ObjectiveTo review the role of chemokine networks in regulating synovial macrophage heterogeneity during osteoarthritis (OA) pathogenesis. Methods A review of recent literature on the developmental origins of OA synovial macrophages, single-cell transcriptomic characteristics, and chemokine signaling pathways was conducted to systematically summarize the functional phenotypes, immunometabolic mechanisms, and regulatory roles of synovial macrophages in OA. Results OA has been established as a low-grade, chronic inflammatory disease affecting the entire joint. Single-cell and spatial transcriptomic studies have confirmed that synovial macrophages are not a single population but rather a dynamic continuum of different functional states, including steady-state barrier-like, inflammatory amplification, fibrosis-related, and lipid-enriched phenotypes. Chemokine networks play a dual crucial role in this process: on one hand, chemokine gradients guide the migration of peripheral monocytes to the synovium and influence their differentiation; on the other hand, synovial macrophages in different states secrete chemokines, mediating transcellular communication between the synovium, subchondral bone, and peripheral nerves. This process reshapes the microenvironment and amplifies local inflammation and pain signals. Current therapeutic strategies targeting macrophage metabolic reprogramming and chemokine axis blockade show potential clinical applications. Conclusion Re-examining the interaction between synovial macrophages and microenvironment and constructing an integrated perspective of “lineage-state-chemokine network” will help to understand the pathological progression mechanism of OA. In the future, it is expected to provide a theoretical framework and intervention targets for the precise immune regulation of OA and the development of new targeted drugs by accurately analyzing the spatiotemporal evolution of macrophage subsets and their interaction with chemokines.
ObjectiveTo summarize the role of chondrocyte mitochondrial homeostasis imbalance in the pathogenesis of osteoarthritis (OA) and analyze its application prospects. Methods The recent literature at home and abroad was reviewed to summarize the mechanism of mitochondrial homeostasis imbalance, the relationship between mitochondrial homeostasis imbalance and the pathogenesis of OA, and the application prospect in the treatment of OA. Results Recent studies have shown that mitochondrial homeostasis imbalance, which is caused by abnormal mitochondrial biogenesis, the imbalance of mitochondrial redox, the imbalance of mitochondrial dynamics, and damaged mitochondrial autophagy of chondrocytes, plays an important role in the pathogenesis of OA. Abnormal mitochondrial biogenesis can accelerate the catabolic reaction of OA chondrocytes and aggravate cartilage damage. The imbalance of mitochondrial redox can lead to the accumulation of reactive oxygen species (ROS), inhibit the synthesis of extracellular matrix, induce ferroptosis and eventually leads to cartilage degradation. The imbalance of mitochondrial dynamics can lead to mitochondrial DNA mutation, decreased adenosine triphosphate production, ROS accumulation, and accelerated apoptosis of chondrocytes. When mitochondrial autophagy is damaged, dysfunctional mitochondria cannot be cleared in time, leading to ROS accumulation, which leads to chondrocyte apoptosis. It has been found that substances such as puerarin, safflower yellow, and astaxanthin can inhibit the development of OA by regulating mitochondrial homeostasis, which proves the potential to be used in the treatment of OA. Conclusion The mitochondrial homeostasis imbalance in chondrocytes is one of the most important pathogeneses of OA, and further exploration of the mechanisms of mitochondrial homeostasis imbalance is of great significance for the prevention and treatment of OA.
In combination with the national health informatization construction in UK during the past ten years, this article introduced the resource construction of decision making knowledge library like British Electronic Medicine Library Clinical Pathway Database and NHS Evidence, as well as the function and application of clinical decision support system (CDSS) like PRODIGY, medical knowledge map and so on, discussed the development characteristics and construction experiences of British health decision support system (HDSS). And aiming directly at Chinese specific circumstances, this article offered some suggestions on promoting China HDSS development, for instance, dynamically integrating CDSS with patients’ diagnosis and treatment procedure through the electronic medical record system, strengthening the resources construction of knowledge library, establishing localized clinical pathway, and so on.
Objective To investigate the regulatory role and molecular mechanisms of TSPAN9-mediated mitocytosis in an interleukin-1β (IL-1β)-induced rat chondrocyte senescence model, and to identify novel therapeutic targets for osteoarthritis (OA). MethodsPrimary knee articular chondrocytes were isolated from the cartilage of knee joints harvested from 1-week-old male Sprague-Dawley rats and maintained in culture. Cell viability was assessed using the cell counting kit 8 (CCK-8) assay, and cell-cycle distribution was analyzed by flow cytometry to determine the optimal concentration and exposure time of IL-1β for model induction, thereby establishing an in vitro chondrocyte senescence model [early-OA (E-OA), middle-OA (M-OA), late-OA (L-OA)] and grouped. Cellular senescence was evaluated by senescence-associated β-galactosidase (SA-β-gal) staining. Real-time quantitative PCR (qRT-PCR) was used to quantify the mRNA expression levels of senescence markers [cyclin-dependent kinase inhibitor 2A (Cdkn2a) and Cdkn1a], extracellular matrix (ECM) catabolic-anabolic genes [collagen type Ⅱ alpha 1 chain (Col2a1), Aggrecan (Acan), matrix metalloproteinase 13 (MMP-13), and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5)], and key mitocytosis-related genes [kinesin family member 5B (KIF5B), TSPAN9, and TSPAN4]. Mitochondrial ultrastructure and mitocytosis-related morphological features were examined by transmission electron microscopy, and changes in mitochondrial membrane potential were assessed using the JC-1 fluorescent probe. To activate TSPAN9 expression, chondrocytes were transduced with a TSPAN9-overexpressing lentivirus (LV-TSPAN9). The experiments included four groups: control group, M-OA group, lentivirus negative control group, and LV-TSPAN9 group. After confirming overexpression efficiency, differences in cellular senescence, mitochondrial homeostasis, and key ECM metabolic indices were compared among the groups. Results Using CCK-8 assays and cell-cycle analysis, the staged rat chondrocyte senescence model induced by IL-1β (5 ng/mL), and defined 12, 24, and 48 hours as the E-OA, M-OA, and L-OA senescence phenotypes were successfully established, respectively. Model validation demonstrated that, with prolonged induction, the proportion of SA-β-gal-positive cells increased markedly, mitochondrial membrane potential progressively declined (P<0.05), and mitochondrial ultrastructural damage became increasingly severe. qRT-PCR showed progressive upregulation of the senescence markers Cdkn2a and Cdkn1a, as well as the ECM catabolic genes MMP-13 and ADAMTS5 (P<0.05), together with sustained downregulation of the ECM anabolic genes Col2a1 and Acan (P<0.05). Notably, the key mitocytosis-related genes KIF5B, TSPAN4, and TSPAN9 displayed a biphasic pattern, with early compensatory upregulation followed by decompensatory decline at the middle-to-late stages. In the M-OA model, TSPAN9 overexpression markedly reversed these pathological changes, restored mitochondrial membrane potential (P<0.05), ameliorated the senescent phenotype and ECM metabolic imbalance, and significantly upregulated the expression of mitocytosis-related genes and proteins (P<0.05), with transmission electron microscope revealing morphological structures suggestive of mitocytosis-related events. Conclusion Impaired mitocytosis is an important pathological mechanism underlying IL-1β-induced chondrocyte senescence, and TSPAN9 overexpression may delay chondrocyte senescence by promoting mitocytosis in concert with KIF5B, thereby facilitating the clearance of damaged mitochondria and restoring intracellular homeostasis.
ObjectiveThis study was aimed to evaluate the clinical efficacy of mechanical thrombectomy using the AngioJet System for the treatment of lower extremity acute arterial embolism and thrombosis.MethodsThe clinical data of 20 patients with acute lower extremity arterial embolism and thrombosis admitted to the Department of Vascular Surgery in the People’s Hospital in Gansu Province where the author worked from September 2016 to March 2017, were retrospectively analyzed. All patients were treated with the AngioJet mechanical thrombectomy system. Clinical data of the patients were retrospectively collected. The clinical efficacy of AngioJet mechanical thrombectomy wasanalyzed.ResultsEighteen (90.0%) of the 20 patients successfully completed the mechanical thrombectomy by using the AngioJet System. The mean time for hospital stay and operation was (4.2±1.4) d and (1.3±0.4) h, respectively. The average doses of urokinase and heparin during operation were (35.80±12.30) ×104 U and (45.10±8.30) mg, respectively. Two patients received a complementary treatment of incision for removing the thrombus. Two patients received catheter-directed thrombolysis after the mechanical thrombectomy, 5 patients received bare-metal stent implantation after balloon expansion. Clinical success was in 16 cases. According to the Cooley standard, 10 patients were in excellent condition,6 in good condition, 2 in fair condition, and 2 in poor condition. There were 2 cases of distal arterial embolization,2 cases of antecardial discomfort of bradycardia, and 4 cases of bleeding at the puncture point, but no serious bleeding complications such as gastrointestinal and intracranial hemorrhage occurred. A total of 16 patients presented myoglobinuria during and after operation. All patients were followed up for 6–12 months. The results of ultrasound examination showed that the artery was patency in 15 cases. One patient died of myocardial infarction in 9 months after surgery,2 patients developed lower extremity ischemia symptoms again after surgery, and 2 patients had lower extremity ulcer caused by lower extremity ischemia symptoms. During the follow-up period, no lower limb necrosis, amputation, and death occurred in the remaining patients.ConclusionsThe AngioJet mechanical thrombectomy system is safe and effective. Combined with the use of catheter-directed thrombolysis and stent implantation, the AngioJet mechanical thrombectomy could lead to quick recovery of the perfusion of the lower extremity and improve the limb salvage rates, exhibiting excellent clinical value.
Objective To investigate the effectiveness of one-stage total knee arthroplasty (TKA) in the treatment of advanced active knee tuberculosis. Methods The clinical data of 38 patients with advanced active knee tuberculosis who received one-stage TKA between January 2011 and December 2020 were retrospectively analyzed. There were 20 males and 18 females. The age ranged from 20 to 84 years, with an average of 52.8 years. The body mass index ranged from 17 to 36 kg/m2, with an average of 23.05 kg/m2. The preoperative C reactive protein (CRP) was (23.49±4.72) mg/L, erythrocyte sedimentation rate (ESR) was (45.95±8.82) mm/1 h. The Hospital for Special Surgery (HSS) score was 48.8±9.1. During the operation, the infected lesions of the knee joint were completely removed, and the operative area was repeatedly soaked with 3% hydrogen peroxide solution and 0.5% povidone iodine solution. The intraoperative pathological examination confirmed the tuberculosis of the knee joint, and systemic anti-tuberculosis treatment was performed. The operation time, postoperative hospitalization stay, postoperative anti-tuberculosis chemotherapy time, and complications were recorded. CRP and ESR were recorded and compared before and after operation. Anteroposterior and lateral X-ray films of the knee joint were taken to evaluate whether the prosthesis had signs of loosening and sinking, and to determine whether there was recurrence of tuberculosis. The knee joint function was evaluated by HSS score. With treatment failure due to any reason as the end event, the survival time of prosthesis was analyzed by Kaplan-Meier survival curve. Results All operations were successfully completed without fracture, vascular and nerve injury, deep vein thrombosis, and other complications. All incisions healed by first intention after operation. The operation time ranged from 80 to 135 minutes, with an average of 102.76 minutes; postoperative hospitalization stay was 5-16 days, with an average of 9.7 days; the duration of postoperative anti-tuberculosis chemotherapy ranged from 1 to 18 months, and the median duration was 12 months. All 38 cases were followed up 3-133 months (mean, 63.7 months). At last follow-up, CRP was (4.88±1.24) mg/L and ESR was (13.00±2.97) mm/1 h, both of which were significantly lower than those before operation (t=20.647, P<0.001; t=20.886, P<0.001). During the follow-up, 3 patients (7.89%) had tuberculosis recurrence. Two patients had tuberculosis recurrence due to withdrawal of anti-tuberculosis chemotherapy at 1 and 2 months after operation, respectively. One patient was cured after debridement, preservation of prosthesis and anti-tuberculosis chemotherapy for 12 months, and 1 patient was cured after oral administration of anti-tuberculosis drugs for 12 months. Another 1 patient had recurrent tuberculosis and mixed infection (Corynebacterium gehreni) at 2 months after operation, and the infection was not controlled after debridement, and finally the thigh was amputated. Except for the patients with recurrent infection, no complications such as prosthesis loosening, periprosthetic fracture, and periprosthetic infection were found. At last follow-up, the HSS score of the knee joint was 86.8±4.8, and the knee joint function significantly improved when compared with that before operation (t=?31.198, P<0.001). Prosthesis survival time was (122.57±5.77) months [95%CI (111.25, 133.88) months], and the 10-year survival rate was 92.1%. Conclusion One-stage TKA combined with postoperative antituberculous chemotherapy in the treatment of advanced active knee tuberculosis can achieve satisfactory infection control and joint function.
Objective To explore the diagnostic efficacy of electrochemical detection of synovial fluid leukocyte esterase (LE) based on glucosyl ester for periprosthetic joint infection (PJI) in rabbits. Methods The enzyme kinetic parameters of the LE-catalyzed reaction based on glucosyl esters were determined electrochemically, and the charge-LE concentration relationship was plotted. Forty-eight healthy New Zealand rabbits were randomly divided into a sham-operation group (blank group), a knee joint metal prosthesis implantation group (control group), and a knee joint metal prosthesis implantation with PJI group (experimental group), with 16 rabbits in each group. The experimental group underwent intra-articular injection of 1×105 CFU/mL Staphylococcus aureus suspension at 7 days after right knee joint prosthesis implantation. The control group underwent intra-articular injection of 1 mL of sterile saline at 7 days after right knee joint prosthesis implantation. The blank group underwent right knee joint capsule incision and suture, followed by intra-articular injection of 1 mL of sterile saline 7 days later. The general condition of the animals was observed after operation. At 28 days after operation, imaging examination, microbiological examination, hematological test, and electrochemical detection of synovial fluid LE were performed. The area (AUC) under the receiver operating characteristic curve (ROC) was used to evaluate the sensitivity and specificity of LE-based detection of PJI. Results The Michaelis constant of the enzymatic reaction of LE catalyzing glucosyl ester was 7.335 mmol/L, and the maximum reaction rate of the enzymatic reaction was 63.750 μmol·L?1·min?1. The calibration curve regression equation for the charge difference (ΔQ)-LE concentration was C(LE)=0.7115ΔQ?14.75, with a determination coefficient R2 of 0.988 4 (95%CI: 0.5698, 0.8532, P<0.001). All animals survived to the end of the experiment. During the period, the experimental group showed signs of joint infection, and the microbiological test results were all positive. The other two groups had no related infection manifestations and the tests were negative. Imaging examination showed that the experimental prosthesis was stable in position, soft tissue swelling around the joint and mild deformation in the joint. There was no obvious swelling in the soft tissue around the joints in the other two groups, and the joints were in good alignment. Synovial fluid and hematological tests revealed that the experimental group exhibited significantly higher levels of LE, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood cell count (WBC), neutrophil count (Neu), and monocytes count (Mon) compared to both the control group and the blank group (P<0.05). Notably, ESR and Mon levels were significantly higher in the control group compared to the blank group (P<0.05). The mentioned indicators, with an AUC>0.9 (P<0.05), possess good diagnostic value for PJI. Among them, CPR and Neu exhibit the highest sensitivity, reaching 93.8%, while LE, ESR, and Mon demonstrate the highest specificity, reaching 100%. Conclusion Both synovial fluid LE and hematological testing exhibit good diagnostic efficacy in the rabbit PJI model, with the method based on electrochemical quantitative detection of glucose-based esters for LE demonstrating higher specificity, sensitivity, and accuracy.
Objective To explore the differences in gut microbiota diversity and structural characteristics among patients with periprosthetic joint infection (PJI), aseptic failure (AF), and osteoarthritis (OA), and to analyze the association between gut microbiota dysbiosis and the occurrence of PJI, thereby providing a new theoretical basis for elucidating the pathogenesis and treatment strategies of PJI in clinical practice. Methods The study enrolled patients with PJI and AF admitted between February 2024 and December 2024, as well as OA patients admitted in February 2024. A total of 52 PJI patients, 19 AF patients, and 29 OA patients who met the selection criteria were included in the analysis. Significant differences were observed among the three groups in terms of gender, age, surgical site, preoperative C-reactive protein levels, and erythrocyte sedimentation rate (P<0.05), while no significant difference was found in American Society of Anesthesiologists (ASA) classification and body mass index (P>0.05). Among the PJI patients, infection staging was as follows: 9 cases in the acute phase, 28 cases in the delayed phase, and 15 cases in the chronic phase; 23 cases were accompanied by sinus tract formation. Fecal samples were collected at different time points: for the PJI group, samples were obtained preoperatively and on postoperative days (7±1) and (14±1); for the AF group, preoperatively and on postoperative day (7±1); and for the OA group, preoperatively only. Metagenomics next-generation sequencing were employed to analyze gut microbiota α-diversity indices (ACE index, Chao1 index, Shannon index, Simpson index, and observed_species index) and differential bacterial genera (screened using the LEfSe algorithm). Results Analysis of gut microbiota diversity showed that the preoperative α-diversity indices (ACE index, Chao1 index, Shannon index, Simpson index, and observed_species index) in the PJI group were significantly lower than those in AF group and OA group (P<0.05). Compared with the AF group on postoperative day (7±1), the α-diversity indices in the PJI group on postoperative day (7±1) were lower, but the difference was not significant (P>0.05); by postoperative day (14±1), these indices further decreased, and the difference was significant (P<0.05). In the PJI group, no significant difference was observed in any of the indices across different time points postoperatively (P>0.05). Analysis of gut microbiota structural characteristics revealed that the PJI group exhibited characteristic dysbiosis both before and after operation. Preoperatively, the PJI group was characterized by enrichment of Pseudomonadota (relative abundance 13.19%), Enterobacteriaceae (Escherichia 3.26%, Klebsiella 1.90%), and opportunistic pathogens such as Enterococcus faecium (0.43%), while the relative abundances of Firmicutes (51.83%) and Bifidobacterium (0.24%) decreased. Postoperatively, the α-diversity in the PJI group further declined, with increased relative abundances of Escherichia and Klebsiella, and the relative abundance of Firmicutes decreased to 40.24%. LEfSe analysis of preoperative gut microbiota composition between the PJI group and AF group indicated that the AF group was predominated by Firmicutes, Bifidobacterium, and Roseburia preoperatively, with greater postoperative microbial stability compared to the PJI group. Conclusion Patients with PJI exhibited a gut microbiota profile characterized by reduced diversity and enrichment of opportunistic pathogens. Postoperative antibiotic treatment further aggravated this dysbiosis, providing new clinical insights into the role of gut microbiota imbalance in the pathogenesis and progression of PJI.
ObjectiveTo evaluate the efficacy and safety of intracavitary treatment for iliac vein compression syndrome（IVCS）with acute lower extremity deep venous thrombosis (DVT).MethodsThe clinical data of 57 patients with IVCS and lower extremity DVT, who undergoing with stent implantation, balloon expansion and Angiojet rheolytic thrombectomy from June 2015 to June 2018, were retrospectively analyzed. The effect of treatment was evaluated by the changes of thigh circumference difference between the affected side and the healthy side, and the thrombosis clearance rate in the operating. In addition, the incidence of post-thrombotic syndrome (PTS) and stent patency rate were analyzed after long-term follow-up based on the change of Villaita scale score and ultrasound examination of lower extremity veins.ResultsThe success rate of surgical technique was 100%, and there was no pulmonary embolism during operating and postoperative. Lower extremity deep vein thrombosis clearance levels Ⅲ 48 cases (84.2%), Ⅱ 9 cases (15.8%), the changes of thigh circumference difference between the affected side and the healthy side from preoperative (5.8±1.7) cm to (3.7±1.0) cm. One year follow-up after operation, the primary patency rate of stent was 86.0% and PTS occurred in 8 patients (14.0%).ConclusionStent implantation, balloon expansion and Angiojet rheolytic thrombectomy for IVCS with acute lower extremity DVT is a safe, effective with low incidence of complications and efficient thrombus clearance.
The incidence of venous thromboembolism (VTE) is relatively high in the elderly population, and the disability, mortality, and medical expenses caused by VTE are also high. However, in a large number of randomized controlled and non-randomized controlled studies related to VTE, sufficient attention has not been paid to the elderly population with multiple underlying diseases. Therefore, the vast majority of research results recommended by VTE guidelines come from younger patients and healthy elderly people, at the same time, most relevant VTE prevention and treatment guidelines or consensus are formulated for hospitalized patients, and for non-hospital elderly populations such as home and elderly care institutions that truly need attention and risk of VTE, their recommended opinions are uncertain. In this context, the Peripheral Vascular Disease Management Branch of the Chinese Geriatrics Society has developed a consensus among Chinese experts on the prevention and treatment of VET in the elderly, based on evidence-based evidence such as domestic and foreign guidelines and relevant research.