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Background: Significant efforts have been devoted to assess the effects of the poly-gamma-glutamic acid (γ-PGA) on crop growth, yield and quality, soil water retention and fertilizer use efficiency. However, few studies have evaluated the effects of γ-PGA on greenhouse gas (GHG) emissions and grain yield from paddy fields with different rice varieties., Methods: In the present study, a split-plot field experiment was performed to comprehensively evaluate the effects of γ-PGA concentrations (i.e., no application [P0] and 25.0 kg ha -1 of γ-PGA fermentation solution [P1]) and rice varieties (i.e., conventional rice [Huanghuazhan, H], red rice [Gangteyou 8024, R] and black rice [Black indica rice, B]) on the grain yield, GHG emissions, global warming potential (GWP), greenhouse gas intensity (GHGI), net ecosystem economic profit (NEEP) and carbon footprint (CF) during 2022 and 2023 rice-growing seasons in central China., Results: Application of γ-PGA significantly affected the GHGs emissions, NEEP and CF. Compared with P0 treatments, P1 treatments significantly increased the NEEP by 1.2-11.2 %, and decreased the GWP by 12.9-35.4 %, the GHGI by 16.5-35.9 % and the CF by 13.8-26.2 % in 2022-2023. Application of γ-PGA showed a tendency to increase the yield. Under γ-PGA application condition, R treatment exhibited the lowest GWP, GHGI and CF, and the highest yield and NEEP compared with B and H treatments., Conclusion: Our results suggest that γ-PGA application is an ecological agricultural management to increase rice yield, reduce greenhouse gas emission and increase economic benefit, and its advantage is more significant for red rice than for other rice varieties., Competing Interests: Declaration of competing interest The authors report no declarations of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To observe the effect of heat-reinforcing needling (HRN) on synovial inflammation, hypoxia-inducible factor-1α (HIF-1α) and glycolytic activity in serum and synovial tissue in rabbits with cold syndrome of rheumatoid arthritis (RA), so as to explore its mechanisms underlying improvement of RA., Methods: A total of 32 rabbits were randomly divided into normal, model, inhibitor and HRN groups, with 8 rabbits in each group. The RA with cold syndrome model was induced by injecting ovalbumin dry powder and Freund's complete adjuvant combined with cold freezing. Rabbits in the inhibitor group were intraperitoneally injected with 2-methoxyestradiol (2.5 mg/kg), rabbits in the HRN group were received HRN at bilateral "Zusanli" (ST36) for 30 min. The treatments were conducted once daily for 14 consecutive days. After the interventions, the knee circumference and pain threshold were measured. The contents of nicotinamide adenine dinucleotide phosphoric (NADPH), Hexokinase II (HK2) and 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) in serum of rabbits were detected by ELISA. The pathological morphology of synovial tissue of the knee joints were observed by HE staining. The positive expressions of tumor necrosis factor (TNF-α), interleukin (IL)-1β, IL-6 and IL-17 in synovial tissue of knee joint were detected by immunohistochemistry. The content of lactic acid in synovial tissue of rabbit knee joint was detected by spectrophotometry. The expression levels of HIF-1α, pyruvate kinase 2 (PKM2) and lactate dehydrogenase (LDHA) in synovial tissue of knee joint were detected by Western blot., Results: After intervention, compared with the normal group, the knee circumference was significantly enlarged ( P <0.05), the pain threshold was significantly decreased ( P <0.05)；the synovial tissue of knee joints showed significant cell proliferation and inflammatory infiltration, the pathological score was significantly increased ( P <0.05)；positive expressions of TNF-α, IL-1β, IL-6 and IL-17, the content of lactic acid in synovial tissue, the contents of NADPH, HK2 and PFKFB3 in serum, and the protein expression levels of HIF-1α, PKM2 and LDHA in synovial tissue were increased (all P <0.05) in the model group. Compared with model group, the circumference of knee joint was significantly decreased ( P <0.05), the pain threshold was significantly increased ( P <0.05)；in synovial tissue, the pathological score was decreased ( P <0.05)；the positive expressions of TNF-α, IL-1β, IL-6 and IL-17 in synovial tissue were decreased ( P <0.05), the lactic acid content in synovial tissue was decreased ( P <0.05)；the contents of NADPH, HK2 and PFKFB3 in serum and the protein expression levels of HIF-1α, PKM2 and LDHA in synovial tissue were decreased ( P <0.05) in inhibitor group and HRN group. Compared with the inhibitor group, the synovial pathological score was significantly increased ( P <0.05), positive expressions of TNF-α, IL-1β, IL-6 and IL-17, the content of lactic acid in synovial tissue, the contents of NADPH, HK2 and PFKFB3 in serum, and the protein expression levels of HIF-1α, PKM2 and LDHA in synovial tissue were increased (all P <0.05) in HRN group., Conclusions: HRN can increase the pain threshold, reduce the knee circumference and inhibit the inflammatory response in rabbits with cold syndrome of RA. The possible mechanism is related to the down-regulation of HIF-1α and glycolysis activity.

Rationale and Objectives: This study aimed to develop and evaluate a radiomics-based model combined with clinical and qualitative radiological (semantic feature [SF]) features to predict immune checkpoint inhibitor-related pneumonitis (CIP) in patients with non-small cell lung cancer (NSCLC) treated with programmed cell death protein 1 inhibitors., Materials and Methods: This was a multicenter retrospective casecontrol study conducted from January 1, 2018, to December 31, 2022, at three centers. Patients with NSCLC treated with anti-PD1 were enrolled and randomly divided into two groups (7:3): training (n = 95) and validation (n = 39). Logistic regression (LR) and support vector machine (SVM) algorithms were used to transform features into the models., Results: The study comprised 134 participants from three independent centers (male, 114/134, 85%; mean [±standard deviation] age, 63.92 [±7.9] years). The radiomics score (RS) models built based on the LR and SVM algorithms could accurately predict CIP (area under the receiver operating characteristics curve [AUC], 0.860 [0.780, 0.939] and 0.861 [0.781, 0.941], respectively). The AUCs for the RS-clinic-SF combined model were 0.903 (0.839, 0.967) and 0.826 (0.688, 0.964) in the training and validation cohorts, respectively. Decision curve analysis showed that the combined models achieved high clinical net benefit across the majority of the range of reasonable threshold probabilities., Conclusion: This study demonstrated that the combined model constructed by the identified features of RS, clinical features, and SF has the potential to precisely predict CIP. The RS-clinic-SF combined model has the potential to be used more widely as a practical tool for the noninvasive prediction of CIP to support individualized treatment planning., Competing Interests: DECLARATION OF COMPETING INTEREST The authors declare that the research was carried out in the absence of commercial or financial relationships that could be construed as a potential competing interest., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Despite ongoing research, the underlying causes of schizophrenia remain unclear. Aspartate and asparagine, essential amino acids, have been linked to schizophrenia in recent studies, but their causal relationship is still unclear. This study used a bidirectional two-sample Mendelian randomization (MR) method to explore the causal relationship between aspartate and asparagine with schizophrenia., Methods: This study employed summary data from genome-wide association studies (GWAS) conducted on European populations to examine the correlation between aspartate and asparagine with schizophrenia. In order to investigate the causal effects of aspartate and asparagine on schizophrenia, this study conducted a two-sample bidirectional MR analysis using genetic factors as instrumental variables., Results: No causal relationship was found between aspartate and schizophrenia, with an odds ratio (OR) of 1.221 (95%CI: 0.483-3.088, P-value = 0.674). Reverse MR analysis also indicated that no causal effects were found between schizophrenia and aspartate, with an OR of 0.999 (95%CI: 0.987-1.010, P-value = 0.841). There is a negative causal relationship between asparagine and schizophrenia, with an OR of 0.485 (95%CI: 0.262-0.900, P-value = 0.020). Reverse MR analysis indicates that there is no causal effect between schizophrenia and asparagine, with an OR of 1.005(95%CI: 0.999-1.011, P-value = 0.132)., Conclusion: This study suggests that there may be a potential risk reduction for schizophrenia with increased levels of asparagine, while also indicating the absence of a causal link between elevated or diminished levels of asparagine in individuals diagnosed with schizophrenia. There is no potential causal relationship between aspartate and schizophrenia, whether prospective or reverse MR. However, it is important to note that these associations necessitate additional research for further validation., (© 2024. The Author(s).)

Objective: Hydrogen sulfide (H 2 S) is associated with depressive-like behavior in rodents. We undertook cross-sectional and longitudinal analyses of plasma levels of H 2 S and its substrate homocysteine (Hcy) in depression and assessed the association of both parameters with psychopathology and cognitive function., Methods: Forty-one patients suffering from depression (PSDs) and 48 healthy volunteers were recruited. PSDs were treated for 8 weeks. Analyzable data were collected from all participants for assessment of their psychopathology and cognitive function. Plasma was collected for determination of levels of H 2 S and Hcy, and data were correlated to determine their potential as plasma biomarkers., Results: Cross-sectional analyses revealed PSDs to have a low plasma H 2 S level and high Hcy level. Longitudinal analyses revealed that 8 weeks of treatment reversed the changes in plasma levels of H 2 S and Hcy in PSDs. Plasma levels of H 2 S and Hcy were associated with psychopathology and cognitive function in depression. The area under the receiver operating characteristic curve (AUC) for a combination of plasma levels of H 2 S and Hcy and expression of the TNF gene (i.e., H 2 S-Hcy-TNF) was 0.848 for diagnosing depression and 0.977 for predicting the efficacy of antidepressant agents., Conclusion: Plasma levels of H 2 S and Hcy reflect changes in psychopathology and cognitive function in depression and H 2 S-Hcy-TNF has the potential to diagnose depression and predict the efficacy of antidepressant medications., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Glioblastoma (GBM) is an extremely aggressive tumor associated with a poor prognosis that impacts the central nervous system. Increasing evidence suggests an inherent association between glucose metabolism dysregulation and the aggression of GBM. Polo-like kinase 4 (PLK4), a highly conserved serine/threonine protein kinase, was found to relate to glioma progression and unfavorable prognosis. As revealed by the integration of proteomics and phosphoproteomics, PLK4 was found to be involved in governing metabolic processes and the PI3K/AKT/mTOR pathway. For the first time, this study supports evidence demonstrating that PLK4 activated PI3K/AKT/mTOR signaling through direct binding to AKT1 and subsequent phosphorylating AKT1 at S124, T308, and S473 to promote tumorigenesis and glucose metabolism in glioma. In addition, PLK4-mediated phosphorylation of AKT1 S124 significantly augmented the phosphorylation of AKT1 S473. Therefore, PLK4 exerted an influence on glucose metabolism by stimulating PI3K/AKT/mTOR signaling. Additionally, the expression of PLK4 protein exhibited a positive correlation with AKT1 phosphorylation in glioma patient tissues. These findings highlight the pivotal role of PLK4-mediated phosphorylation of AKT1 in glioma tumorigenesis and dysregulation of glucose metabolism., Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To observe the effect of electroacupuncture (EA) of scalp acupoint (Dingnieqian-xiexian, MS6) on expression of retinoid-related orphan receptor γT (ROR γ t), interleukin (IL)-17A, IL-10, transfor-ming growth factor-β1 (TGF-β1), IL-6, IL-21, and IL-17A + Thelper cells(Th) 17 and forkhead transcription factor P3 (FOXP3) + regulatory T cells (Treg) differentiation of ischemic cortex in ischemic stroke rats, so as to explore its molecular mechanisms underlying relief of inflammatory injury of ischemic stroke., Methods: A total of 120 male SD rats were randomly assigned to sham operation, model, EA, inhibitor, agonist and EA+agonist groups, with 15 rats in each group. The ischemic stroke model was established by occlusion of the left middle cerebral artery according to Longa's methods. For rats of the EA group and EA+agonist group, EA (2 Hz/100 Hz, 1 mA) was applied to bilateral MS6 for 30 min, once daily for 7 days. Rats of the inhibitor group received intraperitoneal injection of solution of SR1001 (RORγt inhibitor) (2.5 mg/mL, 10 mg/kg), once daily for 7 days. Rats of the agonist and EA+agonist groups received intraperitoneal injection of solution of SR1078 (RORγt agonist) (5 mg/mL, 5 mg/kg) before EA, once daily for 7 days. Rats of the sham operation and model groups were grabbed and fixed in the same way with the other groups. The Zea-longa's score, modified neurological severity score (mNSS) and the neurobehavioral score were assessed before and after the intervention. At the end of experiments, the ischemic cortex tissue was collected. The 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining was used to detect the volume of cerebral infarction. The expression of RORγt mRNA was detected by real-time quantitative PCR；the protein expression levels of RORγt, IL-17A, IL-10 and TGF-β1 were detected by Western blot；the immunoactivity of IL-6 and IL-21 were detected by immunohistochemistry；the fluorescence areas of IL-17A + Th17 and FOXP3 + Treg cells were measured by immunofluorescence and their ratio was calculated in the tissue of ischemic cortex., Results: Relevant to the sham operation group, the model group had a significant increase in the Zea-Longa's score, mNSS score, neurobehavioral score, cerebral infarct volume, expression levels of RORγt mRNA and protein, IL-17A protein, IL-6 and IL-21 immunoactivity, IL-17A + Th17 immunofluorescence intensity, and the ratio of IL-17A + Th17/FOXP3 + Treg ( P <0.01), and an obvious decrease in the expression levels of TGF-β1 and IL-10 proteins and FOXP3 + Treg immunofluorescence intensity ( P <0.01). In contrast to the model group, both EA and inhibitor groups had a significant decrease in the Zea-Longa's score, mNSS score, neurobehavioral score, cerebral infarct volume, expression levels of RORγt mRNA and protein, IL-17A protein, IL-6 and IL-21 immunoactivity, IL-17A + Th17 immunofluorescence intensity, and the ratio of IL-17A + Th17/FOXP3 + Treg ( P <0.01, P <0.05), and a marked increase in the expression levels of TGF-β1 and IL-10 proteins and FOXP3 + Treg immunofluorescence intensity ( P <0.05, P <0.01), while the above indicators of the agonist group were all reversed ( P <0.01, P <0.05). Comparison between the agonist and EA+agonist groups showed that the Zea-Longa's score, mNSS score, neurobehavioral score, cerebral infarct volume, expression levels of RORγt mRNA and protein, IL-17A protein, IL-6 and IL-21 immunoactivity, IL-17A + Th17 immunofluorescence intensity, and the ratio of IL-17A + Th17/FOXP3 + Treg were significantly lower ( P <0.01, P <0.05), and the expression of TGF-β1 and IL-10 proteins and FOXP3 + Treg immunofluorescence intensity were obviously higher ( P <0.01, P <0.05) in the EA+agonist group than in the agonist group, suggesting that EA intervention can effectively weaken the effects of RORγt agonist., Conclusions: EA of scalp acupoint MS6 can effectively improve the neurological function, behavior reaction and reduce cerebral infarct volume in ischemic stroke rats, which may be associated with its functions in down-regulating the expression of RORγt and promoting the balance of IL-17A + Th17/FOXP3 + Treg to alleviate inflammatory injury after ischemic stroke.

Objective: To observe the effects of electro-scalp acupuncture （ESA） on the expression of microglial markers CD206 and CD32, as well as interleukin (IL)-6, IL-1β, and IL-10 in the ischemic cortex of rats with ischemic stroke, and to explore the mechanisms of ESA on alleviating inflammatory damage of ischemic stroke., Methods: Sixty 7-week-old male SD rats were randomly selected, with 15 rats assigned to a sham surgery group. The remaining rats were treated with suture method to establish rat model of middle cerebral artery occlusion (MCAO). The rats with successful model were randomly divided into a model group, a VitD 3 group, and an ESA group, with 15 rats in each group. In the ESA group, ESA was performed bilaterally at the "top-temporal anterior oblique line" with disperse-dense wave, a frequency of 2 Hz/100 Hz, and an intensity of 1 mA. Each session lasted for 30 min, once daily, for a total of 7 days. The VitD 3 group were treated with intragastric administration of 1,25-dihydroxyvitamin D 3 (1,25-VitD 3 ) solution (3 ng/100 g), once daily for 7 days. The neurological deficit scores and neurobehavioral scores were assessed before and after the intervention. After the intervention, the brain infarct volume was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Immunofluorescence double staining was performed to detect the protein expression of CD32 and CD206 in the ischemic cortex. Western blot analysis was conducted to measure the protein expression of IL-6, IL-1β, and IL-10 in the ischemic cortex., Results: Compared with the sham surgery group, the model group showed increased neurological deficit scores and neurobehavioral scores ( P <0.01), increased brain infarct volume ( P <0.01), increased protein expression of CD32, IL-6, and IL-1β in the ischemic cortex ( P <0.01), and decreased protein expression of CD206 and IL-10 in the ischemic cortex ( P <0.01). Compared with the model group, both the ESA group and the VitD 3 group showed decreased neurological deficit scores and neurobehavioral scores ( P <0.01), reduced brain infarct volume ( P <0.01), decreased protein expression of CD32, IL-6, and IL-1β in the ischemic cortex ( P <0.01), and increased protein expression of CD206 and IL-10 in the ischemic cortex ( P <0.01). Compared with the VitD 3 group, the ESA group had lower neurological deficit score ( P <0.05), larger brain infarct volume ( P < 0.05), and lower protein expression of CD32, CD206, IL-1β, and IL-10 in the ischemic cortex ( P <0.01, P <0.05)., Conclusion: ESA could improve neurological function in MCAO rats, and its mechanism may be related to promoting microglial M1-to-M2 polarization and alleviating inflammatory damage.

Objective: To observe the effect of heat-tonifying needling on Keap1-Nrf2/ARE/HO-1 signal transduction pathway in knee synovium in rabbits with cold syndrome type rheumatoid arthritis (RA), so as to explore its mechanisms underl-ying improvement of RA., Methods: New Zealand rabbits were randomly divided into normal control, RA model, uniform reinforcing-reducing acupuncture, twisting reinforcing acupuncture and heat-tonifying acupuncture groups, with 6 rabbits in each group. The cold syndrome type RA model was established by subcutaneous injection of mixture fluid of ovalbumin and Freund's complete adjuvant at the shoulder-back as well as injection of mixture of ovalbumin and normal saline into knee-joint cavity combined with ice-compress freezing. Acupuncture stimulation (uniform reinforcing-reducing, or twisting reinforcing or heat-tonifying) was applied to bilateral "Zusanli"(ST36) for 1 min with the needle retained for 30 min, once a day for 7 consecutive days. The general conditions of rabbits in each group were recorded, the thermal pain threshold (TPT) and perimeter of knee joints was measured. Conditions of the synovium in the knee cavity, hydrops, blood flow signal, articular surface, and related muscles were observed by using a color Doppler ultrasonic diagnostic apparatus, and the blood flow signals inside the synovium (image scores) were divided into 0 (no signals), I (1 or 2 dot-like signal), II (less than half) ad III (more than half). After H.E. staining, the pathological changes (0-3 points) were assessed according to the state of inflammatory cell infiltration, and hyperplasia of synovial matrix and coating cells. The expression levels of Keap1, Nrf2, HO-1 and GSH-PX1 mRNAs in the knee synovium were detected by quantitative real-time PCR, and the expression of knee synovial HO-1 protein was measured by Western blot., Results: In comparison with the normal control group, the model group had a significant increase in the perimeter, pathological score, expression of Nrf2, HO-1 mRNAs and HO-1 protein ( P <0.05), and an obvious decrease in the TPT, expression levels of Keap1 and GSH-PX1 mRNAs ( P <0.05). Relevant to the model group, all the three acupuncture maneuvers reversed modeling-induced increase of perimeter and pathological score ( P <0.05), decrease of TPT and expression of GSH-PX1 mRNA( P <0.05), further down-regulated expression of Keap1 mRNA ( P <0.05), further up-regulated the expression of Nrf2, HO-1 mRNAs and HO-1 protein ( P <0.05). The heat-reinforcing manipulation was significantly superior to uniform reinforcing-reducing and twirling reinforcing manipulations in up-regulating TPT, and expression of Nrf2 mRNA, GSH-PX1 mRNA, HO-1 mRNA and protein ( P <0.05), and in down-regulating pathological score and Keap1 mRNA expression ( P <0.05)., Conclusion: Heat-tonifying, uniform reinforcing-reducing and twirling reinforcing needling manipulations may relieve pain and improve pathological state in RA rabbits, which may be associated with their functions in raising the ability of anti-oxidative stress by regulating Keap1-Nrf2/ARE/ HO-1 signaling pathway, the therapeutic effect of heat-tonifying needling is superior to that of uniform reinforcing-reducing and twirling reinforcing needling.

Sample pretreatment technology plays a vital role in the analysis of complex samples and is key to the entire analytical process. Its main purpose is to separate the substance to be measured from the sample matrix or interfering substances in the sample and to achieve a state in which the instrument can be analyzed and detected. Traditional sample pretreatment techniques include liquid-liquid extraction, liquid-solid extraction, precipitation separation, solvent volatilization-rotary evaporation, filtration, and centrifugation. However, the applications of these methods are limited by their low extraction efficiency, complicated operation, long time consumption, unstable recovery, use of large amounts of organic solvents, and large error rates. Several new sample pretreatment techniques, including solid-phase extraction, magnetic solid-phase extraction, solid-phase microextraction, and dispersive solid-phase extraction, have been developed and rapidly applied to various fields to overcome the shortcomings of traditional sample pretreatment methods. However, the development of adsorbent materials with high selectivity and enrichment capability remains a challenge in sample pretreatment technology, in which adsorbents with excellent adsorption performance are crucial. In recent years, various nanomaterials with remarkable properties have been introduced and applied to sample pretreatment, and numerous nano-extraction materials with diverse functions and high selectivity and enrichment capability have been developed. Hollow nanomaterials are nanoparticles with large voids in their solid shells. Owing to their advantageous properties, which include a large effective surface area, abundant internal space, low density, variety of preparation methods, structural and functional tailorability, short mass transmission path, and high carrying capacity, hollow nanomaterials show great application potential in sample pretreatment. The extraction mechanism of these materials is based on the synergistic effects of π-π stacking, electrostatic, hydrogen-bonding, and hydrophobic interactions to achieve the efficient separation and enrichment of the target analytes. Given their noteworthy physicochemical properties, hollow nanomaterials have gained wide attention in various research fields and are considered a research frontier in the field of materials science. Changing the structure or surface properties of the core and shell can lead to various hollow nanomaterials with unique properties. Such changes can create synergy between the physicochemical properties and structural function of the original core-shell material, leading to novel materials with superior performance compared with the starting materials and broad application prospects in sample pretreatment. Nevertheless, only a few hollow nanomaterials with diverse structures and functions are currently used for sample pretreatment, and their adsorption capacity for target analytes is often unsatisfactory. Consequently, enhancing the adsorption selectivity of these materials toward various analytes is the most important step in sample pretreatment. First, hollow nanomaterials with a large specific surface area and suitable pore size can be designed to achieve the specific adsorption of target analytes of varying sizes. The combination of hollow nanomaterials with other materials presenting desirable adsorption properties could also lead to synergistic effects and enhance the performance of composite hollow nanomaterials. In addition, more green methods to prepare hollow nanomaterials with outstanding selectivity can be explored to achieve the superior adsorption of a specific target analyte. Efforts to synthesize hollow nanomaterials have been met with great success, but the available synthesis methods still suffer from complicated steps, high costs, relatively harsh conditions, and the use of highly toxic substances. This paper summarizes the main types of hollow nanomaterials, their synthesis methods, and research progress on sample pretreatment technologies (solid-phase extraction, solid-phase microextraction, magnetic solid-phase extraction, and dispersive solid-phase extraction) and describes the challenges encountered in the synthesis of hollow nanomaterials. The applications and developments of hollow nanomaterials in sample pretreatment are also discussed.

When plates with edge cracks in the rolling process is straightened by cyclic tensile and compressive stress, the tip of edge crack always accompanied by stress concentration, which leads to crack propagation. In this paper, damage parameters are imported into the plate straightening model based on determining the GTN damage parameters of magnesium alloy materials by inverse finite element calibration method, the influence of different straightening process schemes and prefabricated V-shaped crack geometry on crack growth is analyzed through the way of the combination of simulation and straightening experiment. The results show that the peak values of equivalent stress and equivalent strain under each straightening roll appear at the crack tip. The value of longitudinal stress and equivalent stain decrease with the distance to crack tip becomes larger. The peak value of longitudinal stress appears when the crack circumferential angle is about 100°, and the crack tip is easy to form crack propagation; when the plate passes roll 2 and roll 4, the equivalent stress and strain concentration at the crack tip are most obvious; when the reduction reaches a certain degree, the void volume fraction (VVF) reaches the VVF of the material breaking; with the increase of the entrance reduction, the number of VVF at the crack tip which reaches the material fracture increases, and the length of crack propagation increases; the stress concentration at the tip of V-shaped crack with large length-width ratio is obvious, and the VVF is more likely to reach the VVF at the time of material fracture, crack initiates and propagates easily., (© 2023. The Author(s).)

Objective: To observe the effect of heat-reinforcing needling (HRN) on inflammatory factors and necrotizing apoptosis of synovial cells in synovial tissues of knee joint in rabbits with cold syndrome rheumatoid arthritis (RA), so as to explore its underlying mechanisms in treating RA., Methods: By using the random number table method, 40 New Zealand rabbits were randomly divided into normal, model, antagonist(AG), twist-reinforceing needling (TRN) and HRN groups, with 8 rabbits in each group. The model of cold syndrome RA was established by ovalbumin induction combined with Freund's complete adjuvant injection and cryogenic freezing method. In the AG group, the antagonist TAK-632 (25 mg/kg) was administered intragastrically, once every 2 days, for a total of 7 times. Rabbits of TRN and HRN groups were treated with corresponding acupuncture techniques on bilateral "Zusanli" (ST36) for 30 min, once a day for 14 days. After intervention, the changes of knee skin temperature and circumference were measured. Color Doppler ultrasound was used to observe the joint cavity effusion, synovial thickness and internal blood flow signal. The histomorphological changes of synovial tissues were observed after HE staining. ELISA was used to detect the contents of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in serum. Transmission electron microscope was used to observe the ultrastructure, necrosis and apoptosis of synovial cells. Western blot was used to detect the protein expressions of receptor-interacting protein kinase1 (RIPK1), RIPK3, mixed lineage kinase domain-like protein (MLKL), and phosphorylation （p）-MLKL in synovial tissues., Results: Compared with the normal group, the synovial was diffusely hyperplasia, joint cavity effusion and abnormal blood flow signal were obvious, inflammatory cells were clustered, arranged closely and disordered in the model group. The findings of transmission electron microscopy showed disruption of cell membrane integrity, swollen or ruptured mitochondria, obviously ruptured nucleus, condensed and pyknotic chromatin and nucleolus in the model group. Also, the skin temperature of the knee joint was significantly decreased ( P <0.01), while the circumference of the knee joint, the contents of TNF-α, IL-1β and IL-6 in serum, the protein expressions of RIPK1, RIPK3, p-MLKL and MLKL in synovial tissues were significantly increased ( P <0.01) in the model group. Compared with the model group, synovial tissue hyperplasia, joint cavity effusion, abnormal blood flow signals, synovial cell proliferation, inflammatory cell infiltration, disruption of cell membrane integrity, cell swelling, cell rupture, and nuclear pyknosis were reduced to different degrees in the AG, TRN and HRN groups. Additionally, the skin temperature of the knee joint was increased ( P <0.01, P <0.05), while the circumference of the knee joint, the contents of TNF-α, IL-1β and IL-6 in serum, the expressions of RIPK1, RIPK3, p-MLKL and MLKL in synovial tissues were decreased ( P <0.01, P <0.05) in the AG, TRN and HRN groups. The effects of HRN and AG were notably superior to that of TRN in up-regulating skin temperature of the knee joint, and down-regulating the circumference of the knee joint, the contents of TNF-α, IL-1β and IL-6 in serum, the expressions of RIPK1, RIPK3, p-MLKL and MLKL in synovial tissues ( P <0.01, P <0.05)., Conclusion: HRN can reduce synovial inflammation of knee joint in rabbits with cold syndrome RA, which may be related to its function in inhibiting the necrotizing apoptosis of synovial cells.

Backgroud: The ECG profile of Hypertrophic Cardiomyopathy (HCM) includes ST-segment elevation (STE) that may lead to misdiagnosis of acute ST-segment elevation myocardial infarction (STEMI). This pseudo-STEMI may bring non-essential treatment. We aimed to confirm the ECG differences between HCM featured with pseudo-STEMI and acute STEMI., Material and Methods: We retrospectively enrolled 59 HCM cases (Group A) and 56 acute STEMI cases (Group B). Based on the locations of STE, all the patients were divided into four subgroups, including HCM with STE in anterior leads (Group A1), anterior STEMI (Group B1), HCM with STE in inferior leads (Group A2) and inferior STEMI (Group B2). Several ECG parameters were compared between these subgroups., Results: ECG parameters significantly differed between these groups, especially the number of leads with TWI. We evaluated the diagnostic value of ECG profiles for those groups. ROC analysis showed that for Group A vs. Group B, number of leads with TWI showed the highest AUC value of 0.805 and its cutoff of 2.5, with 76.3% sensitivity and 76.8% specificity. For Group A1 vs. Group B1, it showed the highest AUC value of 0.801 and its cut-off point was 2.5, with 77.1% sensitivity and 79.1% specificity. For Group A2 vs. Group B2, it showed the highest AUC value of 0.822 and the cut-off value was 4.5, with 54.5% sensitivity and 92.3% specificity., Conclusion: ECG plays a valid tool to distinguish "Pseudo-STEMI" HCM from acute STEMI, especially number of leads with TWI., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To observe the effects of heat-reinforcing needling on synovial inflammation and microRNA-155 (miR-155)/Toll-like receptor 4 (TLR4)/nuclear transcription factor-κB (NF-κB) signaling axis, so as to investigate its anti-inflammatory mechanism in rabbits with cold syndrome of rheumatoid arthritis (RA)., Methods: A total of 36 rabbits were randomly divided into normal, model, agonist, inhibitor, heat-reinforcing needling (HRN) and agonist+heat-reinforcing needling (A+HRN) groups, with 6 rabbits in each group. The RA with cold syndrome model was induced by injecting ovalbumin dry powder and Freund's complete adjuvant combined with cold freezing. Rabbits in agonist group were intraperitoneally injected with miR-155 agomir 4.5 OD; rabbits in the inhibitor group were intraperitoneally injected with miR-155 antagomir 6.1 OD; rabbits in HRN group received heat-reinforcing needling at bilateral "Zusanli" (ST36) for 30 min；rabbits in A+HRN group received the same treatment as agonist group, and 30 min later, received the same treatment as the HRN group; rabbits in the normal and model groups were grasped and fixed in the same way, all groups received continuous treatment once a day for 7 d. After modeling, the knee joints of rabbits were examined by ultrasound, the pain threshold and the circumference were determined. After the interventions, the pain threshold and knee circumference were measured; the pathological morphology of synovial tissue of the knee joints were observed by HE staining; the mRNA levels of miR-155 and suppressor of cytokine signaling protein 1 (SOCS1), the expression levels of SOCS1, TLR4, NF-κB p65, interleukin (IL)-1β and IL-17A proteins in synovial tissue of knee joints were detected by real-time PCR and Western blot respectively., Results: Compared with the normal group, the pain threshold was significantly decreased ( P <0.05), and the knee circumference was significantly increased ( P <0.05); the synovial tissue of knee joints showed significant hyperplasia, abundant blood flow signal, joint cavity effusion and obvious inflammatory invasion, the pathological score was significantly increased ( P <0.05), the expressions of miR-155 mRNA and IL-1β, IL-17A, TLR4, NF-κB p65 proteins were significantly increased ( P <0.05), the expressions of SOCS1 mRNA and protein were significantly decreased ( P <0.05) in the model group. Compared with model group, the pain threshold was significantly increased ( P <0.05), the circumference of knee joint was significantly decreased ( P <0.05); in synovial tissue, the pathological score was decreased ( P <0.05), the expression levels of miR-155 mRNA and IL-1β, IL-17A, TLR4, NF-κB p65 proteins were significantly decreased ( P <0.05), and the expressions of SOCS1 mRNA and protein were significantly increased ( P <0.05) in inhibitor group and HRN group, while the above changes in agonist group were reversed ( P <0.05). Compared with the agonist group, the pain threshold was significantly increased ( P <0.05), the knee circumference was significantly decreased ( P <0.05), the synovial pathological score was significantly decreased ( P <0.05), the expressions of miR-155 mRNA and IL-1β, IL-17A, TLR4, NF-κB proteins in synovial tissue were significantly decreased ( P <0.05), and the expression levels of SOCS1 mRNA and protein were significantly increased ( P <0.05) in A+HRN group., Conclusion: The heat-reinforcing needling can increase the pain threshold, reduce the knee circumference and inhibit the inflammatory response in rabbits with RA cold syndrome. The possible mechanism is related to the regulation of miR-155/TLR4/NF-κB signaling axis.

Objective: To observe the effects of heat-reinforcing needling on the expression of purinergic ligand-gated ion channel 7 receptor(P2X7R)，Nodlike receptor protein 3(NLRP3) and Caspase-1 in synovium tissues of knee joint of rabbits with cold syndrome rheumatoid arthritis(RA)，so as to explore the anti-inflammatory mechanism of heat reinforcing needling in the treatment of RA., Methods: Thirty male New Zealand white rabbits were randomly divided into normal group, model group, reinforcing-reducing needling group(RRG), heat-reinforcing needling group(HRG), and antagonist group(AG), with 6 rabbits in each group.The model of cold syndrome RA was established by ovalbumin combined with Freund's adjuvant and cryogenic freezing. Rabbits of RRG and HRG were treated with corresponding acupuncture techniques on both sides of "Zusanli"(ST36) for 30 min, once a day for 7 days; Rabbits of the AG was intraperitoneally injected with A438079(2.5 mg/kg), once a day for 7 days. After intervention, color Doppler ultrasound was used to observe the joint cavity effusion, synovial thickness and internal blood flow signal.The histomorphological changes of synovial tissues were observed by HE staining. Quantitative real-time PCR method was used to detect the mRNA expression levels of P2X7R, NLRP3, and Caspase-1 in synovial tissues. Western blot was used to detect the protein expression of interleukin(IL)-1β, IL-6 and tumor necrosis factor(TNF)-α in synovial tissues., Results: Compared with the normal group, the synovial tissues in the model group was thickened, linear and punctate blood flow signals were increased, joint effusion was obvious, synovial coating cells were enlarged, the synovial matrix was severely hyperplasia, inflammatory cells infiltration was obvious.The mRNAs expression levels of P2X7R, NLRP3, Caspase-1 and IL-1β, IL-6, TNF-α proteins in synovial tissues were significantly increased( P <0.01). Compared with model group, abnormal blood flow signals, synovial thickness, joint effusion, proliferation of synovial matrix, inflammatory cell infiltration and synovial coating cells in the RRG, HRG and AG were improved. The mRNAs expression levels of P2X7R, NLRP3, Caspase-1 and IL-1β, IL-6, TNF-α proteins in synovial tissues were decreased in the RRG, HRG and AG ( P <0.05, P <0.01). Compared with the RRG, the above indexes were lower in the HRG and AG ( P <0.05, P <0.01).There was no significant difference in all indexes above between the HRG and AG ( P <0.01, P <0.05)., Conclusion: Heat reinforcing needling can improve synovial inflammation of RA, which may be related to regulating the expressions of P2X7R/NLRP3/Caspase-1 signaling pathway.

Objective: To observe the effect of scalp acupuncture on the expression of argarginine vasopressin receptor-1a(V 1a R), phosphorylated calmodulin-dependent protein kinase Ⅱ(p-CaMKⅡ), and aquaporin 4(AQP 4 ) at hypothalamus in middle cerebral artery occlusion (MCAO) rats, so as to explore the molecular mechanisms of scalp acupuncture reducing encepha-ledema in acute ischemic stroke., Methods: A total of 96 male SD rats were randomly divided into normal， model, inhibitor and scalp acupuncture groups, with 24 rats in each group. The MCAO model was established by thread occlusion method. The inhibitor group was intraperitoneally injected with V 1a R inhibitor (30 μg/kg)，once a day for 7 consecutive days. In the scalp acupuncture group, acupuncture was applied to bilateral "parietal and temporal anterior oblique line", with rapid insertion of 2 needles at 15° to 20°, twisting at 100 r/min for 1 min, and retaining the needles for 30 min, once a day for 7 consecutive days. The neurologic deficit score (NDS) and neurological score (NS) were evaluated before and after intervention. The positive expression of p-CaMKⅡ and AQP 4 proteins in hypothalamus was detected by immunohistochemistry. The water content of left brain tissue was determined by BIIiot method. The expression of V 1a R mRNA in hypothalamus was detected by real-time PCR., Results: Compared with the normal group, the NDS, NS, hypothalamic V 1a R mRNA expression, water content of the brain tissue, and hypothalamic p-CaMKⅡ and AQP 4 positive expression levels were significantly increased ( P <0.01) in the model group. Compared with the model group, the NDS, NS, hypothalamic V 1a R mRNA expression, water content of the brain tissue, and hypothalamic p-CaMKⅡ and AQP 4 positive expression levels were significantly decreased ( P <0.01) in the inhibitor and scalp acupuncture groups., Conclusion: Regulating the signaling pathway of V 1a R/CaMKⅡ/AQP 4 in hypothalamus may be one of the molecular mechanisms of scalp acupuncture reducing encephaledema in acute ischemic stroke.

Objective: To observe the impact of electro-scalp acupuncture (ESA) on the neural function and inflammatory response of ischemic cortex in the model rats with ischemic stroke and explore the anti-inflammation mechanism of ESA in treatment of ischemic stroke from the perspective of modulating the interleukin 12 (IL-12) mediated JAK (Janus kinase)/STAT (signal transduction and transcription activator) signal pathway., Methods: Ninety male SD rats were randomized into a normal group ( n =16) and a model preparation group ( n =74). In the model preparation group, the model of middle cerebral artery occlusion (MCAO) was duplicated with suture-occlusion method. After modeled successfully, 48 rats with neurological deficit score of 1-3 were divided into a model group, an inhibitor group and an ESA group, 16 rats in each one. In the inhibitor group, IL-12 inhibitor (apilimod, 5 mg/kg) was used via intragastric administration. In the ESA group, the anterior oblique line of vertex-temporal (MS6) was stimulated bilaterally with electric acupuncture, with disperse-dense wave, 2 Hz/100 Hz in frequency, 1 mA in current intensity. The needles were retained for 30 min. The treatment was given once daily and for 7 days in above two intervention groups. Before and after intervention, the neurological deficit score (NDS) and neurobehavioral score (NBS) were assessed in each group. HE staining method was adopted to observe the morphological manifestations of ischemic cortical lesion; the concentrations of IL-12 and IL-12R of the brain tissue in the ischemic cortical lesion were measured by enzyme-linked immunosorbent assay (ELISA); the mRNA expression levels of STAT4 and Tbx21 were detected by real-time PCR technique; and the protein expression of IL-2, tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IL-4 were detected using immunohistochemistry., Results: NDS and NBS in the model group, the inhibitor group and the ESA group were all higher than those in the normal group before intervention ( P <0.01). After intervention, NDS and NBS in the model group were higher than the normal group ( P <0.01); the two scores were all reduced when compared with those before intervention in the inhibitor group and the ESA group ( P <0.01), and lower than those of the model group ( P <0.01). NDS in the ESA group was lower than the inhibitor group ( P <0.05). In the model group, the cells were shrunk and vacuolated in the ischemic cortical lesion. Many normal cells were visible in the ESA group and the inhibitor group. Compared with the normal group, the concentrations of IL-12 and IL-12R , the mRNA expression levels of STAT4 and Tbx21 and the protein expression levels of IL-2, TNF-α and IFN-γ in brain tissue of ischemic cortical lesion were all increased in the model group ( P <0.01), while the protein expression level of IL-4 decreased ( P <0.01). The concentrations of IL-12 and IL-12R, the mRNA expression levels of STAT4 and Tbx21 and the protein expression levels of IL-2, TNF-α and IFN-γ were all reduced ( P <0.01), while the protein expression level of IL-4 increased ( P <0.01) in the ESA group and the inhibitor group when compared with the model group. The concentration of IL-12, the mRNA expression levels of STAT4 and Tbx21 and the protein expression levels of IL-2, TNF-α and IFN-γ in the ESA group were all higher than those of the inhibitor group ( P <0.05); while the concentration of IL-12R and the protein expression level of IL-4 were lower than the inhibitor group ( P <0.05)., Conclusion: Electro-scalp acupuncture may improve the neurological function of the rats with ischemic stroke. The modulation to IL-12 mediated JAK/STAT signaling pathway is the potential molecular mechanism of this therapy for the inflammatory response in ischemic cortical lesion.

Objective: To observe the effect of heat-reinforcing needling on the expression of serum inflammatory factors and autophagy of knee synovial tissue in rheumatoid arthritis (RA) rabbits with cold syndrome, so as to explore its mechanism of anti-inflammatory in the treatment of RA., Methods: Fifty rabbits were randomly divided into normal, model, heat-reinforcing needling, inhibitor and agonist groups ( n =10 rabbits in each group). The model of RA with cold syndrome was established by Freund's adjuvant and ovalbumin mixed solution injection combined with freezing and wind-cold dampness method. Heat-reinforcing needling was applied at "Zusanli" (ST36) for 30 min, once a day for 14 days. Rabbits of the inhibitor and agonist groups were given intraperitoneally injected with autophagy inhibitor 3-methyladenine (3-MA) or autophagy agonist rapamycin, once every 2 days for 7 days. The knee circumference and skin temperature of the rabbits in each group were measured. Color doppler ultrasonography was applied to examine the synovial membrane, joint effusion and blood flow signals in the knee joints of the rabbits in each group. Serum tumor necrosis factor (TNF) -α, interleukin (IL)-1β, IL-6 and C-creactive protein (CRP) were detected by ELISA. Transmission electron microscopy was applied to observe the ultrastructure and autophagosomes of synovial cells. The protein expressions of autophagy-related protein Atg5, serine/threonine protein kinase-dysregulated 51-like kinase 1 (ULK1), microtubule-associated protein light chain 3B (LC3B), and Beclin-1 were detected by Western blot. Fluorescence quantitative PCR was used to detect the mRNA expressions of NOD-like receptor 3 (NLRP3) and nuclear factor-κB (NF-κB)., Results: Compared with the normal group, the circumference of the knee joint was increased ( P <0.01), the skin temperature was decreased ( P <0.01), the knee joint synovium was thickened and the blood flow signal was abundant, the contents of serum TNF-α, IL-1β, IL-6, and CRP were increased ( P <0.01), the protein expressions of Atg5, ULK1, Beclin-1 and LC3BⅡ/LC3BⅠof synovial tissue were significantly decreased ( P <0.01), the mRNA expressions of NLRP3 and NF-κB were increased ( P <0.01) in the model group. In comparison with the model and inhibitor groups, the circumference of the knee joint was decreased ( P <0.01), whlie the skin temperature was increased ( P <0.01), the synovial membrane became thinner and the blood flow signal was wea-kened, the contents of TNF-α, IL-1β, IL-6 and CRP were decreased ( P <0.01), the protein expressions of Atg5, ULK1, Beclin-1 and LC3B Ⅱ/LC3B Ⅰ were increased ( P <0.01), and the mRNA expressions of NLRP3 and NF-κB were decreased ( P <0.01) in the heat-reinforcing needling and agonist groups., Conclusion: Heat-reinforcing needling can alleviate the inflammatory response of the knee joint synovium in RA rabbits with cold syndrome, which may be related to its function in enhancing the autophagy activity of synovial cells and inhibiting the synthesis and release of inflammatory factors TNF-α, IL-1β, IL-6 and CRP.

Ribose plays an important role in the process of life. Excessive ribose in the human cerebrospinal fluid or urine can be used as an early diagnostic marker of leukoencephalopathy. Fluorinated phenylboronic acid combined with 19 F NMR spectroscopy was a powerful method for molecular recognition. However, phenylboronic acid-based sensors for selective detection of ribose are rarely reported in the literature. In this study, the rapid and highly selective recognition of ribose was studied by 19 F NMR and 2-fluorophenylboric acid. It was found that 2-fluoro-phenylboric acid was an appropriate 19 F NMR-based sensor molecule for the determination of ribose under physiological conditions with high selectivity and robust anti-interference ability. When 2-fluorophenylboric acid was used for the detection of ribose in human urine without any sample pretreatment, a limit of detection of 78 μM was obtained at room temperature under given 19 F NMR experimental conditions (400 MHz, 512 scans, ca. 12 min), which can well meet the needs of practical application.

Objective: To compare the clinical therapeutic effect on acute ischemic stroke between Naochang Tongtiao acupuncture (acupuncture for brain-gut homology) and conventional acupuncture, and to explore the possible mechanism., Methods: A total of 64 patients with acute ischemic stroke were randomized into an observation group and a control group, 32 cases in each one. Basic western medical therapy was adopted in both groups. In the observation group, Naochang Tongtiao acupuncture was applied at anterior oblique line of vertex-temporal, Zhongwan (CV 12), Guanyuan (CV 4), Tianshu (ST 25), Zusanli (ST 36), Shangjuxu (ST 37) and Xiajuxu (ST 39). In the control group, conventional acupuncture was applied. The treatment was given once a day, 6 days a week for 3 weeks in both groups. Before and after treatment, National Institution of Health stroke scale (NIHSS) score, serum levels of interleukin-17 (IL-17) and hypersensitive C reactive protein (hs-CRP), and plasma level of trimethylamine oxide (TMAO) were compared in the two groups., Results: After treatment, NIHSS scores, serum levels of IL-17 and hs-CRP, and plasma levels of TMAO were decreased compared before treatment in both groups ( P <0.01), and those in the observation group were lower than the control group ( P <0.05)., Conclusion: Naochang Tongtiao acupuncture can improve the nerve function in patients with acute ischemic stroke, its therapeutic effect is superior to conventional acupuncture, the mechanism may relate to the regulation on inflammatory reaction and the level of intestinal flora metabolite.

The formation of polymeric micro-patterns on various substrates via a photolithography procedure has been widely used in semiconductor fabrication. Standard polymer patterns are usually fabricated via photosensitive polymer varnishes, in which large amounts of potentially harmful solvents with weight ratios over 50 wt% have to be removed. In the current work, a novel pattern-formation methodology via solvent-free electrospun photosensitive polymeric fibrous membranes (NFMs) instead of the conventional photosensitive solutions as the starting photoresists was proposed and practiced. For this purpose, a series of preimidized negative auto-photosensitive polyimide (PSPI) resins were first prepared via the two-step chemical imidization procedure from the copolymerization reactions of 3,3',4,4'-benzophenonetetracarboxylic- dianhydride (BTDA) and two ortho -methyl-substituted aromatic diamines, including 3,3',5,5'-tetramethyl-4,4'-diaminodiphenylmethane (TMMDA) and 3,7-diamino-2,8-dimethyl- dibenzothiophene sulfone (TSN). The derived homopolymer PI-1 (BTDA-TMMDA) and the copolymers, including SPI-2~SPI-6, with the molar ratio of 5~25% for TSN in the diamine units, showed good solubility in polar solvents. Then, a series of PSPI NFMs were fabricated via standard electrospinning procedure with the developed PSPI solutions in N,N -dimethylacetamide (DMAc) with a solid content of 25 wt% as the starting materials. The derived PSPI NFMs showed good thermal stability with 5% weight loss temperatures higher than 500 °C in nitrogen. Meanwhile, the derived PSPIs showed good photosensitivity to the ultraviolet (UV) emitting wavelengths of i-line (365 nm), g-line (405 nm) and h-line (436 nm) of the high-pressure mercury lamps in both forms of transparent films and opaque NFMs. Fine micro-patterns with a line width of around 100 μm were directly obtained from the representative SPI-4 NFM via standard photolithography procedure.

As a neurological disease with high morbidity, disability, and mortality, the pathological mechanism underlying stroke involves complex processes such as neuroinflammation, oxidative stress, apoptosis, autophagy, and excitotoxicity; but the related research on these molecular mechanisms has not been effectively applied in clinical practice. As a form of iron-dependent regulated cell death, ferroptosis was first discovered in the pathological process of cancer, but recent studies have shown that ferroptosis is closely related to the onset and development of stroke. Therefore, a deeper understanding of the relationship between ferroptosis and stroke may lead to more effective treatment strategies. Herein, we reviewed the mechanism(s) underlying the onset of ferroptosis in stroke, the potential role of ferroptosis in stroke, and the crosstalk between ferroptosis and other pathological mechanisms. This will further deepen our understanding of ferroptosis and provide new approaches to the treatment of stroke., 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 © 2022 Fang, Ding, Du, Wang and Li.)

The accuracy of sixteen commonly used internal reference genes was assessed in skeletal muscle-derived satellite cells of Qinchuan cattle at different stages of proliferation and induction of differentiation to determine the most suitable ones. Quantitative real-time PCR and three commonly used algorithmic programs, GeNorm, NormFinder and BestKeeper, were used to evaluate the stability of expression of the candidate internal reference genes (GAPDH, ACTB, PPIA, LRP10, HPRT1, YWHAZ, B2M, TBP, EIF3K , RPS9, UXT, 18S rRNA, RPLP0, MARVELD, EMD and RPS15A) in skeletal muscle-derived satellite cells at 0, 12, 24, 36 and 48 h of growth and after differentiation for 0, 2, 4, 6 and 8 days. The expression of two satellite cell marker genes, CCNA2 and MYF5, was used for validation analysis. The results of the software analyses showed that GAPDH and RPS15A were the most stable reference gene combinations during in vitro proliferation of bovine skeletal muscle-derived satellite cells, RPS15A and RPS9 were the most stable reference gene combinations during in vitro induction of differentiation of the cells, and PPIA was the least stable reference gene during proliferation and differentiation and was not recommended. This study lays the foundation for the selection of reference genes for qRT-PCR during the proliferation and induction of differentiation of bovine skeletal muscle-derived satellite cells., (© 2022. The Author(s).)

Few studies have comprehensively evaluated the impacts of microbial decomposing inoculants on greenhouse gas emissions and economic profit from paddy fields under different water regimes. Here, this study evaluated the effects of microbial decomposing inoculant treatments (straw returning without or with microbial decomposing inoculants (S and SMD)) on rice yield, CH 4 and N 2 O emissions, economic profit and net ecosystem economic profit (NEEP) from paddy fields under different water regimes (continuous flooding (CF) and alternate wetting and drying irrigation (AWD)) in central China with a two-year field experiment. Compared with S treatment, SMD treatment significantly increased the rice yield and crop water productivity by 6.6-7.2% and 5.6-7.9%, respectively. AWD treatment significantly enhanced the crop water productivity by 56.9-73.7% while did not affect rice yield relative to CF treatment. Regardless of water regimes, SMD treatment did not affect N 2 O emissions, but significantly increased CH 4 emissions by 13.8-39.6% relative to S treatment, resulting in a remarkable enhancement of global warming potential by 13.5-32.5%. Compared with S treatment, SMD treatment improved the economic profit and NEEP. By contrast, AWD treatment significantly increased N 2 O emissions by 19.1-64.8% compared with CF treatment, but significantly reduced CH 4 emissions by 35.3-79.1%. Accordingly, AWD treatment significantly decreased the global warming potential by 33.4-73.9% compared with CF treatment. In addition, AWD treatment resulted in 39.9-96.4% higher economic profit and 48.0-124.4% higher NEEP relative to CF treatment. In summary, AWD treatment is a sustainable water regime that can maintain rice yield, mitigate global warming potential, and increase economic income. However, regardless of water regimes, SMD treatment led to higher rice yield and economic profit, as well as higher global warming potential than S treatment, suggesting that other appropriate treatments of crop straw are needed to mitigate CH 4 emissions while improving economic profit for rice sustainable production., Competing Interests: Declaration of competing interest The authors report no declarations of interest., (Copyright © 2021. Published by Elsevier B.V.)

Lower respiratory tract infection (LRTI) induced by respiratory syncytial virus (RSV) is an important cause of hospitalization for infants. Compared with adults, infants are more likely to cause serious respiratory diseases after RSV infection due to the specific immature airway structure and immune system. The balance of immune resistance and immune tolerance of the host is critical to effective virus clearance and disease control. This paper reviews the relationship between RSV infection and respiratory diseases in infancy, the influence factors of the high pathogenicity of RSV infection in early life, as well as the research progress of anti-RSV therapy, and expands the specific molecular events regulating immune resistance and immune tolerance. We expect to present new ideas for the prevention and treatment of RSV-related respiratory diseases in clinical practice.

A counterbalance between immune cells and tumour cells is key to fighting tumours, and immune escape is an important mechanism for the survival of tumour cells in the body. Tumor cells and their cytokines impair the activity of T cells, NK cells, macrophages and other immune cells through various ways, and change the expression of their own surface antigens so as to avoid the clearance of the immune system. Changes in major histocompatibility complex molecules, high expression of programmed death-ligand 1, and the presence of immunosuppressive cells in the tumor microenvironment (TME) are main means by which tumors impair the function of immune cells. During the development of tumours of the digestive system, different mechanisms acting on tumour cells, the TME, and immune cells lead to immune escape and promote tumour progression. In this paper, the mechanisms of immune escape in tumour cells of the digestive system are reviewed to provide a theoretical basis for the immunotherapy of gastrointestinal tumours., 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.)

Objective: To observe the effects of penetrating technique of scalp acupuncture on emotion, sleep and function development in children of autism spectrum disorder (ASD)., Methods: A total of 60 SAD children aged 3 to 6 years were randomized in a control group (music education rehabilitation, n =30) and an observation group (penetrating technique of scalp acupuncture + music education rehabilitation, n =30). In the two groups, the treatment for 3 months was as 1 course, and 2 courses of treatment were required. Before and after treatment, the changes were observed in childhood autism rating scale (CARS), emotion regulation subscale (ER), children's sleep habits questionnaire (CSHQ) and children autism and psycho-educational profile for autistic and developmentally disabled children (C-PEP-3), separately., Results: Compared with the scores before treatment, CARS score, the score of each subscale of CSHQ, e.g. bedtime resistance, sleep onset delay, irregular sleep duration, sleep anxiety, parasomnias and daytime sleepiness as well as the total score of CSHQ were all reduced in children of two groups ( P <0.05); and the score of ER and C-PEP-3 were all increased ( P <0.05) after 6 months' treatment. Compared with the control group, ER score was increased in 3 and 6 months after treatment ( P <0.05), CARS score was reduced ( P <0.05) and C-PEP-3 score was increased obviously ( P <0.05) 6 months after treatment in the observation group; but the scores of the subscale for night waking and sleep disordered breathing did not changed noticeably (P > 0.05)., Conclusion: Penetrating technique of scalp acupuncture improves the emotion and sleep disorder and promotes the function development in ASD children.

Background: Patients with connective tissue disease, such as dermatomyositis (DM), and positive anti-TIF1γ self-antibodies are commonly diagnosed with malignant tumors as a comorbidity. The relationship between anti-TIF1γ self-antibodies and existing malignant tumors has been confirmed by several reports. However, interstitial pneumonia with autoimmune features (IPAF) cases with a positive anti-TIF1γ self-antibody developing to solid malignant tumors are rarely reported now., Case Presentation: Herein, we presented an IPAF patient with anti-TIF1γ self-antibodies. No evidence of malignant tumors was found at the initial visit. However, the patient had developed stage IVB lung squamous cell carcinoma at the 1-year follow-up review., Conclusions: Altogether, this report described a rare case of IPAF patient with anti-TIF1γ self-antibodies developed to advanced lung squamous cell carcinoma in 1 year. The present case highlights more frequent imaging examinations to identify the occurrence of malignant tumors as early as possible in IPAF patients with positive anti-TIF1γ self-antibodies.

Glucose is a significant analyte both in biology and biomedical science, it is of great importance to selectively detect glucose both in body fluids and complex mixture. In this study, a simple 19 F NMR based sensor was synthesized easily, which exhibited a high selectivity and robust anti-interference ability toward glucose detection both in a mixture containing up to 10 saccharides and human urine samples without any pretreatment. Combined with this sensor system, glucose could be well detected in human urine samples and the limit of detection was 0.41 mM by using a 400 MHz NMR spectrometer with 128 scans (ca. 4 min). This method had a potential for specific detection of glucose in complex mixture and diagnosis of diabetes mellitus related diseases in body fluid.

Full functioning of the airway physical barrier depends on cellular integrity, which is coordinated by a series of tight junction (TJ) proteins. Due to airway spasm, edema, and mucus obstruction, positive end-expiratory alveolar pressure (also termed auto-PEEP) is a common pathophysiological phenomenon, especially in acute asthma attack. However, the influence of auto-PEEP on small airway epithelial TJs is currently unclear. We performed studies to investigate the effect of extra pressure on small airway epithelial TJs and its mechanism. The results first confirmed that a novel mechanosensitive receptor, piezo-1, was highly expressed in the airway epithelium of asthmatic mice. Extra pressure induced the degradation of occludin, ZO-1 and claudin-18 in primary human small airway epithelial cells (HSAECs), resulting in a decrease in transepithelial electrical resistance (TER) and an increase in cell layer permeability. Through in vitro investigations, we observed that exogenous pressure stimulation could elevate the intracellular calcium concentration ([Ca 2+ ] i ) in HSAECs. Downregulation of piezo-1 with siRNA and pretreatment with BAPTA-AM or ALLN reduced the degradation of TJs and attenuated the impairment of TJ function induced by exogenous pressure. These findings indicate the critical role of piezo-1/[Ca 2+ ] i /calpain signaling in the regulation of small airway TJs under extra pressure stimulation., 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 Zhou, Zhou, Xu, Du, Li, Li, Zhang, Chen, Perelman and Kolosov.)

Objective: To observe the influence of scalp-acupuncture on the expression of pentraxin 3 (PTX3), Interleukin (IL)-1β, zonula occludens-1(ZO-1) mRNA and Occludin mRNA in striatum in acute ischemic cerebrovascular disease (AICD) rats, so as to investigate its mechanisms underlying improvement of AICD., Methods: Forty-eight male SD rats were randomly allocated to control, model, IL-1Ra and IL-1Ra+scalp-acupuncture groups ( n =12 rats in each group). The AICD model was established by occlusion of the middle cerebral artery (MCAO). Rats of the IL-1Ra group and IL-1Ra+scalp-acupuncture group received intraperitoneal injection of IL-1Ra (0.05 mg·kg -1 ·d -1 ), once daily for 6 days. Scalp acupuncture stimulation was applied to bilateral "Dingnieqianxiexian" (MS6) once daily for 6 days for rats in IL-1Ra+scalp-acupuncture group. Before and after intervention, the neurologic deficit score (NDS) was evalua-ted according to Longa's method. The expression of striatum PTX3 and IL-1β was detected by immunohistochemistry, and ZO-1 mRNA and Occludin mRNA in the striatum tissue were detected by fluorescence quantitative real-time PCR. The Evans Blue (EB) tracer method was used to monitor the degree of blood-brain barrier (BBB) damage., Results: Following modeling, the NDS, EB content and the expression of PTX3 and IL-1β in the striatum tissue were significantly increased, and the ZO-1 mRNA and Occludin mRNA expression was considerably decreased in the model group compared with the control group ( P <0.05). After the interventions and compared with the model group, the NDS, EB content in both IL-1Ra and IL-1Ra+scalp acupuncture groups, and PTX3 in the IL-1Ra group were significantly down-regulated ( P <0.05), while the striatum ZO-1 mRNA and Occludin mRNA expression in both IL-1Ra and IL-1Ra+scalp acupuncture groups, and PTX3 in the IL-1Ra+scalp acupuncture group were obviously up-regulated ( P <0.05), and the expression of IL-1β was obviously down-regulated in the IL-1Ra+scalp acupuncture group ( P <0.05) rather than in the IL-1Ra group ( P >0.05). The effects of scalp acupuncture combined with IL-1Ra were obviously superior to that of IL-1Ra in down-regulating NDS, EB content and IL-1β expression level, and in up-regulating PTX3, ZO-1 mRNA and Occludin mRNA expression levels ( P <0.05)., Conclusion: Scalp acupuncture can improve neurological function and reduce the degree of BBB injury in AICD rats, which may be associated with its function in up-regulating the expression of PTX3 and in promoting the expression of ZO-1 mRNA and Occludin mRNA.

Oversecretion of Mucin5ac (MUC5AC), which is primarily synthesized by goblet cells and is the major gel-forming mucin, is a hallmark of various pulmonary inflammatory diseases. Hypoxia is considered a common pathophysiologic feature in various pulmonary inflammatory diseases. It has been suggested that hypoxia-inducible factor 1α (HIF-1α) acts as a key factor in hypoxia-induced MUC5AC hypersecretion; however, the exact mechanisms that maintain the stability of HIF-1α and support oversecretion by airway epithelial cells under hypoxia are still unclear. With immunohistochemistry, we found overexpression of anterior gradient 2 (AGR2) in the bronchial epithelial cells of hypoxia-treated mice. With specific shRNA transduction, AGR2 was demonstrated to be a key factor in MUC5AC hypersecretion in vitro. Additionally, co-immunoprecipitation, cell immunochemistry and confocal microscopy experiments were performed to explore the interaction between HIF-1α and AGR2 during hypoxia-induced MUC5AC hypersecretion in vitro. The results indicated increased binding and intracytoplasmic colocation of HIF-1α and AGR2. Our findings suggest that AGR2 acts as a key regulator in hypoxia-induced airway MUC5AC hypersecretion by increasing the stability of HIF-1α. Additionally, the elevated expression of AGR2 induced by hypoxia in bronchial epithelial cells likely depends on an XBP-1-associated pathway., (Copyright © 2019. Published by Elsevier Inc.)

Objective: To observe the clinical effect of ZHENG ' Guo - Yan - Re needling technique for diabetic fundus hemorrhage., Methods: With before-after study design, 34 patients with diabetic eyeground hemorrhage were treated with basic treatment (oral administration of antidiabetic medication or insulin injections to ensure blood glucose in the normal range); in addition, acupuncture was given at bilateral Fengchi (GB 20), Taiyang (EX-HN 5), Jingming (BL 1), Cuanzhu (BL 2), Sanyinjiao (SP 6) and Hegu (LI 4). The ZHENG ' Guo - Yan - Re needling technique was applied at Fengchi (GB 20); the heat reinforcing needling technique was applied at Taiyang (EX-HN 5); the slow needle insertion technique was applied at Jingming (BL 1); and the Xique - Dengmei needling technique was applied at Cuanzhu (BL 2); the neutral supplementation and draining method was applied at remaining acupoints. The acupuncture was given once a day, 6 times as one course, and totally 4 courses were given with an interval of 1 day between courses. The follow-up visit was 6 months after treatment. The TCM symptom scores, fundus examination results and vision improvement were observed before and after treatment, and the effect was observed., Results: Compared before treatment, the visual acuity, TCM symptom scores, fundus microaneurysm and hemorrhage points in 34 patients (68 eyes) were significantly improved after treatment ( P <0.05). The total effective rate was 88.2% (60/68) after treatment; at follow-up visit, the visual acuity, TCM symptom scores and fundus pathological changes were all improved ( P <0.05) and stable at the post-treatment level ( P >0.05)., Conclusion: ZHENG ' Guo - Yan - Re needling technique could improve symptoms, promote the absorption of fundus hemorrhage, and improve vision in patients with diabetic fundus hemorrhage.

Objective: To observe the influence of scalp acupuncture on cerebral infarct size and expression of IL-10, IL-6, and IL-1β in the para-hippocampal gyrus in acute ischemic cerebrovascular disease(AICD) rats, so as to investigate its mechanisms underlying improvement of AICD., Methods: Forty-eight male SD rats were randomly allocated to normal control (control), AICD model, medication, and scalp acupuncture groups ( n ＝12 per group). The AICD model was established by occlusion of the middle cerebral artery (MCAO). Rats of the medication group received intraperitoneal injection of Ammonium 1-Pyrrolidinedithiocarbamate (APDC, 100 mg•kg －1 •d －1 ), once daily for 7 days. Scalp acupuncture stimulation was applied to bilateral "Dingnieqianxiexian" (MS6) once daily for 7 days. Before and after intervention, the neurologic deficit score (NDS) and the neurological score (NS) were evaluated according to Longa's and Schäbitz's methods, respectively. At the end of the intervention, the para-hippocampal gyrus and whole brain were collected respectively. The expression levels of IL-10, IL-6 and IL-1β in the para-hippocampal gyrus tissue were detected by immunohistochemistry, and the cerebral infarct volume of the brain was detected by triphenyltetrazollium chloride (TTC) staining after sectioning., Results: Following modeling, the NDS, NS and the expression of IL-10, IL-6 and IL-1β in para-hippocampal gyrus were significantly increased in the model group compared with the control group ( P <0.01). After the intervention, the NDS, NS and infarct volume, and the expression levels of IL-6 and IL-1β in the para-hippocampal gyrus were significantly decreased in both medication and scalp acupuncture groups compared with the model group ( P <0.05), and the expression of IL-10 was further obviously up-regulated in the scalp acupuncture group ( P <0.05) rather than in the medication group ( P >0.05). The effect of scalp acupuncture was obviously superior to that of medication in up-regulating IL-10 expression level ( P <0.05). No significant differences were found between the medication and scalp acupuncture groups in the levels of NDS, NS, infarct volume, IL-6 and IL-1β proteins ( P >0.05)., Conclusion: Scalp acupuncture can improve neurological function and reduce infarct volume in AICD rats, which may be associated with its function in up-regulating the expression of IL-10 and in inhibiting the expression of IL-6 and IL-1β to reduce inflammation reaction.

Objective: To observe the effect of scalp-acupuncture intervention on the expression of Interleukin (IL)-10 mRNA, IL-6 mRNA and tumor necrosis factor (TNF) - α in the parahippocampal gyrus of cerebral ischemia (CI) rats, so as to explore its molecular mechanisms underlying improvement of CI., Methods: A total of 64 male SD rats were randomized into normal control, model, medication and scalp-acupuncture groups ( n ＝16 rats in each group). The focal CI model was established by middle cerebral artery occlusion. Intraperitoneal injection of Ammonium Pyrrolidine Dithiocarbamate (100 mg•kg －1 •d －1 ) was administrated for rats in the medication group, once a day for 7 days. For rats of the scalp-acupuncture group, the acupuncture needles were rapidly inserted into bilateral Dingnieqianxiexian (MS6), followed by twirling the needles at 100 cycles/min for 1 min, once again every 10 min during 20 min' needle retention. The treatment was conducted once a day for 7 days. The neurologic deficit score (0－4 points, impaired consciousness, death, etc.) and neurological function score (motor, sensory and sensory tests, 0－10 points) were assessed according to Longa's (1989) and Schabitz's (2004) methods, respectively. The expression levels of IL-10 mRNA and IL-6 mRNA were detected by fluorescence quantitative PCR, and the expression of TNF-α was detected by immunohistochemistry., Results: After modeling, the neurologic deficit and neurological function scores and the expression levels of IL-10 mRNA, IL-6 mRNA and TNF-α protein in the parahippocampus were significantly increased in the model group than in the normal control group ( P <0.01). Following the intervention, the neurologic deficit and neurological function scores as well as IL-6 mRNA and TNF-α protein expression were significantly down-regulated in both scalp-acupuncture and medication groups ( P <0.05), and the expression of IL-10 mRNA was obviously increased ( P <0.05) relevant to the model group., Conclusion: Scalp-acupuncture can improve neurologic function in CI rats, which is related to its effects in up-regulating the expression of IL-10, then down-regulating the expression of IL-6 and TNF-α (reducing inflammatory response) in the parahippocampal gyrus.

Objective: To observe the effect of scalp-acupuncture intervention on the expression of parahippocampal factor-κB p 65 mRNA (NF-κB p 65 mRNA), IκB mRNA, interleukin-1 β (IL-1 β) and tumor necrosis factor-α (TNF-α) in rats with cerebral ischemia (CI), so as to investigate its molecular mechanisms underlying improving CI by reducing inflammatory response., Methods: A total of 64 SD rats were randomized into normal control, model, medication and scalp-acupuncture groups, with 16 rats in each group. The focal CI model was established by middle cerebral artery occlusion (MCAO). Intraperitoneal injection of Pyrrolidine Dithiocarbamate (100 mg•kg －1 •d －1 ) was administrated for rats in the medication group, once a day for 7 days. For rats of the scalp-acupuncture group, the acupuncture needles were rapidly inserted into bilateral Dingnieqianxiexian (MS 6) and Dingniehouxiexian (MS 7), followed by twirling the needles at 200 cycles/min for 1 min, once again every 10 min during 30 min's needle retention. The treatment was conducted once a day for 7 days. The neurologic deficit score (0－5 points, impaired consciousness, death, etc.) and neurological function score (motor, sensory and sensory tests, 0－10 points) were assessed according to Longa's (1989) and Schäbitz's (2004) methods, respectively. The expression levels of NF-κB p 65 mRNA and IκB mRNA in the parahippocampus gyrus tissue were detected by fluorescence quantitative reverse transcription-PCR, and IL-1 β and TNF-α proteins in the parahippocampus gyrus tissue were detected by immunohistochemistry., Results: After modeling, the neurologic deficit and neurological function scores and the expression levels of NF-κB p 65 mRNA, IL-1 β and TNF-α in the parahip-pocampus were significantly increased in the model group than in the normal group ( P <0.01), while the expression of IκB mRNA was considerably down-regulated ( P <0.01). Following treatment intervention, the neurologic deficit and neurological function scores as well as NF-κB p 65 mRNA, and IL-1 β and TNF-α protein expression were significantly decreased in both scalp-acupuncture and medication groups compared with the model group ( P <0.05, P <0.01), and the decreased expression of IκB mRNA was obviously increased ( P <0.05)．., Conclusion: Scalp-acupuncture can improve neurologic function in cerebral ischemic rats, which is related with its effects in up-regulating the expression of IκB to inhibit the dissociation of NF-κB, then decreasing the expression of IL-1 β and TNF-α (reducing inflammatory response) in the parahippocampal gyrus tissue.

Saxifragifolin D (SD), a traditional Chinese medicine, is a pentacyclic triterpenoid compound first isolated from Androsace umbellata. Various plant triterpenoids have been reported to exhibit antitubercular activity. In this study, THP-1-derived macrophages were infected with an attenuated M. tuberculosis (M.tb) strain, H 37 Ra. Intracellular replication of M.tb was evaluated by counting the colonies after 4 weeks of incubation. The results indicated that SD treatment reduced the intracellular replication of M.tb in THP-1-derived macrophages but not in A549 cells. We performed a phagosome maturation test using confocal microscopy and found that SD treatment partially attenuated the phagosome arrest induced by M.tb infection. These effects were dependent on a VPS34-associated pathway. Immunoprecipitation assays showed that SD increased intracellular UVRAG-linked VPS34, the active VPS34 complex II. However, SD had no effect on the total VPS34 pool. Moreover, the results indicated that the SD-mediated increase in VPS34 complex II activity was mediated by an AMPK-dependent pathway. Collectively, these data indicate that SD may be a promising candidate for treatment of M.tb.

Objective: To explore the specific mechanism of heat-reinforcing needling (HRN) for rheumatoid arthritis (RA) rabbits with cold syndrome based on metabolomics., Methods: A total of 40 healthy rabbits were randomly divided into a normal group, a model group, a reinforcing-reducing needling(RRN) group, a twirling-reinforcing needling (TRN) group and a HRN group ( n =8 rabbits/group). The RA model with cold syndrome was established with ovalbumin and freezing. Except the normal and model groups, RRN, TRN and HRN were given at "Zusanli" (ST 36) in the corresponding acupuncture groups for 30 min, once a day for 7 days. After the interventions, the pain threshold and the local skin temperature of each group were observed. The endogenous metabolites in the serum were analyzed by the gas chromatography mass spectrometry (GC-MS) technology combined with the pattern-recognition method., Results: The pain threshold and the local skin temperature in the model group were lower than those in the normal group ( P <0.05). The pain thresholds and the local skin temperatures in the three acupuncture groups were higher than those in the model group after interventions ( P <0.05), and those in the HRN group were obviously higher than those in the RRN and TRN groups ( P <0.05). The serum metabolites of leucine, valine, isoleucine, and arachidonic acid in the model group were increased compared with those in the normal group ( P <0.05), and the metabolites of α-ketoglutaric acid, citric acid, succinic acid, glucose, inositol, palmitic acid, stearic acid, lactose, d-ribose, and D-mannose were decreased ( P <0.05). The above-mentioned metabolites in the three acupuncture groups were significantly reversed relevant to the model group ( P <0.05), and the effect of HRN group was significantly superior to those of the RRN and TRN groups in regulating α-ketoglutaric acid, citric acid, succinic acid, glucose, inositol, d-ribose, and D-mannose ( P <0.05)., Conclusions: HRN for RA with cold syndrome is effective, which may be related to the specific regulation for the krebs cycle and glycometabolism.

Mussel-inspired approach was attempted to non-covalently functionalize the surfaces of boron nitride (BN) with self-polymerized dopamine coatings in order to reduce the interfacial thermal barrier and enhance the thermal conductivity of BN-containing composites. Compared to the polypropylene (PP) composites filled with pristine BN at the same filler content, thermal conductivity was much higher for those filled with both functionalized BN (f-BN) and maleic anhydride grafted PP (PP-g-ma) due to the improved filler dispersion and better interfacial filler-matrix compatibility, which facilitated the development of more thermal paths. Theoretical models were also applied to predict the composite thermal conductivity in which the Nielsen model was found to fit well with the experimental results, and the estimated effective aspect ratio of fillers well corresponded to the degree of filler aggregation as observed in the morphological study., Competing Interests: The authors have declared that no competing interests exist.

Objective: To observe the influence of scalp-acupuncture on the expression of acid-sensing ion channels (ASICs) 1 a and 2 b of hippocampal CA 1 region in cerebral ischemia (CI) rats, so as to investigate its mechanism underlying improvement of ischemic stroke., Methods: Thirty-two male SD rats were randomly allocated to normal control, model, scalp-acupuncture and Amiloride group ( n =8 in each group). The model of focal CI was established by middle cerebral artery occlusion (MCAO). Scalp acupuncture stimulation was applied to bilateral Dingnieqianxiexian (MS 6) and Dingniehouxiexian (MS 7), once daily for 7 days. Rats of the Amiloride group were fed with Amiloride solution, twice a day for 7 days, and those of the normal control and model groups were grabbled and fixed in the same way with the acupuncture and Amiloride groups. The neurological deficit score was given according to Longa's method. The expression of hippocampal ASIC 1 a and ASIC 2 b was detected by immunohistochemistry, and the Ca 2+ concentration in the hippocampal tissue assayed using flowing cytometry., Results: After the intervention, the neurological deficit score of both the scalp-acupuncture and Amiloride groups were significantly decreased in comparison with pre-treatment ( P <0.01), and the effect of scalp-acupuncture was markedly superior to that of Amiloride in reducing neurological deficit score ( P <0.05). The expression of ASIC 1 a and ASIC 2 b in the hippocampal CA 1 region and hip-pocampal Ca 2+ concentration were significantly up-regulated in the model group compared with the normal control group ( P <0.01), and obviously down-regulated in both scalp-acupuncture and Amiloride groups ( P <0.01, P <0.05),without significant differences between the two treatment groups in the ASIC 1 a and ASIC 2 b expression and Ca 2+ concentration ( P >0.05)., Conclusions: Scalp-acupuncture stimulation can improve neurological function in CI rats, which may be related to its effects in suppressing the increased expression of hippocampal ASIC 1 a and ASIC 2 b proteins and in reducing calcium overload in hip-pocampal neurocytes.

Fibroblast-like synoviocytes (FLS) with aberrant expression of microRNA (miRNA) are critical pathogenic regulators in rheumatoid arthritis (RA). Previous studies have found that overexpression or silencing of miRNA can contribute to the development of miRNA-based therapeutics in arthritis models. In this study, we explored the effects of miR-27a on cell migration and invasion in cultured FLS from RA patients. We found that miR-27a was markedly downregulated in the serum, synovial tissue, and FLS of RA patients. Meanwhile, the expression of follistatin-like protein 1 (FSTL1) was upregulated, which suggests that FSTL1 plays a key role in RA development. The results of a Transwell assay showed that miR-27a inhibited FLS migration and invasion. However, miR-27a inhibition promoted the migration and invasion of FLS. In addition, the down-regulated expression of matrix metalloproteinases (MMP2, MMP9, and MMP13) and Rho family proteins (Rac1, Cdc42, and RhoA) was detected after treatment with miR-27a in RA-FLS by quantitative reverse transcription-PCR and western blot analysis. Then, a luciferase reporter assay validated that miR-27a targeted the 3-untranslated region (3'-UTR) of FSTL1. Moreover, miR-27a caused a significant decrease of FSTL1. In addition, the expression of TLR4 and NFκB was inhibited by miR-27a but increased by FSTL1 overexpression. In conclusion, we found that miR-27a inhibited cell migration and invasion of RA-FLS by targeting FSTL1 and restraining the TLR4/NFκB pathway.

Objective: To observe influences of heat-reinforcing needling (HRN) on scores of traditional Chinese medicine (TCM) symptoms and expression of plasma ATP synthase subunit O ( Atp 5 O ) mRNA and lysosomal V 1 subunit B 2 ( Atp 6 V 1 B 2 ) mRNA in patients with wind-cold-damp retention type rheumatoid arthritis (RA), so as to investigate its biological mechanisms in "heat production"., Methods: Sixty wind-cold-damp retention type RA patients were randomly allocated to HRN group ( n =30) and control group ( n =30). Guanyuan (CV 4), Qihai (CV 6), bilateral Zusanli (ST 36), and local acupoints near the knee-joint were selected for needling stimulation. Patients of the HRN group were treated by manipulating the acupuncture needle with HRN, and those of the control group treated by manipulating the needle with uniform reinforcing-reducing method. The treatments were performed once daily, 5 days a week, and two weeks altogether. The other 30 healthy volunteers were recruited as the normal control group. The TCM symptom scoring system (0-31 points, 11 items as the severities of pain, swelling and tenderness of the knee-joint) was used to evaluate the status of RA, and quantitative real-time PCR (RT-PCR) was used to detect the expression of plasma Atp 5 O mRNA and Atp 6 V 1 B 2 mRNA following removal of red blood cells., Results: After the treatment, the TCM scores of both the HRN and control groups were significantly decreased ( P <0.05), and that of the HRN group was significantly lower than that of the control group ( P <0.05). Before the treatment, the expression levels of plasma Atp 5 O mRNA and Atp 6 V 1 B 2 mRNA in RA patients were significantly lower than those of the normal group ( P <0.05), and after the treatment, the expression levels of plasma Atp 5 O mRNA and Atp 6 V 1 B 2 mRNA were significantly increased in both HRN and control groups compared to pre-treatment in the same one group ( P <0.05), and the up-regulated Atp 5 O mRNA and Atp 6 V 1 B 2 mRNA levels were remarkably higher in the control group than in the HRN group ( P <0.05)., Conclusions: Both heat-producing needling and uniform reinforcing-reducing needling can improve RA patients' clinical symptoms, which may be associated with their actions in up-regulating expressions of plasma Atp 5 O mRNA and Atp 6 V 1 B 2 mRNA.

Data mining has the potential to provide information for improving clinical acupuncture strategies by uncovering hidden rules between acupuncture manipulation and therapeutic effects in a data set. In this study, we performed acupuncture on 30 patients with hemiplegia due to acute ischemic stroke. All participants were pre-screened to ensure that they exhibited immediate responses to acupuncture. We used a twirling reinforcing acupuncture manipulation at the specific lines between the bilateral Baihui (GV20) and Taiyang (EX-HN5). We collected neurologic deficit score, simplified Fugl-Meyer assessment score, muscle strength of the proximal and distal hemiplegic limbs, ratio of the maximal H-reflex to the maximal M-wave (Hmax/Mmax), muscle tension at baseline and immediately after treatment, and the syndromes of traditional Chinese medicine at baseline. We then conducted data mining using an association algorithm and an artificial neural network backpropagation algorithm. We found that the twirling reinforcing manipulation had no obvious therapeutic difference in traditional Chinese medicine syndromes of "Deficiency and Excess". The change in the muscle strength of the upper distal and lower proximal limbs was one of the main factors affecting the immediate change in Fugl-Meyer scores. Additionally, we found a positive correlation between the muscle tension change of the upper limb and Hmax/Mmax immediate change, and both positive and negative correlations existed between the muscle tension change of the lower limb and immediate Hmax/Mmax change. Additionally, when the difference value of muscle tension for the upper and lower limbs was > 0 or < 0, the difference value of Hmax/Mmax was correspondingly positive or negative, indicating the scalp acupuncture has a bidirectional effect on muscle tension in hemiplegic limbs. Therefore, acupuncture with twirling reinforcing manipulation has distinct effects on acute ischemic stroke patients with different symptoms or stages of disease. Improved muscle tension in the upper and lower limbs, reflected by the variation in the Hmax/Mmax ratio, is crucial for recovery of motor function from hemiplegia.

Objective: To observe the influence of scalp acupuncture on levels of high-sensitivity C-reactive protein (hs-CRP), TNF-α, IL-6, and IL-1β levels in patients with acute cerebral infarction (ACl), so as to investigate its mechanism underlying improvement of ACI., Methods: A total of 61 patients with ACI were randomly allocated to scalp acupuncture group (n = 31) and control (medication) group (n = 30). The patients of the control group were routinely treated by administration of Aspirin, Danhong injection, Cytidine Diphosphate for neurotrophy, blood pressure-control and blood-fat lowering medicines, etc., while those of the scalp acupuncture group were treated by routine treatment with the medicines mentioned above plus daily scalp acupuncture stimulation of bilateral Dingnieqianxiexian [MS 6, penetrative needling from Qianding (GV 21) to Xuanli (GB 6)] and Dingniehouxiexian [MS 7, from Baihui (GV 20) to Qubin (GB 7)]. The treatment was conducted once daily for 7 days. Serum hs-CRP, TNF-α, IL-6, and IL-1β contents were assayed by using enzyme linked immunosorbnent assay (ELISA). The therapeutic effects of scalp acupuncture were evaluated by using clinical neurological disfunction scale (NDS, 0-45 points for consciousness, gazing, facial palsy, speech, myodynamia, walking-ability)., Results: (1) Of the 30 and 31 cases in the control and scalp acupuncture groups, 5 (16.7%) and 8 (25.8%) were basically controlled, 9 (30.0%) and 16 (51.6%) experienced remarkable improvement in their symptoms, 12 (40.0%) and 6 (19.4%) were improved, 4 (13.3%) and 1(3.2%) failed, with the effective rates being 86.7% and 96.8%, respectively. The increased levels of serum hs-CRP, TNF-α, IL-6 and IL-1β in ACl patients were reversed on the 3rd and 7th day after scalp acupuncture treatment (P < 0.05, P < 0.01). (2) A positive correlation existed between the NDS score and the serum levels of hs-CRP (r = 0.497, P < 0.01). (3) NDS scores were obviously decreased in both groups on the 7th day after the treatment compared with their baseline data (P < 0.05, P < 0.01)., Conclusion: Scalp acupuncture treatment can improve the ACI patients' clinical symptoms, probably by reducing ACl induced inflammatory reactions.

Ischemic stroke is one of the commonly met diseases in clinical practice nowadays. Acupuncture therapy is widly used in the treatment of sequela of ischemic stroke in China and its mechanisms have been extensively studied in recen years. In the present paper, the authors focus on the development of studies on the mechanism of scalp acupuncture therapy in the treatment of ischemic stroke. Results indicate that scalp acupuncture intervention can 1) improve cerebral blood circulation to promote regional energy metabolism, 2) up-regulate expression of glial cell-line derived neurotrophic factor (GDNF), etc., possibly promoting proliferation and differentiation of neural stem cells in the focal cerebral cortex and hippocampus, 3) reduce contents of excitatory amino acid and increase level of gamma-aminobutyric acid (GABA) to lower neurogenic toxicity, and relieve cerebral injury, 4) ease cerebral vascular immunoinflammatory reactions, 5) regulate blood lipid metabolism to resist cerebral free radical damage, and 6) inhibit cerebral cortical apoptosis. However, these results only revealed very limited intrinsic mechanisms of scalp acupuncture in improving ischemic stroke. Further studies using comprehensive techniques of multi-disciplines as molecular biology, electrophysiology, etc. are definitely needed.