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.

Different reference genomes determine different results: Comparing SNP calling in RAD-seq of Engelhardia roxburghiana using different reference genomes.

Advances in next-generation sequencing (NGS) have significantly reduced the cost and improved the efficiency of obtaining single nucleotide polymorphism (SNP) markers, particularly through restriction site-associated DNA sequencing (RAD-seq). Meanwhile, the progression in whole genome sequencing has led to the utilization of an increasing number of reference genomes in SNP calling processes. This study utilized RAD-seq data from 242 individuals of Engelhardia roxburghiana, a tropical tree of the walnut family (Juglandaceae), with SNP calling conducted using the STACKS pipeline. We aimed to compare both reference-based approaches, namely, employing a closely related species as the reference genome versus the species itself as the reference genome, to evaluate their respective merits and limitations. Our findings indicate a substantial discrepancy in the number of obtained SNPs between using a closely related species as opposed to the species itself as reference genomes, the former yielded approximately an order of magnitude fewer SNPs compared to the latter. While the missing rate of individuals and sites of the final SNPs obtained in the two scenarios showed no significant difference. The results showed that using the reference genome of the species itself tends to be prioritized in RAD-seq studies. However, if this is unavailable, considering closely related genomes is feasible due to their wide applicability and low missing rate as alternatives. This study contributes to enrich the understanding of the impact of SNP acquisition when utilizing different reference genomes.

The interval between staged bilateral total knee arthroplasties does not affect early complications of the second knee or long-term function of the first and second knees.

BACKGROUND: This study explored the optimal time interval between staged bilateral total knee arthroplasty (BTKA) to minimize early complications of the second TKA and maximise the long-term function of the first and second knees. METHODS: We retrospectively reviewed 266 patients who underwent staged BTKA between 2013 and 2018. Groups 1-4 had time intervals between BTKAs of 1-6, 6-12, 12-18, and 18-24 months, respectively. Demographics, postoperative complications within 90 days of the second TKA, Knee Society Score (KSS), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) score were compared among the groups. RESULTS: In total, 54, 96, 75, and 41 patients were assigned to groups 1-4, respectively. Although group 1 had the highest overall complication rate (11.11%), there was no significant difference in the complication rate among the four groups. Also, no significant differences were found among the four groups in functional and patient-reported outcomes, in either the first or second knee at 5 years postoperatively, including KSS-knee, KSS-function, WOMAC-pain, WOMAC-stiffness, and WOMAC-physical function. The interval between BTKA did not influence complications or the function of the second knee. The TKA type (posterior-stabilised vs. medial-pivot) and age did not correlate significantly with any scores. CONCLUSIONS: There was no group difference in early complications of the second TKA, and postoperative function was equivalent between the two knees and did not vary by the interval between surgeries. The results of this study give surgeons and patients more choices. If patients cannot tolerate severe symptoms in the contralateral knee after the first TKA, the second TKA should be performed as early as possible. If knee joint function is not well recovered after the first TKA, and patients are anxious to undergo the second TKA, surgeons can advise patients to postpone the operation based on these results.

Transcriptomics reveals dynamic changes in the "gene profiles" of rat supraspinatus tendon at three different time points after diabetes induction.

OBJECTIVE: There is increasing evidence that type 2 diabetes mellitus (T2DM) is an independent risk factor for the occur of tendinopathy. Therefore, this study is the first to explore the dynamic changes of the "gene profile" of supraspinatus tendon in rats at different time points after T2DM induction through transcriptomics, providing potential molecular markers for exploring the pathogenesis of diabetic tendinopathy. METHODS: A total of 40 Sprague-Dawley rats were randomly divided into normal (NG, n = 10) and T2DM groups (T2DM, n = 30) and subdivided into three groups according to the duration of diabetes: T2DM-4w, T2DM-8w, and T2DM-12w groups; the duration was calculated from the time point of T2DM rat model establishment. The three comparison groups were set up in this study, T2DM-4w group vs. NG, T2DM-8w group vs. NG, and T2DM-12w group vs. NG. Differentially expressed genes (DEGs) in 3 comparison groups were screened. The intersection of the three comparison groups' DEGs was defined as key genes that changed consistently in the supraspinatus tendon after diabetes induction. Cluster analysis, gene ontology (GO) functional annotation analysis and Kyoto encyclopedia of genes and genomes (KEGG) functional annotation and enrichment analysis were performed for DEGs. RESULTS: T2DM-4w group vs. NG, T2DM-8w group vs. NG, and T2DM-12w group vs. NG detected 519 (251 up-regulated and 268 down-regulated), 459 (342 up-regulated and 117 down-regulated) and 328 (255 up-regulated and 73 down-regulated) DEGs, respectively. 103 key genes of sustained changes in the supraspinatus tendon following induction of diabetes, which are the first identified biomarkers of the supraspinatus tendon as it progresses through the course of diabetes.The GO analysis results showed that the most significant enrichment in biological processes was calcium ion transmembrane import into cytosol (3 DEGs). The most significant enrichment in cellular component was extracellular matrix (9 DEGs). The most significant enrichment in molecular function was glutamate-gated calcium ion channel activity (3 DEGs). The results of KEGG pathway enrichment analysis showed that there were 17 major pathways (p < 0.05) that diabetes affected supratinusculus tendinopathy, including cAMP signaling pathway and Calcium signaling pathway. CONCLUSIONS: Transcriptomics reveals dynamic changes in the"gene profiles"of rat supraspinatus tendon at three different time points after diabetes induction. The 103 DEGs identified in this study may provide potential molecular markers for exploring the pathogenesis of diabetic tendinopathy, and the 17 major pathways enriched in KEGG may provide new ideas for exploring the pathogenesis of diabetic tendinopathy.

Model Properties and Clinical Application in the Finite Element Analysis of Knee Joint: A Review.

The knee is the most complex joint in the human body, including bony structures like the femur, tibia, fibula, and patella, and soft tissues like menisci, ligaments, muscles, and tendons. Complex anatomical structures of the knee joint make it difficult to conduct precise biomechanical research and explore the mechanism of movement and injury. The finite element model (FEM), as an important engineering analysis technique, has been widely used in many fields of bioengineering research. The FEM has advantages in the biomechanical analysis of objects with complex structures. Researchers can use this technology to construct a human knee joint model and perform biomechanical analysis on it. At the same time, finite element analysis can effectively evaluate variables such as stress, strain, displacement, and rotation, helping to predict injury mechanisms and optimize surgical techniques, which make up for the shortcomings of traditional biomechanics experimental research. However, few papers introduce what material properties should be selected for each anatomic structure of knee FEM to meet different research purposes. Based on previous finite element studies of the knee joint, this paper summarizes various modeling strategies and applications, serving as a reference for constructing knee joint models and research design.

Single-cell RNA sequencing reveals the impact of mechanical loading on knee tibial cartilage in osteoarthritis.

Articular cartilage degeneration is one of the major pathogenic alterations observed in knee osteoarthritis (KOA). Mechanical stress has been verified to contribute to KOA development. To gain insight into the pathogenic mechanism of KOA development, we investigated chondrocyte subsets under different mechanical loading conditions via single-cell RNA sequencing (scRNA-seq). Articular cartilage tissues from both high mechanical loading (named the OATL group) and low mechanical loading (named the OATN group) surfaces were obtained from the proximal tibia of KOA patients, and scRNA-seq was conducted. Chondrocyte subtypes, including a new subset, HTC-C (hypertrophic chondrocytes-C), and their functions, development and interactions among cell subsets were identified. Immunohistochemical staining was also conducted to verify the existence and location of each chondrocyte subset. Furthermore, differentially expressed genes (DEGs) and their functions between regions with high and low mechanical loading were identified. Based on Gene Ontology terms for the DEGs in each cell type, the characteristic of cartilage degeneration in the OATL region was clarified. Mitochondrial dysfunction may be involved in the KOA process in the OATN region.

Comparison of different degrees of varus deformity correction with open-wedge high tibial osteotomy: a retrospective study over 5 years.

OBJECTIVE: This study aims to investigate the clinical efficacy and complications associated with open-wedge high tibial osteotomy (OWHTO) in the treatment of medial compartment knee osteoarthritis. Additionally, the compensatory changes in the hip, patellofemoral, and ankle regions will be assessed through imaging. METHODS: A retrospective analysis of clinical data pertaining to 86 patients who underwent OWHTO at the Affiliated Hospital of Qingdao University from January 2015 to September 2018 was conducted. The weight-bearing line ratio (WBLR) was measured postoperatively, and patients were categorized into a normal group (50% < WBLR ≤ 62.5%, n = 67) and an overcorrection group (WBLR > 62.5%, n = 19). Various parameters, including hip-knee-ankle angle (HKA), medial proximal tibial angle (MPTA), lateral distal femoral angle (LDFA), joint line convergence angle (JLCA), and posterior tibial slope (PTS), were measured before surgery and at the last follow-up to assess lower limb line correction. The compensatory changes in adjacent joints were evaluated by measuring hip abductor angle (HAA), tibial plafond inclination (TPI), talus inclination angle (TIA), Carton-Deschamps index, lateral patellar tilt (LPT), lateral patellar shift (LPS), medial patellofemoral space, and lateral patellofemoral space in both groups. The American Hospital for Special Surgery (HSS) score and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) of the affected knee were assessed before surgery and at the last follow-up, and the incidence of complications in both groups was analyzed. RESULTS: Postoperative complications occurred in 26.32% (five cases) of the overcorrection group and 5.97% (four cases) of the normal group, with a statistically significant difference (χ2 = 4.548, p = 0.033). No significant differences were observed in HSS and WOMAC between the two groups at the last follow-up. HAA was - 2.44 ± 1.98° in the overcorrection group and - 1.16 ± 2.1° in the normal group, with a statistically significant difference (t = 2.32, p = 0.023). There were no significant differences in other imaging indexes. CONCLUSION: Overcorrection of varus deformity may not significantly impact clinical outcomes within 5 years post-OWHTO but may elevate the incidence of postoperative complications and lead to increased compensatory adduction of the hip.

Identification of CD8+ T cell-related biomarkers and immune infiltration characteristic of rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune rheumatic disease, which do not respond well to current treatment partially. Therefore, further in-depth elucidation of the molecular mechanism and pathogenesis of RA is urgently needed for the diagnosis, personalized therapy and drug development. Herein, we collected 111 RA samples from Gene Expression Omnibus (GEO) database, and conducted differentially expressed genes and GESA analysis. Abnormal activation and imbalance of immune cells in RA were observed. WGCNA was utilized to explore the gene modules and CD8+ T cell-related genes (CRGs) were chosen for KEGG and GO analysis. Besides, to explore biomarkers of RA in depth, machine learning algorithms and bioinformatics analysis were used, and we identified GDF15, IGLC1, and IGHM as diagnostic markers of RA, which was confirmed by clinical samples. Next, ssGSEA algorithms were adopted to investigate the differences in immune infiltration of 23 immune cell subsets between RA and healthy control group. Finally, optimal classification analysis based on consensus clustering combined with ssGSEA algorithms were conducted. GDF15 was revealed that to be positively correlated with mast cells and type 2 T helper cells, but negatively correlated with most other immune cells. On the other hand, IGHM and IGLC1 were negatively correlated with CD56dim natural killer cells, while positively associated with other immune cells. Finally, RA samples in subtype A exhibited a higher immune infiltration status. This study could provide guidance for individualized treatment of RA patients and provide new targets for drug design.

Untargeted metabolomics reveals dynamic changes in metabolic profiles of rat supraspinatus tendon at three different time points after diabetes induction.

Objective: To investigate the dynamic changes of metabolite composition in rat supraspinatus tendons at different stages of diabetes by untargeted metabolomics analysis. Methods: A total of 80 Sprague-Dawley rats were randomly divided into normal (NG, n = 20) and type 2 diabetes mellitus groups (T2DM, n = 60) and subdivided into three groups according to the duration of diabetes: T2DM-4w, T2DM-12w, and T2DM-24w groups; the duration was calculated from the time point of T2DM rat model establishment. The three comparison groups were set up in this study, T2DM-4w group vs. NG, T2DM-12w group vs. T2DM-4w group, and T2DM-24w group vs. T2DM-12w group. The metabolite profiles of supraspinatus tendon were obtained using tandem mass spectrometry. Metabolomics multivariate statistics were used for metabolic data analysis and differential metabolite (DEM) determination. The intersection of the three comparison groups' DEMs was defined as key metabolites that changed consistently in the supraspinatus tendon after diabetes induction; then, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed. Results: T2DM-4w group vs. NG, T2DM-12w group vs. T2DM-4w group, and T2DM-24w group vs. T2DM-12w group detected 94 (86 up-regulated and 8 down-regulated), 36 (13 up-regulated and 23 down-regulated) and 86 (24 up-regulated and 62 down-regulated) DEMs, respectively. Seven key metabolites of sustained changes in the supraspinatus tendon following induction of diabetes include D-Lactic acid, xanthine, O-acetyl-L-carnitine, isoleucylproline, propoxycarbazone, uric acid, and cytidine, which are the first identified biomarkers of the supraspinatus tendon as it progresses through the course of diabetes. The results of KEGG pathway enrichment analysis showed that the main pathway of supraspinatus metabolism affected by diabetes (p < 0.05) was purine metabolism. The results of the KEGG metabolic pathway vs. DEMs correlation network graph revealed that uric acid and xanthine play a role in more metabolic pathways. Conclusion: Untargeted metabolomics revealed the dynamic changes of metabolite composition in rat supraspinatus tendons at different stages of diabetes, and the newly discovered seven metabolites, especially uric acid and xanthine, may provide novel research to elucidate the mechanism of diabetes-induced tendinopathy.

Single-cell RNA sequencing reveals differences between force application and bearing in ankle cartilage.

Chondrocytes are the major functional elements of articular cartilage. Force has been demonstrated to influence the structure and function of articular cartilage and chondrocytes. Therefore, it is necessary to evaluate chondrocytes under different force conditions to gain deep insight into chondrocyte function. Six cartilage tissues from the distal tibia (referred to as the AT group) and five cartilage tissues from the trochlear surface of the talus (referred to as the ATa group) were obtained from 6 donors who had experienced fatal accidents. Single-cell RNA sequencing was used on these samples. A total of 149,816 cells were analyzed. Nine chondrocyte subsets were ultimately identified. Pseudotime analyses, enrichment analyses, cell-cell interaction studies, and single-cell regulatory network inference and clustering were performed for each cell type, and the differences between the AT and ATa groups were analyzed. Immunohistochemical staining was used to verify the existence of each chondrocyte subset and its distribution. The results suggested that reactive oxygen species related processes were active in the force-applied region, while tissue repair processes were common in the force-bearing region. Although the number of prehypertrophic chondrocytes was small, these chondrocytes seemed to play an important role in the ankle.

Single-cell RNA sequencing reveals distinct chondrocyte states in femoral cartilage under weight-bearing load in Rheumatoid arthritis.

Introduction: Rheumatoid arthritis (RA) is a common autoimmune joint disease, the pathogenesis of which is still unclear. Cartilage damage is one of the main manifestations of the disease. Chondrocytes are the main functional component of articular cartilage, which is relevant to disease progression. Mechanical loading affects the structure and function of articular cartilage and chondrocytes, but the effect of weight bearing on chondrocytes in rheumatoid arthritis is still unclear. Methods: In this paper, single-cell RNA sequencing (scRNA-seq) was performed on collected cartilage from the weight-bearing region (Fb group) and non-weight-bearing region (Fnb group) of the femur, and the differences between the Fb and Fnb groups were analyzed by cell type annotation, pseudotime analysis, enrichment analysis, cell interactions, single-cell regulatory network inference and clustering (SCENIC) for each cell type. Results: A total of 87,542 cells were analyzed and divided into 9 clusters. Six chondrocyte subpopulations were finally identified by cellular annotation, and two new chondrocyte subtypes were annotated as immune-associated chondrocytes. The presence of each chondrocyte subpopulation and its distribution were verified using immunohistochemical staining (IHC). In this study, the atlas of femoral cartilage in knee rheumatoid arthritis and 2 new immune-related chondrocytes were validated using scRNA-seq and IHC, and chondrocytes in the weight-bearing and non-weight-bearing regions of the femur were compared. There might be a process of macrophage polarization transition in MCs in response to mechanical loading, as in macrophages. Conclusion: Two new immune-associated chondrocytes were identified. MCs have contrasting functions in different regions, which might provide insight into the role of immune and mechanical loading on chondrocytes in the development of knee rheumatoid osteoarthritis.

Adaptive divergence and genetic vulnerability of relict species under climate change: a case study of Pterocarya macroptera.

BACKGROUND AND AIMS: Understanding adaptive genetic variation and whether it can keep pace with predicted future climate change is critical in assessing the genetic vulnerability of species and developing conservation management strategies. The lack of information on adaptive genetic variation in relict species carrying abundant genetic resources hinders the assessment of genetic vulnerability. Using a landscape genomics approach, this study aimed to determine how adaptive genetic variation shapes population divergence and to predict the adaptive potential of Pterocarya macroptera (a vulnerable relict species in China) under future climate scenarios. METHODS: We applied restriction site-associated DNA sequencing (RAD-seq) to obtain 8244 single-nucleotide polymorphisms (SNPs) from 160 individuals across 28 populations. We examined the pattern of genetic diversity and divergence, and then identified outliers by genetic differentiation (FST) and genotype-environment association (GEA) methods. We further dissected the effect of geographical/environmental gradients on genetic variation. Finally, we predicted genetic vulnerability and adaptive risk under future climate scenarios. KEY RESULTS: We identified three genetic lineages within P. macroptera: the Qinling-Daba-Tianmu Mountains (QDT), Western Sichuan (WS) and Northwest Yunnan (NWY) lineages, which showed significant signals of isolation by distance (IBD) and isolation by environment (IBE). IBD and IBE explained 3.7-5.7 and 8.6-12.8 % of the genetic structure, respectively. The identified GEA SNP-related genes were involved in chemical defence and gene regulation and may exhibit higher genetic variation to adapt to the environment. Gradient forest analysis revealed that the genetic variation was mainly shaped by temperature-related variables, indicating its adaptation to local thermal environments. A limited adaptive potential was suggested by the high levels of genetic vulnerability in marginal populations. CONCLUSIONS: Environmental gradient mainly shaped the population differentiation of P. macroptera. Marginal populations may be at high risk of extinction, and thus proactive management measures, such as assisted gene flow, are required to ensure the survival of these populations.

Recent advance in phytonanomedicine and mineral nanomedicine delivery system of the treatment for acute myeloid leukemia.

Acute myeloid leukemia (AML) is an invasive hematopoietic malignancy caused by excessive proliferation of myeloblasts. Classical chemotherapies and cell transplantation therapies have remarkable efficacy in AML treatment; however, 30-40% of patients relapsed or had refractory disease. The resistance of AML is closely related to its inherent cytogenetics or various gene mutations. Recently, phytonanomedicine are found to be effective against resistant AML cells and have become a research focus for nanotechnology development to improve their properties, such as increasing solubility, improving absorption, enhancing bioavailability, and maintaining sustained release and targeting. These novel phytonanomedicine and mineral nanomedicine, including nanocrystals, nanoemulsion, nanoparticles, nanoliposome, and nanomicelles, offer many advantages, such as flexible dosages or forms, multiple routes of administration, and curative effects. Therefore, we reviewed the application and progress of phytomedicine in AML treatment and discussed the limitations and future prospects. This review may provide a solid reference to guide future research on AML treatment.

Proximal tibia osteotomy with absorbable spacer combined with fibular osteotomy versus high tibial osteotomy for medial compartmental knee osteoarthritis.

PURPOSE: The study aimed to compare the perioperative complications, short-term clinical outcomes, patient-reported outcomes, and radiographic parameters of tibiofibular proximal osteotomy combined with absorbable spacer insertion (TPOASI) and open-wedge high tibial osteotomy (OWHTO) in a two year postoperative time period. METHODS: A total of 160 patients with Kellgren-Lawrence classification grade 3 medial compartmental knee OA were randomized to receive either TPOASI (n = 82) or OWHTO (n = 78). The primary and secondary outcomes were measured preoperatively, postoperatively, and at each follow-up examination. The primary outcomes were the between-group change in the Western Ontario and McMaster Universities Global score (WOMAC). Secondary measures included visual analog scale (VAS), radiographic parameters, American Knee Society Score (KSS), operation time, blood loss, length of incision, hospital stay, and relevant complications. Postoperative radiographic parameters, including the femorotibial angle (FTA), varus angle (VA), and joint line convergence angle (JLCA), were measured to evaluate the correction of varus deformity. RESULTS: No significant differences were found in the baseline data between the two groups. Both methods improved functional status and pain postoperatively. For primary outcomes of both groups, statistical difference was observed in WOMAC scores at the 6-month follow-up (P < 0.001). For secondary outcomes, no statistical difference was observed between the groups during the 2-year follow-up (P > 0.05). For TPOASI vs. OWHTO, the mean hospital stay (6.6 ± 1.3 days vs. 7.8 ± 2.1 days) was shorter (P < 0.001), and both blood loss (70.56 ± 35.58 vs. 174.00 ± 66.33 mL) and complication rate (3.7% vs. 12.8%) were significantly lower (P < 0.005 for both). CONCLUSIONS: Both approaches showed satisfactory functional outcomes and alleviated pain. However, TPOASI is a simple, feasible method with few complications, and it could be widely used.

Effects of advanced glycation end products (AGEs) on the differentiation potential of primary stem cells: a systematic review.

The formation and accumulation of advanced glycation end products (AGEs) have been associated with aging and the development, or worsening, of many degenerative diseases, such as atherosclerosis, chronic kidney disease, and diabetes. AGEs can accumulate in a variety of cells and tissues, and organs in the body, which in turn induces oxidative stress and inflammatory responses and adversely affects human health. In addition, under abnormal pathological conditions, AGEs create conditions that are not conducive to stem cell differentiation. Moreover, an accumulation of AGEs can affect the differentiation of stem cells. This, in turn, leads to impaired tissue repair and further aggravation of diabetic complications. Therefore, this systematic review clearly outlines the effects of AGEs on cell differentiation of various types of primary isolated stem cells and summarizes the possible regulatory mechanisms and interventions. Our study is expected to reveal the mechanism of tissue damage caused by the diabetic microenvironment from a cellular and molecular point of view and provide new ideas for treating complications caused by diabetes.

The mid-term outcomes of mobile bearing unicompartmental knee arthroplasty versus total knee arthroplasty in the same patient.

Objective: To compare the mid-term outcomes of unicompartmental knee arthroplasty (UKA) that was performed in one knee and total knee arthroplasty (TKA) performed in the other knee in the same stage. Methods: This is a retrospective study. A total of 63 patients (126 knees) scheduled for one-stage knee surgery due to osteoarthritis of both knees were selected, and all patients underwent one-stage mobile platform UKA and TKA of the other knee. Differences in general clinical data, functional recovery, complications, and prosthesis revision rates were assessed after UKA and TKA, respectively. The evaluation indicators for knee joint function recovery included the hospital for special surgery knee score (HSS), Joint Forgotten Score (JFS), Knee Injury and Osteoarthritis Outcome Score (KOOS), and Visual analog scale (VAS). Patient preference between UKA and TKA was also recorded. Results: During a mean follow-up of 76.95 months (range, 65.00 to 87.00 months), there were no significant differences in postoperative complications between the two groups (P = 0.299); however, the prosthesis revision rate was higher in the UKA group than in the TKA group (P = 0.023). The incision length, operation time, blood loss, and postoperative drainage volume in the UKA group were significantly (P < 0.001) lower than those in the TKA group: JFS, ROM, and VAS in the UKA group were higher than those in the TKA group (P < 0.001, P = 0.023, P = 0.032), HSS and KOOS in TKA group were significantly (P < 0.001) higher than those in UKA group. At the last follow-up, 40% and 24% of patients preferred TKA and UKA, respectively. Conclusions: TKA was found to be superior to UKA in terms of HSS, KOOS, and VAS, while UKA had more significant advantages in terms of less surgical trauma, better ROM, and higher JFS. Complications were not different between groups, but UKA had a higher rate of prosthesis revision. After a follow-up of at least 5 years, more patients preferred TKA.

Effects of reaction environments on the structure and physicochemical properties of chitosan and its derivatives.

The structural transformation of chitosan caused by reaction environment is one of the main factors affecting its functional properties. Herein, the effects of homogeneous and heterogeneous reactions on the structure and properties of chitosan were investigated. The pretreatment of reaction increased the deacetylation degree (DD) of chitosan and resulted in its degradation. In contrast, the effect of alkali dissolution process on the above characteristics was less than 8 %. In addition, the modification of functional groups and alkaline reaction environment leaded to further degradation and deacetylation of chitosan. The alkali swelling increased the specific surface area of chitosan particles, but not completely destroy its internal structure to ensure the uniformity of reaction. Interestingly, the homogeneous modification of dissolved chitosan at lower temperature reduced the degree of substitution (DS) of its derivatives but made them exhibit self-assembly properties. This study provided theoretical basis for precise preparation and application of chitosan derivatives.

Single-cell RNA sequence presents atlas analysis for chondrocytes in the talus and reveals the potential mechanism in coping with mechanical stress.

Chondrocytes are indispensable for the function of cartilage because they provide the extracellular matrix. Therefore, gaining insight into the chondrocytes may be helpful in understanding cartilage function and pinpointing potential therapeutical targets for diseases. The talus is a part of the ankle joint, which serves as the major large joint that bears body weight. Compared with the distal tibial and fibula, the talus bears much more mechanical loading, which is a risk factor for osteoarthritis (OA). However, in most individuals, OA seems to be absent in the ankle, and the cartilage of the talus seems to function normally. This study applied single-cell RNA sequencing to demonstrate atlas for chondrocyte subsets in healthy talus cartilage obtained from five volunteers, and chondrocyte subsets were annotated. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses for each cell type, cell-cell interactions, and single-cell regulatory network inference and clustering for each cell type were conducted, and hub genes for each cell type were identified. Immunohistochemical staining was used to confirm the presence and distribution of each cell type. Two new chondrocyte subsets were annotated as MirCs and SpCs. The identified and speculated novel microenvironment may pose different directions in chondrocyte composition, development, and metabolism in the talus.

Development and validation of a nomogram to predict complications in patients undergoing simultaneous bilateral total knee arthroplasty: A retrospective study from two centers.

Purpose: Complications were significantly increased 30 days after Simultaneous bilateral total knee arthroplasty (SBTKA). In this study, an individualized nomogram was established and validated to predict the complications within 30 days after SBTKA. Methods: The general data of 861 patients (training set) who received SBTKA in The Affiliated Hospital of Qingdao University between January 1, 2012 and March 31, 2017 were retrospectively analyzed. All patients were divided into complication group (n = 96) and non-complication group (n = 765) according to the incidence of complications within 30 years after SBTKA. Independent risk factors for postoperative SBTKA complications were identified and screened by binary logistic regression analyses, and then a nomogram prediction model was constructed using R software. The area under curve (AUC), calibration curve, and decision curve analysis (DCA) were selected to evaluate the line-chart. Meanwhile, 396 patients receiving SBTKA in the Third Hospital of Hebei Medical University who met the inclusion and exclusion criteria (test set) were selected to verify the nomogram. Results: Five independent predictors were identified by binary logistic regression analyses and a nomogram was established. The AUC of this nomogram curve is 0.851 (95% CI: 0.819-0.883) and 0.818 (95% CI: 0.735-0.900) in the training and testing sets, respectively. In the training set and test set, calibration curves show that nomogram prediction results are in good agreement with actual observation results, and DCA shows that nomogram prediction results have good clinical application value. Conclusion: Older age, lower preoperative hemoglobin level, higher preoperative blood urea nitrogen (BUN) level, longer operation time, ASA grade ≥ III are independent predictors of SBTKA complications within 30 days after surgery. A nomogram containing these five predictors can accurately predict the risk of complications within 30 days after SBTKA.

Evaluating the role of type 2 diabetes mellitus in rotator cuff tendinopathy: Development and analysis of a novel rat model.

Objective: To establish and validate an intact rotator cuff rat model for exploring the pathophysiological effects of type 2 diabetes on the rotator cuff tendon in vivo. Methods: A total of 45 adult male rats were randomly divided into a control group (n = 9) and type 2 diabetes group (n=36). The rats were sacrificed at 2 weeks (T2DM-2w group, n=9), 4 weeks (T2DM-4w group, n=9), 8 weeks (T2DM-8w group, n=9), and 12 weeks (T2DM-12w group, n=9) after successful modeling of type 2 diabetes. Bilateral shoulder samples were collected for gross observation and measurement, protein expression(enzyme-linked immunosorbent assay,ELISA), histological evaluation, biomechanical testing, and gene expression (real-time quantitative polymerase chain reaction, qRT-PCR). Results: Protein expression showed that the expression of IL-6 and Advanced glycation end products (AGEs)in serum increased in type 2 diabetic group compared with the non-diabetic group. Histologically, collagen fibers in rotator cuff tendons of type 2 diabetic rats were disorganized, ruptured, and with scar hyperplasia, neovascularization, and extracellular matrix disturbances, while Bonar score showed significant and continuously aggravated tendinopathy over 12 weeks. The biomechanical evaluation showed that the ultimate load of rotator cuff tendons in type 2 diabetic rats gradually decreased, and the ultimate load was negatively correlated with AGEs content. Gene expression analysis showed increased expression of genes associated with matrix remodeling (COL-1A1), tendon development (TNC), and fatty infiltration (FABP4) in tendon specimens from the type 2 diabetic group. Conclusion: Persistent type 2 diabetes is associated with the rupture of collagen fiber structure, disturbance in the extracellular matrix, and biomechanical decline of the rotator cuff tendon. The establishment of this new rat model of rotator cuff tendinopathy provides a valuable research basis for studying the cellular and molecular mechanisms of diabetes-induced rotator cuff tendinopathy.