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BACKGROUND: The incidence rate for migraine is 12% worldwide, and recurrence is common, which seriously affects the physical and mental health of patients. OBJECTIVE: To observe the clinical effect of Shallow Puncture and More Twirling method of acupuncture in treating migraine and its impact on serum 5-HT and β-EP. METHODS: A total of 76 patients with migraine were randomized into a control group and acupuncture group with 38 cases in each. In the control group, patients were orally administered flunarizine hydrochloride before sleep, 2 capsules once daily for 4 weeks. In the acupuncture group, Shallow Puncture and More Twirling method was adopted for the acupoints of Sizhukong (SJ 23), Toulinqi (GB 15) Shuaigu (GB 8), Xuanlu (GB 5), Fengchi (GB 20), Waiguan (SJ 5), Zulinqi (GB 41). Patients were given acupuncture 3 times per week for 4 weeks. Then, the total VAS (Visual Analogue Scale) scores, composite score of migraine, serum level of 5-HT and β-EP, and the clinical efficacy differences were observed before and after treatment and the side-effects were recorded among the two groups. RESULTS: The total VAS scores and composite score of migraine were significantly reduced among both groups after the treatment (P< 0.05), and the serum level of 5-HT and β-EP was significantly improved (P< 0.05). Compared with control group, the acupuncture group reported lower results in VAS score and migraine composite score (P< 0.05), and higher results in serum 5-HT and β-EP level (P< 0.05). The acupuncture group with shallow puncture and more twirling method showed a total effective rate of 86.5%, which is higher than the control group (78.4%). The difference is statistically significant (P< 0.05). CONCLUSION: Shallow Puncture and More Twirling method was superior to flunarizine hydrochloride in the treatment of clinical symptoms of migraine. Acupuncture also increases the serum level of 5-HT and β-EP in migraine.

Since 2020,the sudden outbreak of the new crown epidemic has brought great influence on China's retail industry.It directly affects how much retail products are sold.People have little choice but to stay at home and are unable to go shopping.Additionally, there is psychologically far less of an inclination to spend, which has a direct impact on the number of retailers and purchasing power.The single offline and single online sales mode has been impacted,and the new retail mode of deep integration of online and offline has developed rapidly.This paper summarizes the benefits, shortcomings, challenges, and opportunities of the new retail industry under the current epidemic background and makes recommendations for the further development of the new retail industry based on an analysis of the current situation of the new retail industry in China.

Background: Oncogenic alterations (gene amplification, mutation, and fusion/rearrangements) of fibroblast growth factor receptor 2 (FGFR2) are rare and occur at varying frequencies across solid tumor types and have become critical therapeutic targets in drug development. First generation FGFR pan-kinase inhibitors non-selectively inhibit FGFR1-4 and are associated with dose limiting toxicities and narrow therapeutic windows. Off-isoform toxicity (FGFR1-hyperphosphatemia; FGFR4-diarrhea) and on-target acquired resistance have led to limited efficacy, which is primarily seen in FGFR2-fusion+ intrahepatic cholangiocarcinoma. Therapies that selectively target FGFR2 remain an unmet need in advanced breast cancer as well as other solid tumor types. RLY-4008 is a novel, oral FGFR2 inhibitor designed to overcome the limitations of pan-FGFR inhibitors (FGFRi) by potently and selectively targeting primary oncogenic FGFR2 alterations and acquired resistance mutations. RLY-4008 is > 200-fold selective over FGFR1, > 80- and > 5000-fold selective over FGFR3 and FGFR4 respectively. Here we describe a phase 1/2 study to investigate the safety and antitumor activity in advanced FGFR2 altered cancers, including breast cancer. Methods: ReFocus is a phase 1/2 open label global study evaluating the safety and efficacy of RLY-4008 (NCT04526106) in adult patients with advanced unresectable and/or metastatic cancers harboring an FGFR2 alteration. Key eligibility criteria include: documented FGFR2 alteration in blood or tissue per local assessment, ECOG performance status of 0-1, disease that is refractory or not adequately responding to standard therapy, has no available standard therapy, or patient is intolerant of, or declined standard therapy (including pan-FGFRi), and measurable or evaluable disease per RECIST 1.1. FGFR2 alteration will be confirmed retrospectively by central laboratory assessment. Part 1 dose escalation employed the Bayesian Optimal Interval (BOIN) design to determine the MTD/RP2D of RLY-4008. Part 2 dose expansion is presently enrolling patients at the RP2D of RLY-4008 and includes 5 cohorts comprised of patients with: 1. FGFR2 fusion+ cholangiocarcinoma previously treated with an FGFRi; 2. FGFR2 fusion+ cholangiocarcinoma not previously treated with an FGFRi; 3. FGFR2 fusion+ solid tumors; 4. FGFR2 mutation+ solid tumors and 5. FGFR2 amplified solid tumors. Solid tumors in cohorts 3, 4 and 5 will have a focus in breast cancer. The primary endpoint is objective response rate (ORR); key secondary endpoints include: duration of response, safety and tolerability, correlation of FGFR2 genotype by central tissue assessment with antitumor response, characterization of PK profile, and quality of life. US enrollment began September 2020 and has expanded into Europe and Asia. Clinical trial information: NCT04526106. Citation Format: Suneel Kamath, David Tai, Irene Moreno, Hani Babiker, Zhaohui Jin, Changhoon Yoo, Fabien Ricard, Kai Yu Jen, Jim Coward, Jia Liu, Frans Opdam, Michael Millward, Mariano Ponz-Sarvise, Jeffrey Yachnin, Richard Kim, Joon Oh Park, Vivek Subbiah, Alison M. Schram. ReFocus: A Phase 1/2 Study of the Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients with Advanced Solid Tumors Including Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-24-01.

Phospholipids are the protective layer of modern cells, but it is challenging for the formation of phospholipids that require a simple abiotic synthesis before the advent of primitive cells. Here, we reported the abiotic synthesis for lysophosphatidic acids (LPAs) with prebiotically plausible reactants in aqueous microdroplets under ambient conditions. The LPAs formation is carried out by fusing two microdroplets streams: one contains glycerol and pyrophosphate in water and the other one contains fatty acids in acetonitrile. Compared with the bulk solution, LPAs were generated in microdroplets without the addition of catalyst and heating. Conditions of reactant concentrations and microdroplet size varied and suggested that LPAs formation occurred near or at the microdroplet surface. The LPAs formation also showed chemoselective toward on chain-length of fatty acids. Finally, the formation of LPAs underwent two-step reactions with glycerol phosphorylation eliminating one water molecule followed by esterification with fatty acids. These results also implicated that pyrophosphate functioned as both catalysts and precursors in prebiotic LPAs synthesis. The approach using fusion aqueous microdroplets has desirable features in studying the substance exchange and interaction in atmosphere.

Spin-coated blend films with complex phase-separated morphology find broad applications while precise tailoring of the morphology is still challenging. In this study, graphene oxide (GO)-based Janus nanosheets were synthesized by interfacial polymerization in a GO nanosheet stabilized Pickering emulsion with polystyrene (PS) and poly(hydroxyethyl methacrylate) synchronously being grafted to the GO nanosheet from the oil and water sides. The Janus nanosheets make the morphology of spin-coated PS/poly(methyl methacrylate)(PMMA) blend films tunable over the full height of the film until the substrate as their preferential assembly at the PS/PMMA interface and attachment on the glass substrate drive the top PS phase to migrate towards the substrate and the bottom PMMA phase to dewet from the substrate towards the air. By varying blend composition and Janus nanosheet loading, morphologies are readily transformed from a PS network on top of PMMA to PS droplets in the PMMA matrix and from PS encapsulated by PMMA to PMMA cavities in the PS network, etc.. This enables generating thin films with various morphologies ranging from a flat surface to cavity-network structures, droplet-matrix structures or bi-continuous structures, etc. at will. Moreover, the morphologies trapped by jammed nanosheets at the interface are super stable against further evolution upon annealing.

These metabolomic patterns may provide new additional evidence and potential insights relevant to the molecular basis of insulin resistance and the etiology of T2D.

Sonodynamic therapy (SDT) can be described as ultrasonic (US) catalysis. Adequate charge separation is considered as effective means to promote reactive oxygen species (ROS). Here, hollow CoP@N-carbon@PEG (CPCs@PEG) nanospheres (∼60 nm) are prepared as sonosensitizers, showing greater ROS generation than pure CoP@PEG under US irradiation. Both

Pouchitis is the most common complication following restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). Fecal calprotectin (FC) is a noninvasive indicator of the intestinal inflammatory status. This study was conducted to evaluate the clinical value of the FC concentration for the diagnosis and risk assessment of pouchitis.This retrospective study involved patients who underwent IPAA for UC at Tianjin Medical University General Hospital from January 2015 to January 2019. The patients were categorized into pouchitis and non-pouchitis groups based on their Pouchitis Disease Activity Index (PDAI) score. Laboratory indicators, including the FC concentration, were collected from both groups.Sixty-six patients with UC after IPAA were included in the study and divided into the non-pouchitis group (FC is a useful biomarker in patients with pouchitis. Patients are advised to regularly undergo FC measurement to monitor for pouchitis. An FC concentration in the range of 143.25-579.60 μg/g is predictive of a high risk for pouchitis, and further examination and preventive treatment are necessary in such patients.KEY MESSAGESFecal calprotectin can be used to quantify pouch inflammation.Fecal calprotectin can be used to predict a high risk of pouchitis.

The α-Fe2O3/In2O3 heterojunctions derived from a bimetal–organic framework of an InFc MOF, endows a high sensitivity (86) to 100 ppm cyclohexane at a working temperature of 225 °C, in the top set for similar types of sensors.

People with Down syndrome often present with balance deficits, which compromise safety during daily activity. While evidence shows that exercise can improve balance in the Down syndrome population, it is unclear if a telehealth method will elicit similar benefits. We aimed to examine the effects of a virtual exercise program on balance in adults with Down syndrome.Eighteen low-active participants with Down syndrome completed a 12-week telehealth exercise program based on the Mann Method. Balance testing took place before and after the intervention, which included: TUG, MCTSIB, FICSIT-4, and FRT. This study was registered as a clinical trial on ClinicalTrials.gov, identifier: NCT04647851.Significant improvement was seen in the TUG (p = .043), FICSIT-4 (p = .019) and FRT (p = .019). All participants achieved maximum scores on the MCTSIB in pre- and post-testing.Balance in low-active adults with Down syndrome significantly improved following the telehealth exercise program, which we attribute to the tailored exercises that address visual/vestibular deficits and hip muscle weakness.

Although phototherapy has attracted extensive attention in antitumor field in recent years, its therapeutic effect is usually unsatisfactory because of the complexity and variability of the tumor microenvironment (TME). Herein, we report novel CoSn(OH)

Information literacy is a core research topic in the field of library and information science. The developmental context of this field can be examined through a long-term retrospective analysis of relevant literature. This study explored the research trends and potential research issues in the top 100 most frequently cited articles on information literacy in higher education published from 2011 to 2020. In addition to a systematic review, this study employed bibliometric methods, including co-citation network analysis, to identify four main research streams in the field of information literacy in higher education: (a) the relationships among students’ information literacy beliefs, competencies, attitudes and behaviour; (b) teachers’, librarians’ and students’ perspectives on information literacy; (c) the relationship between students’ information literacy and epistemic beliefs; and (d) the web search behaviour of digital natives. Accordingly, potential directions for future research and practitioner notes related to information literacy in higher education are proposed herein as a reference for researchers, teachers and policymakers. Implications for practice or policy: For administrators of higher educational institutions, understanding the challenges of new digital technologies and providing training to develop information literacy skills are crucial. For teachers, designing teaching materials and pedagogy based on the latest information literacy standards and framework is useful. Collaboration with professionals from different disciplines is also useful for teachers to integrate information literacy into subject learning activities to cultivate the information literacy competencies of students.

Manually segmenting medical images is expertise-demanding, time-consuming and laborious. Acquiring massive high-quality labeled data from experts is often infeasible. Unfortunately, without sufficient high-quality pixel-level labels, the usual data-driven learning-based segmentation methods often struggle with deficient training. As a result, we are often forced to collect additional labeled data from multiple sources with varying label qualities. However, directly introducing additional data with low-quality noisy labels may mislead the network training and undesirably offset the efficacy provided by those high-quality labels. To address this issue, we propose a Mean-Teacher-assisted Confident Learning (MTCL) framework constructed by a teacher-student architecture and a label self-denoising process to robustly learn segmentation from a small set of high-quality labeled data and plentiful low-quality noisy labeled data. Particularly, such a synergistic framework is capable of simultaneously and robustly exploiting (i) the additional dark knowledge inside the images of low-quality labeled set via perturbation-based unsupervised consistency, and (ii) the productive information of their low-quality noisy labels via explicit label refinement. Comprehensive experiments on left atrium segmentation with simulated noisy labels and hepatic and retinal vessel segmentation with real-world noisy labels demonstrate the superior segmentation performance of our approach as well as its effectiveness on label denoising.

Tumor hypoxia not only promotes the proliferation, invasion and metastasis of cancer cells but also seriously hinders photodynamic therapy (PDT). Here, second near-infrared (NIR-II) photocatalytic O

Dysregulated cholesterol metabolism is a hallmark of colorectal cancer (CRC). However, the usage of cholesterol-lowering agents seemed to have no benefit in CRC patients. In this study, we focused on the cholesterol-nuclear receptors (NRs) axis as a strategy. Cholesterol and its derivatives work as ligands for different nuclear receptors, thus promoting cancer progression. The key NR downstream of cholesterol in CRC is unknown. Here, we treated CRC cells with a cholesterol-lowering agent and lipoprotein-depleted conditioned medium, and then detected the change of the putative NRs. The results revealed that RORα/γ (Retinoic acid receptor-related Orphan Receptor α/γ) levels exhibited the most obvious increases in CRC cells subjected them to cholesterol deprivation. RORα/γ agonists significantly inhibited CRC cells proliferation and migration in vitro and in vivo. Also, RORα/γ overexpression repressed CRC cells proliferation and migration in vitro and in vivo and RORα/γ knockdown promoted it. Mechanistically, RORα/γ agonists promoted c-myc degradation by activating the transcription of the ubiquitinase NEDD4. Intriguingly, the combination of RORα/γ agonists and atorvastatin had a synergistic effect on inhibiting CRC cells. These findings demonstrate that the cholesterol- RORα/γ axis is important for maintaining c-myc protein levels. Combination therapy with atorvastatin and RORα/γ agonist is a promising therapeutic strategy for CRC.

ObjectiveGGC repeat expansions in the human-specificNOTCH2NLCgene have been reported as the cause of neuronal intranuclear inclusion disease (NIID). Given the clinical overlap of cognitive impairment in NIID and cerebral small vessel disease (CSVD), both diseases have white matter hyperintensity on T2-fluid-attenuated inversion recovery sequences of brain MRI, and white matter hyperintensity is a primary neuroimaging marker of CSVD on MRI. Therefore, we hypothesised that the GGC repeat expansions might also contribute to CSVD. To further investigate the relationship betweenNOTCH2NLCGGC repeat expansions and CSVD, we performed a genetic analysis of 814 patients with the disease.MethodsWe performed a comprehensive GGC repeat expansion screening inNOTCH2NLCfrom 814 patients with sporadic CSVD. Their Fazekas score was greater than or equal to 3 points. Repeat-primed PCR and fluorescence amplicon length analyses were performed to identify GGC repeat expansions, and whole-exome sequencing was used to detect any pathogenic mutation in previously reported genes associated with CSVD.ResultsWe identified nine (1.11%) patients with pathogenic GGC repeat expansions ranging from 41 to 98 repeats. The minor allele frequency of expanded GGC repeats inNOTCH2NLCwas 0.55%.ConclusionOur findings suggest that intermediate-length and longer-length GGC repeat expansions inNOTCH2NLCare associated with sporadic CSVD. This provides new thinking for studying the pathogenesis of CSVD.

Post-translational modifications (PTMs) are critical molecular mechanisms that regulate protein functions temporally and spatially in various organisms. Since most PTMs are dynamically regulated, quantifying PTM events under different states is crucial for understanding biological processes and diseases. With the rapid development of high-throughput proteomics technologies, massive quantitative PTM proteome datasets have been generated. Thus, a comprehensive one-stop data resource for surfing big data will benefit the community. Here, we updated our previous phosphorylation dynamics database qPhos to the qPTM (http://qptm.omicsbio.info). In qPTM, 11 482 553 quantification events among six types of PTMs, including phosphorylation, acetylation, glycosylation, methylation, SUMOylation and ubiquitylation in four different organisms were collected and integrated, and the matched proteome datasets were included if available. The raw mass spectrometry based false discovery rate control and the recurrences of identifications among datasets were integrated into a scoring system to assess the reliability of the PTM sites. Browse and search functions were improved to facilitate users in swiftly and accurately acquiring specific information. The results page was revised with more abundant annotations, and time-course dynamics data were visualized in trend lines. We expected the qPTM database to be a much more powerful and comprehensive data repository for the PTM research community.

Continuous fiber-reinforced polymer composites, with their superior combinations of high stiffness, high strength, lightweight, and corrosion resistance, have been leading contenders in various applications ranging from aerospace to ground transportation. The integration with 3D printing allows the composite products to be customized quickly and fabricated inexpensively to meet unique specifications. However, the material-process-property relationships of 3D printed thermoset composites with continuous fiber are insufficiently explored in the field. In this work, a cost-effective 3D printing method is developed based on the direct ink writing method to print UV-curable composites reinforced with continuous carbon fiber. During the printing, the fiber tow is impregnated with an acrylate ink inside the printer head and then extruded onto the printer bed, where it is cured upon UV irradiation. The influences of different material and processing variables, such as the resin viscosity, nozzle size, printing speed, and substrate temperature, on the quality and mechanical properties of composites, are investigated. The porosity, stiffness, and strength of printed symmetric laminate are also examined. Finally, the 3D printing of composite structures and the conformal coating of curved surfaces along a defined printing path are demonstrated. The findings reported in this work could contribute to the rapid design and manufacturing of composite components with unprecedented mechanical properties and emerging functionalities for the automotive, defense, and aerospace industries.

Surgical resection of pheochromocytoma and paraganglioma (PPGL) may be associated with excessive hemodynamic variability. Whether hemodynamic variability occurs in patients with undiagnosed PPGL undergoing unrelated, non-neuroendocrine, operations is unknown.We identified patients who underwent non-neuroendocrine surgical procedures up to 5 y before pathologic diagnosis of PPGL. For each PPGL, two non-PPGL patients were matched based on sex, age, type, and year of operation. Electronic medical records were reviewed for intraoperative blood pressures, heart rates, and hemodynamic variability was assessed with range (maximum-minimum), standard deviation, coefficient of variation, and average real variability.Thirty-seven PPGL patients underwent operations preceding the diagnosis of PPGL: 25 pheochromocytomas, 11 paragangliomas, and one metastatic pheochromocytoma. Median interquartile range tumor size at diagnosis was 35 mm (23 to 60). The time from index operation to PPGL diagnosis was ≤12 mo in 21 (56.8%) patients. In 23 (62.2%) patients, the subsequently diagnosed PPGL was functional. Fifteen (40.5%) PPGL and 20 (27.0%) control patients were preoperatively treated for hypertension (P = 0.149). Maximum intraoperative systolic BP was180 mmHg for 4 (10.8%) PPGL patients and 3 (4.1%) controls (P = 0.219). Two PPGL patients had intraoperative systolic BP230 mmHg. No significant differences were found with all other measures of intraoperative hemodynamic variability. Similarly, in secondary analysis there was no significant difference in intraoperative hemodynamic variability between biochemically active PPGL and their respective controls.Patients with undiagnosed PPGL undergoing a wide variety of non-neuroendocrine operations had intraoperative hemodynamic variability comparable to non-PPGL patients undergoing the same type of procedures.