were analyzed. RESULTS: In the distribution of knee flexion/extension, there were significant differences in maximum knee flexion, minimum knee extension and knee flexion and extension range among 4 groups(P<0.05). In the distribution of internal/external rotation of knee joint, there were significant differences in the range of internal rotation and rotation of knee joint among 4 groups(P<0.05). In the distribution of internal/external turning of knee joint, there were significant differences in the range of internal and external turning of knee joint among 4 groups(P<0.05). The clinical stage progression was positively correlated with the range of motion of knee extension, external rotation, internal and external turning and turning range(P<0.05). It was negatively correlated with knee flexion, internal rotation, flexion extension and rotation range(P<0.05). The internal and external rotation angles of knee joint could be used as independent factors influencing the clinical stage of meniscus injury (P=0.006, 0.019<0.05). CONCLUSION: The knee movement of patients with meniscus injury has obvious changes, and the changes are different under different clinical stages. Gait analysis provides a reliable basis for the kinematic analysis of meniscus injury, helps to better understand the kinematic indexes of joints, and provides a reliable auxiliary diagnosis and treatment plan, which provides a new direction for the follow-up medical research.

[Screw versus Kirschner wire fixation for lateral humeral condyle fractures in children:a meta analysis].

OBJECTIVE: To compare screw versus Kirschner wire fixation in the treatment of lateral humeral condyle fractures in children. METHODS: A systematic search was conducted in PubMed, Embase, the Cochrane library, Web of Science, China National Knowledge Internet(CNKI), Wanfang Datebase from in ception to February 2022. Studies comparing screws and Kirschner wire fixation in the treatment of lateral humeral condyle fractures in children were included. Outcome measures included and excluded by a set of inclusion and exclusion criteria and evaluated for their quality, their excellent and good rate of fracture healing, malunion, delayed union or nonunion, infection, limitation of elbow flexion or extension(>10°) were extracted and analyzed using software Rev Man 5.3. RESULTS: A total of 9 retrospective studies involving 647 patients were included, with 255 patients in the screw fixation group(including screw combined with Kirschner wire) and 392 patients in the Kirschner wire fixation group. Meta analysis showed the following:infection rate in the screw group was significantly lower than that in the Kirschner wire group[OR=0.22, 95%CI(0.09, 0.56), P=0.001]. There were no significant differences between the 2 groups in excellent and good rate of fracture healing, malunion rate(P>0.05). Subgroup analysis showed that infection rate in the screw-only group was significantly lower than that in the Kirschner wire group[OR=0.18, 95%CI(0.05, 0.65), P=0.009]. CONCLUSION: For lateral humeral condyle fractures, Screw fixation alone had a lower infection rate than kirschner wire fixation and screw combined with Kirschner wire fixation. There were no significant differences in the excellent and good rate of fracture healing, malunion. In terms of postoperative efficacy and safety of internal fixation, orthopaedic surgeons are more likely to recommend screws for fixation of lateral humeral condyle fractures in children.

[Meta-analysis of autologous bone grafts and bone substitute for the treatment of tibial plateau fractures].

OBJECTIVE: To explore clinical efficacy of autologous bone grafts and bone substitute for the treatment of tibial plateau fractures by Meta analysis. METHODS: Controlled clinical studies on autogenous bone transplantation and bone substitutes in treating tibial plateau fractures published on PubMed,Web of Science,CNKI,Wanfang and other databases from January 2005 to August 2022 were searched by computer. Literature screening and data extraction were performed according to randomized controlled trial(RCT),and the quality of RCT were evaluated by using intervention meta-analysis criteria in Cochrane manual. Meta-analysis of joint depression,secondary collapse rate of articular surface,blood loss,operative time and infection rate between two methods were performed by Rev Man 5.3 software. RESULTS: Seven RCT studies (424 patients) were included,296 patients in bone replacement group and 128 patients in autograft group. Operative time [MD=-16.79,95%CI(-25.72,-7.85),P=0.000 2] and blood loss[MD=-70.49,95%CI(-79.34,-61.65),P<0.000 01] between two groups had statistically differences,while joint depression[MD=-0.17,95%CI(-0.91,0.58),P=0.66],secondary collapse rate of joint surface[RR=-0.74, 95%CI(0.35,1.57),P=0.43],infection rate [RR=1.21,95%CI(0.31,4.70),P=0.78] between two groups had no differences. CONCLUSION: The effects of bone substitute and autograft for the treatment of tibial plateau fracture have similar effects in terms of joint depression,secondary articular surface collapse rate and infection rate. However,compared with autologous bone transplantation,bone replacement could reduce blood loss and shorten operation time.

[Meta-analysis of the role of fibular fixation in tibiofibular fractures].

OBJECTIVE: To compare the role and importance of fibular fixation in tibiofibular fractures by Meta-analysis. METHODS: The literature related to the comparison of the efficacy of fixation of the fibula with or without fixation on the treatment of tibiofibular fractures was searched through the databases of China Knowledge Network, Wipu, Wanfang, The Cochrane Library, Web of science and Pubmed, and statistical analysis was performed using RevMan 5.3 software. The rates of malrotation, rotational deformity, internal/external deformity, anterior/posterior deformity, non-union, infection, secondary surgery and operative time were compared between the fibula fixation and non-fixation groups. RESULTS: A total of 11 publications were included, six randomised controlled trials and five case-control trials, eight of which were of high quality. A total of 813 cases were included, of which 383 were treated with fibula fixation and 430 with unfixed fibulae.Meta-analysis results showed that fixation of the fibulae in the treatment of tibiofibular fractures reduced the rates of postoperative rotational deformity[RR=0.22, 95%CI(0.10, 0.45), P<0.000 1] and internal/external deformity[RR=0.34, 95%CI(0.14, 0.84), P=0.02] and promoted fracture healing [RR=0.76, 95%CI(0.58, 0.99), P=0.04]. In contrast, the rates of poor reduction [RR=0.48, 95% CI(0.10, 2.33), P=0.36], anterior/posterior deformity[RR=1.50, 95%CI(0.76, 2.96), P=0.24], infection[RR=1.43, 95%CI(0.76, 2.72), P=0.27], secondary surgery[RR=1.32, 95%CI(0.82, 2.11), P=0.25], and operative time[MD=10.21, 95%CI(-17.79, 38.21), P=0.47] were not statistically significant (P>0.05) for comparison. CONCLUSION: Simultaneous fixation of the tibia and fibula is clinically more effective in the treatment of tibiofibular fractures.

Research progress and hotspots on macrophages in osteoarthritis: A bibliometric analysis from 2009 to 2022.

BACKGROUND: Macrophages in the synovium, as immune cells, can be polarized into different phenotypes to play an anti-inflammatory role in the treatment of osteoarthritis. In this study, bibliometric methods were used to search the relevant literature to find valuable research directions for researchers and provide new targets for osteoarthritis prevention and early treatment. METHODS: Studies about the application of macrophages in the treatment of osteoarthritis were searched through the Web of Science core database from 2009 to 2022. Microsoft Excel 2019, VOSviewer, CiteSpace, R software, and 2 online websites were used to analyze the research status and predict the future development of the trend in research on macrophages in osteoarthritis. RESULTS: The number of publications identified with the search strategy was 1304. China and the United States ranked first in the number of publications. Shanghai Jiao Tong University ranked first in the world with 37 papers. Osteoarthritis and Cartilage was the journal with the most publications, and "exosomes," "stem cells," "macrophage polarization," "regeneration," and "innate immunity" may remain the research hotspots and frontiers in the future. CONCLUSION: The findings from the global trend analysis indicate that research on macrophages in the treatment of osteoarthritis is gradually deepening, and the number of studies is increasing. Exosomes may become a research trend and hotspot in the future.

[Meta-analysis of different joint interfaces in total hip arthroplasty under long-term follow-up].

OBJECTIVE: To compare the long-term follow-up effect and complications of ceramic on ceramic (CoC) interface and ceramic on polyethyleneon ceramic (CoP) interface in primary total hip arthroplasty, and provide clinical evidence. METHODS: Search PubMed, EMBase, the CoChrane Library databases, Web of science, Wanfang database, and CNKI from January 2000 to September 2021, screening and inclusion of randomized controlled trials (RCTs) comparing the long-term efficacy and complications of CoC interface and CoP interface in total hip arthroplasty. Literature screening, quality evaluation and data extraction were carried out according to the inclusion and exclusion criteria, using Review Manager 5.3 statistical software. The software was used to perform statistical analysis on joint function, revision, prosthesis fracture, abnormal joint noise, and prosthesis wear rate after CoC or CoP. RESULTS: Seven RCTs studies were included, including 390 cases of hips with CoC artificial joints and 384 cases of hips with CoP artificial joints. The long-term joint function improvement of CoC and CoP artificial joints was similar and there was no significant differences, with an average difference was MD=0.63, 95%CI=(-1.81, 3.07), P=0.61. About the postoperative complications, CoC artificial joints have higher incidence rate of abnormal joint noise, with odds ratio (OR)=11.05, 95%CI=(2.04, 59.84), P=0.005. CoP artificial joints wear faster, with an average MD=-87.11, 95%CI=(-114.40, -59.82), P<0.000 1. There was no significant difference between the two groups in the replacement-related complications such as joint dislocation, prosthesis loosening, osteolysis, and the rate of prosthesis revision caused by various reasons. CONCLUSION: The clinical function results and complications of CoC artificial joints are comparable to those of CoP artificial joints. Although CoP artificial joint prosthesis has a faster wear rate, it does not affect joint function and increase complications, and there is no abnormal joint noise. CoC is expensive and the long-term efficacy is equivalent to CoP. Clinicians should consider cost performance when choosing CoC.

[Platelet-rich plasma vs corticosteroid for treatment of rotator cuff tendinopathy:a Meta-analysis].

OBJECTIVE: To explore clinical effects regrarding functional recovery, pain relief, and range of motion of shoulder of platelet-rich plasma (PRP) injection and corticosteroid(CS) injection in treating rotator cuff tendinopathy. METHODS: Randomized controlled trials (RCT) of PRP injection and CS injection in Cochrane Library, EMBASE(Excerpta Medica Database), PebMed, China knowledge Network(CNKI) and Wanfang database were searched from building database to April 20, 2022. According to inclusion and exclusion criteria, literature screening, data extraction and quality evaluation were carried out between two independent researchers, and extracted data were statistically analyzed by Review Manager 5.4.1 software. Short-term (3-6 weeks), medium-term (8-12 weeks) and long-term (≥24 weeks) visual analogue score (VAS), American Shoulder and Elbow Surgeons (ASES) score, Xi'an Western Ontario Rotator Cuff Index (WORC) and shoulder range of motion (ROM) were compared between two groups. RESULTS: Totally 7 RCT were included with 379 patients, 188 patients in PRP group and 191 patients in CS group. Meta analysis results showed there were no significant difference in VAS, ASES and WORC between short-term group and medium-term group(P>0.05). During long-term follow-up, there were significant differences in ASES score[MD=7.1, 95%CI(2.06, 12.14), P=0.006] and VAS [MD=-1.55, 95%CI(-2.65, 0.55), P=0.002]. There was no significant difference in shoulder ROM between two groups(P>0.05). CONCLUSION: For patients with shoulder cuff tendon disease, there are no significant difference in pain relief and functional recovery during short and medium-term follow-up period. However, RPR injection showed advantages over corticosteroid injection in terms of functional recovery and pain relief during long-term follow-up. There is no significant difference in shoulder range of motion between two groups during the whole follow-up period.

Effectiveness of antibiotics loaded bone cement in primary total knee arthroplasty: A systematic review and meta-analysis.

INTRODUCTION: The application of antibiotics loaded bone cement (ALBC) in the revision of failed total knee arthroplasty (TKA) has been widely accepted to reduce risk of peri-prosthetic infection. However, the prophylactic use of ALBC in primary TKA remains controversial. This study was aimed to identify the prophylactic effect on peri-prosthetic infection and safety of ALBC in primary TKA. HYPOTHESIS: The application of ALBC could reduce the risk of peri-prosthetic infection in primary TKA. MATERIALS AND METHODS: Electronic platforms including PubMed, EMBASE, and CENTRAL were retrieved to identify studies comparing outcomes of prophylactic ALBC and plain cement in primary TKA. For outcomes reported as dichotomous variable and continuous variable, risk ratio (RR) and weighted mean difference (WMD) as well as their 95% confidence intervals (95% CI) were selected as the effect sizes for pooling. While for those outcomes reported the adjusted effect sizes such as odds ratio (OR, derived from multivariate logistic regression), and hazard ratio (HR, derived from multivariate COX proportional hazard model), the reported effect sizes were selected for pooling. RESULTS: A total of 17 studies with 2,074,844 patients (1,093,920 in ALBC group and 980,924 in plain cement group) were eligible for final inclusion. No significant difference was found between ALBC and plain cement groups both for the unadjusted (RR=1.02, 95% CI: 0.86∼1.21, p=0.832) and adjusted (OR=0.94, 95% CI: 0.76∼1.17, p=0.596) peri-prosthetic infection rate. ALBC application was related to significantly increased length of hospital stay (WMD=0.13, 95% CI: 0.10∼0.17, p<0.001). There was no significance on the difference of operation related adverse events between two groups (RR=1.31, 95% CI: 0.68∼2.52, p=0.420). Significantly increased risks of acute renal failure and readmission, and temporarily increased ototoxicity in ALBC group were reported in one of the primary study. DISCUSSION: There is no sufficient evidence supporting decreased peri-prosthetic infection rate with ALBC application in primary TKA. What's more, it must be taken into consideration about the safety and added cost of additional impregnated antibiotics. LEVEL OF EVIDENCE: III; meta-analysis.

[META analysis of mobile bearing and fixed bearing unicondyle replacement for medial knee osteoarthritis].

OBJECTIVE: To evaluate of the clinical effects of mobile-bearing(MB) and fixed-bearing(FB) unicompartmental knee arthroplasty(UKA) in the treatment of knee osteoarthritis by Meta-analysis. METHODS: The literature on FB UKA and MB UKA in the treatment of knee osteoarthritis in PubMed, CNKI, Wanfang, Cochrane and EMBASE database were searched by computer from January 2000 to April 2020. According to the inclusion and exclusion criteria, two authors were selected independently and the selected literature was evaluated for quality.After literature data were extracted, Review Manager 5.3 software was used to analyze knee function score, postoperative activity, revision rate, polyethylene wear rate, pad dislocation, aseptic loosening, postoperative pain, knee arthritis progression, mechanical shaft alignment of lower limbs, and imaging clarity line respectively. RESULTS: A total of 13 literatures were included in this meta-analysis, including 2 randomized controlled studies and 11 cohort studies. A total of 1 871 patients were included, including 913 in FB UKA group and 958 in MB UKA group. Meta analysis results showed that:postoperative knee joint function score[MD=-0.84, 95%CI(-1.46, -0.21), P=0.008] and postoperative knee joint range of motion [MD=-1.51, 95%CI(-2.84, -0.18), P=0.03] in FB UKA group were better than those in MB UKA group. Compared with FB UKA group, MB UKA group had a higher lower limb mechanical axis alignment rate[OR=2.08, 95%CI(1.27, 3.39), P=0.003], and the wear rate of polyethylene [OR=0.11, 95%CI(0.01, 0.91), P=0.04] was lower. There were no differences between two groups in the renovation rate [OR=1.16, 95%CI(0.75, 1.80), P=0.50), liner dislocation rate[OR=3.78, 95%CI(0.93, 15.29), P=0.06], aseptic loosening [OR=2.11, 95%CI(0.81, 5.51), P=0.13], postoperative pain[OR=1.13, 95%CI(0.37, 3.43), P=0.83], osteoarthritis progression[OR=1.28, 95%CI(0.67, 2.47), P=0.46)and imaging radiolucent line[OR=1.62, 95%CI(0.09, 30.22), P=0.75]. CONCLUSION: FB UKA has a higher postoperative functional score and range of motion.MB UKA has more advantages in the correction of lower limb mechanical axis, and the wear rate of polyethylene is also lower. There was no significant difference between the two groups in revision rate, dislocation of the liner, aseptic loosening, postoperative pain, progression of osteoarthritis, and postoperative translucency.