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Major depressive disorder (MDD) is a disease associated with many factors; specifically, environmental, genetic, psychological, and biological factors play critical roles. Recent studies have demonstrated that histone modification may occur in the human brain in response to severely stressful events, resulting in transcriptional changes and the development of MDD. In this review, we discuss five different histone modifications, histone methylation, histone acetylation, histone phosphorylation, histone crotonylation and histone β-hydroxybutyrylation, and their relationships with MDD. The utility of histone deacetylase (HDAC) inhibitors (HDACis) for MDD treatment is also discussed. As a large number of MDD patients in China have been treated with traditional Chineses medicine (TCM), we also discuss some TCM therapies, such as Xiaoyaosan (XYS), and their effects on histone modification. In summary, targeting histone modification may be a new strategy for elucidating the mechanism of MDD and a new direction for MDD treatment.

Nasopharyngeal carcinoma (NPC) is one of the most predominant cancers occurring in China with high morbidity. Lately, large quantities of long non-coding RNAs (lncRNAs) have been highlighted to regulate the biological activities in multiple tumors, including NPC. Our study centered on whether TTN-AS1 was involved in NPC and how it modulated the progression of NPC. Here, RT-qPCR data uncovered that TTN-AS1 expression was conspicuously high in NPC cells. Based on the results of functional assays, TTN-AS1 silence hampered the proliferative, migratory and invasive abilities but stimulated apoptotic capability of NPC cells. After a series of mechanism assays, TTN-AS1 was found to competitively bind with miR-876-5p and recruit UPF1 to enhance NETO2 expression. In addition, TTN-AS1 could be transcriptionally activated by YY1 in NPC cells. It was also found miR-876-5p overexpression or NETO2 down-regulation had inhibitory effects on cell proliferation, migration and invasion in NPC. Moreover, NETO2 up-regulation could restore the suppressive impacts of TTN-AS1 depletion on NPC cell and tumor growth. In conclusion, YY1-activated TTN-AS1 interacted with both miR-876-5p and UPF1 to up-regulate NETO2, thus strengthening NPC cell malignant behaviors, which might provide more useful information for people to develop effective NPC treatments.

Inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) is one of important kinases in inflammation to phosphorylate inhibitor of nuclear factor kappa-B (IκBα) and then activate nuclear factor kappa-B (NF-κB). Inhibition of IKKβ has been a therapeutic strategy for inflammatory and autoimmune diseases. Here we report that IKKβ is constitutively activated in healthy donors and healthy IkkβC46A (cysteine 46 mutated to alanine) knock-in mice although they possess intensive IKKβ–IκBα–NF-κB signaling activation. These indicate that IKKβ activation probably plays homeostatic role instead of causing inflammation. Compared to IkkβWT littermates, lipopolysaccharides (LPS) could induce high mortality rate in IkkβC46A mice which is correlated to breaking the homeostasis by intensively activating p-IκBα–NF-κB signaling and inhibiting phosphorylation of 5ʹ adenosine monophosphate-activated protein kinase (p-AMPK) expression. We then demonstrated that IKKβ kinase domain (KD) phosphorylates AMPKα1 via interacting with residues Thr183, Ser184, and Thr388, while IKKβ helix–loop–helix motifs is essential to phosphorylate IκBα according to the previous reports. Kinase assay further demonstrated that IKKβ simultaneously catalyzes phosphorylation of AMPK and IκBα to mediate homeostasis. Accordingly, activation of AMPK rather than inhibition of IKKβ could substantially rescue LPS-induced mortality in IkkβC46A mice by rebuilding the homeostasis. We conclude that IKKβ activates AMPK to restrict inflammation and IKKβ mediates homeostatic function in inflammation via competitively phosphorylating AMPK and IκBα.

Uterine rupture and postterm pregnancy pose a number of life-threatening complications to both mother and child, including severe intra-abdominal bleeding and peritonitis, birth injury, hypoxia, and fetal loss. This report presents a rare case of a 20-year-old female experiencing fetal demise at 60 weeks of pregnancy, with uterine rupture and bone tissue discharge from her vagina without severe intra-abdominal bleeding and peritonitis. The mild clinical course despite complete uterine rupture was due to the firm adhesion of the amniotic sac to the uterus caused by inflammation. The adhesion of the intestines to the rupture site prevented dehiscence of the ruptured wound. Suppuration and bone tissue discharge relieved the pressure on the patient's abdominal cavity and prevented subsequent occurrence of severe peritonitis. Radiologists mistakenly regarded the thick amniotic sac wall on the right side of the uterine wall as a right cornual pregnancy with uterine rupture caused by chronic inflammation. This report aims to bring awareness of this rare condition to medical students and radiologists.

Context FSH may have independent actions on bone remodeling and body fat regulation. Cross-sectionally, we have shown that serum FSH is associated with bone mineral density (BMD) and body fat in older postmenopausal women, but it remains unknown whether FSH predicts bone and fat changes. Objective We examined whether baseline FSH level is associated with subsequent bone loss or body composition changes in older adults. Setting, Design, Participants We studied 162 women and 158 men (mean age 82 ± 4 years) from the Age, Gene/Environment Susceptibility (AGES)-Bone Marrow Adiposity cohort, a substudy of the AGES-Reykjavik Study of community-dwelling older adults. Skeletal health and body composition were characterized at baseline and 3 years later. Main Outcomes Annualized change in BMD and body composition by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). Models were adjusted for serum estradiol and testosterone levels. Results There was no evidence for an association between baseline FSH level and change in BMD or body composition by DXA or QCT. For femoral neck areal BMD, adjusted mean difference (95% CI) per SD increase in FSH was 1.3 (-0.7 to 3.3) mg/cm2/y in women, and -0.2 (-2.6 to 2.2) mg/cm2/y in men. For visceral fat, adjusted mean difference (95% CI) per SD increase in FSH was 1.80 (-0.03 to 3.62) cm2/y in women, and -0.33 (-3.73 to 3.06) cm2/y in men. Conclusions Although cross-sectional studies and studies in perimenopausal women have demonstrated associations between FSH and BMD and body composition, in older adults, FSH level is not associated with bone mass or body composition changes.

The immediate-early protein BRLF1 plays important roles in lytic infection of Epstein-Barr virus (EBV), in which it activates lytic viral transcription and replication. However, knowledge of the influence of BRLF1 on cellular gene expression and transcriptional reprogramming during the early lytic cycle remains limited. In the present study, deep RNA-sequencing analysis identified all differentially expressed genes (DEGs) and alternative splicing in B lymphoma cells subjected to wild-type and BRLF1-deficient EBV primary infection. The BRLF1-dependent cellular DEGs were annotated, and major differentially enriched pathways were related to DNA replication and transcription, immune and inflammatory responses, cytokine-receptor interactions and chemokine signaling and metabolic processes. Furthermore, analysis of BRLF1-binding proteins by mass spectrometry shows that BRLF1 binds to and cooperates with several transcription factors and components of the spliceosome and then influences both RNA polymerase II-dependent transcription and pre-mRNA splicing. The RTA-binding RRE motifs or specific motifs of unique cooperative transcription factors in viral and cellular DEG promoter regions indicate that BRLF1 employs different strategies for regulating viral and cellular transcription. Thus, our study characterized BRLF1-dependent cellular and viral transcriptional profile during primary infection and then revealed the comprehensive virus-cell interaction and alterations of transcription during EBV primary infection and lytic replication.

Mingbiao Ma,1– 3,* Minjun Chu,1,2,* Lvyan Tao,3– 5,* Jue Li,1,2 Xiaojuan Li,1,2 Hailin Huang,1,2 Kexuan Qu,6 Haiping Wang,1,2 Li Li,3– 5 Tingyi Du1– 3 1Department of Clinical Laboratory, Kunming Children’s Hospital, Kunming, Yunnan, People’s Republic of China; 2Department of Clinical Laboratory, Children’s Hospital Affiliated to Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 3Yunnan Key Laboratory of Children’s Major Disease Research, Kunming Children’s Hospital, Kunming, Yunnan, People’s Republic of China; 4Yunnan Institute of Pediatrics, Kunming Children’s Hospital, Kunming, Yunnan, People’s Republic of China; 5Kunming Key Laboratory of Children Infection and Immunity, Kunming Children’s Hospital, Kunming, Yunnan, People’s Republic of China; 6Department of Blood Transfusion, Kunming Children’s Hospital, Kunming, Yunnan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li LiYunnan Institute of Pediatrics, Kunming Children’s Hospital, Kunming, Yunnan, People’s Republic of ChinaEmail lili@etyy.cnTingyi DuDepartment of Clinical Laboratory, Kunming Children’s Hospital, Kunming, Yunnan, People’s Republic of ChinaEmail dutingyi@etyy.cnPurpose: The present study investigated the prevalence characteristics of oxacillin susceptible mecA-positive Staphylococcus aureus (OS-MRSA) in a children’s hospital in Kunming from January 2019 to December 2020.Methods: A total of 499 S. aureus strains were included in the study and tested for oxacillin susceptibility using the VITEK 2 Compact automated antimicrobial susceptibility test system. All oxacillin-susceptible strains were detected mecA and mecC by polymerase chain reaction (PCR). E-test was used to compare the minimum inhibitory concentration (MIC) values of methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), and OS-MRSA for oxacillin, cefoxitin, penicillin, vancomycin, erythromycin, and clindamycin. Molecular typing of OS-MRSA was performed by MLST and SCCmec typing. Toxin genes were detected by PCR.Results: Forty-five OS-MRSA strains were detected, for an overall rate of 9.02% (45/499). The MICs of MSSA, OS-MRSA, and MRSA against oxacillin were concentrated at 0.38, 0.38, and 12 μg/mL, respectively; the cefoxitin MICs of MSSA and MRSA were concentrated at 2 and 32 μg/mL respectively; and MICs of OS-MRSA were concentrated at 2 and 8 μg/mL; penicillin, vancomycin and erythromycin MICs against MSSA, OS-MRSA, and MRSA showed same centralized points and were 32, 1, and 256 μg/mL, respectively; the MICs of clindamycin against MSSA were 0.5 μg/mL, while that against OS-MRSA and MRSA were concentrated at 256 μg/mL. Molecular typing of OS-MRSA was dominated by ST59-SCCmec IV. The carrier rates of hemolysin genes (hl-a, hl-d) and fibrinogen-binding clumping factor genes (clfA, clfB) were 100% in OS-MRSA, followed by 40% (18/45) for enterotoxin genes (sea, seb).Conclusion: OS-MRSA has a high detection rate in children, and main molecular typing is ST59-SCCmecIV in Kunming. The identification ability of automated antibacterial drug sensitivity test detection systems for OS-MRSA is very limited. A combination of phenotypic analysis and molecular detection should be used to improve OS-MRSA identification.Keywords: Staphylococcus aureus, MRSA, OS-MRSA, children, oxacillin

Genes with cross-cancer aberrations are most likely to be functional genes or potential therapeutic targets. Here, we found a total of 137 genes were ectopically expressed in eight cancer types, of which Holliday junction recognition protein (HJURP) was significantly upregulated in prostate cancer (PCa). Moreover, patients with higher HJURP mRNA and protein levels had poorer outcomes, and the protein levels served as an independent prognosis factor for the overall survival of PCa patients. Functionally, ectopic HJURP expression promoted PCa cells proliferation in vitro and in vivo. Mechanistically, HJURP increased the ubiquitination of cyclin-dependent kinase inhibitor 1 (CDKN1A) via the GSK3β/JNK signaling pathway and decreased its stability. This study investigated the role of HJURP in PCa proliferation and may provide a novel prognostic and therapeutic target for PCa.

Excessive tissue deformation near cartilage lesions and acute inflammation within the knee joint after anterior cruciate ligament (ACL) rupture and reconstruction surgery accelerate the loss of fixed charge density (FCD) and subsequent cartilage tissue degeneration. Here, we show how biomechanical and biochemical degradation pathways can predict FCD loss using a patient-specific finite element model of an ACL reconstructed knee joint exhibiting a chondral lesion. Biomechanical degradation was based on the excessive maximum shear strains that may result in cell apoptosis, while biochemical degradation was driven by the diffusion of pro-inflammatory cytokines. We found that the biomechanical model was able to predict substantial localized FCD loss near the lesion and on the medial areas of the lateral tibial cartilage. In turn, the biochemical model predicted FCD loss all around the lesion and at intact areas; the highest FCD loss was at the cartilage-synovial fluid-interface and decreased towards the deeper zones. Interestingly, simulating a downturn of an acute inflammatory response by reducing the cytokine concentration exponentially over time in synovial fluid led to a recovery of FCD content in the cartilage. Our novel numerical approach suggests that in vivo FCD loss can be estimated in injured cartilage following ACL injury and reconstruction. Significance: Our novel modeling platform can benefit the prediction of PTOA progression and the development of treatment interventions such as disease-modifying drug testing and rehabilitation strategies. This article is protected by copyright. All rights reserved.

To obtain astragalus polysaccharide (APS)-magnetic graphene oxide (MGO) nanoparticles (NPs), MGO was prepared by chemical co-precipitation, and then loaded with APS NPs. After the physical characterization of the material was analyzed, it was adopted to treat patients with sepsis injury to study its mechanism. Then, changes in cytokine levels in the patient’s myocardial tissue were analyzed. Giving that septic myocardial injury-related neutrophil gelatinase (neutrophil gelatinase-associated lipocalin (NGAL) and cystatin) was related to hemodynamics, changes in the patient’s hemodynamic indicators were analyzed before and after the addition of nanomaterials. Moreover, changes of the patient’s gelatinase markers before and after the preparation of nanomaterials were also analyzed. The results showed that the Fe3O4 magnetic NPs were coated on the surface of GO while successfully adsorbing APS. The sample recovery rate was more than 100%, and the relative standard deviation was 0.48%. The in vitro release showed that the NPs were easily released in an acidic environment. Clinical trials showed that the levels of pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-β, etc.) in myocardial tissue were dramatically decreased (P < 0.05), while the levels of anti-inflammatory cytokines (IL-2, IL-4, etc.) were greatly increased (P < 0.05). The NGAL level at the arterial and venous ends both decreased remarkably (P < 0.05). The total mass transfer ratio (Mtr) increased obviously while the mass adsorption rate (Mad) decreased significantly (P < 0.05). In addition, hemodynamic indicators such as cardiac output (CO) and diastolic arterial pressure (DAP) all improved notably.

Human blood cells (HBCs) play essential roles in multiple biological processes but their roles in development of uterine polyps are unknown. Here we implemented a Mendelian randomization (MR) analysis to investigate the effects of 36 HBC traits on endometrial polyps (EPs) and cervical polyps (CPs). The random-effect inverse-variance weighted method was adopted as standard MR analysis and three additional MR methods (MR-Egger, weighted median, and MR-PRESSO) were used for sensitivity analyses. Genetic instruments of HBC traits was extracted from a large genome-wide association study of 173,480 individuals, while data for EPs and CPs were obtained from the UK Biobank. All samples were Europeans. Using genetic variants as instrumental variables, our study found that both eosinophil count (OR 0.85, 95% CI 0.79–0.93, P = 1.06 × 10−4) and eosinophil percentage of white cells (OR 0.84, 95% CI 0.77–0.91, P = 2.43 × 10−5) were associated with decreased risk of EPs. The results were robust in sensitivity analyses and no evidences of horizontal pleiotropy were observed. While we found no significant associations between HBC traits and CPs. Our findings suggested eosinophils might play important roles in the pathogenesis of EPs. Besides, out study provided novel insight into detecting uterine polyps biomarkers using genetic epidemiology approaches.

Robert's uterus is a rare Müllerian malformation first characterized by a French gynecologist Héléne Robert in 1969. It represents an asymmetric division of the uterine cavity. A 45-year-old female patient presented with vaginal bleeding and vague abdominal pain for the course of 20 days, with a blood human chorionic gonadotropin level of 10331.00 mIU/mL, and a gestational sac in the right uterine horn without a fetal heart beat revealed by the ultrasound. Ectopic pregnancy in the right uterine horn seemed to be the most likely diagnosis. Laparoscopic and hysteroscopic attempts to terminate the pregnancy failed. A pelvic magnetic resonance imaging (MRI) performed after the surgery demonstrated Robert's uterus with pregnancy in the blind hemicavity. When a pregnancy sac has been revealed by an ultrasound but nothing has been found by a hysteroscopy, a possibility of uterine malformation should be considered. Radiologists and gynecologists should consider the application of MRI for diagnosis of congenital Müllerian uterine anomalies.

Background: The association between activity level after anterior cruciate ligament (ACL) reconstruction (ACLR) and development of posttraumatic osteoarthritis (PTOA) remains unclear. This study investigated the relationship of patient-reported outcomes and progressive cartilage degenerative changes at 3 years after ACLR. Hypothesis: Higher activity levels, as measured by Marx scores, are significantly correlated with early cartilage degeneration after ACLR. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 35 patients (16 women; mean age, 31.0 ± 7.6 years) with isolated ACLR and without pre-existing arthritis were prospectively enrolled. Patients reported Marx activity scores and Knee injury and Osteoarthritis Outcome Score (KOOS) scores and underwent T1ρ magnetic resonance imaging (MRI) preoperatively, 6 months, 1 year, 2 years, and 3 years after ACLR with soft tissue graft (22 autograft). The change in cartilage relaxation times between preoperative and 3-year imaging was used to identify cartilage degeneration, defined as an increase in T1ρ values by 14.3%. Correlation between Marx activity levels, KOOS scores, and T1ρ degeneration was performed with the Spearman rank test. The Fisher exact test was used to test for association between Marx activity score cutoffs and degeneration. The Student t test was used to compare Whole-Organ Magnetic Resonance Imaging Score (WORMS) and T1ρ relaxation times. Significance was defined as P < .05. Results: Sixteen patients (45.7%) showed evidence of cartilage degeneration at 3 years, most frequently in the medial compartment (n = 12; 34%). Higher Marx activity scores at 3 years correlated with cartilage degeneration in the medial femur (rho = 0.34; P = .045), and medial tibia (rho = 0.43; P = .01). A Marx score of 11 or greater at 3 years was significantly associated with medial compartment degeneration ( P = .03), with a positive predictive value of 52.6%. No Marx score cutoff at years 1 or 2 predicted future cartilage degeneration. The KOOS Quality of Life score was inversely correlated with cartilage degeneration (rho = 0.38; P = .02). WORMS did not correlate with degeneration of the medial compartment. Conclusion: Increased activity at 3 years after ACLR was significantly associated with increased risk of medial compartment PTOA. While further research is needed to fully define these relationships, patients may be counseled that return to Marx activity levels of greater than 11 may be associated with a higher risk of medial compartment cartilage degeneration.

Background Previous studies have demonstrated that blood urea nitrogen (BUN) is strongly associated with sepsis. However, no data are currently available regarding the association of BUN levels and neonatal sepsis. Thus, this study aimed to investigate the role of BUN in predicting the presence and severity of neonatal sepsis. Methods In this study, we enrolled 925 neonates. Among them, 737 neonates were diagnosed with sepsis, including 426 neonates with severe sepsis. Neonates with hyperbilirubinemia (n = 188) served as controls. We collected complete clinical and laboratory data were collected. Multivariate logistic regression analysis was performed to identify the potential independent risk factor for neonatal sepsis. Receiver operating characteristic (ROC) curve analysis was used to evaluate the prediction accuracy of BUN in predicting neonatal sepsis. All statistical analyses were performed using the statistical package SPSS 24.0. Results Neonates with sepsis and severe sepsis had a higher level of BUN. The prevalence of neonates with severe sepsis was dramatically increased according to BUN tertiles. Correlation analysis showed that BUN levels were positively correlated with the levels of infection marker procalcitonin (PCT) and high-sensitivity C-reactive protein (hsCRP). Multiple logistic regression analysis showed that BUN was an independent risk factor for the presence and severity of neonatal sepsis. ROC curve analysis showed that BUN had a well discriminatory power in predicting sepsis (area under curve (AUC) = 0.69, 95% CI, 0.66–0.74, p

Objective: To compare the distribution of “mean corpuscular hemoglobin”-MCV, “mean corpuscular volume”-MCH, “hemoglobin”-HGB, “hemoglobin A”-HbA and “hemoglobin A2”-HbA2 in α and β thalassemia hematology screening between Li and Han nationality, and analyze the best diagnostic cut-off value. Methods: Select 7816 middle school students from Li nationality area as the research object, collect peripheral blood for blood cell analysis, hemoglobin electrophoresis and thalassaemia gene detection, and compare the difference in hematological parameters of common thalassemia genotype between Li and Han nationalities. Taking the genetic test results as the gold standard, construct the receiver operator characteristic curve (ROC curve) of relevant hematology parameters, calculate the Youden index and take its maximum diagnostic cut-off point as the best critical value. Results: Comparison of hematological parameters of common thalassemia genotypes showed that the average value of MCH and MCV of -α3.7/-α4.2 type in Li nationality was lower than that of Han nationality, and the average value of HbA2 of CD41-42/βN type was higher than that of Han nationality, there was no significant difference among other genotypes. ROC curve analysis shows that the MCH, MCV, and HGB values have poor diagnostic efficiency for thalassaemia, HbA has a slightly better diagnostic efficiency for α thalassaemia, and the optimal cut-off values of HbA for Li and Han nationalities are 96.95% and 97.75%, respectively; HbA2 has better screening efficiency for β-thalassemia, and the optimal cut-off values of HbA2 for Li and Han nationalities are 4.20% and 3.45% respectively. Conclusion: In the prevention and control screening of thalassaemia in the Li and Han nationalities, hemoglobin electrophoresis technology has a better diagnostic efficiency.

Matrix metalloproteinase-9 (MMP-9) belongs to the MMP family and has been widely investigated. Excessive MMP-9 expression can enhance extracellular matrix degradation and promote plaque instability. Studies have demonstrated that MMP-9 levels are higher in vulnerable plaques than in stable plaques. Additionally, several human studies have demonstrated that MMP-9 may be a predictor of atherosclerotic plaque instability and a risk factor for future adverse cardiovascular and cerebrovascular events. MMP-9 deficiency or blocking MMP-9 expression can inhibit plaque inflammation and prevent atherosclerotic plaque instability. All of these results suggest that MMP-9 may be a useful predictive biomarker for vulnerable atherosclerotic plaques, as well as a therapeutic target for preventing atherosclerotic plaque instability. In this review, we describe the structure, function, and regulation of MMP-9. We also discuss the role of MMP-9 in predicting and preventing atherosclerotic plaque instability.

The transition of alveolar type II epithelial cells into fibroblasts has been reported to cause and/or aggravate pulmonary fibrosis (PF), which is characterized by fibroblast proliferation, an enhanced production and accumulation of ECM (extracellular matrix), alveolar wall damage and functional capillary unit loss. Traditional Chinese medicine Emodin has been reported to inhibit TGF‐β‐induced epithelial‐mesenchymal transition (EMT) in alveolar epithelial cells through Notch signalling. In the present study, neutrophil elastase (NE, also known as ELA2) treatment promoted EMT, Notch1 cleavage (NICD/Notch1 ratio increase) and NICD nuclear translocation in RLE‐6TN cells and A549 cells. The promotive roles of NE treatment in these events were significantly reversed by Notch1 knockdown. Traditional Chinese medicine Emodin treatment remarkably inhibited the enzyme activity of NE, suppressed EMT, Notch1 cleavage and NICD nuclear translocation within RLE‐6TN and A549 cells, while NE treatment significantly reversed the effects of Emodin. Moreover, in RLE‐6TN, the effects of NE on EMT, Notch1 cleavage and NICD nuclear translocation were remarkably attenuated by Emodin treatment and more attenuated by the combination of Emodin and neutrophil elastase inhibitor Sivelestat or notch signal pathway inhibitor DAPT. In conclusion, we revealed the involvement of NE‐induced Notch1 cleavage in the functions of Emodin suppressing NE‐caused EMT in RLE‐6TN cells and A549 cells. This novel mechanism of Emodin inhibiting EMT might extend the application of Emodin in PF treatment.

Objective.The aim of this multireader exercise was to assess the reliability and change over time of erosion measurements in patients with rheumatoid arthritis (RA) using high-resolution peripheral quantitative computed tomography (HR-pQCT).Methods.HR-pQCT scans of 23 patients with RA were assessed at baseline and 12 months. Four experienced readers examined the dorsal, palmar, radial, and ulnar surfaces of the metacarpal head (MH) and phalangeal base (PB) of the second and third digits, blinded to time order. In total, 368 surfaces (23 patients´ 16 surfaces) were evaluated per timepoint to characterize cortical breaks as pathological (erosion) or physiological, and to quantify erosion width and depth. Reliability was evaluated by intraclass correlation coefficients (ICC), percentage agreement, and Light k; change over time was defined by means ± SD of erosion numbers and dimensions.Results.ICC for the mean measurements of width and depth of the pathological breaks ranged between 0.819–0.883, and 0.771–0.907, respectively. Most physiological cortical breaks were found at the palmar PB, whereas most pathological cortical breaks were located at the radial MH. There was a significant increase in both the numbers and the dimensions of erosions between baseline and follow-up (P= 0.0001 for erosion numbers, width, and depth in axial plane;P= 0.001 for depth in perpendicular plane).Conclusion.This exercise confirmed good reliability of HR-pQCT erosion measurements and their ability to detect change over time.

Purpose. To investigate the serum changes of oxidative stress markers and the relationship between these factors and visual field (VF) progression in patients with primary angle closure glaucoma (PACG). Methods. A case-control and a prospective cohort study. A total of 94 patients with PACG and 89 normal controls were enrolled. Furthermore, 94 PACG subjects were followed up for at least two years (once every six months). All participants were evaluated for serum levels of superoxide dismutase (SOD), total antioxidant status (TAS), hydrogen peroxide (H2O2), malondialdehyde (MDA), glutathione peroxidase, glutathione reductase, and detailed eye and systematic examination. Binary logistic regression analysis and Cox regression analysis were performed. Results. The serum levels of SOD and TAS in the PACG group were significantly lower than those in the control group (p<0.001). Meanwhile, PACG subjects had significantly higher levels of MDA and H2O2 than the normal control subjects (p<0.001). Serum levels of TAS (OR=0.773, 95%CI=0.349−0.714, p<0.001), SOD (OR=0.975, 95%CI=0.955−0.995, p<0.001), MDA (OR=1.155, 95%CI=1.080−1.235, p<0.001), and H2O2 (OR=1.216, 95%CI=1.142−1.295, p<0.001) were independent risk/protective factors for PACG. TAS levels (HR=0.041, 95%CI=0.008–0.218, p<0.001), SOD levels (HR=0.983, 95%CI=0.971–0.994, p=0.003), and MDA levels (HR=1.010, 95%CI=1.001–1.018, p=0.015) at baseline were associated with visual field progression. Kaplan–Meier curves reveal that patients with TAS<0.95/SOD<143/MDA>12 had a significantly higher percentage of PACG progression (p<0.05). Conclusions. Decreased levels of TAS and SOD as well as increased levels of MDA at baseline were associated with VF progression in patients with PACG. These findings suggest that oxidative stress was involved in the onset and development of PACG.

Neutrophil extracellular traps (NETs) are characterized as extracellular DNA fibers comprised of histone and cytoplasmic granule proteins. NETs were first described as a form of innate response against pathogen invasion, which can capture pathogens, degrade bacterial toxic factors, and kill bacteria. Additionally, NETs also provide a scaffold for protein and cell binding. Protein binding to NETs further activate the coagulation system which participates in thrombosis. In addition, NETs also can damage the tissues due to the proteins they carry. Many studies have suggested that the excessive formation of NETs may contribute to a range of diseases, including thrombosis, atherosclerosis, autoimmune diseases, and sepsis. In this review, we describe the structure and components of NETs, models of NET formation, and detection methods. We also discuss the molecular mechanism of NET formation and their disease relevance. Modulation of NET formation may provide a new route for the prevention and treatment of releated human diseases.

The purpose of this proof-of-concept study was to develop three-dimensional patient-specific mechanobiological knee joint models to simulate alterations in the fixed charged density (FCD) around cartilage lesions during the stance phase of the walking gait. Two patients with anterior cruciate ligament (ACL) reconstructed knees were imaged at 1 and 3 years after surgery. The magnetic resonance imaging (MRI) data were used for segmenting the knee geometries, including the cartilage lesions. Based on these geometries, finite element (FE) models were developed. The gait of the patients was obtained using a motion capture system. Musculoskeletal modeling was utilized to calculate knee joint contact and lower extremity muscle forces for the FE models. Finally, a cartilage adaptation algorithm was implemented in both FE models. In the algorithm, it was assumed that excessive maximum shear and deviatoric strains (calculated as the combination of principal strains), and fluid velocity, are responsible for the FCD loss. Changes in the longitudinal T1ρ and T2 relaxation times were postulated to be related to changes in the cartilage composition and were compared with the numerical predictions. In patient 1 model, both the excessive fluid velocity and strain caused the FCD loss primarily near the cartilage lesion. T1ρ and T2 relaxation times increased during the follow-up in the same location. In contrast, in patient 2 model, only the excessive fluid velocity led to a slight FCD loss near the lesion, where MRI parameters did not show evidence of alterations. Significance: This novel proof-of-concept study suggests mechanisms through which a local FCD loss might occur near cartilage lesions. In order to obtain statistical evidence for these findings, the method should be investigated with a larger cohort of subjects.

Osteosarcoma (OS) is a common malignant tumor in the world. Circular RNAs are endogenous non-coding RNAs that have been linked to the development of cancer. However, the role of circ_001569 in OS progression is still unclear. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circ_001569, microRNA-185-5p (miR-185-5p) and flotillin-2 (FLOT2). The abilities of cell proliferation, migration and invasion were evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and Transwell assays, respectively. Also, western blot analysis was performed to assess the levels of epithelial–mesenchymal transition (EMT)-related proteins and FLOT2 protein. Besides, the dual-luciferase reporter assay was used to verify the interactions among circ_001569, miR-185-5p and FLOT2. Circ_001569 expression was increased in OS tissues and cells, and its knockdown reduced the proliferation, migration, invasion and EMT of OS cells. MiR-185-5p could interact with circ_001569. Inhibition of miR-185-5p could recover the suppression effects of silenced-circ_001569 on the proliferation and metastasis of OS cells. Furthermore, FLOT2 was a target of miR-185-5p. Overexpressed FLOT2 could restore the inhibition effects of miR-185-5p mimic on the proliferation and metastasis of OS cells. Also, FLOT2 expression was regulated by circ_001569 and miR-185-5p. In addition, circ_001569 knockdown also reduced the OS tumor growth in vivo. Circ_001569 might act as an oncogene in OS progression by regulating the miR-185-5p/FLOT2 axis, which provided a reliable new approach for the treatment of OS patients.

Background: There is growing evidence suggesting a link between patellofemoral joint (PFJ) osteoarthritis in anterior cruciate ligament (ACL)–reconstructed knees and altered joint alignment. Purpose: To determine whether patellar alignment differs between participants with and without ACL reconstruction (ACLR) and to identify possible associations between patellar alignment and PFJ osteoarthritis features over 3 years. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 37 participants with ACLR (sex, 23 male; mean ± SD age, 28.1 ± 7.4 years) and 20 healthy controls (13 male; 30.4 ± 4.8 years) participated. Patients underwent magnetic resonance imaging: (1) sagittal T2-weighted fat-saturated fast spin echo images to calculate patellar alignment, (2) sagittal 3-dimensional intermediate-weighted fast spin echo Cube sequence for clinical morphological grading (modified Whole-Organ Magnetic Resonance Imaging Score [WORMS]), and (3) sagittal combined T1ρ/T2 mapping sequence for performing voxel-based relaxometry. Patellar alignment of the ACLR knees were assessed at 6 months (baseline). One-way analysis of variance was used to compare patellar alignment among the ACLR (at 6 months), contralateral, and control knees. Within the ACLR group, a logistic regression model was used to identify if patellar alignment measures at baseline were risk factors for worsening of PFJ structural changes over 3 years. Statistical parametric mapping was used to evaluate the longitudinal associations between patellar alignment and cartilage relaxation times at 3 years. Results: When compared with control knees, ACLR knees exhibited a laterally and anteriorly displaced patella ( P = .045 and P = .041), less flexion ( P = .031), and less lateral spin ( P = .012). Furthermore, excessive lateral displacement was a significant predictor of worsening of WORMS ( P = .050). Lateral displacement was positively correlated with increased T1ρ and T2 in the patellar and trochlear cartilage at 3 years. Patellar lateral spin revealed similar negative findings. Conclusion: Participants with ACLR exhibited a laterally and anteriorly displaced patella, less flexion, and less lateral spin when compared with healthy controls. Excessive patellar lateral displacement was the strongest predictor to the development of PFJ osteoarthritis features longitudinally.

The purpose of this study was to analyze the relationship between postsurgical tibial translation (TT) and tibial rotation (TR) with cartilage matrix changes using quantitative magnetic resonance imaging, specifically voxel-based relaxometry with T1ρ and T2 mapping sequences. Knee magnetic resonance imaging's (MRI's) of 51 patients with unilateral anterior cruciate ligament injury, no concomitant ligamentous injury, history of osteoarthritis (OA), and previous knee surgery were scanned prior to surgery. Thirty-four patients completed follow-up MRI scans at 6-month, 1- and 2-year post-reconstruction and were included in this study. Knee biomechanics, T1ρ, and T2 were calculated using an in-house Matlab program. Compared to the contralateral knee, the injured knee demonstrated significantly increased anterior TT at baseline (P < .001), 6-month (P < .001), 1- (P = .001), and 2-year (P < .001). Furthermore, patients were divided into groups based on TT at 6-month. When compared to patients with normal TT, those with increased anterior TT at 6-month displayed significantly longer T1ρ and T2 relaxation times in 10.4% and 7.4% of the voxels in the injured medial tibia at 1-year, respectively, as well as 12.4% and 9.8% of the voxels in the injured medial tibia at 2-year, respectively. Our results demonstrate an association between abnormal tibiofemoral position and early degradative changes to the articular cartilage matrix of the injured knee. Clinical significance: These findings suggest that altered tibiofemoral position following ACL reconstruction is associated with early degeneration of knee cartilage. Future prospective studies employing longer follow-up times are warranted to evaluate the relationship between abnormal tibiofemoral position and the early onset of posttraumatic OA.

Background: Joint space assessment for rheumatoid arthritis (RA) by ordinal conventional radiographic scales is susceptible to floor and ceiling effects. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides superior resolution, and may detect earlier changes. The goal of this work was to compare existing 3D methods to calculate joint space width (JSW) metrics in human metacarpophalangeal (MCP) joints with HR-pQCT and reach consensus for future studies. Using the consensus method, we established reproducibility with repositioning as well as feasibility for use in second-generation HR-pQCT scanners.Methods: Three published JSW methods were compared using datasets from individuals with RA from three research centers. A SPECTRA consensus method was developed to take advantage of strengths of the individual methods. Using the SPECTRA method, reproducibility after repositioning was tested and agreement between scanner generations was also established.Results: When comparing existing JSW methods, excellent agreement was shown for JSW minimum and mean (ICC 0.987-0.996) but not maximum and volume (ICC 0.000-0.897). Differences were identified as variations in volume definitions and algorithmic differences that generated high sensitivity to boundary conditions. The SPECTRA consensus method reduced this sensitivity, demonstrating good scan-rescan reliability (ICC >0.911) except for minimum JSW (ICC 0.656). There was strong agreement between results from first- and second-generation HR-pQCT (ICC >0.833).Conclusions: The SPECTRA consensus method combines unique strengths of three independently-developed algorithms and leverages underlying software updates to provide a mature analysis to measure 3D JSW. This method is robust with respect to repositioning and scanner generations, suggesting its suitability for detecting change.

Intrauterine growth restriction (IUGR) is a common fetal development disorder which has great impact on neonatal health. Insulin-like growth factor-1 (IGF1) has an important role in regulating fetal growth. Whether IGF1 DNA methylation was associated with IUGR has not been studied. Placenta samples from IUGR (n = 27) and normal delivery (n = 29) were collected whereas basic information of mothers and infants were also collected. RT-PCR was performed to examine IGF1 transcriptions and bisulfite sequencing PCR was used for DNA methylation analysis. Gene expression analysis found IUGR had significantly lower IGF1 transcription compared to control group (IUGR: 0.330 ± 0.351; control group: 1.001 ± 0.800, t = 3.995, P IGF1 were all highly methylated and there is no difference on DNA methylation rate between IUGR and control group (IUGR: 75%; control group: 81%; P = 0.09). Interestingly, in both IUGR and control groups, male fetus had significantly higher methylation rate than female fetus (IUGR: male: 87%; female: 74%, P = 0.016; control: male: 82%; female: 69%, P = 0.012). There was no correlation between IGF1gene expression and DNA methylation rate (r = 0.095, P = 0.063). Intrauterine fetal growth restriction placenta had significantly lower IGF1gene expression; however, IGF1 DNA methylation level was similar. A potential fetus gender difference was also found in IGF1 DNA methylation rate.