Myeloid-derived suppressor cells alleviate adverse ventricular remodeling after acute myocardial infarction.

The fundamental pathophysiological mechanism in the progression of chronic heart failure following acute myocardial infarction (AMI) is ventricular remodeling, in which innate and adaptive immunity both play critical roles. Myeloid-derived suppressor cells (MDSCs) have been demonstrated to function in a range of pathological conditions, such as infections, inflammation, autoimmune diseases, and tumors. However, it is unclear how MDSCs contribute to cardiac remodeling following AMI. This study aimed to identify the function and underlying mechanism of MDSCs in controlling cardiac remodeling following AMI. Following AMI in mice, MDSCs frequencies changed dynamically, considerably increased on day 7 in blood, spleens, lymph nodes and hearts, and decreased afterwards. Consistently, mice with AMI displayed enhanced cardiac function on day 14 post-AMI, reduced infract size and higher survival rates on day 28 post-AMI following the adoptive transfer of MDSCs. Furthermore, MDSCs inhibited the inflammatory response by decreasing pro-inflammatory cytokine (TNF-α, IL-17, Cxcl-1, and Cxcl-2) expression, up-regulating anti-inflammatory cytokine (TGF-ß1, IL-10, IL-4, and IL-13) expression, reducing CD3+ T cell infiltration in the infarcted heart and enhancing M2 macrophage polarization. Mechanistically, MDSCs improved the release of anti-inflammatory factors (TGF-ß1 and IL-10) and decreased the injury of LPS-induced cardiomyocytes in vitro in a manner dependent on cell-cell contact. Importantly, blockade of IL-10 partially abolished the cardioprotective role of MDSCs. This study found that MDSCs contributed to the restoration of cardiac function and alleviation of adverse cardiac remodeling after AMI possibly by inhibiting inflammation.

Molecular characterization of a single-negative-stranded RNA virus from the rice blast fungus Magnaporthe oryzae isolate NJ39.

A novel negative-sense single-stranded RNA mycovirus, designated as "Magnaporthe oryzae mymonavirus 1" (MoMNV1), was identified in the rice blast fungus Magnaporthe oryzae isolate NJ39. MoMNV1 has a single genomic RNA segment consisting of 10,515 nucleotides, which contains six open reading frames. The largest open reading frame contains 5837 bases and encodes an RNA replicase. The six open reading frames have no overlap and are arranged linearly on the genome, but the spacing of the genes is small, with a maximum of 315 bases and a minimum of 80 bases. Genome comparison and phylogenetic analysis indicated that MoMNV1 is a new member of the genus Penicillimonavirus of the family Mymonaviridae.

Clinical patterns and risk factors for multiorgan involvement in IgG4-Related disease patients.

Background: IgG4-related disease with multiorgan involvement predicts higher disease activity, thus, it is necessary to identify whether IgG4-related disease involves multiple organs at the early stage. To further clarify the clinical characteristics and risk factors for IgG4-related disease with multiorgan involvement, we conducted an observational study. Methods: We retrospectively analysed the clinical data of 160 patients who were primarily diagnosed with IgG4-related disease at the First Affiliated Hospital of Zhengzhou University from January 2015 to January 2021. According to the number of involved organs, patients were divided into two groups: multiorgan involvement and nonmultiorgan involvement. Patients were divided into a multiorgan group and a nonmultiorgan group according to multiple organ involvement. Results: There were 82 cases identified with multiorgan involvement and 78 cases diagnosed with no multiorgan involvement in this series. Most cases were elderly and male (p > 0.05). The most frequently affected organs in IgG4-RD were the lymph nodes (50.6 %), pancreas (38.7 %) and salivary glands (35.6 %). Multivariate analysis showed that eosinophilia, IgG4>2*ULN, lymph node involvement, salivary gland involvement and lung involvement were independent risk factors for multiorgan involvement (p < 0.05). Conclusions: The main issues in clinical practice are how to accurately diagnose the disease and screen the more vulnerable organs.

Evaluation framework for conversational agents with artificial intelligence in health interventions: a systematic scoping review.

OBJECTIVES: Conversational agents (CAs) with emerging artificial intelligence present new opportunities to assist in health interventions but are difficult to evaluate, deterring their applications in the real world. We aimed to synthesize existing evidence and knowledge and outline an evaluation framework for CA interventions. MATERIALS AND METHODS: We conducted a systematic scoping review to investigate designs and outcome measures used in the studies that evaluated CAs for health interventions. We then nested the results into an overarching digital health framework proposed by the World Health Organization (WHO). RESULTS: The review included 81 studies evaluating CAs in experimental (n = 59), observational (n = 15) trials, and other research designs (n = 7). Most studies (n = 72, 89%) were published in the past 5 years. The proposed CA-evaluation framework includes 4 evaluation stages: (1) feasibility/usability, (2) efficacy, (3) effectiveness, and (4) implementation, aligning with WHO's stepwise evaluation strategy. Across these stages, this article presents the essential evidence of different study designs (n = 8), sample sizes, and main evaluation categories (n = 7) with subcategories (n = 40). The main evaluation categories included (1) functionality, (2) safety and information quality, (3) user experience, (4) clinical and health outcomes, (5) costs and cost benefits, (6) usage, adherence, and uptake, and (7) user characteristics for implementation research. Furthermore, the framework highlighted the essential evaluation areas (potential primary outcomes) and gaps across the evaluation stages. DISCUSSION AND CONCLUSION: This review presents a new framework with practical design details to support the evaluation of CA interventions in healthcare research. PROTOCOL REGISTRATION: The Open Science Framework (https://osf.io/9hq2v) on March 22, 2021.

Protective effects of methyl protodioscin against lipid disorders and liver injury in hyperlipidemic gerbils.

Methyl protodioscin (MPD) is the main component of total diosgenin, which was reported to reduce cholesterol and triglyceride levels potentially. This study aimed to investigate the beneficial effects of MPD against lipid disorder in hyperlipidemic gerbils induced by a high-fat diet (HFD). Hyperlipidemia was induced in gerbils by feeding them with HFD for six weeks, and a daily oral dose of MPD solution (25 and 50 mg/kg/day) was administered. This study investigated blood lipid levels and hepatic lipid accumulation in hyperlipidemic gerbils. The potential mechanism of MPD was explored by detecting the expression level of genes, including SREBPs, ACC, FASN, HMGCR, PCSK9, and LDL-R. The results showed that MPD treatment decreased the body weight, the relative weight of the liver, blood lipid, and hepatic lipid levels of gerbils fed with HFD. The administration of MPD alleviates liver steatosis and injury in gerbils fed with an HFD. MPD treatment reduced the expression of HMGCR, increased the expression of LDL-R, and decreased the expression of PCSK9 for cholesterol reduction. Additionally, MPD treatment reduced the expression of hepatic ACC and FASN for triglycerides reduction. The underlying mechanisms for these effects are attributed to MPD-induced inhibition of protein expression of LXR, SREBP1, and SREBP2. This study demonstrates that MPD protects gerbils against lipid disorders and liver injury by suppressing hepatic SREBPs expression.

Community composition and abundance of complete ammonia oxidation (comammox) bacteria in the Lancang River cascade reservoir.

The construction of the reservoir has changed the nitrogen migration and transformation processes in the river, and a large amount of sediment deposition in the reservoir may also lead to the spatial differentiation of complete ammonia oxidation (comammox) bacteria. The study investigated the abundance and diversity of comammox bacteria in the sediments of three cascade reservoirs, namely, Xiaowan, Manwan, and Nuozhadu on the Lancang River in China. In these reservoirs, the average amoA gene abundance of clade A and clade B of comammox bacteria, ammonia-oxidizing archaea (AOA), and ammonia-oxidizing bacteria (AOB) was 4.16 ± 0.85 × 105, 1.15 ± 0.33 × 105, 7.39 ± 2.31 × 104, and 3.28 ± 0.99 × 105 copies g-1, respectively. The abundance of clade A was higher than that of other ammonia oxidizing microorganisms. The spatial variation of comammox bacteria abundance differed among different reservoirs, but the spatial variation trends of the two clades of comammox bacteria in the same reservoir were similar. At each sampling point, clade A1, clade A2, and clade B coexisted, and clade A2 was usually the dominant species. The connection between comammox bacteria in the pre-dam sediments was looser than that in non-pre-dam sediments, and comammox bacteria in pre-dam sediments exhibited a simpler network structure. The main factor affecting comammox bacteria abundance was NH4+-N, while altitude, temperature, and conductivity of overlying water were the main factors affecting comammox bacteria diversity. Environmental changes caused by differences in the spatial distribution of these cascade reservoirs may be the main driver of the changes of community composition and abundance of comammox bacteria. This study confirms that the construction of cascade reservoirs results in niche spatial differentiation of comammox bacteria.

Directional droplet bouncing on a moving superhydrophobic surface.

Droplets directionally bouncing off moving superhydrophobic solid surfaces are universal in nature and are crucial in many biological, sustainable, environmental, and engineering applications. However, their underlying physics and regulation strategies remain relatively unknown. This paper demonstrates that the maximum directional acceleration of a post-impact droplet mainly occurs in the spreading stage and that the orientational velocity of the droplet mainly originates in the early impingement process. Furthermore, it clarifies the underlying physics based on momentum transfer process imposed by the boundary layer of impacts and proposes a strategy for regulating the directional droplet velocity using a comprehensive formula. Finally, it shows that directional bouncing reduces the flight momentum of a small flying device by 10%-22%, and the experimental values agree closely with the predicted values. This study reveals the droplet bounce orientation mechanism imposed by moving substrates, provides manipulation methods, and makes positive and meaningful discussions of practical applications.

Long non-coding RNA BC002811 Promotes Gastric Cancer Metastasis by Regulating SOX2 Binding to the PTEN Promoter.

There is increasing evidence that long non-coding RNAs (lncRNAs) are involved in the pathogenesis and progression of gastric cancer (GC), however, the underlying mechanisms remain poorly understood. In this study, we identified lncRNA BC002811 as a critical regulator of GC development and progression. BC002811 was upregulated in GC tissues and cell lines, and that high expression of BC002811 was indicative of a reduction in overall survival of GC patients. Our research reveals that BC002811 promoted GC cell proliferation, migration, invasion, and inhibition of apoptosis in vitro, as well as accelerated tumor growth and metastasis in vivo. We also found that BC002811 upregulated MMP2 and MMP9 and promoted GC cell metastasis partially through downregulating PTEN expression. BC002811 may act as a molecular decoy for the transcription factor SOX2, thereby inhibiting the transcription of PTEN by blocking SOX2 binding to the PTEN promoter. Our study advances the understanding of the role of BC002811 in the pathogenesis of GC and provides new molecular targets for therapeutic intervention against GC metastasis.

Stratified analysis of multiple management of gastric cancer: A population-based study of incidence, mortality and DALY.

The aim was to illuminate the difference in incidence, mortality, and disability-adjusted life-years (DALYs) of gastric cancer (GC) between the United States of America (US) and China. The multiple management was analyzed with stratification to explore an effective survival improvement strategy. The Global Burden of Disease Study data was analyzed to assess GC morbidity, mortality and DALYs from 1990 to 2019 in the US and China. The age-period-cohort model was established to generate estimation of metrics. Verification was completed and stratified analysis of the multiple management was performed by accessing data of Surveillance, Epidemiology, and End Results database in 1992 to 2019. Continuous downtrends in GC incidence, mortality and DALYs from 1990 to 2019 and persistent uptrends in 1-, 3-year survival from 1992 to 2019 were observed in the US population. In the Chinese population, the overall trends of incidence, mortality and DALYs decreased with a fluctuating manner. The lower overall survival rates were observed in elderly, unmarried patients, distant disease and poor grade, as well as patients lacking of medical treatment (P < .05). In stratified analyses, single local therapy decreased and the other modalities increased over time across different stages. Moreover, combined treatment and single systemic therapy decreased, but single local and conservative therapy increased with age. The study quantified the incidence, GC-specific mortality and DALYs in the US and China and estimated stage profiles, 1- and 3-year survival in the US. The heavy burden on later-onset GC (>70) and potential increase on early-onset GC (<40) needed to be addressed. Combined modalities and single chemotherapy were becoming more widely used over time, however, their uses decreased with age because of poor physical fitness. Our findings provide new insights into management tailoring appropriately to specific subgroups contributes to the increasing survival rate.

Molecular characterization of a novel botourmiavirus with inverted complementary termini from the rice blast fungus Magnaporthe oryzae isolate HF04.

A novel positive-sense single-stranded RNA mycovirus, designated as "Magnaporthe oryzae botourmiavirus 10" (MoBV10), was identified in the rice blast fungus Magnaporthe oryzae isolate HF04. MoBV10 has a single genomic RNA segment consisting of 2,448 nucleotides, which contains a single open reading frame encoding an RNA-dependent RNA polymerase. Genome comparison and phylogenetic analysis indicated that MoBV10 is a new member of the genus Betascleroulivirus in the family Botourmiaviridae. The 5'- and 3'-terminal sequences of the genomic RNA of MoBV10 have inverted complementarity and potentially form a panhandle structure, which is very rare in RNA viruses.

Patient Perspectives on Innovative Telemonitoring Enhanced Care Program for Chronic Heart Failure (ITEC-CHF): Usability Study.

BACKGROUND: Telemonitoring enables care providers to remotely support outpatients in self-managing chronic heart failure (CHF), but little is known about the usability and patients' willingness to engage with this technology. OBJECTIVE: This study aims to evaluate feedback from patients with CHF following participation in the Innovative Telemonitoring Enhanced Care program for CHF (ITEC-CHF) study. METHODS: The telemonitoring intervention consisted of three components: remote weight monitoring, structured telephone support, and nurse-led collaborative care. Participants were provided with electronic weighing scales (W550; ForaCare), and a computer tablet (Galaxy Tab A; Samsung). They were asked to weigh themselves on the provided scales daily. Telemonitoring was integrated with a personal assistance call service and a nurse care service according to their workflows in usual care. Feedback on the usability of ITEC-CHF was collected via survey from study participants following 6 months of receiving telemonitoring care for their body weight. Survey responses were provided on a 5-point Likert scale and through open-ended questions to determine participants' perceived benefits and barriers to using ITEC-CHF. RESULTS: A total of 67 participants (49/67, 73% male), with a mean age of 69.8 (SD 12.4) years completed the survey. The majority of participants agreed or strongly agreed that the ITEC-CHF program was easy to use (61/67, 91%), easy to navigate (51/65, 78%), useful (59/65, 91%), and made them feel more confident in managing their weight (57/67, 85%). Themes related to participants' perceptions of telemonitoring included increased support for early intervention of clinical deterioration, improved compliance to daily weighing, a sense of reassurance, and improved self-care and accountability, among others. CONCLUSIONS: ITEC-CHF was rated highly on usability and was well accepted by users as part of their routine self-management activities. Participants were willing to use telemonitoring because they perceived a broad spectrum of benefits for CHF management. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ID ACTRN 12614000916640; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366691.

Dihydromyricetin promotes apoptosis, suppresses proliferation and tumor necrosis factor-α-mediated nuclear factor kappa-B activation in nasopharyngeal carcinoma CNE-2 cell.

OBJECTIVE: To investigate the efficacy of dihydromyricetin (DMY) on nasopharyngeal carcinoma (NPC) cell proliferation, apoptosis and to reveal the underlying mechanism in vitro experiments. METHODS: The CNE-2 cell line was treated with different concentrations of DMY and the effects of DMY on cell viability and proliferation were evaluated using cell counting kit-8 (CCK-8) assay and plate colony formation assay. Cellular apoptosis was detected by flow cytometry following Annexin V fluorescein isothiocyanate/propidine iodide staining. Nuclei morphology was observed under a fluorescence microscope following Hoechst 333258 staining. The expression of phosphorylated inhibitor of nuclear factor kappa-B kinase subunit beta (p-IKKß), phosphorylated inhibitor of nuclear factor kappa-B kinase subunit alpha (p-IKKα), inhibitor of nuclear factor kappa-B alpha (IκB-α), nuclear factor kappa-B (NF-κB)/p65 was examined by Western blot analysis and the nuclear translocation of NF-κB/p65 was observed using a confocal laser scanning microscopy. RESULTS: DMY inhibited the proliferative capability and colony formation of NPC CNE-2 cells. Meanwhile, DMY induced apoptosis of CNE-2 cells in a dose and time-dependent manner via upregulating B-cell lymphoma-2 associated X, but downregulating B-cell lymphoma-2 and pro-caspase-3. Importantly, we found that DMY suppressed tumor necrosis factor alpha (TNF-α)-mediated NF-κB activation via inhibiting p-IKKß, p-IKKα and blocking NF-κB subunit p65. CONCLUSION: Our experiments demonstrated that DMY had significant antiproliferative and apoptosisinducing effects on CNE-2 cells. Additionally, DMY promoted inactivation of p-IKKß, p-IKKα, and blocked the nuclear translocation of NF-κB subunit p65. These results suggest that DMY may be an important therapeutic approach for NPC.

Complete nucleotide sequence of a novel botourmiavirus from the rice blast fungus Magnaporthe oryzae isolate SH05.

A novel mycovirus with the proposed name "Magnaporthe oryzae botourmiavirus 9" (MoBV9) was found in the rice blast fungus Magnaporthe oryzae isolate SH05. The virus has a positive single-stranded RNA genome of 2,812 nucleotides and contains a single open reading frame predicted to encode an RNA-dependent RNA polymerase that is closely related to those of some unclassified viruses of the family Botourmiaviridae, including Plasmopara viticola lesion associated ourmia-like virus 44, Plasmopara viticola lesion associated ourmia-like virus 47, and Cladosporium uredinicola ourmiavirus 1. Genome sequence comparisons and phylogenetic analysis supported the notion that MoBV9 is a new member of the family Botourmiaviridae.

A call for better understanding of social media in surveillance and management of noncommunicable diseases.

Using social media for health purposes has attracted much attention over the past decade. Given the challenges of population ageing and changes in national health profile and disease patterns following the epidemiologic transition, researchers and policy-makers should pay attention to the potential of social media in chronic disease surveillance, management and support. This commentary overviews the evidence base for this inquiry and outlines the key challenges to research laying ahead. The authors provide concrete suggestions and recommendations for developing a research agenda to guide future investigation and action on this topic.

Integrated analysis of microRNA and transcription factors in the bone marrow of patients with acute monocytic leukemia.

Acutemonocytic leukemia (AMoL) is a distinct subtype of acute myeloid leukemia (AML) with poor prognosis. However, the molecular mechanisms and key regulators involved in the global regulation of gene expression levels in AMoL are poorly understood. In order to elucidate the role of microRNAs (miRNAs/miRs) and transcription factors (TFs) in AMoL pathogenesis at the network level, miRNA and TF expression level profiles were systematically analyzed by miRNA sequencing and TF array, respectively; this identified 285 differentially expressed miRNAs and 139 differentially expressed TFs in AMoL samples compared with controls. By combining expression level profile data and bioinformatics tools available for predicting TF and miRNA targets, a comprehensive AMoL-specific miRNA-TF-mediated regulatory network was constructed. A total of 26 miRNAs and 23 TFs were identified as hub nodes in the network. Among these hubs, miR-29b-3p, MYC, TP53 and NFKB1 were determined to be potential AMoL regulators, and were subsequently extracted to construct sub-networks. A hypothetical pathway model was also proposed for miR-29b-3p to reveal the potential co-regulatory mechanisms of miR-29b-3p, MYC, TP53 and NFKB1 in AMoL. The present study provided an effective approach to discover critical regulators via a comprehensive regulatory network in AMoL, in addition to enhancing understanding of the pathogenesis of this disease at the molecular level.

Effects of Different Telemonitoring Strategies on Chronic Heart Failure Care: Systematic Review and Subgroup Meta-Analysis.

BACKGROUND: Telemonitoring studies in chronic heart failure are characterized by mixed mortality and hospitalization outcomes, which have deterred the uptake of telemonitoring in clinical practice. These mixed outcomes may reflect the diverse range of patient management strategies incorporated in telemonitoring. To address this, we compared the effects of different telemonitoring strategies on clinical outcomes. OBJECTIVE: The aim of this systematic review and subgroup meta-analysis was to identify noninvasive telemonitoring strategies attributing to improvements in all-cause mortality or hospitalization outcomes for patients with chronic heart failure. METHODS: We reviewed and analyzed telemonitoring strategies from randomized controlled trials (RCTs) comparing telemonitoring intervention with usual care. For each strategy, we examined whether RCTs that applied the strategy in the telemonitoring intervention (subgroup 1) resulted in a significantly lower risk ratio (RR) of all-cause mortality or incidence rate ratio (IRR) of all-cause hospitalization compared with RCTs that did not apply this strategy (subgroup 2). RESULTS: We included 26 RCTs (N=11,450) incorporating 18 different telemonitoring strategies. RCTs that provided medication support were found to be associated with a significantly lower IRR value than RCTs that did not provide this type of support (P=.01; subgroup 1 IRR=0.83, 95% CI 0.72-0.95 vs subgroup 2 IRR=1.02, 95% CI 0.93-1.12). RCTs that applied mobile health were associated with a significantly lower IRR (P=.03; IRR=0.79, 95% CI 0.64-0.96 vs IRR=1.00, 95% CI 0.94-1.06) and RR (P=.01; RR=0.67, 95% CI 0.53-0.85 vs RR=0.95, 95% CI 0.84-1.07). CONCLUSIONS: Telemonitoring strategies involving medication support and mobile health were associated with improvements in all-cause mortality or hospitalization outcomes. These strategies should be prioritized in telemonitoring interventions for the management of patients with chronic heart failure.

Use of eHealth in the management of pulmonary arterial hypertension: review of the literature.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a severe chronic condition associated with poor quality of life and high risks of mortality and hospitalisation. The utilisation of novel diagnostic technologies has improved survival rates although the effectiveness of Electronic Health (eHealth) interventions in patients with a chronic cardiopulmonary disease remains controversial. As the effectiveness of eHealth can be established by specific evaluation for different chronic health conditions, the aim of this study was to explore and summarise the utilisation of eHealth in PAH. METHOD: We searched PubMed, CINAHL and Embase for all studies reporting clinical trials on eHealth solutions for the management of PAH. No limitations in terms of study design or date of publication were imposed. RESULTS: 18 studies (6 peer-reviewed journal papers and 12 conference papers) were identified. Seven studies addressed the accuracy, safety or reliability of eHealth technologies such as intra-arterial haemodynamic monitoring of the pulmonary artery pressure, self-administered 6-Minute walk test App, computerised step-pulse oximeter and ambulatory impedance cardiography. Two studies evaluated eHealth as part of the medical management and showed a reduction in hospitalisation rate. CONCLUSIONS: The evidence of eHealth supporting the management of people with PAH is limited and only embraced through a few studies of small sample size and short-term duration. Given the proposed clinical benefits in heart failure, we postulate that the evaluation of eHealth for the clinical management of PAH is highly warranted.

The Effects of Telemonitoring on Patient Compliance With Self-Management Recommendations and Outcomes of the Innovative Telemonitoring Enhanced Care Program for Chronic Heart Failure: Randomized Controlled Trial.

BACKGROUND: Telemonitoring enables care providers to remotely support outpatients in self-managing chronic heart failure (CHF), but the objective assessment of patient compliance with self-management recommendations has seldom been studied. OBJECTIVE: This study aimed to evaluate patient compliance with self-management recommendations of an innovative telemonitoring enhanced care program for CHF (ITEC-CHF). METHODS: We conducted a multicenter randomized controlled trial with a 6-month follow-up. The ITEC-CHF program comprised the provision of Bluetooth-enabled scales linked to a call center and nurse care services to assist participants with weight monitoring compliance. Compliance was defined a priori as weighing at least 4 days per week, analyzed objectively from weight recordings on the scales. The intention-to-treat principle was used to perform the analysis. RESULTS: A total of 184 participants (141/184, 76.6% male), with a mean age of 70.1 (SD 12.3) years, were randomized to receive either ITEC-CHF (n=91) or usual care (control; n=93), of which 67 ITEC-CHF and 81 control participants completed the intervention. For the compliance criterion of weighing at least 4 days per week, the proportion of compliant participants in the ITEC-CHF group was not significantly higher than that in the control group (ITEC-CHF: 67/91, 74% vs control: 56/91, 60%; P=.06). However, the proportion of ITEC-CHF participants achieving the stricter compliance standard of at least 6 days a week was significantly higher than that in the control group (ITEC-CHF: 41/91, 45% vs control: 23/93, 25%; P=.005). CONCLUSIONS: ITEC-CHF improved participant compliance with weight monitoring, although the withdrawal rate was high. Telemonitoring is a promising method for supporting both patients and clinicians in the management of CHF. However, further refinements are required to optimize this model of care. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12614000916640; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366691.

Dolichosin A, a coumestan isolated from Glycine tabacina, inhibits IL-1ß-induced inflammation in SW982 human synovial cells and suppresses RANKL-induced osteoclastogenesis: From network pharmacology to experimental pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Glycine tabacina (Labill.) Benth has been used as a traditional Chinese herbal medicine for the treatment of rheumatoid arthritis (RA) and joint infection. It is also one of the sources of the renowned native herbal medicine 'I-Tiao-Gung' in Taiwan. AIM OF THE STUDY: This study aimed to investigate anti-arthritic effects and underlying mechanisms of dolichosin A (DoA), a coumestan compound isolated from G. tabacina, by the integration of network pharmacology and experimental pharmacology. MATERIALS AND METHODS: Putative therapeutic targets and potential pharmacological mechanisms of DoA for RA treatment were predicted by network pharmacology approach. The regulated network of DoA acting on RA was constructed using Cytoscape 3.7.1. Anti-arthritic effects of DoA and predicted mechanisms were further validated using IL-1ß-induced SW982 human synovial cell model and RANKL-induced osteoclastogenesis model. RESULTS: A regulatory network of DoA-targets-pathways-RA was successfully constructed using network pharmacology approach. In this network, 65 candidate targets of DoA related to its therapeutic effect on RA were identified and the functional enrichment analysis revealed that these candidate targets were significantly involved in 12 central signaling pathways such as PI3K/AKT pathway, MAPK pathway and osteoclast differentiation. Furthermore, we found that DoA could significantly inhibit IL-1ß-induced inflammation in SW982 human synovial cells, as evidenced by the decreased levels of pro-inflammatory mediators (TNF-α, IL-6 and COX-2) and MMP-3. DoA also suppressed RANKL-induced osteoclastogenesis in vitro, as evidenced by decreased number of TRAP-positive multinucleated osteoclasts and reduced TRAP activity. Further experimental mechanism evidence confirmed the predicted results of network pharmacology that the blockade of PI3K/AKT and MAPK pathways activation was closely associated with these regulated processes of DoA. CONCLUSIONS: Our results demonstrated that DoA exhibited strong anti-arthritic activity through suppressing PI3K/AKT and MAPK pathways activation in activated synovial cells and osteoclasts, suggesting its potential as a hopeful candidate for the development of novel agents for the prevention and treatment of RA.

Outcomes of a feasibility trial using an innovative mobile health programme to assist in insulin dose adjustment.

OBJECTIVE: Intensification of diabetes therapy with insulin is often delayed for people with suboptimal glycaemic control. This paper reports on the feasibility of using an innovative mobile health (mHealth) programme to assist a diabetes insulin dose adjustment (IDA) service. METHODS: Twenty adults with diabetes referred to a tertiary hospital IDA service were recruited. They were provided with a cloud-based mobile remote monitoring system-the mobile diabetes management system (MDMS). The credentialled diabetes educator (CDE) recorded the time taken to perform IDA utilising the MDMS versus the conventional method-which is a weekly adjustment of insulin doses by a CDE through telephone contact based on three or more daily blood glucose readings. Participants and staff completed a feedback questionnaire. RESULTS: The CDE spent 55% less time performing IDA using MDMS than using the conventional method. The participants were satisfied with MDMS use and the CDEs reported improved efficiency. CONCLUSION: Incorporating a mHealth programme for an IDA service has the potential to improve service delivery efficiencies while simultaneously improving the patient experience.