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Metal oxide nanoparticles encapsulated and nitrogen-doped carbon nanotubes was prepared by a novel low-temperature metal-catalyzed synthesis strategy from carbon nitride as anodic materials of high-performance lithium-ion batteries.

Objective EMPOwER, a double-blind, randomised, phase 3 study, evaluated the efficacy and safety of erenumab in adults with episodic migraine from Asia, the Middle East, and Latin America. Methods Randomised patients (N = 900) received monthly subcutaneous injections of placebo, erenumab 70 mg, or 140 mg (3:3:2) for 3 months. Primary endpoint was change from baseline in monthly migraine days at Month 3. Other endpoints included achievement of ≥50%, ≥75%, and 100% reduction in monthly migraine days, change in monthly acute migraine-specific medication treatment days, patient-reported outcomes, and safety assessment. Results At baseline, mean (standard deviation) age was 37.5 (9.9) years, 81.9% were women, and monthly migraine days was 8.2 (2.8). At Month 3, change from baseline in monthly migraine days (primary endpoint) was −3.1, −4.2, and −4.8 days for placebo, erenumab 70 mg, and erenumab 140 mg, respectively, with a statistically significant difference for erenumab versus placebo (P = 0.002 [70 mg], P Conclusions This study of erenumab in patients with episodic migraine from Asia, the Middle East, and Latin America met all primary and secondary endpoints. A consistent numerical benefit was observed with erenumab 140 mg versus erenumab 70 mg across all efficacy endpoints. These findings extend evidence of erenumab’s efficacy and safety to patients under-represented in previous trials. ClinicalTrials.gov identifier: NCT03333109

Migraine is one of top 5 medical conditions that contribute to Years Lived with Disability and affects approximately 1 billion people from around the world. To date, preventive treatment and acute therapies for migraine are limited, have undesirable side effects and are poorly tolerated in patients. In the last few decades, considerable advances in our understanding of migraine and its pathophysiology have paved the way for the development of targeted treatment options. Calcitonin gene-related peptide (CGRP) plays an integral role in the neurobiology of migraine, and new classes of drugs that target the CGRP pathway have included gepants and CGRP pathway monoclonal antibodies. Serotonin 5-HT1F receptor agonists—namely ditans—have also been developed to treat acute migraine. Lastly, non-invasive neuromodulation offers another treatment option for migraine patients who prefer treatments that have fewer side effects and are well tolerated. In this review, we discussed emerging treatment options for migraine that were made available in recent years. Ann Acad Med Singapore 2020;49:226–35 Key words: Calcitonin gene-related peptide monoclonal antibody, Gepants, Headache, Lasmiditan, Neuromodulation

Management of migraine in adolescents poses a great challenge, as many of the approved pharmacological migraine preventive agents have age restrictions. Following favorable safety and efficacy reports of the new class agent calcitonin gene-related peptide (CGRP) monoclonal antibody for use in migraine prevention, there is growing interest in its application in pediatric migraine. We present here a case series detailing our experience of using erenumab, a CGRP monoclonal antibody, in six adolescent patients. Two patients had a reduction of at least 50% in the mean number of monthly migraine days, one patient reported subjective improvement, while three patients did not respond to the first dose of erenumab and discontinued treatment. One patient reported constipation associated with erenumab use. We speculate that CGRP monoclonal antibody could potentially be a viable option in adolescent patients with migraine. Further evidences that support efficacy and safety of erenumab in this group is needed.

Background: Hand-foot-and-mouth disease (HFMD) is a common childhood illness caused by enteroviruses. Oseltamivir (OS), a neuraminidase inhibitor, has been frequently used as an adjunctive therapy for the treatment of HFMD. Solid evidence, however, is lacking regarding the efficacy of such adjunctive therapy. This work is to conduct a meta-analysis of randomized clinical trials (RCTs) to assess the efficacy of oseltamivir for HFMD in children.Methods: Eligible studies from inception to October 10, 2020 were identified by searching six databases (PubMed, Embase, CENTRAL, CNKI, Wanfang, and VIP database). Quality of evidence was assessed using the Cochrane Collaboration tool.Results: Of a total of 91 entries, 11 RCTs involving 977 HFMD children were included in the final analysis. The results showed that the therapy combined with oseltamivir was more effective, with higher effective rate (RR, 0.84; 95% CI, 0.80 to 0.87; p < 0.01), shorter fever clearance time (days) (SMD, −0.74; 95% CI, −1.12 to −0.35; p < 0.01), shorter rash regression time (days) (MD, −0.89; 95% CI, −1.05 to −0.72; p < 0.01) and shorter clinical cure time (SMD, −1.08; 95% CI, −1.55 to −0.61; p < 0.01). No significant difference was observed in the risk of adverse reactions between the groups with and without oseltamivir.Conclusion: The use of oseltamivir as adjunctive therapy shows effectiveness and no increased risk of adverse reactions for the treatment of HFMD in children.

Migraine is one of top 5 medical conditions that contribute to Years Lived with Disability and affects approximately 1 billion people from around the world. To date, preventive treatment and acute therapies for migraine are limited, have undesirable side effects and are poorly tolerated in patients. In the last few decades, considerable advances in our understanding of migraine and its pathophysiology have paved the way for the development of targeted treatment options. Calcitonin gene-related peptide (CGRP) plays an integral role in the neurobiology of migraine, and new classes of drugs that target the CGRP pathway have included gepants and CGRP pathway monoclonal antibodies. Serotonin 5-HT

Metabolomics offers a noninvasive methodology to identify metabolic markers for pathogenesis and diagnosis of diseases. This work aimed to characterize circulating metabolic signatures of benign thyroid nodule (BTN) and papillary thyroid carcinoma (PTC) via serum-plasma matched metabolomics. A cohort of 1,540 serum-plasma matched samples and 114 tissues were obtained from healthy volunteers, BTN and PTC patients enrolled from 6 independent centers. Untargeted metabolomics was determined by liquid chromatography-quadrupole time-of-flight mass spectrometric and multivariate statistical analyses. The use of serum-plasma matched samples afforded a broad-scope detection of 1,570 metabolic features. Metabolic phenotypes revealed significant pattern differences for healthy versus BTN and healthy versus PTC. Perturbed metabolic pathways related mainly to amino acid and lipid metabolism. It is worth noting that, BTN and PTC showed no significant differences but rather overlap in circulating metabolic signatures, and this observation was replicated in all study centers. For differential diagnosis of healthy versus thyroid nodules (BTN + PTC), a panel of 6 metabolic markers, namely myo-inositol, α-N-phenylacetyl-L-glutamine, proline betaine, L-glutamic acid, LysoPC(18:0) and LysoPC(18:1) provided area under the curve of 97.68% in the discovery phase and predictive accuracies of 84.78-98.18% in the 4 validation centers. Taken together, serum-plasma matched metabolomics showed significant differences in circulating metabolites for healthy versus nodules but not for BTN versus PTC. Our results highlight the true metabolic nature of thyroid nodules, and potentially decrease overtreatment that exposes patients to unnecessary risks.

Extracellular vesicles (EVs) from mesenchymal stromal cells (MSCs) have previously been shown to protect against brain injury caused by hypoxia-ischemia (HI). The neuroprotective effects have been found to relate to the anti-inflammatory effects of EVs. However, the underlying mechanisms have not previously been determined. In this study, we induced oxygen-glucose deprivation in BV-2 cells (a microglia cell line), which mimics HI in vitro, and found that treatment with MSCs-EVs increased the cell viability. The treatment was also found to reduce the expression of pro-inflammatory cytokines, induce the polarization of microglia towards the M2 phenotype, and suppress the phosphorylation of selective signal transducer and activator of transcription 3 (STAT3) in the microglia. These results were also obtained in vivo using neonatal mice with induced HI. We investigated the potential role of miR-21a-5p in mediating these effects, as it is the most highly expressed miRNA in MSCs-EVs and interacts with the STAT3 pathway. We found that treatment with MSCs-EVs increased the levels of miR-21a-5p in BV-2 cells, which had been lowered following oxygen-glucose deprivation. When the level of miR-21a-5p in the MSCs-EVs was reduced, the effects on microglial polarization and STAT3 phosphorylation were reduced, for both the in vitro and in vivo HI models. These results indicate that MSCs-EVs attenuate HI brain injury in neonatal mice by shuttling miR-21a-5p, which induces microglial M2 polarization by targeting STAT3.

Background: Hand-foot-and-mouth disease (HFMD) is a common childhood illness caused by enteroviruses. Oseltamivir (OS), a neuraminidase inhibitor, has been frequently used as an adjunctive therapy for the treatment of HFMD. Solid evidence, however, is lacking regarding the efficacy of such adjunctive therapy. This work is to conduct a meta-analysis of randomized clinical trials (RCTs) to assess the efficacy of oseltamivir for HFMD in children. Methods: Eligible studies from inception to 10th October 2020 were identified by searching six databases (PubMed, Embase, CENTRAL, CNKI, Wanfang, and VIP database). Quality of evidence was assessed using the Cochrane Collaboration tool. Findings: Of a total of 91 entries, 11 RCTs involving 977 HFMD children were included in the final analysis. The results showed that the therapy combined with oseltamivir was more effective, with higher effective rate (RR, 0·84; 95% CI, 0·80 to 0·87; p < 0·01), shorter fever clearance time (days) (SMD, -0·74; 95%CI, -1·12 to -0·35; p < 0.01), shorter rash regression time (days) (MD, -0·89; 95%CI, -1·05 to -0·72; p < 0·01) and shorter clinical cure time (SMD, -1·08; 95%CI, -1·55 to -0·61; p < 0·01). No significant difference was observed in the risk of adverse reactions between the groups with and without oseltamivir. Interpretation: The use of oseltamivir as adjunctive therapy shows effectiveness and no increased risk of adverse reactions for the treatment of HFMD in children. Funding Statement: This study was supported by grant from the National Natural Science Foundation of China (81903390). Declaration of Interests: The authors have nothing to disclose.

Background Pathogenesis and diagnostic biomarkers for diseases can be discovered by metabolomic profiling of human fluids. If the various types of coronary artery disease (CAD) can be accurately characterized by metabolomics, effective treatment may be targeted without using unnecessary therapies and resources. Objectives The authors studied disturbed metabolic pathways to assess the diagnostic value of metabolomics-based biomarkers in different types of CAD. Methods A cohort of 2,324 patients from 4 independent centers was studied. Patients underwent coronary angiography for suspected CAD. Groups were divided as follows: normal coronary artery (NCA), nonobstructive coronary atherosclerosis (NOCA), stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI). Plasma metabolomic profiles were determined by liquid chromatography–quadrupole time-of-flight mass spectrometry and were analyzed by multivariate statistics. Results We made 12 cross-comparisons to and within CAD to characterize metabolic disturbances. We focused on comparisons of NOCA versus NCA, SA versus NOCA, UA versus SA, and AMI versus UA. Other comparisons were made, including SA versus NCA, UA versus NCA, AMI versus NCA, UA versus NOCA, AMI versus NOCA, AMI versus SA, significant CAD (SA/UA/AMI) versus nonsignificant CAD (NCA/NOCA), and acute coronary syndrome (UA/AMI) versus SA. A total of 89 differential metabolites were identified. The altered metabolic pathways included reduced phospholipid catabolism, increased amino acid metabolism, increased short-chain acylcarnitines, decrease in tricarboxylic acid cycle, and less biosynthesis of primary bile acid. For differential diagnosis, 12 panels of specific metabolomics-based biomarkers provided areas under the curve of 0.938 to 0.996 in the discovery phase (n = 1,086), predictive values of 89.2% to 96.0% in the test phase (n = 933), and 85.3% to 96.4% in the 3-center external sets (n = 305). Conclusions Plasma metabolomics are powerful for characterizing metabolic disturbances. Differences in small-molecule metabolites may reflect underlying CAD and serve as biomarkers for CAD progression.

Metabolomics offers a noninvasive methodology to identify metabolic markers for pathogenesis and diagnosis of diseases. This work aimed to characterize circulating metabolic signatures of benign thyroid nodule (BTN) and papillary thyroid carcinoma (PTC) via serum-plasma matched metabolomics. A cohort of 1,540 serum-plasma matched samples and 114 tissues were obtained from healthy volunteers, BTN and PTC patients enrolled from 6 independent centers. Untargeted metabolomics was determined by liquid chromatography-quadrupole time-of-flight mass spectrometric and multivariate statistical analyses. The use of serum-plasma matched samples afforded a broad-scope detection of 1,570 metabolic features. Metabolic phenotypes revealed significant pattern differences for healthy versus BTN and healthy versus PTC. Perturbed metabolic pathways related mainly to amino acid and lipid metabolism. It is worth noting that, BTN and PTC showed no significant differences but rather overlap in circulating metabolic signatures, and this observation was replicated in all study centers. For differential diagnosis of healthy versus thyroid nodules (BTN + PTC), a panel of 6 metabolic markers, namely myo-inositol, α-N-phenylacetyl-L-glutamine, proline betaine, L-glutamic acid, LysoPC(18:0) and LysoPC(18:1) provided area under the curve of 97.68% in the discovery phase and predictive accuracies of 84.78-98.18% in the 4 validation centers. Taken together, serum-plasma matched metabolomics showed significant differences in circulating metabolites for healthy versus nodules but not for BTN versus PTC. Our results highlight the true metabolic nature of thyroid nodules, and potentially decrease overtreatment that exposes patients to unnecessary risks.

Objective To explore the effects of sliding-cup with different parameters on energy metabolism in the body by observing the effect of sliding-cup along the governor vessel on transcutaneous partial pressures of oxygen and carbon dioxide in Mingmen ( GV 4) in sub-healthy people. Methods A total of 10 sub-healthy adults at rest were observed and sliding-cup along the governor vessel were conducted with three different parameters, jar-pressure of −0.01∼−0.02 MPa with sliding-cup for 5 min, jar-pressure of −0.02∼−0.03 MPa with sliding-cup for 5 min and jar-pressure of −0.02∼−0.03 MPa with sliding-cup for 3 min. PeriFlux System5000 PF5040 module was employed to monitor the changes of transcutaneous partial pressures of oxygen (tcpO 2 ) and carbon dioxide (tcpCO 2 ) in GV 4 at 0 min, 5 min, 10 min, 15 min, 20 min, 25 min and 30 min after sliding-cup with above different interventions in sub-healthy subjects. Results After sliding-cup, tcpO 2 increased at first and then decreased over time; there was no difference in tcpO 2 after sliding-cupping with different parameters (all P >0.05). After sliding-cup, tcpCO 2 decreased; there was no difference in tcpCO 2 after sliding-cup with different parameters (all P >0.05). Conclusion Sliding-cup has a sustained effect on the body and can speed up the energy metabolism in the body.

One three-dimensional coordination polymer material, {[Cu3(nbta)2(bpfp)2(H2O)2](H2O)2}n (H3nbta = 5-nitro-1,2,3-benzenetricarboxylic acid, bpfp = bis(4-pyridylformyl)piperazine), is synthesized and structurally characterized. X-Ray structural analysis shows that the compound exhibits a three-dimensional structure featuring an unusual 3-nodal 4-connected topology. The compound is further characterized by elemental analysis, infrared spectrum, thermogravimetric analysis, and UV–vis absorption spectrum. Importantly, the compound exhibits efficient heterogeneous catalytic activity to the Knoevenagel reaction at room temperature. Moreover, the recyclability and heterogeneity of the reaction were also explored.

We investigated the influence of gut microbiotal metabolism on the pharmacokinetics of berberine in healthy male Africans and Chinese. The Cmax and AUC in the Africans were 2.67-fold and 2.0-fold higher than the Chinese, respectively. Microbiotal compositions by 16S rRNA pyrosequencing showed higher abundance of the genera Prevotella, Bacteroides and Megamonas (34.22, 13.88 and 10.68%, respectively) in the Chinese than the Africans (30.08, 9.43 and 0.48%, respectively). Scatter plot showed a strong negative correlation between the microbiotal abundance and the berberine AUC, especially for the genus Prevotella (r = −0.813) and its species. A more extensive metabolism was observed in Chinese with 1.83-fold higher metabolites, possibly contributing to the lower AUC than the Africans. In conclusion, significant PK differences of berberine were observed between Africans and Chinese, which is partly attributable to variations in gut microbiota and its corresponding metabolic capacity.

Intelligent resource includes the knowledge, hardware and software resources even workflow and human resource, etc. From the point of view of enterprise information management, the service composition is an essential element for companies’ informatization construction. Therefore, the paper describes a web service composition framework for semantically-annotated web service. Based on the state of art ontology technology, an OWL-S process model for the CAM software is established to describe resource service. Then a service discovery process which mainly consists of services’ property matching algorithm for words is set up. A backward chaining framework for service composition is employed to dynamically compose resource services finally.

K-601 is an herbal formulation for influenza consisting of Lonicera japonica, Isatis indigotica, Rheum palmatum, Phellodendron chinense and Scutellaria baicalensis. In this work, we characterized the chemical constituents in K-601, identified the absorbed compounds and determined their pharmacokinetics in 6 Chinese and African volunteers by liquid chromatography with time-of-flight mass spectrometry. Similarity evaluation for chromatographic fingerprint of nine different batches showed values above 0.983. Totally, 50 components were identified in K-601. Then, 15 major prototype compounds and 17 metabolites were identified in human plasma. Major metabolic pathways included glucuronidation, sulfation, methylation, demethylation and reduction. The pharmacokinetics of the most abundant prototype compounds, berberine, jatrorrhizine, palmatine and magnoflorine were determined. Significant pharmacokinetic differences were observed between the African and Chinese subjects. The AUCs of the African is about 4–10 fold higher than that of the Chinese for the three benzylisoquinoline alkaloids. Magnoflorine, an aporphine alkaloid, was absorbed better in the Chinese than in the African. The biotransformation of K-601 by human intestinal microflora was also investigated. The major reactions included hydroxylation, methylation, demethylation, acetylation and reduction. Glucuronidation and sulfation were not observed with fecal flora. These results may be important and useful in linking data from pharmacological assays and clinical effects.

The anticancer activities of ginsenosides are widely reported. The structure-activity relationship of ginsenosides against cancer is not well elucidated because of the unavailability of these compounds. In this work, we developed a transformation method to rapidly produce rare dehydroxylated ginsenosides by acid treatment. The optimized temperature, time course and concentration of formic acid were 120°C, 4 h and 0.01%, respectively. From 100 mg of Rh1, 8.3 mg of Rk3 and 18.7 mg of Rh4 can be produced by acid transformation. Similarly, from 100 mg of Rg3, 7.4 mg of Rk1 and 15.1 mg of Rg5 can be produced. From 100 mg of Rh2, 8.3 mg of Rk2 and 12.7 mg of Rh3 can be generated. Next, the structure-activity relationships of 23 ginsenosides were investigated by comparing their cytotoxic effects on six human cancer cells, including HCT-116, HepG2, MCF-7, Hela, PANC-1 and A549. The results showed that: (1) the cytotoxic effect of ginsenosides is inversely related to the sugar numbers; (2) sugar linkages rank as C-3 > C-6 > C-20; (3) the protopanaxadiol-type has higher activities; (4) having the double bond at the terminal C20-21 exhibits stronger activity than that at C20-22; and (5) 20(S)-ginsenosides show stronger effects than their 20(R)-stereoisomers.