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Supplementary Data from Selective Cytotoxicity to HER2-Positive Tumor Cells by a Recombinant e23sFv-TD-tBID Protein Containing a Furin Cleavage Sequence

Purpose: The HER2 antigen is a recognized target on breast cancer cells for immunotherapy. To overcome the immunogenicity and systemic toxicity of traditional immunotoxins, a novel human immunoproapoptotic molecule was developed and its antitumor activity was investigated.Experimental Design: Recombinant e23sFv-TD-tBID, consisting of a single-chain anti-HER2 antibody fragment linked to a human active truncated Bid by a 10–amino acid residue furin cleavage sequence, was bacterially expressed. Purified e23sFv-TD-tBID was tested for binding, internalization, and cytotoxic activity in cell and for tumor localization and antitumor activity in athymic nude mice bearing established human tumor xenografts.Results: e23sFv-TD-tBID selectively binds to HER2-positive cells and induces apoptotic cell death in vitro and in vivo. An investigation of its mechanism of action has revealed that e23sFv-TD-tBID was internalized on binding to the surface of HER2-positive tumor cells, proteolytically cleaved and transported directly to cytosol. The antitumor activity of e23sFv-TD-tBID was shown in a dose-dependent manner when injected i.p. into immunodeficient mice bearing human breast carcinomas. Moreover, this immunoproapoptotic protein, either given as a single dose or in combination with chemotherapy agents, significantly inhibited tumor growth without any observed toxic side effects on mice. Magnetic resonance imaging further showed the specific targeting and good penetration of tumors by e23sFv-TD-tBID in vivo. The therapeutic value of e23sFv-TD-tBID to human was shown by its cytotoxic effects on primary patient-derived breast tumor cells but not on endothelial cells.Conclusion: These data suggest that recombinant e23sFv-TD-tBID has therapeutic potential for HER2-positive tumors and warrant further testing for clinical applications. Clin Cancer Res; 16(8); 2284–94. ©2010 AACR.

We previously reported the selective killing of HER2-positive tumor cells by a class of immunoproapoptotic proteins containing single-chain antibody, translocation domain of Pseudomonas exotoxin A (domain II; PEA II), and constitutively active human apoptotic molecules. In this study, a novel class of antitumor immunoproapoptotic proteins was explored to mediate tumor-specific apoptosis both in vitro and in vivo. Three furin cleavage sequences, including a synthetic polyarginine tract, and two furin cleavable sequences from PEA and diphtheria toxin were respectively used to replace PEA II in the previously constructed immunoproapoptotic protein. When produced and secreted by the genetically modified Jurkat cells, the novel targeted proapoptotic proteins selectively bound to HER2, which is often overexpressed on tumor cell surface. Followed by receptor-mediated endocytosis and furin cleavage in the endosome, the recombinant proteins could translocate into the cytosol, leading to irreversible cell death. Moreover, delivery of these proteins by either i.m. plasmid injection or i.v. injection of plasmid-expressing Jurkat cells led to tumor regression and prolonged animal survival in a nude mouse xenograft tumor model, indicating in vivo antitumor activity of the recombinant proteins. We conclude that the new class of immunoproapoptotic proteins show comparable activity with PEA II–containing counterpart and provide an attractive therapeutic alternative as they contain much less exogenous fragments. [Cancer Res 2007;67(24):11830–39]

Supplementary Figures 1-3 from Recombinant Immunoproapoptotic Proteins with Furin Site Can Translocate and Kill HER2-Positive Cancer Cells

BACKGROUND Complex tibial plateau fractures can seriously affect quality of life and physical and mental health of patients. The anatomical relationship between the proximal tibial bone and soft tissue is complex, resulting in different types of tibial plateau fractures. Violent trauma can lead to displaced fracture, serious soft tissue injury, and potentially, dislocation of the knee joint. Therefore, tibial plateau fractures are extremely unstable. AIM To assess the use of locking compression plate (LCP) + T-type steel plate for postoperative weight bearing and functional recovery of complex tibial plateau fractures. METHODS Ninety-seven patients with complex tibial plateau fractures who underwent surgery at our hospital were selected for retrospective study. Forty-nine patients had been treated with LCP + T-type steel plate limited internal fixation (study group), and 48 patients with bilateral ordinary steel plate support (control group). The operation process index, postoperative rehabilitation related index, Rasmussen score of the knee joint, tibial plateau varus angle (TPA), tibial plateau retroversion angle (PA), and surgical complications of the two groups were compared. RESULTS The operation time and intraoperative bone graft volume in the study group were lower than those in the control group (P < 0.05). There were no significant differences in surgical bleeding, anterior external incision length, postoperative drainage, hospital stay duration, and fracture healing time between the groups (P > 0.05). There was no significant difference in the TPA and PA angle between the groups immediately and 18 mo after surgery (P > 0.05). At 12 mo after surgery, the Rasmussen scale score was higher in the study group than in the control group (P < 0.05). There was no significant difference in the Rasmussen scale score at 18 mo after surgery, and the radiology score at 12 and 18 mo after surgery, between the two groups (P > 0.05). The postoperative complication rate in the study group (3.77%) was lower than that in the control group (15.09%; P < 0.05). CONCLUSION LCP + T-type steel plate internal fixation has advantages in terms of minimizing trauma and enabling early postoperative functional exercise, promoting functional recovery and lower limb weight-bearing, and reducing postoperative complications.

Background: Malrotation is the most common form of malunion in closed intramedullary nailing of femoral shaft fractures. We introduced the lesser trochanter vanishing angle (LTVA) and discussed the use of the LTVA as a guide for rotation alignment in femoral shaft fractures treated by intramedullary nails. Methods: One hundred and seven femurs derived from 107 cadaver specimens aged more than 70 years were included in this study. All of the femur specimens were scanned by computed tomography (CT). The CT data were imported into Mimics software, and then all the measurements were processed in the software. The LTVA and femoral anteversion angle (FAA) were the main measurements taken. Results: Ultimately, 107 femurs derived from 107 cadaver specimens, including 60 right femurs and 47 left femurs, were included in this study. Among the 107 cadaver specimens, 41 were male and 66 were female. The mean age of cadaver specimens was 84.2±6.4 years. The mean FAA was 16.9±7.6 degrees for a total of 107 femurs. The mean LTVA was 31.7±12.4 degrees, of which the LTVA of the left femur was 32.2±12.9 degrees and the LTVA of the right femur was 30.9±11.8 degrees. LTVA was significantly correlated with FAA (r=0.5273, PConclusion: The LTVA is significantly positively correlated with the FAA, and the LTVA can be used as a guide for rotation alignment in femoral shaft fractures treated by intramedullary nails.

Osteoarthritis (OA) is a progressive degenerative joint disease whose molecular mechanism has not been revealed clearly, and there is still no effective approach to cure OA completely. Recently, reactive oxygen species (ROS) are exposed as an important mediator of OA's inflammatory response, and it has been regarded as a therapeutic target for OA treatment. MnO2 nanoparticles possess good biocompatibility and can act as an artificial nanoenzyme to scavenge ROS in various diseases effectively. In this study, the modified Stober method was applied to synthesize hollow MnO2 (H-MnO2) and H-MnO2 was modified with NH2-PEG-NH2, which possesses excellent biological stability and biocompatibility. It induced a change in the articular cartilage structure changes in vivo, with the knee tissue staining and micro-CT scanning of the whole knee suggesting that H-MnO2 nanoparticles could effectively remove ROS and significantly relieve the inflammatory response of OA without obvious side effects. This study reveals the therapeutic effects of MnO2-based nanomedicine toward OA, which provides potential alternative therapeutic options for patients with inflammation tissue.

Background: Osteoarthritis (OA), one of the most important causes leading to joint disability, was considered as an untreatable disease. A series of genes were reported to regulate the pathogenesis of OA, including microRNAs, Long non-coding RNAs and Circular RNA. So far, the expression profiles and functions of lncRNAs, mRNAs, and circRNAs in OA are not fully understood. Objective: The present study aimed to identify differentially expressed genes in OA. Methods: The present study conducted RNA-seq to identify differentially expressed genes in OA. Ontology (GO) analysis was used to analyze the Molecular Function and Biological Process. KEGG pathway analysis was used to perform the differentially expressed lncRNAs in biological pathways. Results: Hierarchical clustering revealed a total of 943 mRNAs, 518 lncRNAs, and 300 circRNAs, which were dysregulated in OA compared to normal samples. Furthermore, we constructed differentially expressed mRNAs mediated protein-protein interaction network, differentially expressed lncRNAs mediated trans-regulatory networks, and competitive endogenous RNA (ceRNA) to reveal the interaction among these genes in OA. Bioinformatics analysis revealed that these dysregulated genes were involved in regulating multiple biological processes, such as wound healing, negative regulation of ossification, sister chromatid cohesion, positive regulation of interleukin-1 alpha production, sodium ion transmembrane transport, positive regulation of cell migration, and negative regulation of inflammatory response. To the best of our knowledge, this study for the first time, revealed the expression pattern of mRNAs, lncRNAs and circRNAs in OA. Conclusion: This study provided novel information to validate these differentially expressed RNAs may be as possible biomarkers and targets in OA.

Transition-metal-catalyzed alkyne hydration reaction has attracted considerable interest in the past decades because this approach would lead to the facile and efficient formation of synthetically ...

Sandy grassland in northern China is a fragile ecosystem with poor soil fertility. Exploring how plant species regulate growth and nutrient absorption under the background of nitrogen (N) deposition is crucial for the management of the sandy grassland ecosystem. We carried out a field experiment with six N levels in the Hulunbuir Sandy Land of China from 2014 to 2016 and explored the Agropyron michnoi Roshev. responses of both aboveground and belowground biomasses and carbon (C), N and phosphorus (P) concentrations in the plant tissues and soil. With increasing N addition, both aboveground and belowground biomasses and C, N and P concentrations in the plant tissues increased and exhibited a single-peak curve. C:N and C:P ratios of the plant tissues first decreased but then increased, while the trend for the N:P ratio was opposite. The peak values of aboveground biomass, belowground biomass and C concentration in the plant tissues occurred at the level of 20 g N/(m2·a), while those of the N and P concentrations in the plant tissues occurred at the level of 15 g N/(m2·a). The maximum growth percentages of aboveground and belowground biomasses were 324.2% and 75.9%, respectively, and the root to shoot ratio (RSR) decreased with the addition of N. N and P concentrations in the plant tissues were ranked in the order of leaves>roots>stems, while C concentration was ranked as roots>leaves>stems. The increase in N concentration in the plant tissues was the largest (from 34% to 162%), followed by the increase in P (from 10% to 33%) and C (from 8% to 24%) concentrations. The aboveground biomass was positively and linearly correlated with leaf C, N and P, and soil C and N concentrations, while the belowground biomass was positively and linearly correlated with leaf N and soil C concentrations. These results showed that the accumulation of N and P in the leaves caused the increase in the aboveground biomass, while the accumulation of leaf N resulted in the increase in the belowground biomass. N deposition can alter the allocation of C, N and P stoichiometry in the plant tissues and has a high potential for increasing plant biomass, which is conducive to the restoration of sandy grassland.

Using monodentate aliphatic amine [NH(CH3)2] as structural modifier, a new discrete iodocuprate hybrid, i.e. Cu2I2[NH(CH3)2]2 (1), has been solvothermally constructed and structurally characterized. 1 features a cubane-like [Cu4I4] core decorated by four [NH(CH3)2] ligands. It possesses a wide band gap and moderate thermal stability, exhibiting a strong orange light emission with the high photoluminescence quantum yield of 59.9%. The Hirshfeld surface analyses, X-ray photoelectron spectroscopy and theoretical studies of title compound have also been performed.

Elastography complements traditional medical imaging modalities by mapping tissue stiffness to identify tumors in the endocrine system, and machine learning models can further improve diagnostic accuracy and reliability. Our objective in this review was to summarize the applications and performance of machine-learning-based elastography on the classification of endocrine tumors. Two authors independently searched electronic databases, including PubMed, Scopus, Web of Science, IEEEXpress, CINAHL, and EMBASE. Eleven (n = 11) articles were eligible for the review, of which eight (n = 8) focused on thyroid tumors and three (n = 3) considered pancreatic tumors. In all thyroid studies, the researchers used shear-wave ultrasound elastography, whereas the pancreas researchers applied strain elastography with endoscopy. Traditional machine learning approaches or the deep feature extractors were used to extract the predetermined features, followed by classifiers. The applied deep learning approaches included the convolutional neural network (CNN) and multilayer perceptron (MLP). Some researchers considered the mixed or sequential training of B-mode and elastographic ultrasound data or fusing data from different image segmentation techniques in machine learning models. All reviewed methods achieved an accuracy of ≥80%, but only three were ≥90% accurate. The most accurate thyroid classification (94.70%) was achieved by applying sequential training CNN; the most accurate pancreas classification (98.26%) was achieved using a CNN–long short-term memory (LSTM) model integrating elastography with B-mode and Doppler images.

Summary The Povarov reaction, a formal [4 + 2] cycloaddition between N-aryl imines and electron-rich dienophiles, has been defined as an efficient method to approach tetrahydroquinolines and has been well established in the past decades. In general, electron-rich heterosubstituted alkenes have served as the most popular dienophiles to achieve the exclusive regioselectivity. However, the use of Lewis acids and Bronsted acids as catalysts is required in these transformations, and, to our knowledge, the Povarov reaction of electron-rich heterosubstituted alkynes has not been reported. Here, we disclose a catalyst-free Povarov reaction of formyl-ynamides with anilines for the rapid and practical synthesis of a diverse range of valuable quindolines, which not only represents the first Povarov reaction of ynamides to the best of our knowledge but also constitutes a very rare example of a catalyst-free ynamide cyclization reaction. This formal [1 + 2 + 3] annulation shows a reversed regioselectivity compared with the previous protocols.

Rearrangement reactions have attracted considerable interest over the past decades due to their high bond-forming efficiency and atom economy in the construction of complex organic architectures. In contrast to the well-established [3,3]-rearrangement, [1,3] O-to-C rearrangement has been far less vigorously investigated, and stereospecific [1,3]-rearrangement is extremely rare. Here, we report a metal-free intramolecular hydroalkoxylation/[1,3]-rearrangement, leading to the practical and atom-economical assembly of various valuable medium-sized lactams with wide substrate scope and excellent diastereoselectivity. Moreover, such an asymmetric cascade cyclization has also been realized by chiral Brønsted acid-catalyzed kinetic resolution. In addition, biological tests reveal that some of these medium-sized lactams displayed their bioactivity as antitumor agents against melanoma cells, esophageal cancer cells and breast cancer cells. A mechanistic rationale for the reaction is further supported by control experiments and theoretical calculations., Stereospecific [1,3]-rearrangements are rarely reported method to efficiently build complex organic architectures. Here, the authors describe a metal-free intramolecular hydroalkoxylation/[1,3]-rearrangement sequence affording medium-sized lactams with wide scope, also in an asymmetric fashion.

BACKGROUND The lesser trochanter (LT) posterior cortical extension (LTPE) fragment is important for joint stability during reconstruction in unstable pertrochanteric hip fractures. This study aimed to investigate the morphological characteristics of the LT fragments using three-dimensional computed tomography (3-D CT) reconstruction and to compare clinical outcomes in different subgroups of 31A2 fractures. MATERIAL AND METHODS A retrospective study included CT images of 58 cases of 31A2 type unstable pertrochanteric fractures, using the Arbeitsgemeinschaft für Osteosynthesefragen and Orthopedic Trauma Association (AO/OTA) classification. After 3-D CT reconstruction, all the displaced fragments were reduced and the morphologic parameters of the LT fragments were measured. RESULTS At the mid-level of the LT, the mean cortical extension of the LT fragment was 33.5 mm in the posterior wall (83%), 19.0 mm in the medial wall (53%). The mean distal cortical extension from the lower edge of the LT was 13.0 mm. The LT fragment occupied 38% of the whole cortical circumference. Comparison of the subgroups showed that the LT fragment of A2.3 had a larger cortical extension in the posterior, medial, and distal cortex. The mean fracture collapse was 4.7 mm in A2.2 fractures and 5.4 mm in A2.3 fractures (p=0.311). Despite the increased size of the LT fragment in subtype A2.3 fracture compared with subtype A2.2 fracture, this did not influence the clinical outcome. CONCLUSIONS The 3-D morphology of the LT fragment from CT imaging provided a better understanding of the characteristics of subgroups of unstable pertrochanteric fractures, which may improve and guide implant choice.

A metal-free intramolecular tandem sequence involving alkoxylation, Claisen rearrangement and lactone expansion has been achieved., Alkene carbooxygenation has attracted considerable attention over the past few decades as this approach provides an efficient access to various oxygen-containing molecules, especially the valuable O-heterocycles. However, examples of catalytic alkene carbooxygenation via a direct C–O cleavage are quite scarce, and the C–O cleavage in these cases is invariably initiated by transition metal-catalyzed oxidative addition. We report here a novel Brønsted acid-catalyzed intramolecular alkoxylation-initiated tandem sequence, which represents the first metal-free intramolecular alkoxylation/Claisen rearrangement. Significantly, an unprecedented Brønsted acid-catalyzed intramolecular alkene insertion into the C–O bond via a carbocation pathway was discovered. This method allows the stereocontrolled synthesis of valuable indole-fused bridged [4.2.1] lactones, providing ready access to biologically relevant scaffolds in a single synthetic step from an acyclic precursor. Moreover, such an asymmetric cascade cyclization has also been realized by employing a traceless chiral directing group. Control experiments favor the feasibility of a carbocation pathway for the process. In addition, biological tests showed that some of these newly synthesized indole-fused lactones exhibited their bioactivity as antitumor agents against different breast cancer cells, melanoma cells, and esophageal cancer cells.

A metal-free intramolecular alkoxylation-initiated cascade cyclization of allyl ether-tethered ynamides has been developed. Various highly functionalized 3-isochromanones can be obtained in generally good to excellent yields under mild reaction conditions. Moreover, this asymmetric cyclization has also been realized via a stereocontrolled [3,3] rearrangement by employing a traceless chiral directing group. In addition, an unexpected [1,3] O-to-C rearrangement is observed in the case of the ynamide substrate bearing a phenyl-substituted alkene, which is distinctively different from the related gold catalysis.

Chiral Brønsted acid-catalysed asymmetric synthesis has received tremendous interest over the past decades, and numerous efficient synthetic methods have been developed based on this approach. However, the use of chiral Brønsted acids in these reactions is mostly limited to the activation of imine and carbonyl moieties, and the direct activation of carbon-carbon triple bonds has so far not been invoked. Here we show that chiral Brønsted acids enable the catalytic asymmetric dearomatization reactions of naphthol-, phenol- and pyrrole-ynamides by the direct activation of alkynes. This method leads to the practical and atom-economic construction of various valuable spirocyclic enones and 2H-pyrroles that bear a chiral quaternary carbon stereocentre in generally good-to-excellent yields with excellent chemo-, regio- and enantioselectivities. The activation mode of chiral Brønsted acid catalysis revealed in this study is expected to be of broad utility in catalytic asymmetric reactions that involve ynamides and the related heteroatom-substituted alkynes.

Objective. To investigate if 3D printed guides and preoperative planning can accurately control femoral stem anteversion. Methods. A prospective comparative study was carried out from 2018 to 2020, including 53 patients who underwent hip arthroplasty for femoral neck fracture. The target rotation center of the femoral head is determined by three-dimensional planning. In group A, planning was made by 2D templates. In group B, preoperative 3D planning and 3D printed osteotomy/positioning guides were performed. After the operation, 3D model registration was performed to calculate the accuracy of anteversion restoration. Results. We screened 60 patients and randomized a total of 53 to 2 parallel study arms: 30 patients to the group A (traditional operation) and 23 patients to the group B (3D preoperative planning and 3D printed guide). There were no significant differences in demographic or perioperative data between study groups. The restoration accuracy of group A was 5.42 ° ± 3.65 ° and of group B was 2.32 ° ± 1.89 ° . The number and rate of abnormal cases was 15 (50%) and 2 (8.7%), respectively. Significant statistical differences were found in angle change, restoration accuracy, and number of abnormal cases. Conclusion. Three-dimensional preoperative planning and 3D printed guides can improve the accuracy of the restoration of femoral anteversion during hip arthroplasty.

Background There is no consensus in the literature about the ideal classification of the distal radius fracture for the clinical practice. The traditional Melone classification system divides the distal radius into four basic components, the shaft, radial styloid, dorsal medial fragment, and volar medial fragment. The aim of this study was to identify fracture lines in comminuted distal radius fractures using three-dimensional mapping of computed tomography (CT) images to test the hypothesis that fracture fragments can be divided according to the Melone classification. Methods Fifty-nine consecutive OTA/AO 23C3 fractures presented at the hospital between January 2018 and October 2019 were retrospectively reviewed. The fracture lines were characterized in the axial, sagittal, and coronal CT planes. After reducing the fractures in a three-dimensional (3D) model, the fracture lines were plotted from the CT images and were then superimposed on one another and oriented to fit a standard template. The area of articular surfaces was measured and compared to quantify the differences between the radial bone fragments. Results Thirty-five cases (59.3%) in this study fit the Melone classification and 24 cases (40.7%) did not. On the radiocarpal surface, there was a greater concentration of fracture lines in the dorsal area of the radius than in the volar area. On the distal radioulnar joint (DRUJ), the fracture lines were focused around two specific concentrated regions. For the articular surface area, the mean area of the radial styloid, volar medial fragment, and dorsal medial fragment was 141.13 ± 90.16 mm2, 147.79 ± 75.94 mm2, and 79.05 ± 70.73 mm2, respectively. There was a significant difference in articular surface area for the Melone fragments (P = 0.002). Conclusions The Melone classification system is not suitable for characterizing all C3 fractures. The findings of this study confirm that the dorsal medial fragments are relatively comminuted and small. Extra care should be given to these small fragments when reducing the fracture.

To explore the physiological and ecological adaptability of different dominant species during grassland community succession, we measured soil nutrients, plant biomass and C, N and P contents of two dominant species using the method of spatial sequences instead of chronosequences in the successive series of Agropyron michnoi community - A. michnoi + A. cristatam community - A. cristatam community in Hulunbuir Grassland. During the succession progress, the contents of soil total C, total C, available N and available P increased significantly. The N and P contents and N/P of leaves, stems and roots of A. michnoi and A. cristatam increased significantly, while the C/N showed opposite response. The leaf C content of A. michnoi and the C contents of leaves, stems and roots of A. cristatam significantly increased. The leaf C/P of A. michnoi and the C/P of leaves and roots of A. cristatem increased significantly, while the C/P of stems and roots of A. michnoi and the stem C/P of A. cristatem decreased significantly. In the community co-dominated by A. michnoi and A. cristatam, A. michnoi improved its interspecific competitiveness by reducing C content in stems and roots and increasing the C content in leaves, while A. cristatem adapted to environmental changes by reducing root to shoot ratio and reproductive ratio. A. michnoi was limited by N availability (N/P14) in different communities, while A. cristatem was limited by P availability in single dominant community(N/P16)and by both N and P in co-dominant community (14N/P16). The index of stoichiometric homoeostasis of foliar N of A. michnoi in the single dominant community and the co-dominant community were 5.92 and 2.94, respectively, indicating higher N stability, while the index of stoichiometric homoeostasis plant of foliar P of A. cristatem in the single dominant community and the co-dominant community were 4.12 and 3.37, respectively, which indicated higher P stability.为了探究草地群落演替过程中不同优势种的生理生态适应性,本研究采用空间代替时间序列的方法,分析呼伦贝尔草地米氏冰草群落—米氏冰草+冰草群落—冰草群落演替系列的土壤养分、两优势种的生物量及C、N和P含量。结果表明: 随着米氏冰草群落—米氏冰草+冰草群落—冰草群落的演替,土壤全碳、全氮、速效氮及速效磷含量均显著升高;米氏冰草和冰草叶、茎和根的N、P含量及N/P均显著升高,而各构件的C/N降低;米氏冰草叶的C含量及冰草叶、茎和根的C含量均显著升高。米氏冰草叶C/P及冰草根和叶C/P均显著升高,而米氏冰草根和茎C/P及冰草茎C/P均显著下降。在米氏冰草+冰草共优势种群落中,米氏冰草通过降低茎和根C含量,增加叶C的积累,提高其种间竞争力, 而冰草通过降低根冠比和生殖比来适应环境变化。米氏冰草在不同群落中均受N限制(N/P14);而冰草在单优势种群落中受P限制(N/P16),在共优势种群落中受N和P限制(14N/P16)。在单优势种群落和共优势种群落中,米氏冰草叶N化学计量内稳性指数分别为5.92和2.94,具有较高的氮内稳性,冰草叶P化学计量内稳性指数分别为4.12和3.37,具有较高的磷内稳性。.

Objective. Unstable pertrochanteric fractures are usually treated with internal fixation, and the integrity of the anteromedial cortex is an important factor for stability and healing. In this study, we described and analyzed the three-dimensional mapping technology and morphological characteristics of pertrochanteric fractures. Methods. Fifty-nine pertrochanteric fractures (OTA/AO 2007 types 31A2) were retrospectively reviewed. Computed tomographic (CT) images for all fractures were superimposed on a standard template. Medial wall integrity was analyzed, and three-dimensional fracture maps were created. Results. Pertrochanteric fractures always have a posterior defect in the medial cortex. The mean width of the defect, in our study, was 21.5 mm (SD: 6.1 mm, range: 10–40 mm), 56.3% (SD: 13.7%, range: 27.5-100%). Bone segments that contact by the anteromedial cortex were 16.5 mm (SD: 5.3 mm, range: 0-29 mm). Conclusion. The integrity of the anteromedial cortex should be considered during internal fixation of femoral trochanteric fractures. These morphological characteristics could be used to form postoperative cortical contact and improve stability of the fixation. Three-dimensional mapping technology can help establish a typical fracture model, thereby improving doctors’ understanding of fracture characteristics.

Papillary thyroid cancer (PTC) is a kind of thyroid cancer and frequently presents with epithelial-mesenchymal transition (EMT). MicroRNAs (miRNAs) were previously reported to be associated with PTC. Thus, this study aims to define the role of microRNA-520a-3p (miR-520a-3p) in PTC through the JAK/STAT signaling pathway by targeting JAK1. The PTC and normal thyroid tissues of 137 PTC patients were collected. First of all, the expression pattern of miR-520a-3p, JAK1, JAK2, STAT3, E-cadherin, and vimentin in PTC was identified. The relationship between miR-520a-3p and JAK1 was predicted and analyzed. And a series of miR-520a-3p mimic or inhibitor, or siRNA JAK1 introduced into PTC cells were applied to examine the effect of miR-520a-3p on PTC cell viability, migration, invasion, cell cycle, apoptosis, and EMT. Meanwhile, the regulatory effect of miR-520a-3p and JAK1 on the JAK/STAT signaling pathway was also determined. The expression of JAK1, JAK2, STAT3, and vimentin increased yet miR-520a-3p and E-cadherin decreased in PTC tissue. JAK1 was negatively regulated by miR-520a-3p. Functionally, EMT induction was prevented by miR-520a-3p upregulation through downregulating JAK1. When upregulating miR-520a-3p or silencing JAK1 in PTC cells, PTC cell viability, migration, and invasion were inhibited yet cell apoptosis promoted with cells arrested at G1 phase, indicating that miR-520a-3p prevented PTC progression by downregulating JAK1. Moreover, miR-520a-3p elevation or JAK1 inhibition inactivated the JAK/STAT signaling pathway. Collectively, miR-520a-3p prevents cancer progression through inactivating the JAK/STAT signaling pathway by downregulating JAK1 in PTC.

A gold-catalyzed intermolecular reaction of ynamides with 3-indolyl azides via the presumable a-imino gold carbenes has been developed, providing an alternative and efficient way for the synthesis of valuable 3-amino-b-carbolines in generally good to excellent yields. Importantly, this new protocol involves an unexpected 1,2-alkyl migration pathway.

Ethnopharmacological relevance The Gnaphalium affine D. Don is used in China as a folk medicine to treat gout, anti-inflammatory, antitussive and expectorant activities. The aim of this study was to evaluate the potential of the extract of G. affine to treat hyperuricemia and acute gouty arthritis in animal model. Materials and methods G. affine extract was evaluated in an experimental model with potassium oxonate (PO) induced hyperuricemia in mice which was used to evaluate anti-hyperuricemia activity and xanthine oxidase (XO) inhibition. Therapies for acute gouty arthritis was also investigated on monosodium urate (MSU) crystal induced paw edema model. Results G. affine extract showed expressive results on active in reducing serum uric acid (Sur) through effect renal mGLUT9 and mURAT1 mainly and inhibit XO activity in vivo . The extract of G. affine also showed significant anti-inflammatory activity and reduced the paw swelling on MSU crystal-induced paw edema model. Meanwhile, eight major compounds were identified by HPLC-ESI-QTOF-MS/MS. Conclusions The extract of G. affine showed significant effect on evaluated models and therefore may be active agents for the treatment of hyperuricemia and acute gouty arthritis.

Background and Objective Object reassembly is a key technology in scenarios such as surgical planning and broken object restoration. Based on previous research, this work intends to explore the general tasks of 3D object reassembly, including conventional object reconstruction and bone fracture reduction. Methods We introduce an efficient and robust region-pair-relation descriptor, which incorporates strong geometric constraints and remains invariant to rotation and translation. We segment the fractured objects using balanced cluster tree, and develop a coarse-to-fine method for object reassembly. The matching quality of potential region contact pairs at different depths is estimated recursively from the root of the tree. Once the best contact pairs are determined, the least squares method is implemented to obtain the matching results. In addition, we also provide a semi-interactive manipulation to deal with the complex objects. Results For most types of broken objects, our approach can generate high accuracy matching results within 10 s, with the cluster tree depth equals to 11. It allows the automatic reassembly of different-sized fragments. For bone fracture blocks with cancellous structures, a semi-interactive operation is integrated so that the precise matching can also be achieved in 30 s. Conclusion The proposed framework can be expanded to various object reassembly tasks in either automated or semi-automated manner, including the fracture reduction problem which used to be an intensive manual process. Therefore, our work shows significant advantages in medical applications.

In order to improve the life of gun barrel influenced by periodic transient thermal shock during firing, it is necessary to establish the heat conduction model of gun barrel to study the temperature field and its variation rule. Therefore, a mathematical model of two-dimensional nonlinear heat conduction is established. The governing equations and boundary conditions are linearized by Kirchhoff’s variation, and the finite difference equations of internal nodes and boundary nodes are derived using energy balance method and alternating difference implicit scheme. Based on the numerical results of the classics interior ballistic, temperature distribution of some 12.7 mm machine gun barrel during 120 successive firing rounds under the firing specification of the GJB3484-98 is calculated numerically. The temperature field of the external surface of the barrel is tested and the variation law of the temperature field is obtained. Comparison with experimental results shows good agreement with the simulation. The research results provided scientific basic for the studies of new barrel materials and coatings.

Flaps, or more accurately and standard termed Surgical Flaps, is a viable tissue block that has its own blood circulation and can survive by itself.

A biphasic chiral recognition system based on chiral ligand exchange with Cu(II)-N-n-dodecyl-L-proline and hydroxypropyl-β-cyclodextrin as an additive was developed to enantioseparate aromatic β-amino acids by high-speed counter-current chromatography. The biphasic chiral recognition system was established with an n-butanol/water (1:1, v/v) solvent system by adding N-n-dodecyl-L-proline and Cu(II) ions to the organic phase and hydroxypropyl-β-cyclodextrin to the aqueous phase. Several separation parameters, such as temperature, pH value, and chiral selector concentration, were systematically investigated by enantioselective liquid-liquid extraction. Under the optimal separation conditions, 54.5 mg of (R,S)-β-phenylalanine and 74.3 mg of (R,S)-β-3,4-dimethoxyphenylalanine were baseline enantioseparated. More importantly, the synergistic enantiorecognition mechanism, based on the Cu(II)-N-n-dodecyl-L-proline and hydroxypropyl-β-cyclodextrin, was discussed for the first time.

A novel Brønsted acid-catalyzed oxidative C-H functionalization of alkynyl thioethers has been developed. This method allows the practical synthesis of valuable isothiochroman-3-ones in mostly moderate to good yields under mild reaction conditions and features a broad substrate scope and wide functional group tolerance. Moreover, this metal-free oxidation can also be used to promote formal N-H insertion involving an unexpected 1,2-sulfur migration, affording useful 1,4-benzothiazin-3-ones.

Background Fracture reduction quality is of paramount importance for osteosynthesis. The aim of this study was to report the outcome of an inferior cortical buttress non-anatomic reduction pattern and internal fixation for displaced femoral neck fractures (Garden types III and IV) in young adults. Methods A retrospective analysis of 46 displaced femoral neck fractures was performed, which were treated by closed reduction and internal fixation with parallel cannulated screws. There were 20 males and 26 females, with an average age of 50.3 years (19–60). According to the inferior cortical reduction quality seen in recorded intraoperative fluoroscopy, the patients were divided into two groups. Group I (n = 30) was anatomic cortical apposition as the two inferior cortices were smoothly contacted, and group II (n = 16) was buttress cortical apposition as the two inferior cortices were located in positive support contact (Gotfried reduction pattern). With a mean follow-up of 22.0 months, femoral neck length, neck–shaft angle, and clinical outcomes were compared. Results Thirty-nine patients (84.8%) achieved uneventful fracture union. Complications occurred in seven patients, six in group I (20%) and one in group II (6.3%), including displacement to varus, neck shortening, early fixation failure, nonunion, and avascular necrosis of the femoral head. No significant difference existed in the complication rate between the two groups (p = 0.216). Four patients (13.3%) in group I were converted to prosthetic replacement, but none in group II. Conclusions For closed reduction and fixation of displaced femoral neck fractures in young adults, an inferior cortical buttress reduction pattern, though non-anatomic, can produce sustainable fracture stability and predictable clinical outcomes.

Objectives: To calculate the probability of iatrogenic perforation when screws seem to be safe on radiographs. A risk zone (RZ) gradient is mapped to help surgeons determine the suitable screw positions. Methods: Using computed tomography data and image-processing software, 24 proximal femurs were reconstructed. The anteroposterior, lateral, and axial views were then simulated, and the safe zone and RZ were identified and calculated on the axial graphs. Each original axial graph was zoomed and compiled to match a calculated average image, and a gradient figure of the RZs was visualized. Results: All 24 femoral necks had cortical perforation RZs. The average risk percentage was 23.7%. The individual risk per quadrant was as follows: anterosuperior 2.5%, posteroinferior 3.8%, posterosuperior 6.7%, and anteroinferior 10.7%. Four safe and cortex-touching zones and a safe region were identified in femoral neck for 6.5-mm screws. Conclusions: Surgeons should be wary of screws that appear close to the cortex on both radiographs, especially in the posterosuperior and anteroinferior quadrants, because such screws probably perforate the cortex. To minimize iatrogenic perforation, screw position should be assessed using a gradient figure of the RZs.

The use of a dinuclear Cu2(II)-β-cyclodextrin complex (Cu2-β-CyD) as a chiral selector (CS) was successfully applied to chiral high speed counter-current chromatography (HSCCC) for the enantioseparation of aromatic α-hydroxycarboxylic acids. α-cyclohexylmandelic acid (CHMA) as a case was studied to optimize the separation temperature, the pH value of the aqueous phase, and the concentration of the chiral selector, which were comparatively studied between Cu2-β-CyD and native β-cyclodextrin (β-CyD) as CSs. The thermodynamic parameters of the formation of the complex between the enantiomers and the CSs were obtained, and the complex formation constants between the enantiomers and Cu2-β-CyD or β-CyD were determined using induced circular dichroism technology. The results indicate that Cu2-β-CyD can remarkably improve the enantioseparation compared with β-CyD, mainly due to the ion-pairing interactions between the deprotonation of carboxyl group of CHMA and the Cu(II) ion of Cu2-β-CyD. Five of other aromatic α-hydroxycarboxylic acids were also enantioseparated successfully by HSCCC using Cu2-β-CyD as a CS.

Background The goal of this study was to investigate whether ceftriaxone combination therapy is associated with better clinical outcomes than respiratory fluoroquinolone monotherapy for adults with community-acquired pneumonia (CAP). We conducted a meta-analysis of published studies. Methods Using the PubMed, EMBASE, and Cochrane Library databases, we performed a literature search of available randomized controlled trials (RCTs) published as original articles before September 2017. Results Nine RCTs, involving 1520 patients, were included in the meta-analysis. The pooled relative risks (RRs) for the efficacy of ceftriaxone combination therapy versus respiratory fluoroquinolones monotherapy were 0.96 (95% CI: 0.92–1.01), based on clinically evaluable populations, and 0.93 (95% CI: 0.88–0.99) based on intention-to-treat (ITT) populations. No statistically significant differences were observed in microbiological treatment success (pooled RR = 0.99, 95% CI: 0.90–1.09), although drug-related adverse events were significantly lower with ceftriaxone combination therapy than with respiratory fluoroquinolones monotherapy (pooled RR = 1.27, 95% CI: 1.04–1.55). Conclusions Current evidence showed that the efficacy of ceftriaxone combination therapy was similar to respiratory fluoroquinolone monotherapy for hospitalized CAP patients, and was associated with lower drug-related adverse events.