Evolution and function analysis of auxin response factors reveal the molecular basis of the developed root system of Zygophyllum xanthoxylum.

BACKGROUND: As a xerophytic shrub, forming developed root system dominated with lateral roots is one of the effective strategies for Zygophyllum xanthoxylum to adapt to desert habitat. However, the molecular mechanism of lateral root formation in Z. xanthoxylum is still unclear. Auxin response factors (ARFs) are a master family of transcription factors (TFs) in auxin-mediated biological processes including root growth and development. RESULTS: Here, to determine the relationship between ARFs and root system formation in Z. xanthoxylum, a total of 30 potential ZxARF genes were first identified, and their classifications, evolutionary relationships, duplication events and conserved domains were characterized. 107 ARF protein sequences from alga to higher plant species including Z. xanthoxylum are split into A, B, and C 3 Clades, consisting with previous studies. The comparative analysis of ARFs between xerophytes and mesophytes showed that A-ARFs of xerophytes expanded considerably more than that of mesophytes. Furthermore, in this Clade, ZxARF5b and ZxARF8b have lost the important B3 DNA-binding domain partly and completely, suggesting both two proteins may be more functional in activating transcription by dimerization with AUX/IAA repressors. qRT-PCR results showed that all A-ZxARFs are high expressed in the roots of Z. xanthoxylum, and they were significantly induced by drought stress. Among these A-ZxARFs, the over-expression assay showed that ZxARF7c and ZxARF7d play positive roles in lateral root formation. CONCLUSION: This study provided the first comprehensive overview of ZxARFs and highlighted the importance of A-ZxARFs in the lateral root development.

Ventral tegmental area dopaminergic circuits participates in stress-induced chronic postsurgical pain in male mice.

BACKGROUND: Chronic postsurgical pain (CPP) markedly impairs patients' quality of life. Research has shown that chronic stress may extend incisional nociception in male mice. Dopaminergic (DAergic) neurons in the ventral tegmental area (VTA) are integral to stress-related mental disorders (including major depressive disorder, anxiety disorders, and PTSD) and pain. However, the impact of chronic social defeat stress (CSDS) on mesolimbic dopamine (DA) transmission in the development of CPP is yet to be established. It remains uncertain whether the dopamine signals in the rostral anterior cingulate cortex (rACC), which regulate pain, derive from the VTA. This study aims to explore the role of VTA-rACC dopaminergic circuits in a mouse model of CPP induced by CSDS. METHODS: We conducted CSDS on C57BL/6 J wild-type male mice (n = 12-16 mice/group) and DAT-cre male mice (n = 10-12 mice/group). After 10 days of CSDS, a left posterior plantar incision was made to establish a mouse model of CPP. Paw withdrawal thresholds (PWTs) were evaluated using Von-Frey fibre stimulation. The open field test (OFT) and elevated plus maze test (EPM) were used to assess pain-related negative emotions. We used immunofluorescence staining and Western Blot to analyse D1, D2, c-Fos, and TH expression. DAergic fibre projections in the VTA-rACC neural pathway were traced using retrograde tracing and immunofluorescence staining. Optogenetics and Chemogenetics were employed to manipulate DAergic neurons in the VTA and their axons in the rACC. RESULTS: The ipsilateral PWTs in male C57BL/6 J mice significantly decreased after surgery, returning to baseline after seven days. Conversely, in CSDS mice, ipsilateral PWTs remained reduced for at least 30 days post-incision. A significant reduction in TH-positive neurons expressing c-Fos in the VTA of CPP mice was observed 15 days post-incision. Activating DAergic neurons significantly improved ipsilateral PWTs and locomotor performance in the OFT and EPM in CPP mice post-incision. Additionally, D1 expression in the rACC was found to decrease in CPP mice, and this reduction counteracted the increase in PWTs caused by activating DAergic neuron axon terminals in the rACC. CONCLUSION: CSDS results in chronicity of postsurgical nociception and anxiety-like negative emotions, with alterations in DA transmission playing a role in CPP. Specific activation of DAergic neurons mitigates nociceptive responses and anxiety-like bahaviors, possibly mediated by D1 receptors in the rACC.

DUSP5 regulated by YTHDF1-mediated m6A modification promotes epithelial-mesenchymal transition and EGFR-TKI resistance via the TGF-ß/Smad signaling pathway in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) patients have a dismal survival rate because of cancer metastasis and drug resistance. The study aims to identify the genes that concurrently modulate EMT, metastasis and EGFR-TKI resistance, and to investigate the underlying regulatory mechanisms. METHODS: Cox regression and Kaplan-Meier analyses were applied to identify prognostic oncogenes in LUAD. Gene set enrichment analysis (GSEA) was used to indicate the biological functions of the gene. Wound-healing and Transwell assays were used to detect migratory and invasive ability. EGFR-TKI sensitivity was evaluated by assessing the proliferation, clonogenic survival and metastatic capability of cancer cells with treatment with gefitinib. Methylated RNA immunoprecipitation (MeRIP) and RNA immunoprecipitation (RIP) analyses established the level of m6A modification present on the target gene and the protein's capability to interact with RNA, respectively. Single-sample gene set enrichment (ssGSEA) algorithm used to investigate levels of immune cell infiltration. RESULTS: Our study identified dual-specificity phosphatase 5 (DUSP5) as a novel and powerful predictor of adverse outcomes for LUAD by using public datasets. Functional enrichment analysis found that DUSP5 was positively enriched in EMT and transforming growth factor-beta (TGF-ß) signaling pathway, a prevailing pathway involved in the induction of EMT. As expected, DUSP5 knockdown suppressed EMT via inhibiting the canonical TGF-ß/Smad signaling pathway in in vitro experiments. Consistently, knockdown of DUSP5 was first found to inhibit migratory ability and invasiveness of LUAD cells in in vitro and prevent lung metastasis in in vivo. DUSP5 knockdown re-sensitized gefitinib-resistant LUAD cells to gefitinib, accompanying reversion of EMT progress. In LUAD tissue samples, we found 14 cytosine-phosphate-guanine (CpG) sites of DUSP5 that were negatively associated with DUSP5 gene expression. Importantly, 5'Azacytidine (AZA), an FDA-approved DNA methyltransferase inhibitor, restored DUSP5 expression. Moreover, RIP experiments confirmed that YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), a m6A reader protein, could bind DUSP5 mRNA. YTHDF1 promoted DUSP5 expression and the malignant phenotype of LUAD cells. In addition, the DUSP5-derived genomic model revealed the two clusters with distinguishable immune features and tumor mutational burden (TMB). CONCLUSIONS: Briefly, our study discovered DUSP5 which was regulated by epigenetic modification, might be a potential therapeutic target, especially in LUAD patients with acquired EGFR-TKI resistance.

Liraglutide Reduces Alcohol Consumption, Anxiety, Memory Impairment, and Synapse Loss in Alcohol Dependent Mice.

Glucagon-like peptide 1 (GLP-1) analogues have been commercialized for the management of type 2 diabetes. Recent studies have underscored GLP-1's role as a modulator of alcohol-related behavior. However, the role of the GLP-1 analogue liraglutide on alcohol-withdrawal responses have not been fully elucidated. Liraglutide binds to the G-protein-coupled receptor and activates an adenylyl cyclase and the associated classic growth factor signaling pathway, which acts growth factor-like and neuroprotective properties. The underlying neurobiological mechanisms of liraglutide on alcohol withdrawal remains unknown. This study endeavored to explore the effects of liraglutide on the emotion and memory ability of alcohol-withdrawal mice, and synaptic morphology in the medial prefrontal cortex (mPFC) and the hippocampus (HP), and thus affects the relapse-like drinking of alcohol-withdrawal mice. The alcohol-withdrawal group was reintroduced to a 20% v/v alcohol and water through the two-bottle choice for four consecutive days, a period referred to as alcohol re-drinking. Male C57BL/6J mice were exposed to a regimen of 20% alcohol and water for a duration of 6 weeks. This regimen established the two-bottle choice model of alcohol exposure. Learning capabilities, memory proficiency, and anxiety-like behavior were evaluated using the Morris water maze, open field, and elevated plus maze paradigms. Furthermore, synaptic morphology and the levels of synaptic transport-related proteins were assessed via Golgi staining and Western Blot analysis after a two-week alcohol deprivation period. Alcohol re-drinking of alcohol-withdrawal mice was also evaluated using a two-bottle choice paradigm. Our findings indicate that liraglutide can substantially decrease alcohol consumption and preference (p < 0.05) in the alcohol group and enhance learning and memory performance (p < 0.01), as well as alleviate anxiety-like behavior (p < 0.01) of alcohol-withdrawal mice. Alcohol consumption led to a reduction in dendritic spine density in the mPFC and HP, which was restored to normal levels by liraglutide (p < 0.001). Furthermore, liraglutide was found to augment the levels of synaptic transport-related proteins in mice subjected to alcohol withdrawal (p < 0.01). The study findings corroborate that liraglutide has the potential to mitigate alcohol consumption and ameliorate the memory impairments and anxiety induced by alcohol withdrawal. The therapeutic efficacy of liraglutide might be attributed to its role in counteracting synapse loss in the mPFC and HP regions and thus prevented relapse-like drinking in alcohol-withdrawal mice.

Identification of antimicrobial peptide genes from transcriptomes in Mandarin fish (Siniperca chuatsi) and their response to infection with Aeromonas hydrophila.

Mandarin fish (Siniperca chuatsi) is a valuable freshwater fish species widely cultured in China. Its aquaculture production is challenged by bacterial septicaemia, which is one of the most common bacterial diseases. Antimicrobial peptides (AMPs) play a critical role in the innate immune system of fish, exhibiting defensive and inhibitory effects against a wide range of pathogens. This study aimed to identify the antimicrobial peptide genes in mandarin fish using transcriptomes data obtained from 17 tissue in our laboratory. Through nucleotide sequence alignment and protein structural domain analysis, 15 antimicrobial peptide genes (moronecidin, pleurocidin, lysozyme g, thymosin ß12, hepcidin, leap 2, ß-defensin, galectin 8, galectin 9, apoB, apoD, apoE, apoF, apoM, and nk-lysin) were identified, of which 9 antimicrobial peptide genes were identified for the first time. In addition, 15 AMPs were subjected to sequence characterization and protein structure analysis. After injection with Aeromonas hydrophila, the number of red blood cells, hemoglobin concentration, and platelet counts in mandarin fish showed a decreasing trend, indicating partial hemolysis. The expression change patterns of 15 AMP genes in the intestine after A. hydrophila infection were examined by using qRT-PCR. The results revealed, marked up-regulation (approximately 116.04) of the hepcidin gene, down-regulation of the piscidin family genes expression. Moreover, most AMP genes were responded in the early stages after A. hydrophila challenge. This study provides fundamental information for investigating the role of the different antimicrobial peptide genes in mandarin fish in defense against A. hydrophila infection.

Policy implementation deviation of government purchase of old age care services in Jiangsu, China: based on empirical and policy analysis.

BACKGROUND: Government purchase of social forces to participate in old age care services can release the burden of social care. Current research on performance evaluation in this field mainly focussed on the establishment of appropriate evaluation indices. However, discussion on the policy implementation deviation is scarce. This study aimed to evaluate the performance of China's local government purchase of old age care services, analyse the characteristics of related policies and explore their deviation. METHODS: The persons who participated in the Training of the Trainer (ToT) organized by the Red Cross Society were enrolled. The policy documents were obtained from the official websites. The K-means cluster was used to determine the project performance grades. We compared the project performance grades between service objects and undertakers with different characteristics utilizing the non-parametric test. Based on the framework of 'Collaborative Participation - Project Performance Objective', we analysed the content of relevant policy aiding by NVivo 12. RESULTS: Data of project performance were collected from 306 participants. The standardized mean score of the efficiency dimension was the lowest (0.70 ± 0.24). The projects were divided into four grades: poor (17.0%), average (27.5%), good (12.4%) and excellent (43.1%). There were statistically significant differences in project performance grades only between advanced ageing groups (Z = 2.429, P = 0.015). As well, the policy also mentioned that the services focus should be tilted towards the oldest old. The purchasers mainly involved the Ministry of Civil Affairs and Health management departments in the policy. Respite services were less mentioned in the responsibilities of the undertakers. The requirement for efficiency and effectiveness was mentioned in less than half of the policy documents. CONCLUSION: Policy attention is needed for the responsibilities and functions of the intermediate purchasing force, as well as more precise directions and responsibilities of undertakers. The purchasers and undertakers should improve management abilities and capacity of old age care services and focus on associated factors to achieve the best marginal benefit. In addition, the embedded performance evaluation needs to be updated periodically to bridge the deviation between policy implementation and policy formulation.

A multi-stakeholder collaboration model of dementia-friendly communities: Experiences from Nanjing, China.

The care for people with dementia (PwD) in low- and middle-income countries (LMICs) is dominated by home care and supplemented sporadically by public care provided using public resources. In the context of community resources cannot meet the demand for high-quality services for PwD, dementia-friendly communities (DFCs) provide ideas for alleviating this situation by integrating resources from multiple stakeholders. However, there is still a considerable gap between the capacity of services and the demand of PwD. Based on the experience of elderly services and DFCs construction in Nanjing, China, this study developed a stakeholder collaboration model and clarified the collaborative relationship among stakeholders such as the government, communities, and medical institutions in meeting the needs of PwD. This work summarizes the partnerships and specific actions of stakeholders and highlights the importance of facilitating resource integration to provide comprehensive services.

Epidemiology and risk factors of oral frailty among older people: an observational study from China.

OBJECTIVES: This study aimed to compare the prevalence of oral frailty among community-dwelling older people in Nanjing, China with the usage of different measurements, and to investigate the potential risk factors of oral frailty. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A total of 338 community-dwelling older people in Nanjing, China were recruited. METHODS: Oral frailty was measured based on the Oral Frailty Index-8 (OFI-8) scale and other measurement methods including the number of natural teeth (TN), repetitive saliva-swallowing test (RSST), and oral diadochokinesis (ODK). The chi-square test and the binary logistic regression analysis were performed to identify potential risk factors for oral frailty. RESULTS: There were 310 participants included in the analysis. Prevalence of oral frailty by using the OFI-8, OFI-8 + TN, OFI-8 + ODK, OFI-8 + TN + ODK and RSST measurement methods were 69.0%, 27.4%, 51.9%, 21.0% and 2.9%, respectively. Passive smoking (OR = 2.04; 95%CI 1.03-4.03), being widowed/unmarried (OR1 = 2.53; 95%CI 1.25-5.10; OR2 = 2.94; 95%CI 1.12-7.77), pre-frailty (OR = 1.76; 95%CI 1.03-3.01), frailty (OR = 3.01; 95%CI 1.39-6.54), and aged 80 years and above (OR = 3.99; 95%CI 1.35-11.81) were found to be risk factors of oral frailty by the usage of the four kinds of measurement methods. CONCLUSIONS AND IMPLICATIONS: The definition and diagnostic criteria of oral frailty are strongly needed to be unified in future research. Only subjective assessment is not enough for assessing oral frailty. Among objective indicators, RSST is not suitable as a screening method for oral frailty. In addition, objective indicators including TN and ODK should be valued for early screening and preventive interventions. The risk factors of oral frailty include physical frailty, passive smoking, and being widowed.

Constraint-induced movement therapy alleviates motor impairment by inhibiting the accumulation of neutrophil extracellular traps in ischemic cortex.

Stroke is a major cause of mortality and morbidity and most acute strokes are ischemic. Evidence-based medicine has demonstrated the effectiveness of constraint-induced movement therapy (CIMT) in the recovery of motor function in patients after ischemic stroke, but the specific treatment mechanism remains unclear. Herein, our integrated transcriptomics and multiple enrichment analysis studies, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) studies show that CIMT conduction broadly curtails immune response, neutrophil chemotaxis, and chemokine-mediated signaling pathway, CCR chemokine receptor binding. Those suggest the potential effect of CIMT on neutrophils in ischemic mice brain parenchyma. Recent studies have found that accumulating granulocytes release extracellular web-like structures composed of DNA and proteins called neutrophil extracellular traps (NETs), which destruct neurological function primarily by disrupting the blood-brain barrier and promoting thrombosis. However, the temporal and spatial distribution of neutrophils and their released NETs in parenchyma and their damaging effects on nerve cells remain unclear. Thus, utilizing immunofluorescence and flow cytometry, our analyses uncovered that NETs erode multiple regions such as primary motor cortex (M1), striatum (Str), nucleus of the vertical limb of the diagonal band (VDB), nucleus of the horizontal limb of the diagonal band (HDB) and medial septal nucleus (MS), and persist in the brain parenchyma for at least 14 days, while CIMT can reduce the content of NETs and chemokines CCL2 and CCL5 in M1. Intriguingly, CIMT failed to further reduce neurological deficits after inhibiting the NET formation by pharmacologic inhibition of peptidylarginine deiminase 4 (PAD4). Collectively, these results demonstrate that CIMT could alleviate cerebral ischemic injury induced locomotor deficits by modulating the activation of neutrophils. These data are expected to provide direct evidence for the expression of NETs in ischemic brain parenchyma and novel insights into the mechanisms of CIMT protecting against ischemic brain injury.

The immune imbalance between follicular regulatory and helper T cells in myelin oligodendrocyte glycoprotein IgG-associated disease.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a newly defined inflammatory demyelinating disease of the central nervous system. Currently, no immuno-modulatory treatment has been approved for MOGAD. We explored the function of follicular regularoty T (Tfr) and follicular helper T (Tfh) cells in patients with MOGAD. The number of circulating Tfr and Tfh cells and their expression of functional markers were accessed by flow cytometry. Circulating Tfr, Tfh, and B cells were further sorted and co-cultured in vitro to examine the influence of Tfr on Tfh-mediated B cell differentiation. In patients with MOGAD, the percentage of circulating PD-1hi Tfh cells elevated while the frequency of circulating activated Tfr cells decreased significantly. The Tfh/Tfr ratios positively correlated with the percentage of plasmblasts. In vitro, Tfh cells from patients with MOGAD exhibited a stronger capacity to promote the differentiation of plasmablasts through producing interleukin (IL)-21 than non-Tfh cells from patients, whereas Tfr cells suppressed this Tfh-mediated plasmablasts expansion, to a similar extent of IL-1 receptor antagonist (IL-1Ra). In conclusion, we revealed an immune imbalance of Tfr and Tfh cells in MOGAD. Tfr and IL-1Ra could be potential therapeutic targets in MOGAD.

Apatinib plus etoposide in pretreated patients with advanced triple-negative breast cancer: a phase II trial.

BACKGROUND: Treatment options for pretreated triple-negative breast cancer (TNBC) are limited. This study aimed to evaluate the efficacy and safety of apatinib, an antiangiogenic agent, in combination of etoposide for pretreated patients with advanced TNBC. METHODS: In this single-arm phase II trial, patients with advanced TNBC who failed to at least one line of chemotherapy were enrolled. Eligible patients received oral apatinib 500 mg on day 1 to 21, plus oral etoposide 50 mg on day 1 to 14 of a 3-week cycle until disease progression or intolerable toxicities. Etoposide was administered up to six cycles. The primary endpoint was progression-free survival (PFS). RESULTS: From September 2018 to September 2021, 40 patients with advanced TNBC were enrolled. All patients received previous chemotherapy in the advanced setting, with the median previous lines of 2 (1-5). At the cut-off date on January 10, 2022, the median follow-up was 26.8 (1.6-52.0) months. The median PFS was 6.0 (95% confidence interval [CI]: 3.8-8.2) months, and the median overall survival was 24.5 (95%CI: 10.2-38.8) months. The objective response rate and disease control rate was 10.0% and 62.5%, respectively. The most common adverse events (AEs) were hypertension (65.0%), nausea (47.5%) and vomiting (42.5%). Four patients developed grade 3 AE, including two with hypertension and two with proteinuria. CONCLUSIONS: Apatinib combined with oral etoposide was feasible in pretreated advanced TNBC, and was easy to administer. CLINICAL TRIAL REGISTRATION: Chictr.org.cn, (registration number: ChiCTR1800018497, registration date: 20/09/2018).

Repetitive Transcranial Magnetic Stimulation of the Brain After Ischemic Stroke: Mechanisms from Animal Models.

Stroke is a common cerebrovascular disease with high morbidity, mortality, and disability worldwide. Post-stroke dysfunction is related to the death of neurons and impairment of synaptic structure, which results from cerebral ischemic damage. Currently, transcranial magnetic stimulation (TMS) techniques are available to provide clinically effective interventions and quantitative diagnostic and prognostic biomarkers. The development of TMS has been 40 years and a range of repetitive TMS (rTMS) protocols are now available to regulate neuronal plasticity in many neurological disorders, such as stroke, Parkinson disease, psychiatric disorders, Alzheimer disease, and so on. Basic studies in an animal model with ischemic stroke are significant for demonstrating potential mechanisms of neural restoration induced by rTMS. In this review, the mechanisms were summarized, involving synaptic plasticity, neural cell death, neurogenesis, immune response, and blood-brain barrier (BBB) disruption in vitro and vivo experiments with ischemic stroke models. Those findings can contribute to the understanding of how rTMS modulated function recovery and the exploration of novel therapeutic targets. The mechanisms of rTMS in treating ischemic stroke from animal models. rTMS can prompt synaptic plasticity by increasing NMDAR, AMPAR and BDNF expression; rTMS can inhibit pro-inflammatory cytokines TNF and facilitate the expression of anti-inflammatory cytokines IL-10 by shifting astrocytic phenotypes from A1 to A2, and shifting microglial phenotypes from M1 to M2; rTMS facilitated the release of angiogenesis-related factors TGFß and VEGF in A2 astrocytes, which can contribute to vasculogenesis and angiogenesis; rTMS can suppress apoptosis by increasing Bcl-2 expression and inhibiting Bax, caspase-3 expression; rTMS can also suppress pyroptosis by decreasing caspase-1, IL-1ß, ASC, GSDMD and NLRP1 expression. rTMS, repetitive transcranial magnetic stimulation; NMDAR, N-methyl-D-aspartic acid receptors; AMPAR: α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors; BDNF, brain-derived neurotrophic factor; VEGF, vascular endothelial growth factor; GSDMD: cleaved Caspase-1 cleaves Gasdermin D; CBF: cerebral blood flow.

MEX3A induces the development of thyroid cancer via targeting CREB1.

Thyroid cancer is a prevalent form of endocrine cancer, and its global incidence has been steadily increasing. MEX3A is a protein that is known to be highly expressed in various human malignant tumors, including thyroid cancer, and it has been linked to patient prognosis. However, the molecular mechanisms underlying MEX3A's tumorigenic capabilities in thyroid cancer are not fully understood. In this study, we aimed to investigate the role of MEX3A in thyroid cancer. We confirmed that MEX3A was overexpressed in both thyroid cancer tissues and cell lines. Additionally, we found a positive correlation between high levels of MEX3A and the AJCC stage. To further understand the functional significance of MEX3A in thyroid cancer, we depleted MEX3A expression in B-CPAP and TPC-1 cells. Interestingly, we observed a significant reduction in thyroid cancer cell proliferation and migration, as well as ameliorated cell apoptosis and arrested tumor growth upon MEX3A depletion. These findings strongly suggested that MEX3A played a critical role in the development of thyroid cancer. Furthermore, our study uncovered an important interaction between MEX3A and CREB1 (cAMP response element-binding protein 1). The interaction between MEX3A and CREB1 appeared to contribute to the tumor-promoting effects of MEX3A in thyroid cancer by directly targeting CREB1. Silencing CREB1 was observed to alleviate the malignant phenotypes promoted by MEX3A in thyroid cancer cells. Together, this study highlighted the importance of the MEX3A-CREB1 interaction in thyroid cancer development and suggested the therapeutic potential of targeting MEX3A for the treatment of this disease.

Economic evaluations of electronic health interventions for people with age-related cognitive impairment and their caregivers: A systematic review.

OBJECTS: Dementia has physical, social and economic impacts, causing considerable distress for people with age-related cognitive impairment (PWACI) and their caregivers. Electronic health (e-health) interventions can provide convenient education to improve the coping competence of caregivers and have become an important approach to supporting them. Understanding the economic evidence of e-health interventions will facilitate the decision making and implementation of integrating e-health into routine health services. The present review aimed to appraise economic evidence related to e-health interventions for PWACI and their caregivers. METHODS: We systematically searched multiple cross-disciplinary databases from inception to February 28, 2023. Two reviewers independently selected the trials, assessed the quality, and checked the data. A descriptive-analytical narrative method was used to analyze the review findings. RESULTS: Thirteen studies were analyzed, including 12 randomized controlled trials and one quasi-experimental study. All included studies were conducted in developed countries. The included studies reported limited economic information. There were six cost-effectiveness analysis, five cost-consequence analysis and one partial economic evaluation. The included studies were heterogeneous, and varied in quality. The results demonstrated that e-health multicomponent interventions can reduce the cost of health service utilization in short term (10-104 weeks). CONCLUSIONS: Few studies calculated the incremental cost-effectiveness ratio to evaluate the cost-effectiveness of e-health interventions. Preliminary evidence indicates that e-health interventions can reduce the cost of health service utilization in the short term, but the cost-effectiveness of e-health interventions hasn't been identified. More robust evidence is needed to clarify the value of e-health interventions for PWACI and their caregivers.

Clinical evaluation of percutaneous endovascular radiofrequency ablation for portal vein tumor thrombus: experience in 120 patients.

BACKGROUND: Portal vein tumor thrombosis (PVTT) secondary to primary liver carcinoma (PLC) is commonly associated with poor prognosis and poses great challenge. This study was to evaluate the efficacy and safety of percutaneous endovascular radiofrequency ablation (RFA) in treatment of PVTT. METHODS: Consecutive patients who were performed endovascular RFA because of PVTT in single-institution in recent 8 years were retrospectively reviewed, compared with patients who underwent only sequential transcatheter arterial chemoembolization (TACE) during the contemporary period. Patency of portal vein, complications, and overall survival (OS) were investigated. RESULTS: One hundred and 20 patients who underwent endovascular RFA and 96 patients who underwent only sequential TACE were included. No severe complications happened in both groups. Except the higher rates of severe fever and moderate pain in the study group, no difference was found in the incidence of side effects and complications. The effective rate in the study group was (78.3%, 94/120) significantly higher than the comparison group (35.4%, 34/96). The median survival time and 1-3 years cumulative survival rates in the study group were 15.7 months and 42.5%, 21.7%, 2.5%, respectively, and 11.3 months, 21.9%, 9.4%, 0 correspondingly in the comparison group, without significant difference. Type of PVTT and Child-Pugh classification of liver function were independent risk factors, and OS was significantly improved by endovascular RFA and subsequent therapy. CONCLUSION: Endovascular RFA is technically safe and feasible for unresectable PLC and PVTT to improve the prognosis and quality of life.

Multimorbidity patterns and the association with health status of the oldest-old in long-term care facilities in China: a two-step analysis.

BACKGROUND: The increasing prevalence of multimorbidity has created a serious global public health problem in aging populations. Certain multimorbidity patterns across different age ranges and their association with health status remain unclear. The main aim of this study is to identify multimorbidity patterns discrepancies and associated health status between younger-old and oldest-old. METHODS: The Ethics Committee of Nanjing Medical University approved the study protocol (No.2019-473). Convenience sampling method was used to recruit older adults aged ≥ 60 years with multimorbidity from July to December 2021 from 38 Landsea long-term care facilities in China. The multimorbidity patterns were analyzed using network analysis and two-step cluster analysis. One-Way ANOVA was utilized to explore their association with health status including body function, activity of daily living, and social participation. A Sankey diagram visualized the flow of health status within different multimorbidity patterns. This study is reported following the STROBE guidelines. RESULTS: A total of 214 younger-old (60-84 years) and 173 oldest-old (≥ 85 years) were included. Leading coexisting diseases were cardiovascular disease (CD), metabolic and endocrine disease (MED), neurological disease (ND), and orthopedic disease (OD). Cluster 1 (53, 24.8%) of CD-ND (50, 94.3%; 31, 58.8%), cluster 2 (39, 18.2%) of MED-ND-CD (39, 100%; 39, 100%; 37, 94.9%), cluster 3 (37, 17.3%) of OD-CD-MED-ND (37, 100%; 33, 89.2%; 27, 73.0%; 16, 43.2%), and cluster 4 (34, 15.9%) of CD-MED (34, 100%; 34, 100%) were identified in the younger-old. In the oldest-old, the primary multimorbidity patterns were: cluster 1 (33, 19.1%) of CD-respiratory disease-digestive disease-urogenital disease (CD-RD-DSD-UD) (32, 97.0%; 9, 27.3%; 8, 24.2%; 7, 21.2%), cluster 2 (42, 24.3%) of ND-CD-MED (42, 100%; 35, 83.3%; 14, 33.3%), cluster 3 (28, 16.2%) of OD-CD-MED (28, 100%; 25, 89.3%; 18, 64.3%), and cluster 4 (35, 20.2%) of CD-MED (35, 100%; 35, 100%). Younger-old with CD-ND or MED-ND-CD, and oldest-old with ND-CD-MED have worse health status compared with other multimorbidity patterns (e.g., CD-MED and OD-CD-MED). CONCLUSION: Discrepancies in common patterns of multimorbidity across age groups suggest that caregivers in long-term care facilities should consider changes in multimorbidity patterns with ageing when developing prevention plans for individualized management. Neurological disease concurrent with other diseases was the major determinant of health status, especially for the oldest-old. Interventions targeting multimorbidity need to be focused, yet generic. It is essential to assess complex needs and health outcomes that arise from different multimorbidity patterns and manage them through an interdisciplinary approach and consider their priorities to gain high-quality primary care for older adults living in long-term care facilities.

Impact of pesticides exposure during neurodevelopmental period on autism spectrum disorders - A focus on gut microbiota.

Accumulating evidence indicates exposure to pesticides during the crucial neurodevelopmental period increases susceptibility to many diseases, including the neurodevelopmental disorder known as autism spectrum disorder (ASD). In the last few years, it has been hypothesized that gut microbiota dysbiosis is strongly implicated in the aetiopathogenesis of ASD. Recently, new studies have suggested that the gut microbiota may be involved in the neurological and behavioural defects caused by pesticides, including ASD symptoms. This review highlights the available evidence from recent animal and human studies on the relationship between pesticides that have the potential to disturb intestinal microbiota homeostasis, and ASD symptoms. The mechanisms through which gut microbiota dysbiosis may trigger ASD-like behaviours induced by pesticides exposure during the neurodevelopmental period via the altered production of bacterial metabolites (short chain fatty acids, lipids, retinol, and amino acid) are also described. According to recent research, gut microbiota dysbiosis may be a major contributor to the symptoms of ASD associated with pesticides exposure. However, to determine the detailed mechanism of action of gut microbiota on pesticide-induced ASD behaviours, actual population exposure scenarios from epidemiological studies should be used as the basis for the appropriate exposure pattern and dosage to be used in animal studies.

Artificial intelligence of digital morphology analyzers improves the efficiency of manual leukocyte differentiation of peripheral blood.

BACKGROUND AND OBJECTIVE: Morphological identification of peripheral leukocytes is a complex and time-consuming task, having especially high requirements for personnel expertise. This study is to investigate the role of artificial intelligence (AI) in assisting the manual leukocyte differentiation of peripheral blood. METHODS: A total of 102 blood samples that triggered the review rules of hematology analyzers were enrolled. The peripheral blood smears were prepared and analyzed by Mindray MC-100i digital morphology analyzers. Two hundreds leukocytes were located and their cell images were collected. Two senior technologists labeled all cells to form standard answers. Afterward, the digital morphology analyzer unitized AI to pre-classify all cells. Ten junior and intermediate technologists were selected to review the cells with the AI pre-classification, yielding the AI-assisted classifications. Then the cell images were shuffled and re-classified without AI. The accuracy, sensitivity and specificity of the leukocyte differentiation with or without AI assistance were analyzed and compared. The time required for classification by each person was recorded. RESULTS: For junior technologists, the accuracy of normal and abnormal leukocyte differentiation increased by 4.79% and 15.16% with the assistance of AI. And for intermediate technologists, the accuracy increased by 7.40% and 14.54% for normal and abnormal leukocyte differentiation, respectively. The sensitivity and specificity also significantly increased with the help of AI. In addition, the average time for each individual to classify each blood smear was shortened by 215 s with AI. CONCLUSION: AI can assist laboratory technologists in the morphological differentiation of leukocytes. In particular, it can improve the sensitivity of abnormal leukocyte differentiation and lower the risk of missing detection of abnormal WBCs.

Electroacupuncture Zusanli (ST36) Relieves Somatic Pain in Colitis Rats by Inhibiting Dorsal Root Ganglion Sympathetic-Sensory Coupling and Neurogenic Inflammation.

Referred somatic pain triggered by hyperalgesia is common in patients with inflammatory bowel disease (IBD). It was reported that sprouting of sympathetic nerve fibers into the dorsal root ganglion (DGR) and neurogenic inflammation were related to neuropathic pain, the excitability of neurons, and afferents. The purpose of the study was to explore the potential and mechanism of electroacupuncture (EA) at Zusanli (ST36) for the intervention of colon inflammation and hyperalgesia. Sprague-Dawley (SD) was randomly divided into four groups, including control, model, EA, and sham-EA. Our results showed EA treatment significantly attenuated dextran sulfate sodium- (DSS-) induced colorectal lesions and inflammatory cytokine secretion, such as TNF-α, IL-1ß, PGE2, and IL-6. EA also inhibited mechanical and thermal pain hypersensitivities of colitis rats. Importantly, EA effectively abrogated the promotion effect of DSS on ipsilateral lumbar 6 (L6) DRG sympathetic-sensory coupling, manifested as the sprouting of tyrosine hydroxylase- (TH-) positive sympathetic fibers into sensory neurons and colocalization of and calcitonin gene-related peptide (CGRP). Furthermore, EA at Zusanli (ST36) activated neurogenic inflammation, characterized by decreased expression of substance P (SP), hyaluronic acid (HA), bradykinin (BK), and prostacyclin (PGI2) in colitis rat skin tissues corresponding to the L6 DRG. Mechanically, EA treatment reduced the activation of the TRPV1/CGRP, ERK, and TLR4 signaling pathways in L6 DRG of colitis rats. Taken together, we presumed that EA treatment improved colon inflammation and hyperalgesia, potentially by suppressing the sprouting of sympathetic nerve fibers into the L6 DGR and neurogenic inflammation via deactivating the TRPV1/CGRP, ERK, and TLR4 signaling pathways.

Magnetic MXene-based molecularly imprinted electrochemical sensor for methylmalonic acid.

A novel magnetic Ti3C2Tx-MXene/Fe3O4 composite was prepared from Ti3C2Tx and magnetic Fe3O4. The characterizations by electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM) exhibited that the Ti3C2Tx/Fe3O4 nanomaterial presented an outstanding conductivity and a large specific area, which could improve the electron transfer rate, leading to the amplification of the sensor's signal. Furthermore, an ultrasensitive molecularly imprinted electrochemical sensor based on MXene/Fe3O4 composites was fabricated for detecting methylmalonic acid (MMA) with high selectivity. The current intensity of differential pulse voltammetry of the sensor presented a good linear relationship with the logarithm of MMA concentration ranging from 9 × 10-15 mol L-1 to 9 × 10-13 mol L-1. The detection limit of the sensor was 2.33 × 10-16 mol L-1. The fabricated sensor was utilized for detecting MMA in human serum samples with excellent recoveries. Therefore, this method significantly improved the sensitivity of detection, and constitutes an  affordable sensing platform for trace detection of organic carboxylic acid.