A Smartphone Application-Based Remote Rehabilitation System for Post-Total Knee Arthroplasty Rehabilitation: A Randomized Controlled Trial.

BACKGROUND: Remote rehabilitation after total knee arthroplasty has gradually gained popularity in recent years. This study aimed to determine whether smartphone application-based remote rehabilitation could outperform home-based rehabilitation and outpatient guidance in terms of 12-week outcomes following primary unilateral total knee arthroplasty. METHODS: Patients who underwent primary unilateral total knee arthroplasty were recruited and randomly divided into a telerehabilitation group and a control group. A total of 100 patients were examined, with 50 each assigned to the telerehabilitation and control groups. In the telerehabilitation group, a telerehabilitation application was installed on the smartphones of the participants to allow postdischarge guidance. The primary outcomes were knee range of motion (ROM) at 12 weeks postoperatively. Secondary outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index, Knee Society Score, The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), Five Times Sit-to-Stand Test (5xSST), Single-Leg Stance Test (SLST), satisfaction, rehabilitation costs, complication rate, and 90-day readmission rate. All outcomes were collected at 2, 6, and 12 weeks after surgery. RESULTS: At 12 weeks postoperatively, the telerehabilitation patients significantly outperformed the controls in terms of knee ROM (124 ± 8.7 versus 119 ± 5.5 P = .01), SF-36 (physiological function) (61.5 ± 20.3 versus 45.5 ± 18.1 P = .000), SF-36 (role-physical) (49.3 ± 41.5 versus 27.7 ± 28.9 P = .012), SLST (13.0 ± 9.1 versus 9.1 ± 5.9 P = .026), and 5xSST (17.7 ± 4.3 versus 19.4 ± 3.5 P = .043). No significant differences were found between groups in the Western Ontario and McMaster Universities Osteoarthritis Index score, Knee Society Score, rehabilitation costs, 90-day readmission rate, or incidence of adverse events. CONCLUSION: Our study showed that smartphone app-based remote rehabilitation worked better than home-based rehabilitation with outpatient guidance in terms of short-term results in ROM, SLST, and 5xSST.

LSD1-Demethylated LINC01134 Confers Oxaliplatin Resistance Through SP1-Induced p62 Transcription in HCC.

BACKGROUND AND AIMS: Oxaliplatin (OXA) is one of the most common chemotherapeutics in advanced hepatocellular carcinoma (HCC), the resistance of which poses a big challenge. Long noncoding RNAs (lncRNAs) play vital roles in chemoresistance. Therefore, elucidating the underlying mechanisms and identifying predictive lncRNAs for OXA resistance is needed urgently. METHODS: RNA sequencing (RNA-seq) and fluorescence in situ hybridization (FISH) were used to investigate the OXA-resistant (OXA-R) lncRNAs. Survival analysis was performed to determine the clinical significance of homo sapiens long intergenic non-protein-coding RNA 1134 (LINC01134) and p62 expression. Luciferase, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and chromatin isolation by RNA purification (ChIRP) assays were used to explore the mechanisms by which LINC01134 regulates p62 expression. The effects of LINC01134/SP1/p62 axis on OXA resistance were evaluated using cell viability, apoptosis, and mitochondrial function and morphology analysis. Xenografts were used to estimate the in vivo regulation of OXA resistance by LINC01134/SP1/p62 axis. ChIP, cell viability, and xenograft assays were used to identify the demethylase for LINC01134 up-regulation in OXA resistance. RESULTS: LINC01134 was identified as one of the most up-regulated lncRNAs in OXA-R cells. Higher LINC01134 expression predicted poorer OXA therapeutic efficacy. LINC01134 activates anti-oxidative pathway through p62 by recruiting transcription factor SP1 to the p62 promoter. The LINC01134/SP1/p62 axis regulates OXA resistance by altering cell viability, apoptosis, and mitochondrial homeostasis both in vitro and in vivo. Furthermore, the demethylase, lysine specific demethylase 1 (LSD1) was responsible for LINC01134 up-regulation in OXA-R cells. In patients with HCC, LINC01134 expression was positively correlated with p62 and LSD1 expressions, whereas SP1 expression positively correlated with p62 expression. CONCLUSIONS: LSD1/LINC01134/SP1/p62 axis is critical for OXA resistance in HCC. Evaluating LINC01134 expression in HCC will be effective in predicting OXA efficacy. In treatment-naive patients, targeting the LINC01134/SP1/p62 axis may be a promising strategy to overcome OXA chemoresistance.

Hematopoietic cell kinase enhances osteosarcoma development via the MEK/ERK pathway.

Osteosarcoma (OS) is a sarcoma with high rates of pulmonary metastases and mortality. The mechanisms underlying tumour generation and development in OS are not well-understood. Haematopoietic cell kinase (HCK), a vital member of the Src family of kinase proteins, plays crucial roles in cancer progression and may act as an anticancer target; however, the mechanism by which HCK enhances OS development remains unexplored. Therefore, we investigated the role of HCK in OS development in vitro and in vivo. Downregulation of HCK attenuated OS cell proliferation, migration and invasion and increased OS cell apoptosis, whereas overexpression of HCK enhanced these processes. Mechanistically, HCK expression enhanced OS tumorigenesis via the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway; HCK upregulation increased the phosphorylation of MEK and ERK and promoted epithelial-mesenchymal transition, with a reduction in E-cadherin in vitro. Furthermore, HCK downregulation decreased the tumour volume and weight in mice transplanted with OS cells. In conclusion, HCK plays a crucial role in OS tumorigenesis, progression and metastasis via the MEK/ERK pathway, suggesting that HCK is a potential target for developing treatments for OS.

What Is the Optimal Timing for Reading the Leukocyte Esterase Strip for the Diagnosis of Periprosthetic Joint Infection?

BACKGROUND: The leucocyte esterase (LE) strip test often is used to diagnose periprosthetic joint infection (PJI). In accordance with the manufacturer's directions, the LE strip test result is read 3 minutes after exposing it to joint fluid, but this has not been supported by robust research. Moreover, we have noted that the results of the LE strip test might change over time, and our previous studies have found that centrifugation causes the results of the LE strip test to degrade. Still, there is no evidence-based recommendation as to when to read the LE strip test to maximize diagnostic accuracy, in general, and the best reading times for the LE strip test before and after centrifugation need to be determined separately, in particular. QUESTIONS/PURPOSES: (1) What is the optimal timing for reading LE strip test results before centrifugation to diagnose PJI? (2) What is the optimal timing for reading LE strip test results after centrifugation to diagnose PJI? METHODS: This study was a prospective diagnostic trial. In all, 120 patients who were scheduled for revision arthroplasty and had signs of infection underwent joint aspiration in the outpatient operating room between July 2018 and July 2019 and were enrolled in this single-center study. For inclusion, patients must have had a diagnosis of PJI or nonPJI, valid synovial fluid samples, and must not have received antibiotics within 2 weeks before arthrocentesis. As such, 36 patients were excluded; 84 patients were included for analysis, and all 84 patients agreed to participate. The 2018 International Consensus Meeting Criteria (ICM 2018) was used for the classification of 49 patients with PJI (score ≥ 6) and 35 without PJI (score ≤ 2). The classification was used as the standard against which the different timings for reading LE strips were compared. All patients without PJI were followed for more than 1 year, during which they did not report the occurrence of PJI. All patients were graded against the diagnostic criteria regardless of their LE strip test results. In 83 patients, one drop of synovial fluid (50 µL) was applied to LE strips before and after centrifugation, and in one patient (without PJI), the sample was not centrifuged because the sample volume was less than 1.5 mL. The results of the strip test were read on an automated colorimeter. Starting from 1 minute after centrifugation, these strips were automatically read once every minute, 15 times (over a period of 16 minutes), and the results were independently recorded by two observers. Results were rated as negative, ±, 1+, and 2+ upon the machine reading. Grade 2+ (dark purple) was used as the threshold for a positive result. An investigator who was blinded to the study performed the statistics. Optimal timing for reading the LE strip before and after centrifugation was determined by using receiver operative characteristic (ROC) analysis. The specificity, sensitivity, and positive predictive and negative predictive values were calculated for key timepoints. RESULTS: Before centrifugation, the area under the curve was the highest when the results were read at 5 minutes (0.90 [95% CI 0.83 to 0.98]; sensitivity 0.88 [95% CI 0.75 to 0.95]; specificity 0.89 [95% CI 0.72 to 0.96]). After centrifugation, the area under the curve was the highest when the results were read at 10 minutes (0.92 [95% CI 0.86 to 0.98]; sensitivity 0.65 [95% CI 0.50 to 0.78]; specificity 0.97 [95% CI 0.83 to 1.00]). CONCLUSION: The LE strip test results are affected by time and centrifugation. For samples without centrifugation, we found that 5 minutes after application was the best time to read LE strips. We cannot deny the use of centrifuges because this is an effective way to solve the sample-mingling problem at present. We recommend 10 minutes postapplication as the most appropriate time to read LE strips after centrifugation. Multicenter and large-sample size studies are warranted to further verify our conclusion. LEVEL OF EVIDENCE: Level II, diagnostic study.

Activator of thyroid and retinoid receptor increases sorafenib resistance in hepatocellular carcinoma by facilitating the Warburg effect.

Sorafenib resistance is a major challenge in the therapy for advanced hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms of HCC resistance to sorafenib remain unclear. Activator of thyroid and retinoid receptor (ACTR, also known as SRC-3), overexpressed in HCC patients, plays an important oncogenic role in HCC; however, the link between ACTR and sorafenib resistance in HCC is unknown. Our study demonstrated that ACTR was one of the most upregulated genes in sorafenib-resistant HCC xenografts. ACTR increases sorafenib resistance through regulation of the Warburg effect. ACTR promotes glycolysis through upregulation of glucose uptake, ATP and lactate production, and reduction of the extracellular acidification and the oxygen consumption rates. Glycolysis regulated by ACTR is vital for the susceptibility of HCC to sorafenib in vitro and in vivo. Mechanistically, ACTR knockout or knockdown decreases the expression of glycolytic enzymes. In HCC patients, ACTR expression is positively correlated with glycolytic gene expression and is associated with poorer outcome. Furthermore, ACTR interacts with the central regulator of the Warburg effect, c-Myc, and promotes its recruitment to glycolytic gene promoters. Our findings provide new clues regarding the role of ACTR as a prospective sensitizing target for sorafenib therapy in HCC.

Management of intraoperative acetabular fracture in primary total hip arthroplasty.

BACKGROUND: Intraoperative acetabular fracture(IAF) is a rare complication of primary total hip arthroplasty(THA). The previous reports have lacked a sufficiently large number of subjects to allow for an analysis of the causes and appropriate treatment of this problem. METHODS: Between 2015 to 2018, 4888 primary THA were enrolled. We retrospectively reviewed the records in our Total Joint Registry Database and found that 24 patients (24 hips) had sustained intraoperative acetabular fractures. Twenty-four patients(16 females and 8males)were all treated with a posterolateral approach using uncemented components. Twenty patients(83.3%)underwent supplemental screw fixation, of which 2 patients were treated with steel plate fixation. Two patients' femoral heads were used as a graft. In 4 patients(16.7%), the acetabular components were judged to be stable despite the fracture and no additional treatment was performed. All patients were evaluated clinically with Harris Hip Scores (HHS) and radiographically with serial X-rays which follow up for a mean period of 34.0 ± 12.6 months. We evaluated the anatomic locations, causes, treatments, and outcome of the fractures to study the treatment method and effect of intraoperative acetabular fracture during operation. RESULTS: The fracture rate associated with uncemented components was 0.49%. In 17(70.8%) of these patients, the fracture was noted during the impaction of the real acetabular component. Six patients(25%)with Ankylosing Spondylitis had fractures, 4 in the anterior wall, and 1 in the anterior column, because the patient with hip joint fusion needs a to pre-osteotomy before the dislocation. The HHS score increased from 30.8 ± 9.7 preoperatively to 90.2 ± 4.2 postoperatively. All the latest x-ray showed that the fracture did not move, and there is no translucent line formed in the acetabular cup bone interface. CONCLUSION: Intraoperative acetabular fractures are rare complications of THA, and most commonly occur during the implantation of the acetabular components. It is necessary to prevent the occurrence of fractures as much as possible even if the fractures are found during the operation. It should be noted that patients with ankylosing spondylitis involving hip joints during THA surgery must be careful to prevent IAFs during dislocation and pre-osteotomy.

Single-cell RNA-seq analysis reveals the progression of human osteoarthritis.

OBJECTIVES: Understanding the molecular mechanisms underlying human cartilage degeneration and regeneration is helpful for improving therapeutic strategies for treating osteoarthritis (OA). Here, we report the molecular programmes and lineage progression patterns controlling human OA pathogenesis using single-cell RNA sequencing (scRNA-seq). METHODS: We performed unbiased transcriptome-wide scRNA-seq analysis, computational analysis and histological assays on 1464 chondrocytes from 10 patients with OA undergoing knee arthroplasty surgery. We investigated the relationship between transcriptional programmes of the OA landscape and clinical outcome using severity index and correspondence analysis. RESULTS: We identified seven molecularly defined populations of chondrocytes in the human OA cartilage, including three novel phenotypes with distinct functions. We presented gene expression profiles at different OA stages at single-cell resolution. We found a potential transition among proliferative chondrocytes, prehypertrophic chondrocytes and hypertrophic chondrocytes (HTCs) and defined a new subdivision within HTCs. We revealed novel markers for cartilage progenitor cells (CPCs) and demonstrated a relationship between CPCs and fibrocartilage chondrocytes using computational analysis. Notably, we derived predictive targets with respect to clinical outcomes and clarified the role of different cell types for the early diagnosis and treatment of OA. CONCLUSIONS: Our results provide new insights into chondrocyte taxonomy and present potential clues for effective and functional manipulation of human OA cartilage regeneration that could lead to improved health.

miR-223-3p Inhibits Human Osteosarcoma Metastasis and Progression by Directly Targeting CDH6.

Cadherin-6 (CDH6) is aberrantly expressed in cancer and closely associated with tumor progression. However, the functions of CDH6 in human osteosarcoma and the molecular mechanisms underlying CDH6 in osteosarcoma oncogenesis remain poorly understood. In this work, we assessed the role of CDH6 in human osteosarcoma and identified that the expression of CDH6 was closely related with the overall survival and poor prognosis of osteosarcoma patients. MicroRNAs (miRNAs) have been implicated as important epigenetic regulators during the progression of osteosarcoma. Using dual-luciferase reporter assays, we showed that miR-223-3p suppresses CDH6 expression by directly binding to the 3' UTR of CDH6. miR-223-3p overexpression significantly inhibited cell invasion, migration, growth, and proliferation by suppressing the CDH6 expression in vivo and in vitro. Besides, CDH6 overexpression in the miR-223-3p-transfected osteosarcoma cells effectively rescued the inhibition of cell invasion, migration, growth, and proliferation mediated by miR-223-3p. Additionally, Kaplan-Meier analysis suggests that the expression of miR-223-3p predicts favorable clinical outcomes for osteosarcoma patients. Moreover, the expression of miR-223-3p was downregulated in osteosarcoma patients and was negatively associated with the expression of CDH6. Collectively, these data highlight that miR-223-3p/CDH6 axis is an important novel pleiotropic regulator and could early predict the metastatic potential in human osteosarcoma treatments.

Raddeanoside R13 inhibits breast cancer cell proliferation, invasion, and metastasis.

Pulsatilla chinensis is one of the 50 famous fundamental herbs used in traditional Chinese medicine. Saponins are the main components of P. chinensis. Although the anti-proliferative function of saponins has been established in plenty types of cancer, the role of saponins on tumor invasion and metastasis has not been reported, and the mechanisms of how saponins exert the anti-tumor functions are still poorly characterized. Here, we demonstrate that, in breast cancer (BC) cells, raddeanoside R13, a component of saponins extracted from P. chinensis, exhibits strong anti-proliferative and anti-metastasis ability, accompanied by cell cycle arrest, apoptosis, autophagy, and reversion of epithelial-mesenchymal transition (EMT). Raddeanoside R13 (R13) inhibits BC cell proliferation via the activation of G1/S checkpoint transitions, concomitant with a marked decrease of the positive cell cycle regulators, including cyclin D1, cyclin A, and cyclin B1. R13 induces BC cell apoptosis accompanied by the increased levels of cleaved PARP and caspase-3. R13 inhibits BC cell migration and invasion and regulates the expression of the markers of EMT, which plays a critical role in cancer cell migration and invasion. Moreover, R13 suppresses BC tumor growth and metastasis in nude mice. These data highlight the important role of R13 in BC cell proliferation and progression and suggest that R13 may be a useful drug for BC therapy.

Hematopoietic pre-B cell leukemia transcription factor interacting protein is overexpressed in gastric cancer and promotes gastric cancer cell proliferation, migration, and invasion.

Hematopoietic pre-B cell leukemia transcription factor interacting protein (HPIP) has been shown to play an important role in the development and progression of some cancers. However, the role of HPIP in gastric cancer (GC) is unclear. Here, we show that HPIP is upregulated in most GC patients and promotes GC cell proliferation, migration, and invasion. In GC patients, HPIP positively associates with tumor size and nodal metastasis, and negatively associates with tumor differentiation. Hematopoietic pre-B cell leukemia transcription factor interacting protein increases GC cell proliferation through activation of G1 /S and G2 /M cell cycle transitions, accompanied by a marked increase of the positive cell cycle regulators, including cyclin D1, cyclin A, and cyclin B1. Hematopoietic pre-B cell leukemia transcription factor interacting protein enhances GC cell migration and invasion, and modulates epithelial-mesenchymal transition, which plays a key role in cancer cell migration and invasion. These data underscore the critical role of HPIP in GC cell proliferation and progression and suggest that HPIP inhibition may be a useful therapeutic strategy for GC treatment.

HPIP is upregulated in liver cancer and promotes hepatoma cell proliferation via activation of G2/M transition.

Hematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein (HPIP) has been shown to play a role in cancer development and progression. However, the detailed role of HPIP in cancer cell growth and the exact mechanism by which HPIP regulates cancer cell proliferation remains unclear. Here, we report that HPIP is overexpressed in most of 328 liver cancer patients and regulates hepatoma cell proliferation through G2/M checkpoint activation. HPIP increased anchorage-dependent and -independent growth of human liver cancer cell lines. The amino acid region 531-631 of HPIP was important for its modulation of liver cancer cell growth. The increased effects of HPIP on liver cancer cell proliferation were associated with activation of the G2/M cell-cycle concomitant with a marked increase of cyclin B1 and the inhibition of the negative G2/M phase regulator GADD45α. HPIP knockdown dramatically suppressed the growth of HepG2 liver cancer cells in nude mice. These data highlight the important role of HPIP in liver cancer cell growth and suggest that HPIP may be a good target for liver cancer therapy.

Current advances of photobiomodulation therapy in treating knee osteoarthritis.

Knee osteoarthritis (KOA) is manifested by low-grade joint inflammation, irreversible cartilage degeneration, subchondral bone remodeling and osteophyte formation. It is one of the most prevalent degenerative diseases in the elderly. KOA usually results in chronic joint pain, physical impairment even disability bringing a huge socioeconomic burden. Unfortunately, there is so far no effective interventions to delay the progression and development of KOA. There is a pressing need for explorations and developments of new effective interventions. Photobiomodulation therapy (PBMT), also known as low-level light therapy (LLLT), has attracted widespread attention in treating KOA because it is drug-free, non-invasive, safe and useful with rarely reported side effects. It provides the biological stimulatory effects primarily by enhancing the activity of mitochondrial cytochrome c oxidase. This stimulation, in turn, fosters cell proliferation and tissue regeneration. In addition to this, the paper provides a concise overview of the light parameters and the effectiveness of PBMT when applied in the treatment of KOA patients in clinical settings. It also delves into the experimental evidence supporting the modulatory effects of PBMT and its potential underlying mechanisms in addressing synovitis, cartilage degeneration, and pain resolution.

Macrophage polarization in osteoarthritis progression: a promising therapeutic target.

Osteoarthritis (OA) is one of the leading causes of pain and disability in the elderly. Synovitis, cartilage destruction and osteophyte formation histologically manifest OA. Unfortunately, there is currently no effective therapy to delay its progression and the underlying mechanisms of OA require further exploration. Macrophage is a main cellular component of joint synovium. It is highly plastic and can be stimulated to polarize to different phenotypes, namely, the pro-inflammatory phenotype (M1) and the anti-inflammatory/tissue-repairing phenotype (M2). Ample evidence has demonstrated the vital roles of macrophages in the progression of OA. Imbalanced M1/M2 ratio is significantly related to OA severity indicating macrophage polarization might be a promising therapeutic target for OA. In this review, we summarized the involvements of polarized macrophages in synovitis, cartilage degradation, osteophyte formation and OA-related chronic pain. Promising therapies targeting macrophage polarization including the intra-articular cell/derivates-based therapy and the alternative non-invasive intervention such as photobiomodulation therapy were reviewed as well.

Using mesh in capsule anatomical reconstruction to enhance the stability of high-dislocation-risk hip arthroplasty: a randomized controlled trial.

BACKGROUND: Dislocation is a common complication after total hip arthroplasty (THA). This study aimed to compare the outcomes of mesh reconstruction versus conventional capsular repair in maintaining capsular integrity and preventing dislocation after THA. METHODS: This was a prospective, randomized controlled study of consecutive patients. A total of 124 high-dislocation-risk THAs were identified and randomized into two groups, one using mesh reconstruction and the other using the conventional capsular repair method. Perioperative data and radiological data were collected. Patients were followed up regularly. The main indices were the capsular integrity assessed by magnetic resonance imaging (MRI) and hip dislocation rate. The secondary indices included the Harris hip score (HHS), complications, and satisfaction. RESULTS: A total of 106 patients completed the follow-up and the average follow-up times were 19 ± 3.1 and 18 ± 3.3 months. The operation time of the mesh group was longer than that of the conventional group (P < 0.001). There were minor differences in acetabular anteversion and abduction angle, and the other data showed no differences. MRI results indicated that the success rate of capsular repair was higher in the mesh group (50 hips, 98%) than in the conventional group (37 hips, 67%) (P < 0.001), and the others failed the repair. Three dislocations occurred in the conventional group, while none occurred in the mesh group. The preoperative HHS (30 points) and postoperative HHS (82 points) of the mesh group were similar to those (35 points, 83 points) of the conventional group (P = 0.164, P = 0.328). Satisfaction had no difference (P = 0.532). CONCLUSIONS: Compared to conventional repair, mesh reconstruction can effectively maintain capsular integrity and decrease dislocation risk after THA without increasing complications. LEVEL OF EVIDENCE: Therapeutic study, Level IA.

Long-term outcomes of arthroscopic synovectomy and core decompression through multiple small bone holes for early-stage avascular necrosis of the femoral head.

OBJECTIVE: This study described a minimally invasive approach for the management of early-stage avascular necrosis of the femoral head, which integrated arthroscopic intra-articular decompression and core decompression by drilling multiple small holes. METHOD: A total of 126 patients with 185 hip avascular necrosis were included between March 2005 and January 2008, and the hips were classified, based on the Association Research Circulation Osseous staging system, into stage I (n = 43), stage II (n = 114), and stage III (n = 28). Arthroscopic intra-articular inspection and debridement, along with drilling of multiple small holes for core decompression, were performed. The Modified Harris hip score system and radiographs were used to assess the pre- and post-surgery outcomes. RESULTS: One hundred and three patients (involving 153 hips) were followed up successfully for an average of 10.7 ± 3.4 years (range: 9-12 years). After surgery, the overall survival rate was 51.6% (79 hips), and the clinical survival rates were 79%, 72%, 52%, 32%, and 10% for patients with stage I, IIa, IIb, IIc, and III, respectively. The outcomes of patients with Association Research Circulation Osseous Stages I or IIA were better than those of other stages, while hips with a large necrotic area had poor results. This approach preserved the original biomechanical strength of the femoral head after core decompression and eliminated arthritis factors in the hip joint. CONCLUSION: The core decompression with multiple small-size holes is an effective method for treating early-stage avascular necrosis of the femoral head, particularly in those with pathological changes in the hip joint. LEVEL OF EVIDENCE: Therapeutic study, Level IV.

Automatic assessment of knee osteoarthritis severity in portable devices based on deep learning.

BACKGROUND: For knee osteoarthritis, the commonly used radiology severity criteria Kellgren-Lawrence lead to variability among surgeons. Most existing diagnosis models require preprocessed radiographs and specific equipment. METHODS: All enrolled patients diagnosed with KOA who met the criteria were obtained from **** Hospital. This study included 2579 images shot from posterior-anterior X-rays of 2,378 patients. We used RefineDet to train and validate this deep learning-based diagnostic model. After developing the model, 823 images of 697 patients were enrolled as the test set. The whole test set was assessed by up to 5 surgeons and this diagnostic model. To evaluate the model's performance we compared the results of the model with the KOA severity diagnoses of surgeons based on K-L scales. RESULTS: Compared to the diagnoses of surgeons, the model achieved an overall accuracy of 0.977. Its sensitivity (recall) for K-L 0 to 4 was 1.0, 0.972, 0.979, 0.983 and 0.989, respectively; for these diagnoses, the specificity of this model was 0.992, 0.997, 0.994, 0.991 and 0.995. The precision and F1-score were 0.5 and 0.667 for K-L 0, 0.914 and 0.930 for K-L 1, 0.978 and 0.971 for K-L 2, 0.981 and 0.974 for K-L 3, and 0.988 and 0.985 for K-L 4, respectively. All K-L scales perform AUC > 0.90. The quadratic weighted Kappa coefficient between the diagnostic model and surgeons was 0.815 (P < 0.01, 95% CI 0.727-0.903). The performance of the model is comparable to the clinical diagnosis of KOA. This model improved the efficiency and avoided cumbersome image preprocessing. CONCLUSION: The deep learning-based diagnostic model can be used to assess the severity of KOA in portable devices according to the Kellgren-Lawrence scale. On the premise of improving diagnostic efficiency, the results are highly reliable and reproducible.

A simple, universal and multifunctional template agent for personalized treatment of bone tumors.

Bone tumors occur in bone or its accessory tissues. Benign bone tumors are easy to cure and have good prognosis, while malignant bone tumors develop rapidly and have poor and high mortality. So far, there is no satisfactory treatment method. Here, we designed a universal template vector for bone tumor therapy that simultaneously meets the needs of bone targeting, tumor killing, osteoclast suppression, and tumor imaging. The template is composed of a polydopamine (PDA) core and a multifunctional surface. PDA has excellent biosafety and photothermal performance. In this study, alendronate sodium (ALN) is grafted to enable its general bone targeting function. PDA core can carry a variety of chemotherapy drugs, and the rich ALN group can carry a variety of metal ions with an imaging function. Therefore, more personalized treatment plans can be designed for different bone tumor patients. In addition, the PDA core enables photothermal therapy and enhanced chemotherapy. Through template drug Doxorubicin (DOX) and template imaging ion Fe (Ⅱ), we systematically verified the therapeutic effect, imaging effect, and inhibition of bone dissolution of the agent on Osteosarcoma (OS), a primary malignant bone tumor, in vivo. In conclusion, our work provides a more general template carrier for the clinical treatment of bone tumors, through which personalized treatment of bone tumors can be achieved.

The Comparison between Mini-Subvastus Approach and Medial Parapatellar Approach in TKA: A Prospective Double-Blinded Randomized Controlled Trial.

OBJECTIVE: Minimal invasive approach has been increasingly used in total knee arthroplasty (TKA) and more is expected of early rehabilitation in terms of pain release and recovery of knee function. The approach type is one of the major factors that determines the early rehabilitation after TKA. The purpose of this study is to determine whether mini-subvastus approach (MSVA) is superior to the traditional medial parapatellar approach (MPA) in TKA. METHODS: From 2018 to 2019, a randomized double-blinded prospective study was conducted on 58 patients who underwent simultaneous bilateral TKA. The subjects included eight men and 50 women, with an average age of 65 years. One side was randomized using MSVA and the other side using MPA. Visual analog scale (VAS), operative duration, recovery time to straight leg raising (SLR), range of motion (ROM), HSS score, release rate of lateral retinaculum, satisfaction rate were recorded and compared. Paired-samples T test were used for quantitative data and chi-square test for qualitative data. RESULTS: There was no statistical difference in the ratio of left and right sides, preoperative ROM, VAS, HSS score, muscular strength of lower limbs, KL grade, operative order, and operative duration between the two groups. The average ROM (118.91 ± 8.21 vs. 107.60 ± 7.99, t = 14.320, p = 0.0000) and HSS score (72.03 ± 4.55 vs. 61.22 ± 4.36, t = 13.095, p = 0.0000) on POD 3, VAS in rest and motion on POD 1 and 3, the recovery time to SLR (1.17 ± 0.38 vs. 3.09 ± 0.76, t = 19.902, p = 0.0000), and the satisfaction rate on POD 1 (96.55% vs. 74.14%, χ2  = 9.9251, p = 0.0016) were superior in the MSVA group over MPA group. ROM in rest and motion and HSS score on POD 30 had no difference. The release rate of lateral retinaculum was less in the MSVA group than in the MPA group. The mean value of HKA, FFC, and FTC and the proportion of outliers did not differ significantly between the two groups. CONCLUSIONS: Compared with MPA, MSVA can make ROM of knee and SLR recover earlier, reduce postoperative pain after TKA, improve the early postoperative satisfaction and reduce the lateral release rate. MSVA can be used as a favorable measure in the concept of enhanced recovery after surgery (ERAS).

Isobavachalcone prevents osteoporosis by suppressing activation of ERK and NF-κB pathways and M1 polarization of macrophages.

Estrogen receptors alpha (ERα), a member of the nuclear receptor protein family, was found to play an important role in maintaining bone mass. Its downstream signaling proteins such as ERK and NF-κB were reported to be involved in development of osteoporosis, which meant that targeting ERα might be an effective strategy for searching for new drugs to prevent bone loss. In this study, we demonstrate that isobavachalcone (ISO), as one of bioactive compounds isolated from Psoralea corylifoliaLinn, has high affinity with ERα. The effects of ISO are investigated on receptor activator of NF-κB ligand (RANKL)-induced osteocalstogenesis. It is reported that ISO inhibits the RANKL-mediated increase of osteoclast-related genes MMP9, cathepsink and TRAR in RAW264.7 cells. Moreover, in vitro experiment shows that ISO exhibits an inhibitory effect on ERK and NF-κB signaling pathway, and suppresses RANKL-induced expression of osteoclast-related transcription factors NFATc1 and c-Fos. However, the impact of ISO in these molecules is eliminated by the application of ERα antagonist AZD9496.We further verified pharmacological effects of ISO in ovariectomized osteoporotic mice, and ISO significantly prevented bone loss and decreased M1 polarization of macrophages from marrow and spleen. Collectively, our data suggest that ISO prevents osteoporosis via suppressing activation of ERK and NF-κB signaling pathways as well as M1 polarization of macrophages.

Posteromedial Corner Release with the Knee in Figure-of-Four Position vs Conventional Position for Varus Knee Arthroplasty.

OBJECTIVE: To introduce posteromedial corner release with the knee in the figure-of-four position versus the conventional position for varus knee arthroplasty. METHODS: This is a retrospective study. From March 2015 to September 2019, a series of 123 patients (139 knees) with varus knee were randomly and blindly allocated to experimental group (60 patients; 68 knees) and control group (57 patients; 65 knees). Patients in experimental group underwent posteromedial corner release with the knee in the figure-of-four position; and patients in control group with the knee in the conventional position. If soft tissue balance was not completely achieved or the medial gap was still tight, an additional loosening technique were used to achieve symmetric medial and lateral space in both groups. Time for soft tissue balancing was defined as the time from the start of the spacer test to the end of the balance test. Length of release was defined as the distance from the osteotomy surface of the tibial plateau to the farthest structures released. The rating system of Hospital for Special Surgery (HSS) knee score was used to evaluate the clinical results. Quantitative variables were described as mean and standard deviation, and compared by one-way analysis of variance. RESULTS: The mean age of experimental group and control group was 70.2 ± 8.7 years and 68.7 ± 6.2 years, respectively (P > 0.05). Preoperatively, the mean HSS score of the groups was 38.2 ± 11.3 and 39.1 ± 10.7, respectively (P > 0.05). The mean varus knee angle was 19.7° ± 9.3° and 19.3° ± 10.7°, respectively (P > 0.05). The mean time for soft tissue balancing was 8.4 ± 3.3 min and 11.3 ± 6.9 min in experimental and control group, respectively (P < 0.05). The mean length of releasing posteromedial corner structures was 35.5 ± 13.4 mm and 27.3 ± 9.7 mm in experimental and control group, respectively (P < 0.05). Additional special loosening techniques were performed in eight knees in experimental group and seven knees in control group. The HSS scores 5 years after surgery were 95.1 ± 16.9 and 94.8 ± 17.2 respectively (P > 0.05). No complications were found during the follow-up time, and the clinical symptoms were observed to be significantly improved in the patients. CONCLUSION: The posteromedial corner can be released more extensively and thoroughly when the knee is placed in the figure-of-four position during varus knee arthroplasty.