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The path to accurate diagnosis and predictable treatment of DDH parallels the many advances that application of the scientific method has allowed in the specialty of orthopedic surgery. The development of academic centers that focus on research and education in childhood hip disorders, as well as a growing number of centers that focus on hip problems in adolescents and young adults, assure a continuous and changing "history" of this common childhood hip condition.

The path to accurate diagnosis and predictable treatment of DDH parallels the many advances that application of the scientific method has allowed in the specialty of orthopedic surgery. The development of academic centers that focus on research and education in childhood hip disorders, as well as a growing number of centers that focus on hip problems in adolescents and young adults, assure a continuous and changing "history" of this common childhood hip condition.The emergence of human coronaviruses (HCoVs), especially the current pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), engender severe threats to public health globally. Despite the outstanding breakthrough of new vaccines and therapeutic medicines in the past years, HCoVs still undergo unpredictable mutations, thus demanding more effective diagnostic and therapeutic strategies. Benefitting from the unique physicochemical properties and multiple nano-bio interactions, nanomaterials hold promising potential to fight against various HCoVs, either by providing sensitive and economic nanosensors for rapid viral detection, or by developing translatable nanovaccines and broad-spectrum nanomedicines for HCoV treatment. ZCL278 concentration Herein, we systemically summarized the recent applications of nanoagents in diagnostics and therapeutics for HCoV-induced diseases, as well as their limitations and perspectives against HCoV variants. We believe this review will promote the design of innovative theranostic nanoagents for the current and future HCoV-caused pandemics.Breast cancer is the most commonly diagnosed cancer in women and is one of the leading causes of death from cancer in women worldwide. Despite the significant benefits of using conventional chemotherapy in the treatment of breast cancer, one of its subtypes, the triple-negative breast cancer, is still a challenge in clinical practice. Recent studies have been investigating the role of the immune system in breast cancer and the development of immunotherapy. Although recently the use of atezolizumab, an anti-PD-L1 monoclonal antibody, combined with chemotherapy was approved, an important step in the treatment of patients with triple-negative metastatic breast cancer, the use of immunotherapy to treat breast tumors remains a major challenge. In this systematic literature review, following PRISMA guidelines, we searched for clinical trials using immunotherapy in the treatment of metastatic triple-negative breast cancer published until March 2020 in the databases EMBASE, PubMed and Cochrane Central Register of Controlled Trials (CENTRAL), with no language restrictions. We did not contact the authors of the clinical trials to obtain additional information. Two researchers independently collected the data and assessed the quality of this study. The literature shows that immunotherapy with anti-PD-1/PD-L1 agents is emerging as a new treatment option in breast cancer. On the other hand, when compared to other types of cancer in which several agents have already been approved, the research is still in its infancy. The use of anti-PD-1/PD-L1 agents as monotherapy revealed encouraging results in the metastatic setting, especially when administered in the early course of the disease, although combination strategies with chemotherapy appear to increase its efficacy. The main limitation of this study is the approach of cancer only in advanced stages.Repeated data are increasingly collected in studies to investigate the trajectory of change in measurements over time. Determining a link between one repeated measurement with another that is considered as the biomarker for disease progression, may provide a new target for drug development. When a third variable is associated with one of the two measurements, partial correlation after eliminating the effect of that variable is able to provide reliable estimate for association as compared to the existing raw correlation for repeated data. We propose using linear regression models to compute residuals by modeling a relationship between each measurement and a third variable. The computed residuals are then used in a linear mixed model (implemented by SAS Proc Mixed) to compute partial correlation for repeated data. Alternatively, the partial correlation may be computed as the average of partial correlations at each visit. We provide two real examples to illustrate the application of the proposed partial correlation, and conduct extensive numerical studies to compare the proposed partial correlation coefficients.Spatial skills decline in older adults, particularly those with cognitive challenges, leaving them less confident to navigate their environment. Spatial training has been shown to help with this decline and engaging in music has benefitted the spatial skills of musicians. A paucity of research explores ways that music could serve as spatial training for older adults. This study explored music classes as spatial training for older adults in three ways 1) Success rates staying spatially oriented on the instrument. 2.) Ability to read written music. 3.) Outcomes on a spatial orientation test taken pre- and post-intervention. We developed and tested a six-week marimba class that targeted spatial training principles for older adults with predementia or early dementia. We assessed the spatial skills with the Orientation Test from the Test of Visual Perceptual Skills pre- and post-intervention. Their scores increased an average of 0.71, a clinically meaningful change (d = 0.3). Participants also demonstrated high frequencies of remaining oriented on the instrument, and more participants self-selected to read music without notes (p less then 0.01) over the course of the intervention. With future research, music-based training may be one way to support spatial skills during cognitive decline.As one of the fundamental components of Astragalus membranaceus, astragaloside IV (AST IV) exerts protective effects against cerebral ischemia-reperfusion injury (CIRI). Nevertheless, the underlying mechanisms have not yet been conclusively elucidated. To do so, here, we report on the regulatory effects of Nrf2 on NLRP3 inflammasome-mediated pyroptosis. CIRI was induced by middle cerebral artery occlusion-reperfusion (MCAO/R) in Sprague Dawley rats and modeled by oxygen and glucose deprivation/reoxygenation (OGD/R) in SH-SY5Y cells. Cerebral infarct volume and neurological deficit score served as indices to evaluate MCAO/R injury. In addition, the CCK-8 assay was used to assess cell viability, the LDH leakage rate was used as a quantitative index, and propidium iodide (PI) staining was used to visualize cells after OGD/R injury. The NLRP3/Caspase-1/GSDMD pathway, which produces the pores in the cell membrane that are central to the pyroptosis process, was assessed to investigate pyroptosis. Nrf2 activation wa activation. Particularly revealing was that the Nrf2 inhibitor ML385 partly blocked the above effects of AST IV. Taken together, these results demonstrate that AST IV alleviates CIRI through inhibiting NLRP3 inflammasome-mediated pyroptosis via activating Nrf2.A balance between bone formation by osteoblasts and bone resorption by osteoclasts is necessary to maintain bone health and homeostasis. As a cancer of plasma cells, multiple myeloma (MM) is accompanied with rapid bone loss and fragility fracture. Bortezomib has been used as a first-line for treating MM for decades. Recently, the potential protection of bortezomib on osteoporosis (OP) is reported; however, the specific mechanism involving bortezomib-mediated antiosteoporotic effect is undetermined. In the present study, we assessed the effects of in vitro bortezomib treatment on osteogenesis and osteoclastogenesis and the protective effect on bone loss in ovariectomized (OVX) mice. Our results indicated that bortezomib treatment increased osteogenic differentiation of MC3T3-E1 cells as evidenced by increased levels of matrix mineralization and osteoblast-specific markers. In bortezomib-treated bone marrow monocytes (BMMs), osteoclast differentiation was suppressed, substantiated by downregulated tartrate-resistant acid phosphatase- (TRAP-) positive multinucleated cells, areas of actin rings, pit formation, and osteoclast-specific genes. Mechanistically, bortezomib exerted a protective effect against OP through the Smad ubiquitination regulatory factor- (SMURF-) mediated ubiquitination pathway. Furthermore, in vivo intraperitoneal injection of bortezomib attenuated the bone microarchitecture in OVX mice. Accordingly, our findings corroborated that bortezomib might have future applications in the treatment of postmenopausal OP.Food-derived bioactive peptides are considered as the important sources of natural bioactive ingredients. Approximately 3094 peptides were identified by nESI-LC-MS/MS in the hydrolyzed yak milk residue. Peptide KALNEINQF (T10) is the strongest antioxidant peptide. The damage model of H2O2-induced human umbilical vein endothelial cells (HUVECs) was used to evaluate the antioxidant effect. After treatment with 25, 50, or 100 μg/mL T10 peptide, T10 obviously decreased H2O2-induced damage and increased the cell survival. Comparing with the H2O2-induced damage group, superoxide dismutase (SOD) activities were significantly increased 1.03, 1.1, and 1.33 times, and glutathione reductase (GR) activities were significantly increased 1.11, 1.30, and 1.43 times, respectively. Malondialdehyde (MDA) also reduced 1.41, 1.54, and 1.72 times, respectively. T10 inhibited H2O2-induced apoptosis in HUVECs, and protein expressions of the apoptosis-related genes bcl-2 and bax were increased and decreased by 1.95 and 1.44 times, respectively, suggesting T10 decreases apoptosis of the mitochondria-dependent pathway. Comparing with the H2O2-induced damage group, the RNA expressions of Nrf2, HO-1, and NQO1 were significantly increased by 2.00, 2.11, and 1.94 times; the protein expressions of p-Nrf2, HO-1, and NQO1 were significantly increased by 2.67, 1.73, and 1.04 times; and Keap1 was downregulated by 3.9 and 1.32 times, respectively. T10 also regulated the Nrf2 pathway and expressions of related genes (Keap1, HO-1, and NQO1), and blocking the Nrf2 pathway in the model decreased the protective effect of T10. Taken together, T10 peptide isolated from yak milk residue has a protective effect against H2O2-induced damage in HUVECs and the molecular mechanisms are involved in the regulation of Nrf2 signaling pathway and cell apoptosis.Warburgia ugandensis Sprague (W. ugandensis), widely distributed in Africa, is a traditional medicinal plant used for the treatment of various diseases including cancer. We intended to evaluate the anticolorectal cancer (CRC) activities of the crude extract from W. ugandensis (WUD) and reveal the underlying molecular mechanisms of its action. We found that WUD inhibited the proliferation of HT-29 and HCT116 cells in a time- and dose-dependent manner and induced intracellular ROS generation. The inhibitory effect of WUD on the proliferation of HT-29 and HCT116 cells could be attenuated by NAC (a ROS scavenger) in a dose-dependent manner. WUD induced G0/G1 phase arrest, down-regulated the protein expression of Cyclin D1 via ROS accumulation in HT-29 cells. In search of the molecular mechanism involved in WUD-induced Cyclin D1 down-regulation, it was found that WUD can suppress PI3K/Akt/GSK3β signaling pathway in HT-29 cells. Next, it was found that WUD also activated apoptosis, poly-ADP ribose polymerase 1 (PARP1) cleavage and down-regulated pro-caspase 3 in HT-29 and HCT116 cells.