Biomimetic, self-coacervating adhesive with tough underwater adhesion for ultrafast hemostasis and infected wound healing.

Massive bleeding and wound infection due to severe traumas pose a huge threat to the life and health of sufferers; therefore, it is of clinical importance to fabricate adhesives with rapid hemostatic and superior antibacterial capabilities. However, the weak wet adhesion and insufficient function of existing bioadhesives limits their practical application. In this study, a sandcastle worm protein inspired polyelectrolyte self-coacervate adhesive of poly-γ-glutamic acid (PGA) and lysozyme (LZM) was developed. The adhesive exhibited strong underwater adhesion to various surfaces (>250 kPa for solid plates and >50 kPa for soft tissues) and maintained a 80 kPa even when soaked in water for 7 days. Rat liver and tail defect bleeding models revealed that the hemostatic efficiency was superior to that of commercial samples. The in vitro antimicrobial tests showed that the bacterial inhibition to Staphylococcus aureus and Escherichia coli reached almost 100%. Additionally, the infected wound regeneration model demonstrated that the healing rate of the adhesive group was about 100% within 15 days, which was greater than that of the control group. In vitro and in vivo experiments proved that this facilely prepared adhesive will be a promising material to fulfil the integration functions for rapid wound closure and facilitating wound healing.

Impact of ecological reserves on the local residents' health: Evidence from a natural experiment in China.

The potential influence of natural ecosystems on human health has been widely acknowledged globally. Nevertheless, the causality of such a correlation among the middle-aged and older populations in developing countries awaits further investigations. This study aims to understand how a specific natural ecosystem change, namely the establishment of ecological reserves, improves the physical and mental health of middle-aged and older residents in China. Two batches of national key eco-function zones (NKEFZs) in 2011 and 2016 are selected as a quasi-experiment; and a total of 128,755 middle-aged and older residents from a combined data set from the China Family Panel Studies (CFPS) and China Health and Retirement Longitudinal Studies (CHARLS) from 2010 to 2020. A difference-in-differences method was used to identify the causal effects of the natural ecosystem improvement on human health outcomes. The results indicate significant and sustained improvements in the physical health of local middle-aged and elderly residents following the implementation of the NKEFZs policy. Notably, ecological reserves with a water conservation function and those in Karst area have the most salient effects on physical health. Furthermore, this study shows that the creation of ecological reserves improves the mental health of middle-aged and older residents, with the effect varying based on changes in physical health. This study provides new insights into the positive impact of natural ecosystem improvement on human health outcomes, in particular physical and mental health.

An exopolysaccharide from Lactobacillus pentosus YY-112: structure and effect on the human intestinal microbiota.

The development of novel prebiotics, which could regulate the intestinal microbiota, may help prevent and treat intestinal diseases. Here, we studied a homogeneous polysaccharide, LPE-2, produced by Lactobacillus pentosus YY-112 during fermentation. Methylation and gas chromatography-mass spectrometry analysis, combined with nuclear magnetic resonance results, suggested that the structural unit of LPE-2 comprises a branched mannan moiety and a linear glucan moiety. In vitro simulated intestinal fermentation showed that LPE-2 reduced harmful intestinal gas production and promoted short-chain fatty acid production (especially propionic acid). Moreover, it reduced the relative abundance of Escherichia-Shigella, increased that of Bifidobacterium and Lactobacillus, and had a stronger regulatory effect on intestinal flora in women than in men. The potential sex-specific prebiotic effects of LPE-2 on human intestinal health, were possibly related to its mannan branch with (1→2) and (1→3) linkages and backbones with flexible α configurations, which are sheared and degraded/utilized easier by Bifidobacterium and Lactobacillus.

Understanding teachers' online professional learning: A "community of inquiry" perspective on the role of Chinese middle school teachers' sense of self-efficacy, and online learning achievement.

Teachers' online professional development (PD) has been valued as a crucial and effective way to promote teaching competencies. Forming a professional learning community has been recognized as a means to promote effective PD. Within this realm of research, the Community of Inquiry (CoI) framework was deemed as a collaborative-constructivist process model that describes successful online learning experiences. The CoI has been associated with many psychological and educational variables, such as learning achievement and self-efficacy. This study leveraged on the CoI framework to assess teachers' online professional learning quality and explored its relationship with their self-efficacy and online professional learning achievement. A total of 456 teacher participants from Chinese middle schools participated in our study. A suite of questionnaires (the Community of Inquiry Questionnaire, the Teacher Efficacy Scale, and the Perceived Online Learning Achievement Scale) was distributed. Linear regression, PROCESS Macro mediation, and moderation analyses were run on the data to answer the research questions. Results revealed a significant relationship between teachers' online learning quality and their self-efficacy and learning achievement. The mediating roles of self-efficacy and learning achievement were confirmed. The moderating role of time spent on receiving online professional learning was also recognized. Implications and future directions were discussed.

Transforms of Cell Surface Glycoproteins Charge Influences Tumor Cell Metastasis via Atypically Inhibiting Epithelial-Mesenchymal Transition Including Matrix Metalloproteinases and Cell Junctions.

Cell communication and signal transduction rely heavily on the charge on the cell surface. The cell surface is negatively charged, with glycoproteins on the cell membrane providing a large percentage of the charge. Sialic acid is found on the outermost side of glycan chains and contributes to glycoprotein's negative charge. Sialic acid is highly expressed in tumor cells and plays an important role in tumor metastasis and immune escape by interacting with extracellular ligands. However, the specific effect of negative charge changes on glycoproteins is still poorly understood. In this study, we used 9-azido sialic acid (9Az-Sia) to create artificial epitopes on glycoproteins via metabolic glycan labeling, and we attached charged groups such as amino and carboxyl to 9Az-Sia via a click reaction with dibenzocyclooctyne (DBCO). The charge of glycoproteins was changed by metabolic glycan labeling and click modification. The results showed that the migration and invasion ability of the MDA-MB-231 cell labeled with 9Az-Sia was significantly reduced after the modification with amino groups rather than carboxyl groups. Epithelial-mesenchymal transition (EMT) is the biological process of metastatic tumor cells, with an increasing ability of tumor cells to migrate and invade. In particular, the expression of adhesion molecules increased in the amine-linked group, whereas the expression of matrix metalloproteinases (MMPs) increased significantly, which is not identical to EMT characteristics. In vivo experiments have demonstrated that the loss of negative charge on glycoproteins has an inhibitory effect on tumors. In conclusion, modifying the positive charge on the surface of glycoproteins can inhibit tumor cell metastasis and has great potential for tumor therapy.

Induction of Metabolic Reprogramming in Kidney by Singlet Diradical Nanoparticles.

Polycyclic aromatic compounds with an open-shell singlet diradical ground state, namely singlet diradicals, have recently gained attention in the fields of organic electronics, photovoltaics, and spintronics owing to their unique electronic structures and properties. Notably, singlet diradicals exhibit tunable redox amphoterism, which makes them excellent redox-active materials for biomedical applications. However, the safety and therapeutic efficacy of singlet diradicals in biological systems have not yet been explored. Herein, the study presents a newly designed singlet diradical nanomaterial, diphenyl-substituted biolympicenylidene (BO-Ph), exhibiting low cytotoxicity in vitro, non-significant acute nephrotoxicity in vivo, and the ability to induce metabolic reprogramming in kidney organoids. Integrated transcriptome and metabolome analyses reveal that the metabolism of BO-Ph stimulates glutathione (GSH) synthesis and fatty acid degradation, increases the levels of intermediates in the tricarboxylic acid (TCA) and carnitine cycles, and eventually boosts oxidative phosphorylation (OXPHOS) under redox homeostasis. Benefits of BO-Ph-induce metabolic reprogramming in kidney organoids include enhancing cellular antioxidant capacity and promoting mitochondrial function. The results of this study can facilitate the application of singlet diradical materials in the treatment of clinical conditions induced by mitochondrial abnormalities in kidney.

The metabolic score for insulin resistance as a predictor of clinical outcome in stroke patients treated by intravenous thrombolysis.

BACKGROUND AND PURPOSE: Insulin resistance is associated with clinical outcomes among patients with ischemic stroke. We aimed to investigate the association between metabolic score for insulin resistance (METS-IR) and clinical outcomes in stroke patients treated by intravenous thrombolysis (IVT). METHODS: We recruited participants treated with IVT from a prospective registry including 3 stroke centers. Poor outcome was defined as a modified Rankin scale score ≥ 3 points at 90 days after the index stroke. We performed logistic regression models to investigate the association between METS-IR and the risk of poor outcome. We used the receiver operative characteristic to assess the discriminative ability and the restricted cubic spline to explore the relationship between METS-IR and the poor outcome. RESULTS: This study enrolled a total of 1074 patients (median age, 68; 63.8% male). Three hundred sixty (33.5%) patients had poor outcome after IVT. METS-IR was associated with the risk of the poor outcome with the increase of confounding factors in models (odds ratio [OR], 1.078; 95% confidence interval [CI], 1.058-1.099; P < 0.001). The area under the curve for METS-IR for predicting the poor outcome was 0.790 (95% CI, 0.761-0.819). The restricted cubic spline revealed an increasing and non-linear association between METS-IR and the poor outcome (P for non-linearity < 0.001). CONCLUSION: Our study found that METS-IR was associated with an increased risk of poor outcome after IVT. Further studies are warranted to investigate the efficacy of anti-diabetic agents regarding IR on clinical outcomes after IVT.

Inhibiting virus replication and excessive inflammatory response: Mechanism of combined prescription of Ma-Xing-Shi-Gan decoction and Xiao-Chai-Hu decoction against influenza virus.

ETHNOPHARMACOLOGICAL RELEVANCE: The combined prescription of two classical decoctions (Ma-Xing-Shi-Gan decoction with Xiao-Chai-Hu decoction), named as San-Yang-He-Zhi (SYHZ) decoction, has been widely used for the treatment of influenza virus (IFV) infections for decades. AIM OF THE STUDY: This study aimed to evaluate the anti-influenza effect of SYHZ decoction and explore the underlying mechanism. MATERIALS AND METHODS: The ingredients of SYHZ decoction were analyzed by mass spectrometry. An animal model of IFV infection was established by challenging C57BL/6J mice with PR8 virus. Three groups of mice were infected with lethal or non-lethal doses of IFV, then followed by oral administration of phosphate-buffered saline (PBS), or SYHZ, or oseltamir; blank control mice (without IFV infection) were treated with PBS. Survival rate, Lung index, colon length, body weight loss and IFV viral load were measured 7 days post infection; histology and electron-microscopy examinations of lung tissue were performed; cytokine and chemokine levels in lung and serum were measured; and the intestinal metagenome, the cecum metabolome, and the lung transcriptome were analyzed. RESULTS: SYHZ treatment significantly improved survival rate compared with PBS (40% vs 0%); improved lung index, colon length, and body weight loss; and alleviated lung histological damage and viral load. SYHZ-treated mice had significantly lower levels of IL-1ß, TNF-α, IL-6, CCL2, CXCL10 in lung and serum, and increased levels of multiple bioactive components in cecum. Pro-inflammatory cytokines, Toll- and NOD-like receptors, pro-apoptosis molecules, and lung-injury-related proteins were downregulated in SYHZ mice, whereas surfactant protein and mucin were upregulated. The NOD-like receptor pathway, Toll-like receptor pathway, and NF-κB pathway were downregulated by SYHZ treatment. CONCLUSIONS: SYHZ decoction alleviated IFV infection in a mouse model. Multiple bioactive ingredients of SYHZ may inhibit replication of IFV and suppress excessive immune response.

Developing the Metacognitive Awareness of Grit Scale for a better understanding of learners of English as a foreign language.

The prominent impact of metacognition on learners' academic achievement is widely discussed. Learners armed with appropriate metacognitive strategies should witness enhancement in learning performance. Similarly, the concept of grit is also valued as a crucial factor contributing to the improvement of academic achievement. Nevertheless, discussion of the relationship between metacognition and grit or their collective influence on other educational and psychological variables is limited, not to mention that an instrument measuring learners' metacognitive awareness of grit is a desideratum. Hence, by incorporating the constructs of metacognition and grit, the present research developed a measurement scale to address this need, named the Metacognitive Awareness of Grit Scale (MCAGS). The MCAGS consists of four components and initially included 48 items. It was later distributed to 859 participants for the purpose of scale validation. Confirmatory factor analysis was applied to evaluate the scale's validity and explore the factor-item relationship. A final model containing 17 items was retained. Implications and future directions were discussed.

A Questionnaire Survey on Extrapulmonary Tuberculosis Control and Prevention - China, 2021.

What is already known about this topic?: Tuberculosis (TB) is a multisystem disease that might affect any organ. Currently, the National TB Program (NTP) issued by the State Council of China, only covers pulmonary tuberculosis (PTB), and the status of extrapulmonary tuberculosis (EPTB) remains unclear nationwide. What is added by this report?: The survey conducted by China CDC reported that there were no specific health facilities responsible for diagnosis, treatment and management of EPTB in China, while more than half of counties thought it should be included into NTP. What are the implications for public health practice?: China should include EPTB into NTP to achieve the target of End-TB strategy, a world free of TB. Zero deaths, disease and suffering due to TB.

Baicalin ameliorates multidrug-resistant Pseudomonas aeruginosa induced pulmonary inflammation in rat via arginine biosynthesis.

Multidrug-resistance (MDR) Pseudomonas aeruginosa (P. aeruginosa) is a lethal gram-negative pathogen causing hospital-acquired and ventilator-associated pneumonia, which is difficult to treat. Our previous studies confirmed that baicalin, an essential bioactive component in Scutellaria baicalensis Georgi, exhibited anti-inflammatory effects in an acute pneumonia rat model induced by MDR P. aeruginosa. However, this effect of baicalin in constrast its low bioavailability, and its mechanism of action is still unknown. Thus, this study investigated whether the therapeutic effects of baicalin against MDR P. aeruginosa acute pneumonia are owing to the regulation of gut microbiota and their metabolites using pyrosequencing of the 16S rRNA genes in rat feces and metabolomics. As a result, baicalin attenuated the inflammation by acting directly on neutrophils and regulated the production of the inflammatory cytokines TNF-α, IL-1ß, IL-6, and IL-10. The mechanisms were through down-regulation of TLR4 and inhibition of NF-κB. Furthermore, pyrosequencing of the 16S rRNA genes in rat feces revealed that baicalin regulated the composition of gut microbial communities. At the genus level, baicalin efficiently increased the abundance of Ligilactobacillus, Lactobacillus and Bacteroides, but decreased the abundance of Muribaculaceae and Alistipes. Further, arginine biosynthesis was analyzed as the core pathway regulated by baicalin via combination with predicting gut microbiota function and targeted metabolomics. In conclusion, this study has demonstrated that baicalin relieved inflammatory injury in acute pneumonia rat induced by MDR P. aeruginosa via arginine biosynthesis associated with gut microbiota. Baicalin could be a promising and effective adjunctive therapy for lung inflammation caused by MDR P. aeruginosa infection.

The moderating effect of participation in online learning activities and perceived importance of online learning on EFL teachers' teaching ability.

With the sudden outbreak of COVID-19, many educational contexts shifted from traditional face-to-face instruction to online and remote modes of delivery. This inspired a surge of scholarly attention in various countries to disclose the status and perceptions of stakeholders regarding online education. However, most of the existing studies in second/foreign language contexts are limited to students' and teachers' perceived emotions and experiences in e-instruction. Moreover, the extent to which online participation and the perceived importance of e-education influence teachers' teaching ability has been widely overlooked. To fill this gap, this study explored the moderating influence of EFL teachers' participation in online learning activities and the perceived importance of online learning on their teaching ability. In doing so, a questionnaire was spread and filled in by 453 Chinese EFL teachers with different backgrounds. The results of Structural Equation Modeling (SEM) obtained by Amos (v. 24) indicated that individual/demographic factors do not affect teachers' perceived importance of online learning. It was also demonstrated that the perceived importance of online learning and learning time does not predict EFL teachers' teaching ability. Furthermore, the results reveal that EFL teachers' teaching ability does not predict their perceived importance of online learning. However, teachers' participation in online learning activities predicted and explained 66% of the variance in their perceived importance of online learning. The study has implications for EFL teachers and teacher trainers in that it improves their awareness of the value of technologies in L2 education and practice.

Dendrobium officinale Xianhu 2 polysaccharide helps forming a healthy gut microbiota and improving host immune system: An in vitro and in vivo study.

Dendrobium officinale is widely consumed owing to its numerous beneficial effects. We aimed to characterize polysaccharides of Dendrobium officinale (DOP) from the stems of Dendrobium officinale Xianhu 2 and clarify whether it benefit the intestinal microbiota and the immune system. The DOP weighed 291 kDa and comprised mannose, glucose, galactose, and rhamnose at 59.31:33.31:1.00:0.51 M ratio. In in vitro/vivo studies, DOP significantly increased benign intestinal microbe proportion (Lactobacillus, etc.), but reduced harmful bacteria (Escherichia_Shigella) (P < 0.05), and significantly increased butyric acid production (P < 0.05). Concentrations of 2 g/L DOP for in vitro fermentation and 100 mg/kg body weight for the mouse model were effective. In mice, DOP significantly reduced CRP, CD3, CD4, and TNF-α levels and increased C4 levels (P < 0.05). DOP might influence the immune system indirectly through regulation of the gut microbiota. Its possible regulation mechanism was that DOP reduced CD4+ Th cells proliferation so that reduced the secretion of TNF-α.

Does local government competition affect the dependence on polluting industries? Evidence from China's land market.

Many countries have formulated strict environmental regulation policies, but unfortunately, environmental pollution is still severe. We believe that this phenomenon may result from institutional factors. We study whether local government competition affects the dependence on polluting industries and test it with the transaction data of China's land market. We find that the decline in the economic ranking of cities increases the scale of land transferred to polluting industries, and the more the ranking decline, the larger the scale of land in polluting industries. Besides, we analyze the impact of the first decline in the urban economic ranking, finding that the land transfer scale of polluting industries exhibits a trend of slowing down after a rapid rise in the short term. Heterogeneity analysis shows that officials with lower education levels and before-retirement age will dependent more on polluting industries to a greater extent when they face local government competition, and cities with economic growth lower than the national average will increase their dependence on polluting industries to a greater extent. This paper provides new insights into the causes of the environmental governance dilemma, which also highlights the need to weaken economic indicators and strengthen environmental indicators in government performance assessment.

Detection of Glucose Based on Noble Metal Nanozymes: Mechanism, Activity Regulation, and Enantioselective Recognition.

Glucose monitoring is essential to evaluate the degree of glucose metabolism disorders. The enzymatic determination has been the most widely used method in glucose detection because of its high efficiency, accuracy, and sensitivity. Noble metal nanomaterials (NMs, i.e., Au, Ag, Pt, and Pd), inheriting their excellent electronic, optical, and enzyme-like properties, are classified as noble metal nanozymes (NMNZs). As the NMNZs are often involved in two series of reactions, the oxidation of glucose and the chromogenic reaction of peroxide, here the chemical mechanism by employing NMNZs with glucose oxidase (GOx) and peroxidase (POD) mimicking activities is briefly summarized first. Subsequently, the regulation strategies of the GOx-like, POD-like and tandem enzyme-like activities of NMNZs are presented in detail, including the materials, size, morphology, composition, and the reaction condition of the representative NMs. In addition, in order to further mimic the enantioselectivity of enzyme, the design of NMNZs with enantioselective recognition of d-glucose and l-glucose by using different chiral compounds (DNA, amino acids, and cyclodextrins) and molecular imprinting is further described in this review. Finally, the feasible solutions to the existing challenges and a vision for future development possibilities are discussed.

Directional methanolysis of kitchen waste for the co-production of methyl levulinate and fatty acid methyl esters: Catalytic strategy and machine learning modeling.

To add value to ordinary kitchen waste, heterogeneous acid-base catalytic methanolysis was conducted to produce high-value liquid biofuels, methyl levulinate (ML) and fatty acid methyl esters (FAMEs). Yields of 53.3 % ML and 98.5 % FAME were achieved by methanolysis of kitchen waste under the co-catalysis of carbon-silica composite (C/Si-SO3H) and zirconium modified ultrastable Y zeolite (Zr/USY). These target products can be easily recovered from the methanolic phase and can be purified at the end of the reaction. The collaborative combination of C/Si-SO3H and Zr/USY exhibited higher activity than their commercial counterpart. This strategy can be applied to differently composed kitchen waste and kitchen waste with different water content. Product yields were predicted using an artificial neural network method, and the relative importance of the influencing factors was investigated by the random forest method. The systematic insight gained from this work supports the value-added utilization of kitchen waste.

Unstable platform training in tennis players / Treinamento em plataforma instável em tenistas / Entrenamiento en plataforma inestable en tenistas

ABSTRACT Introduction: The constant maintenance of muscular strength is a highly relevant care in training for tennis practice. The unstable platform is developed with the improvement of modern and technological resources, and the need to verify its effects on the athletes' physical fitness is requested. Objective: Study the effect of unstable platform training on tennis players' balance ability and assertiveness. Methods: 12 male tennis-practicing students of the Beijing Sports University School of Education 2020 class were randomly selected as research volunteers. Through a literature search, data statistics, and other methods, they were randomly divided into an experimental group and a control group. After 6 weeks of traditional training in the control group and the addition of unstable platform balance training in the experimental group, the results were compared. Results: The ability to stand with eyes open on the dominant leg was significantly improved in the experimental group. After routine training and balance training, the athletes in the experimental group had a great improvement in the assertiveness of passes (P<0.05), and the stability of the service was also improved (P<0.05). Conclusion: After training, all physical abilities were improved. The unstable platform training is a valid resource to improve athletes' balance and assertiveness ability. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A constante manutenção da força muscular é um cuidado altamente relevante no treinamento para a prática do tênis. A plataforma instável é desenvolvida com o aperfeiçoamento de recursos modernos e tecnológicos e a necessidade de verificar os seus efeitos sobre a aptidão física dos atletas é requisitada. Objetivo: Estudar o efeito do treinamento em plataforma instável sobre a capacidade de equilíbrio e assertividade dos tenistas. Métodos: Um total de 12 estudantes masculinos praticantes de tênis da classe 2020 da Escola de Educação da Universidade Esportiva de Beijing foram selecionados aleatoriamente como voluntários de pesquisa. Através de pesquisas bibliográficas, estatísticas de dados e outros métodos, eles foram divididos aleatoriamente em grupo experimental e grupo controle. Após 6 semanas de treinamento tradicional ao grupo controle e a adição de um treinamento de equilíbrio em plataforma instável no grupo experimental, comparou-se os resultados. Resultados: A capacidade de ficar em pé com os olhos abertos sobre a perna dominante foram significativamente aprimorados no grupo experimental. Após o treinamento de rotina e o treinamento de equilíbrio, os atletas do grupo experimental tiveram uma grande melhora na assertividade dos passes (P<0,05), e a estabilidade do saque também foi aprimorada(P<0,05). Conclusão: Após o treinamento, todas as habilidades físicas foram melhoradas. O treinamento em plataforma instável é um recurso válido para aprimorar a capacidade de equilíbrio e assertividade dos atletas. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El mantenimiento constante de la fuerza muscular es un cuidado muy relevante en el entrenamiento para la práctica del tenis. La plataforma inestable se desarrolla con la mejora de los recursos modernos y tecnológicos y se solicita la comprobación de sus efectos sobre la aptitud física de los deportistas. Objetivo: Estudiar el efecto del entrenamiento en plataforma inestable sobre la capacidad de equilibrio y asertividad de los tenistas. Métodos: Un total de 12 estudiantes varones practicantes de tenis de la clase 2020 de la Escuela de Educación de la Universidad de Deportes de Pekín fueron seleccionados al azar como voluntarios para la investigación. Mediante la búsqueda de literatura, la estadística de datos y otros métodos, se dividieron aleatoriamente en grupo experimental y grupo de control. Tras 6 semanas de entrenamiento tradicional en el grupo de control y la adición del entrenamiento de equilibrio en plataforma inestable en el grupo experimental, se compararon los resultados. Resultados: La capacidad de mantenerse en pie con los ojos abiertos sobre la pierna dominante mejoró significativamente en el grupo experimental. Después del entrenamiento de rutina y del entrenamiento de equilibrio, los atletas del grupo experimental tuvieron una gran mejora en el asertividad de los pases (P<0,05), y también mejoró la estabilidad del saque (P<0,05). Conclusión: Tras el entrenamiento, todas las capacidades físicas mejoraron. El entrenamiento en plataforma inestable es un recurso válido para mejorar la capacidad de equilibrio y asertividad de los deportistas. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Slower progression of amyotrophic lateral sclerosis with external application of a Chinese herbal plaster-The randomized, placebo-controlled triple-blinded ALS-CHEPLA trial.

Background: Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterized by gradually increasing damage to the upper and lower motor neurons. However, definitive and efficacious treatment for ALS is not available, and oral intake in ALS patients with bulbar involvement is complicated due to swallowing difficulties. Hypothesis/purpose: This study investigated whether the external plaster application of the herbal composition Ji-Wu-Li efficiently slows ALS progression because prior studies obtained promising evidence with oral herbal applications. Study design: The randomized, triple-blinded study compared the efficacy, safety, and tolerability of the application of Ji-Wu-Li plaster (JWLP) with placebo plaster (PLAP). Methods: In total, 120 patients with definite ALS, clinically probable ALS, or clinically probable laboratory-supported ALS were randomized in a 1:1 ratio to receive JWLP or PLAP. Patients were treated and observed for 20 weeks. The primary outcome was the ALSFRS-R score, while the secondary outcomes were the ALS-SSIT score and weight loss. Results: The mean±SD decrease in the ALSFRS-R over 20 weeks differed by 0.84 points in a group comparison (JWLP, -4.44 ± 1.15; PLAP, -5.28 ± 1.98; p = 0.005). The mean increase in the ALS-SSIT over 20 weeks differed by 2.7 points in a group comparison (JWLP, 5.361.15; PLAP, 8.06 ± 1.72; p < 0.001). The mean weight loss over 20 weeks differed by 1.65 kg in a group comparison (JWLP, -3.98 ± 2.61; PLAP, -5.63 ± 3.17; p = 0.002). Local allergic dermatitis suspected as causal to the intervention occurred in 10 of 60 participants in the JWLP group and 9 of 60 participants in the PLAP group. Systemic adverse events were mild, temporary, and considered unrelated to the intervention. Conclusion: The JWLP showed clinical efficacy in the progression of ALS, as measured by the ALSFRS-R, ALS-SSIT, and weight loss in a randomized, placebo-controlled trial. Because skin reactions occurred in both groups, the covering material needs improvement. All of the Ji Wu Li herbal ingredients regulate multiple mechanisms of neurodegeneration in ALS. Hence, JWLP may offer a promising and safe add-on therapy for ALS, particularly in patients with bulbar involvement, but a confirmative long-term multicentre study is required.

Naoxintong Capsule for Secondary Prevention of Ischemic Stroke: A Multicenter, Randomized, and Placebo-Controlled Trial.

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION: The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).