Immunogenic profiling of Mycobacterium tuberculosis Rv1513 reveals its ability to switch on Th1 based immunity.

Tuberculosis (TB) is one of the infectious diseases caused by the pathogen Mycobacterium tuberculosis that continuously threatens the global human health. Bacillus Calmette-Guérin (BCG) vaccine is the only vaccine that has been used clinically to prevent tuberculosis in recent centuries, but its limitations in preventing latent infection and reactivation of tuberculosis do not provide full protection. In this study, we selected the membrane-associated antigen Rv1513 of Mycobacterium. In order to achieve stable expression and function of the target gene, the prokaryotic expression recombinant vector pET30b-Rv1513 was constructed and expressed and purified its protein. Detection of IFN- γ levels in the peripheral blood of TB patients stimulated by whole blood interferon release assay (WBIA) and multi-microsphere flow immunofluorescence luminescence (MFCIA) revealed that the induced production of cytokines, such as IFN-γ and IL-6, was significantly higher than that in the healthy group. Rv1513 combined with adjuvant DMT (adjuvant system liposomes containing dimethyldioctadecylammonium bromide (DDA), monophospholipid A (MPL), and trehalose-660-dibenzoic acid (TDB)) was used to detect serum specific antibodies, cytokine secretion from splenic suprasplenic cell supernatants, and multifunctional T-cell levels in splenocytes in immunised mice. The levels of IFN-γ, TNF-α, and IL-2 secreted by mouse splenocytes were found in the Rv1513+DMT group and the BCG+Rv1513+DMT group. The serum levels of IgG and its subclasses and the number of IFN-γ+T cells, TNF-α+T and IFN-γ+TNF-α+T cells in the induced CD4+/CD8+T cells in mice were significantly higher than those in the BCG group, and the highest levels were found in the BCG+Rv1513+DMT group. These findings suggest that Rv1513/DMT may serve as a potential subunit vaccine candidate that may be effective as a booster vaccine after the first BCG vaccination.

Risk factor analysis and establishment of a nomogram model to predict blood loss during total knee arthroplasty.

PURPOSE: The risk factors for excessive blood loss and transfusion during total knee arthroplasty (TKA) remain unclear. The present study aimed to determine the risk factors for excessive blood loss and establish a predictive model for postoperative blood transfusion. METHODS: This retrospective study included 329 patients received TKA, who were randomly assigned to a training set (n = 229) or a test set (n = 100). Univariate and multivariate linear regression analyses were used to determine risk factors for excessive blood loss. Univariate and multivariate logistic regression analyses were used to determine risk factors for blood transfusion. R software was used to establish the prediction model. The accuracy and stability of the models were evaluated using calibration curves, consistency indices, and receiver operating characteristic (ROC) curve analysis. RESULTS: Risk factors for excessive blood loss included timing of using a tourniquet, the use of drainage, preoperative ESR, fibrinogen, HCT, ALB, and free fatty acid levels. Predictors in the nomogram included timing of using a tourniquet, the use of drainage, the use of TXA, preoperative ESR, HCT, and albumin levels. The area under the ROC curve was 0.855 (95% CI, 0.800 to 0.910) for the training set and 0.824 (95% CI, 0.740 to 0.909) for the test set. The consistency index values for the training and test sets were 0.855 and 0.824, respectively. CONCLUSIONS: Risk factors for excessive blood loss during and after TKA were determined, and a satisfactory and reliable nomogram model was designed to predict the risk for postoperative blood transfusion.

Radiographic evaluation of robot-assisted versus manual total hip arthroplasty: a multicenter randomized controlled trial.

BACKGROUND: The effectiveness of robot-assisted surgery remains contentious due to the lack of high-quality randomized controlled trials (RCTs) to elevate the level of evidence. We aimed to evaluate the postoperative radiographic outcomes of robot-assisted (RAS-THA) versus manual (M-THA) total hip arthroplasty. METHODS: This multicenter RCT was performed from March 1, 2021 to December 1, 2021. Patients were randomly assigned to routine M-THA or to RAS-THA that used the TRex-RS orthopedic joint surgical navigation system. The primary outcome was to compare the acetabular component orientation, femoral stem alignment, femoral canal fill ratio, and leg length discrepancy between RAS-THA and M-THA using postoperative radiography. Subgroup analyses of the two groups stratified by surgical approach, gender, and BMI were also conducted. RESULTS: Seventy-three participants were randomly allocated to the RAS-THA group, while seventy-two participants were assigned to the M-THA group. Compared to the M-THA group, the RAS-THA group exhibited less variability in the preoperative planning of the vertical center of rotation (VCOR; P < 0.001), demonstrated a significant advantage in femoral stem alignment (P = 0.004), and showed pronounced decreases in inequality and in the variability in leg length discrepancy (P < 0.001). There was no significant difference in the Lewinnek safe-zone ratio (P = 0.081) and the femoral canal fill ratio (P > 0.05) between the two groups. Further subgroup analysis also showed that the RAS-THA group had fewer horizontal center of rotation (HCOR) and leg length differences when stratified by surgical approach, gender, and overweight status. CONCLUSION: This RCT found that, regardless of the surgical approach, gender, or body mass index, RAS-THA can effectively improve the postoperative VCOR and significantly reduce the variability of leg length difference. RAS-THA should be considered an effective method to enhance surgical precision by achieving less variability in challenging patients with leg length discrepancies. TRIAL REGISTRATION: ChiCTR2100044124.

Prospective randomized controlled trial on the accuracy of prosthesis positioning in total hip arthroplasty assisted by a newly designed whole-process robotic arm.

INTRODUCTION: The purpose of this article is to study whether the newly designed whole-process total hip arthroplasty (THA) robotic arm can improve the accuracy of prosthesis placement in THA. METHOD: In this study, 72 patients undergoing THA were prospectively included and randomly divided into two groups. The experimental group was treated with THA assisted by a newly designed robotic arm. The control group received THA with conventional surgical methods. The imaging data were compared after operation. RESULT: Compared with the conventional operation, the whole-process robotic arm can more accurately place the acetabular prosthesis in the anteversion safe zone of 5 ~ 25°, but in terms of the inclination angle, whether the reference is the safe zone of 30 ~ 50° or 30 ~ 45°, there is no statistical difference between the two groups. The average lower limb length discrepancy (LLLD) in the experimental group was 3.77 ± 8.31 mm longer than contralateral side, while the counterpart in the control group was 8.39 ± 9.11 mm, with significant difference (P = 0.029). The femoral prosthesis was fixed in neutral position in 35 (100%) cases in the experimental group and only 30 (83.3%) in the control group (P = 0.036). There was no significant difference in the recovery of hip offset, femoral anteversion, and canal fill ratio (CFR) between the two groups. CONCLUSION: Robotic arm can improve the accuracy of anteversion of acetabular cup, restore the consistency of the length of lower limbs, and more accurately implant the femoral prosthesis to the neutral position in the coronal position. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2100044124 (date of registration: 2021-3-11).

The effect of BMI on the mid-term clinical outcomes of mobile-bearing unicompartmental knee arthroplasty.

OBJECTIVE: To evaluate the impact of body mass index (BMI) on the mid-term clinical outcomes and survival in patients receiving a mobile-bearing unicompartmental knee arthroplasty (UKA). METHODS: We retrospectively collected data from 355 patients who underwent UKA from June 2006 to June 2015, with a mean follow-up of 106.5 ± 22.5 months. Patients were assigned into four groups based on their BMI before surgery: normal weight group (BMI 18.5 ~ 22.9 kg/m2), overweight group (23 ~ 24.9 kg/m2), obesity group (25 ~ 29.9 kg/m2), and severe obesity group (≥ 30 kg/m2). The knee society score (KSS), knee society function score (KSFS), hospital for special surgery score (HSS), and range of motion (ROM) were assessed before the operation and at the last follow-up. The femorotibial angle (FTA) was assessed after the operation immediately and at the last follow-up. Kaplan-Meier survival analysis was performed among the four groups. RESULTS: The KSS, KSFS, and HSS in all groups were markedly improved compared with the preoperative values (p<0.001), but the ROM score was not significantly different (p>0.05). There were significant differences in KSS (p<0.001) and HSS (p = 0.004) across the four BMI groups, and these differences were due to the severe obesity group. All groups exhibited an inclination of knee varus deformity at the last follow-up (p < 0.05). Moreover, no marked difference in the implant survival rate was found among the different groups (p = 0.248), or in the survival curves (p = 0.593). CONCLUSIONS: BMI does not influence the implant survival rate. The postoperative functional and quality-of-life scores were significantly improved in all groups. Obese (BMI ≥30 kg/m2) individuals should not be excluded from UKA.

Robotic-arm assisted versus conventional technique for total knee arthroplasty: early results of a prospective single centre study.

PURPOSE: The purpose of this study was to compare the early functional outcomes between robotic-arm assisted total knee arthroplasty (RATKA) and conventional manual total knee arthroplasty (TKA). METHODS: This prospective cohort study included 52 patients (26 RATKA and 26 TKA). All procedures were performed by a single experienced surgeon using identical approach and implant designs. Post-operative evaluation consisted of the risks of inflammatory and blood loss, the accuracy of mechanical alignment, post-operative pain, peri-operative and post-operative functional outcomes, and complications for 30 days after index surgery. RESULTS: There was no statistical difference in baseline characteristics of patients between two groups (p > 0.05). There was a trend that the operative time of RATKA was prolonged compared with manual TKA (p < 0.0001). However, the risks of infection and blood loss did not increase accordingly (p > 0.05). No statistical difference was found in the correction of mechanical alignment between two groups (p > 0.05). The RATKA was associated with reduced pain post-operatively in day 1 (p < 0.05). Afterwards, there was no systematic difference in VAS score from day two to three post-operatively (p > 0.05). There was no significant difference in functional recovery (p > 0.05). No complication occurred in both groups. CONCLUSION: Although the operative time was prolonged in RATKA, it did not increase the risks of infection and blood loss. There was no significant difference in radiological or functional outcomes between RATKA and conventional manual TKA. RATKA might be related to reduced pain after surgery.

Potential factors in postoperative dislocation of Oxford phase III mobile bearing UKA in Chinese patients: a single-center retrospective study.

BACKGROUND: Bearing dislocation is the main complication after mobile bearing unicompartmental knee arthroplasty. The purpose of this study was to analyze the potential risk factors of bearing dislocation after Oxford phase III mobile bearing unicompartmental knee arthroplasty in Chinese patients. METHODS: We retrospectively investigated 492 patients (578 knees) who underwent Oxford phase III mobile bearing unicompartmental knee arthroplasty in our institution between February 2009 and June 2019. The patients were divided into two groups based on surgeons' annual surgical volume. Those with/ without bearing dislocation were compared based on patient, surgeon and implant factors. RESULTS: Among the 492 patients, 21 (4.3%, 4 men and 17 women) experienced bearing dislocation. Of these, 14 (4.0%) were in the high surgical volume group and 7 (5.1%) were in the low surgical volume group. Multivariate analysis revealed that trauma to the operated leg and daily life involving high knee flexion cumulatively predicted bearing dislocation (p < 0.05). CONCLUSIONS: Trauma to the operated leg and daily life involving high knee flexion were risk factors for bearing dislocation after Oxford phase III mobile bearing unicompartmental knee arthroplasty.

GMSRI: A Texture-Based Martian Surface Rock Image Dataset.

CNN-based Martian rock image processing has attracted much attention in Mars missions lately, since it can help planetary rover autonomously recognize and collect high value science targets. However, due to the difficulty of Martian rock image acquisition, the accuracy of the processing model is affected. In this paper, we introduce a new dataset called "GMSRI" that is a mixture of real Mars images and synthetic counterparts which are generated by GAN. GMSRI aims to provide a set of Martian rock images sorted by the texture and spatial structure of rocks. This paper offers a detailed analysis of GMSRI in its current state: Five sub-trees with 28 leaf nodes and 30,000 images in total. We show that GMSRI is much larger in scale and diversity than the current same kinds of datasets. Constructing such a database is a challenging task, and we describe the data collection, selection and generation processes carefully in this paper. Moreover, we evaluate the effectiveness of the GMSRI by an image super-resolution task. We hope that the scale, diversity and hierarchical structure of GMSRI can offer opportunities to researchers in the Mars exploration community and beyond.

[A comparative research on the treatment of ankle fracture with dislocation between emergency surgery and selective surgery].

OBJECTIVE: To investigate the differences between emergency surgery and selective surgery treatment of ankle fractures with dislocation. METHODS: In the study, 40 patients with ankle fracture and dislocation were treated and followed up from May 2013 to May 2014, and all the data were collected and analyzed. The subjects involved 29 male patients and 11 female patients. The patients were randomly separated into two groups, and the patients in group A were given surgical intervention within 6 hours after injury, while those in group B were initially given close reduction and given selective operation when the soft tissue condition got better. Group A contained 13 male patients and 7 female patients with average age of 37.10; Group B consisted of 15 male and 5 female, with average age of 37.85. RESULTS: The Baird-Jackson score was applied for assessment of the patients' outcomes. According to the score, the outcomes were classified into excellent, good, fair, and poor. In group A (emergency group), the outcomes were 13 (65.0%), 4 (20.0%), 3 (15.0%), and 0, respectively. In group B (selective group), they were 11 (55.0%), 7 (35.0%), 2 (10.0%), and 0, respectively. The numbers of the patients from excellent to poor were 24 (55.0%), 11 (27.5%), 5 (12.5%), and 0, respectively. CONCLUSION: There is no significant difference in postoperative function between the two groups, however, early surgical intervention can benefit in accomplishing anatomical reduction much easier and shortening the time of hospitalization, which is cost-saving for the patients.

Improved radiographic outcomes and decreased complications rate on the femoral side can be achieved by a novel designed whole-process robotic assisted hip system for total hip arthroplasty: a prospective randomized controlled trial.

Postoperative complications due to inaccurate prosthesis positioning are the main causes of early revision. The aim of this study was to (1) determine whether novel designed whole-process robotic assisted hip system allowed better radiographic outcomes and lower complications risk on the femoral side particularly stem subsidence compared to conventional THA, and to (2) identify the comparison of early clinical outcomes. 72 patients were initially enrolled and randomly divided into 2 groups. Finally, only 65 patients (31 RA-THAs, 34 C-THAs) were analyzed who had full 18-month follow-up data. Radiographic follow-up was performed at immediate and 6-month postoperatively, while clinical follow-up at 18-month postoperatively. Stem-related radiographic outcomes, femoral side complications and clinical scores were compared. The robotic arm allowed better radiographic outcomes of the femoral side, including a higher canal fill ratio (CFR) at B1 (P = 0.040), more neutral stem alignment (P = 0.029), lower subsidence (P = 0.023) and lower leg length discrepancy (LLD) (P = 0.010). In addition, low CFR at B1 (P = 0.001) was found the risk factor for subsidence. However, early clinical outcomes were consistent between both groups. The novel designed whole-process robotic assisted hip system covers both femoral and acetabular side operations. It allows accurate and safe manipulation of femoral side, including better stem-related radiographic outcomes and lower risk of subsidence and LLD. However, no advantage of robotic system in early clinical score was identified. Clinical trial registration number: ChiCTR2100044124.

A new designed full process coverage robot-assisted total hip arthroplasty: a multicentre randomized clinical trial.

OBJECTIVE: To compare the effect of a new complete robot-assisted total hip arthroplasty (RA-THA) with that of the manual total hip arthroplasty (MTHA) and to verify the accuracy and safety of the former. METHODS: Overall, 148 patients were enroled from 3 March 2021 to 28 December 2021 in this study and classified into RA-THA ( n =74 patients) and MTHA ( n =74 patients) groups. The sex, age, operative side, BMI, diagnosis, other basic information, operative time, acetabular prosthesis anteversion and inclination, femoral prosthesis anteversion and angulation, femoral prosthesis filling rate, leg length discrepancy (LLD), Harris hip score, and visual analogue scale (VAS) score of the two groups were compared. RESULTS: No significant differences were observed in the two groups regarding sex, age, operative side, BMI, diagnosis, Harris hip score, VAS score, acetabular inclination, acetabular prosthesis anteversion, femoral prosthesis anteversion, combined anteversion, and femoral prosthesis filling rate ( P >0.05). The operative time was significantly longer in the RA-THA group than in the MTHA group (106.71±25.22 min vs. 79.42±16.16 min; t=7.30, P <0.05). The femoral angulation (1.78°±0.64°) and LLD (2.87±1.55 mm) in the RA-THA group were significantly lesser than those in the MTHA group (2.22°±1.11° and 5.81±6.27 mm, respectively; t=-2.95 and t=-3.88, P <0.05). CONCLUSION: The complete RA-THA has some advantages over the traditional procedure in restoring the lower limb length and controlling the femoral prosthesis angulation. Thus, this study verifies the accuracy and safety of the robot-assisted system.

Construction and expression of Mycobacterium tuberculosis fusion protein SHR3 and its immunogenicity analysis in combination with various adjuvants.

Tuberculosis (TB) today remains the leading cause of global deaths due to infectious bacterial pathogens. The Bacillus Calmette-Guérin (BCG) vaccine is the only vaccine clinically used to prevent TB. However, its limitations in preventing latent infection and TB reactivation mean that it does not provide comprehensive protection. In this study, we successfully constructed and expressed the multistage fusion protein, SHR3, and used whole blood IFN-γ release assay (WBIA) with flow cytometry to detect antigen specificity, further confirmed by enzyme-linked immunosorbent assay (ELISA). SHR3 and its subfractional proteins stimulated the level of IFN-γ production by lymphocytes from M. tb-infected patients, inducing the production of single-positive and double-positive CD4+ and CD8+ T cells with IFN-γ and IL-2, at levels significantly higher than those of healthy controls. The fusion protein and complex adjuvant group (SHR3/DMT) induced mice to produce significantly higher levels of IgG antibodies and their subclasses, with IgG2a/IgG1 results showing a convergent Th1-type response; mice in the BCG + SHR3/DMT group induced secretion of the highest levels of IL-2, and TNF-α, irrespective of stimulation with purified protein derivative or SHR3. These findings suggest that SHR3/DMT could be a potential subunit vaccine candidate that may serve as an effective booster vaccine after BCG primary immunization.

Genetic Variations of MSTN and Callipyge in Tibetan Sheep: Implications for Early Growth Traits.

Tibetan sheep are vital to the ecosystem and livelihood of the Tibetan Plateau; however, traditional breeding methods limit their production and growth. Modern molecular breeding techniques are required to improve these traits. This study identified a single nucleotide polymorphism (SNP) in myostatin (MSTN) and Callipyge in Tibetan sheep. The findings indicated notable associations between MSTN genotypes and growth traits including birth weight (BW), body length (BL), chest width (ChW), and chest circumference (ChC), as well as a particularly strong association with cannon circumference (CaC) at 2 months of age. Conversely, Callipyge polymorphisms did not have a significant impact on Tibetan sheep. Moreover, the analyses revealed a significant association between sex and BW or hip width (HW) at 2 months of age and ChW, ChC, and CaC at 4 months of age. Furthermore, the study's results suggested that the genotype of MSTN as a GA was associated with a notable sex effect on BW, while the genotype of Callipyge (CC) showed a significant impact of sex on CaC at 2 months of age. These results indicated that the SNP of MSTN could potentially serve as a molecular marker for early growth traits in Tibetan sheep.

Causal relationship between serum metabolites and juvenile idiopathic arthritis: a mendelian randomization study.

BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is a condition that occurs when individuals under the age of 16 develop arthritis that lasts for more than six weeks, and the cause is unknown. The development of JIA may be linked to serum metabolites. Nevertheless, the association between JIA pathogenesis and serum metabolites is unclear, and there are discrepancies in the findings across studies. METHODS: In this research, the association between JIA in humans and 486 serum metabolites was assessed using genetic variation data and genome-wide association study. The identification of causal relationships was accomplished through the application of univariate Mendelian randomization (MR) analysis. Various statistical methods, including inverse variance weighted and MR-Egger, were applied to achieve this objective. To ensure that the findings from the MR analysis were trustworthy, a number of assessments were carried out. To ensure the accuracy of the obtained results, a range of techniques were utilised including the Cochran Q test, examination of the MR-Egger intercept, implementation of the leave-one-out strategy, and regression analysis of linkage disequilibrium scores. In order to identify the specific metabolic pathways associated with JIA, our primary objective was to perform pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes. RESULTS: Two-sample summary data MR analyses and sensitivity analyses showed that five metabolites were significantly causally associated with JIA, including two risk factors-kynurenine (odds ratio [OR]: 16.39, 95% confidence interval [CI]: 2.07-129.63, p = 5.11 × 10- 6) and linolenate (OR: 16.48, 95% CI: 1.32-206.22, p = 0.030)-and three protective factors-3-dehydrocarnitine (OR: 0.32, 95% CI: 0.14-0.72, p = 0.007), levulinate (4-oxovalerate) (OR: 0.40, 95% CI: 0.20-0.80, p = 0.010), and X-14,208 (phenylalanylserine) (OR: 0.68, 95% CI: 0.51-0.92, p = 0.010). Furthermore, seven metabolic pathways, including α-linolenic acid metabolism and pantothenate and CoA biosynthesis, are potentially associated with the onset and progression of JIA. CONCLUSION: Five serum metabolites, including kynurenine and 3-dehydrocarnitine, may be causally associated with JIA. These results provide a theoretical framework for developing effective JIA prevention and screening strategies.

Fatigue database of additively manufactured alloys.

Fatigue is a process of mechanical degradation that is usually assessed based on empirical rules and experimental data obtained from standardized tests. Fatigue data of engineering materials are commonly reported in S-N (the stress-life relation), ε-N (the strain-life relation), and da/dN-ΔK (the relation between the fatigue crack growth rate and the stress intensity factor range) data. Fatigue and static mechanical properties of additively manufactured (AM) alloys, as well as the types of materials, parameters of AM, processing, and testing are collected from thousands of scientific articles till the end of 2022 using natural language processing, machine learning, and computer vision techniques. The results show that the performance of AM alloys could reach that of conventional alloys although data dispersion and system deviation are present. The database (FatigueData-AM2022) is formatted in compact structures, hosted in an open repository, and analyzed to show their patterns and statistics. The quality of data collected from the literature is measured by defining rating scores for datasets reported in individual studies and through the fill rates of data entries across all the datasets. The database also serves as a high-quality training set for data processing using machine learning models. The procedures of data extraction and analysis are outlined and the tools are publicly released. A unified language of fatigue data is suggested to regulate data reporting for the fatigue performance of materials to facilitate data sharing and the development of open science.

Fatigue database of complex metallic alloys.

The past few decades have witnessed rapid progresses in the research and development of complex metallic alloys such as metallic glasses and multi-principal element alloys, which offer new solutions to tackle engineering problems of materials such as the strength-toughness conflict and deployment in harsh environments and/or for long-term service. A fatigue database (FatigueData-CMA2022) is compiled from the literature by the end of 2022. Data for both metallic glasses and multi-principal element alloys are included and analyzed for their statistics and patterns. Automatic extraction and manual examination are combined in the workflow to improve the efficiency of processing, the quality of published data, and the reusability. The database contains 272 fatigue datasets of S-N (the stress-life relation), ε-N (the strain-life relation), and da/dN-ΔK (the relation between the fatigue crack growth rate and the stress intensity factor range) data, together with the information of materials, processing and testing conditions, and mechanical properties. The database and scripts are released in open repositories, which are designed in formats that can be continuously expanded and updated.

Sirtuins in osteoarthritis: current understanding.

Osteoarthritis (OA) is a common disease characterized by severe chronic joint pain, that imposes a large burden on elderly people. OA is a highly heterogeneous disease, and multiple etiologies contribute to its progression. Sirtuins (SIRTs) are Class III histone deacetylases (HDACs) that regulate a comprehensive range of biological processes such as gene expression, cell differentiation, and organism development, and lifespan. Over the past three decades, increasing evidence has revealed that SIRTs are not only important energy sensors but also protectors against metabolic stresses and aging, and an increasing number of studies have focused on the functions of SIRTs in OA pathogenesis. In this review, we illustrate the biological functions of SIRTs in OA pathogenesis from the perspectives of energy metabolism, inflammation, autophagy and cellular senescence. Moreover, we offer insights into the role played by SIRTs in regulating circadian rhythm, which has recently been recognized to be crucial in OA development. Here, we provide the current understanding of SIRTs in OA to guide a new direction for OA treatment exploration.

Senescence-responsive miR-33-5p promotes chondrocyte senescence and osteoarthritis progression by targeting SIRT6.

Osteoarthritis (OA) is a prevalent disease among elderly individuals that is caused by cartilage degeneration. Chondrocyte senescence involved in the development of OA, and antisenescence therapies have been proposed for OA treatment. In our study, we identified the role of a microRNA, miR-33-5p, in promoting chondrocyte senescence and OA progression. miR-33-5p expression was upregulated under senescence conditions. miR-33-5p-mimic transfection can induce cellular senescence, while transfection of a miR-33-5p-inhibitor in chondrocytes alleviated senescence induced by IL-1ß. Moreover, SIRT6 expression was downregulated under IL-1ß treatment, and could be restored by miR-33-5p-inhibitor transfection. Luciferase assays revealed that miR-33-5p targeted the SIRT6 mRNA 3' UTR. In addition, SIRT6 mRNA expression showed negative correlations with senescence and OA degree in human cartilage. Bioinformatic analysis also confirmed the pro-senescence effect of miR-33-5p. Furthermore, periodic intraarticular injection of agomiR-33-5p induced cartilage loss and OA-like cartilage changes. To conclude, we revealed the pro-senescence and cartilage-destructive effect of miR-33-5p, whose expression was elevated under various senescence conditions, and showed that SIRT6 was one of its targets. Therefore, miR-33-5p is a potential therapeutic target for treating OA.

The influence of prosthetic positioning and proximal femoral morphology on leg length discrepancy and early clinical outcomes of cementless total hip arthroplasty.

BACKGROUND: Leg length discrepancy (LLD) is a common complication of total hip arthroplasty (THA). However, the relationship between femoral prosthesis filling, proximal femoral morphology, and acetabular prosthesis positioning with postoperative LLD and clinical outcomes is unclear. The aims of this study were to investigate the influence of canal flare index (CFI), canal fill ratio (CFR), center of rotation (COR), and femoral offset (FO) on (1) postoperative LLD; and (2) clinical outcomes in the two stem designs with different coating distribution. METHODS: The study cohort included 161 patients who underwent primary cementless THA between January 2021 and March 2022 with either proximal coating or full coating stems. Multivariate logistic regression was used to assess the effect of CFI, CFR, COR, and FO on postoperative LLD, and linear regression to assess their effect on clinical outcomes. RESULTS: No statistical difference was found in clinical outcomes or postoperative LLD between the two groups. High CFI (p = 0.014), low ΔVCOR (p = 0.012), and Gender (p = 0.028) were found independent risk factors for LLD one day postoperative. High CFI was also an independent risk factor for postoperative subjectively perceived LLD (p = 0.013). CFR at the level of 2 cm below the LT (p = 0.017) was an independent risk factor for Harris Hip Score. CONCLUSIONS: Proximal femoral morphology and acetabular prosthesis positioning but not femoral prosthesis filling affected the LLD. High CFI was an independent risk factor for postoperative LLD and subjectively perceived LLD, and low ΔVCOR was also an independent risk factor for postoperative LLD. Women were susceptible to postoperative LLD.