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BACKGROUND Warfarin for the prevention of non-valvular atrial fibrillation related thromboembolic stroke in patients on maintenance haemodialysis is controversial. Despite the exclusion of haemodialysis patients in randomised control trials, the American Heart Association/American College of Cardiology has recommended warfarin in high-risk AF patients. AIM We retrospectively examined the utility of warfarin anticoagulation therapy in our prevalent haemodialysis patients over 10 years of follow-up. METHODS Eligible patients were retrospectively identified and stratified to two cohorts based on whether warfarin was prescribed. The outcomes of interest were ischaemic stroke, haemorrhagic stroke and death from any cause. Rate ratio and cox proportional hazard regression model were compare the differences in outcome between the two cohorts. The Kaplan-Meier method was used to analyse survival. RESULTS Three ischaemic strokes and four haemorrhagic strokes occurred in the unexposed group of 166 patients over 484.44 patient-years follow-up. One ischaemic stroke and no cases of haemorrhagic stroke occurred in the exposed warfarin group of 16 patients over 39.32 patient-years of follow-up. 87% of patients in both groups were indigenous. More than 90% of each cohort was had CHA2DS2VaSc score ≥2. 101 deaths occurred in the follow-up period, ninety in the unexposed group and eleven in the warfarin group. A non-statistically significant trend towards increasing mortality was observed in the warfarin group (Hazard ratio =1.63, p=0.13). CONCLUSION This retrospective study of prevalent haemodialysis patients with co-existing history of non-valvular AF failed to demonstrate sufficient evidence for the routine use of warfarin for prophylaxis of thromboembolic stroke. This article is protected by copyright. All rights reserved.

Liangliang Li,1– 3 Jun Fu,2 Chi Xu,2 Ming Ni,2 Wei Chai,2 Libo Hao,2 Yonggang Zhou,2 Jiying Chen2 1Medical School of Chinese PLA, Beijing, People’s Republic of China; 2Department of Orthopedics, The First Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of ChinaCorrespondence: Jiying Chen; Libo HaoDepartment of Orthopedics, The First Medical Centre, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, People’s Republic of ChinaTel +86 13901078832; Tel +86 13901078832Fax +86 010 68216336Email chenjiying_301@163.com; haolibo301@sina.comBackground: This study aimed to compare the clinical data of ankylosing spondylitis (AS) patients who underwent unilateral and bilateral total hip arthroplasty (THA) due to advanced hip involvement. Furthermore, to determine the factors associated with bilateral THA.Methods: Utilizing a single-institution database, we selected 373 consecutive AS patients undergoing primary THA from 2012 to 2017 and compared the clinical characteristics and anti-tumor necrosis factor (TNF) therapy of the patients who underwent unilateral and bilateral THA. Logistic regression was used to identify factors associated with bilateral THA.Results: Bilateral THA was performed in 67.3% (n=251) of the patients. Male patients had a higher frequency of undergoing bilateral THA compared with female ones (P< 0.05). The proportion of the patients who had bilateral onset in hips, administration of TNF inhibitors, flexion contracture in the hip, and a BASRI-hip score of 4 was significantly higher in patients with bilateral THA than that with unilateral THA (P< 0.05). Patients with bilateral THA experienced longer disease duration than those with unilateral THA (P< 0.05). The results of the logistic regression showed that factors related to bilateral THA were bilateral onset in hips, administration of TNF inhibitors, a BASRI-hip score of 4, and an erythrocyte sedimentation rate (ESR) level (P< 0.05).Conclusion: Bilateral THA is more common in AS patients with advanced hip involvement. Bilateral onset in hips, a BASRI-hip score of 4, and a higher level of ESR are risk factors associated with bilateral THA, while anti-TNF therapy is a protective factor reducing the progression of hip involvement to bilateral THA.Keywords: ankylosing spondylitis, hip involvement, bilateral total hip arthroplasty, anti-TNF therapy

This study aimed to investigate the efficacy of the albumin/fibrinogen ratio (AFR) in the assessment of malnutrition and to compare its ability to predict early postoperative periprosthetic joint infection (PJI) in patients with aseptic revisions.Four hundred sixty-six patients undergoing revision total hip or knee arthroplasty between February 2017 and December 2019 were recruited in this retrospective study. We compared the differences in nutritional parameters between patients undergoing revision for septic and aseptic reasons. We used multivariate logistic regression and assessed the association between nutritional parameters and risk of PJI. 207 patients with aseptic revision were then evaluated for the incidence of acute postoperative infection within 90 days. The predictive ability of nutritional markers was assessed by receiver operating characteristic curves.In the multivariate logistic regression analysis, low albumin level (adjusted OR 1.56, 95% CI 1.16-2.08, P = .003), low prognostic nutritional index (PNI) (adjusted OR 1.57, 95% CI 1.01-2.43, P.043), and low AFR (adjusted OR 2.54, 95% CI 1.92-3.36, P.001) were independently associated with revision surgery for septic reasons. In accordance with the receiver operating characteristic analysis, the AFR exhibited a greater area under the curve value (0.721) than did the prognostic nutritional index and albumin. An elevated AFR (≥11.7) was significantly associated with old age, joint type, high Charlson comorbidity index, high American Society of Anesthesiologist, and diabetes (P.05).Our findings demonstrated AFR may be an effective biomarker to assess nutrition status and predict acute PJIs after revision TJA.

Background Rheumatoid arthritis is a long-term systemic disease that primarily affects multiple synovial joints throughout the body. Some patients with severe joint effusion even require repeated arthrocentesis or arthroscopic debridement to relieve symptoms, which causes them much suffering mentally and physically. This text-mining study was designed to find potential drugs that target key genes in this disease. Methods Firstly, we performed text mining by two keywords ("rheumatoid synovitis" and "joint effusion") to get a common set of genes. Secondly, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis performed on these genes, and protein-protein interaction (PPI) network was constructed. Subsequently, the significant genes clustered in the PPI network were chose to execute genedrug interaction analysis for potential drug discovery. Results Through text mining, 68 overlapping genes were identified as an initial set of key genes. Construction of the initial gene set's PPI network showed that 25 genes clustered in a significant gene module. Ultimately, 8 out of 25 genes could be targetable by a total of 19 drugs. Conclusions The final 8 genes (PTGS2, TNF, VEGFA, IL1B, CCL2, VWF, IL6, and ESR1) and 19 drugs may provide significant therapeutic value for rheumatoid arthritis patients with joint effusion.

Aims It can be extremely challenging to determine whether to perform reimplantation in patients who have contradictory serum inflammatory markers and frozen section results. We investigated whether patients with a positive frozen section at reimplantation were at a higher risk of reinfection despite normal ESR and CRP. Methods We retrospectively reviewed 163 consecutive patients with periprosthetic joint infections (PJIs) who had normal ESR and CRP results pre-reimplantation in our hospital from 2014 to 2018. Of these patients, 26 had positive frozen sections at reimplantation. The minimum follow-up time was two years unless reinfection occurred within this period. Univariable and multivariable logistic regression analyses were performed to identify the association between positive frozen sections and treatment failure. Results Treatment failure occurred in eight (30.77%) of the 26 PJI patients with positive frozen sections at reimplantation, compared with 13 (9.49%) of 137 patients with negative results. In the multivariate analysis, positive frozen section increased the risk of failure (odds ratio 4.70; 95% confidence interval (CI) 1.64 to 13.45). The mean number of months to reinfection was lower in the positive frozen section group than in the control group (p = 0.041). While there were nine (34.62%) patients with positive frozen section and 25 (18.25%) patients with negative frozen section who had prolonged antibiotic use (p = 0.042), the mean duration of antibiotic use was comparable in two groups. Synovial white blood cell count (p = 0.137) and polymorphonuclear leucocyte percentage (p = 0.454) were not associated with treatment failure in logistic regression model. Conclusion Positive frozen section at reimplantation was independently associated with subsequent failure and earlier reinfection, despite normal ESR and CRP levels pre-reimplantation. Surgeons should be aware of the risk of treatment failure in patients with positive frozen sections and carefully consider benefits of reimplantation. Cite this article: Bone Joint J 2021;103-B(5):916–922.

Background Patients with native joint septic arthritis are one of the highest risk groups for developing complications following total joint arthroplasty (TJA), especially periprosthetic joint infection(PJI). There is a paucity of information on the risk factors for developing PJI and the optimal treatment modality of the native septic joint that can mitigate that risk. This multicenter study aimed to determine these risk factors, including prior treatment. Methods A retrospective study of 233 TJAs performed, following prior septic arthritis at five institutions, was conducted. Comorbidities, organism profile, prior surgery, etiology of septic arthritis, and other relevant variables were reviewed. The primary outcome was the development of PJI, defined by Musculoskeletal Infection Society criteria. Bivariate and multivariate analyses were performed to identify risk factors for PJI. Results Overall, the PJI rate was 12.4% in patients who underwent TJA after native septic arthritis. Predisposing risk factors for PJI included antibiotic-resistant organisms, male gender, diabetes, and a postsurgical cause of septic arthritis eg open reduction internal fixation. When controlling for potential confounders, multivariate analysis revealed that male gender, diabetes, and a postoperative etiology were predictors of PJI. The definitive treatment modality for the septic joint did not affect the rate of PJI for both arthroscopy vs irrigation and debridement (I&D), and two-stage exchange vs single-stage procedure. Discussion This study has identified several risk factors for developing PJI in patients with prior septic joint arthritis, some of which are modifiable. The initial treatment modality of the native septic joint has no bearing on the development of PJI after TJA.

S-oxiracetam (S-ORC), a nootropic drug, was used to protect against ischemic stroke by lessening the blood brain barrier dysfunction and inhibiting neuronal apoptosis. However, the potential effects of S-ORC in the recovery of cognitive functions after ischemic stroke and the underlying mechanisms remains unclear. In this study, middle cerebral artery occlusion/reperfusion (MCAO/R) in rats was used as the animal model. By using Y-maze test, Morris water maze, triphenyl tetrazolium chloride (TTC) staining, terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate (dUTp) nick end labeling (TUNEL) assay, hematoxylin and eosin, immunohistochemical staining and western blot to evaluate the protective effect of S-ORC on cognitive recovery, we were able to confirm that S-ORC ameliorated spatial learning impairment, tissue loss, and hippocampal neuronal apoptosis and injury induced by MCAO/R in rats. These cognitive effects were achieved by restoring the normal function of synaptophysin and increasing PSD95 expression in the hippocampus. Furthermore, we found that methyllycaconitine, the antagonist of α7 nicotinic acetylcholine receptor (α7nAChR), and LY294002, the inhibitor of phosphoinositide 3-kinase (PI3K), were able to block the cognitive effects of S-ORC after MCAO/R in rats. In conclusion, α7nAChR and PI3K are key molecules that mediated the signaling pathway leading to S-ORC-induced cognitive restoration after MCAO/R.

Cardiac endothelium communicates closely with adjacent cardiac cells by multiple cytokines and plays critical roles in regulating fibroblasts proliferation, activation, and collagen synthesis during cardiac fibrosis. E26 transformation-specific (ETS)-related gene (ERG) belongs to the ETS transcriptional factor family and is required for endothelial cells (ECs) homeostasis and cardiac development. This study aims at investigating the potential role and molecular basis of ERG in fibrotic remodeling within the adult heart. We observed that ERG was abundant in murine hearts, especially in cardiac ECs, but decreased during cardiac fibrosis. ERG knockdown within murine hearts caused spontaneously cardiac fibrosis and dysfunction, accompanied by the activation of multiple Smad-dependent and independent pathways. However, the direct silence of ERG in cardiac fibroblasts did not affect the expression of fibrotic markers. Intriguingly, ERG knockdown in human umbilical vein endothelial cells (HUVECs) promoted the secretion of endothelin-1 (ET-1), which subsequently accelerated the proliferation, phenotypic transition, and collagen synthesis of cardiac fibroblasts in a paracrine manner. Suppressing ET-1 with either a neutralizing antibody or a receptor blocker abolished ERG knockdown-mediated deleterious effect in vivo and in vitro. This pro-fibrotic effect was also negated by RGD (Arg-Gly-Asp)-peptide magnetic nanoparticles target delivery of ET-1 small interfering RNA to ECs in mice. More importantly, we proved that endothelial ERG overexpression notably prevented pressure overload-induced cardiac fibrosis. Collectively, endothelial ERG alleviates cardiac fibrosis via blocking ET-1-dependent paracrine mechanism and it functions as a candidate for treating cardiac fibrosis. • ERG is abundant in murine hearts, especially in cardiac ECs, but decreased during fibrotic remodeling. • ERG knockdown causes spontaneously cardiac fibrosis and dysfunction. • ERG silence in HUVECs promotes the secretion of endothelin-1, which in turn activates cardiac fibroblasts in a paracrine manner. • Endothelial ERG overexpression prevents pressure overload-induced cardiac fibrosis.

Purpose The study assessed the correlation among the patients’ perception of leg length discrepancy (LLD) after total hip arthroplasty (THA) in patients with unilateral Crowe type IV developmental dysplasia of the hip (DDH) and the four methods of measuring the leg length in the full-length standing anteroposterior radiographs. Methods Sixty patients with unilateral Crowe type IV DDH were recruited in this retrospective study between January 2012 and January 2019. Four methods of measurement were used: 1) TD-TP: distance between the inferior aspect of teardrop (TD) and the midpoint of tibial plafond (TP); 2) CH-TP: distance between the center of the hip (CH) or acetabular cup and the TP; 3) GT-TP: distance between the apex of greater trochanter (GT) and the TP; and 4) FL+TL: the sum of femoral length (FL) and tibial length (TL). Results Association was found among the patients’ perception on LLD with difference in TD-TP (OR=1.157), and the difference in FL+TL (OR=1.166). The area under the curve of the difference in FL+TL and the difference TD-TP (0.704 and 0.679) was significantly higher than those of the difference in CH-TP and the difference in GT-TP (0.564 and 0.483). With the calculated threshold of LLD set at 9.0 mm, the sensitivity and specificity of the difference in TD-TP and the difference in FL+TL were 57.7%, 79.4% and 61.5%, 79.4%, respectively. Conclusion Patients’ perception on LLD had good correlation and reliability on the difference of FL+TL and the difference of TD-TP on both sides in the full-length standing anteroposterior radiographs after THA in patients with unilateral Crowe type IV DDH. The calculated threshold of the difference in FL+TL and the difference in TD-TP was set at 9.0 mm to assess the patients’ perception on LLD.

Lung cancer is the leading cause of cancer-related mortality worldwide. Patients with locally advanced non-small cell lung cancer (NSCLC) have lower overall survival. Studies have shown that some patients with unresectable stage III NSCLC develop disease progression after initial chemoradiotherapy, and new treatment is needed to improve the prognosis of these patients. The rapid development of therapy has greatly changed and continued to renew the treatment strategy of advanced NSCLC. However, the clinical treatment for patients with the wild-type gene remains problematic, and chemotherapy with platinum are not yet considered satisfactory. Herein, we are reporting a case of a patient with wild-type gene mutation locally advanced NSCLC who was treated with neoadjuvant therapy by using combined targeted anti-PD-1 immunotherapy and chemotherapy. The percentage of tumor cells with membranous PD-L1 staining (tumor proportion score) was 90% or greater. After receiving all three cycles of treatment, the patient underwent video-assisted right upper lung lobectomy and wedge resection plus radical mediastinal lymph node dissection. Pathological section samples showed a pathological complete response. This experience has led us to believe that the subgroup of patients with unresectable advanced NSCLC may benefit from this strategy and may have an opportunity for radical surgery.

Introduction: We aimed to explore the risk factors for periprosthetic joint infection (PJI) after primary artificial hip and knee joint replacements by performing a case-control study. Methodology: The clinical data of patients receiving primary hip and knee joint replacements were retrospectively analyzed. The case group included 96 patients who suffered from PJI, comprising 42 cases of hip joint replacement and 54 cases of knee joint replacement. Another 192 patients who received joint replacement at the ratio of 1:2 in the same period and did not suffer from PJI were selected as the control group. Differences between the two groups were compared in regard to etiology, pathogen, blood type, urine culture, body mass index (BMI), surgical time, intraoperative blood loss, postoperative 1st day and total drainage volumes, length of hospitalization stay, and history of surgery at the affected sites. Results: Gram-positive bacteria were the main pathogens for PJI. The most common infection after hip joint replacement was caused by Staphylococcus epidermidis, which accounted for 38.10%, while Staphylococcus aureus was mainly responsible for the infection of knee joint (40.74%). High BMI, long surgical time, large postoperative drainage volume, long hospitalization stay, history of surgery at incisions, previous use of immunosuppressants, preoperative hypoproteinemia and superficial infection were independent risk factors (p < 0.05). Conclusions: PJI after primary replacement was mainly caused by gram-positive bacteria, and patients with high BMI, long surgical time, large postoperative drainage volume, long hospitalization stay, history of surgery at incisions, previous use of immunosuppressants, preoperative hypoproteinemia and superficial infection were more vulnerable.

Purpose The diagnosis of persistent infection at reimplantation of two-stage revision arthroplasty for periprosthetic joint infection (PJI) remains challenging. Several studies have shown the benefit of serum interleukin-6 (IL-6) in diagnosing periprosthetic joint infection (PJI). Recent data indicated serum IL-6 could be promising in differentiating persistent infection. The purpose of this study was to validate the efficacy of serum IL-6 in diagnosing persistent infection at reimplantation. Methods A retrospective review of 86 PJI patients with a two-stage exchanged hip arthroplasty from 2013 to 2017 was conducted. Persistent infection was defined using the modified Musculoskeletal Infection Society (MSIS) criteria combined with follow-up results. Serum IL-6 at reimplantation were collected and compared among patients with or without persistent infection. Receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic performance and optimal cut-off value of serum IL-6 at reimplantation. Results Sixteen cases were diagnosed as persistent infection at reimplantation. There was no significant difference in serum IL-6 levels between cases with persistent infection and controls (7.89 pg/ml vs. 5.56 pg/ml; P = 0.179). The area under the ROC curve (AUC) for serum IL-6 in diagnosing persistent infection at reimplantation was 0.59 (95% confidential interval [CI] 0.40–0.77). With the calculated threshold set at 8.12 pg/ml, the corresponding sensitivity, specificity, positive predictive value, and negative predictive values were 38%, 88%, 38%, and 87%, respectively. Conclusion Serum IL-6 is inadequate in diagnosing persistent infection at reimplantation for two-stage revision arthroplasty. With the serum IL-6 threshold set at 8.12 pg/ml, the specificity to rule out persistent infection is high, but the sensitivity to predict persistent infection is not satisfactory.

Background Diagnosing acute periprosthetic joint infection remains a challenge. Several studies have proposed different acute cutoffs resulting in the International Consensus Meeting recommending a cutoff of 100 mg/L, 10,000 cell/μL and 90% for serum C-reactive protein (CRP), synovial white blood cell count (WBC), and polymorphonuclear percentage (PMN%), respectively. However, establishing cutoffs are difficult as the control group is limited to rare early aseptic revisions, and performing aspiration in asymptomatic patients is difficult because of a fear of seeding a well-functioning joint arthroplasty. This study (1) assessed the sensitivity of current thresholds for acute periprosthetic joint infection (PJI) and (2) identified associated factors for false negatives. Methods We retrospectively reviewed patients with acute PJIs (n = 218), defined as less than 6 weeks from index arthroplasty, treated between 2000 and 2017. Diagnosis of PJI was based on 2 positive cultures of the same pathogen from the periprosthetic tissue or synovial fluid samples. Sensitivities of International Consensus Meeting cutoff values of CRP, synovial WBC, and PMN% were evaluated according to organism type. Multiple logistic regression analysis was performed to determine associated factors for false negatives. Results Overall, the sensitivity of CRP, synovial WBC, and PMN% for acute PJI was 55.3%, 59.6%, and 50.5%, respectively. Coagulase-negative Staphylococcus (CNS) demonstrated the lowest sensitivity for both CRP (37.5%) and WBC (55.6%). CNS infection was identified as an independent risk factor for false-negative CRP. Conclusions Current thresholds for acute PJI may be missing approximately half of PJIs. Low virulent organisms, such as CNS, may be responsible for these false negatives. Current thresholds for acute PJI must be reexamined.

Summary Background It is not known whether age alone or the increased comorbidities in older patients are responsible for the higher rate of periprosthetic joint infection (PJI) in older patients. Aim To test the hypothesis that age alone is not a risk factor for PJI after total joint arthroplasty. Methods This retrospective study included the review of 23,966 patients undergoing primary total hip and knee arthroplasty between January 1st, 2010 and December 31st, 2016 at a single institution. Patients who developed PJI, as defined by International Consensus Meeting criteria, were identified. All enrolled patients were divided into three groups that included patients aged Findings The incidence of PJI in the entire cohort was 0.72% (171 out of 23,966). Multivariate analysis adjusting for all variables, except age, demonstrated that, compared to the patients aged Conclusion When adjusting for confounding variables, age alone is not a risk factor for PJI. Studies evaluating the influence of age on the incidence of PJI should take into account the other confounding variables that contribute to PJI.

Aims Preoperative aspiration culture and intraoperative cultures play pivotal roles in periprosthetic joint infection (PJI) diagnosis and pathogen identification. But the discordance between preoperative aspiration culture and intraoperative synovial fluid culture remains unknown. We aim to determine (1) the discordance between preoperative and intraoperative synovial fluid (SF) culture and. (2) compared to intraoperative synovial fluid cultures, the sensitivity of preoperative aspiration fluid culture. Then the following question is tried to be answered: Are intraoperative synovial fluid re-cultures necessary if the preoperative aspiration culture is positive? Materials and methods Between 2015 and 2019, 187 PJI patients managed with surgeries were included in this study. Compared to intraoperative synovial fluid culture, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of preoperative aspiration culture were calculated. Then, the discordance between preoperative aspiration culture and intraoperative SF culture was analyzed. Results The sensitivity of preoperative aspiration culture was 81.29% compared to intraoperative synovial fluid cultures. Concordance was identified in 147 PJI (78.61%) patients and culture discordance occurred in 40 patients (21.39%). In these discordant PJI patients, 24 patients (60%) were polymicrobial and no intraoperative synovial fluid culture growth was found in 16 PJI cases (40%). Preoperative monomicrobial staphylococcus results had a sensitivity of and a specificity of 80.43% and 83.16%, respectively. Preoperative polymicrobial results had the lowest sensitivity. Conclusions The intraoperative synovial fluid re-cultures are necessary if the preoperative aspiration culture is positive and the discordance between preoperative aspiration culture and intraoperative synovial fluid culture should be noted especially when Streptococcus spp. and more than one pathogen was revealed by preoperative aspiration culture. Level of evidence: Level III.

BACKGROUND Lupus nephritis (LN) is common feature of Systemic Lupus Erythematosus (SLE) and affects 50% of patients with SLE. Racial differences in incidence and prevalence have been well documented worldwide. In Australia, higher incidence and prevalence of SLE had been previously reported in Aboriginal and Torres Strait Australians compared to non-Indigenous Australians. AIM to describe the differences in clinical features and lupus biomarkers between Aboriginal and Torres Strait Islander Australian and non-Indigenous Australian LN patients. METHODS We retrospectively identified all consecutive biopsy-proven LN patients in our institution and compared the clinical features and lupus biomarkers between Aboriginal and Torres Strait Islander Australians and non-indigenous Australians. RESULTS Of the thirty-three consecutive biopsy proven LN patients, twenty-six self-identified as of Aboriginal and Torres Strait Islander descent. The estimated incidence of lupus nephritis in Aboriginal and Torres Strait Islander Australian and non-Indigenous Australians were 5.08 and 0.47 per 100,000 patient years respectively. Neurological manifestations (23.08% vs 0%), haematological manifestations (46.50 % vs 16.67) and right heart catheter proven pulmonary arterial hypertension (23.08% vs 0%) were more frequently observed amongst Indigenous Australian patients compared to non-Indigenous Australian patients. The incidence of positive Extractable Nuclear Antigen (ENA) was also higher among Indigenous Australian patients (84.62% vs 57.14%). CONCLUSION Our study further supports the observation that lupus in Aboriginal and Torres Strait Islander Australians were of a 'distinct phenotype' compared to non-Indigenous Australians. Future research should be aimed at delineating the reason for this observed difference. This article is protected by copyright. All rights reserved.

Proteasomal activity is compromised in diabetic hearts that contributes to proteotoxic stresses and cardiac dysfunction. Osteocrin (OSTN) acts as a novel exercise-responsive myokine and is implicated in various cardiac diseases. Herein, we aim to investigate the role and underlying molecular basis of OSTN in diabetic cardiomyopathy (DCM). Mice received a single intravenous injection of the cardiotrophic adeno-associated virus serotype 9 to overexpress OSTN in the heart and then were exposed to intraperitoneal injections of streptozotocin (STZ, 50 mg/kg) for consecutive 5 days to generate diabetic models. Neonatal rat cardiomyocytes were isolated and stimulated with high glucose to verify the role of OSTN in vitro. OSTN expression was reduced by protein kinase B/forkhead box O1 dephosphorylation in diabetic hearts, while its overexpression significantly attenuated cardiac injury and dysfunction in mice with STZ treatment. Besides, OSTN incubation prevented, whereas OSTN silence aggravated cardiomyocyte apoptosis and injury upon hyperglycemic stimulation in vitro. Mechanistically, OSTN treatment restored protein kinase G (PKG)-dependent proteasomal function, and PKG or proteasome inhibition abrogated the protective effects of OSTN in vivo and in vitro. Furthermore, OSTN replenishment was sufficient to prevent the progression of pre-established DCM and had synergistic cardioprotection with sildenafil. OSTN protects against DCM via restoring PKG-dependent proteasomal activity and it is a promising therapeutic target to treat DCM.

Background:. Patients undergoing total joint arthroplasty (TJA) following septic arthritis are at higher risk for developing periprosthetic joint infection (PJI). Minimal literature is available to guide surgeons on the optimal timing of TJA after completing treatment for prior native joint septic arthritis. This multicenter study aimed to determine the optimal timing of TJA after prior septic arthritis and to examine the role of preoperative serology in predicting patients at risk for developing PJI. Methods:. A total of 207 TJAs were performed after prior septic arthritis from 2000 to 2017 at 5 institutions. Laboratory values, prior treatment, time from the initial infection, and other variables were recorded. Bivariate analyses were performed to identify the association between the time from septic arthritis to TJA and the risk of developing subsequent PJI. A subanalysis was performed between patients who underwent TJA in 1 setting (n = 97) compared with those who underwent 2-stage arthroplasties (n = 110). Receiver operating characteristic (ROC) curve analysis was performed for serum markers prior to TJA in predicting the risk of a subsequent PJI. Results:. The overall PJI rate was 12.1%. Increasing time from septic arthritis treatment to TJA was not associated with a reduction of PJI, whether considering time as a continuous or categorical variable, for both surgical treatment cohorts (all p > 0.05). Although the ROC curve analysis found that the optimal threshold for timing of TJA from the initial treatment was 5.9 months, there was no difference in the PJI rate when the overall cohort was dichotomized by this threshold and when stratified by 1-stage compared with 2-stage TJA. There was no significant difference in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level prior to conversion TJA between patients who subsequently developed PJI and those who did not. Conclusions:. Serum markers have limited value in predicting subsequent PJI in patients who undergo TJA after prior septic arthritis. There was no optimal interim period between septic arthritis treatment and subsequent TJA; thus, delaying a surgical procedure does not appear to reduce the risk of PJI. Level of Evidence:. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background and objective The purpose of this study was to estimate the diagnostic performance of synovial fluid polymerase chain reaction (PCR) in periprosthetic hip and knee infection, and whether synovial fluid PCR has greater diagnostic significance than conventional methods. Methods The literature databases PubMed, Scopus, and the Web of Science were searched for English articles describing periprosthetic joint infection (PJI) diagnosis by synovial fluid PCR. Articles were limited to the period between January 1990 and December 2019. Subsequently, conventional methods that were used on at least two occasions were included for further analysis. Data analysis was performed using the Meta-DiSc and Stata software. Results Eleven studies with 1360 cases were included in the meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) of synovial fluid PCR were 0.70 (95% CI 0.66–0.74), 0.92 (95% CI 0.90–0.93), and 37.4 (95% CI 17.77–78.74), respectively. Conclusions Synovial fluid PCR provides an effective tool for rapid diagnosis of PJI, and also in the early stages of culture-negative bacterial infections.

Aims Periprosthetic joint infection (PJI) is a serious complication of total joint arthroplasty. We performed a retrospective cohort study to evaluate (1) the change of coagulation profile in two-staged arthroplasty patients and (2) the relationship between coagulation profile and the outcomes of reimplantation. Method Between January 2011 and December 2018, a total of 202 PJI patients who were operated on with two-staged arthroplasty were included in this study initially. This study continued for 2 years and the corresponding medical records were scrutinized to establish the diagnosis of PJI based on the 2014 MSIS criteria. The coagulation profile was recorded at two designed points, (1) preresection and (2) preimplantation. The difference of coagulation profile between preresection and preimplantation was evaluated. Receiver operating characteristic curves (ROC) were used to evaluate the diagnostic efficiency of the coagulation profile and change of coagulation profile for predicting persistent infection before reimplantation. Results The levels of APTT, INR, platelet count, PT, TT, and plasma fibrinogen before spacer implantation were significantly higher than before reimplantation. No significant difference was detected in the levels of D-dimer, ACT, and AT3 between the two groups. The AUC of the combined coagulation profile and the change of combined coagulation profile for predicting persistent infection before reimplantation was 0.667 (95% CI 0.511, 0.823) and 0.667 (95% CI 0.526, 0.808), respectively. Conclusion The coagulation profile before preresection is different from before preimplantation in two-staged arthroplasty and the coagulation markers may play a role in predicting infection eradication before reimplantation when two-stage arthroplasty is performed. Level of evidence Level III, diagnostic study.

Rehabilitation robots are kinds of robots working together with humans to help patients in functional recovery or to assist people to move normally. Since compliance and safety during a robot-aided therapy period are important, impedance control takes both the effect and procedure in rehabilitation into consideration. Different impedance parameters (for example, inertia, damping ratio, and stiffness) are designed to ensure a robot with desired compliance and safe operation. Flexibility in the selection of those parameters ensures that impedance control makes full use of information collected in robot-aided physical therapy. This paper presents a short review of the implementation of impedance control in lower-limb rehabilitation robots. We first show the basic structure of impedance control. Then, we present an overview of the implementation of various impedance-control methods in lower-limb rehabilitation robots. Finally, we explain the limitations. challenges, and the trend in the field of rehabilitation robotics.

Background Negative regulatory T cells (Tregs) not only deplete effector T cells but also inhibit the clearance of HIV during infection, which may allow Tregs to be used as informative diagnostic markers. To facilitate both diagnosis and treatment, a thorough understanding of these regulators by characterizing them on temporal and spatial scales is strongly required. Methods Hundred HIV‐infected/AIDS patients, including 87 males, with an average age of 35.8 years, as well as 20 healthy controls, were enrolled. Flow cytometry was used to analyze CD3+T cells, CD4+T cells, and CD8+T cells to evaluate the immune status of the participants. Then, a group of representative negative regulatory T cells, including CD4+PD‐1+T cells, CD4+PD‐1highT cells, CD8+PD‐1+T cells, and CD4+CD25high Tregs was also analyzed to explore their effects on disease progression and intercorrelation. Results The percentages of CD4+PD‐1+T cells and CD4+CD25highTregs increased in patients with the same ultrahigh significance. Temporally, the patients with both intermediate‐stage and late‐stage disease had higher percentages of CD4+PD‐1+T cells; however, the percentage of CD4+CD25highTregs only increased in the patients with late‐stage disease. In addition, CD4+PD‐1+T cells but not CD4+CD25highTregs were negatively correlated with the absolute CD4+T cell count. Spatially, no correlations between CD4+PD‐1+T cells and CD4+CD25highTregs were observed, which suggests these Tregs function differently during immunosuppression. Conclusions This study characterized negative regulatory T cells in HIV‐infected/AIDS patients at both temporal and spatial scales and found that CD4+CD25+Tregs and CD4+PD‐1+T cells could be used as potential diagnostic markers for identifying different disease stages and monitoring disease progression., At late‐stage (CD4+T cells 500/μl). The percentage of CD4+CD25highTregs in the group of CD4+T cells 500/μl. It reveals that the CD4+PD‐1+T cells increased in patients when their absolute CD4+ is less than 500/μl, while CD4+CD25highTregs only increased when absolute CD4+ count is lower than 500/μL. This new discovery indicated that CD4+CD25highTregs are generated at a later stage of HIV infection, which could be used as a clinical indicator for poor disease status. We also found the percentage of CD4+PD‐1+T had a negative correlation with absolute CD4+ count in the HIV infected/AIDS patients and the percentage of CD4+CD25highTregs was not correlated with absolute CD4+ count. This provides a new quantitative maker for evaluating the progress of immunosuppression.

Background Periprosthetic joint infection is a serious complication after total joint arthroplasty and polymicrobial PJI which compose a subtype of PJI often indicate worse outcomes compared to monomicrobial periprosthetic joint infection. However, a literature review suggested that there were limited number studies evaluating the risk factors of polymicrobial PJI. Materials and methods Between 2015 January and 2019 December, a total of 64 polymicrobial PJI patients and 158 monomicrobial PJI patients in a tertiary center were included in this study and corresponding medical records were scrutinized. The diagnosis of PJI was based on 2014 MSIS criteria. Logistic regression was used to identify the association between various variables and polymicrobial PJI and ROC curve was used to identify their efficiency. Results The prevalence of polymicrobial PJI is 28.3% in our cohorts. After adjusting for the presence of sinus, previous and knee infection, isolation of enterococci (OR, 3.025; 95%CI (1.277,7.164) p = 0.012), infection with atypical organisms (OR, 5.032;95%CI: (1.470,17.229) p = 0.01), infection with gram-negative organisms (OR, 2.255; 95%CI (1.011,5.031) p = 0.047), isolation of streptococcus spp. (OR, 6; 95%CI (2.094,17.194) p = 0.001), and infection with CNS (OfR, 2.183;95%CI (1.148,4.152) p = 0.017) were risk factors of polymicrobial PJI compared to monomicrobial PJI. However, knee infection is related to a decreased risk of polymicrobial PJI with an adjusted OR = 0.479 (p = 0.023). Conclusion This study demonstrated that the prevalence of polymicrobial PJI is 28.3% in PJI patients. Moreover, the presence of sinus tract and previous joint revisions were risk factors for identifying different bacterial species in the intraoperative specimens. Therefore, in these PJI cases, it is necessary to examine multiple specimens of both intraoperative tissue and synovial fluid for increasing the detection rate and obtaining resistance information.

BACKGROUND Most of the widely used methods for the assessment of keloid treatment are subjective grading scales based on the opinion of an individual clinician or patient. There is a growing need for objective methods to evaluate keloid treatment. OBJECTIVE This study aimed to evaluate the value of laser speckle contrast imaging (LSCI) as an objective method for the assessment of dual-wavelength laser therapy for keloids. METHODS This prospective study included 21 patients with 54 keloids. All patients were treated with a combined 585-nm pulsed dye laser and 1,064 nm neodymium-doped yttrium aluminum garnet dual-wavelength laser at 4 weeks to 6 weeks intervals. Keloids were assessed using the Vancouver Scar Scale (VSS) and LSCI. RESULTS The total VSS score significantly decreased after 4 sessions of treatment (p < .05). Blood perfusion in keloids as measured by LSCI was significantly reduced after treatment (p < .05). The improvement of chest keloids in terms of the total VSS score and blood perfusion was significantly greater than that of scapular keloids (p < .05). There was a positive correlation between decreased perfusion and reduced total VSS score (R2 = 0.84). CONCLUSION Blood perfusion in keloids significantly decreased after dual-wavelength laser therapy. Laser speckle contrast imaging is a promising objective method for assessing the improvement of keloids treated with laser therapy.

Background The success of debridement, antibiotics, and implant retention (DAIR) in early periprosthetic joint infection (PJI) largely depends on the presence of a mature biofilm. At what time point DAIR should be disrecommended is unknown. This multicenter study evaluated the outcome of DAIR in relation to the time after index arthroplasty. Methods We retrospectively evaluated PJIs occurring within 90 days after surgery and treated with DAIR. Patients with bacteremia, arthroscopic debridements, and a follow-up Results We included 769 patients. Treatment failure occurred in 294 patients (38%) and was similar between time intervals from index arthroplasty to DAIR: the failure rate for Week 1–2 was 42% (95/226), the rate for Week 3–4 was 38% (143/378), the rate for Week 5–6 was 29% (29/100), and the rate for Week 7–12 was 42% (27/65). An exchange of modular components was performed to a lesser extent in the early post-surgical course compared with the late course (41% vs 63%, respectively; P < .001). The causative microorganisms, comorbidities, and durations of symptoms were comparable between time intervals. Conclusions DAIR is a viable option in patients with early PJI presenting more than 4 weeks after index surgery, as long as DAIR is performed within at least 1 week after the onset of symptoms and modular components can be exchanged.

In terms of developmental dysplasia of the hip (short for DDH), several classification systems have been proposed [1–5]. Most literature is published applicating Crowe’s classification system, because it could be suggestive and instructive for surgery. In 1979, Crowe et al. [1] proposed a four-type system classifying the degree of hip dislocation regarding the ratio of proximal displacement distance of the femoral head in relation to the height of the pelvis or the femoral head, resulting in a calculated coefficient, which converts into one of the four types. Crowe practiced as a hand surgeon after that, so this system was used worldwide and never ameliorative for improvement. In 1987, Eftekhar et al [6] proposed a four-type classification system based on the presence or absence of pseudoacetabulum and overlap between the true acetabulum and the false one. In 1996, Hartofilakidis et al. [4] used the pathology of the dysplastic acetabulum to distinguish between three different types of dysplasia, with subtypes discriminating between a primary and a secondary acetabulum and the relation of the head in relation to these structures. In 2008, Hartofilakidis [7] proposed subtypes on the presence or absence of false acetabulum, and in 2013, he analyzed the clinical outcome of THA based on different subtypes [8]. With the classification of Crowe being increasingly popular, especially in the English literature, it may be the best choice for a classification system with the data available today [9]. In 2016, Ma et al. reported different results between hips of Crowe type IV subtypes on the presence or absence of false acetabulum [10]. High dislocation of hip dysplasia is the most serious type of developmental dysplasia of the hip (short for DDH), which is very difficult to reconstruct the original acetabulum and reset the rotation center to equal both legs and avoid nerve injury after total hip arthroplasty (short for THA). Placing the acetabular component at the true hip center has been shown to provide successful long-term results [11]. However, placement of the acetabular component in the original acetabulum location may result in nerve injury by excessive leg lengthening. This can be addressed by subtrochanteric shortening osteotomy (short for SSTO) first described as a treatment for congenital dislocation of the hip in older children [12], which demands accurate anatomical knowledge and technical expertise for durable results. It was later applied to patients with THA [13]. The shortening subtrochanteric osteotomy (short for SSTO) combined with total hip arthroplasty was a good way to solve the difficulty and showed a good outcome of long-term follow-up. Many authors have reported SSTO with un-cemented THA [14–20]. SSTO procedure was complicated and challenging to surgeons. In clinical experience, for Crowe IV type developmental dysplasia of the hip, we found that some cases did not need SSTO and could get reduction while others hardly could not get reduction unless SSTO. With understanding and reviewing both the Crowe and Hartofilakidis classification systems, we presumed that the presence or absence of secondary false acetabulum may result in different biomechanical patterns of proximal femur and pelvis, which may lead to differences in the anatomical morphology of the proximal femur, affecting the depth of implantation of the prosthesis, and thus affecting the reduction and necessity of SSTO. Currently, the S-ROM prosthesis was recognized as the best prosthetic option for severe femoral deformity such as Crowe type IV DDH. This article was designed to investigate the surgical options between the presence and absence of secondary false acetabulum in the treatment of Crowe IV DDH with the S-ROM prosthesis. If difference presents, it is necessary to classify the Crowe IV type DDH into two subtypes depending on if false acetabulum exists or not, which facilitates and instructs surgery.

Oxidative stress and cardiomyocyte apoptosis play critical roles in doxorubicin (DOX)-induced cardiotoxicity. Previous studies indicated that fibronectin type III domain-containing 5 (FNDC5) and its cleaved form, irisin, could preserve mitochondrial function and attenuate oxidative damage as well as cell apoptosis, however, its role in DOX-induced cardiotoxicity remains unknown. Our present study aimed to investigate the role and underlying mechanism of FNDC5 on oxidative stress and cardiomyocyte apoptosis in DOX-induced cardiotoxicity. Cardiomyocyte-specific FNDC5 overexpression was achieved using an adeno-associated virus system, and then the mice were exposed to a single intraperitoneal injection of DOX (15 mg/kg) to generate DOX-induced cardiotoxicity. Herein, we found that FNDC5 expression was downregulated in DOX-treated murine hearts and cardiomyocytes. Fndc5 deficiency resulted in increased oxidative damage and apoptosis in H9C2 cells under basal conditions, imitating the phenotype of DOX-induced cardiomyopathy in vitro, conversely, FNDC5 overexpression or irisin treatment alleviated DOX-induced oxidative stress and cardiomyocyte apoptosis in vivo and in vitro. Mechanistically, we identified that FNDC5/Irisin activated AKT/mTOR signaling and decreased DOX-induced cardiomyocyte apoptosis, and moreover, we provided direct evidence that the anti-oxidant effect of FNDC5/Irisin was mediated by the AKT/GSK3β/FYN/Nrf2 axis in an mTOR-independent manner. And we also demonstrated that heat shock protein 20 was responsible for the activation of AKT caused by FNDC5/Irisin. In line with the data in acute model, we also found that FNDC5/Irisin exerted beneficial effects in chronic model of DOX-induced cardiotoxicity (5 mg/kg, i.p., once a week for three times, the total cumulative dose is 15 mg/kg) in mice. Based on these findings, we supposed that FNDC5/Irisin was a potential therapeutic agent against DOX-induced cardiotoxicity.

Gait is believed to be an advanced behavioral biometric that can be perceived at a large distance from a camera without subject cooperation and hence is favorable for many applications in surveillance and forensics. However, appearance differences caused by human aging may significantly reduce the performance of gait recognition. Modeling the aging process on gait features is one of the possible solutions to this problem, and it may inspire more potential applications, such as finding lost children and examining health status. To the best of our knowledge, this topic has not been studied in the literature. Motivated by the fact that aging effects are mainly reflected in the shape and appearance deformations of the gait feature, we propose a baseline algorithm for gait-based age progression and regression using a generic geometric transformation between different age groups, in conjunction with the gait energy image, which is an appearance-based gait feature frequently used in the gait analysis community, to render gait aging and reverse aging effects simultaneously. Various evaluations were conducted through gait-based age group classification and cross-age gait identification to validate the performance of the proposed method, in addition to providing several insights for future research on the subject.

Summary Background Although a large number of studies have identified obesity as an independent risk factor for the development of periprosthetic joint infection (PJI), the synergistic impacts of obesity with other factors on PJI remain unknown. Additionally, few studies have specifically explored the risk factors of PJI within a Chinese population. Aims To investigate the association between obesity and PJI in a Chinese population, and identify synergistic impacts of obesity with other risk factors on the development of PJI. Methods Three hundred and seven patients at a single institution with a diagnosis of PJI following primary total hip or knee arthroplasty, treated from 2008 to 2015, were identified. Each case was matched with two controls who did not develop PJI after primary total hip or knee arthroplasty in the study period using propensity score matching for several important parameters. Multi-variable logistic regression models were used to estimate the association between body mass index (BMI) and the risk of developing PJI. Interaction and stratified analyses were conducted according to age, sex, type of surgery, smoking status, alcohol use, diabetes, inflammatory arthritis, liver disease and renal disease. Findings The multiple logistic analyses showed that obesity was associated with increased risk of PJI [odds ratio (OR) 2.48; 95% confidence interval (CI) 1.66–3.69]. When analysed as a continuous variable, BMI was also associated with increased risk of PJI (OR per 1 kg/m2 increase in BMI 1.08; 95% CI 1.02–1.14). In the interaction analysis, patients who were obese and smoked had a higher OR of developing PJI than non-smokers who were obese (OR 3.54 vs 1.55, P-value for interaction=0.031). Similarly, the OR was much higher for patients with both obesity and inflammatory arthritis than for patients who were obese with no history of inflammatory arthritis (OR 3.9 vs 1.55, P-value for interaction=0.029). No other significant interactions were found in the association between obesity and PJI. Conclusion Obesity is an independent risk factor for the development of PJI in the Chinese Han population. Surgeons should be aware that obese patients who smoke or have inflammatory arthritis are at additional increased risk of PJI.

Studies on the highly pathogenic avian influenza (HPAI) H5N1 suggest that wild bird migration may facilitate its long-distance spread, yet the role of wild bird community composition in its transmission risk remains poorly understood. Furthermore, most studies on the diversity–disease relationship focused on host species diversity without considering hosts’ phylogenetic relationships, which may lead to rejecting a species diversity effect when the community has host species that are only distantly related. Here, we explored the influence of waterbird community composition for determining HPAI H5N1 occurrence in wild birds in a continental-scale study across Europe. In particular, we tested the diversity–disease relationship using both host species diversity and host phylogenetic diversity. Our results provide the first demonstration that host community composition—compared with previously identified environmental risk factors—can also effectively explain the spatial pattern of H5N1 occurrence in wild birds. We further show that communities with more higher risk host species and more closely related species have a higher risk of H5N1 outbreaks. Thus, both host species diversity and community phylogenetic structure, in addition to environmental factors, jointly influence H5N1 occurrence. Our work not only extends the current theory on the diversity–disease relationship, but also has important implications for future monitoring of H5N1 and other HPAI subtypes., SCOPUS: ar.j, info:eu-repo/semantics/published

Cardiomyocyte apoptosis is a key event in the process of doxorubicin (DOX)-induced cardiotoxicity. Our previous study found that rosmarinic acid (RA) could attenuate pressure overload-induced cardiac dysfunction via cardiac fibroblasts (CFs), however its effect in DOX-induced cardiotoxicity remains unknown. In the present study, mice were subjected to a single intraperitoneal injection of DOX (15mg/kg) to generate DOX-induced cardiotoxicity. Histological examination, echocardiography, and molecular markers were used to evaluate the effects of RA. Neonatal rat cardiomyocytes (CMs) and CFs were used to verify the protective effect of RA in vitro. Conditioned medium derived from RA-treated CFs were prepared to illustrate the effect of RA on paracrine interplay between CFs and CMs. We found that RA significantly alleviated DOX-induced cardiomyocyte apoptosis and cardiac dysfunction in vivo, which, however, had almost negligible beneficial effect on DOX directly induced cardiomyocyte apoptosis in vitro. Mechanistically, CFs-derived Fas L was responsible for DOX-induced cardiomyocyte apoptosis, and RA treatment could decrease Fas L expression in CFs and its release to the conditioned medium by suppressing nuclear factor of activated T cells (NFAT) activation and metalloproteinase 7 (MMP7) expression, and exerted the anti-apoptotic effect on CMs via CFs. Ionomycin, and activator of NFAT, abrogated RA-mediated protective effect on cardiomyocyte apoptosis and cardiac dysfunction. In summary, RA alleviated cardiomyocyte apoptosis by inhibiting the expression and release of Fas L in CFs via a paracrine manner, moreover, NFAT as well as MMP7 inhibition were responsible for the suppression of Fas L. RA could be a powerful new therapeutic agent to mitigate cardiomyocyte apoptosis, thereby improving DOX-induced cardiotoxicity.

Glutamate, the most abundant excitatory neurotransmitter in the nervous system, can induce biophotonic activity and transmission in mouse brain slices. As a signaling molecule, aspartate is not considered to be an independent neurotransmitter during the long evolution process, which may be just a co-transmitter or neuromodulator. In the view of structure and physiological similarities of aspartate and glutamate, as well as some differences between them, we attempted to investigate whether aspartate could also induce biophotonic activity in mouse brain slices and its effect characteristics. The ultraweak biophoton imaging system (UBIS) was used to carry out a real-time observation of biophoton activity induced by aspartate in mouse brain slices. It was found that the biophotonic emissions induced by aspartate at different concentrations (12.5 mM, 25 mM and 50 mM) presented concentration-dependent effects and 50 mM aspartate could obviously induce biophoton activities with the characteristic changes of initiation, maintenance, washing and reapplication, which were also different from that induced by 50 mM glutamate as reported before. Considering the species differences in excitatory neurotransmitters, these findings indicate that aspartate-induced biophotonic activity may imply the evolutionary differences in the animal brains.

B7-H3, one of the costimulatory members participating in checkpoint pathway, has been shown to be upregulated after hepatitis B virus (HBV) infection. To further explore the clinical significance of dynamic B7-H3 expression during the progression of HBV infection, we systematically investigated the expression pattern of B7-H3 and the correlation of B7-H3 expression with the ratio of T lymphocyte subsets and clinical parameters at different stages in the course of the disease. Flow cytometry and enzyme-linked immunosorbent assay data showed that soluble form of B7-H3 (sB7-H3) was positively correlated with the frequency of Treg cells in acute hepatitis B (AHB), chronic hepatitis B (CHB), and hepatocellular carcinoma patients with HBV infection (HBV-HCC). Membrane form of B7-H3 (mB7-H3) expressed on Treg cells and monocytes was positively correlated with the frequency of Treg cells in CHB. SB7-H3 had relationship with mB7-H3 expressed on Treg cells and monocytes at different stages during HBV infection, except for HBV-HCC. MB7-H3 expressed on Treg cells was positively correlated with that on monocytes in AHB, CHB, HBV-liver cirrhosis, and HBV-HCC. The B7-H3 expression was positively correlated with aspartate aminotransferase and alanine aminotransferase levels in CHB and sB7-H3 level was higher in late tumor/node/metastasis (TNM) stage in HCC. Higher mB7-H3 expression was associated with greater tumor size, later TNM stage, and worse prognosis in HBV-HCC indicated by immunohistochemistry. Taken together, these results suggested that B7-H3 might contribute to the progression of HBV infection by triggering inhibitory signals in effector T cells and it was closely associated with the progression and poor prognosis during HBV infection. B7-H3 could be utilized as a potential clinical indicator and a potential target for therapeutic strategies against HBV infection.

C1q/tumor necrosis factor-related protein-3 (CTRP3) shows striking homologies of genomic structure to the adiponectin. In this study, we aimed to investigate the protective role of CTRP3 against sepsis-induced cardiomyopathy. Here, we overexpressed CTRP3 in myocardium by direct intramyocardial injection and constructed a model of lipopolysaccharide (LPS)-induced sepsis in mice. Our results demonstrated that cardiac-specific overexpression of CTRP3 remarkably attenuated myocardial dysfunction and increased the phosphorylation level of AMPKα during LPS-induced sepsis. The anti-inflammatory effects of CTRP3, as determined by decreased mRNA levels of TNF-α, IL-6 and a lower protein expression of phosphorylated NF-κB p65 and IκBα, was detected in mice following LPS treatment. Additionally, CTRP3 suppressed cardiac apoptosis induced by LPS in mice as indicated by terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) staining and western blot for Cleaved-caspase3, Bax and Bcl-2. In conclusion, CTRP3 could protect against sepsis-induced myocardial dysfunction in mice. The cardioprotective effects of CTRP3 might be mediated by activating AMPKα signaling pathway and blunting inflammatory response and apoptosis.

BACKGROUND Barbed suture has reported time-saving and safety benefits for wound closure in total joint arthroplasty (TJA). However, this technique requires further investigation. The aim of this study was to use a prospective, randomized, self-controlled study to further determine the efficiency and safety of this technology and to introduce our modified suturing method through a randomized, self-controlled trial. MATERIAL AND METHODS From August 2015 to December 2016, 84 patients (hip 46, knee 38) who had undergone primary simultaneous bilateral total knee or hip arthroplasties were enrolled in this study. Barbed sutures were randomized and used on one side, and traditional sutures (Vicryl) were used on the other side. RESULTS Closure time was shorter with the barbed sutures: 6.25 min (12.00 min vs. 18.25 min, p=0.000) for hip and 5.54 min (13.18 min vs. 18.71 min, p=0.000) for knee. There was no difference in the complication rate for the 2 groups. The total cost of our suturing strategy (Quill) was 872.3 RMB, which is 375.1 RMB higher than the total cost of the standard suture method (Vicryl). However, the traditional barbed suturing method (Quill) cost 2195.6 RMB. CONCLUSIONS Barbed suturing was a fast and safe method for wound closure in TJA. We also recommend our modified suturing strategy, especially in countries where operation cost was not associated with operation time.

Background Pigmented villonodular synovitis (PVNS) is a relatively rare, locally aggressive, and potentially recurrent synovial disease of large joints. The purpose of this study was to investigate (1) the disease recurrence rate and (2) the treatment outcomes including Harris hip scores, complications, and revision following cementless total hip arthroplasty (THA) with ceramic-on-ceramic (CoC) articulation in patients with PVNS. Methods Twenty-two patients (14 females and 8 males) with histologically confirmed PVNS underwent cementless THA using CoC bearings between 2000 and 2013. Three patients with less than 5-year follow-up were excluded. The mean age was 35.2 years (range, 22–58 years) with a mean follow-up of 8.6 years (range, 6.9–10.8 years). A control group was matched in a 2:1 ratio with the PVNS group for age, sex, body mass index (BMI), year of surgery, and American Society of Anesthesiologists score (ASA). Postoperative outcome variables included disease recurrence, Harris Hip Scores (HHS) at the latest follow-up, complications (dislocation, squeaking, ceramic fracture), and any-cause revision. A Kaplan-Meier implant survivorship curve with 95% confidence interval (CI) of the two groups was generated. Results No recurrence of PVNS was noted in the follow-up period. The HSS in the PVNS group was 92.6 ± 5.5, which was similar to the control group (93.4 ± 4.6, p = 0.584) at the last follow-up visit. No patients sustained dislocation, osteolysis, or any ceramic fracture within the study duration. One patient in the PVNS group had a complication of squeaking, but did not require revision. Another patient in the PVNS group underwent revision surgery due to aseptic loosening. There was no significant difference in revision rates between the two groups (p = 1.000). The implant survivorship free of any revision was 90.0% (95% CI, 73.2% to 100%) in the PVNS group and 92.5% (95% CI, 82.6% to 100%) in the control group at 10 years (p = 0.99). Conclusions For young and active patients with end-stage PVNS of the hips, cementless THA using CoC bearing has similar functional outcome scores, a low complication rate, and similar implant survivorship compared to the control group.

Cognition and pain share common neural substrates and interact reciprocally: chronic pain compromises cognitive performance, whereas cognitive processes modulate pain perception. In the present study, we established a non-drug-dependent rat model of context-based analgesia, where two different contexts (dark and bright) were matched with a high (52°C) or low (48°C) temperature in the hot-plate test during training. Before and after training, we set the temperature to the high level in both contexts. Rats showed longer paw licking latencies in trials with the context originally matched to a low temperature than those to a high temperature, indicating successful establishment of a context-based analgesic effect in rats. This effect was blocked by intraperitoneal injection of naloxone (an opioid receptor antagonist) before the probe. The context-based analgesic effect also disappeared after optogenetic activation or inhibition of the bilateral infralimbic or prelimbic sub-region of the prefrontal cortex. In brief, we established a context-based, non-drug dependent, placebo-like analgesia model in the rat. This model provides a new and useful tool for investigating the cognitive modulation of pain.

Anxiety is a common comorbidity associated with chronic pain, which results in chronic pain complexification and difficulty in treatment. Electroacupuncture (EA) is commonly used to treat chronic pain and anxiety. However, the underlying mechanisms of the EA effect are largely unknown. Here, we showed that a circuitry underlying chronic pain induces anxiety disorders, and EA can treat them by regulating such circuitry. Using chemogenetic methods, we found that chemogenetic activation of the rostral anterior cingulate cortex (rACC) glutamatergic output to the thalamus induced anxiety disorders in control rats. Then, chemogenetic inhibition of the rACC-thalamus circuitry reduced anxiety-like behavior produced by intraplantar injection of the complete Freund’s adjuvant (CFA). In this study, we examined the effects of EA on a rat model of CFA-mediated anxiety-like behaviors and the related mechanisms. We found that chemogenetic activation of the rACC-thalamus circuitry effectively blocked the effects of EA on chronic pain-induced anxiety-like behaviors in CFA rats. These results demonstrate an underlying rACC-thalamus glutamatergic circuitry that regulates CFA-mediated anxiety-like behaviors. This study also provides a potential mechanistic explanation for EA treatment of anxiety caused by chronic pain.

Aims The aim of this study was to further evaluate the accuracy of ten promising synovial biomarkers (bactericidal/permeability-increasing protein (BPI), lactoferrin (LTF), neutrophil gelatinase-associated lipocalin (NGAL), neutrophil elastase 2 (ELA-2), α-defensin, cathelicidin LL-37 (LL-37), human β-defensin (HBD-2), human β-defensin 3 (HBD-3), D-dimer, and procalcitonin (PCT)) for the diagnosis of periprosthetic joint infection (PJI), and to investigate whether inflammatory joint disease (IJD) activity affects their concentration in synovial fluid. Methods We included 50 synovial fluid samples from patients with (n = 25) and without (n = 25) confirmed PJI from an institutional tissue bank collected between May 2015 and December 2016. We also included 22 synovial fluid samples aspirated from patients with active IJD presenting to Department of Rheumatology, the first Medical Centre, Chinese PLA General Hospital. Concentrations of the ten candidate biomarkers were measured in the synovial fluid samples using standard enzyme-linked immunosorbent assays (ELISA). The diagnostic accuracy was evaluated by receiver operating characteristic (ROC) curves. Results BPI, LTF, NGAL, ELA-2, and α-defensin were well-performing biomarkers for detecting PJI, with areas under the curve (AUCs) of 1.000 (95% confidence interval, 1.000 to 1.000), 1.000 (1.000 to 1.000), 1.000 (1.000 to 1.000), 1.000 (1.000 to 1.000), and 0.998 (0.994 to 1.000), respectively. The other markers (LL-37, HBD-2, D-dimer, PCT, and HBD-3) had limited diagnostic value. For the five well-performing biomarkers, elevated concentrations were observed in patients with active IJD. The original best thresholds determined by the Youden index, which discriminated PJI cases from non-PJI cases could not discriminate PJI cases from active IJD cases, while elevated thresholds resulted in good performance. Conclusion BPI, LTF, NGAL, ELA-2, and α-defensin demonstrated excellent performance for diagnosing PJI. However, all five markers showed elevated concentrations in patients with IJD activity. For patients with IJD, elevated thresholds should be considered to accurately diagnose PJI. Cite this article: Bone Joint J 2021;103-B(1):32–38.