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Chronic diabetic wounds are an important healthcare challenge. High concentration glucose, high level of matrix metalloproteinase-9 (MMP-9), and long-term inflammation constitute the special wound environment of diabetic wounds. Tissue necrosis aggravates the formation of irregular wounds. All the above factors hinder the healing of chronic diabetic wounds. To solve these issues, a glucose and MMP-9 dual-response temperature-sensitive shape self-adaptive hydrogel (CBP/GMs@CelINS) was designed and constructed with polyvinyl alcohol (PVA) and chitosan grafted with phenylboric acid (CS-BA) by encapsulating insulin (INS) and gelatin microspheres containing celecoxib (GMs@Cel). Temperature-sensitive self-adaptive CBP/GMs@CelINS provides a new way to balance the fluid-like mobility (self-adapt to deep wounds quickly, approximately 37 °C) and solid-like elasticity (protect wounds against external forces, approximately 25 °C) of self-adaptive hydrogels, while simultaneously releasing insulin and celecoxib on-demand in the environment of high-level glucose and MMP-9. Moreover, CBP/GMs@CelINS exhibits remodeling and self-healing properties, enhanced adhesion strength (39.65 ± 6.58 kPa), down-regulates MMP-9, and promotes cell proliferation, migration, and glucose consumption. In diabetic full-thickness skin defect models, CBP/GMs@CelINS significantly alleviates inflammation and regulates the local high-level glucose and MMP-9 in the wounds, and promotes wound healing effectively through the synergistic effect of temperature-sensitive shape-adaptive character and the dual-responsive system.

Hypoxia, excessive reactive oxygen species (ROS), impaired angiogenesis, lasting inflammation, and bacterial infection, are key problems impeding diabetic wound healing. Particularly, controllable oxygen release and ROS scavenging capacities are critical during the wound healing process. Here, an injectable hydrogel based on hyaluronic acid

Ginsenoside Rh4 inhibited inflammation, oxidative stress and apoptosis in mice with gastric ulcers through modulation of MAPK/NF-κB and PGE2-Cox pathways, thereby ameliorating gastric injury.

The cross-disciplinary integration of acupuncture with modern medicine is an important guarantee to maintain its advantages. Based on 13896 acupuncture articles and 404726 references in the Web of Science Core Database, this paper analyzes the cross-disciplinary integration of acupuncture and modern medicine. It was found that the trend of cross-disciplinary integration between acupuncture and modern medicine is more and more obvious. Neurosciences, Anesthesiology, Oncology, Obstetrics & Gynecology, Psychiatry, and Gastroenterology & Hepatology are the subjects with the most crossover and integration, accounting for 56% of the total disciplines. At the same time, more studies have begun to use modern medical methods to study the mechanism of acupuncture. Biochemistry & Molecular Biology, Pharmacology & Pharmacy, and Medicine, Research & Experimental have been major areas of interdisciplinary collaboration in recent years. China, the United States, and South Korea are the three countries with the largest number of publications. Among them, Chinese scholars pay more attention to the role of acupuncture in the treatment of neurological diseases, Korean scholars pay more attention to drug acupuncture, especially bee venom acupuncture, and American scholars pay more attention to the role of acupuncture in pain management. However, acupuncture has less cross-disciplinary cooperation with heart and cardiovascular system, peripheral vascular disease, and even less with non-medical disciplines. Using modern medical technology and methods to carry out research on the mechanism of acupuncture and moxibustion and strengthen the cooperation with informatics, statistics, physics and other disciplines may be an important direction for the modernization of acupuncture.关键词: 针灸; 跨学科; 学科范围

Ginsenosides are the main pharmacologically active constituents of ginseng which have been used in East Asian countries for centuries to modulate blood pressure, metabolism and immune function. Following the technological advances in isolation, purification and mass production, their mechanisms of action are gradually elucidated, providing solid basis for clinical applications. Ginseng extracts (total ginsenosides) and ginsenoside Rg3, CK, Rd have been marketed or entered clinical trials as drugs or dietary supplements. Despite the proven safety and efficacy of some ginsenosides, their applications are hindered by inferior pharmacokinetics such as low solubility, poor membrane permeability and metabolic instability. Nanoparticle formulation of drugs and implantable drug depots are effective strategies to improve the pharmacokinetics of therapeutic agents by enhancing solubility, providing protection, facilitating intracellular transport, and enabling sustained and controlled release. This mini-review summarizes the recent advances in systemic delivery of ginsenosides using liposomes, micelles, albumin-based nanoparticles, and inorganic nanoparticles, as well as local delivery of ginsenosides by electronspun fibrous membranes and hydrogels.

Diabetic wound healing remains challenging owing to the risk for bacterial infection, hypoxia, excessive glucose levels, and oxidative stress. Glucose-activated cascade reactions can consume glucose and eradicate bacteria, avoiding the direct use of hydrogen peroxide (H

To analyse the current status and publication trends of funded studies in nursing-related research from 2008 to 2018, available in the Web of Science.A longitudinal bibliometric analysis of publications of funded studies in nursing-related research, obtained from the Web of Science, was conducted.On 10 May 2019, we accessed 77,772 funded studies (2008-2018) from the Web of Science. Bibliometric methods and indicators were used to classify the publications and summarize the overall number, countries/regions, institutions, journals, and other parameters of the publications.The global output of nursing-related funded research publications increased significantly over time. The three leading countries with the highest number of funded publications were the United States, Australia, and the United Kingdom, with the United States accounting for 15 of the top 20 institutions associated with funded publications, which mostly included institutions of higher education. The most common disciplines of these publications were oncology, psychiatry, and paediatrics. The top three journals that published the largest number of nursing-related funded publications were the Journal of Clinical Nursing, the Journal of Advanced Nursing, and the International Journal of Nursing Studies. Keywords with the highest frequency of occurrence included "nurses," "qualitative research," "older people," "quality of life," "depression," "cancer," and "children."Nursing-related research has been drawing increasing attention over the years. Analysing the output of funded publications and monitoring the new dynamics of the international development of academic research in the field of nursing are crucial for determining future directions of nursing-related research development.The results of this study will provide a reference for scholars to evaluate the current utilization efficiency of global nursing-related research funding and demonstrate the development and trends in nursing-related research.目标: 分析2008年至2018年科学网上护理相关研究方面获资助论文的现状和发表趋势。 设计: 对科学网护理相关研究方面获资助论文发表进行纵向文献计量分析。 方法: 2019年5月10日,我们查阅了科学网上77,772篇获资助论文(2008年至2018年)。采用文献计量学方法和指标对发表文章进行分类,并对发表文章的总数、国家/地区、机构、期刊等参数进行汇总。 结果: 随着时间的推移,获资助的护理相关研究文章的全球产出显著增加。获资助文章数量最多的三个主要国家是美国、澳大利亚和英国,在与获资助文章有关的前20所院校中,美国占15所,其中大部分是高等教育机构。这些文章中最常见的学科是关于肿瘤学、精神病学和儿科学。发表获资助的护理相关文章数量最多的三大期刊是《临床护理杂志》、《高级护理期刊》和《国际护理研究杂志》。出现频率最高的关键词包括“护士”、“定性研究”、“老年人”、“生活质量”、“抑郁”、“癌症”和“儿童”。 结论: 近年来,护理相关研究越来越受到重视。分析获资助文章的产出并监测护理领域的国际学术研究发展的新动态,对于确定未来护理相关研究发展方向至关重要。 影响: 本研究的结果将为学者们评价当前全球护理相关研究经费的利用效率,展示护理相关研究的发展和趋势提供参考。.

Osteochondral defects are most commonly characterized by damages to both cartilage and underlying subchondral bone tissues, thus developing bi-layered scaffold that can concurrently regenerate these two specific lineages becomes challenge. In this study, the highly biomimetic bi-layered scaffolds were successfully prepared using human-like-collagen (HLC), hyaluronan (HA) and nano hydroxyapatite (HAP) particles, combined with “liquid phase synthesis” technology, freeze-drying and chemical cross-linking techniques, which was simulated the composition of natural extracellular matrix to repair osteochondral defects. This novel bilayer osteochondral graft had a seamlessly integrated layer structure, suitable pore size, high levels of porosity, and excellent mechanical properties. In vitro cell experiments of the bilayer scaffold indicated that the scaffold could promote the proliferation and adhesion of human bone marrow mesenchymal stem cells. In vivo osteochondral defects and micro-CT experiment revealed that bilayer scaffolds showed complete closure of the defect. Histology confirmed collagen and glycosaminoglycans were deposited in the new matrix of hyaline cartilage and bone in the bilayer scaffold group. Therefore, the developed bionic bilayer scaffold enhanced the regeneration of hyaline cartilage through subchondral bone formation and lateral host-tissue integration. In conclusion, this bilayer scaffold based on HLC could be used as the desired strategy for osteochondral defects regeneration.

Ginsenoside compound K (CK) with a wide range of pharmacological activities has been widely used in the healthcare product industry. However, the application of CK is limited by low productivity and difficult separation. The purpose of this study is to convert ginsenoside Rb1 into CK by improving conversion efficiency in novel “green” reaction medium-deep eutectic solvent (DES). Talaromyces purpureogenus was selected from ginseng rhizosphere soil to produce β-glucosidase with high activity and purity to transform ginsenosides, and Mn2+ was found to be an enzyme promoter. Among the DES based on choline chloride as hydrogen-bond receptor, choline chloride:ethylene glycol (ChCl:EG = 2:1) was the most promising solvent in maintaining enzyme activity and stability. In the presence of 30% v/v ChCl:EG = 2:1, the half-life of β-glucosidase was increased by 96%, the solubility of F2 was increased by 120%, and CK yield was increased by 54% compared with those in the buffer. Fourier transform infrared, circular dichroism, and fluorescence spectroscopy confirmed that DES did not destroy the structure and conformation of β-glucosidase. In addition, 80.6% CK conversion was obtained at 60 °C, pH 4.5, 48 h and 8 mM Rb1, which provided a feasible method for efficiently producing CK.

Fuzhuan brick tea (FBT) is a Chinese dark tea that is famous for its significant health benefits, in which Eurotium cristatum (E. cristatum) strains play a vital role in its postfermentation process. In this study, eurocristatine with hypoglycemic activity was discovered for the first time and purified from the spores of E. cristatum growing in FBT. Eurocristatine (98%) was obtained by D-101 macroporous resin-based column chromatography and preparative high performance liquid chromatography (HPLC) with a C18 column as the stationary phase and 35% acetonitrile in ultrapure water as the mobile phase. Hypoglycemic activity in a Hep-G2 cell hypoglycemic model was used as a screening indicator during purification. The chemical structure of eurocristatine was characterized by ESI/MS, 1H NMR and 13C NMR analyses. The antidiabetic effects of eurocristatine were verified in high-fat diet/streptozocin-induced type 2 diabetes mellitus (T2DM) rats. The results showed that eurocristatine significantly reduced fasting blood glucose. Our study demonstrated that eurocristatine, as a newly discovered hypoglycemic active substance, could be considered a potential candidate for the treatment of diabetes and its complications.

Background Adolescent electronic cigarette (e-cigarette) use is an emerging global public health concern as nicotine addiction may be established among this vulnerable population. Its study has generated a burgeoning body of research charactering a wide spectrum. However, the development and current status of research on this alarming issue have been inadequately examined in an objective, systematic and visualized way. This bibliometric analysis aims to fill this gap by providing a comprehensive overview of scientific literature in relation to adolescent e-cigarette use. Methods A total of 943 eligible papers published from 2011 to 2021 were retrieved from Web of Science Core Collection. Performance analysis was used with various bibliometric indicators to examine the publication trend, most prolific countries, institutions, authors, journals, and highly cited articles. Science mapping based on VOSviewer was employed to visualize the collaboration networks between countries and authors, research hotspots, and their evolutions. Results Publications on adolescent e-cigarette use has increased significantly during the past decade. The USA dominated this field in all aspects and the University of Southern California was the most productive institution. There were clear collaborative author groupings, but their transnational collaborations were generally weak. Major research themes were identified in the extant literature, including epidemiology and KABs; risk factors; health implications; gateway effect; and prevention interventions. The keywords such as ‘vapor’, ‘flavor’, ‘advertising’, ‘dual use’ reflected research emphases in early studies while ‘bullying’, ‘COVID-19’, ‘social norms’, and ‘heated tobacco products’ were the emerging research trends. Conclusion This study is presumed to provide an overall picture of research on adolescent e-cigarette use, which may help scholars and public health practitioners stay abreast of the research developments and serve as a reference and entry point for further investigation into this multifaceted phenomenon.

Breast cancer (BC) has replaced lung cancer as the most common cancer worldwide. Ginsenoside CK (CK) can effectively inhibit triple-negative breast cancer (TNBC), the occurrence and development of which are associated with glutamine addiction. However, the connection between CK and glutamine metabolism in TNBC proliferation and the mechanism of cell death induction remains unclear. Here, we found that high glutamine-addicted TNBC cells were particularly sensitive to CK treatment. CK exerted antitumour activity against TNBC by suppressing glutamine consumption and glutamate production via downregulation of glutaminase 1 (GLS1) expression. CK treatment further decreased cellular ATP production, reduced the utilisation of amino acids associated with glutamine metabolism, and induced glutathione (GSH) depletion and reactive oxygen species (ROS) accumulation, consequently triggering apoptosis in TNBC. Furthermore, CK decreased GLS1 expression in SUM159 xenograft mouse mammary tumours and significantly inhibited tumour growth with few side effects. Together, our data provide a powerful theoretical basis for the application of CK as a glutamine metabolic inhibitor in TNBC treatment.

Background Nursing professionalism is highly significant to the development of nursing. Florence Nightingale was the founder and leader of modern nursing, and Nightingale’s nursing professionalism has a significant impact on nursing in China and all over the world. In the new era, a new understanding of Nightingale’s nursing professionalism should be developed, and its positive role in nursing reshaped. Methods A total of 1,557 nurses and nursing students from 27 provincial administrative regions of China were surveyed using a customized questionnaire. Their recognitions of Nightingale’s nursing professionalism were evaluated based on scores, and statistical differences between and within the groups were analyzed using an Analysis of Variance (ANOVA). The elements of Nightingale’s nursing professionalism were extracted by the exploratory factor method and a principal component analysis. Results The Cronbach’s α of the questionnaire was 0.965, and the two groups did not differ significantly (p > 0.05). Based on the standard that the cumulative contribution rate of common factor should be > 85%, three common factors of Nightingale’s nursing professionalism, including professional emotion, professional ability and professional ethics, were extracted based on the Scree plot. Conclusions This study aimed to explore the connotation of Nightingale’s nursing professionalism. Our survey indicates that Nightingale’s nursing professionalism is highly recognized by nurses and nursing students in China. Its connotation includes professional emotion, ability and ethics. Nursing education and nursing management should fully utilize the leading role of Nightingale and guide the professional behaviors of nurses to be consistent with Nightingale’s nursing professionalism, thus, improving the degree of nurse professionalism.

Preventing bacterial infection in situ and accelerating skin generation simultaneously are essentially important for wound healing. Herein, a mussel-inspired Ag nanozyme-based bilayer hydrogel is constructed to address the above concerns. The bilayer hydrogel is composed of a layer with large pores absorbing the wound exudate and allowing oxygen exchange and a layer with small pores keeping the wound moist and preventing bacterial invasion. Benefitting from the polydopamine (PDA) coating-reduced Ag nanoparticles (AgNPs), the hydrogel exhibits high near infrared (NIR) absorption at 808 nm to generate hyperthermia and NIR-enhanced peroxidase (POD-like) activity to produce hydroxyl radicals (•OH), which endows the hydrogel with excellent antibacterial properties when combined with the released Ag+. In addition, the hydrogel presents adhesiveness due to the catechol group on a PDA molecule. The in vivo test results demonstrate that the bilayer hydrogel can accelerate infected skin generation by facilitating collagen deposition, decreasing tumour necrosis factor-α secretion, and promoting vascular endothelial growth factor expression.

To improve mechanical strength, polyvinyl alcohol hydrogels were often prepared through freeze-thaw method. However, they usually exhibited micropores limiting their applications. Hence, macroporou...

As nursing becomes a first-level discipline, the central focus of the development process of nursing science is the independent exploration of the future path of nursing care. Although many countries have made efforts to develop nursing as an independent discipline, no remarkable advancement has been achieved due to the incorrect understanding of the relationship between nursing and medicine and the improper comprehension of other factors involved in the process of nursing reform. Teaching and practicing nursing also face many problems. Based on our understanding of the relationship between nursing and medicine and through a careful analysis of the existing problems in the current nursing discipline, this paper provides some insights into the future directions of nursing development by exploring the independently developing nursing discipline in foreign countries.

To determine the nature and extent of the emerging field of “health law” scholarship in China, we retrieved 2956 publications about various aspects of health law published up through 2014 in 268 journals from the “Chinese Social Science Citation Index” and from the list of Chinese “Core Journals” maintained by the Peking University Library. By bibliometric analysis, we observed some interesting results which were different from our expectations. The collaboration network among Chinese health law (CHL) authors was relatively small, loose, unstable and early in its development. Kan Tian and Lixin Yang were leading authors, Renmin University of China was the primary institution, and Beijing was the predominant region studying Chinese health law (CHL). Kan Tian ranked 1st in the collaboration network and Lixin Yang published the most number of articles on CHL. Comprehensive universities made up the majority of institutions studying CHL, while medical colleges did not focus on health law research, possibly due to medical schools focusing mainly on clinical education and not attaching as much importance to social and humanistic aspects of medicine. Food safety, health administration, and the general principles of civil law were the main areas of focus in CHL research, which is basically in line with what we expected.

In this study, single factor experiments and orthogonal test were designed to fabricate a novel poly(vinyl alcohol) (PVA), human-like collagen (HLC) and sodium alginate (SA) composite hydrogel as w...

Ginsenosides, as major active components of ginseng, possess various pharmacological activities, including anti-tumor, anti-diabetic and hypotensive effects. However, the sedative and hypnotic effect of ginsenosides and the involved mechanism remain unclear. In the present study, the hypnotic effect of rare protopanaxadiol-type (PD) ginsenosides, consisting of Rg3, Rk1, Rg5, and protopanaxatriol-type (PT) ginsenosides, consisting of Rh1, Rk3, Rh4, was investigated and compared in rodent models through behavioral pharmacology methods. Both rare PD and PT ginsenosides decreased spontaneous locomotion activity in normal mice and reduced sleep latency, and extended sleep duration in pentobarbital-treated mice. Moreover, PD and PT ginsenosides attenuated the insomnia induced by caffeine in mice. These hypnotic effects of PD and PT ginsenosides were potentiated by 5-hydroxytryptophan (5-HTP), a precursor of serotonin, and inhibited by p-chlorophenylalanine (PCPA), a 5-HT synthesis inhibitor. Flumazenil (FLU, a specific gamma aminobutyric acid (GABA) antagonist) also impaired the hypnotic effect of both PD and PT ginsenosides. The aforementioned results indicated that PD and PT ginsenosides exhibit sedative and hypnotic activity, and PT ginsenosides show higher activity than PD ginsenosides at high doses (96 mg kg−1). Furthermore, the bioactivity of these two types of ginsenosides might be mediated via the serotonergic and GABAergic systems.

Protopanaxatriol saponin (PPT) has excellent anti-cancer, anti-diabetes, and anti-anemia effects, but its effect on intestinal bacteria has rarely been studied. In this study, we investigated whether PPT has the ability to improve intestinal health in antibiotic-treated mice. Model mice were constructed using a broad-spectrum antibiotic, cephalosporin. The composition of the gut microbiota and relative concentration of short-chain fatty acids (SCFAs), short-chain fatty acid receptor proteins (GPR41, GPR43 and GPR109A), tight junction components (ZO-1 and occludin) and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-22 and IFN-γ) were determined. The results showed that PPT improved the composition of the gut microbiota, increased the concentration of SCFAs as well as receptor proteins and tight junction proteins, and decreased the pro-inflammatory cytokines. These findings indicate that PPT has a protective effect on intestinal microbes and enhances the integrity of the intestinal barrier as well as alleviates colonic inflammation in antibiotic-treated mice.

To enhance the stability of recombinant human collagen α1(I) chains (rhCOL1A1) in production and purification stages, a gene fragment fusing COL1A1 and insulin protein coding domains was synthesized and inserted into the pPIC9K expression vector. The fusion peptide-expressing Pichia pastoris strain was created by transformation. After optimization of shake flask cultures, the ultimate intracellular expression level of the insulin-collagen α1(I) chain fusion protein (INS-COL1A1) reached about 300 mg·L− 1, and no obvious protein degradation was found in the fermentation and purification processes. The His-tagged recombinant fusion protein was detected by western blotting and was effectively purified using Ni2 +-chelating chromatography. A prominent improvement in the stability of INS-COL1A1 was observed compared to rhCOL1A1 in vitro, and the rhCOL1A1 released from the fusion protein was studied by LC–MS/MS and in bioassays. The results showed that the purified rhCOL1A1 was consistent with the native protein in amino acid composition and had a similar biological compatibility. To our knowledge, this is the first study to demonstrate the use of insulin as a fusion protein to improve the stability of easily degradable proteins.

The objective of this study was to assess the effect of a modified human-like collagen calcium complex on osteoporosis mice. BHK ( Baby Hamster Kidney ) cells were used to compare the cytotoxicity of different calcium reagents with the MTT test. Six-week-old male mice (n = 80) were randomly divided into eight groups: a blank group (blank), control group (control), human-like collagen calcium group (HLC-Ca), thiolated human-like collagen calcium group (SH-HLC-Ca), phosphorylated human-like collagen calcium group (Pi-HLC-Ca), gluconate group (Glc-Ca), calcium carbonate group (CaCO 3 ) and D-cal group (B). A systematic analysis of the results available in vivo after 3 months of treatment was presented. The effects of several Ca supplements on osteoporosis mice were investigated by detecting serum calcium, alkaline phosphate activity (ALP), bone hydroxyproline (BHP) and bone mineral density (BMD). The results proved that the BMD and BHP of osteoporosis mice were significantly increased in the Pi-HLC-Ca group, while serum calcium and ALP were decreased. Therefore, Pi-HLC-Ca is likely a good calcium supplement for clinical applications. In this review, the advantage of Pi-HLC-Ca in preventing and delaying osteoporosis is highlighted. In addition to the current progress, further investigations are necessary to reveal the relative influences of collagen and calcium proportions on the long-term clinical effects of osteoporosis.

Ginsenoside Rh4, as a bioactive component obtained from Panax notoginseng, has excellent pharmacological properties. However, its role in regulating gut microbiota and intestinal inflammation is still poorly understood. Thus, the aim of this study is to investigate the effect of Rh4 on gut microbiota, especially antibiotic-induced microbiota perturbation, and the underlying mechanisms. C57BL/6 mice were given different doses of Rh4 after the establishment of a gut microbiota disturbance model with antibiotics. Our data revealed that Rh4 administration could greatly improve the pathological phenotype, gut barrier disruption, and intestinal inflammation in mice that had been antibiotic-induced. Notably, it was found that Rh4 significantly inhibited the TLR4-MyD88-MAPK signaling pathway. In addition, Rh4 treatment could significantly increase the number of short chain fatty acids (SCFAs) and bile acids (BAs). These changes were accompanied with beneficial alterations in gut microbiota diversity and composition. In conclusion, Rh4 improves intestinal inflammation and induces potentially beneficial changes in the gut microbiota, which are conducive to revealing host-microbe interactions.

Additional file 1. The guidelines for practicing quadriceps strengthening exercises and Baduanjin qigong for KOA patients in this study.

Additional file 3. CONSORT 2010 checklist of information to include when reporting a randomized trial.

Gastric cancer (GC) is the leading causes of cancer-related death worldwide. Surgery remains the cornerstone of gastric cancer treatment, and new strategies with adjuvant chemotherapy are currently gaining more and more acceptance. Ginsenoside Rh4 has excellent antitumor activity. Conversely, the mechanisms involved in treatment of GC are not completely understood. In this study, we certified that Rh4 showed strong anti-GC efficiency in vitro and in vivo. MTT and colony formation assays were performed to exhibit that Rh4 significantly inhibited cellular proliferation and colony formation. Results from the wound healing assay, transwell assays, and Western blotting indicated that Rh4 restrained GC cell migration and invasion by reversing epithelial–mesenchymal transition (EMT). Further validation by proteomic screening, co-treatment with disitertide, and SIX1 signal silencing revealed that SIX1, a target of Rh4, induced EMT by activating the TGF-β/Smad2/3 signaling pathway. In summary, our discoveries demonstrated the essential basis of the anti-GC metastatic effects of Rh4 via suppressing the SIX1–TGF-β/Smad2/3 signaling axis, which delivers a new idea for the clinical treatment of GC.

BackgroundExercise is recommended as a core treatment for individuals with KOA. However, the optimal exercise program to promote long-term compliance for KOA patients is not clear. The aim of this study is to compare the effects of the combination exercise program (quadriceps strengthening exercises (QSE) plus Baduanjin qigong) versus QSE alone on older adults with knee osteoarthritis (KOA). MethodsA two-arm, quasi-experimental trial with repeated measurements was used. As a cluster randomized trial, participants from one community center were assigned to combination exercise group while participants from the other center were assigned to QSE group. We assessed pain intensity, physical function, self-efficacy, and HRQoL with standardized instruments at baseline, 3 and 6 months. Results87 participants with KOA who aged above 60 completed the study. Over the 6 months, There were significant time by group interaction effects on pain intensity (F = 44.419, p < 0.001), physical function (F = 46.904, p < 0.001) and self-efficacy (F = 49.754, p < 0.001), as well as in the physical component summary (F = 15.205, p < 0.001) and mental component summary of SF-12 (F = 19.205, p < 0.001), with the combination exercise group exhibiting significantly greater improvements in all outcomes than QSE group. ConclusionsCombination exercise treatment is more effective than QSE for relieving pain, increasing physical functioning, and improving self-efficacy, and quality of life in community-dwelling KOA older adults. Also, it could promote long-term compliance for KOA community patients.Trial registrationChinese Clinical Trails Registry number ChiCTR2000033387 (retrospectively registered). Registered 30 May 2020

Fuzhuan brick tea (FBT) is a Chinese dark tea that is famous for its significant health benefits, in which

Objective To assess the overall trends in the development and citation impact of high-impact papers in nursing research worldwide to gain insight into the focus areas of nursing research. Background Bibliometric method is proved to be effective in analysing the papers' characteristics, and it gained considerable interest from the scientific community in recent years. An analysis of the characteristics and intrinsic patterns of high-impact papers in nursing research will provide an objective reflection of the research hot spots. Nursing managers can pointedly increase funding amount and strengthen research cooperation in order to put the scientific results into management practice. Methods Bibliometric methods and visualization software were used to comprehensively analyse high-impact papers in nursing research in terms of development trends, countries/regions, distribution of subject areas, research institutes, collaborative networks and subject terms. Results There were 6,886 papers between 2008 and 2018. The number of papers increased from 528 in 2008 to 723 in 2015, and then remained above 600 in 2016 and 2017. These papers were mainly distributed in nursing, oncology, paediatrics, gynaecology, teaching and education, and cardiac and cardiovascular systems and were cited by 128,845 papers that came from 89 Web of Science subject areas. Papers in nursing research accounted for the largest share of these citations. The top five countries in the world in terms of the number of high-impact papers were the United States, Australia, the United Kingdom, Canada and Sweden. The research institutions with the highest number of high-impact papers worldwide were the University of California System, the University of Pennsylvania, the University of North Carolina, the University of London and the University of Technology Sydney. In this data set, it was shown that research collaborative circles have been formed in the United States, Australia, Canada and Europe; the subject-term analysis indicated that 'women' and 'students' have always been high-interest populations for high-impact papers and that cancer is still one of the greatest threats to human health. Furthermore, the subject terms of high-impact papers in nursing research have gradually evolved from 'disease' and 'therapy' to 'symptoms'. Conclusion In recent years, the number of high-impact papers published each year in nursing research has grown over time. Nursing has been shown to be a highly specialized subject, and the majority of its high-impact papers have been published by research institutions. Although cross-regional collaborations are beginning to emerge, there is much room for improvement in this regard. Finally, women, students, cancer and symptomatic care are the current focus areas in nursing research. Implications for nursing management This study informs nursing managers within the nursing research field about subject areas, collaborative networks and hot topics. It is beneficial to pay attention to studies, manage scientific outputs, allocate resources, seek cooperation and improve the work efficiency of scientific research management.

By combining DEAE-cellulose-52 and Sepharose-CL-6B chromatography, a heteropolysaccharide ECIP-1A with an average molecular weight of 24,336 Da was isolated from the hyphae of Eurotium cristatum. The main components of the monosaccharides of ECIP-1A were mannose, glucose and galactose, and their molar ratio is 4.003: 0.592: 4.58. Analysis of the immunomodulatory activity showed that ECIP-1A could significantly promote the proliferation of RAW264.7 cells and induce the production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and nitric oxide (NO) by RAW264.7 cells. The results therefore suggested that ECIP-1A, as an immunomodulator, may have potential application prospects in the food and pharmaceutical industries.

Lung adenocarcinoma (LAC) is a common lung cancer with a high malignancy that urgently needs to be treated with effective drugs. Ginsenoside Rh4 exhibits outstanding antitumor activities. However, few studies reported its effects on growth, metastasis and molecular mechanisms in LAC. Here, Rh4 is certified to show a strong anti-LAC efficiency in vitro and in vivo. Results of flow cytometry and Western blot are obtained to exhibited that Rh4 markedly restrained cellular proliferation and colony formation by arresting the cell cycle in the G1 phase. Results from a wound healing assay and transwell assays demonstrated that Rh4 is active in the antimigration and anti-invasion of LAC. The analysis of Western blot, immunofluorescence and RT-qPCR confirmed that Rh4 reverses the epithelial–mesenchymal transition (EMT) through upregulating the gene expression of E-cadherin and downregulating that of snail, N-cadherin and vimentin. In vivo results from immunohistochemistry show consistent trends with cellular studies. Furthermore, Rh4 suppresses the Janus kinases2/signal transducer and activator of the transcription3 (JAK2/STAT3) signaling pathway stimulated by TGF-β1. Silencing the STAT3 signal or co-treating with AG490 both enhanced the EMT attenuation caused by Rh4, which revealed that Rh4 suppressed EMT via inhibiting the JAK2/STAT3 signaling pathway. These findings explore the capacity and mechanism of Rh4 on the antimetastasis of LAC, providing evidence for Rh4 to LAC therapy.

Advanced lung cancer is becoming a chronic disease threatening human life and health. Cachexia has been recognized as the most common problem associated with advanced lung cancer. Lung cancer-induced cachexia seriously affects patients' quality of life. The present article summarizes the pathogenesis of advanced lung cancer-induced cachexia from three aspects: anorexia, cytokines, and energy and metabolic abnormalities. In addition, the present article proposes corresponding nursing measures based on cachexia pathogenesis to improve the quality of life and survival rate of cachectic patients with advanced lung cancer by combining continuously advancing treatment regimens and effective nursing. The present article also provides references for healthcare professionals when administering related treatments and nursing care.

Ginsenoside Rk1 is a substance derived from ginseng and exhibits various activities such as anti-diabetic, anti-inflammatory and anti-cancer effects; however, its anti-tumor effect and target signaling mechanism in lung adenocarcinoma are not well understood. Here, we show that Rk1, a natural drug product, can function as an antitumor modulator that induces apoptosis in lung adenocarcinoma cells by inhibiting NF-κB transcription and triggering cell cycle arrest. Mechanistically, Rk1 suppressed the proliferation and clonal formation of two lung adenocarcinoma cell lines (A549 and PC9) in vitro and caused G1 phase cell arrest. In the A549 xenograft model, Rk1 significantly inhibited tumor growth and had few toxic side effects on normal organs. Western blotting results showed that Rk1 increased the protein expression of Bax, cleaved caspase-3, -8, and -9, and PARP, decreased the expression of Bcl-2 and blocked the NF-κB signaling pathway. Furthermore, ginsenoside Rk1 also reduced the high expression of PD-L1 in lung adenocarcinoma cells by inhibiting NF-κB signaling. These data revealed a previously unreported antitumor mechanism of Rk1, providing new ideas and an experimental basis for further study of the mechanism of action of Rk1 in lung adenocarcinoma.

The primary goal of the present study is to discover new drug treatments by topology analysis of drug associations and their therapeutic group network. To this end, we collected 19,869 papers dated from 1946 to 2015 that are related to autism treatment from PubMed. We extracted 145 drugs based on MeSH terms and their synonyms (the total number is 6624) within the same ATC classification hierarchy and used them to find drug associations in the collected datasets. We introduced a new topology-driven method that incorporates various network analyses including co-word network, clique percolation, weak component, pathfinding-based analysis of therapeutic groups, and detection of important drug interaction within a clique. The present study showed that the in-depth analysis of the drug relationships extracted from the literature-based network sheds new light on drug discovery research. The results also suggested that certain drugs could be repurposed for autism treatment in the future. In particular, the results indicated that the discovered four drugs such as Tocilizumab, Tacrolimus, Prednisone, and Sulfisoxazole are worthy of further study in laboratory experiments with formal assessment of possible effects on symptoms, which may provide psychologists, physicians, and researchers with data-based scientific hypotheses in autism-drug discovery.

The rare ginsenoside Compound K (C-K) is attracting more attention because of its good physiological activity and urgent need. There are many pathways to obtain ginsenoside C-K, including chemical and biological methods. Among these, the conversion of PPD-type ginsenosides by enzymatic hydrolysis is a trend due to its high efficiency and mild conditions. For effectively extracting from the other panaxadiol saponins, the conversion process for ginsenoside C-K was investigated using snailases in this study. The univariate experimental design and response surface methodology were used to determine the optimal hydrolysis conditions for the conversion of ginsenoside Rb1 into ginsenoside C-K by snailases. The optimum conditions were as follows: pH 5.12, temperature 51 °C, ratio of snailase/substrate 0.21, and reaction time 48 h. On the basis of these parameters, the addition of 1.0 mmol·L− 1 ferric ion was found to significantly improve the enzymolysis of snailases for the first time. With the above conditions, the maximum conversion rate reached 89.7%, suggesting that the process can obviously increase the yield of ginsenoside C-K. The bioassay tests indicated that the ginsenoside C-K showed anti-tumor activity in a series of tumor cell lines. Based on these results, we can conclude that the process of rare ginsenoside C-K production by enzymolysis with snailase is feasible, efficient, and suitable for the industrial production and application.

The use of ginsenosides in cancer therapy has been intensively investigated. The ginsenoside Rh4 (Rh4), a rare saponin obtained from Panax notoginseng, dissolves in water more readily than total saponins, making this compound easier to use in anti-cancer pharmaceutics. Here, we investigated the antiproliferative activity and mechanisms of Rh4 in colorectal cancer, both in vivo and in vitro. A colorectal cancer xenograft model showed that Rh4 significantly inhibited tumor growth with few side effects. CCK-8 assays, flow cytometric analysis, Western blotting and immunohistochemistry revealed that Rh4 effectively suppressed colorectal cancer cell proliferation via inducing G0/G1 phase arrest, caspase-dependent apoptosis and autophagic cell death but was not significantly cytotoxic to normal colon epithelial cells. Furthermore, apoptosis played a dominant role in Rh4-induced cell death, as the pan-caspase inhibitor Z-VAD-FMK blocked cell death to a greater extent than the autophagy inhibitor 3-methyladenine. Moreover, Rh4 increased reactive oxygen species (ROS) accumulation and subsequently activated the JNK-p53 pathway. An ROS scavenger and JNK and p53 inhibitors significantly attenuated Rh4-induced apoptosis and autophagy. Thus, the present study is the first to illustrate that Rh4 triggers apoptosis and autophagy via activating the ROS/JNK/p53 pathway in colorectal cancer cells, providing basic scientific evidence that Rh4 shows great potential as an anti-cancer agent.

Skin defects are an important and pressing clinical problem. The use of hydrogels as a regenerative scaffold presents a promising approach to cure skin defects by inducing dermal reconstruction. Although synthetic material hydrogels display good mechanical properties, their poor biocompatibility restricts their application. To develop a good dermal substitute, we have successfully prepared hydrogels that mimic the extracellular matrix of the human body and can be used for tissue engineering skin scaffolds. The hydrogels were synthesized by adding hyaluronic acid (HA) and carboxylated chitosan (CCS) to human-like collagen (HLC) that can be used to tissue engineering skin scaffolds and using transglutaminase as a crosslinking agent. The mechanical characteristics of the hydrogels were explored by cyclic compressive mechanical tests and a uniaxial tension protocol. The compressive stress of HLC/HA/CCS (GEL4) hydrogel reached 0.2136 ± 0.034 MPa when the compressive strain reached 60%. The tensile strain of GEL4 was 126.99 ± 2.38%. The hydrogels significantly promoted adhesion, proliferation and migration of L929 cells, demonstrating the good biocompatibility of the hydrogels. For in vivo analysis, we constructed a full-thickness skin defect model and demonstrated that the hydrogels could effectively prevent invasion of the wound by outside bacteria and certificate that they are beneficial in promoting wound healing over pathologic healing. Subcutaneous implantation experiments revealed that the degradation period of the hydrogels with HA and CCS is suitable for the healing cycle of skin tissue, and the inflammatory reaction could be reduced to a very short time, indicating the good histocompatibility of the hydrogels. Therefore, the hydrogels are favourable, soft and porous materials that demonstrate good potential for skin repair, drug delivery, cartilage treatment and other tissue engineering applications.

Bacterial infection and oxidative stress are two critical problems for chronic infected wound healing. Here, molybdenum disulfide nanosheets (MoS2 NSs) with triple enzyme-like activities are loaded onto carbon nanotubes (CNTs) and incorporated into multifunctional hydrogels aiming to eradicate bacteria and eliminate free radicals. The nanozyme activities of MoS2 are significantly enhanced through CNTs and near-infrared irradiation. The hydrogel exhibits significant antibacterial performance attributed to the peroxidase-like activity (catalyzing hydrogen peroxide (H2 O2 ) into hydroxyl free radicals (•OH)) under acidic conditions, glutathione loss, and photothermal therapy. Additionally, the nanozyme can mimic the superoxide-like activity to transform the superoxide radicals (O2•- ) into H2 O2 and oxygen (O2 ), then H2 O2 is further depleted into O2 via the catalase-like activity, benefitting from which and •OH scavenging ability, the hydrogel shows excellent scavenging free radical ability in neutral environment and provides abundant O2 for wound healing. The multifunctional hydrogel, crosslinked by dynamic boron ester bonds, exhibits adhesiveness, self-healing, and shape-adaptivity, which can fill the cavity of irregular wounds and promote the nanozyme to play the role with maximum efficiency. The hydrogels notably accelerate the skin reconstruction through killing bacteria, clearing ROS, promoting collagen deposition and angiogenesis.

Ginsenoside Rk3 is a natural prebiotic found in ginseng, has excellent pharmacological efficacy, especially antitumor effects, and can greatly benefit human health. Here, we investigated the impact of Rk3 intake on modulation of the gut microbiota and their metabolites as well as its effect on low-grade inflammation in mice. C57BL/6JFandd mice were administered different doses of Rk3 for two weeks after establishment of an antibiotic-mediated gut microbiota disturbance model. Interestingly, Rk3 intake induced substantial changes in the gut microbiota composition, enriched the Bacteroides, Alloprevotella and Blautia genera, and effectively ameliorated gut microbiota dysbiosis, with significantly decreased Firmicutes/Bacteroidetes ratios. These changes were accompanied by beneficial alterations in gut microbiota diversity and improved short-chain fatty acid levels. In addition, we found that Rk3 intervention repaired intestinal barrier dysfunction by increasing the expression of tight junction proteins (ZO-1, Occludin and Claudin-1), reducing colonic inflammatory cytokine levels, and suppressing TNF-α, IL-1β, and IL-6 overproduction. In conclusion, Rk3 improves intestinal inflammation and induces potentially beneficial changes in the gut microbiota, and these findings help elucidate host-microbe interactions.

Yanbing Su,1 Chao Long,2 Qi Yu,1 Juan Zhang,1 Daisy Wu,3 Zhiguang Duan1 1School of Management, Shanxi Medical University, Taiyuan, People’s Republic of China; 2School of Medicine, Stanford University, Palo Alto, CA, 3Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA Purpose: This study aimed to investigate the multiple collaboration types, quantitatively evaluate the publication trends and review the performance of institutions or countries (regions) across the world in COPD research.Materials and methods: Scientometric methods and social network analysis were used to survey the development of publication trends and understand current collaboration in the field of COPD research based on the Web of Science publications during the past 18years.Results: The number of publications developed through different collaboration types has increased. Growth trends indicate that the percentage of papers authored through multinational and domestic multi-institutional collaboration (DMIC) have also increased. However, the percentage of intra-institutional collaboration and single-authored (SA) studies has reduced. The papers that produced the highest academic impact result from international collaboration. The second highest academic impact papers are produced by DMIC. Out of the three, the papers that are produced by SA studies have the least amount of impact upon the scientific community. A handful of internationally renowned institutions not only take the leading role in the development of the research within their country (region) but also play a crucial role in international research collaboration in COPD. Both the amount of papers produced and the amount of cooperation that occurs in each study are disproportionally distributed between high-income countries (regions) and low-income countries (regions). Growing attention has been generated toward research on COPD from more and more different academic domains.Conclusion: Despite the rapid development in COPD research, collaboration in the field of COPD research still has room to grow, especially between different institutions or countries (regions), which would promote the progress of global COPD research. Keywords: research collaboration, social network analysis, COPD, citation frequency

Background: TB is one of the top 10 causes of death and the leading cause from a single infectious agent. The study characterize the developmental trends and collaboration features in the field of tuberculosis (TB) at the national level and identify high-impact countries. Methods: Scientometrics and social network analysis methods were used to analyze the research situation and collaboration behaviors based on TB research indexed in Web of Science from 1998 to 2017. Results: The publication output, national collaborative rate, and collaborative level have steadily increased from 1998 to 2017. However, domestic publications still account for a substantial proportion of a nation's publications. Over time, the numbers of national publications and international collaborative publications have increased in total, but the growth trend of their share as a proportion of total national publications is not significant. The United States of America has the largest number of highly cited publications, while Denmark, the Netherlands, Switzerland, and Sweden have higher values of average relative citation than do other countries. Notably, the United Kingdom and South Africa have established the strongest and most stable collaboration. Conclusions: There was increasing research activity and collaboration in the field of TB during the period 1998 to 2017, but growth shows wide variability between countries. Further comprehensive and full collaboration should be promoted.

Ginsenoside CK is one of the intestinal bacterial metabolites of ginsenoside prototype saponins, such as ginsenoside Rb1, Rb2, Rc, and Rd. Poor water solubility and low bioavailability have limited its application. The nanogel carriers could specifically deliver hydrophobic drugs to cancer cells. Therefore, in this study, a nanogel was constructed by the formation of Schiff base bonds between hydrazide-modified carboxymethyl cellulose (CMC-NH2) and aldehyde-modified β-cyclodextrin (β-CD-CHO). A water-in-oil reverse microemulsion method was utilized to encapsulate ginsenoside CK via the hydrophobic cavity of β-CD. β-CD-CHO with a unique hydrophobic cavity carried out efficient encapsulation of CK, and the drug loading and encapsulation efficiency were 16.4% and 70.9%, respectively. The drug release of CK-loaded nanogels (CK-Ngs) in vitro was investigated in different pH environments, and the results showed that the cumulative release rate at pH 5.8 was 85.5% after 140 h. The methylthiazolyldiphenyl-tetrazolium bromide (MTT) toxicity analysis indicated that the survival rates of A549 cells in CK-Ngs at 96 h was 2.98% compared to that of CK (11.34%). In vivo animal experiments exhibited that the inhibitory rates of CK-Ngs against tumor volume was 73.8%, which was higher than that of CK (66.1%). Collectively, the pH-responsive nanogel prepared herein could be considered as a potential nanocarrier for CK to improve its antitumor effects against lung cancer.

Ginsenoside Rh4, as a bioactive component obtained from Panax notoginseng, has excellent pharmacological efficacy especially antitumor effects. However, its anticancer effects and target mechanisms in regulating human esophageal cancer are still poorly understood. Here, the results suggested that Rh4 exhibited potent anti-esophageal cancer effects in vivo and in vitro. Flow cytometric analysis and Western Blot showed that Rh4 significantly inhibited the growth by inducing G1 phase arrest. In parallel, Rh4 inhibited aerobic glycolysis in esophageal cancer cells by hindering lactate production, glucose uptake and ATP production; reducing the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR); suppressing aerobic glycolysis-related protein expression. Mechanistic studies demonstrated that AKT is a possible target of Rh4, which suppresses aerobic glycolysis. Rh4 administration resulted in AKT deregulation, whereas treatment with insulin abolished the inhibitory effect of Rh4 on aerobic glycolysis. In contrast, treatment with AKT inhibitors or siRNA that silenced AKT enhanced the inhibitory effect of Rh4 on aerobic glycolysis. Moreover, molecular docking results indicated that Rh4 was able to bind to the interdomain region of AKT. Interestingly, the results revealed that Rh4 also inhibited the expression of PD-L1 via the AKT/mTOR pathway. Taken together, our findings provide important insights into the anti-esophageal cancer effects of Rh4 via suppressing aerobic glycolysis and PD-L1 expression, which indicated Rh4 could be as promising drug for clinical treatment.

This study involved the development of a β-glucosidase-catalyzed hydrolysis method based on a deep eutectic solvent (DES), choline chloride-ethylene glycol 2:1, and continuous feed technique to overcome the difficulty of high-concentration ginsenoside hydrolysis. A productivity of 142 mg·L−1·h−1 was achieved with the following conditions: 30 vol% DES, pH 5.0, 55 °C, and substrate concentration of 12 mM. In the presence of DES, the affinity and catalytic efficiency of β-glucosidase to Rd increased by 49 and 64%, respectively, which promoted the continuation of hydrolysis. Moreover, conformation of β-glucosidase was mostly retained, as confirmed by spectral information. Through a combination of a substrate fed-batch technique to reduce the inhibitory effects of substrates and products, the CK conversion rate increased by 44% compared to traditional single-batch in pure buffer. This report describes a practical method for the continuous conversion of natural compounds through biological processes and solvent engineering.