BACKGROUND:Because of its anti-inflammatory and antioxidant activities,Apelin-13 plays an effective role in the treatment of common clinical diseases such as neuroinflammation,cardiovascular injury and pneumonia.However,there is no relevant basic research on whether Apelin-13 also has a good effect in the treatment of inflammatory bone loss. OBJECTIVE:To explore the therapeutic effect and mechanism of Apelin-13 on inflammatory bone loss,in order to find potential drugs for the treatment of inflammatory bone loss. METHODS:(1)In vitro experiment:RAW264.7 cells were divided into three groups:control group,lipopolysaccharide group and treatment group.The control group was only added with DMEM complete medium;lipopolysaccharide group was added with lipopolysaccharide(100 ng/mL)induced inflammation DMEM medium;and the treatment group was added with 10 nmol/L Apelin-13+lipopolysaccharide induced inflammation DMEM medium.Then,24 hours after lipopolysaccharide induced inflammation,western blot was used to detect the marker proteins inducible nitric oxide synthase and CD86 of M1 macrophages,and cell immunofluorescence was extracted to detect the expression of inducible nitric oxide synthase.Finally,the same amount of receptor activator of nuclear factor-κB ligand(RANKL;50 ng/ml)was added to the control group,lipopolysaccharide group and treatment group to induce osteoclasts.The results of osteoclast induction were evaluated by tartrate-resistant acid phosphatase staining and F-actin staining after 6 days of induction.(2)In vivo experiment:Eighteen male C57bl/6 mice were randomly divided into three groups:sham group,lipopolysaccharide group and treatment group.The sham group received intraperitoneal injection of 0.1 mL of PBS;the lipopolysaccharide group was injected with 0.1 mL of PBS diluent containing lipopolysaccharide(5 mg/kg);and the treatment group was injected with 0.1 mL of PBS diluent containing lipopolysaccharide(5 mg/kg)+Apelin-13(100 μg/kg).After 7 days of continuous intraperitoneal injection,the mice in each group were killed on the 8th day,and two femurs of each mouse were collected.Half of them were scanned by micro-CT and analyzed by bone mineral density,and the other half were stained by hematoxylin-eosin staining RESULTS AND CONCLUSION:(1)In vitro experiment:Western blot results showed that the expressions of inducible nitric oxide synthase and CD86 in the lipopolysaccharide group were significantly higher than those in the control group,and Apelin-13 could significantly inhibit the M1 polarization of macrophages induced by lipopolysaccharide.Cell immunofluorescence results also showed that the expression of inducible nitric oxide synthase in the treatment group was lower than that in the lipopolysaccharide group.Besides,tartrate-resistant acid phosphatase staining and F-actin staining results showed that Apelin-13 inhibited the abnormal activation and bone resorption of lipopolysaccharide induced osteoclasts.(2)In vivo experiment:The results of micro-CT showed that systemic inflammation led to significant bone loss in the distal femur,while Apelin-13 could significantly inhibit bone loss in vivo.Hematoxylin-eosin staining results also showed that Apelin-13 could effectively alleviate inflammation induced bone loss in the distal femur of mice.To conclude,Apelin-13 can alleviate bone loss induced by systemic inflammation by inhibiting M1 polarization of macrophages,inhibiting abnormal activation of osteoclasts and bone resorption.

BACKGROUND:With the aging of the global population,the incidence rate of osteoporosis is also increasing.It is very important to further understand its pathogenesis and propose new therapeutic targets.Recent studies have shown that ferroptosis is closely related to the pathogenesis of some bone diseases,such as inflammatory arthritis,osteoporosis and osteoarthritis. OBJECTIVE:To summarize the previous studies on the mechanism of ferroptosis in osteoporosis,so as to provide new therapeutic ideas and potential therapeutic targets for osteoporosis. METHODS:The first author used the computer to search the documents published from 2000 to 2022 in CNKI,WanFang,VIP,PubMed and Web of Science with the key words of"ferroptosis,osteoporosis,osteoblasts,osteoclasts,iron chelators,reactive oxygen species,nuclear factor erythroid 2-related factor 2,heme oxygenase-1,glutathione peroxidase 4,review"in Chinese and English.A total of 70 articles were finally included according to the inclusion criteria. RESULTS AND CONCLUSION:Ferroptosis is significantly different from necrosis,apoptosis and autophagy.In terms of cell morphology and function,it does not have the morphological characteristics of typical necrosis,nor does it have the characteristics of traditional apoptosis,such as cell contraction,chromatin condensation,the formation of apoptotic bodies and the disintegration of cytoskeleton.Contrary to autophagy,ferroptosis does not form a classical closed bilayer membrane structure(autophagic vacuole).Morphologically,ferroptosis is mainly manifested by obvious contraction of mitochondria,increased membrane density,and reduction or disappearance of mitochondrial cristae,which are different from other cell death modes.Iron overload can destroy bone homeostasis by significantly inhibiting osteogenic differentiation and stimulating osteoclast formation,leading to osteoporosis.Iron overload interferes with the differentiation of stem cells to osteoblasts,leading to a weakened osteoblast function and further imbalance of bone metabolism in the body,which eventually leads to osteoporosis.Stimulated by iron overload,osteoclast bone resorption is enhanced and bone loss exceeds new bone formation.Iron chelators have been proved to have osteoprotective effects by inhibiting osteoclast activity and stimulating osteogenic differentiation of osteoblasts.Its potential mechanism is related to inhibiting osteoclast differentiation and promoting osteoblast differentiation.Antioxidants can prevent reactive oxygen species production and inhibit bone absorption,thus improving bone metabolism and effectively preventing osteoporosis.

BACKGROUND:In addition to apoptosis,recent studies have discovered novel forms of programmed cell death in periprosthetic osteolysis,which is involved in regulating local chronic inflammation and the outcome of osteoblast and osteoclast under pathological conditions.This has an important value for the treatment and prognosis of periprosthetic osteolysis. OBJECTIVE:To provide new ideas and strategies for the prevention and treatment of periprosthetic osteolysis by summarizing studies on the novel forms of programmed cell death. METHODS:The first author used the computer to search the articles published from 2005 to 2022.Chinese search terms"wear particles,periprosthetic osteolysis,programmed cell death,apoptosis,autophagy,pyroptosis,necrotizing apoptosis,iron death"were used to search the databases of CNKI,WanFang and VIP.English search terms"osteolysis,wear debris,wear particles,peri*prosthetic osteolysis,PPOL,aseptic loosening,autophagy,regulated cell death,programmed cell death,apoptosis,pyroptosis,autophagic cell death,autophagy,necroptosis,ferroptosis"were used for search in PubMed and Web of Science databases.A total of 68 articles were finally included according to the inclusion criteria. RESULTS AND CONCLUSION:(1)Inadequate or excessive activation of autophagy can cause cell death,inhibit bone formation,and promote bone resorption,leading to bone metabolism disorders and osteolysis.(2)Recent studies have paid close attention to pyroptosis in periprosthetic osteolysis,where the Nod-like receptor,pyrin containing 3 inflammasome plays an important role in local inflammation.Inhibiting pyroptosis can effectively alleviate osteolysis.(3)In vitro studies have shown that necroptosis can inhibit the formation and function of osteoblasts and osteoclasts,affecting the process of osteolysis and destruction.(4)Ferroptosis is the newest form of programmed cell death,which is regulated by complex signaling pathways and mechanisms,but is not yet fully understood.(5)Autophagy,pyroptosis,necroptosis,and ferroptosis play important roles in the development of periprosthetic osteolysis,and their associated signaling pathways and genes require further investigation.

Osteoarthritis(OA)is a chronic progressive osteoarthropathy in the elderly.Osteoclast activation plays a crucial role in the occurrence of subchondral bone loss in early OA.However,the specific mechanism of osteoclast differentiation in OA remains unclear.In our study,gene expression profiles related to OA disease progression and osteoclast activation were screened from the Gene Expression Omnibus(GEO)repository.GEO2R and Funrich analysis tools were employed to find differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses demonstrated that chemical carcinogenesis,reactive oxygen species(ROS),and response to oxidative stress were mainly involved in osteoclast differentiation in OA subchondral bone.Furthermore,fourteen DEGs that are associated with oxidative stress were identified.The first ranked differential gene,heme oxygenase 1(HMOX1),was selected for further validation.Related results showed that osteoclast activation in the pathogenesis of OA subchondral bone is accompanied by the downregulation of HMOX1.Carnosol was revealed to inhibit osteoclastogenesis by targeting HMOX1 and upregulating the expression of antioxidant protein in vitro.Meanwhile,carnosol was found to alleviate the severity of OA by inhibiting the activation of subchondral osteoclasts in vivo.Our research indicated that the activation of osteoclasts due to subchondral bone redox dysplasia may serve as a significant pathway for the advancement of OA.Targeting HMOX1 in subchondral osteoclasts may offer novel insights for the treatment of early OA.

OBJECTIVE: To investigate the surgical technique and the short-term effectivenss of lateral unicompartmental knee arthroplasty (LUKA) through lateral approach in the treatment of valgus knee and to calculate the maximum value of the theoretical correction of knee valgus deformity. METHODS: A retrospective analysis was performed on 16 patients (20 knees) who underwent LUKA and met the selection criteria between April 2021 and July 2022. There were 2 males and 14 females, aged 57-85 years (mean, 71.5 years). The disease duration ranged from 1 to 18 years, with an average of 11.9 years. Knee valgus was staged according to Ranawat classification, there were 6 knees of type Ⅰ, 13 knees of type Ⅱ, and 1 knee of type Ⅲ. All patients were assigned the expected correction value of genu valgus deformity by preoperative planning, including the correction value of lateral approach, intra-articular correction value, and residual knee valgus deformity value. The actual postoperative corrected values of the above indicators were recorded and the theoretical maximum correctable knee valgus deformity values were extrapolated. The operation time, intraoperative blood loss, incision length, hospital stay, hip-knee-ankle angle (HKA), mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibia angle (mMPTA), joint line convergence angle (JLCA), posterior tibial slope (PTS), range of motion (ROM), Hospital for Special Surgery (HSS) score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score were also recorded for effectiveness evaluation. RESULTS: The patients' incision length averaged 13.83 cm, operation time averaged 85.8 minutes, intraoperative blood loss averaged 74.9 mL, and hospital stay averaged 6.7 days. None of the patients suffered any significant intraoperative neurological or vascular injuries. All patients were followed up 10-27 months, with a mean of 17.9 months. One patient with bilateral knee valgus deformities had intra-articular infection in the left knee at 1 month after operation and the remaining patients had no complication such as prosthesis loosening, dislocation, and infection. The ROM, HSS score, and WOMAC score of knee joint significantly improved at each time point after operation when compared to those before operation, and the indicators further improved with time after operation, the differences were all significant ( P<0.05). Imaging measurement showed that HKA, mLDFA, JLCA, and PTS significantly improved at 3 days after operation ( P<0.05) except for mMPTA ( P>0.05). Postoperative evaluation of the knee valgus deformity correction values showed that the actual intra-articular correction values ranged from 0.54° to 10.97°, with a mean of 3.84°. The postoperative residual knee valgus deformity values ranged from 0.42° to 5.30°, with a mean of 3.59°. The actual correction values of lateral approach ranged from 0.21° to 12.73°, with a mean of 4.26°. CONCLUSION LUKA through lateral approach for knee valgus deformity can achieve good early effectiveness. Preoperative planning can help surgeons rationally allocate the correction value of knee valgus deformity, provide corresponding treatment strategies, and the maximum theoretical correction value of knee valgus deformity can reach 25°.
Male ; Female ; Humans ; Arthroplasty, Replacement, Knee/methods* ; Retrospective Studies ; Blood Loss, Surgical ; Osteoarthritis, Knee/surgery* ; Knee Joint/surgery*

Objective:To evaluate the feasibility and clinical outcomes of navigation-assisted total knee arthroplasty (TKA) using adjusted restricted kinematic alignment (arKA).Methods:Data of 14 consecutive cases of OrthoPilot navigation-assisted TKA using arKA from October 2019 to September 2021 were retrospectively analyzed, including 3 males and 9 females. The average age was 67.71±8.96 years with mean body mass index (BMI) 25.94±3.12 kg/m 2. 27 consecutive patients who underwent navigation-assisted TKA using aMA during the same period were assessed as the control group. There were no significant differences in gender, age or BMI between the two groups. Intraoperative parameters including operative duration, tibia resection angle, frontal femoral angle, axial femoral angle, joint line translation, medial and lateral gap in extension and flexion position were recorded. Radiographic parameters including hip-knee-ankle (HKA) angle, coronal femoral component angle (cFCA), coronal tibial component angle (cTCA), sagittal femoral component angle (sFCA) and sagittal tibial component angle (sTCA) were measured. Functional outcomes were assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Hospital for Special Surgery (HSS) score. Surgery-related complications were recorded. Results:All cases were followed up. The mean follow-up of arKA group was 18.57±6.98 months and follow-up of aMA group was 22.15±4.91 months. The intraoperative tibial resection was 3.07°±1.00° in arKA group versus 0.67°±0.56° in aMA group ( P<0.05). The lateral cutting height of tibia was 9.07±1.82 mm in arKA group versus 6.89±2.94 mm in aMA group ( P<0.05). The lateral gap in flexion was 1.71±0.83 mm in arKA group versus 1.04±0.71 mm in aMA group ( P<0.05). The difference of medial-lateral flexion laxity was 1.14±0.86 mm in arKA group versus 0.41±0.75 mm in aMA group ( P<0.05). The postoperative HKA angle was 174.10°±1.63° in arKA group versus 177.12°±2.07° in aMA group ( P<0.05). The cTCA was 87.58°±0.85° in arKA group versus 89.14°±1.23° in aMA group ( P<0.05). The cFCA was 93.10°±1.75° in arKA group versus 90.41°±3.01° in aMA group ( P<0.05). There was no statistical difference between the two groups in sFCA (1.30°±0.82° vs. 1.56°±1.19°), sTCA (87.16°±0.95° vs. 87.79°±1.04°) and femoral notching (7.1% vs. 11.1%). The preoperative HSS score in arKA group was 46.07±4.68 and HSS score at 1 month postoperatively was 73.86±3.48 ( P<0.05). The preoperative HSS score in aMA group was 47.04±4.52 and HSS score at 1 month postoperatively was 74.04±3.57 ( P<0.05). There was no statistical difference between the two groups in WOMAC score (12.93±2.37 vs. 12.63±2.34) and HSS score (86.86±2.74 vs. 86.11±2.95) at 6 months postoperatively. 2 cases (14.3%) in arKA group and 5 cases (18.5%) in aMA group had deep venous thrombosis (χ 2=0.12, P=0.733). Conclusion:Navigation-assisted TKA using arKA offers the surgeons a new alignment option for severe knee deformity with satisfactory clinical outcomes, the arKA technique has advantages in soft tissue protection and gap balance regulation compared to aMA technique.

Objective:To explore the early learning curve of OrthoPilot navigation assisted total knee arthroplasty (TKA).Methods:Data of 40 consecutive cases of OrthoPilot navigation assisted TKA completed by the same surgical team in our department were retrospectively analyzed. According to the operation order, 40 cases were divided into the original phase group (the first 20 cases) and the subsequent phase group (the second 20 cases). In original phase group, the average age was 69.85±6.86 years with mean body mass index 24.10±2.88 kg/m 2, preoperative HSS score 48.80±5.33, preoperative knee ROM 87.05°±11.02° and preoperative alignment deviation of 7.40°±5.59°. In subsequent phase group, the average age was 66.65±7.92 years with mean body mass index 22.85±3.15 kg/m 2, preoperative HSS score 49.00±5.47, preoperative knee ROM 85.80°±11.65° and preoperative alignment deviation of 8.22°±5.21°. Perioperative data such as operative duration, incision length, hemoglobin drop and postoperative hospital stay, radiographic outcomes including hip-knee-ankle angle (HKAA), mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), sagittal femoral component angle (sFCA), sagittal tibial component angle (sTCA), joint line convergence angle (JLCA), and functional scores were compared between the two groups. Results:All 40 cases were followed up for 24-33 months (mean, 27.38± 2.73 months). No severe postoperative complications such as infection and loosening occurred during the follow-up. The mean operative duration was 112.35±25.49 min in original phase group versus 82.10±10.96 min in subsequent phase group ( P< 0.05). The durations of tibial cutting was 11.95±3.27 min in original phase group versus 7.35±2.23 min in subsequent phase group ( P< 0.05); the femoral planning + cutting time was 20.95±6.91 min in original phase group versus 16.60±4.78 min in subsequent phase group, and trial + prosthesis implantation time was 39.65±7.72 min in original phase group versus 25.10±5.72 min in subsequent phase group,which was significantly higher in original phase group. There was no significant difference in other perioperative data such as incision length, hemoglobin drop and postoperative hospital stay between the two groups. As for radiographic outcomes, there was no statistical difference between the two groups in the postoperative angular deviation of HKAA (0.70°±0.80° vs. 0.80°±1.06°), mLDFA (0.89°±0.91° vs. 1.00°±0.86°), mMPTA (0.77°±0.53° vs. 0.76°±1.03°), sFCA (0.73°±0.48° vs. 0.87°±1.06°), sTCA (0.95°±0.58° vs. 1.16°±1.14°) and JLCA (0.27°±0.25° vs. 0.39°±0.18°). In original phase group, the HSS scores preoperative and 3 days postoperative were 48.80±5.33 and 60.05±5.10 respectively, and those in subsequent phase were 49.00±5.47 and 60.75±4.47 respectively, and both groups showed satisfactory functional recovery. There was no significant difference in HSS scores at all follow-up time points between two phases, as well as ROM (113.20°±9.82° vs. 113.50°±12.44°) and FJS-12 scores (78.00°±10.98° vs. 76.65°±10.29°) at 2 years postoperatively. Conclusion:In this study, we described a time-related early learning curve for OrthoPilot navigation-assisted TKA, in which the operative duration tended to be shorter after the first 20 cases. However, benefiting from good operative accuracy and repeatability, satisfactory radiographic and functional outcomes can be obtained in early stage of the learning curve.

Objective:To compare the prosthesis locations and postoperative hip functions between supercapsular percutaneously-assisted total hip (SuperPATH) approach and traditional posterolateral approach (PLA) in total hip arthroplasty.Methods:A retrospective analysis was conducted of the 107 patients who had undergone unilateral total hip arthroplasty at Department of Orthopedic Surgery, The First Affiliated Hospital to Soochow University from August 2016 to February 2019. They were divided into 2 groups according to their surgical approaches. In the SuperPATH group of 54 cases, there were 20 males and 34 females with an age of (64.3±9.1) years; in the PLA group of 53 cases, there were 20 males and 33 females with an age of (62.2±10.6) years. The 2 groups were compared in terms of abduction angle, ratio of abduction angle to safety zone, anteversion angle, ratio of anteversion angle to safety zone, retroversion angle, incidence of retroversion, and differences in eccentricity and lower limb length on the first day after operation, and Harris hip scores at 1 week, 3 months and the last follow-up postoperatively. Their complications were also recorded as well.Results:There were no statistically significant differences in the preoperative general data between the 2 groups, showing comparability ( P>0.05). The postoperative imaging data were complete for the 107 patients who had been followed up satisfactorily for 14 to 36 months (average, 25 months). The SuperPATH group had significantly larger retroversion angle (13.6°±9.6°) and incidence of retroversion (18.5%, 10/54), significantly smaller difference in eccentricity [0.26 (0.13,0.49) cm], and significantly higher Harris hip score [(74.8±7.8) points] at one week after surgery than those in the PLA group [3.0°±1.0°; 5.7%, 3/53; 0.38 (0.13,0.70) cm; (72.0±6.7) points] ( P<0.05). There were no statistically significant differences between the 2 groups in abduction angle, ratio of abduction angle to safety zone, anteversion angle, ratio of anteversion angle to safety zone, difference in lower limb length, or Harris hip scores at 3 months or the last follow-up postoperatively (all P>0.05). Follow-ups in both groups observed no more than one case of dislocation which responded to manual reduction. Conclusion:The minimally invasive SuperPATH approach may obtain better femoral eccentricity and higher early hip function scores than the traditional posterolateral approach, but may lead to a higher incidence of retroversion after prosthesis placement.

The posterior iliac crescent fracture is a typical manifestation of injury to the posterior ring in the lateral extrusion type Ⅱ of the Young-Burgess classification for pelvic fractures. In recent years, scholars have put forward new ideas about injury mechanisms, imaging features, classification, pelvic stability and surgical procedures of this type of fractures. Minimally invasive reduction and internal fixation with percutaneous screws has been used more and more widely in the treatment of posterior iliac crescent fractures. This article reviews the clinical features, classification, treatment, problems and prospects of these fractures.

Objective To investigate the preliminary clinical efficacy of percutaneous plate internal fixation with fracture reduction oriented forcep in the treatment of lower humeral fractures. Methods A retrospective case control study was conducted to analyze the clinical data of 46 patients with lower humeral fractures admitted to Wuzhong People's Hospital of Suzhou from October 2013 to March 2015. There were 25 males and 21 females, aged 19-76 years, with an average age of 45. 7 years. A total of 22 patients ( percutaneous group) were treated with minimally invasive percutaneous internal fixation with self-developed fracture reduction oriented forcep according to the dimensionality reduction method (DRM). The other 24 patients (control group) were treated with open reduction internal fixation. The length of incision, operation time, intraoperative blood loss, fracture healing time, the American Foot and Ankle Surgery Association ( AOFAS ) ankle-hindfoot score at the last follow-up, and postoperative complications were compared between the two groups. Results All patients were followed up for 12-24 months, with an average of 14. 6 months. There were statistically significant differences between percutaneous group and control group in incision length [(7.1 ±0.8)cm vs. (8.8 ±0.7)cm, operation time [(32.5 ±4.9)min vs. (39.2 ±4.3)min], intraoperative blood loss [(8.0 ±2.7) ml vs. (31.0 ± 11.4)ml], and fracture healing time (16.4 ±2.3)weeks vs. (19.5 ±2.9)weeks], respectively (all P<0.05). In percutaneous group, the AOFAS ankle-hindfoot score was (92.3 ±5.9)points (range, 75-99 points ) , and the overall results were good and excellent in 21/22 ( 96％) including excellent results in 18 patients, good in three, fair in one and poor in 0. In control group, the AOFAS ankle-hindfoot score was (91.8 ±4.9)points (range, 76-99 points), and the overall results were good and excellent in 23/24 (96％) including excellent results in 20 patients, good in three, fair in one and poor in 0. There was no significant difference in the excellent and good rate between two groups (P>0. 05). Poor wound healing was observed in one patient in control group. No case of nonunion was found in either group. Conclusion For lower humeral fractures, the percutaneous plate internal fixation with fracture reduction oriented forcep has the characteristics of simple operation, shortened operation time, reduced soft tissue injury and blood loss, and quick healing of the fracture, which is worthy of clinical application.