Search

Teng-Jiao Zhang,1,2 Jing-Jing Zhang,1,2 Zong-Yang Qu,1,2 Hong-Ye Zhang,1,2 Yong Qiu,1,2 Zhen Hua1,2 1Department of Anesthesiology, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China; 2Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Zhen HuaDepartment of Anesthesiology, Beijing Hospital, National Center of Gerontology, No. 1 Dahua Road, Beijing 100730, People’s Republic of ChinaTel/Fax +86 10 8513 6409Email huazhen3038@bjhmoh.cnPurpose: Erector spinae plane block (ESPB) is a newly reported interfascial plane block in pain management, and it can block the nerves exactly in line with the area of the posterior lumbar surgery. The objective of this research was to determine the effectiveness of pre-operative ESPB in enhancing recovery of posterior lumbar surgery.Patients and Methods: A total of 60 patients undergoing open posterior lumbar decompression surgery under general anesthesia were randomized into two groups. T12 group was performed pre-operatively bilateral ESPB with ropivacaine at the T12 level, but control group did not receive the block. The primary outcome was the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) score at 10 minutes after extubation. Secondary outcomes included intraoperative sufentanil consumption, postoperative morphine consumption, first time to ambulation after surgery and hospital length of stay after surgery. All participants were followed up to hospital discharge.Results: The mean (SD) MOAA/S scores at 10 minutes after extubation were 4.2 (95% CI, 4.0 to 4.4), and 3.4 (95% CI, 3.2 to 3.6) in the T12 and control groups (P < 0.001), respectively. Intraoperative sufentanil consumption (P =0.007) and postoperative morphine consumption (P =0.003) were lower in the T12 group than in the control group. Although first time to ambulation after surgery was sooner in the T12 group than in the control group (P =0.003), hospital length of stay was similar (P=0.054).Conclusion: Pre-operative bilateral ESPB at T12 can enhance recovery after posterior lumbar surgery and reduce perioperative opioid consumption.Keywords: posterior lumbar surgery, erector spinae plane block, enhanced recovery after surgery, regional anesthesia

Precision measurements by the Alpha Magnetic Spectrometer (AMS) on the International Space Station of the deuteron (D) flux are presented. The measurements are based on 21×10^{6} D nuclei in the rigidity range from 1.9 to 21 GV collected from May 2011 to April 2021. We observe that over the entire rigidity range the D flux exhibits nearly identical time variations with the p, ^{3}He, and ^{4}He fluxes. Above 4.5 GV, the D/^{4}He flux ratio is time independent and its rigidity dependence is well described by a single power law ∝R^{Δ} with Δ&#95;{D/^{4}He}=-0.108±0.005. This is in contrast with the ^{3}He/^{4}He flux ratio for which we find Δ&#95;{^{3}He/^{4}He}=-0.289±0.003. Above ∼13  GV we find a nearly identical rigidity dependence of the D and p fluxes with a D/p flux ratio of 0.027±0.001. These unexpected observations indicate that cosmic deuterons have a sizable primarylike component. With a method independent of cosmic ray propagation, we obtain the primary component of the D flux equal to 9.4±0.5% of the ^{4}He flux and the secondary component of the D flux equal to 58±5% of the ^{3}He flux.

Mulching to conserve moisture has become an important agronomic practice in saline soil cultivation, and the effects of the dual stress of salinity and microplastics on soil microbes are receiving increasing attention. In order to investigate the effect of polyethylene microplastics on the microbial community of salinized soils, this study investigated the effects of different types (chloride and sulphate) and concentrations (weak, medium, and strong) of polyethylene (PE) microplastics (1% and 4% of the dry weight mass of the soil sample) on the soil microbial community by simulating microplastic contamination in salinized soil environments indoors. The results showed that:PE microplastics reduced the diversity and abundance of microbial communities in salinized soils and were more strongly affected by sulphate saline soil treatments. The relative abundance of each group of bacteria was more strongly changed in the sulphate saline soil treatment than in the chloride saline soil treatment. At the phylum level, the relative abundance of Proteobacteria was positively correlated with the abundance of fugitive PE microplastics, whereas the relative abundances of Bacteroidota, Actinobacteriota, and Acidobacteria were negatively correlated with the abundance of fugitive PE microplastics. At the family level, the relative abundances of Flavobacteriaceae, Alcanivoracaceae, Halomonadaceae, and Sphingomonasceae increased with increasing abundance of PE microplastics. The KEGG metabolic pathway prediction showed that the relative abundance of microbial metabolism and genetic information functions were reduced by the presence of PE microplastics, and the inhibition of metabolic functions was stronger in sulphate saline soils than in chloride saline soils, whereas the inhibition of genetic information functions was weaker than that in chloride saline soils. The secondary metabolic pathways of amino acid metabolism, carbohydrate metabolism, and energy metabolism were inhibited. It was hypothesized that the reduction in metabolic functions may have been caused by the reduced relative abundance of the above-mentioned secondary metabolic pathways. This study may provide a theoretical basis for the study of the effects of microplastics and salinization on the soil environment under the dual pollution conditions.

Dachaihu Decoction is a classic prescription with the function of harmonizing Shaoyang and purging away internal stasis of heat, which was specially developed by Master ZHANG Zhongjing for the concurrent disease of Shaoyang and Yangming. A large number of international studies have shown that Dachaihu Decoction has liver protection, gallbladder benefit, anti-inflammatory, and other pharmacological effects and is mostly used in modern clinical treatment of acute pancreatitis, acute cholecystitis, cholelithiasis, and other digestive diseases. This paper combined bibliography and statistics and selected the ancient book database and CNKI database to search the relevant literature on Dachaihu decoction, verify the composition and dosage, processing method, main diseases, and modern clinical application, and predict its quality markers(Q-markers) based on the &quot;five principles&quot; of Q-markers. The results suggest that saikosaponin a, baicalin, and 6-gingerol can be selected as potential Q-markers for Dachaihu Decoction, so as to provide a basis for the clinical research of traditional Chinese medicine and the development and application of compound preparations.

Introduction: The root of Bupleurum scorzonerifolium Willd. (BS) is officially recognized in the Chinese Pharmacopoeia. In contrast, the aerial part of BS (ABS), accounting for 80% of BS, is typically discarded, causing potential waste of medicinal resources. ABS has shown benefits in the treatment of inflammation-related diseases in China and Spain, and the material basis underlying its anti-inflammatory effects must be systematically elucidated for the rational use of ABS., Objective: We aimed to screen and validate the anti-inflammatory quality markers (Q-markers) of ABS and to confirm the ideal time for ABS harvesting., Methods: The chemical components and anti-inflammatory effects of ABS from 10 extracted parts were analyzed by UPLC-Q-TOF-MS/MS and in a lipopolysaccharide (LPS)-induced cell model. Anti-inflammatory substances were screened by Pearson bivariate analysis and gray correlation analysis, and the anti-inflammatory effects were verified in a zebrafish tail-cutting inflammation model. HPLC was applied to measure the Q-marker contents of ABS in different harvesting periods., Results: Ten ABS extracts effectively alleviated the increase in LPS-induced proinflammatory cytokines in RAW 264.7 cells. Forty components were identified from them, among which 27 were common components. Eight components were correlated with anti-inflammatory effects, which were confirmed to reverse the expression of proinflammatory and anti-inflammatory factors in a zebrafish model. Chlorogenic acid, hypericin, rutin, quercetin, and isorhamnetin can be detected by HPLC, and the maximum contents of these five Q-markers were obtained in the sample harvested in August., Conclusion: The anti-inflammatory Q-markers of ABS were elucidated by chromatographic-pharmacodynamic-stoichiometric analysis, which served as a crucial basis for ABS quality control., (© 2023 John Wiley & Sons, Ltd.)

We present the precision measurements of 11 years of daily cosmic positron fluxes in the rigidity range from 1.00 to 41.9 GV based on 3.4×10^{6} positrons collected with the Alpha Magnetic Spectrometer (AMS) aboard the International Space Station. The positron fluxes show distinctly different time variations from the electron fluxes at short and long timescales. A hysteresis between the electron fluxes and the positron fluxes is observed with a significance greater than 5σ at rigidities below 8.5 GV. On the contrary, the positron fluxes and the proton fluxes show similar time variation. Remarkably, we found that positron fluxes are modulated more than proton fluxes with a significance greater than 5σ for rigidities below 7 GV. These continuous daily positron fluxes, together with AMS daily electron, proton, and helium fluxes over an 11-year solar cycle, provide unique input to the understanding of both the charge-sign and mass dependencies of cosmic rays in the heliosphere.

To explore the effect of biochar on greenhouse gas emissions and the carbon footprint of a corn farmland ecosystem under drip irrigation with film in an arid region, biochar treatments with different application rates[0 (CK), 15 (C15), 30 (C30), and 45 t·hm -2 (C45)] were established. The seasonal changes in soil greenhouse gases (CO 2 , N 2 O, and CH 4 ) and their comprehensive warming potential in the maize farmland ecosystem were monitored for two consecutive years after a one-time application of biochar. The carbon emissions caused by agricultural production activities and their carbon footprint were estimated using the life cycle assessment method. Compared with that in CK, the cumulative CO 2 emissions in the crop growing season decreased by 17.6%-24.7%, the cumulative N 2 O emissions decreased by 71.1%-110.4%, and the global warming potential decreased by 19.5%-25.9%. In the second year of the crop growing season after biochar application, the cumulative CO 2 emissions were reduced by 19.2%-40.6%, the cumulative N 2 O emissions were reduced by 38.7-46.7%, and the comprehensive warming potential was reduced by 19.7%-40.5%. For two consecutive years, the treatment of C15 and C30 increased the cumulative absorption of CH 4 to different degrees, whereas the treatment of C45 significantly decreased the cumulative absorption of CH 4 . C15 and C45 were the treatments with the least carbon footprint per unit yield in the current and the succeeding year of biochar application, and their carbon footprint per unit yield was 10.1% and 26.2% lower than that of CK, respectively. Soil greenhouse gas emissions showed the most contribution to the carbon footprint of the maize farmland ecosystem (38.1%-59.2%), followed by nitrogen fertilizer production (19.8%-33.4%), electric energy production (6.7%-8.8%), and plastic film mulching (4.4%-7.4%). Biochar contributed 5.7%-13.8% to the ecosystem's carbon footprint. The application of 30 t·hm -2 biochar had a better effect on carbon reduction, carbon fixation, and yield increase in the farmland ecosystem. Improving the biochar production process and transportation route, increasing nitrogen use efficiency, and developing water-saving and energy-saving irrigation technology are important ways to reduce the carbon footprint of farmland ecosystems in arid regions.

Abstract: The efficacy of acupuncture in treating pain diseases has been recognized in clinical practice, and its mechanism of action has been a hot topic in academic acupuncture research. Previous basic research on acupuncture analgesia has focused mostly on the nervous system, with few studies addressing the immune system as a potential pathway of acupuncture analgesia. In this study, we investigated the effect of electroacupuncture (EA) on the β-endorphins (β-END) content, END-containing leukocyte type and number, sympathetic neurotransmitter norepinephrine (NE), and chemokine gene expression in inflamed tissues. To induce inflammatory pain, about 200 µL of complete Frester adjuvant (CFA) was injected into the unilateral medial femoral muscle of adult Wistar rats. Electroacupuncture treatment was performed for 3 days beginning on day 4 after CFA injection, with parameters of 2/100 Hz, 2 mA, and 30 minutes per treatment. The weight-bearing experiment and enzyme-linked immunosorbent assay showed that EA treatment significantly relieved spontaneous pain-like behaviors and increased the level of β-END in inflamed tissue. Injection of anti-END antibody in inflamed tissue blocked this analgesic effect. Flow cytometry and immunofluorescence staining revealed that the EA-induced increase in β-END was derived from opioid-containing ICAM-1 + /CD11b + immune cells in inflamed tissue. In addition, EA treatment increased the NE content and expression of β2 adrenergic receptor (ADR-β2) in inflammatory tissues and upregulated Cxcl1 and Cxcl6 gene expression levels. These findings provide new evidence for the peripheral analgesic effect of acupuncture treatment by recruiting β-END-containing ICAM-1 + /CD11b + immune cells and increasing the β-END content at the site of inflammation., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

We report the properties of primary cosmic-ray sulfur (S) in the rigidity range 2.15 GV to 3.0 TV based on 0.38×10^{6} sulfur nuclei collected by the Alpha Magnetic Spectrometer experiment (AMS). We observed that above 90 GV the rigidity dependence of the S flux is identical to the rigidity dependence of Ne-Mg-Si fluxes, which is different from the rigidity dependence of the He-C-O-Fe fluxes. We found that, similar to N, Na, and Al cosmic rays, over the entire rigidity range, the traditional primary cosmic rays S, Ne, Mg, and C all have sizeable secondary components, and the S, Ne, and Mg fluxes are well described by the weighted sum of the primary silicon flux and the secondary fluorine flux, and the C flux is well described by the weighted sum of the primary oxygen flux and the secondary boron flux. The primary and secondary contributions of the traditional primary cosmic-ray fluxes of C, Ne, Mg, and S (even Z elements) are distinctly different from the primary and secondary contributions of the N, Na, and Al (odd Z elements) fluxes. The abundance ratio at the source for S/Si is 0.167±0.006, for Ne/Si is 0.833±0.025, for Mg/Si is 0.994±0.029, and for C/O is 0.836±0.025. These values are determined independent of cosmic-ray propagation.

We present the precision measurements of 11 years of daily cosmic electron fluxes in the rigidity interval from 1.00 to 41.9 GV based on 2.0×10^{8} electrons collected with the Alpha Magnetic Spectrometer (AMS) aboard the International Space Station. The electron fluxes exhibit variations on multiple timescales. Recurrent electron flux variations with periods of 27 days, 13.5 days, and 9 days are observed. We find that the electron fluxes show distinctly different time variations from the proton fluxes. Remarkably, a hysteresis between the electron flux and the proton flux is observed with a significance of greater than 6σ at rigidities below 8.5 GV. Furthermore, significant structures in the electron-proton hysteresis are observed corresponding to sharp structures in both fluxes. This continuous daily electron data provide unique input to the understanding of the charge sign dependence of cosmic rays over an 11-year solar cycle.

Introduction: Recent research has focused on the local control of articular inflammation through neuronal stimulation to avoid the systemic side effects of conventional pharmacological therapies. Electroacupuncture (EA) has been proven to be useful for inflammation suppressing and pain reduction in knee osteoarthritis (KOA) patients, yet its mechanism remains unclear., Methods: In the present study, the KOA model was established using the intra-articular injection of sodium monoiodoacetate (MIA) (1 mg/50 μL) into the knee cavity. EA was delivered at the ipsilateral ST36-GB34 acupoints. Hind paw weight-bearing and withdrawl thresholds were measured. On day 9, the histology, dep enrichment proteins, cytokines contents, immune cell population of the synovial membrane of the affected limbs were measured using HE staining, Masson staining, DIA quantitative proteomic analysis, flow cytometry, immunofluorescence staining, ELISA, and Western Blot. The ultrastructure of the saphenous nerve of the affected limb was observed using transmission electron microscopy on the 14th day after modeling., Results: The result demonstrated that EA intervention during the midterm phase of the articular inflammation alleviated inflammatory pain behaviors and cartilage damage, but not during the early phase. Mid-term EA suppressed the levels of proinflammatory cytokines TNF-α, IL-1β, and IL-6 in the synovium on day 9 after MIA by elevating the level of sympathetic neurotransmitters Norepinephrine (NE) in the synovium but not systemic NE or systemic adrenaline. Selective blocking of the sympathetic function (6-OHDA) and β2-adrenergic receptor (ICI 118,551) prevented the anti-inflammatory effects of EA. EA-induced increment of the NE in the synovium inhibited the CXCL1-CXCR2 dependent overexpression of IL-6 in the synovial macrophages in a β2-adrenergic receptor (AR)-mediated manner., Discussion: These results revealed that EA activated sympathetic noradrenergic signaling to control local inflammation in KOA rats and contributed to the development of novel therapeutic neurostimulation strategies for inflammatory diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Zhang, Su, Wang, Li, Liu, Wan, Qu, Jing and He.)

Objective: To investigate the anti-coronavirus potential and the corresponding mechanisms of the two ingredients of Reduning Injection: quercetin and luteolin., Methods: A pseudovirus system was designed to test the efficacy of quercetin and luteolin to inhibit SARS-CoV-2 infection and the corresponding cellular toxicity. Luteolin was tested for its activities against the pseudoviruses of SARS-CoV-2 and its variants. Virtual screening was performed to predict the binding sites by Autodock Vina 1.1.230 and PyMol. To validate docking results, surface plasmon resonance (SPR) was used to measure the binding affinity of the compounds with various proteins of the coronaviruses. Quercetin and luteolin were further tested for their inhibitory effects on other coronaviruses by indirect immunofluorescence assay on rhabdomyosarcoma cells infected with HCoV-OC43., Results: The inhibition of SARS-CoV-2 pseudovirus by luteolin and quercetin were strongly dose-dependent, with concentration for 50% of maximal effect (EC 50 ) of 8.817 and 52.98 µmol/L, respectively. Their cytotoxicity to BHK21-hACE2 were 177.6 and 405.1 µmol/L, respectively. In addition, luetolin significantly blocked the entry of 4 pseudoviruses of SARS-CoV-2 variants, with EC 50 lower than 7 µmol/L. Virtual screening and SPR confirmed that luteolin binds to the S-proteins and quercetin binds to the active center of the 3CLpro, PLpro, and helicase proteins. Quercetin and luteolin showed over 99% inhibition against HCoV-OC43., Conclusions: The mechanisms were revealed of quercetin and luteolin inhibiting the infection of SARS-CoV-2 and its variants. Reduning Injection is a promising drug for COVID-19., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Bupleurum scorzonerifolium (BS) is one of the sources of Bupleuri Radix, which was first recorded in Shennong's classic of materia medica. It has a medicinal history of 2000 years and is now widely used for the treatment of depression clinically. However, the material basis of antidepressant effects is unclear, and the quality evaluation method is lacking. The paper aims to investigate the antidepressant quality markers (Q-markers) of BS by electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS). Firstly, the rat depression model was established by using chronic unpredictable mild stress (CUMS) combined with the solitary confinement method to evaluate the pharmacodynamics of BS. After verification of the antidepressant effect of BS, UPLC-ESI-Q-TOF-MS was used to analyze BS and the blood components of BS. A total of 34 components were identified in BS, in which 8 components, including saikosaponin a (SSa), saikosaponin c (SSc), saikosaponin d (SSd), saikosaponin b 1 (SSb 1 ), saikosaponin b 2 (SSb 2 ), glycyrrhetinic acid, nootkatone and valerenic acid, were detected in serum. SSa, SSc, SSd, SSb 1 and SSb 2 were found as metabolites, and glycyrrhetinic acid, nootkatone and valerenic Acid were identified as the prototypes in the blood. The depression model of zebrafish was established with reserpine to verify the antidepressant effect of the potential eight active components. The results showed that all these components could markedly improve the depressive behavior of zebrafish, increase the content of 5-HT and reduce the cortisol content. Finally, according to the principles of effectiveness, accessibility and measurability for Q-markers, SSa, SSc, and SSd were confirmed as Q-markers of BS, and the contents of 3 Q-markers in 10 batches of BS from different origins were determined to be 0.0728-1.465%. In addition, the total contents of 3 Q-markers in BS produced in Lindian, Heilongjiang Province, were higher than those in other origins. This paper provided a reliable method for the quality evaluation of BS for depression treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To investigate the mechanism of electroacupuncture (EA) "Zusanli" (ST36) in delaying colon "inflammation-cancer transformation" in mice by anti-inflammatory., Methods: C57BL/6J mice were randomly divided into normal, model and EA groups, with 12 mice in each group. The mouse model of colorectal cancer (CRC) was established by intrape-ritoneal injection of azomethane (AOM) and feeding dextran sodium sulfate (DSS). At the beginning of the 2 nd cycle, EA was applied to bilateral ST36 for 30 min once every other day for 12 times. The number of colon tumors in each group was observed, and the weight and length of colon were recorded. The contents of interleukin (IL)-1β, IL-6, IL-17A, IL-23, tumor necrosis factor (TNF)-α and CXC chemokine ligand 1 (CXCL1) of serum and colon tissue were detected by MSD multifactorial assay.The apoptosis of local cells in colon tumor was observed by TUNEL staining. Cell proliferation in colon tumor was observed by immunohistochemistry., Results: Compared with the normal group, the colon length was significantly shortened ( P <0.05) and the colon mass was significantly increased ( P <0.001) in the model group, the contents of IL-1β, IL-6, TNF-α, IL-17A and CXCL1 of serum and colon tissue were significantly increased ( P <0.05, P <0.01, P <0.001), and the content of IL-23 was increased in colon tissue ( P <0.05) in the model group. Compared with the model group, the colon mass was decreased ( P <0.05) and the contents of IL-1β, IL-6, TNF-α and IL-17A in serum were decreased ( P <0.05), while the contents of IL-17A, CXCL1 and IL-23 in colon tissue were decreased ( P <0.05) in the EA group, the percentage of local apoptotic cells in the EA group was increased ( P <0.001), the percentage of PCNA positive cells was decreased ( P <0.001), the number of tumors and the tumor volume were significantly decreased ( P <0.01, P <0.05). The contents of IL-6, TNF-α, IL-17A and IL-23 in serum of CRC mice were positively correlated with tumor burden ( P <0.05).The contents of IL-1β, TNF-α, CXCL1 and IL-23 in colon tissue of CRC mice were positively correlated with tumor burden ( P <0.05)., Conclusion: Electroacupuncture at ST36 can inhibit the inflammatory response of AOM/DSS inflammatory associated CRC mice and delay the "inflammation-cancer transformation" of colon.

This study is to develop a method for isolation, identification, and quantitative determination of dammarane-type triterpene saponins in the Panax notoginseng fruits (PNF). The saponins were isolated by a serious of chromatographic methods, and their structures were elucidated on the basis of spectroscopic evidence and comparison with those of literature reports. Quantitative assay was performed on an ultra-performance liquid chromatography-UV (UPLC-UV) method. As a result, 22 saponins were isolated from the extract of PNF, among them, compound 1 was a new saponin, named as malonylgypenoside IX, compounds 3 - 10 , and 14-18 were isolated from the PNF for the first time. As to quantitative analysis, the calibration curves showed good linearity ( r  > 0.998) within the concentration range, and the method validation provided good reproducibility and sensitivity for the quantification of eight major saponins with precision and accuracy of less than 3.0%.

Objective: The aim of this study was to evaluate the efficacy of acupuncture, an alternative medicine therapy, as a preventive treatment for menstruation-related migraine (MRM)., Patients and Methods: This was a prospective, multicenter, double-dummy, participant-blinded, randomized controlled clinical trial conducted in China between 1 April 2013, and 30 April 2014. The participants were enrolled from four study centers and randomized to into either the acupuncture group, which received 24 sessions of acupuncture at traditional acupoints plus placebo, or the medication group, which received sham acupuncture plus naproxen. The primary endpoint was change from the baseline average number of migraine days per perimenstrual period over cycles 1-3. The secondary endpoints included changes from the baseline average number of migraine days outside the perimenstrual period, mean number of migraine hours during and outside the perimenstrual period, mean visual analog scale score during and outside the perimenstrual period, ≥50% migraine responder rate, and the proportion of participants who used acute pain medication over cycles 1-3 and 4-6., Results: A total of 172 women with MRM were enrolled; 170 in the intention-to-treat analyses. Our primary outcome reported a significant between-group difference that favored the acupuncture group (95% CI, 0.17-0.50; P < 0.001), with the average reduction of migraine days per perimenstrual period from the baseline was 0.94 (95% CI, 0.82-1.07) in the acupuncture group and 0.61 (95% CI, 0.50-0.71) in the medication group over cycles 1-3., Conclusion: This study showed that compared to medication, acupuncture reduces the number of migraine days experienced by patients with MRM. For patients who received the acupuncture treatment over three cycles, the preventive effect of the therapy was sustained for six cycles., Clinical Trial Registration: [https://www.isrctn.com/ISRCTN57133712], identifier [ISRCTN15663606]., 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 Liu, Zhang, Liu, He, Lyu, Zeng, Zhao, Wang, Qu, Nie, Guo, Zhang, Lu, Wang, Li, Jing and Wang.)

This study aimed to decipher the pharmacodynamic material basis and mechanism of herbal pair Bupleurum scorzonerifolium-Paeonia lactiflora(BS-PL) against liver cancer based on UPLC-Q-TOF-MS and network pharmacology. MTT assay and human hepatocellular carcinoma HepG2 cells were used to screen the effective part of BS-PL, the active components of which were further analyzed and identified by UPLC-Q-TOF-MS. Next, we applied Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) to screen the active ingredients with OB≥30%. Then TCMSP and SwissTargetPrediction were used to collect and predict component targets, followed by the search of liver cancer-related targets with GeneCards and DisGeNET. The intersection targets were obtained using Venny 2.1.0. Protein-protein interaction(PPI) network was constructed using STRING to uncover the core targets, which were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis based on DAVID. Finally, the effects of active ingredients on the expression of main proteins enriched in the key pathways of HepG2 cells were verified by Western blot. The results indicated that compared with 30%, 50%, and 70% ethanol extracts of BS-PL, the n-butanol extraction part(CSYZ) from 95% ethanol extract of BS-PL exhibited the best anti-tumor effect. UPLC-Q-TOF-MS revealed 31 ingredients, 14 of which showed OB≥30%. A total of 220 intersection targets were obtained, from which 35 were selected as the key targets under the condition of two times the median of degree. Among the 215 items with P&lt;0.05 obtained through GO enrichment analysis, 154 were classified into biological processes, 22 into cell components and 39 into molecular functions. KEGG enrichment analysis revealed 95 significantly affected signaling pathways, and the ones(sorted in a descending order by P value) closely related to the anti-liver cancer effect of herbal pair were PI3 K-AKT signaling pathway, TNF signaling pathway, MAPK signaling pathway, HIF-1 signaling pathway, and ErbB signaling pathway. Finally, the PI3 K/AKT signaling pathway involving the largest number of targets was extrapolated, and it was found that this pathway contained 15 core targets and 8 active components. Experimental verification showed that the effective components of BS-PL significantly inhibited the expression of p-PI3 K and p-AKT, consistent with the prediction results of network pharmacology. In conclusion, the main pharmacodynamic substances of BS-PL against liver cancer are 14 components like saikosaponin a, saikosaponin d, and paeoniflorin, which exert the anti-liver cancer effect by regulating PI3 K/AKT pathway.

We present the precision measurement of 2824 daily helium fluxes in cosmic rays from May 20, 2011 to October 29, 2019 in the rigidity interval from 1.71 to 100 GV based on 7.6×10^{8} helium nuclei collected with the Alpha Magnetic Spectrometer (AMS) aboard the International Space Station. The helium flux and the helium to proton flux ratio exhibit variations on multiple timescales. In nearly all the time intervals from 2014 to 2018, we observed recurrent helium flux variations with a period of 27 days. Shorter periods of 9 days and 13.5 days are observed in 2016. The strength of all three periodicities changes with time and rigidity. In the entire time period, we found that below ∼7  GV the helium flux exhibits larger time variations than the proton flux, and above ∼7  GV the helium to proton flux ratio is time independent. Remarkably, below 2.4 GV a hysteresis between the helium to proton flux ratio and the helium flux was observed at greater than the 7σ level. This shows that at low rigidity the modulation of the helium to proton flux ratio is different before and after the solar maximum in 2014.

Background: Labial arteriovenous malformations (AVMs), usually with accompanying cosmetic defects, pain, and bleeding, are aggressive with a high risk of recurrence and the absence of effective treatment. In the present report, we have described a technique of sclerotherapy for labial AVMs., Methods: Patients with labial AVMs were treated with percutaneous ethanol sclerotherapy with or without polyvinyl alcohol particle embolization. The efficiency, complications, and recurrence rate were analyzed with imaging studies and clinical follow-up data., Results: All 15 patients had received one or more treatment sessions, of whom 8 had experienced a cure (53.3%) and 5 had experienced remission (33.3%). The two patients who had not experienced an effective result were awaiting further treatment at the last follow-up examination. Four patients (26.7%) who had undergone ethanol sclerotherapy combined with polyvinyl alcohol particle embolization had experienced recurrence. No patient who had undergone only sclerotherapy had developed recurrence at a mean follow-up of 17.2 ± 8.1 months. Thirteen patients had experienced transient complications, including swelling, mild bleeding, and blistering. One patient had a postoperative scar of ∼0.5 cm., Conclusions: Ethanol sclerotherapy appears effective as a treatment of labial AVMs. Careful application of the treatment could reduce the occurrence of complications., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Platelet-derived growth factors (PDGFs) and PDGF receptors (PDGFRs) are expressed in a variety of tumors. Activation of the PDGF/PDGFR signaling pathway is associated with cancer proliferation, metastasis, invasion, and angiogenesis through modulating multiple downstream pathways, including phosphatidylinositol 3 kinase/protein kinase B pathway and mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. Therefore, targeting PDGF/PDGFR signaling pathway has been demonstrated to be an effective strategy for cancer therapy, and accordingly, some great progress has been made in this field in the past few decades. This review will focus on the PDGF isoforms and their binding with the related PDGFRs, the PDGF/PDGFR signaling and regulation, and especially present strategies and inhibitors developed for cancer therapy, and the related clinical benefits and side effects., (Copyright © 2022. Published by Elsevier B.V.)

Sleep disorder emerges as a common comorbidity in children with autism spectrum disorder (ASD), and the interaction between the core symptoms of ASD and its sleep disorder remains unclear. Repetitive transcranial magnetic stimulation (rTMS) was used on the bilateral dorsolateral prefrontal cortex (DLPFC) to investigate the efficacy of rTMS on the core symptoms of ASD and comorbid sleep problems as well as the mediation role of the ASD symptoms between rTMS intervention and sleep improvement. A total of 41 Chinese children with ASD and who met the criteria in the fifth edition of the American Diagnostic and Statistical Manual of Mental Disorders were recruited, and 39 of them (mean age: 9.0 ± 4.4 years old; the male-female ratio was 3.9: 1) completed the study with the stimulating protocol of high frequency on the left DLPFC and low frequency on the right DLPFC. They were all assessed three times (before, at 4 weeks after, and at 8 weeks after the stimulation) by the Children's Sleep Habits Questionnaire (CSHQ), Strengths and Difficulties Questionnaire (SDQ), Childhood Autism Rating Scale, Repetitive Behavior Questionnaire-2, and Short Sensory Profile (SSP). The repeated-measures ANOVA showed that the main effect of "intervention time" of CSHQ ( F = 25.103, P < 0.001), SSP ( F = 6.345, P = 0.003), and SDQ ( F = 9.975, P < 0.001) was statistically significant. By Bayesian mediation analysis, we only found that the total score of SSP mediated the treating efficacy of rTMS on CSHQ (αβ = 5.11 ± 1.51, 95% CI: 2.50-8.41). The percentage of mediation effect in total effect was 37.94%. Our results indicated the treating efficacy of rTMS modulation on bilateral DLPFC for both autistic symptoms and sleep disturbances. The sensory abnormality of ASD mediated the improvement of rTMS on sleep problems of ASD., 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 Gao, Wang, Song, Tian, Qu, Han and Zhang.)

We present the precision measurement of the daily proton fluxes in cosmic rays from May 20, 2011 to October 29, 2019 (a total of 2824 days or 114 Bartels rotations) in the rigidity interval from 1 to 100 GV based on 5.5×10^{9} protons collected with the Alpha Magnetic Spectrometer aboard the International Space Station. The proton fluxes exhibit variations on multiple timescales. From 2014 to 2018, we observed recurrent flux variations with a period of 27 days. Shorter periods of 9 days and 13.5 days are observed in 2016. The strength of all three periodicities changes with time and rigidity. The rigidity dependence of the 27-day periodicity is different from the rigidity dependences of 9-day and 13.5-day periods. Unexpectedly, the strength of 9-day and 13.5-day periodicities increases with increasing rigidities up to ∼10  GV and ∼20  GV, respectively. Then the strength of the periodicities decreases with increasing rigidity up to 100 GV.

Introduction: The thyroid cancer incidence has been increasing all over the world. However, the aetiology of thyroid cancer remains unclear. A growing body of evidence suggested exposure to persistent organic pollutants (POPs) may play a role in the initiation of thyroid cancer, but the results are generally inconsistent across studies. This review aims to synthesise the evidence for the health effects of POPs on the risk of thyroid cancer., Methods and Analysis: This protocol was reported in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA) statements. A comprehensive search, including electronic database search (eg, PubMed, Embase, ProQuest and CNKI), website search and manual search, will be performed to identify all eligible studies. The Population, Exposure, Comparator and Outcome framework was used to clarify the inclusion and exclusion criteria. The Newcastle-Ottawa Scale will be used to assess the quality of included studies. Maximally adjusted effect estimates from individual studies will be summarised with random-effect models in a conservative manner. I 2 statistics and Q-tests will be used to test the heterogeneity across studies. We will perform extensive sensitivity analyses, such as confounding risk ratio (confounding), E-value, fixed-effect models, excluding the most relatively weighted study, including only the high-quality studies and many predesigned subgroup analyses, etc. The findings will be reported in accordance to the PRISMA guidelines., Ethics and Dissemination: Ethical approval is not required in this systematic review of published literatures. The results will be published in a peer-reviewed journal and presented at relevant conferences., Prospero Registration Number: CRD42020181343., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We report the properties of sodium (Na) and aluminum (Al) cosmic rays in the rigidity range 2.15 GV to 3.0 TV based on 0.46 million sodium and 0.51 million aluminum nuclei collected by the Alpha Magnetic Spectrometer experiment on the International Space Station. We found that Na and Al, together with nitrogen (N), belong to a distinct cosmic ray group. In this group, we observe that, similar to the N flux, both the Na flux and Al flux are well described by the sums of a primary cosmic ray component (proportional to the silicon flux) and a secondary cosmic ray component (proportional to the fluorine flux). The fraction of the primary component increases with rigidity for the N, Na, and Al fluxes and becomes dominant at the highest rigidities. The Na/Si and Al/Si abundance ratios at the source, 0.036±0.003 for Na/Si and 0.103±0.004 for Al/Si, are determined independent of cosmic ray propagation.

Acupuncture is an effective alternative therapy for pain management. Evidence suggests that acupuncture relieves pain by exciting somatic afferent nerve fibers. However, the mechanism underlying the interaction between neurons in different layers of the spinal dorsal horn induced by electroacupuncture (EA) remains unclear. The aim of this study was to explore the mechanism of EA relieving inflammatory muscle pain, which was associated with activation of the spontaneous firing of low-threshold mechanoreceptor (LTM) neurons and inhibition of wide dynamic range (WDR) neuronal activities in the spinal dorsal horn of rats. Inflammatory muscle pain was induced by injecting complete Freund's adjuvant into the right biceps femoris muscle. EA with intensity of threshold of A fibers (Ta) in Liangqiu (ST34) muscle considerably inhibited the abnormal spontaneous activities of electromyography (EMG) due to muscle inflammation. While EA with intensity of C-fiber threshold (Tc) increased the abnormal activities of EMG. EA with Ta also ameliorated the imbalance of weight-bearing behavior. A microelectrode array with 750-μm depth covering 32 channels was used to record the neuronal activities of WDR and LTM in different layers of the spinal dorsal horn. The spontaneous firing of LTM neurons was enhanced by EA-Ta, while the spontaneous firing of WDR neurons was inhibited. Moreover, EA-Ta led to a significant inverse correlation between changes in the frequency of WDR and LTM neurons ( r = -0.64, p < 0.05). In conclusion, the results indicated that EA could alleviate inflammatory muscle pain, which was associated with facilitation of the spontaneous firing of LTM neurons and inhibition of WDR neuronal activities. This provides a promising evidence that EA-Ta could be applied to relieve muscular inflammatory pain in clinical practice., 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 Duan-Mu, Zhang, Shi, Su, Wan, Wang, Qu, He, Wang and Jing.)

Background: Patients undergoing lumbar spine surgery usually suffer severe pain in the postoperative period. The erector spinae plane block (ESPB), first published in 2016, can anesthetize the ventral and dorsal rami of thoracic nerves and produce an extensive multi-dermatomal sensory block., Aim: To assess whether bilateral ultrasound-guided ESPB at a lower thoracic level could improve pain control and quality of recovery in patients undergoing lumbar spine surgery., Methods: A total of 60 patients aged 18-80 years scheduled to undergo lumbar spine surgery with general anesthesia were randomly assigned to two groups: ESPB group (preoperative bilateral ultrasound-guided ESPB at T10 vertebral level) and control group (no preoperative ESPB). Both groups received standard general anesthesia. The main indicator was the duration to the first patient controlled intravenous analgesia (PCIA) bolus., Results: In the ESPB group, the duration to the first PCIA bolus was significantly longer than that in the control group (h) [8.0 (4.5, 17.0) vs 1.0 (0.5, 6), P < 0.01], and resting and coughing numerical rating scale (NRS) scores at 48 h post operation were significantly lower than those in the control group ( P < 0.05). There was no significant difference between the two groups regarding resting and coughing NRS scores at 24 h post operation. Sufentanil consumption during the operation was significantly lower in the ESPB group than in the control group ( P < 0.01), while there was no significant difference between the two groups regarding morphine consumption at 24 or 48 h post operation. In the ESPB group, Modified Observer's Assessment of Alertness/Sedation score within 20 min after extubation was higher and duration in the post-anesthesia care unit was shorter than those in the control group ( P < 0.01)., Conclusion: In patients undergoing lumbar spine surgery, ultrasound-guided ESPB at a lower thoracic level improves the analgesic effect, reduces opioid consumption, and improves postoperative recovery., Competing Interests: Conflict-of-interest statement: None declared., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Electroacupuncture (EA) is widely used in clinical practice to relieve migraine pain. 5-HT 7 receptor (5-HT 7 R) has been reported to play an excitatory role in neuronal systems and regulate hyperalgesic pain and neurogenic inflammation. 5-HT 7 R could influence phosphorylation of protein kinase A (PKA)- or extracellular signal-regulated kinase 1 / 2 (ERK 1 / 2 )-mediated signaling pathways, which mediate sensitization of nociceptive neurons via interacting with cyclic adenosine monophosphate (cAMP). In this study, we evaluated the role of 5-HT 7 R in the antihyperalgesic effects of EA and the underlying mechanism through regulation of PKA and ERK 1 / 2 in trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC). Hyperalgesia was induced in rats with dural injection of inflammatory soup (IS) to cause meningeal neurogenic inflammatory pain. Electroacupuncture was applied for 15 min every other day before IS injection. Von Frey filaments, tail-flick, hot-plate, and cold-plated tests were used to evaluate the mechanical and thermal hyperalgesia. Neuronal hyperexcitability in TNC was studied by an electrophysiological technique. The 5-HT 7 R antagonist (SB269970) or 5-HT 7 R agonist (AS19) was administered intrathecally before each IS application at 2-day intervals during the 7-day injection protocol. The changes in 5-HT 7 R and 5-HT 7 R-associated signaling pathway were examined by real-time polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) analyses. When compared with IS group, mechanical and thermal pain thresholds of the IS + EA group were significantly increased. Furthermore, EA prevented the enhancement of both spontaneous activity and evoked responses of second-order trigeminovascular neurons in TNC. Remarkable decreases in 5-HT 7 R mRNA expression and protein levels were detected in the IS + EA group. More importantly, 5-HT 7 R agonist AS19 impaired the antihyperalgesic effects of EA on p-PKA and p-ERK 1 / 2 . Injecting 5-HT 7 R antagonist SB-269970 into the intrathecal space of IS rats mimicked the effects of EA antihyperalgesia and inhibited p-PKA and p-ERK 1 / 2 . Our findings indicate that 5-HT 7 R mediates the antihyperalgesic effects of EA on IS-induced migraine pain by regulating PKA and ERK 1 / 2 in TG and TNC., 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. The handling editor declared a past co-authorship with one of the authors, X-HJ., (Copyright © 2021 Liu, Xu, Qu, Zhao, Zhang, Li, Lyu, Wang, Jing and Li.)

Objective: To compare the effect of electroacupuncture (EA) and transcutaneous electrical acupoint stimulation (TEAS) of skin and muscle layers of "Liangqiu" (ST34) area on inflammatory muscular pain in rats, so as to study the role of different-layer afferent nerve fibers in acupuncture analgesia., Methods: A total of 120 male SD rats were used in the present study, including 8 rats used for determining the excitatory threshold of Aδ(Ta) and C (Tc) afferent nerve fibers, 48 employed for comparing the analgesic effect of EA and TEAS at intensities of Ta and Tc, and 64 for observing the effect of EA and TAES stimulation of ipsilateral (Ipsi), contralateral (Contra) ST34 and ipsilateral LI4 at Ta and Tc intensities. Inflammatory muscle pain was induced by injection of complete Freund's adjuvant (CFA) into the right biceps femoris muscle. In the second part of the present study, 48 rats were randomly and equally divided into control, model, TEAS-Ta, TEAS-Tc, EA-Ta and EA-Tc groups, while in the 3rd part, 64 rats were randomly and equally divided into control, model, Ipsi-ST34-TEAS, Contra-ST34-TEAS, Ipsi-ST34-EA, Contra-ST34-EA, Ipsi-LI4-TEAS and Ipsi-LI4-EA groups. TEAS or EA was applied to the skin and muscle layers, respectively. Before and after modeling, the animal was forced to stand on a bipedal equilibrator, the difference in body mass distribution of both feet (bearing difference) was used to assess the pain severity. The frequency of myoelectrical discharges of the right bicep femoris muscle in responding to electrical stimulation of the spot between the 4 th and 5 th toes of the ipsilateral hindlimb at an intensity of two-folds of C-fiber excitatory threshold was recorded., Results: 1) The bearing difference between the bilateral hindlimbs was markedly higher in the model group than in the control group ( P <0.01), and significantly lower at the 2 nd and 3 rd day in the EA-Ta and EA-Tc, and TEAS-Tc groups relevant to the model group ( P <0.05, P <0.01). 2) The frequency of C-fiber reflex induced electromyogram (EMG) activities were significantly decreased at 0 and 1 min after TEAS of both ipsilateral ST34 at Tc, and 0 min after TEAS of the contralateral ST34 at Tc (rather than at Ta and not LI4 even at Tc) in comparison with pre-TEAS, and 0, 1 and 2 min after TEAS of ipsilateral ST34 at Tc, and 0 min after TEAS of contra-ST34 at Tc compared with the model group, respectively ( P <0.01, P <0.05). In comparison with pre-EA, the frequency of C-fiber reflex induced EMG activities were significantly decreased at 0 and 1 min after EA of the ipsilateral ST34 at Ta, and 0 min after EA of the contra-ST34 at Ta. In addition, the frequency of C-fiber reflex induced EMG activities were decreased at 0, 1 and 2 min after EA of the ipsilateral ST34 at Tc, and 0 and 1 min after EA of the contra-ST34 at Tc, as well as 0 min after EA of LI4 at Tc ( P <0.01, P <0.05).In comparison with the model group, the frequency of C-fiber reflex induced EMG activities are significantly decreased at 0, and 1 min after EA of the ipsilateral ST34 at Ta, and 0 min after EA of the contra-ST34 at Ta. In addition, the frequency of C-fiber reflex induced EMG activities were decreased at 0, 1 ,2,and 3 min after EA of the ipsilateral ST34 at Tc, and 0 and 1 min after EA of the contra-ST34 at Tc, as well as 0 min after EA of LI4 at Tc, respectively ( P <0.01, P <0.05)., Conclusion: TEAS-ST34 at Tc and EA-ST34 at both Ta and Tc can alleviate pain behavior in inflammatory pain rats, which may be related to its effect in activating the afferent nerve fiber in different layers of ST34 area.

Four new malonylginsenosides, malonylnotoginsenoside Fe (1), malonylnotoginsenoside Ra 1 (2), malonylgypenoside LXXV (3), and malonylginsenoside Mc (4), together with two known analogues, malonylfloralginsenoside Rc 1 (5) and malonylginsenoside Rc (6), were isolated from the fresh fruits of Panax notoginseng. Their structures were determined by MS and NMR experiments. The anti-proliferative activities of the malonylginsenosides (1-6) against SH-SY5Y human neuroblastoma cell line were evaluated using the MTT assay., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Precise knowledge of the charge and rigidity dependence of the secondary cosmic ray fluxes and the secondary-to-primary flux ratios is essential in the understanding of cosmic ray propagation. We report the properties of heavy secondary cosmic ray fluorine F in the rigidity R range 2.15 GV to 2.9 TV based on 0.29 million events collected by the Alpha Magnetic Spectrometer experiment on the International Space Station. The fluorine spectrum deviates from a single power law above 200 GV. The heavier secondary-to-primary F/Si flux ratio rigidity dependence is distinctly different from the lighter B/O (or B/C) rigidity dependence. In particular, above 10 GV, the F/Si/B/O ratio can be described by a power law R^{δ} with δ=0.052±0.007. This shows that the propagation properties of heavy cosmic rays, from F to Si, are different from those of light cosmic rays, from He to O, and that the secondary cosmic rays have two classes.

We report the observation of new properties of primary iron (Fe) cosmic rays in the rigidity range 2.65 GV to 3.0 TV with 0.62×10^{6} iron nuclei collected by the Alpha Magnetic Spectrometer experiment on the International Space Station. Above 80.5 GV the rigidity dependence of the cosmic ray Fe flux is identical to the rigidity dependence of the primary cosmic ray He, C, and O fluxes, with the Fe/O flux ratio being constant at 0.155±0.006. This shows that unexpectedly Fe and He, C, and O belong to the same class of primary cosmic rays which is different from the primary cosmic rays Ne, Mg, and Si class.

Purpose: The present study aimed to investigate the effects of miR-504 in cervical cancer., Methods: Normal and cervical cancer tissue specimens derived from TCGA and GTEx databases were employed to analyze the miR-504 and PAICS (one of potential target gene of miR-504) expression. Kaplan-Meier strategy was applied to analyze the prognostic powers of miR-504 and PAICS. The proliferation, clonogenic ability, invasion, and migration of cervical cancer cells (C-33A and HeLa) were detected using Cell Counting Kit 8, colony formation, and transwell assays. Pearson correlation analysis was used to assess the correlation between miR-504 and PAICS, which was confirmed using luciferase reporter assay. The mRNA and protein levels were detected by qRT-PCR and western blot, respectively., Results: TCGA data revealed that miR-504 expression might be decreased in cervical cancer, which was correlated with unfavorable prognosis. Further experiments exhibited that abnormal miR-504 expression negatively affected malignant cellular behaviors in cervical cancer, including proliferation, colony formation, invasion, and migration. PAICS was identified as a putative target of miR-504, and negatively related with miR-504 expression. PAICS expression was increased in cervical cancer and its high-regulation-induced worse outcomes of patients with cervical cancer. Rescue experiments indicated that PAICS restricted the impacts of miR-504 in cervical cancer cells. Analysis of western blot suggested that overexpression of PAICS overturned the miR-504-induced EMT inactivation., Conclusion: Our observations elucidated that miR-504, acting as a suppressor for the progression of cervical cancer, inhibits cell proliferation, invasion and migration, and mediates EMT via negatively regulating PAICS.

We report the observation of new properties of primary cosmic rays, neon (Ne), magnesium (Mg), and silicon (Si), measured in the rigidity range 2.15 GV to 3.0 TV with 1.8×10^{6}  Ne, 2.2×10^{6}  Mg, and 1.6×10^{6}  Si nuclei collected by the Alpha Magnetic Spectrometer experiment on the International Space Station. The Ne and Mg spectra have identical rigidity dependence above 3.65 GV. The three spectra have identical rigidity dependence above 86.5 GV, deviate from a single power law above 200 GV, and harden in an identical way. Unexpectedly, above 86.5 GV the rigidity dependence of primary cosmic rays Ne, Mg, and Si spectra is different from the rigidity dependence of primary cosmic rays He, C, and O. This shows that the Ne, Mg, and Si and He, C, and O are two different classes of primary cosmic rays.

Background: In recent years, with the popularity of laryngeal mask airway (LMA) for the management of clinical anesthesia, the influence of the LMA on the position and blood flow of the internal jugular vein (IJV) has attracted an increasing amount of attention., Aim: To investigate the effect of placement of different types of LMA (Supreme LMA, Guardian LMA, I-gel LMA) on the position and blood flow of the right IJV., Methods: This was a prospective randomized controlled trial. A total of 102 patients aged 18-75 years who were scheduled to undergo laparoscopic abdominal surgery with general anesthesia were randomly assigned to three groups: Supreme LMA (group 1), Guardian LMA (group 2), and I-gel LMA (group 3) groups. The main indicator was the overlap index (OI) of IJV and the common carotid artery (CCA) at the high, middle, and low points before and after the placement of the LMA. The second indicators were the proportion of ultrasound-simulated needle crossing the IJV and CCA, and the cross-sectional area and blood flow velocity of the IJV before and after placement of the LMA at the middle point., Results: Data from 100 patients were included in the statistical analysis. The OI increased significantly after placement of the LMA in the three groups at the three points ( P < 0.01), except group 2 at the low point. In group 2 and group 3, the OI was lower than that in group 1 after LMA insertion at the high point ( P < 0.0167). At the middle point, after LMA insertion, the proportion of simulated needle crossing the IJV significantly decreased in all three groups ( P < 0.05), and the proportion in group 2 was higher than that in group 3 ( P < 0.0167). The proportion of simulated needle crossing the CCA or both the IJV and CCA significantly increased in group 1 and group 2 ( P < 0.05), which increased with no statistical significance in group 3. After LMA insertion, the cross-sectional area of ​​the IJV significantly increased, while the blood flow velocity significantly decreased ( P < 0.01). There was no significant difference among the three groups., Conclusion: The placement of Supreme, Guardian, and I-gel LMA can increase the OI, reduce the success rate of IJV puncture, increase the incidence of arterial puncture, and cause congestion of IJV. Type of LMA did not influence the difficulty of IJV puncture. Therefore when LMA is used, ultrasound is recommended to guide the IJV puncture., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Precision measurements by the Alpha Magnetic Spectrometer (AMS) on the International Space Station of ^{3}He and ^{4}He fluxes are presented. The measurements are based on 100 million ^{4}He nuclei in the rigidity range from 2.1 to 21 GV and 18 million ^{3}He from 1.9 to 15 GV collected from May 2011 to November 2017. We observed that the ^{3}He and ^{4}He fluxes exhibit nearly identical variations with time. The relative magnitude of the variations decreases with increasing rigidity. The rigidity dependence of the ^{3}He/^{4}He flux ratio is measured for the first time. Below 4 GV, the ^{3}He/^{4}He flux ratio was found to have a significant long-term time dependence. Above 4 GV, the ^{3}He/^{4}He flux ratio was found to be time independent, and its rigidity dependence is well described by a single power law ∝R^{Δ} with Δ=-0.294±0.004. Unexpectedly, this value is in agreement with the B/O and B/C spectral indices at high energies.

Precision results on cosmic-ray electrons are presented in the energy range from 0.5 GeV to 1.4 TeV based on 28.1×10^{6} electrons collected by the Alpha Magnetic Spectrometer on the International Space Station. In the entire energy range the electron and positron spectra have distinctly different magnitudes and energy dependences. The electron flux exhibits a significant excess starting from 42.1&#95;{-5.2}^{+5.4}  GeV compared to the lower energy trends, but the nature of this excess is different from the positron flux excess above 25.2±1.8  GeV. Contrary to the positron flux, which has an exponential energy cutoff of 810&#95;{-180}^{+310}  GeV, at the 5σ level the electron flux does not have an energy cutoff below 1.9 TeV. In the entire energy range the electron flux is well described by the sum of two power law components. The different behavior of the cosmic-ray electrons and positrons measured by the Alpha Magnetic Spectrometer is clear evidence that most high energy electrons originate from different sources than high energy positrons.

Background: Acupuncture has been recommended as an alternative therapy for migraine. Emerging evidence suggests that the 5-HT 7 receptor (5-HT 7 R) plays a significant facilitatory role in descending modulation in migraine pathophysiology, and that activation of 5-HT 7 R in the descending pathway is involved in migraine central sensitisation., Objective: To investigate the ability of electroacupuncture (EA) to ameliorate central sensitisation via modulation of 5-HT 7 R in the descending pain pathways using a rat model of migraine induced by repetitive dural electrical stimulation (DES)., Design: 64 male Sprague-Dawley rats were randomly divided into four groups: Normal group; DES group (receiving dural electrical stimulation only); DES+GB20 group (DES model group treated with EA at GB20); and DES+Sham group (DES model group treated with EA at a non-traditional (sham) acupuncture point). The presence of cutaneous allodynia was determined by measuring facial and hind-paw withdrawal latencies to electronic von-Frey. The expression of 5-HT 7 R in the descending pathways (periaqueductal grey, raphe magnus nucleus, and trigeminal nucleus caudalis) was assessed using immunofluorescence and Western blotting., Results: Facial and hind-paw withdrawal thresholds were significantly increased in the DES+GB20 group compared with the untreated DES group. The expression of 5-HT 7 R was significantly decreased in the DES+GB20 group compared with the DES group (one-way analysis of variance (ANOVA), P<0.05). No significant differences in behaviour or expression were found between the rats in the DES+Sham group and the untreated DES group (one-way ANOVA, P>0.05)., Conclusion: EA at GB20 may ameliorate central sensitisation in migraine by inhibiting the activation of 5-HT 7 receptors in the descending pain pathway in a rat model of migraine.

Precision measurements of cosmic ray positrons are presented up to 1 TeV based on 1.9 million positrons collected by the Alpha Magnetic Spectrometer on the International Space Station. The positron flux exhibits complex energy dependence. Its distinctive properties are (a) a significant excess starting from 25.2±1.8  GeV compared to the lower-energy, power-law trend, (b) a sharp dropoff above 284&#95;{-64}^{+91}  GeV, (c) in the entire energy range the positron flux is well described by the sum of a term associated with the positrons produced in the collision of cosmic rays, which dominates at low energies, and a new source term of positrons, which dominates at high energies, and (d) a finite energy cutoff of the source term of E&#95;{s}=810&#95;{-180}^{+310}  GeV is established with a significance of more than 4σ. These experimental data on cosmic ray positrons show that, at high energies, they predominantly originate either from dark matter annihilation or from other astrophysical sources.

We present high-statistics, precision measurements of the detailed time and energy dependence of the primary cosmic-ray electron flux and positron flux over 79 Bartels rotations from May 2011 to May 2017 in the energy range from 1 to 50 GeV. For the first time, the charge-sign dependent modulation during solar maximum has been investigated in detail by leptons alone. Based on 23.5×10^{6} events, we report the observation of short-term structures on the timescale of months coincident in both the electron flux and the positron flux. These structures are not visible in the e^{+}/e^{-} flux ratio. The precision measurements across the solar polarity reversal show that the ratio exhibits a smooth transition over 830±30 days from one value to another. The midpoint of the transition shows an energy dependent delay relative to the reversal and changes by 260±30 days from 1 to 6 GeV.

A precision measurement of the nitrogen flux with rigidity (momentum per unit charge) from 2.2 GV to 3.3 TV based on 2.2×10^{6} events is presented. The detailed rigidity dependence of the nitrogen flux spectral index is presented for the first time. The spectral index rapidly hardens at high rigidities and becomes identical to the spectral indices of primary He, C, and O cosmic rays above ∼700  GV. We observed that the nitrogen flux Φ&#95;{N} can be presented as the sum of its primary component Φ&#95;{N}^{P} and secondary component Φ&#95;{N}^{S}, Φ&#95;{N}=Φ&#95;{N}^{P}+Φ&#95;{N}^{S}, and we found Φ&#95;{N} is well described by the weighted sum of the oxygen flux Φ&#95;{O} (primary cosmic rays) and the boron flux Φ&#95;{B} (secondary cosmic rays), with Φ&#95;{N}^{P}=(0.090±0.002)×Φ&#95;{O} and Φ&#95;{N}^{S}=(0.62±0.02)×Φ&#95;{B} over the entire rigidity range. This corresponds to a change of the contribution of the secondary cosmic ray component in the nitrogen flux from 70% at a few GV to <30% above 1 TV.

We present the precision measurement from May 2011 to May 2017 (79 Bartels rotations) of the proton fluxes at rigidities from 1 to 60 GV and the helium fluxes from 1.9 to 60 GV based on a total of 1×10^{9} events collected with the Alpha Magnetic Spectrometer aboard the International Space Station. This measurement is in solar cycle 24, which has the solar maximum in April 2014. We observed that, below 40 GV, the proton flux and the helium flux show nearly identical fine structures in both time and relative amplitude. The amplitudes of the flux structures decrease with increasing rigidity and vanish above 40 GV. The amplitudes of the structures are reduced during the time period, which started one year after solar maximum, when the proton and helium fluxes steadily increase. Above ∼3  GV the p/He flux ratio is time independent. We observed that below ∼3  GV the ratio has a long-term decrease coinciding with the period during which the fluxes start to rise.

UV radiation is the primary cause of skin photoaging, which results in an increase in matrix metalloproteinases and degradation of collagen. Developing new natural antioxidant as photoprotective agents has become a popular area of research. Orobanche cernua Loefling is a parasitic plant that is rich in phenylethanoid glycosides (PhGs). This study investigated the photoprotective effects of the ethanolic extract of Orobanche cernua Loefling (OC) and its principal component acteoside on UVB-induced photoaging as well as their underlying molecular mechanisms in normal human dermal fibroblasts (NHDFs). Biological testing demonstrated that OC and acteoside possessed significant photoprotective activities, reducing MMP and IL-6 levels while improving type-I procollagen synthesis in UVB-irradiated NHDFs. Further study showed that the protective mechanisms were the improvement of transcription factor Nrf2-mediated antioxidant defensive system, suppression of MAPK/AP-1 and activation of the TGF-β/Smad pathway. Together, our results suggested that OC might be a promising antiphotoaging agent against UV radiation-induced skin damage., (© 2018 The American Society of Photobiology.)

The brain of Down syndrome (DS) patients exhibits fewer interneurons in the cerebral cortex, but its underlying mechanism remains unknown. By morphometric analysis of cortical interneurons generated from DS and euploid induced pluripotent stem cells (iPSCs), we found that DS GABA neurons are smaller and with fewer neuronal processes. The proportion of calretinin over calbindin GABA neurons is reduced, and the neuronal migration capacity is decreased. Such phenotypes were replicated following transplantation of the DS GABAergic progenitors into the mouse medial septum. Gene expression profiling revealed altered cell migratory pathways, and correction of the PAK1 pathway mitigated the cell migration deficit in vitro. These results suggest that impaired migration of DS GABAergic neurons may contribute to the reduced number of interneurons in the cerebral cortex and hippocampus in DS patients., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

We report on the observation of new properties of secondary cosmic rays Li, Be, and B measured in the rigidity (momentum per unit charge) range 1.9 GV to 3.3 TV with a total of 5.4×10^{6} nuclei collected by AMS during the first five years of operation aboard the International Space Station. The Li and B fluxes have an identical rigidity dependence above 7 GV and all three fluxes have an identical rigidity dependence above 30 GV with the Li/Be flux ratio of 2.0±0.1. The three fluxes deviate from a single power law above 200 GV in an identical way. This behavior of secondary cosmic rays has also been observed in the AMS measurement of primary cosmic rays He, C, and O but the rigidity dependences of primary cosmic rays and of secondary cosmic rays are distinctly different. In particular, above 200 GV, the secondary cosmic rays harden more than the primary cosmic rays.

We report the observation of new properties of primary cosmic rays He, C, and O measured in the rigidity (momentum/charge) range 2 GV to 3 TV with 90×10^{6} helium, 8.4×10^{6} carbon, and 7.0×10^{6} oxygen nuclei collected by the Alpha Magnetic Spectrometer (AMS) during the first five years of operation. Above 60 GV, these three spectra have identical rigidity dependence. They all deviate from a single power law above 200 GV and harden in an identical way.

To study the effects of different variable temperature drying modes on active components of roots of Salvia miltiorrhiza f. alba, and provide basis for its industrialized drying process. In order to ensure the content of active components, variable temperature drying modes were designed: low temperature at 30 ℃ and high temperature at 60 ℃, low temperature at 30 ℃ and high temperature at 70 ℃, low temperature at 30 ℃ and high temperature at 80 ℃, low temperature at 40 ℃ and high temperature at 60 ℃, low temperature at 40 ℃ and high temperature at 70 ℃, low temperature at 40 ℃ and high temperature at 80 ℃ and air dry oven was used for variable temperature drying process. Then HPLC method was used to determine the changes of active components in roots of S. miltiorrhiza f. alba under different temperature modes; and SPSS 17.0 was used to analyze the data. The results showed that the samples, which were first dried at 40 ℃ for six hours and then dried at 80 ℃ for three hours, had the highest contents in dihydrotanshinone, cryptotanshinone, tanshinone Ⅰ and tanshinone ⅡA as compared with other kinds of drying methods, and the contents were 0.35, 2.76, 0.78, 4.47 mg•g⁻¹, respectively. Additionally, as compared with samples dried in the shade, the contents of dihydrotanshinone, cryptotanshinone and tanshinone Ⅰ were increased 2.9% (P>0.05), 45.3% (P<0.05) and 34.5% (P<0.05), respectively; however, the content of tanshinone ⅡA was decreased by 44.1% (P<0.05). The water-soluble active components (rosmarinic acid and salvianolic acid B) of roots of S. miltiorrhiza f. alba, had the highest contents when the samples were first dried at 30 ℃ for six hours and then 70 ℃ for three hours, and the contents were 3.83,55.44 mg•g⁻¹, increased by 62.3% (P<0.05) and 109.1% (P<0.05) respectively as compared with the samples dried in the shade. Variable temperature drying can significantly affect the contents of active components in roots of S. miltiorrhiza f. alba. As compared with the traditional process of shade-drying process, low temperature drying can significantly increase the content of water-soluble active components and also with significant promotion effect on the liposoluble components such as tanshinone ⅡA, cryptotanshinone and tanshinone Ⅰ. The variable temperature drying mode, can effectively shorten the process of drying and provide theoretical basis for industrial processing of roots of S. miltiorrhiza f. alba., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Most migraine patients suffer from cutaneous allodynia; however, the underlying mechanisms are unclear. Calcitonin gene-related peptide (CGRP) plays an important role in the pathophysiology of migraine, and it is therefore, a potential therapeutic target for treating the pain. In the present study, a rat model of conscious migraine, induced by repeated electrical stimulation of the superior sagittal sinus, was established and treated with electroacupuncture at Fengchi (GB20) (depth of 2-3 mm, frequency of 2/15 Hz, intensity of 0.5-1.0 mA, 15 minutes/day, for 7 consecutive days). Electroacupuncture at GB20 significantly alleviated the decrease in hind paw and facial withdrawal thresholds and significantly lessened the increase in the levels of CGRP in the trigeminal ganglion, trigeminal nucleus caudalis and ventroposterior medial thalamic nucleus in rats with migraine. No CGRP-positive cells were detected in the trigeminal nucleus caudalis or ventroposterior medial thalamic nucleus by immunofluorescence. Our findings suggest that electroacupuncture treatment ameliorates migraine pain and associated cutaneous allodynia by modulating the trigeminovascular system ascending pathway, at least in part by inhibiting CGRP expression in the trigeminal ganglion., Competing Interests: Conflicts of interest: None declared.

Two new phenolic acids forsythiayanoside C (1) and forsythiayanoside D (2), were isolated from the fruits of Forsythia suspense (Thunb.) Vahl. Their structures were elucidated on the basis of chemical and spectral analysis, including 1D, 2D NMR analyses, HRESIMS and CD spectrometry. The cytotoxic and antioxidant activities testing showed that compound 2 exhibited free radical scavenging activity.