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Objective: To propose a new technique to treat lumbar spinal stenosis with median approach endoscopic decompression combined with interspinous process implant fusion and evaluate the initial clinical outcome.Methods: This study involved 30 patients who had neurogenic commitment claudication over 2 years and were resistant to conservative therapy. All cases were treated using the median approach endoscopic decompression combined with interspinous process implant fusion in 2006. Clinical signs and radicular pain were noted and evaluated preoperatively and at the 1st month and 3rd month postoperatively. Japanese Orthopedic Association (JOA) score was used to evaluate leg and back pain. X-ray films at flexion and extension were applied to evaluate the range of motion at involved segments.Results: There was a significant increase in JOA score postoperatively, but no significant difference preoperatively or postoperatively between the two groups.The range of motion at involved segments was significantly higher in the control group.Conclusions: The median approach endoscopic decompression is an ideal method for bilateral radiculopathy resulting from lumbar spinal canal stenosis. The combination with interspinous process implant fusion can stabilize the spine.The initial clinical outcome is exllent. Preservation of adjacent level disease can be assessed only in long-term follow-up. [ABSTRACT FROM AUTHOR]

Objective: The conventional approaches for treatment of thoracolumbar diseases require extensive surgical exposure, often leading to postoperative pain and morbidity. Thoracoscopic-assisted surgery in these regions usually requires an extended recovery period due to the placement of drainage. We developed an innovative retroperitoneal-extrapleural approach to thoracolumbar involvement by an extra-diaphragmatic technique using dedicated instruments. Neither incision nor reconstruction of the diaphragm was necessary. Exposure to the lateral part of the thoracolumbar vertebrae could be achieved without crus resection. This study is aimed to evaluate the clinical outcomes of this new surgical procedure.Methods: A total of 9 cases (5 cases of thoracolumbar fracture-dislocation, 1 each of spinal infection, tumor, thoracolumbar scoliosis and ossification of posterior longitudinal ligament) were subjected to the study. The average age of the patients was 52.3 years. The results were compared with the control group consisting of thoracoscopic surgery subgroup (5 patients, mean age 52.1 years) and conventional surgery subgroup (12 patients, mean age 61.3 years).Results: Compared with the control group, the average period of bed confinement and mean intra- and postoperative blood loss decreased significantly. Pulmonary complications were avoided in all cases. The surgical time was shortened, postoperative pain was reduced, and early postoperative ambulation became possible.Conclusion: The diaphragm-preserving retroperitoneal-extrapleural approach that we developed is a valid minimally invasive alternative for the treatment of thoracolumbar diseases. [ABSTRACT FROM AUTHOR]

Objective: To investigate the opportune time of secondary definitive surgery for patients with multiple injuries from earthquakes based on the acute physiology and chronic health evaluation II (APACHE II) score and the principles of damage control.Methods: Twenty-one patients with critical earthquake injuries were treated with damage control strategies, followed by medical support and surgical intervention to restore their physical potential in the intensive care unit (ICU). Successive APACHE II scoring was adopted to evaluate the patients'physiological status, and then, internal fixation of fractures and other definitive operations were performed.Results: All the patients were effectively treated with few complications, low deformity rate and no death.Conclusions: Appropriate evaluation of patients?physiological potential, right decision on surgical time and proper operative method can reduce the rates of complications, disability and death for patients with critical earthquake injuries. [ABSTRACT FROM AUTHOR]

Background: Ribosome engineering is a semi-empirical technique used to select antibiotic-resistant mutants that exhibit altered secondary metabolism. This method has been demonstrated to effectively select mutants with enhanced synthesis of natural products in many bacterial species, including actinomycetes. Myxobacteria are recognized as fascinating producers of natural active products. However, it remains uncertain whether this technique is similarly effective in myxobacteria, especially for the heterologous production of epothilones in Myxococcus xanthus., Results: Antibiotics that target the ribosome and RNA polymerase (RNAP) were evaluated for ribosome engineering of the epothilone-producing strain M. xanthus ZE9. The production of epothilone was dramatically altered in different resistant mutants. We screened the mutants resistant to neomycin and rifampicin and found that the yield of epothilones in the resistant mutant ZE9N-R22 was improved by sixfold compared to that of ZE9. Our findings indicate that the improved growth of the mutants, the upregulation of epothilone biosynthetic genes, and specific mutations identified through genome re-sequencing may collectively contribute to the yield improvement. Ultimately, the total titer of epothilones achieved in a 10 L bioreactor reached 93.4 mg/L., Conclusions: Ribosome engineering is an efficient approach to obtain M. xanthus strains with enhanced production of epothilones through various interference mechanisms. Here, we discuss the potential mechanisms of the semi-empirical method., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To compare the accuracy and efficiency between the model development method and the software development method, which design and develop 3D printed integral anatomical acetabular prosthesis to be used in total hip arthroplasty(THA) for patients with Crowe type Ⅱ and Ⅲ developmental dysplasia of the hip(DDH). Methods: Fifteen patients with end-stage hip osteoarthritis due to Crowe type Ⅱ and Ⅲ DDH who underwent THA in the Orthopedics Department of the First Affiliated Hospital of Bengbu Medical College between January 2015 and June 2023 were selected in this study retrospectively. There were 1 male (1 hip) and 14 females (17 hips) with a mean age of (55.1±9.1) years. There were 12 hips with Crowe type Ⅱ, 6 hips with Crowe type Ⅲ. The preoperative pelvis three-dimensional CT data in those patients were used to design integral anatomical acetabular prosthesis. The model development group used 3D printing technology to print life-size pelvis models. The acetabulum was reamed and the acetabulum cup was inserted into the socket according to conventional THA procedures. The bone defect above the acetabulum cup was filled with bone wax. The Mimics and 3-matic software were used to simulate the THA procedures, design and install the integrated anatomical acetabular prosthesis in the software development group. The operation time, the size of the acetabular cup, the volume and surface area of the acetabulum bone defect, the acetabular cup's inclination and anteversion, the horizontal distance and the vertical distance of hip rotation center were compared between the two methods. Results: The study in the two groups were all based on the data of 18 hips in the 15 patients. The horizontal and vertical distances of rotation center in the model development group and software development group was (32.08±1.80) mm, (32.17±2.40) mm and (14.36±1.53) mm, (15.11±1.45) mm, respectively (both P >0.05). The cup size in model development group was (48.56±1.15)mm, and it was (48.77±1.22) mm in the software group ( P =0.160). The anteversion and inclination of the acetabular cup in the model and software groups were 23.79°±6.31°, 30.49°±11.03° and 15.17°±0.52°, 40.24°±0.58°, respectively (both P <0.01). The volume and surface area of the acetabulum bone defect in the model development group was (5.06±2.86) mm 3 and (8.31±2.21) mm 2 , respectively, while it was (4.01±2.56)mm 3 and (6.83±2.71) mm 2 , respectively, in the software development group (both P <0.05). The work time in the model development group was (24.43±0.68) h and (0.47±0.12) h in the software development group, respectively ( P <0.001). Conclusion: Compared with the 3D printing model development method, the application of Mimics and 3-matic software to design and develop integrated anatomical acetabular prosthesis in total hip arthroplasty for Crowe type Ⅱ and Ⅲ DDH show advantages of convenience, high efficiency and more accuracy.

Decoding DNA methylation sites through nanopore sequencing has emerged as a cutting-edge technology in the field of DNA methylation research, as it enables direct sequencing of native DNA molecules without the need for prior enzymatic or chemical treatments. During nanopore sequencing, methylation modifications on DNA bases cause changes in electrical current intensity. Therefore, constructing deep neural network models to decode the electrical signals of nanopore sequencing has become a crucial step in methylation site identification. In this study, we utilized nanopore sequencing data containing diverse DNA methylation types and motif sequence diversity. We proposed a feature encoding method based on current signal clustering and leveraged the powerful attention mechanism in the Transformer framework to construct the PoreFormer model for identifying DNA methylation sites in nanopore sequencing. The model demonstrated excellent performance under conditions of multi-class methylation and motif sequence diversity, offering new insights into related research fields., (© The Author(s) 2024. Published by Oxford University Press.)

Exercise has emerged as one of the important and effective non-drug therapies used for management of type 2 diabetes (T2D) in certain nations. The present report summarizes the latest findings from the research on the beneficial effect of exercise on T2D. The objectives were to provide references for the theoretical study and the clinical practice of exercise-based management of T2D, in addition to identify the limitations of the existing literature, thereby provide direction for future research in this field., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Impaired brain glucose metabolism is an early indicator of Alzheimer's disease (AD); however, the fundamental mechanism is unknown. In this study, we found a substantial decline in isocitrate dehydrogenase 3β (IDH3β) levels, a critical tricarboxylic acid cycle enzyme, in AD patients and AD-transgenic mice's brains. Further investigations demonstrated that the knockdown of IDH3β induced oxidation-phosphorylation uncoupling, leading to reduced energy metabolism and lactate accumulation. The resulting increased lactate, a source of lactyl, was found to promote histone lactylation, thereby enhancing the expression of paired-box gene 6 (PAX6). As an inhibitory transcription factor of IDH3β, the elevated PAX6 in turn inhibited the expression of IDH3β, leading to tau hyperphosphorylation, synapse impairment, and learning and memory deficits resembling those seen in AD. In AD-transgenic mice, upregulating IDH3β and downregulating PAX6 were found to improve cognitive functioning and reverse AD-like pathologies. Collectively, our data suggest that impaired oxidative phosphorylation accelerates AD progression via a positive feedback inhibition loop of IDH3β-lactate-PAX6-IDH3β. Breaking this loop by upregulating IDH3β or downregulating PAX6 attenuates AD neurodegeneration and cognitive impairments., (© 2024. The Author(s).)

The chromosomal position effect can significantly affect the transgene expression, which may provide an efficient strategy for the inauguration of alien genes in new hosts, but has been less explored rationally. The bacterium Myxococcus xanthus harbors a large circular high-GC genome, and the position effect in this chassis may result in a thousand-fold expression variation of alien natural products. In this study, we conducted transposon insertion at TA sites on the M. xanthus genome, and used enrichment and dilution indexes to respectively appraise high and low expression potentials of alien genes at insertion sites. The enrichment sites are characteristically distributed along the genome, and the dilution sites are overlapped well with the horizontal transfer genes. We experimentally demonstrated the enrichment sites as high expression integration sites (HEISs), and the dilution sites unsuitable for gene integration expression. This work highlights that HEISs are the plug-and-play sites for efficient expression of integrated genes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Curcumae Longae Rhizoma (turmeric), Curcumae Radix and Curcumae Rhizoma are derived from the Curcuma species, and have gradually become three of the most commonly used medicinal herbs in China due to their different origins, processing methods and medicinal part. These three herbs have certain similarities in morphology, chemical composition, and pharmacological effects. All three of these herbs contain curcuminoids and volatile oil compounds, which exhibit anti-inflammatory, anti-tumor, antioxidant, and neuroprotective properties, although modern clinical applications have their own requirements. At present, there is no systematic guidelines for the clinical application of these three of Curcuma species; consequently, there is a high risk of unwanted phenomena associated with the mixing and indiscriminate use of these herbs. In this review, we focus predominantly on morphology, chemical composition, and the pharmacological activity of these three Curcuma herbs and summarize the current status of research in this field. Our goal is to provide a better understanding of clinical value of these Curcuma species so that we can provide reference guidelines for their further development, utilization and rational clinical application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Quan, Yin, Li, Wang, Zheng, Feng, Zhao and Li.)

Soil biodiversity plays an important role in both agricultural productivity and ecosystem functions. Cover crop species influence the primary productivity of the ecosystem and basal resources. However, it remains poorly understood how different cover crop treatments influence the community of soil nematodes in an orchard ecosystem. In this study, field experiments were conducted to investigate the effects of cover crop treatments with different species numbers, i.e., no cover crop (CK), two cover crop species (C2), four cover crop species (C4), and eight cover crop species (C8), on weed biomass, together with composition, abundance, and metabolic footprint of soil nematode community in a kiwifruit orchard. As compared to the CK group, the groups of cover crop treatments had lower weed biomass, which decreased with the increase of the cover crop diversity. Moreover, for the abundance of total nematodes, fungivores exhibited higher levels in C4 and C8 treatments than that in CK, bacterivores had a higher abundance in C4 treatment, and plant parasites had a higher abundance in C2 and C8 treatments. Cover crop treatments also changed the structure of nematode community and enhanced the nematode interactions and complexity of nematode community network. In addition, C4 increased the Wasilewska index but decreased the plant-parasite index. The metabolic footprints of fungivores were higher in cover crop treatments compared with CK, and C4 and C8 also increased the functional metabolic footprint of nematode. Soil nematode faunal analysis based on nematode metabolic footprints showed that C8 improved the soil nutrient status and food wed stability. Mantel test and redundancy analysis showed that soil microbial biomass nitrogen and carbon, organic carbon, nitrate nitrogen, moisture content, pH, and cover crop biomass were the main factors that affect soil nematode community. In conclusion, cover crop treatments with four or eight plant species displayed a positive role in weed control, improvement of soil health, and promotion of energy flow in the soil food web through the increase in the metabolic footprints of nematodes in kiwifruit orchard., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Qi, Zhang, Zhang, Liu, Zhao, Yang and Wang.)

Hydrogen (H 2 ) has been widely used in the chemical industry as a reducing agent. As the researches move along, increasing attention has been paid to its biological functions. The selective antioxidant effect of hydrogen is considered to be the main reason for medical applications. So far, many studies have confirmed its potential protective effects on ischemia/reperfusion injury of multiple organs, neurodegenerative diseases, bone and joint diseases, and respiratory diseases, opening a new era in the medical research and application of H 2 . Increasing studies have focused on its biological effects and molecular mechanisms in the treatment of different diseases. In this paper, we review the biological effects, molecular mechanisms and methods of H 2 supply. We do hope that the advances in materials science can be better translated into medical applications and solve clinical problems. The medical application of H 2 is promising, and how to prepare an H 2 sustained-release system to achieve a sustained and stable H 2 supply in the body and ultimately improve the therapeutic effect of H 2 is a problem worthy of further investigation., Competing Interests: None

Background: Diabetic nephropathy (DN) is a microangiopathy of type 2 diabetes mellitus (T2DM), which can damage the kidney through various ways and mechanisms due to the nature of the disease, involving the renal interstitium and glomeruli. However, in the early stage of the disease, patients only showed kidney volume increase and glomerular hyperthyroidism, and typical symptoms that are difficult to arouse individual attention were noticed., Aim: To observe the expression of serum retinol-binding protein (RBP) and urinary N-acetyl-β-D-glucosaminidase (NAG) in patients with DN, and to analyze their value in disease prediction, so as to provide new targets for early diagnosis and treatment of DN., Methods: The baseline data of 50 T2DM patients treated in our hospital between January 2021 and December 2022 were retrospectively reviewed and included in group A. The baseline data of 50 patients with type 2 DN admitted to our hospital during the same period were collected and included in group B. The baseline data and serum RBP and urine NAG expression were compared between the two groups to analyze their value in the early prediction of DN., Results: There was no significant difference in age, gender, duration of diabetes, combined hyperlipidemia and combined hypertension between the two groups ( P > 0.05); the expression of urinary NAG and serum RBP in group B was higher than that in group A, and the difference was statistically significant ( P < 0.05); a multiple logistic regression model was established, and the results showed that urinary NAG and serum RBP were related to the presence or absence of injury in diabetic patients, and overexpression of urinary NAG and serum RBP may be risk factors for renal injury in T2DM patients (OR > 1, P < 0.05); receiver operating curve curve was plotted, and the results showed that the area under the curve of urinary NAG and serum RBP expression alone and in combination for predicting DN was > 0.80, and the predictive value was satisfactory; bivariate Spearman linear correlation analysis showed that there was a positive correlation between urinary NAG and serum RBP expression in patients with DN ( r = 0.566, P = 0.000)., Conclusion: The increased expression of urinary NAG and serum RBP may be the risk factors leading to the progression of T2DM to DN. The possibility of DN can be considered in patients with urinary NAG and serum RBP overexpression by examining the expression of urinary NAG and serum RBP in patients with T2DM in clinical practice., Competing Interests: Conflict-of-interest statement: All authors have no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Increased tau acetylation at K274 and K281 has been observed in the brains of Alzheimer's disease (AD) patients and animal models, and mitochondrial dysfunction are noticeable and early features of AD. However, the effect of acetylated tau on mitochondria has been unclear until now. Here, we constructed three type of tau forms, acetylated tau mutant by mutating its K274/K281 into Glutamine (TauKQ) to mimic disease-associated lysine acetylation, the non-acetylation tau mutant by mutating its K274/K281 into Arginine (TauKR) and the wild-type human full-length tau (TauWT). By overexpression of these tau forms in vivo and in vitro, we found that, TauKQ induced more severe cognitive deficits with neuronal loss, dendritic plasticity damage and mitochondrial dysfunctions than TauWT. Unlike TauWT induced mitochondria fusion, TauKQ not only induced mitochondria fission by decreasing mitofusion proteins, but also inhibited mitochondrial biogenesis via reduction of PGC-1a/Nrf1/Tfam levels. TauKR had no significant difference in the cognitive and mitochondrial abnormalities compared with TauWT. Treatment with BGP-15 rescued impaired learning and memory by attenuation of mitochondrial dysfunction, neuronal loss and dendritic complexity damage, which caused by TauKQ. Our data suggested that, acetylation at K274/281 was an important post translational modification site for tau neurotoxicity, and BGP-15 is a potential therapeutic drug for AD., Competing Interests: Declaration of competing interest We all authors stated that we have no conflicts of interest. Qian Liu, Xin Wang, Yu Hu, Jun-Ning Zhao, Chun-Hui Huang, Ting Li, Bing-Ge Zhang, Ye He, Yan-Qing Wu, Zai-Jun Zhang, Guo-Ping Wang, Gong-Ping Liu., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the rate of periprosthetic joint infection (PJI) revision surgeries and clinical information of hip-/knee- PJI cases nationwide from 2015 to 2017 in China. Methods: An epidemiological investigation. A self-designed questionnaire and convenience sampling were used to survey 41 regional joint replacement centers nationwide from November 2018 to December 2019 in China. The PJI was diagnosed according to the Musculoskeletal Infection Association criteria. Data of PJI patients were obtained by searching the inpatient database of each hospital. Questionnaire entries were extracted from the clinical records by specialist. Then the differences in rate of PJI revision surgery between hip- and knee- PJI revision cases were calculated and compared. Results: Total of 36 hospitals (87.8%) nationwide reported data on 99 791 hip and knee arthroplasties performed from 2015 to 2017, with 946 revisions due to PJI (0.96%). The overall hip-PJI revision rate was 0.99% (481/48 574), and it was 0.97% (135/13 963), 0.97% (153/15 730) and 1.07% (193/17 881) in of 2015, 2016, 2017, respectively. The overall knee-PJI revision rate was 0.91% (465/51 271), and it was 0.90% (131/14 650), 0.88% (155/17 693) and 0.94% (179/18 982) in 2015, 2016, 2017, respectively. Heilongjiang (2.2%, 40/1 805), Fujian (2.2%, 45/2 017), Jiangsu (2.1%, 85/3 899), Gansu (2.1%, 29/1 377), Chongqing (1.8%, 64/3 523) reported relatively high revision rates. Conclusions: The overall PJI revision rate in 34 hospitals nationwide from 2015 to 2017 is 0.96%. The hip-PJI revision rate is slightly higher than that in the knee-PJI. There are differences in revision rates among hospitals in different regions.

Introduction: Impressive advances in immunotherapy especially immune checkpoint inhibitors have made great progress in treating multiple cancers but can also cause serious even incurable immune-related adverse events, mostly found in colitis, dermatitis, hepatitis, and thyroiditis patients. Rare autoimmune hematologic toxicities have been reported in the literature, but are poorly described. Aplastic anaemia induced by immune checkpoint inhibitors is a life-threatening autoimmune disease; however, only a few cases have been reported in the literature. Objective: To characterize and evaluate Aplastic anaemia associated with different ICI regimens in public database and review the literature. Methods: We described a case series of patients experiencing Aplastic anaemia while on immune checkpoint inhibitors. We also mined the Food and Drug Administration's Adverse Event Reporting System and used reporting odds ratio, the proportional reporting ratio, the Bayesian confidence propagation neural network and the multi-item gamma Poisson shrinker algorithms to achieve the data of the suspected adverse events of Aplastic anaemia-induced by immune checkpoint inhibitors between January 2011 and June 2022. Results: Thirteen patients with Aplastic anaemia events while on immune checkpoint inhibitors were included in our case series, and seven of them had a fatal outcome. In FAERS, a total of 38 individual case safety reports (immune checkpoint inhibitors) with different ICI regimens were retrieved, of which 25 (65.79%) were reported as monotherapy and 13 (34.2%) had a fatal outcome. The reporting odds ratio was significant for nivolumab (reporting odds ratio 3.05, 95%CI 1.73-5.38), pembrolizumab (reporting odds ratio 2.33, 95%CI 1.16-4.67), avelumab (reporting odds ratio 12.63, 95%CI 3.15-50.62) and ipilimumab/nivolumab (ROR 2.57, 95%CI 1.15-5.72). Conclusion: There is a significant reporting signal of Aplastic anaemia with several ICI agents. Clinicians should raise awareness and monitor this potentially fatal adverse event., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Guo, Zhao, Liu, Gao, Guo and Cheng.)

UV induced photoaging is the main external factor of skin aging. In this study, we tested the protective effects of tetrahydrocurcumin on UV-induced skin photoaging of KM mice and researched the multi-target mechanism through RNA sequencing technology. Mouse experiments show that tetrahydrocurcumin strongly changed in skin appearance, epidermal thickness, and wrinkle-related parameters in UV-irradiated mice. RNA-seq result show that we found 29 differentially expressed mRNA transcripts in UV mice relative to Ctrl rats (18 up-regulated and 11 down-regulated) and 7 significantly dysregulated mRNAs were obtained in the THC group compared to the UV group (1 up-regulated and 6 down-regulated), respectively. Spink7, Edn3, Stab2 may be the key target genes of tetrahydrocurcumin in preventing aging. Bioinformatics analysis shows that the response to muscle contraction and melanin biosynthetic GO term and Inflammation related pathway such as PPAR, MAPK would involve in effects of tetrahydrocurcumin. The results of this study indicated that tetrahydrocurcumin can improve the appearance through anti-inflammatory, improving extracellular matrix and inhibiting melanin production. It could be suggested as a protective measure in the prevention of UV-induced photoaging., Competing Interests: The authors declare no conflict of interest., (© 2022 Published by Elsevier Ltd.)

Background: The rat sciatic nerve crush injury model is one of the most commonly used models to research peripheral nerve injury (PNI), however, the evaluation of the model preparation lacks exact standards. This study aimed to investigate accurately assessment methods for research concerning the rat sciatic nerve crush injury., Methods: The sciatic nerve crush injury model of was performed using the FST toothless forceps. The corresponding locations and pressures of different ratchet strengths were assessed by using CMAP, behavioral, and morphological methods., Results: In each group of PNI, motor and sensory functions were gradually restricted on the injured side of rats as the applied pressure increased. CMAP was more sensitive to nerve injury arising out of the force values obtained from the forceps., Conclusions: As a sensitive indicator for PNI, the neuroelectrophysiological examination was more likely to reflect the morphological changes of injured nerves. These findings may provide a standardized approach to sciatic crush injury modelling., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Objective: To develop a new method to restore hip rotation center exactly and rapidly in total hip arthroplasty (THA) with the assistance of three dimensional (3D) printing technology and evaluate its clinical and radiological outcomes., Methods: From March 2014 to July 2018, a total of 17 patients (five hips of four men and 16 hips of 13 women) with end-stage osteoarthritis secondary to developmental dysplasia of the hip who underwent THA were analyzed and followed up retrospectively. The average age is 58.00 ± 8.12 years (range from 45 to 71 years). Simulated operations were performed on 3D printed hip models for preoperative planning. The morphology of Harris fossa and acetabular notches were recognized and restored to locate the acetabular center. The size of bone defect was measured by the bone wax method. The agreement on the size of acetabular cup and bone defect between simulated operations and actual operations were analyzed. Harris Hip Score (HHS) was used to evaluate the recovery of hip joint function. The vertical distance and horizontal distance of the rotation center on the pelvis plain radiograph were measured, which were used to assess the efficacy of restoring hip rotation center and acetabular cup migration., Results: The mean sizes of bone defect in simulated operations and THA were 4.58 ± 2.47 cm 2 and 4.55 ± 2.57 cm 2 respectively. There was no significant difference statistically between the sizes of bone defect in simulated operations and the actual sizes of bone defect in THA (t = 0.03, P = 0.97). The sizes of the acetabular cup of simulated operations on 3D print models showed a high rate of coincidence with the actual sizes in the operations (ICC = 0.93). All 17 patients were available for clinical and radiological follow-up. The average follow-up time was 18.35 ± 6.86 months (range, 12-36 months. The average HHS of the patients was improved from (38.33 ± 6.07) preoperatively to the last follow-up (88.61 ± 3.44) postoperatively. The mean vertical and horizontal distances of hip rotation center on the pelvic radiographs were restored to 15.12 ± 1.25 mm and 32.49 ± 2.83 mm respectively. No case presented dislocation or radiological signs of loosening until last follow-up., Conclusions: The application of 3D printing technology facilitates orthopedists to recognize the morphology of Harris fossa and acetabular notches, locate the acetabular center and restore the hip rotation center rapidly and accurately., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Vascular endothelial cells are exposed to shear stresses with disturbed vs. laminar flow patterns, which lead to proinflammatory vs. antiinflammatory phenotypes, respectively. Effective treatment against endothelial inflammation and the consequent atherogenesis requires the identification of new therapeutic molecules and the development of drugs targeting these molecules. Using Connectivity Map, we have identified vitexin, a natural flavonoid, as a compound that evokes the gene-expression changes caused by pulsatile shear, which mimics laminar flow with a clear direction, vs. oscillatory shear (OS), which mimics disturbed flow without a clear direction. Treatment with vitexin suppressed the endothelial inflammation induced by OS or tumor necrosis factor-α. Administration of vitexin to mice subjected to carotid partial ligation blocked the disturbed flow-induced endothelial inflammation and neointimal formation. In hyperlipidemic mice, treatment with vitexin ameliorated atherosclerosis. Using SuperPred, we predicted that apurinic/apyrimidinic endonuclease1 (APEX1) may directly interact with vitexin, and we experimentally verified their physical interactions. OS induced APEX1 nuclear translocation, which was inhibited by vitexin. OS promoted the binding of acetyltransferase p300 to APEX1, leading to its acetylation and nuclear translocation. Functionally, knocking down APEX1 with siRNA reversed the OS-induced proinflammatory phenotype, suggesting that APEX1 promotes inflammation by orchestrating the NF-κB pathway. Animal experiments with the partial ligation model indicated that overexpression of APEX1 negated the action of vitexin against endothelial inflammation, and that endothelial-specific deletion of APEX1 ameliorated atherogenesis. We thus propose targeting APEX1 with vitexin as a potential therapeutic strategy to alleviate atherosclerosis., Competing Interests: The authors declare no competing interest.

The transcription suppressor factor FBI-1 (the factor that binds to inducer of short transcripts-1) is an important regulator of hepatocellular carcinoma (HCC). In this work, the results showed that FBI-1 promoted the Warburg effect and enhances the resistance of hepatocellular carcinoma cells to molecular targeted agents. Knockdown of FBI-1 via its small-interfering RNA (siRNA) inhibited the ATP level, lactate productions, glucose uptake or lactate dehydrogenase (LDH) activation of HCC cells. Transfection of siFBI-1 also decreased the expression of the Warburg-effect-related factors: hypoxia-inducible factor-1 alpha (HIF-1α), lactate dehydrogenase A (LDHA), or GLUT1, and the epithelial-mesenchymal transition-related factors, Vimentin or N-cadherin. The positive correlation between the expression of FBI-1 with HIF-1α, LDHA, or GLUT1 was confirmed in HCC tissues. Mechanistically, the miR-30c repressed the expression of HIF-1α by binding to the 3'-untranslated region (3'-UTR) of HIF-1α in a sequence-specific manner, and FBI-1 enhanced the expression of HIF-1α and HIF-1α pathway's activation by repressing the expression of miR. By modulating the miR-30c/HIF-1α, FBI-1 promoted the Warburg effect or the epithelial-mesenchymal transition of HCC cells and promoted the resistance of HCC cells to molecular targeted agents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Yang, Huang, Lv, Yang, Zhao, Zhao and Sun.)

This study aims to build a radiological model based on standard MR sequences for detecting methylguanine methyltransferase (MGMT) methylation in gliomas using texture analysis. A retrospective cross-sectional study was undertaken in a cohort of 53 glioma patients who underwent standard preoperative magnetic resonance (MR) imaging. Conventional visual radiographic features and clinical factors were compared between MGMT promoter methylated and unmethylated groups. Texture analysis extracted the top five most powerful texture features of MR images in each sequence quantitatively for detecting the MGMT promoter methylation status. The radiomic signature (Radscore) was generated by a linear combination of the five features and estimates in each sequence. The combined model based on each Radscore was established using multivariate logistic regression analysis. A receiver operating characteristic (ROC) curve, nomogram, calibration, and decision curve analysis (DCA) were used to evaluate the performance of the model. No significant differences were observed in any of the visual radiographic features or clinical factors between different MGMT methylated statuses. The top five most powerful features were selected from a total of 396 texture features of T1, contrast-enhanced T1, T2, and T2 FLAIR. Each sequence's Radscore can distinguish MGMT methylated status. A combined model based on Radscores showed differentiation between methylated MGMT and unmethylated MGMT both in the glioblastoma (GBM) dataset as well as the dataset for all other gliomas. The area under the ROC curve values for the combined model was 0.818, with 90.5% sensitivity and 72.7% specificity, in the GBM dataset, and 0.833, with 70.2% sensitivity and 90.6% specificity, in the overall gliomas dataset. Nomogram, calibration, and DCA also validated the performance of the combined model. The combined model based on texture features could be considered as a noninvasive imaging marker for detecting MGMT methylation status in glioma., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Cholesterol gallstone (CG) is a common, frequent biliary system disease in China, with a complex and multifactorial etiology. Declined gallbladder motility reportedly contributes to CG pathogenesis. Furthermore, interstitial Cajal-like cells (ICLCs) are reportedly present in human and guinea pig gallbladder tissue. ICLCs potentially contribute to the regulation of gallbladder motility, and aberrant conditions involving the loss of ICLCs and/or a reduction in its pacing potential and reactivity to cholecystokinin may promote CG pathogenesis. This review discusses the association between ICLCs and CG pathogenesis and provides a basis for further studies on the functions of ICLCs and the etiologies of CG., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Accurate prediction of neoantigens and the subsequent elicited protective anti-tumor response are particularly important for the development of cancer vaccine and adoptive T-cell therapy. However, current algorithms for predicting neoantigens are limited by in vitro binding affinity data and algorithmic constraints, inevitably resulting in high false positives. In this study, we proposed a deep convolutional neural network named APPM (antigen presentation prediction model) to predict antigen presentation in the context of human leukocyte antigen (HLA) class I alleles. APPM is trained on large mass spectrometry (MS) HLA-peptides datasets and evaluated with an independent MS benchmark. Results show that APPM outperforms the methods recommended by the immune epitope database (IEDB) in terms of positive predictive value (PPV) (0.40 vs. 0.22), which will further increase after combining these two approaches (PPV = 0.51). We further applied our model to the prediction of neoantigens from consensus driver mutations and identified 16,000 putative neoantigens with hallmarks of 'drivers'., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hao, Wei, Shu, Zhang, Xu and Zhao.)

Inherited predispositions to acute lymphoblastic leukemia have been well investigated in pediatric patients, but studies on adults, particularly Chinese patients, are limited. In this study, we conducted a genome-wide association study in 466 all-age Chinese patients with Acute lymphoblastic leukemia (ALL) and 1,466 non-ALL controls to estimate the impact of age on ALL susceptibility in the Chinese population. Among the 17 reported loci, 8 have been validated in pediatric and 1 in adult patients. The strongest association signal was identified at ARID5B locus and gradually decreased with age, while the signal at GATA3 exhibited the opposite trend and significantly impact on adult patients. With genome-wide approaches, germline variants at 2q14.3 rank as the top inherited predisposition to adult patients (e.g., rs73956024, P = 4.3 × 10 -5 ) and separate the genetic risk of pediatric vs. adult patients ( P = 3.6 × 10 -6 ), whereas variants at 15q25.3 (e.g., rs11638062) have a similar impact on patients in different age groups (overall P = 2.9 × 10 -7 ). Our analysis highlights the impact of age on genetic susceptibility to ALL in Chinese patients.

Background and Aims: Rotator cuff tendinopathy is common and is related to pain and dysfunction. However, the pathological mechanism of rotator cuff injury and shoulder pain is unclear. Objective: to investigate the pathological mechanism of rotator cuff injury and shoulder pain, and screen out the marker proteins related to rotator cuff injury by proteomics., Methods: Subacromial synovium specimens were collected from patients undergoing shoulder arthroscopic surgery. The experimental group were patients with rotator cuff repair surgery, and the control group were patients with habitual dislocation of the shoulder joint. Pathological examination was performed, and then followed by non-labeled quantitative proteomic detection. Finally, from analysis of the biological information of the samples, specific proteins related to rotator cuff injury and shoulder pain were deduced by functional analysis of differential proteins., Results: All the patients in experimental groups were representative. A large number of adipocytes and inflammatory cells were found in the pathological sections of the experimental group; the proteomics analysis screen identified 80 proteins with significant differences, and the analysis of protein function revealed that S100A11 ( p  = 0.011), PLIN4 ( p  = 0.017), HYOU1 ( p  = 0.002) and CLIC1 ( p  = 0.007) were closely related to oxidative stress and chronic inflammation., Conclusion: Rotator cuff injury is closely related to oxidative stress and chronic inflammatory response, and the results suggest that the expression of S100A11, PLIN4, HYOU1 and CLIC1 in the synovium of rotator cuff injury provides a new marker for the study of its pathological mechanism., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

In this research, a very practical QuEChERS-GC-MS/MS analytical approach for 74 pesticide residues in herb based on retention index was established. This novel analytical approach has two important technical advantages. One advantage is to quickly screen pesticide compounds in herbs without having to use a large number of pesticide standard substances at the beginning of the experiment. The other advantage is to assist in identifying the target pesticide compound accurately. A total of 74 kinds of pesticides were quickly prescreened in all chuanxiong rhizoma samples. The results showed that three kinds of pesticides were screened out in all the samples, including chlorpyrifos, fipronil, and procymidone, and the three pesticides were qualitatively and quantitatively determined. The RSD values for interday and intraday variation were acquired to evaluate the precision of the analytical approach, and the overall interday and intraday variations are not more than 1.97% and 3.82%, respectively. The variations of concentrations of the analyzed three pesticide compounds in sample CX16 are 0.74%-4.15%, indicating that the three pesticides in the sample solutions were stable in 48 h. The spiked recoveries of the three pesticides are 95.22%, 93.03%, and 94.31%, and the RSDs are less than ± 6.0%. The methodological verification results indicated the good reliability and accuracy of the new analytical method. This research work is a new application of retention index, and it will be a valuable tool to assist quickly and accurately in the qualitative and quantitative analysis of multipesticide residues in herbs., Competing Interests: The authors declare they have no conflicts of interest., (Copyright © 2021 Peng Tan et al.)

Background: Endothelial cells play a key role in the cytokine storm caused by influenza A virus. MicroRNA-155 (miR-155) is an important regulator in inflammation. Its role in the inflammatory response to influenza A infection, however, has yet to be elucidated. In this study, we explored the role as well as the underlying mechanism of miR-155 in the cytokine production in influenza A-infected endothelial cells., Methods: Human pulmonary microvascular endothelial cells (HPMECs) were infected with the influenza A virus strain H1N1. The efficiency of H1N1 infection was confirmed by immunofluorescence. The expression levels of proinflammatory cytokines and miR-155 were determined using real-time polymerase chain reaction. A dual-luciferase reporter assay characterized the interaction between miR-155 and sphingosine-1-phosphate receptor 1 (S1PR1). Changes in the target protein levels were determined using Western blot analysis., Results: MiR-155 was elevated in response to the H1N1 infection in HPMECs (24 h post-infection vs. 0 h post-infection, 3.875 ± 0.062 vs. 1.043 ± 0.013, P = 0.001). Over-expression of miR-155 enhanced inflammatory cytokine production (miR-155 mimic vs. negative control, all P < 0.05 in regard of cytokine levels) and activation of nuclear factor kappa B in infected HPMECs (miR-155 mimic vs. negative control, P = 0.004), and down-regulation of miR-155 had the opposite effect. In addition, S1PR1 was a direct target of miR-155 in the HPMECs. Inhibition of miR-155 enhanced the expression of the S1PR1 protein. Down-regulation of S1PR1 decreased the inhibitory effect of the miR-155 blockade on H1N1-induced cytokine production and nuclear factor kappa B activation in HPMECs., Conclusion: MiR-155 maybe modulate influenza A-induced inflammatory response by targeting S1PR1.

In December 2019, an outbreak of unexplained pneumonia was reported in Wuhan, China. The World Health Organization officially named this disease as novel coronavirus disease 2019 (COVID-19). Liver injury was observed in patients with COVID-19, and its severity varied depending on disease severity, geographical area, and patient age. Systemic inflammatory response, immune damage, ischemia-reperfusion injury, viral direct damage, drug induce, mechanical ventilation, and underlying diseases may contribute to liver injury. Although, in most cases, mild liver dysfunction is observed, which is usually temporary and does not require special treatment, the importance of monitoring liver injury should be emphasized for doctors. The risk of COVID-19 infection of liver transplantation recipients caused more and more concerns. In this article, we aimed to review the available literature on liver injury in COVID-19 to highlight the importance of monitoring and treating liver injury in COVID-19., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

PRDM (PRDI-BF1 and RIZ homology domain containing) family members are sequence-specific transcriptional regulators involved in cell identity and fate determination, often dysregulated in cancer. The PRDM15 gene is of particular interest, given its low expression in adult tissues and its overexpression in B-cell lymphomas. Despite its well characterized role in stem cell biology and during early development, the role of PRDM15 in cancer remains obscure. Herein, we demonstrate that while PRDM15 is largely dispensable for mouse adult somatic cell homeostasis in vivo, it plays a critical role in B-cell lymphomagenesis. Mechanistically, PRDM15 regulates a transcriptional program that sustains the activity of the PI3K/AKT/mTOR pathway and glycolysis in B-cell lymphomas. Abrogation of PRDM15 induces a metabolic crisis and selective death of lymphoma cells. Collectively, our data demonstrate that PRDM15 fuels the metabolic requirement of B-cell lymphomas and validate it as an attractive and previously unrecognized target in oncology.

Background: Hypertension in the elderly with cognitive impairment has been one of the global health issues. Mild cognitive impairment (MCI) is the state of transition between the normal aging process and cognitive changes of unformed dementia. Diagnosis and treatment of MCI are the keys to prevent dementia, and hypertension is one of the important influencing factors of MCI. Our preclinical experiment found that Yizhi Qingxin Decoction (YQD) could effectively reduce the blood pressure of spontaneously hypertensive rats (SHR), improve their spatial learning and memory abilities in Morris water maze, and play a neuroprotective role. The objective is to estimate the safety and efficacy of YQD (capsules) in the treatment of hypertension in the elderly with MCI (deficiency of kidney essence syndrome) through this study., Methods: According to the random number generated by the block random method, 100 participants will be randomly and equally divided into the treatment group (YQD) or the control group (Ginkgo biloba extract tablets). The conversion rate of dementia will be used as the main evaluating indicator by the CDR scale. The MoCA scale, MMSE scale, ADCS-MCI-ADL-24 scale, CGIC-KDS scale, and 24-h ambulatory blood pressure will be used as the secondary evaluating indicator. Safety will be evaluated based on specific manifestations of adverse reactions and the incidence of adverse events., Objective: The objective is to estimate the curative effect of YQD (capsules) on hypertension in the elderly with MCI (deficiency of kidney essence syndrome), and to evaluate the safety of its clinical application., Trial Registration: Chinese Clinical Trial Registry (ICTRP member): ChiCTR2000030292.

A novel and facile visible-light-mediated alkylation of indoles and nitroalkenes has been developed. In this protocol, rose bengal acts as a photosensitizer, and environmentally benign water was used as the green and efficient reaction medium. Indoles reacted smoothly with nitroalkenes under the irradiation of visible-light and generated corresponding 3-(2-nitroalkyl)indoles in moderate to good yields (up to 87%)., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Music or other background sounds are often played in barns as environmental enrichment for animals on farms or to mask sudden disruptive noises. Previous studies looking at the effects of this practice on non-human animal well-being and productivity have found contradictory results. However, there is still a lack of discussion on whether piglets have the ability to distinguish different types of music. In this study, we exposed piglets to different music conditions to investigate whether the piglets preferred certain music types, in which case those types would have the potential to be used as environmental enrichment. In total, 30 piglets were tested for music type preference to determine whether growing pigs respond differently to different types of music. We used music from two families of instruments (S: string, W: wind) and with two tempos (S: slow, 65 beats/min (bpm); F: fast, 200 bpm), providing four music-type combinations (SS: string-slow; SF: string-fast; WS: wind-slow; WF: wind-fast). The piglets were given a choice between two chambers, one with no music and the other with one of the four types of music, and their behaviour was observed. The results showed that SS and WF music significantly increased residence time (P<0.01) compared with the other music conditions. Compared with the control group (with no music), the different music conditions led to different behavioural responses, where SS music significantly increased lying (P<0.01) and exploration behaviour (P<0.01); SF music significantly increased tail-wagging behaviour (P<0.01); WS music significantly increased exploration (P<0.01); and WF music significantly increased walking, lying, standing and exploration (all P<0.01). The results also showed that musical instruments and tempo had little effect on most of the behaviours. Fast-tempo music significantly increased walking (P=0.02), standing (P<0.01) and tail wagging (P=0.04) compared with slow-tempo music. In conclusion, the results of this experiment show that piglets are more sensitive to tempo than to musical instruments in their response to musical stimulation and seem to prefer SS and WF music to the other two types. The results also suggest a need for further research on the effect of music types on animals.

Objective: Wear-induced aseptic loosening has been accepted as one of the main reasons for failure of total hip arthroplasty. Ceramic wear debris is generated following prosthesis implantation and plays an important part in the upregulation of inflammatory factors in total hip arthroplasty. The present study investigates the influence of ceramic debris on osteoblasts and inflammatory factors., Methods: Ceramic debris was prepared by mechanical grinding of an aluminum femoral head and added to cultures of MC3T3-E subclone 14 cells at different concentrations (i.e. 0, 5, 10, and 15 μg/mL). Cell proliferation was evaluated using a Cell Counting Kit (CCK-8), and cell differentiation was assessed by mRNA expression of alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). In addition, cell bio-mineralization was evaluated through alizarin red S staining, and release of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) was measured through enzyme-linked immunosorbent assays (ELISA). Furthermore, mRNA expression of Smad1, Smad4, and Smad5 and protein expression of phosphorylated Smad1, Smad4, and Smad5 were measured by reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting., Results: The ceramic debris had irregular shapes and sizes, and analysis of the size distribution using a particle size analyzer indicated that approximately 90% of the ceramic debris was smaller than 3.2 μm (2.0 ± 0.4 μm), which is considered clinically relevant. The results for mRNA expression of ALP, OCN, and OPN and alizarin red S staining indicated that cell differentiation and bio-mineralization were significantly inhibited by the presence of ceramic debris at all tested concentrations (P < 0.05, and the values decreased gradually with the increase of ceramic debris concentration), but the results of the CCK-8 assay showed that cell proliferation was not significantly affected (P > 0.05; there was no significant difference between the groups at 1, 3, and 5 days). In addition, the results of ELISA, RT-PCR, and western blotting demonstrated that ceramic debris significantly promoted the release of inflammatory factors, including TNF-α, IL-β, and IL-6 (P < 0.05, and the values increased gradually with the increase of ceramic debris concentration), and also greatly reduced the mRNA expression of Smad1, Smad4, and Smad5 (the values decreased gradually with the increase of ceramic debris concentration) as well as protein expression of phosphorylated Smad1, Smad4, and Smad5., Conclusion: Ceramic debris may affect differentiation and bio-mineralization of MC3T3-E subclone 14 cells through the bone morphogenetic protein/Smad signaling pathway., (© 2019 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Background: Chronic stable angina (CSA) is a cardiovascular disease with high prevalence. At present, drug treatment is still the main measure of stable angina pectoris. Traditional Chinese medicine has a long history in the treatment of CSA. Qi stagnation and Blood stasis syndrome is a common syndrome of CSA. Xinnaoning (XNN) capsule is considered as an effective adjuvant treatment for CSA with the efficacy of promoting qi and blood circulation but lack of high-quality clinical evidence. The purpose of this study is to evaluate the efficacy and safety of XNN capsule compared with placebo by clinical trial., Methods: This multicenter, randomized, double-blind, placebo-controlled trial will be conducted with a total of 240 participants diagnosed with chronic stable angina (qi stagnation and blood stasis syndrome). The participants will be randomized (1:1) into groups receiving either XNN or placebo for 12 weeks. After a 2-week run-in period, they will receive either XNN or placebo (3 pills, 3 times daily) for 12 weeks on the basis of conventional therapy. The primary outcomes include changes in the integral scores of angina symptoms. The secondary outcome measures include changes in the total score of traditional Chinese medicine syndrome, severity grading of angina pectoris, the number of angina pectoris per week, nitroglycerin dosage, score of seattle angina scale, serum homocysteine, incidence of cardiovascular events. Safety outcomes will also be assessed. Adverse events will be monitored throughout the trial., Results: This study will investigate whether XNN capsule can alleviate clinical symptoms, and improve quality of life of patients with chronic stable angina (qi stagnation and blood stasis syndrome). The results of this study will provide clinical evidence for the application of XNN capsule in the treatment of chronic stable angina., Trial Registration: ClinicalTrials.gov: NCT03914131.

Purpose: To compare the effect of apixaban and low molecular weight heparin (LMWH) in the prevention and treatment of deep venous thrombosis (DVT) after total knee arthroplasty in older adult patients., Materials and Methods: A total of 220 patients (average age of 67.8±6.4 years) undergoing total knee arthroplasty were randomly selected as research subjects and were divided into apixaban and LMWH groups (110 in each group)., Results: The incidence of DVT was lower in the apixaban group than in the LMWH group (5.5% vs. 20.0%, p =0.001). Activated partial thromboplastin times (35.2±3.6 sec vs. 33.7±2.2 sec, p =0.010; 37.8±4.6 sec vs. 34.1±3.2 sec, p <0.001; 39.6±5.1 sec vs. 35.7±3.0 sec, p =0.032) and prothrombin times (14.0±1.0 sec vs. 12.8±0.9 sec, p <0.001; 14.5±1.2 sec vs. 13.0±1.1 sec, p <0.001; 15.3±1.4 sec vs. 13.2±1.3 sec, p =0.009) in the apixaban group at 1 week after surgery, 3 weeks after surgery, and the end of treatment were higher than those in the LMWH group. Platelet and fibrinogen levels in the apixaban group were lower than those of the LMWH group. Also, capillary plasma viscosity and erythrocyte aggregation in the apixaban group at 1 week after surgery, 3 weeks after surgery, and the end of treatment were lower than those in the LMWH group., Conclusion: Apixaban, which elicits fewer adverse reactions and is safer than LMWH, exhibited better effects in the prevention and treatment of DVT after total knee arthroplasty in older adults., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2019.)

Aryl-heteroatom (C-X) bonds ubiquitously exist in organic, medicinal, and material chemistry, but a universal method to construct diverse C-X bonds is lacking. Here we report our discovery of a convenient and efficient approach to construct various C-X bonds using arylammonium salts as the substrate via an S N Ar process. This strategy features mild reaction condition, no request of transition metal catalyst, and easy formation of various C-X bonds (C-S, C-Si, C-Sn, C-Ge, C-Se, C-N). The method was successfully applied to a late-stage functionalization of an existing antibiotic drug, to a Clickable reaction of NBD-based ammonium salt as turn-on fluorescent probe to recognize L-cysteine and homocysteine, and to the synthesis of a DNA encoded library (DEL) bearing different C-X bonds., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Parkinson's disease (PD) is a common degenerative neurological disease leading to a series of familial, medical, and social problems. Although it is known that the major characteristics of PD pathophysiology are the dysfunction of basal ganglia due to injury/loss of dopaminergic neurons in the substantia nigra pars compacta dopaminergic and exhaustion of corpus striatum dopamine, therapeutic modalities for PD are limited in clinical settings up to date. It is of utmost importance to better understand PD pathophysiology and explore new solutions for this serious neurodegenerative disorder. Our recent work and those of others suggest that the delta-opioid receptor (DOR) is neuroprotective and serves an antiparkinsonism role in the brain. This review summarizes recent progress in this field and explores potential mechanisms for DOR-mediated antiparkinsonism., (© 2018 John Wiley & Sons Ltd.)

The aim of the present study was to investigate whether modified Huangqi Chifeng decoction (MHCD) could be an effective treatment against Doxorubicin-induced nephrosis in rats and whether it regulates autophagy via the phosphoinositide-3 kinase/mammalian target of rapamycin (PI3K/mTOR) signaling pathway. A total of 40 male Sprague-Dawley rats were randomly divided into blank, model, telmisartan and MHCD groups. The rat model of nephrosis was induced by intragastric administration of Doxorubicin for 8 weeks. Rats were housed in metabolic cages and urine was collected once every 2 weeks to measure 24-h protein levels. Blood samples were obtained from the abdominal aorta and levels of albumin (ALB), total cholesterol (TCH), triacylglyceride (TG) and serum creatinine (Scr) were assessed. Renal pathological changes were examined using hematoxylin-eosin, Masson's trichome and periodic acid-Schiff staining. Podocytes and autophagosomes were observed using an electron microscope. The expression and distribution of microtubule-associated proteins 1A/1B light chain 3B (LC3), LC3-I, LC3-II, beclin-1, PI3K and mTOR were determined using immunohistochemistry and western blotting. At weeks 6 and 8, 24-h proteinuria significantly decreased in the MHCD group compared with the model group (P<0.05). Compared with the model group, the MHCD group exhibited significantly reduced levels of TG, TCH and Scr, as well as significantly increased ALB levels (P<0.05). MHCD was demonstrated to prevent glomerular and podocyte injury. The number of autophagosomes was significantly decreased and the expression of beclin-1, LC3, LC3-I and LC3-II was inhibited following MHCD treatment compared with the model group (P<0.05). MHCD treatment significantly increased the expression of PI3K and mTOR in Doxorubicin nephrotic rats compared with the model group (P<0.05). In conclusion, MHCD was demonstrated to ameliorate proteinuria and protect against glomerular and podocyte injury by inhibiting excessive autophagy via the PI3K/mTOR signaling pathway.

Aberrant expression of miR-206 has been repeatedly found and demonstrated to play crucial roles in cancers. However, the role of miR-206 in brain glioma remains unclear. To address this issue, we detected miR-206 expression of 60 gliomas and 18 normal peritumor tissues, and found that miR-206 is significantly down-regulated in gliomas. Further in silico analysis of 198 glioma samples from the Chinese Glioma Genome Atlas (CGGA) indicated that miR-206 is significantly down-regulated in high grade gliomas and that miR-206 predicts favorable patients' prognosis. Notably, we found that miR-206 expression is negatively correlated with Ki-67 staining, indicating a proliferative inhibition of miR-206 in gliomas. To explore the crucial role of miR-206 in gliomas, we constructed miR-206 stably overexpressed LN229 glioma cell lines and found that the proliferation is significantly inhibited. Through flow cytometry (FCM) analyses, we found that the apoptotic rate is increased and the cell cycle is arrested in LN229 cells after overexpression of miR-206. Bioinformatic analysis, qPCR, western blot and luciferase assay indicated that the Forkhead Box Protein 1 (FOXP1) is a direct target of miR-206 in gliomas. Overexpression of FOXP1 could partially rescue the proliferative inhibition in the miR-206 stably overexpressed LN229 cells. In summary, our results suggest that miR-206 might function as a tumor suppressor of gliomas by inhibition of proliferation and could serve as a promising candidate for therapeutic applications in glioma by targeting FOXP1., Competing Interests: None., (IJCEP Copyright © 2018.)

Objectives: As promising alternative to current metallic biomaterials, the porous Mg scaffold with a 3-D open-pore framework has drawn much attention in recent years due to its suitable biodegradation, biocompatibility, and mechanical properties for human bones. This experiment's aim is to study the mechanical properties, biosafety, and osteogenesis of porous Mg-Zn alloy., Methods: A porous Mg-2Zn-0.3Ca (wt%) alloy was successfully prepared by infiltration casting, and the size of NaCl particles was detected by a laser particle size analyzer. The microstructure of the Mg-2Zn-0.3Ca alloy was characterized by the stereoscopic microscope and Sirion Field emission scanning electron microscope. X-ray computerized tomography scanning (x-CT) was used to create the 3-D image. The degradation rate was measured using the mass loss method and the pH values were determined together. The engineering stress-strain curve, compressive modulus, and yield strength were tested next. The bone marrow stromal cells (BMSC) were cultured in vitro. The CCK-8 method was used to detect the proliferation of the BMSC. Alkaline phosphatase (ALP) and alizarin red staining were used to reflect the differentiation effects. After co-culturing, cell growth on the material's surface was observed by scanning electron microscope (SEM). The cell adhesion was tested by confocal microscopy., Results: The obtained results showed that by using near-spherical NaCl filling particles, the porous Mg alloy formed complete open-cell foam with a very uniform size of pores in the range of 500-600 μm. Benefitting from the small size and uniform distribution of pores, the present porous alloy exhibited a very high porosity, up to 80%, and compressive yield strength up to 6.5 MPa. The degradation test showed that both the pH and the mass loss rate had similar change tendency, with a rapid rise in the early stage for 1-2 day's immersion and subsequently remaining smooth after 3 days. In vitro cytocompatibility trials demonstrated that in comparison with Ti, the porous alloy accelerated proliferation in 1, 3, 5, and 7 days (P < 0.001), and the osteogenic differentiation test showed that the ALP activity in the experimental group was significantly higher (P = 0.017) and has more osteogenesis nodules. Cell adhesion testing showed good osteoconductivity by more BMSC adhesion around the holes. The confocal microscopy results showed that cells in porous Mg-based alloy had better cytoskeletal morphology and were larger in number than in titanium., Conclusions: These results indicated that this porous Mg-based alloy fabricated by infiltration casting shows great mechanical properties and biocompatibilities, and it has potential as an ideal bone tissue engineering scaffold material for bone regeneration., (© 2018 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Intracranial 'kissing' aneurysms are rare types of multiple aneurysms referring to two adjacent aneurysms arising from identical or different arteries with separate origins and partially adherent walls. The present study reported a 54-year-old female patient, who was identified with a 'kissing' aneurysm in the A3 segment of the bilateral anterior cerebral arteries, as demonstrated by head computed tomography and emergency cerebral digital subtraction angiography analysis. In total, 12 days following the clipping of the aneurysms, the patient was discharged with a Modified Rankin Scale=0 and recovered well with no neurological deficits. Based on previous literature, it was indicated that the majority of patients with 'kissing' aneurysm have a good prognosis and the cure rate is as high as 96.8%. However, the recovery rate may not be that high as the sample size is not large enough to thoroughly demonstrate the complete prognosis of 'kissing' aneurysms.

Objectives: The present study aimed to investigate the overall effect of quercetin on mouse bone marrow mesenchymal stem cell (BMSC) proliferation and osteogenic differentiation in vitro ., Materials and Methods: BMSCs were treated with different concentrations of quercetin for 6 days. The effects of quercetin on cell proliferation were assessed at predetermined times using Cell Counting Kit-8 (CCK-8) assay. The cells were then treated with quercetin, estrogen, or an estrogen receptor (ER) antagonist (which was also administered in the presence of quercetin or estrogen) for 7 or 21 days. The effects of quercetin on BMSC osteogenic differentiation were analyzed by an alkaline phosphatase (ALP) assay kit, Alizarin Red S staining (ARS), quantitative real-time PCR (qPCR), and western blotting., Results: The CCK-8 and ALP assays and ARS staining showed that quercetin significantly enhanced BMSC proliferation, ALP activity, and extracellular matrix production and mineralization, respectively. The qPCR results indicated that quercetin promoted osterix (OSX) , runt-related transcription factor 2 (RUNX2) , and osteopontin (OPN) transcription in the presence of osteoinduction medium, and the western blotting results indicated that quercetin enhanced bone morphogenetic protein 2 (BMP2), Smad1, Smad4, RUNX2, OSX, and OPN expression and Smad1 phosphorylation. Treatment with the ER inhibitor ICI182780 blocked the effects of quercetin., Conclusions: Our data demonstrated that quercetin promotes BMSC proliferation and osteogenic differentiation. Quercetin enhances BMP signaling pathway activation and upregulates the expression of downstream genes, such as OSX , RUNX2 , and OPN , via the ER.

Central nervous system (CNS) infection of C57BL/6 mice with the TE strain of Sindbis virus (SINV) provides a valuable animal model for studying the pathogenesis of alphavirus encephalomyelitis. While SINV TE inoculated intracranially causes little mortality, 20-30 % of mice inoculated intranasally (IN) died 8 to 11 days after infection, the period during which immune cells typically infiltrate the brain and clear infectious virus. To examine the mechanism behind the mortality, mice infected IN with SINV TE were monitored for evidence of neurological disease, and those with signs of severe disease (moribund) were sacrificed and tissues collected. Mice showing the usual mild signs of encephalomyelitis were concurrently sacrificed to serve as time-matched controls (sick). Sixty-eight per cent of the moribund mice, but none of the sick mice, showed upper gastrointestinal bleeding due to gastric ulceration. Clinical disease and gastrointestinal pathology could not be attributed to direct viral infection of tissues outside of the CNS, and brain pathology and inflammation were comparable in sick and moribund mice. However, more SINV antigen was present in the brains of moribund mice, and clearance of infectious virus from the CNS was delayed compared to sick mice. Lower levels of SINV-specific IgM and fewer B220 + B cells were present in the brains of moribund mice compared to sick mice, despite similar levels of antiviral IgM and IgG in serum. These findings highlight the importance of the local antibody response in determining the outcome of viral encephalomyelitis and offer a model system for understanding individual variation in this response.

Purpose: Imatinib dramatically reduces gastrointestinal stromal tumor (GIST) 18 F-FDG uptake, providing an early indicator of treatment response. Despite decreased glucose internalization, many GIST cells persist, suggesting that alternative metabolic pathways are used for survival. The role of mitochondria in imatinib-treated GIST is largely unknown. Experimental Design: We quantified the metabolic activity of several human GIST cell lines. We treated human GIST xenografts and genetically engineered Kit V558del/+ mice with the mitochondrial oxidative phosphorylation inhibitor VLX600 in combination with imatinib and analyzed tumor volume, weight, histology, molecular signaling, and cell cycle activity. In vitro assays on human GIST cell lines were also performed. Results: Imatinib therapy decreased glucose uptake and downstream glycolytic activity in GIST-T1 and HG129 cells by approximately half and upregulated mitochondrial enzymes and improved mitochondrial respiratory capacity. Mitochondrial inhibition with VLX600 had a direct antitumor effect in vitro while appearing to promote glycolysis through increased AKT signaling and glucose transporter expression. When combined with imatinib, VLX600 prevented imatinib-induced cell cycle escape and reduced p27 expression, leading to increased apoptosis when compared to imatinib alone. In Kit V558del/+ mice, VLX600 alone did not induce tumor cell death, but had a profound antitumor effect when combined with imatinib. Conclusions: Our findings show that imatinib alters the metabolic phenotype of GIST, and this may contribute to imatinib resistance. Our work offers preclinical proof of concept of metabolic targeting as an effective strategy for the treatment of GIST. Clin Cancer Res; 24(4); 972-84. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background/aims: Dexamethasone (Dex) induces injuries to human osteoblasts. In this study, we tested the potential role of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Lnc-MALAT1) in this process., Materials: Two established human osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts were treated with Dex. Lnc-MALAT1 expression was analyzed by quantitative real-time polymerase chain reaction assay. Cell viability, apoptosis, and death were tested by the MTT assay, histone-DNA assay, and trypan blue staining assay, respectively. AMP-activated protein kinase (AMPK) signaling was evaluated by western blotting and AMPK activity assay., Results: Lnc-MALAT1 expression was downregulated by Dex treatment in the established osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts. The level of Lnc-MALAT1 was decreased in the necrotic femoral head tissues of Dex-administered patients. In osteoblastic cells and primary human osteoblasts, forced overexpression of Lnc-MALAT1 using a lentiviral vector (LV-MALAT1) inhibited Dex-induced cell viability reduction, cell death, and apoptosis. Conversely, transfection with Lnc-MALAT1 small interfering RNA aggravated Dex-induced cytotoxicity. Transfection with LV-MALAT1 downregulated Ppm1e (protein phosphatase, Mg2+/ Mn2+-dependent 1e) expression to activate AMPK signaling. Treatment of osteoblasts with AMPKα1 short hairpin RNA or dominant negative mutation (T172A) abolished LV-MALAT1-induced protection against Dex-induced cytotoxicity. Furthermore, LV-MALAT1 induced an increase in nicotinamide adenine dinucleotide phosphate activity and activation of Nrf2 signaling. Dex-induced reactive oxygen species production was significantly attenuated by LV-MALAT1 transfection in osteoblastic cells and primary osteoblasts., Conclusion: Lnc-MALAT1 protects human osteoblasts from Dex-induced injuries, possibly via activation of Ppm1e-AMPK signaling., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8 + T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies.

The mechanism of human β-defensin 3 (HBD-3) in methicillin-resistant Staphylococcus aureus (MRSA-induced infection of implant drug-resistant bacteria biofilm in the mouse tibial bone marrow was studied. Healthy adult male Sprague-Dawley rats with average weight of 230 g were selected to construct the infection model of MRSA-induced implant drug-resistant bacteria biofilm in the mouse left tibial bone marrow. The drugs were intraperitoneally injected after 24 h medullary cavity infection, and the experimental groups included the model group, HBD-3 group, and vancomycin group (20 rats in each group). The model group was injected with 10 ml saline, HBD-3 group was injected with 10 ml of 8 µg/ml (1 MIC) and vancomycin group was injected with 10 ml of 0.5 µg/ml (1 MIC), five animals in each group were sacrificed on the 1, 7, 14 and 21 days, respectively. Observation was carried out on whether there was swelling and purulent secretion on the local wound; 1 ml venous sinus blood of eye socket was collected for blood routine examination and blood culture, and the laser scanning confocal microscopy was used to observe the morphology of the biofilm on the implant surface and the number of viable bacteria. Immunohistochemical staining was adopted to test the expression of nuclear factor-κB (NF-κB) and toll-like receptor 4 (TLR-4), and ELISA method was used to test interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), IL-1α and interferon-γ (INF-γ)-inducible protein-10 (IP-10) expression levels. There was no death due to infection in the HBD-3 group or vancomycin group, 1 case with significant wound swelling was found, respectively, in each group, but there was no purulent secretion. The percentage of the total white blood cells and neutrophil granulocytes as well as the biofilm morphology and the number of viable bacteria in the model group was gradually increased with time, while those in the HBD-3 group and vancomycin group were decreased with time. The comparative difference among groups was statistically significant (P<0.05); those in the HBD-3 group and vancomycin group at each time-point was decreased significantly compared with the model group, and the difference among groups was statistically significant (P<0.05), but in terms of the comparison between the HBD-3 group and vancomycin group, the difference was not significantly different (P>0.05). The NF-κB and TLR-4 expressions in the model group and vancomycin group were not significantly changed at each time-point, those in the HBD-3 group began to increase on the 1st day, and reached the peak on the 7th day and began to decline on the 14th day, and the comparative difference at each time-point was statistically significant (P<0.05); those in the HBD-3 group were significantly higher than the model group and vancomycin group at each time-point and the difference was statistically significant (P<0.05). The IL-10, TNF-α, IL-1α, and IP-10 expressions in the model group at each time were significantly higher than the other two groups and the difference was statistically significant (P<0.05); in terms of the comparison between the HBD-3 group and vancomycin group, the difference was not statistically significant (P>0.05). In conclusion, β-defensin 3 can inhibit the bacterial growth by regulating inflammation and immune responses in the MRSA-induced implant drug-resistant bacteria biofilm infection in the mouse tibial bone marrow.