Deficient gait function despite effect index of the Western Ontario and McMaster university osteoarthritis index score considered cured one year after bilateral total knee arthroplasty.

BACKGROUND: To clarify the value of gait analysis and its consistency with traditional scoring scales for the evaluation of knee joint function after total knee arthroplasty (TKA). METHODS: This study included 25 patients with knee osteoarthritis (KOA) who underwent bilateral TKA, and 25 conditionally matched healthy individuals, categorised into the experimental and control groups, respectively. Patients in the experimental group underwent gait analysis and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) evaluation before and 1 year after TKA. Weight-bearing balance and walking stability were assessed using discrete trends of relevant gait indicators. Pearson's correlation analysis was performed on the gait and WOMAC score data of the experimental group before and after TKA. RESULTS: One year after TKA, patients' gait indices (except gait cycle) were significantly better than before surgery, but significantly worse than that of the control group (P < 0.01). The shape of patients' plantar pressure curves did not return to normal. Additionally, the discrete trend of related gait indicators reflecting weight-bearing balance and walking stability were smaller than before TKA, but still greater than that of the control group. The WOMAC scores of patients 1 year after TKA were significantly lower than those before TKA (P < 0.001), and the efficacy index was > 80%. The WOMAC scores and gait analysis results were significantly correlated before TKA (P < 0.05). CONCLUSIONS: Gait analysis should be used in conjunction with scoring scales to assess joint functions.

Laser-induced transverse voltage effect inc-axis inclined LaxSr1-xTiO3thin films prepared by MOCVD.

Light and thermal detectors based on the laser-induced transverse voltage (LITV) effect have garnered significant interest for their rapid and broad spectral response. In this study, we prepared the La-doped SrTiO3(STO) epitaxial thin films on the 12° inclined single crystal LaAlO3(LAO) (100) substrates using our home-designed metal-organic chemical vapor deposition system. Under the illumination of a 248 nm laser, the LITV signals of LaxSr1-xTiO3films were observed and showed dependence on the La doping level, which can be explained by the changes in the light absorption coefficient, thermal conductivity, and optical penetration depth. The optimized LITV signal was observed with a peak voltage of 23.25 V and a decay time of 106 ns under the laser power density of 1.0 mJ mm-2. The high peak voltage and fast response time of LaxSr1-xTiO3show great potential in the field of light and thermal detection.

TSP-1 increases autophagy level in cartilage by upregulating HSP27 which delays progression of osteoarthritis.

This study aimed to determine whether Thrombospondin-1 (TSP-1) can be used as a biomarker to diagnose early osteoarthritis (OA) and whether it has a chondroprotective effect against OA. We examined TSP-1 expression in cartilage, synovial fluid, and serum at different time points after anterior cruciate ligament transection (ACLT) surgery in rats. Subsequently, TSP-1 was overexpressed or silenced to detect its effects on extracellular matrix (ECM) homeostasis, autophagy level, proliferation and apoptosis in chondrocytes. Adenovirus encoding TSP-1 was injected into the knee joints of ACLT rats to test its effect against OA. Combined with proteomic analysis, the molecular mechanism of TSP-1 in cartilage degeneration was explored. Intra-articular injection of an adenovirus carrying the TSP-1 sequence showed chondroprotective effects against OA. Moreover, TSP-1 expression decreases with OA progression and can effectively promote cartilage proliferation, inhibit apoptosis, and helps to sustain the balance between ECM anabolism and catabolism. Overexpression of TSP-1 also can increase autophagy by upregulating Heat Shock Protein 27 (HSP27, hspb1), thereby enhancing its effect as a stimulator of autophagy. TSP-1 is a hopeful strategy for OA treatment.

Transcriptome analysis of mRNAs, lncRNAs, and miRNAs in the skeletal muscle of Tibetan chickens at different developmental stages.

Introduction: As a valuable genetic resource, native birds can contribute to the sustainable development of animal production. Tibetan chickens, known for their special flavor, are one of the important local poultry breeds in the Qinghai-Tibet Plateau. However, Tibetan chickens have a slow growth rate and poor carcass traits compared with broilers. Although most of the research on Tibetan chickens focused on their hypoxic adaptation, there were fewer studies related to skeletal muscle development. Methods: Here, we performed the transcriptional sequencing of leg muscles from Tibetan chicken embryos at E (embryonic)10, E14, and E18. Results: In total, 1,600, 4,610, and 2,166 DE (differentially expressed) mRNAs, 210, 573, and 234 DE lncRNAs (long non-coding RNAs), and 52, 137, and 33 DE miRNAs (microRNAs) were detected between E10 and E14, E10 and E18, and E14 and E18, respectively. Functional prediction showed several DE mRNAs and the target mRNAs of DE lncRNAs and DE miRNAs were significantly enriched in sarcomere organization, actin cytoskeleton organization, myofibril, muscle fiber development, and other terms and pathways related to muscle growth and development. Finally, a lncRNA-miRNA-mRNA ceRNA (competing endogenous RNA) network associated with muscle growth and development, which contained 6 DE lncRNAs, 13 DE miRNAs, and 50 DE mRNAs, was constructed based on the screened DE RNAs by Gene Ontology (GO) enrichment. These DE RNAs may play a critical regulatory role in the skeletal muscle development of chickens. Discussion: The results provide a genomic resource for mRNAs, lncRNAs, and miRNAs potentially involved in the skeletal muscle development of chickens, which lay the foundation for further studies of the molecular mechanisms underlying skeletal muscle growth and development in Tibetan chickens.

Breast conservation therapy decreased heart-specific mortality in breast cancer patients compared with mastectomy.

AIM: To investigate the impacts of breast conservation therapy (BCT) and mastectomy on heart-specific mortality in breast cancer patients. METHODS: Patients with primary breast cancer registered in the Surveillance, Epidemiology, and End Results (SEER) database between Jan 1998 and Dec 2015 were included. Patients were divided into either breast conservation therapy or mastectomy group. To compare mortality caused by heart diseases in breast cancer patients with BCT or mastectomy, univariate and multivariate regression after propensity score matching (PSM) were performed. Kaplan-Meier analysis was also used to evaluate heart-specific survival between two groups. RESULTS: 132,616 patients with breast cancer were enrolled in this study. After PSM, four risk factors including age, race, marital status and types of surgery were identified significantly associated with death from heart diseases. Heart-specific survival analysis further showed that overall, BCT poses a lower risk to heart-specific mortality compared with mastectomy. CONCLUSION: Compared with mastectomy, BCT significantly decreased heart-specific mortality in breast cancer patients.

WGCNA-based identification of potential targets and pathways in response to treatment in locally advanced breast cancer patients.

Locally advanced breast cancer patients have a poor prognosis; however, the relationship between potential targets and the response to treatment is still unclear. The gene expression profiles of breast cancer patients with stages from IIB to IIIC were downloaded from The Cancer Genome Atlas. We applied weighted gene co-expression network analysis and differentially expressed gene analysis to identify the primary genes involved in treatment response. The disease-free survival between low- and high-expression groups was analyzed using Kaplan-Meier analysis. Gene set enrichment analysis was applied to identify hub genes-related pathways. Additionally, the CIBERSORT algorithm was employed to evaluate the correlation between the hub gene expression and immune cell types. A total of 16 genes were identified to be related to radiotherapy response, and low expression of SVOPL, EDAR, GSTA1, and ABCA13 was associated with poor overall survival and progression-free survival in breast cancer cases. Correlation analysis revealed that the four genes negatively related to some specific immune cell types. The four genes were downregulated in H group compared with the L group. Four hub genes associated with the immune cell infiltration of breast cancer were identified; these genes might be used as a promising biomarker to test the treatment in breast cancer patients.

Pain Empathy and Its Association with the Clinical Pain in Knee Osteoarthritis Patients.

Objective: Knee osteoarthritis (KOA) is a painful chronic disorder. Evidence has shown that a history of chronic pain plays an important role in shaping empathy. Empathy, a valuable indicator of social functioning that refers to an individual's ability to share the experiences of others, however, has been overlooked in KOA patients. This study aimed to investigate empathy and its association with clinical pain in KOA patients. Methods: KOA patients (n=47) and healthy controls (HCs, n=44) completed two empathy-for-pain tasks: a pain judgment task in which participants judged whether a person in an image felt pain or not, and a pain rating task in which they estimated pain intensity for themselves and others. The Interpersonal Reactivity Index was used to measure participants' trait empathy, and clinical severity and psychological factors were assessed using relevant instruments. Results: Compared to HCs, KOA patients showed higher accuracy when judging pain and non-pain images and reported overall higher pain intensity when rating for themselves and others. KOA patients also showed greater personal distress than HCs in terms of their self-reported empathy. Moreover, pain catastrophizing particularly mediated the relationship between pain severity and pain ratings for others, and depression, anxiety, and pain catastrophizing all mediated the association between pain severity and empathy-induced personal distress. Conclusion: These findings suggest that patients with KOA have increased empathy, demonstrated by elevated sensitivity to pain-related scenes and intense emotional responses.

Gait Analysis of Bilateral Knee Osteoarthritis and Its Correlation with Western Ontario and McMaster University Osteoarthritis Index Assessment.

Background and objectives: Objective, accurate, and intuitive evaluation of knee joint function in patients with knee osteoarthritis (KOA) is important. This study aimed to clarify the gait characteristics of patients with bilateral KOA and their correlation with Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Materials and Methods: 20 patients with bilateral KOA and 20 conditionally matched healthy individuals were enrolled in the experimental and control groups, respectively. Footscan and CODA motion gait analysis systems were used to analyse the gait parameters. Gait spatiotemporal parameters and knee joint motion parameters were collected. Weight-bearing balance and walking stability were assessed using discrete trends of relevant gait indicators. Patients in the experimental group were evaluated using WOMAC. Pearson's correlation analysis was performed on the gait data and WOMAC score data of the experimental group. Results: Velocity, cadence, step length, and stride length of the experimental group were significantly lower than those of the control group (p < 0.01). Step time and gait cycle were significantly greater in the experimental group than in the control group (p < 0.01). Total stance and double-stance times of the experimental group were significantly greater than those of the control group (p < 0.01), whereas the single-stance time was shorter than that of the control group (p < 0.01). The range of motion and maximum flexion angle in the experimental group were significantly lower than those in the control group (p < 0.01), and the minimum angle of knee extension was greater than that in the control group (p < 0.01). The discrete trend of weight-bearing balance and walking stability gait index in the experimental group was greater than that in the control group. The WOMAC score and gait analysis were significantly correlated (p < 0.05). Conclusions: The gait function of patients with KOA is significantly worse than that of normal people. The WOMAC scale and gait analysis can be used to assess KOA severity from different perspectives with good consistency.

Characterization of lncRNA/circRNA-miRNA-mRNA network to reveal potential functional ceRNAs in the skeletal muscle of chicken.

Skeletal muscle, comprising approximately 40% of body mass, is a highly complex and heterogeneous tissue serving a multitude of functions in the organism. Non-coding RNAs (ncRNAs) are known to participate in skeletal muscle development as critical regulators. However, the regulatory mechanisms of ncRNAs on chicken muscle traits are not well understood. In the present study, we collected the leg muscle from male embryos of Tibetan chicken at embryonic (E) 10 and E18 for RNA sequencing. A total of 6,583 differentially expressed mRNAs (DEMs) including 3,055 down-regulated and 3,528 up-regulated were identified in E18. We identified 695 differentially expressed lncRNAs (DELs) (187 down-regulated and 508 up-regulated) and 1,906 differentially expressed circRNAs (DECs) (1,224 down-regulated and 682 up-regulated) in E18. Among the 130 differentially expressed miRNAs (DEMIs), 59 were up-regulated and 71 were down-regulated in E18. Numerous DEMs and target genes for miRNAs/lncRNAs were significantly enriched in the muscle system process and cell cycle. We constructed a miRNA-gene-pathway network by considering target relationships between genes related to skeletal muscle development and miRNAs. A competing endogenous RNA (ceRNA) network was also constructed by integrating competing relationships between DEMs, DELs, and DECs. Several DELs and DECs were predicted to regulate the ADRA1B, ATP2A2, ATP2B1, CACNA1S, CACNB4, MYLK2, and ROCK2 genes. We discovered the crosstalk between the ncRNAs and their competing mRNAs, which provides insights into ceRNA function and mechanisms in the skeletal muscle development of chicken.

α2-macroglobulin-rich serum as a master inhibitor of inflammatory factors attenuates cartilage degeneration in a mini pig model of osteoarthritis induced by "idealized" anterior cruciate ligament reconstruction.

Post-traumatic osteoarthritis is a special type of osteoarthritis and a common disease, with few effective treatments available. α2-Macroglobulin (α2M) is important to chondral protection in post-traumatic osteoarthritis. However, its injection into xenogeneic joint cavities involves safety hazards, limiting clinical applications. Exploring serum α2M-enriching strategies and the therapeutic effect and mechanism of α2M-rich serum (α2MRS) autologous joint injection to treat post-traumatic osteoarthritis has significant value. In the present study, a unique filtration process was used to obtain α2MRS from human and mini pig serum. We evaluated the potential of α2MRS in protecting against post-surgery cartilage degeneration. We identify the potential of α2MRS in reducing the expression of inflammatory cytokines and factors that hasten cartilage degeneration in post-operative conditions leading to post-traumatic osteoarthritis. The potential of α2MRS was analyzed in interleukin-1ß induced human chondrocytes and mini pig models. In the chondrocyte model, α2MRS significantly promoted human chondrocyte proliferation and reduced apoptosis and chondrocyte catabolic cytokine gene transcription and secretion. The anterior cruciate ligament autograft reconstruction model of mini pigs was randomized into groups, operated on, and injected with α2MRS or saline. The results showed that α2MRS injection significantly suppressed the levels of inflammatory factors, improved gait, and showed significantly lower cartilage degeneration than the groups that did not receive α2MRS injections. This study highlights the chondroprotective effects of α2MRS, elucidated its potential applications against cartilage degeneration, and could provide a basis for the clinical translation of α2MRS.

The Level of Histone Deacetylase 4 is Associated with Aging Cartilage Degeneration and Chondrocyte Hypertrophy.

Purpose: To determine the role of histone deacetylase 4 (HDAC4)-controlled chondrocyte hypertrophy in the onset and development of age-related osteoarthritis (OA). Methods: Morphological analysis of human knee cartilages was performed to observe structural changes during cartilage degeneration. HDAC4 expression was deleted in adult aggrecan (Acan)-CreERT2; HDAC4fl/fl transgenic mice. The onset and development of age-related OA were investigated in transgenic and control mice using hematoxylin and eosin (H&E) and Safranin O staining. Furthermore, the progression of ACLT-induced OA following adenovirus-mediated HDAC4 overexpression was explored in rats. The expression levels of genes related to hypertrophy, cartilage matrix and its digestion, and chondrocyte proliferation were investigated using qPCR. Immunohistochemistry (IHC) was used to explore the mechanisms underlying HDAC4-controlled age-related changes in OA progression. Results: In human cartilage, we performed morphological analysis and IHC, the results showed that hypertrophy-related structural changes are related to HDAC4 expression. Age-related OA was detected early (OARSI scores 2.7 at 8-month-old) following HDAC4 deletion in 2-month-old mice. Furthermore, qPCR and IHC results showed changes in hypertrophy-related genes Col10a1, Runx2 and Sox9 in chondrocytes, particularly in the expression of Runt-related transcription factor 2 (Runx2, 13.29±0.99 fold). The expression of the main cartilage matrix-related genes Col2a1 and Acan decreased, that of cartilage matrix digestion-related gene MMP-13 increased, while that of chondrocyte proliferation-related genes PTHrP, Ihh and Gli1 changed. In contrast, rat cartilage's qPCR and IHC results showed opposite outcomes after HDAC4 overexpression. Conclusion: Based on the results above, we concluded that HDAC4 expression regulates the onset and development of age-related OA by controlling chondrocyte hypertrophy. These results may help in the development of early diagnosis and treatment of age-related OA.

Benefits of post-mastectomy radiation for T4N0M0 breast cancer patients: A SEER Database study.

PURPOSE: To evaluate the impact of post-mastectomy radiation therapy (PMRT) in breast cancer patients with stage T4N0M0. METHOD: Patients diagnosed with breast cancer of T4N0M0 from Jan 2010 to Dec 2015 were extracted from SEER database. Multivariable logistic regression was used to analyze the factors associated with PMRT. Univariate and multivariate COX regression were used to analyze factors that might be associated with breast cancer specific survival (BCSS) and overall survival (OS) of patients. Kaplan-Meier analysis was performed to evaluate BCSS and OS in different subtypes of patients. RESULT: Multivariable logistic regression showed that patients ≥ 71 years were less intend to have PMRT. Multivariate Cox analysis showed that married statue, HR+/Her- and HR+/Her+ subtypes, were independent predictors of improved BCSS and OS, and use of PMRT could improve BCSS and OS . PMRT was beneficial for OS in all subtypes breast cancer patients, but BCSS benefit was observed only in TNBC patients. CONCLUSION: The use of PMRT improves OS in all T4N0M0 patients, but in terms of BCSS, it only beneficial for TNBC patients.

Improving the symptoms of post-traumatic osteoarthritis by α2-macroglobulin-rich serum.

PURPOSE: Altered joint loading by trauma induces joint degeneration, eventually leading to the generation of post-traumatic osteoarthritis (PTOA). Recent studies have shown that α2-macroglobulin (A2M) inhibits PTOA, induced by anterior cruciate ligament transection (ACLT), pathogenesis by regulating proinflammatory cytokines and matrix metalloproteinases. However, the application of A2M is limited due to high prices. Therefore, the aim of this study is to explore the novel preparation of A2M. MATERIALS AND METHODS: The early change of A2M in synovial fluid and serum was measured by ELISA. Ultra-filtered centrifugation was performed to prepare α2-macroglobulin-rich serum (A2MRS). The bioactivity of A2M in A2MRS was detected by improved Ellis and Gollas-Galvan method. The effects of A2MRS on PTOA were observed using immunohistochemistry, safranine O staining, micro X-ray, fluorescence molecular tomography etc. RESULTS: The concentration of A2M in PTOA group was significantly higher than that in Sham group in synovial fluid on the third day after ACLT in rat PTOA model. On the contrary, a significant downregulation of A2M levels in PTOA group was observed compared to the Sham group in serum at the seventh day after ACLT. Secondly, A2MRS was prepared successfully, and the concentration and bioactivity of A2M in A2MRS was significantly higher than that in serum. Lastly, A2MRS not only reduced notably the production of secondary cartilage ossification, type 10 collagen and matrix metalloproteinase 13, but also increased profoundly the generation of type 2 collagen, aggrecan, and chondrocytes' number. CONCLUSION: Our results indicate that A2MRS has protective effects on PTOA.

Comparison of posterior cruciate retention and substitution in total knee arthroplasty during gait: a systematic review and meta-analysis.

BACKGROUND: To compare the gait patterns between posterior cruciate retention and substitution in total knee arthroplasty (TKA). METHODS: Electronic databases including the PubMed, Embase, CINAHL, Web of Science, and Cochrane databases were searched to identify clinical trials investigating posterior cruciate retention versus substitution in TKA. The outcome measurements were the kinematic gait parameters (flexion at heel strike, maximum flexion during loading response, flexion range during loading, minimal flexion at terminal stance, maximal flexion at the swing, and total flexion during the gait cycle), Knee Society Score (KSS), knee flexion, knee extension, and walking speed. Statistical software Review Manager 5.4 and Stata 14.0 were used for data analysis. RESULTS: There were finally 9 studies included in this meta-analysis. The results did not reveal differences between posterior cruciate retention (CR) and posterior cruciate substitution (PS) groups in TKA, in terms of kinematic gait parameters, knee extension, walking speed, and KSS. However, the PS group had a significantly larger knee flexion angle than that in the CR group [weighted mean difference = - 3.20, 95% CI - 6.13 to - 0.28, P = 0.03]. CONCLUSION: Both the posterior cruciate retention and posterior cruciate substitution lead to obvious improvements in patient function and have their advantages in getting a good cup position. The PS design is significantly better on the knee flexion, while there are no statistical differences in kinematic gait parameters and outcome scores between them. This might indicate that surgeons do not necessarily need a PS design to substitute the posterior cruciate ligament during TKA.

The administration of tranexamic acid for corrective surgery involving eight or more spinal levels: A systematic review and meta-analysis.

As the number of fusion levels increases, the complexity of spinal correction surgery also increases. Thus, we conducted this study to determine the safety and efficacy of tranexamic acid (TXA) involving eight or more spinal fusion levels. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Assessing the Methodological Quality of Systematic Reviews (AMSTAR) guidelines, a search of the PubMed, Embase, CENTRAL, Web of Science, and ClinicalTrials.gov databases was conducted for relevant studies published prior to May 30, 2019. The primary outcomes, including blood loss and transfusion requirement, and the secondary outcomes, including general indices, postoperative hemoglobin, and coagulation function, were analyzed using Rev Man 5.3.5 software and STATA version 12.0. Eight randomized controlled trials (473 participants) were included in the study. Compared to the control treatments, TXA reduced intraoperative blood loss, total blood loss, transfusion volume, and prothrombin time. There were no significant differences between the TXA and non-TXA groups in transfusion rate, operative time, hospital stay, complications, hemoglobin level, and other coagulation function parameters. In the pediatric subgroup analysis, TXA additionally improved hemoglobin levels, platelet count, and prothrombin time international normalized ratio. The present meta-analysis showed that TXA reduced blood loss and transfusion volume in both adults and children. In pediatric patients, TXA led to a greater benefit in postoperative hemoglobin levels and coagulation function. Intravenous TXA is safe and effective in children with eight or more spinal corrective levels.

Zinc finger protein 521 attenuates osteoarthritis via the histone deacetylases 4 in the nucleus.

To determine whether zinc finger protein 521 (Zfp521) has a chondroprotective effect by maintaining extracellular matrix (ECM) homeostasis to attenuate osteoarthritis (OA). In chondrocytes, Zfp521 was overexpressed or silenced to detect its effects on proliferation, apoptosis, and ECM homeostasis. Adenovirus encoding Zfp521 was injected into the knee joints of anterior cruciate ligament transection rats to test its efficacy against OA. Combined with proteomic analysis, the molecular mechanism of Zfp521 in cartilage degeneration was further explored. An intra-articular injection of adenovirus carrying a Zfp521 sequence showed a chondroprotective effect against OA. The molecular mechanism around Zfp521 was classified at the molecular, cellular, histological, and functional levels. It was reported that Zfp521 could effectively promote cartilage proliferation, inhibit apoptosis, and maintain the balance of anabolism and catabolism of ECM. Moreover, it was confirmed that Zfp521 exerted its effect better by upregulating histone deacetylases 4 (HDAC4) in the nucleus and was significantly weakened in the absence of HDAC4 in the nucleus. Overall, Zfp521 better exerts its efficacy against OA by increasing the HDAC4 content in the nucleus, making it a promising strategy for OA treatment.

Comparison of Walking Quality Variables between End-Stage Osteonecrosis of Femoral Head Patients and Healthy Subjects by a Footscan Plantar Pressure System.

Background and Objectives: Osteonecrosis of the femoral head (ONFH) is a progressive disease with a complex etiology and unknown pathogenesis. Gait analysis can objectively assess the functional behavior of the foot, thus revealing essential aspects and influencing factors of gait abnormalities. The aim of this study was to evaluate the differences in spatiotemporal parameters, static and dynamic plantar pressure parameters, and symmetry indices between patients with ONFH and healthy subjects. Materials and Methods: The study population consisted of 31 ONFH patients and 31 healthy volunteers. Gait parameters were obtained from the plantar pressure analysis system for both the ONFH and healthy groups. The symmetry index was calculated according to a formula, including spatiotemporal parameters, static and dynamic plantar pressure distribution, percentage of regional impulse, and percentage of the restricted contact area. Results: Compared with healthy controls, patients with ONFH had slower walking speed, shorter step length and stride length, and increased stride time, stance time, and percentage of stance. patients with ONFH had lower plantar static pressure on the affected side and higher contralateral plantar static pressure during stance than controls. During walking, the peak pressures in all regions on the affected side and the peak pressure in the toe 1 and metatarsal 3 regions on the healthy side were lower in ONFH patients than in controls. The percentage of contact area and regional impulse in the heel of both limbs were higher in ONFH patients than in the control group. The symmetry indexes of stride time, stance time, step length, maximum force, impulse and contacted area were significantly increased in ONFH patients compared to controls, with decreased symmetry. Conclusions: Osteonecrosis of the femoral head leads to characteristic changes in plantar pressure distribution. These changes may be interpreted as an attempt by patients with ONFH to reduce the load on the affected limb. Plantar pressure analysis may assist in the diagnosis of ONFH and can provide an objective quantitative indicator for the assessment of subsequent treatment outcomes.

Molybdenum isotopes unmask slab dehydration and melting beneath the Mariana arc.

How serpentinites in the forearc mantle and subducted lithosphere become involved in enriching the subarc mantle source of arc magmas is controversial. Here we report molybdenum isotopes for primitive submarine lavas and serpentinites from active volcanoes and serpentinite mud volcanoes in the Mariana arc. These data, in combination with radiogenic isotopes and elemental ratios, allow development of a model whereby shallow, partially serpentinized and subducted forearc mantle transfers fluid and melt from the subducted slab into the subarc mantle. These entrained forearc mantle fragments are further metasomatized by slab fluids/melts derived from the dehydration of serpentinites in the subducted lithospheric slab. Multistage breakdown of serpentinites in the subduction channel ultimately releases fluids/melts that trigger Mariana volcanic front volcanism. Serpentinites dragged down from the forearc mantle are likely exhausted at >200 km depth, after which slab-derived serpentinites are responsible for generating slab melts.

Drivers and suppressors of triple-negative breast cancer.

To identify regulators of triple-negative breast cancer (TNBC), gene expression profiles of malignant parts of TNBC (mTNBC) and normal adjacent (nadj) parts of the same breasts have been compared. We are interested in the roles of estrogen receptor ß (ERß) and the cytochrome P450 family (CYPs) as drivers of TNBC. We examined by RNA sequencing the mTNBC and nadj parts of five women. We found more than a fivefold elevation in mTNBC of genes already known to be expressed in TNBC: BIRC5/survivin, Wnt-10A and -7B, matrix metalloproteinases (MMPs), chemokines, anterior gradient proteins, and lysophosphatidic acid receptor and the known basal characteristics of TNBC, sox10, ROPN1B, and Col9a3. There were two unexpected findings: 1) a strong induction of CYPs involved in activation of fatty acids (CYP4), and in inactivation of calcitriol (CYP24A1) and retinoic acid (CYP26A1); and 2) a marked down-regulation of FOS, FRA1, and JUN, known tethering partners of ERß. ERß is expressed in 20 to 30% of TNBCs and is being evaluated as a target for treating TNBC. We used ERß+ TNBC patient-derived xenografts in mice and found that the ERß agonist LY500703 had no effect on growth or proliferation. Expression of CYPs was confirmed by immunohistochemistry in formalin-fixed and paraffin-embedded (FFPE) TNBC. In TNBC cell lines, the CYP4Z1-catalyzed fatty acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) increased proliferation, while calcitriol decreased proliferation but only after inhibition of CYP24A1. We conclude that CYP-mediated pathways can be drivers of TNBC but that ERß is unlikely to be a tumor suppressor because the absence of its main tethering partners renders ERß functionless on genes involved in proliferation and inflammation.

Inflammatory factors are crucial for the pathogenesis of post-traumatic osteoarthritis confirmed by a novel porcine model: "Idealized" anterior cruciate ligament reconstruction" and gait analysis.

OBJECTIVE: To determine whether idealized anterior cruciate ligament reconstruction (IACL-R) restores normal gait features, and whether inflammatory factors are involved in the pathogenesisof post-traumatic osteoarthritis (PTOA). METHODS: Fourteen mature female minipigs were allocated to a sham group (n = 7) or an IACL-R group (n = 7). Load asymmetry during gait was recorded using a pressure-sensing walkway measurement system to evaluate the gait features of the right knee joint before and after surgery. Inflammatory factors (including interleukin [IL]-1α, IL-1ß, IL-2, IL-6, IL-8, IL-18, tumor necrosis factor-α, and granulocyte-macrophage colony-stimulating factor) in synovial fluid were measured using Luminex assays before and after surgery. Cartilage integrity and the subchondral bone plate of the right knee were evaluated using histology and imaging at 3 months postoperatively. RESULTS: Swing time and stance time returned to their preoperative values on day 31, while maximum force, contact area, peak force ,and impulse returned to their preoperative values on day 45 after the surgery in the IACL-R group (P = 0.073, 0.053, 0.107, 0.052, 0.152, and 0.059, respectively).Thus, IACL-R restored normal gait. Compared with their preoperative concentrations, all tested inflammatory factors showed significantly increased concentrations in the synovial fluid in the IACL-R group, especially at 3, 7, and 15 days postoperatively. X-ray, computed tomography, magnetic resonance imaging, and histological data showed severe cartilage damage in the IACL-R model. CONCLUSION: IACL-R restored normal gait features but caused significant cartilage damage, indicating that significantly elevated inflammatory factors maybe crucial for the pathogenesis of PTOA.