OBJECTIVE: To introduce the etiology and prevention of bone cement implantation syndrome (BCIS). METHODS: The literature about BCIS at home and abroad in recent years was extensively reviewed, and the incidence, clinical manifestations, etiology, and prevention of BCIS were summarized and analyzed. RESULTS: The clinical manifestations of BCIS are diverse. The etiology of BCIS is not completely clarified, and it may be related to circulating methyl methacrylate-mediated model, embolus-mediated model, histamine release and hypersensitivity response, complement activation and multimodal model. BCIS prevention begins with the identification of high-risk patients in preoperative evaluation and communication between surgeon and anesthesiologist about the choice of implant type, surgical procedure, and technique to minimize the risk of cardiovascular complications in high-risk patients with multiple or severe risk factors or comorbidities. Preoperative assessment and optimization of a patient's cardiovascular reserve is also critical to prevent BCIS. CONCLUSION BCIS is a possible complication after hip joint arthroplasty, and its pathogenesis needs to be further research in order to provide new ideas for prevention and treatment.
Humans ; Bone Cements/adverse effects* ; Postoperative Complications/etiology* ; Arthroplasty, Replacement, Hip/adverse effects* ; Risk Factors ; Syndrome ; Methylmethacrylate/adverse effects*

Objective:To elucidate the molecular mechanisms through which high-dose dexamethasone exerts long-term effects on bone marrow mesenchymal stem cells (BMSCs), specifically its role in suppressing osteogenic differentiation, accelerating cellular senescence, triggering the senescence-associated secretory phenotype (SASP), and inducing apoptosis.Methods:Primary rat BMSCs were isolated and treated with high-dose dexamethasone (1×10 -4 mol/L) to establish the experimental group, while untreated cells served as the control. The gene and protein expression levels of osteogenic markers, bone alkaline phosphatase (bALP) and Runt-related transcription factor 2 (Runx2), were analyzed in both groups. Cellular senescence was evaluated using senescence-associated β-galactosidase (SA-β-gal) staining. The expression of senescence-related markers (P16 and P21), components of the senescence-associated secretory phenotype (SASP), including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and interferon (IFN)-γ, as well as apoptosis-related proteins (Bcl-2, Bax, and Cleaved-Caspase-3), and key factors of the Nrf2/HO-1 signaling pathway were assessed at both transcriptional and protein levels using qRT-PCR, immunofluorescence, and Western-blot analyses. These comprehensive evaluations aimed to determine the senescent state, apoptotic features, and alterations in osteogenic differentiation of BMSCs. Results:Following treatment with dexamethasone and subsequent withdrawal, both qRT-PCR and Western blot analyses indicated a significant reduction in the expression of the osteogenic markers bALP and Runx2 at both mRNA and protein levels. The proportion of SA-β-gal positive cells was markedly higher in the dexamethasone group (74.33%±6.89%) than in the control group (20.30%±1.57%, t=17.300, P<0.001). qRT-PCR analysis revealed upregulated mRNA expression of the senescence-related genes P16 and P21 after dexamethasone treatment, which was further supported at the protein level by immunofluorescence showing increased P21 expression. Western-blot results confirmed that protein expression levels of P16 and P21 were significantly elevated in the dexamethasone group (7.025±0.255 and 6.362±0.456, respectively) compared with the control group (1.016±0.115 and 0.816±0.172; both P<0.05). Furthermore, gene expression levels of the senescence-associated secretory phenotype (SASP) factors TNF-α and IL-1β were significantly increased (TNF-α: 3.539±0.599 vs. 0.742±0.095; IL-1β: 4.469±0.331 vs. 0.799±0.175; both P<0.05), and their protein expression was consistently upregulated as validated by Western-blot. Additionally, protein expression levels of TNF-α, IL-1β, and IFN-γ were significantly higher in the dexamethasone-treated group (3.476±0.932 vs. 0.945±0.095; 4.111±0.220 vs. 0.762±0.105; 2.155±0.240 vs. 0.656±0.104; all P<0.05).Western-blot analysis also demonstrated that protein expression of Nrf2 and HO-1 was significantly suppressed in the dexamethasone group (0.21±0.07 and 0.19±0.06, respectively) compared with the control group (1.13±0.15 and 0.92±0.21; P<0.05). Moreover, Western-blot analysis revealed that the expression levels of the pro-apoptotic proteins Bax and Cleaved-Caspase-3 were significantly up, regulated in the dexamethasone, treated BMSCs (Bax: 3.673±0.397 vs. 0.453±0.111; Cleaved-Caspase-3: 3.863±0.399 vs. 0.465±0.057), while the expression of the anti-apoptotic protein Bcl-2 was markedly down, regulated (0.959±0.073 vs. 2.126±0.195), with all differences being statistically significant ( P<0.05). Conclusions:High-dose dexamethasone treatment of BMSCs, followed by withdrawal of dexamethasone, induces cellular senescence and enhances the expression of the senescence-associated secretory phenotype (SASP) through suppression of the Nrf2/HO-1 signaling pathway. Concurrently, it promotes apoptosis by activating the mitochondrial apoptotic pathway, collectively leading to impaired osteogenic differentiation of BMSCs.

Objective:To explore the early- to mid-term therapeutic efficacy of using porous-coated metaphyseal sleeves to reconstruct severe bone defects in revision total knee arthroplasty (rTKA).Methods:A retrospective analysis was conducted of the clinical data of the 39 patients (40 knees) who had undergone rTKA by porous-coated metaphyseal sleeve reconstruction at Department of Orthopaedics, West China Hospital, Sichuan University between May 2017 and September 2023. The cohort included 6 males (6 knees) and 33 females (34 knees), with an age of (67.0±9.7) years. The revision was to cure periprosthetic infection after TKA in 12 knees, to correct prosthesis loosening in 19 knees, to treat periprosthetic fracture in 4 knees, to stabilize postoperative joint instability in 4 knees, and to manage postoperative joint stiffness in 1 knee. All patients underwent standard revision procedures, including removal of the original prosthesis, management of bone defects, implantation of revision prosthesis, and adjustment of ligamentous balance and fixation. The patients' surgical time, intraoperative blood loss, incidence of complications, as well as visual analogue scale (VAS), knee range of motion, and Hospital for Special Surgery (HSS) knee joint scores at the last follow-up were recorded.Results:The surgical time was (2.7±0.8) hours, and intraoperative blood loss (337.5±165.4) mL for this cohort. All the 39 patients were followed up for (4.8±2.1) years after surgery. At the last follow-up, their VAS pain score was 2.0 (1.0, 2.0) points, their knee range of motion reached 116.3°±12.2°, and their total score, pain score, and function score of the HSS system were respectively 87.0 (82.8, 89.3) points, 25.0 (22.8, 29.0) points, and 61.0 (60.0, 62.0) points, all showing statistically significant improvements compared with their preoperative values [(6.8±1.7) points, 70.4°±15.2°, (43.1±9.6) points, (9.3±3.1) points, and (33.8±10.1) points] ( P<0.05). In all patients, incisions healed at one stage after surgery, and no complications such as deep vein thrombosis or neurovascular injury occurred. Complications included popliteal artery thrombosis in 1 patient (1 knee) immediately after surgery, acute infection in 1 patient (1 knee) at 3 years after surgery, and periprosthetic fracture due to a traffic accident in 1 patient (1 knee) at 4 years after surgery, and distal prosthesis-related pain in 3 patients (3 knees). Conclusion:Use of porous-coated metaphyseal sleeves in rTKA to reconstruct severe bone defects exhibits favorable early- to mid-term therapeutic outcomes.

Objective:To elucidate the molecular mechanisms through which high-dose dexamethasone exerts long-term effects on bone marrow mesenchymal stem cells (BMSCs), specifically its role in suppressing osteogenic differentiation, accelerating cellular senescence, triggering the senescence-associated secretory phenotype (SASP), and inducing apoptosis.Methods:Primary rat BMSCs were isolated and treated with high-dose dexamethasone (1×10 -4 mol/L) to establish the experimental group, while untreated cells served as the control. The gene and protein expression levels of osteogenic markers, bone alkaline phosphatase (bALP) and Runt-related transcription factor 2 (Runx2), were analyzed in both groups. Cellular senescence was evaluated using senescence-associated β-galactosidase (SA-β-gal) staining. The expression of senescence-related markers (P16 and P21), components of the senescence-associated secretory phenotype (SASP), including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and interferon (IFN)-γ, as well as apoptosis-related proteins (Bcl-2, Bax, and Cleaved-Caspase-3), and key factors of the Nrf2/HO-1 signaling pathway were assessed at both transcriptional and protein levels using qRT-PCR, immunofluorescence, and Western-blot analyses. These comprehensive evaluations aimed to determine the senescent state, apoptotic features, and alterations in osteogenic differentiation of BMSCs. Results:Following treatment with dexamethasone and subsequent withdrawal, both qRT-PCR and Western blot analyses indicated a significant reduction in the expression of the osteogenic markers bALP and Runx2 at both mRNA and protein levels. The proportion of SA-β-gal positive cells was markedly higher in the dexamethasone group (74.33%±6.89%) than in the control group (20.30%±1.57%, t=17.300, P<0.001). qRT-PCR analysis revealed upregulated mRNA expression of the senescence-related genes P16 and P21 after dexamethasone treatment, which was further supported at the protein level by immunofluorescence showing increased P21 expression. Western-blot results confirmed that protein expression levels of P16 and P21 were significantly elevated in the dexamethasone group (7.025±0.255 and 6.362±0.456, respectively) compared with the control group (1.016±0.115 and 0.816±0.172; both P<0.05). Furthermore, gene expression levels of the senescence-associated secretory phenotype (SASP) factors TNF-α and IL-1β were significantly increased (TNF-α: 3.539±0.599 vs. 0.742±0.095; IL-1β: 4.469±0.331 vs. 0.799±0.175; both P<0.05), and their protein expression was consistently upregulated as validated by Western-blot. Additionally, protein expression levels of TNF-α, IL-1β, and IFN-γ were significantly higher in the dexamethasone-treated group (3.476±0.932 vs. 0.945±0.095; 4.111±0.220 vs. 0.762±0.105; 2.155±0.240 vs. 0.656±0.104; all P<0.05).Western-blot analysis also demonstrated that protein expression of Nrf2 and HO-1 was significantly suppressed in the dexamethasone group (0.21±0.07 and 0.19±0.06, respectively) compared with the control group (1.13±0.15 and 0.92±0.21; P<0.05). Moreover, Western-blot analysis revealed that the expression levels of the pro-apoptotic proteins Bax and Cleaved-Caspase-3 were significantly up, regulated in the dexamethasone, treated BMSCs (Bax: 3.673±0.397 vs. 0.453±0.111; Cleaved-Caspase-3: 3.863±0.399 vs. 0.465±0.057), while the expression of the anti-apoptotic protein Bcl-2 was markedly down, regulated (0.959±0.073 vs. 2.126±0.195), with all differences being statistically significant ( P<0.05). Conclusions:High-dose dexamethasone treatment of BMSCs, followed by withdrawal of dexamethasone, induces cellular senescence and enhances the expression of the senescence-associated secretory phenotype (SASP) through suppression of the Nrf2/HO-1 signaling pathway. Concurrently, it promotes apoptosis by activating the mitochondrial apoptotic pathway, collectively leading to impaired osteogenic differentiation of BMSCs.

Objective:To explore the early- to mid-term therapeutic efficacy of using porous-coated metaphyseal sleeves to reconstruct severe bone defects in revision total knee arthroplasty (rTKA).Methods:A retrospective analysis was conducted of the clinical data of the 39 patients (40 knees) who had undergone rTKA by porous-coated metaphyseal sleeve reconstruction at Department of Orthopaedics, West China Hospital, Sichuan University between May 2017 and September 2023. The cohort included 6 males (6 knees) and 33 females (34 knees), with an age of (67.0±9.7) years. The revision was to cure periprosthetic infection after TKA in 12 knees, to correct prosthesis loosening in 19 knees, to treat periprosthetic fracture in 4 knees, to stabilize postoperative joint instability in 4 knees, and to manage postoperative joint stiffness in 1 knee. All patients underwent standard revision procedures, including removal of the original prosthesis, management of bone defects, implantation of revision prosthesis, and adjustment of ligamentous balance and fixation. The patients' surgical time, intraoperative blood loss, incidence of complications, as well as visual analogue scale (VAS), knee range of motion, and Hospital for Special Surgery (HSS) knee joint scores at the last follow-up were recorded.Results:The surgical time was (2.7±0.8) hours, and intraoperative blood loss (337.5±165.4) mL for this cohort. All the 39 patients were followed up for (4.8±2.1) years after surgery. At the last follow-up, their VAS pain score was 2.0 (1.0, 2.0) points, their knee range of motion reached 116.3°±12.2°, and their total score, pain score, and function score of the HSS system were respectively 87.0 (82.8, 89.3) points, 25.0 (22.8, 29.0) points, and 61.0 (60.0, 62.0) points, all showing statistically significant improvements compared with their preoperative values [(6.8±1.7) points, 70.4°±15.2°, (43.1±9.6) points, (9.3±3.1) points, and (33.8±10.1) points] ( P<0.05). In all patients, incisions healed at one stage after surgery, and no complications such as deep vein thrombosis or neurovascular injury occurred. Complications included popliteal artery thrombosis in 1 patient (1 knee) immediately after surgery, acute infection in 1 patient (1 knee) at 3 years after surgery, and periprosthetic fracture due to a traffic accident in 1 patient (1 knee) at 4 years after surgery, and distal prosthesis-related pain in 3 patients (3 knees). Conclusion:Use of porous-coated metaphyseal sleeves in rTKA to reconstruct severe bone defects exhibits favorable early- to mid-term therapeutic outcomes.

OBJECTIVE: To summarize research progress on application of Cup-cage reconstruction in revision of chronic pelvic discontinuity (CPD) in patients undergoing total hip arthroplasty (THA). METHODS: Relevant literature at home and abroad in recent years was reviewed to summarize the principles of the Cup-cage reconstruction, preoperative patient assessment, intraoperative skills, clinical and radiological effectiveness, limitations, and postoperative complications. RESULTS: For the treatment of CPD, the Cup-cage reconstruction achieved long-term acetabular cup bone ingrowth, CPD healing, and biologic fixation of the prosthesis by restoring pelvic continuity. Preoperative evaluation of the surgical site and general condition is necessary. The main intraoperative objectives are to reconstruct pelvic continuity, restore the center of rotation of the hip, and avoid neurovascular injury. Current studies have demonstrated significant clinical and radiological effectiveness as well as acceptable prosthesis survival rates after operation. Nevertheless, there is a lack of evidence regarding the staging of CPD, the optimal surgical approach and internal fixation, and the factors influencing postoperative prosthesis survival remain undefined. CONCLUSION Cup-cage reconstruction can be an effective treatment for CPD after THA, but there is still a need to explore CPD staging, Cup-cage approach and internal fixation, and influencing factors on prosthesis survival.
Humans ; Arthroplasty, Replacement, Hip/methods* ; Hip Prosthesis ; Acetabulum/surgery* ; Reoperation ; Plastic Surgery Procedures/methods* ; Prosthesis Failure ; Postoperative Complications/etiology* ; Hip Joint/surgery*

OBJECTIVE: To review the role of dendritic cells (DC) in immune metabolism of rheumatoid arthritis (RA). METHODS: Literature on the role of DC in the immune metabolism of RA was extensively reviewed in recent years, and the metabolic characteristics of RA, the role of DC in RA, the correlation between the immune metabolism of DC and pathogenesis of RA, and the treatment were summarized and analyzed. RESULTS: DC promotes the progression of RA under hypoxia, increased glycolysis, inhibition of oxidative phosphorylation, and decreased lipid metabolism. Moreover, many DCs (especially conventional DC and monocyte-derived DC) have different functions and phenotypic characteristics in RA, which are closely related to the occurrence and development of RA. CONCLUSION DC plays an important role in the immune metabolism of RA, and immunometabolism therapy based on DC can provide targeted therapy for the treatment of RA.
Dendritic Cells/immunology* ; Arthritis, Rheumatoid/immunology* ; Humans ; Glycolysis ; Oxidative Phosphorylation ; Lipid Metabolism ; Animals

Objective:To analyze the clinical efficacy of internal fixation and prosthesis revision in the treatment of periprosthesis fracture after total knee arthroplasty.Methods:A total of 35 patients (35 knees) with periprosthetic fractures after total knee arthroplasty were retrospectively analyzed from January 2008 to January 2022 in the Department of Orthopaedics, West China Hospital, Sichuan University, including 13 males and 22 females, aged 71.4±4.1 years (range, 62-81 years). Left knee 19 cases, right knee 16 cases. There were 20 cases of Rorabeck type II and 15 cases of Rorabeck type III. The initial replacement was performed using a fixed platform post-stabilized knee prosthesis, which was fixed with bone cement. Patients with Rorabeck type II were treated with internal fixation alone (internal fixation group) and patients with Rorabeck type III underwent revision with replacement prosthesis (revision group). The Hospital for Special Surgery (HSS) score, range of motion (ROM) of knee joint, alignment of lower extremity and incidence of postoperative complications were compared between the two groups.Results:All patients successfully completed the operation and were followed up for 5.2±3.6 years (range, 1-12 years). Intraoperative blood loss was 680±102 ml (range, 420-1100 ml). The operative time in the internal fixation group was 105±17 min, which was less than 140±21 min in the revision group, and the difference was statistically significant ( t=-5.450, P<0.001). There was no complication of nerve or blood vessel injury during the operation. Five cases in the internal fixation group had unsatisfactory lower extremity force lines (>3° deviation from normal) after surgery, and all lower extremity force lines in the revision group were satisfied, and the difference in the satisfaction rate of lower extremity force lines between the two groups was not statistically significant ( P=0.057). The fracture healing time, knee ROM and HSS scores at the last follow-up were 5.1±1.3 months, 86°±5° and 84±5 in the internal fixation group and 4.8±1.5 months, 83°±6° and 82±4 in the revision group. One case in the revision group was diagnosed postoperatively with periprosthetic infection with pathogen culture suggestive of Candida albicans, recurrent anterior knee sinus tracts and patellar ectasia, which progressed to osteomyelitis, and mid-thigh amputation was performed 1 year after revision. Conclusion:The stability of prosthesis is an important reference for the treatment of periprosthetic fractures after total knee arthroplasty. Strong internal fixation in patients with unloosened prosthesis and revision with replacement of prosthesis in patients with loose prosthesis can achieve good knee joint function.

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

Effective bone repair and regeneration is crucial for treating skeletal tissue defects, including osteonecrosis, nonunion fractures, osteoporosis, and various other bone deficiencies. Exosomes, as cellular secretory vesicles, are pivotal in mediating intercellular communication through their cargo of proteins, lipids, and nucleic acids. Mesenchymal stem cell-derived exosomes, in particular, have emerged as promising agents in bone repair and regeneration, showing potential for practical application and clinical translation. Nonetheless, their functional capacity and therapeutic efficacy require enhancement. This review delineates exosome optimization strategies aimed at augmenting secretion and functionality, alongside the incorporation of exosome-functionalized biomaterials for bone healing. Evidence indicates that physical stimulation, molecular interventions, and small-molecule or biomaterial stimuli are effective in increasing exosome output. Moreover, engineering exosomes and their parental cells can further potentiate their therapeutic function. The amalgamation of exosomes with biomaterials represents a burgeoning approach in bone tissue engineering, offering novel therapeutic avenues. This comprehensive analysis aims to guide future applications and the clinical adoption of exosomes in bone tissue restoration.