Therapeutic effects of treat and repair strategy in pediatric patients with pulmonary arterial hypertension and simple congenital heart defects.

Surgical indications for patients with pulmonary arterial hypertension (PAH) and congenital heart defects are controversial. The treat and repair strategy has demonstrated efficacy in adult populations, but there have been no studies on pediatric patients. This study included pediatric patients with PAH and simple congenital heart defects who underwent corrective repair between 2012 and 2021. According to the preoperative treatment strategies, the patients were divided into a regular strategy group (Group 1) and a treat-and-repair strategy group (Group 2). Postoperative recovery and follow-up results were compared between the two groups. A total of 33 patients were included in this study. Group 1 consisted of 19 patients, whereas Group 2 consisted of 14 patients. The pulmonary vascular resistance index in Group 2 was higher than that in Group 1 (10.9 ± 4.1 vs. 8.2 ± 1.6 WU, p = 0.031). There were no differences in postoperative recovery between the two groups (p > 0.05). During follow-up, five patients were lost (three in Group 1 and two in Group 2). The median follow-up period was 59 months. One patient died in Group 1, and two patients died in Group 2. There was no significant difference in the survival curve (p = 0.39). At the last follow-up, another seven patients had experienced a non-low-risk condition, with a total of three non-low-risk patients in Group 1 and seven in Group 2, including one patient in each group who had a history of ICU admission. According to the ROC curve, a preoperative PVRi <8.2 WU×m2 can predict postoperative persistent low-risk state, PVRi <5.2 WU×m2 can avoid postoperative death and/or ICU administration. In pediatric patients with PAH and simple congenital heart defects, the treat and repair strategies may provide surgery opportunities, PVRi should be <8 WU×m2, and <5.2 WU×m2 is the best choice.

Single-cell sequencing reveals the impact of endothelial cell PIEZO1 expression on thoracic aortic aneurysm.

INTRODUCTION: Thoracic aortic aneurysm (TAA) is a severe vascular disease that threatens human life, characterized by focal dilatation of the entire aortic wall, with a diameter 1.5 times larger than normal. PIEZO1, a mechanosensitive cationic channel, monitors mechanical stimulations in the environment, transduces mechanical signals into electrical signals, and converts them into biological signals to activate intracellular signaling pathways. However, the role of PIEZO1 in TAA is still unclear. METHODS: We analyzed a single-cell database to investigate the expression level of PIEZO1 in TAA. We constructed a conditional knockout mouse model of Piezo1 and used the PIEZO1 agonist Yoda1 to intervene in the TAA model mice established by co-administration of BAPN and ANG-II. Finally, we explored the effect of Yoda1 on TAA in vitro. RESULTS AND DISCUSSION: We observed decreased PIEZO1 expression in TAA at both RNA and protein levels. Single-cell sequencing identified a specific reduction in Piezo1 expression in endothelial cells. Administration of PIEZO1 agonist Yoda1 prevented the formation of TAA. In PIEZO1 endothelial cell conditional knockout mice, Yoda1 inhibited TAA formation by interfering with PIEZO1. In vivo and in vitro experiments demonstrated that the effect of Yoda1 on endothelial cells involved macrophage infiltration, extracellular matrix degradation, and neovascularization. This study highlights the role of PIEZO1 in TAA and its potential as a therapeutic target, providing opportunities for clinical translation.

Research hotspots and trends of complementary and alternative therapy for neuropathic pain: A bibliometric analysis.

BACKGROUND: Neuropathic pain (NP) is a common type of pain in clinic. Due to the limited effect of drug treatment, many patients with NP are still troubled by this disease. In recent years, complementary and alternative therapy (CAT) has shown good efficacy in the treatment of NP. As the interest in CAT for NP continues to grow, we conducted a bibliometric study of publications on CAT treatment for NP. The aim of this study is to analyze the development overview, research hotspots and future trends in the field of CAT and NP through bibliometric methodology, so as to provide a reference for subsequent researchers. METHODS: Publications on CAT in the treatment of NP from 2002 to 2022 were retrieved from the Web of Science Core Collection. Relevant countries, institutions, authors, journals, keywords, and references were analyzed bibliometrically using Microsoft Excel 2021, bibliometric platform, VOSviewer, and CiteSpace. RESULTS: A total of 898 articles from 46 countries were published in 324 journals, and they were contributed by 4455 authors from 1102 institutions. The most influential country and institution are China (n = 445) and Kyung Hee University (n = 63), respectively. Fang JQ (n = 27) and Evidence-Based Complementary and Alternative Medicine (n = 63) are the author and journal with the most publications in this field. The clinical efficacy, molecular biological mechanisms and safety of CAT for NP are currently hot directions. Low back pain, postherpetic neuralgia, acupuncture, and herbal are the hot topics in CAT and NP in recent years. CONCLUSION: This study reveals the current status and hotspots of CAT for NP. The study also indicates that the effectiveness and effect mechanism of acupuncture or herbs for treating emotional problems caused by low back pain or postherpetic neuralgia may be a trend for future research.

Four new species of Anyphaena Sundevall, 1833 from Xizang, China (Araneae, Anyphaenidae).

Four new species of the genus Anyphaena Sundevall, 1833 collected from Xizang, China, are described: A.cibagou Wang & Mi, sp. nov. (♂♀), A.linzhi Wang & Mi, sp. nov. (♂♀), A.shufui Wang & Mi, sp. nov. (♀) and A.yejiei Wang & Mi, sp. nov. (♀). Diagnostic photos of the habitus and copulatory organs and a distributional map are provided.

Ncf1 knockout in SMCs exacerbates angiotensin II-induced aortic aneurysm and dissection by activating the STING pathway.

AIMS: Aortic aneurysm and dissection (AAD) is caused by the progressive loss of aortic smooth muscle cells (SMCs) and is associated with a high mortality rate. Identifying the mechanisms underlying SMC apoptosis is crucial for preventing AAD. Neutrophil cytoplasmic factor 1 (Ncf1) is essential in reactive oxygen species (ROS) production and SMC apoptosis; Ncf1 absence leads to autoimmune diseases and chronic inflammation. Here, the role of Ncf1 in angiotensin II (Ang II)-induced AAD was investigated. METHODS AND RESULTS: Ncf1 expression increased in injured SMCs. Bioinformatics analysis identified Ncf1 as a mediator of AAD-associated SMC damage. Ncf1 expression is positively correlated with DNA replication and repair in SMCs of AAD aortas. AAD incidence increased in Ang II-challenged Sm22CreNcf1fl mice. Transcriptomics showed that Ncf1 knockout activated the stimulator of interferon genes (STING) and cell death pathways. The effects of Ncf1 on SMC death and the STING pathway in vitro were examined. Ncf1 regulated the hydrogen peroxide-mediated activation of the STING pathway and inhibited SMC apoptosis. Mechanistically, Ncf1 knockout promoted the ubiquitination of nuclear factor erythroid 2-related factor 2 (NRF2), thereby inhibiting the negative regulatory effect of NRF2 on the stability of STING mRNA and ultimately promoting STING expression. Additionally, the pharmacological inhibition of STING activation prevented AAD progression. CONCLUSIONS: Ncf1 deficiency in SMCs exacerbated Ang II-induced AAD by promoting NRF2 ubiquitination and degradation and activating the STING pathway. These data suggest that Ncf1 may be a potential therapeutic target for AAD treatment.

Sliding limited penetrable visibility graph for establishing complex network from time series.

This study proposes a novel network modeling approach, called sliding window limited penetrable visibility graph (SLPVG), for transforming time series into networks. SLPVG takes into account the dynamic nature of time series, which is often affected by noise disturbances, and the fact that most nodes are not directly connected to distant nodes. By analyzing the degree distribution of different types of time series, SLPVG accurately captures the dynamic characteristics of time series with low computational complexity. In this study, the authors apply SLPVG for the first time to diagnose compensation capacitor faults in jointless track circuits. By combining the fault characteristics of compensation capacitors with network topological indicators, the authors find that the betweenness centrality reflects the fault status of the compensation capacitors clearly and accurately. Experimental results demonstrate that the proposed model achieves a high accuracy rate of 99.1% in identifying compensation capacitor faults. The SLPVG model provides a simple and efficient tool for studying the dynamics of long time series and offers a new perspective for diagnosing compensation capacitor faults in jointless track circuits. It holds practical significance in advancing related research fields.

Stereocontrol in an intermolecular Schmidt reaction of equilibrating hydroxyalkyl allylic azides.

A selective intermolecular Schmidt reaction of equilibrating hydroxyalkyl allylic azides is reported to afford N-hydroxyalk-1-en-3-yl lactams in modest to high yields. For prochiral and chiral ketones, modest to high 1,5-diastereoselectivity was achieved, and the mechanistic analysis is supported by DFT calculation.

Neural interface-based motor neuroprosthesis in post-stroke upper limb neurorehabilitation: An individual patient data meta-analysis.

OBJECTIVE: To determine the efficacy of neural interface-, including brain-computer interface (BCI), based neurorehabilitation through conventional and individual patient data (IPD) meta-analysis, and to assess clinical parameters associated with positive response to neural interface-based neurorehabilitation. DATA SOURCES: PubMed, EMBASE, and Cochrane Library databases up to February 2022 were reviewed. STUDY SELECTION: Studies using neural interface-controlled physical effectors (FES and/or powered exoskeletons) and reported Fugl-Meyer Assessment-upper extremity (FMA-UE) scores were identified. This meta-analysis was prospectively registered on PROSPERO (#CRD42022312428). PRISMA guidelines were followed. DATA EXTRACTION: Change in FMA-UE scores were pooled to estimate the mean effect size. Subgroup analyses were performed on clinical parameters and neural interface parameters with both study-level variables and IPD. DATA SYNTHESIS: Forty-six studies containing 617 patients were included. Twenty-nine studies involving 214 patients reported IPD. FMA-UE score increased by a mean of 5.23 (95% CI: 3.85 to 6.61). Systems that used motor attempt resulted in greater FMA-UE gain than motor imagery, as did training lasting >4 versus ≤4 weeks. On IPD analysis, the mean time-to-improvement above MCID was 12 weeks (95% CI: 7 to not reached). At 6 months, 58% improved above MCID (95% CI: 41 to 70%). Patients with severe impairment (p=0.042) and age >50 years (p=0.0022) correlated with the failure to improve above the MCID on univariate log-rank tests. However, these factors were only borderline significant on multivariate Cox analysis (HR 0.15, p = 0.08 and HR 0.47, p = 0.06, respectively). CONCLUSION: Neural interface-based motor rehabilitation resulted in significant though modest reductions in post-stroke impairment and should be considered for wider applications in stroke neurorehabilitation.

Current Understanding of Timing of Surgical Repair for Ventricular Septal Rupture following Acute Myocardial Infarction.

BACKGROUND: Ventricular septal rupture (VSR) is a mechanical issue that can occur following an acute myocardial infarction (AMI) and has a high mortality rate. It requires a comprehensive, team-based approach for prompt diagnosis and maintaining stable blood flow. While the occurrence of VSR has lessened over the past hundred years and advancements have been made in treatment techniques, the mortality rate within 30 days can still surpass 40 percent. Surgery is the primary treatment method. For patients with stable blood flow, it's generally considered safer to perform surgery 4-6 weeks after the AMI to repair the VSR. However, the timing of surgery for patients with early instability in their blood flow is still a topic of debate. SUMMARY: There's a lack of set criteria and standards to determine the best time for surgery in patients with VSR following an infarction who have unstable blood flow, especially when considering the use of blood circulation support devices and other techniques for maintaining blood flow that are used in clinical settings. KEY MESSAGES: This review outlines the features of different mechanical circulatory support devices utilized in treating VSR, along with the current scoring system designed to direct the treatment approach for VSR patients.

Healthcare-associated infection management in 62 ICUs for patients with congenital heart disease in China: a survey study.

OBJECTIVES: All patients with congenital heart disease (CHD) receive postoperative management in ICUs. Infection prevention and control (IPC) has a significant impact on prognosis. This study provides a preliminary understanding of the fundamental aspects of IPC in ICUs following CHD surgery in China. METHODS: From September to October 2023, we initiated a survey on healthcare-associated infection (HAI) management in hospitals that perform CHD surgeries independently. The questionnaires were jointly completed by the ICU physicians and IPC personnel. Duplicate or unqualified questionnaires were excluded from the study. The contents of our questionnaires covered hospital and ICU capacity, performance of the infection control department, HAI surveillance, implementation of IPC measures, and antimicrobial stewardship (AMS). Qualified questionnaires were compared according to the volume of annual CHD surgeries performed in different ICUs. Group 1 was defined as volume more than 300 cases and group 2 was defined as volume less than or equal to 300 cases. RESULTS: Sixty-two of the 118 questionnaires were completed, with a response rate of 53%. The CHD surgical volume in 2022 of the 62 hospitals was 36342, accounting for 52% of the annual CHD surgical volume (69 672) across the country. The postoperative infection rates obtained from the 15 ICUs varied from 1.3 to 15%, with a median rate of 4.5%. A total of 16 ICUs provided data on drug-resistant bacteria, Klebsiella pneumoniae exhibiting the highest frequency. More than 95% of ICUs have established complete HAI management systems. Information-based HAI surveillance was conducted in 89% of ICUs. Approximately 67% of ICUs stopped prophylactic antibiotics within 48 hours after surgery. In complex cases, carbapenems were administered empirically in 89% of ICUs. Group 1 had an advantage over group 2 in preventing multi-drug-resistant organisms (all instruments should be used alone 100% vs. 86%, P =0.047; cleaning and disinfection of environmental surfaces, 100% vs. 81%, P =0.035; antibiotic consumption control 85% vs. 61%, P =0.044) and in preventing surgical site infections (perioperative blood glucose monitoring, 88% vs. 67%, P =0.048). However, Group 1 did not perform well in preventing catheter-related bloodstream infection (delayed catheter removal due to convenience of laboratory tests, 31% vs. 6%, P =0.021) and catheter-associated urinary tract infection (delayed catheter removal due to muscle relaxant administration, 88% vs. 58%, P =0.022). CONCLUSIONS: A relatively complete HAI management system has been established throughout the country in ICUs for CHD patients. Information-based surveillance of HAI needs to be promoted, and actions should be taken to facilitate the implementation of IPC measures and AMS bundles. Training and feedback are critical for implementing IPC measures.

Computational exploration of the significance of COPS6 in cancer: Functional and clinical relevance across tumor types.

BACKGROUND: The COP9 signalosome subunit 6 (COPS6) has been implicated in cancer progression, while its precise role in most types of cancer remains elusive. AIM: To investigate the functional and clinical relevance of COPS6 across various tumor types using publicly available databases. METHODS: We used R software and online analysis databases to analyze the differential expression, prognosis, mutation and related functions of COPS6 in pan-cancer. RESULTS: Differential expression analysis and survival analysis demonstrated that COPS6 was highly expressed and associated with high-risk profiles in the majority of cancer types. Possible associations between COPS6 expression level and prognostic outcomes were found using data from public databases. Mutational analysis revealed that missense mutations were the predominant type of COPS6 mutation. Additionally, positive correlations were identified between COPS6 expression level and tumor mutational burden and microsatellite instability in most types of cancer. Immune infiltration analysis demonstrated a negative correlation between COPS6 expression level and CD8+ T cell infiltration in certain types of cancer. The correlation between COPS6 expression level and cancer-associated fibroblast infiltration exhibited heterogeneity, in which a positive correlation was found in head and neck squamous cell carcinoma and tenosynovial giant cell tumor, and a negative correlation was identified in diffuse large B-cell lymphoma and thymoma. The correlation between COPS6 expression level and macrophage infiltration was closely related to macrophage type. Gene co-expression and enrichment analysis highlighted transcription elongation factor B polypeptide 2 and G protein pathway suppressor 1 were significantly and positively associated with COPS6 expression level. These genes were predominantly involved in processes, such as ubiquitin-mediated proteolysis and human immunodeficiency virus 1 infection. CONCLUSION: In conclusion, this study systematically explored the significance of COPS6 across different tumor types, providing a solid foundation for considering COPS6 as a novel biomarker in cancer research.

Differences in Physiological Performance and Gut Microbiota between Deep-Sea and Coastal Aquaculture of Thachinotus Ovatus: A Metagenomic Approach.

Aquaculture has become the fastest growing sector in global agriculture. The environmental degradation, diseases, and high density of mariculture has made for an inevitable shift in mariculture production from coastal to deep-sea areas. The influence that traditional coastal and emerging deep-sea farming environments exert on aquatic growth, immunity and gut microbial flora is unclear. To address this question, we compared the growth performance, physiological indicators and intestinal microbiological differences of deep-sea and coastal aquaculture in the Guangxi Beibu Gulf of China. The results showed that the growth performance and the complement of C3 and C4 (C3, C4), superoxide dismutase (SOD), and lysozyme (LYS), these physiological and biochemical indicators in the liver, kidney, and muscle of Trachinotus ovatus (T. ovatus), showed significant differences under different rearing conditions. Metagenome sequencing analysis showed Ascomycota, Pseudomonadota, and Bacillota were the three dominant phyla, accounting for 52.98/53.32 (coastal/deep sea), 24.30/22.13, and 10.39/11.82%, respectively. Aligned against the CARD database, a total of 23/2 (coastal/deep-sea) antibiotic resistance genes were screened and grouped into 4/2 genotypes. It indicated that compared with deep-sea fish, higher biological oxygen levels (3.10 times), inorganic nitrogen (110.00 times) and labile phosphate levels (29.00 times) in coastal waters might contributed to the existence of eutrophication with antibiotic resistance. The results of the study can provide complementary data on the study of the difference between deep-sea farming and traditional coastal farming, serving as a reference to future in-depth work on the transformation of fisheries development and scientific standardization of deep-sea farming.

Assessing causality between second-hand smoking and potentially associated diseases in multiple systems: A two-sample Mendelian randomization study.

INTRODUCTION: The global disease burden may be exacerbated by exposure to passive smoking (SHS), with the workplace being a primary location for such exposure. Numerous epidemiological studies have identified SHS as a risk factor for diseases affecting various systems, including cardiovascular, respiratory, immune, endocrine, and nervous systems. The conventional observational study has certain methodological constraints which can be circumvented through a Mendelian randomization (MR) study. Our MR study intends to investigate the causal link between workplace exposure to SHS and the potential associated diseases. METHODS: Summary statistics data involving European participants was sourced from three databases: the UK Biobank, the FinnGen study, and the European Bioinformatics Institute. Genetic variants linked with exposure to SHS in the workplace were identified as instrumental variables. The MR was carried out using inverse variance weighted (IVW), MR-Egger, and weighted median methods. Sensitivity tests were also undertaken within the MR to evaluate the validity of the causality. RESULTS: According to the IVW model, genetically determined atrial fibrillation (AF) and stroke [P= 6.64E-04 and 5.68E-07, odds ratio = 2.030 and 2.494, 95% confidence interval = 1.350,3.051 and 1.743,3.569] were robustly associated with exposure to SHS in the workplace. Suggestive associations were found between workplace SHS and myocardial infarction (MI), asthma, and depression. CONCLUSIONS: The MR study demonstrates that exposure to SHS in the workplace is a significant risk factor for AF and stroke in European individuals. Whether workplace exposure to SHS influences other diseases and the causality between them requires further exploration. IMPLICATIONS: This study explored the causality between exposure to SHS in the workplace and potential associated diseases in multiple systems, including MI, AF, stroke, lung cancer, asthma, allergic disease, type 2 diabetes, and depression, using a MR study. The MR study can circumvent the methodological constraints of observational studies and establish a causal relationship. The two-sample MR analysis provides evidence supporting the causal association of frequent workplace SHS with AF and stroke. Individuals exposed to SHS in the workplace may also have a heightened risk of MI, asthma, and depression. However, whether SHS affects other diseases and the causality between them requires further investigation. To our knowledge, this is the first two-sample MR study to determine the causal relationship between SHS and potential diseases. As exposure to SHS in the workplace is a prevalent issue and may contribute to a global disease burden. The reduction of exposure following the introduction of smoke-free laws has led to a decrease in the admission rate for cardiac events and an improvement in health indicators. It is crucial to further advance smoke-free policies and their implementation.

A role of inflammaging in aortic aneurysm: new insights from bioinformatics analysis.

Introduction: Aortic aneurysms (AA) are prevalent worldwide with a notable absence of drug therapies. Thus, identifying potential drug targets is of utmost importance. AA often presents in the elderly, coupled with consistently raised serum inflammatory markers. Given that ageing and inflammation are pivotal processes linked to the evolution of AA, we have identified key genes involved in the inflammaging process of AA development through various bioinformatics methods, thereby providing potential molecular targets for further investigation. Methods: The transcriptome data of AA was procured from the datasets GSE140947, GSE7084, and GSE47472, sourced from the NCBI GEO database, whilst gene data of ageing and inflammation were obtained from the GeneCards Database. To identify key genes, differentially expressed analysis using the "Limma" package and WGCNA were implemented. Protein-protein intersection (PPI) analysis and machine learning (ML) algorithms were employed for the screening of potential biomarkers, followed by an assessment of the diagnostic value. Following the acquisition of the hub inflammaging and AA-related differentially expressed genes (IADEGs), the TFs-mRNAs-miRNAs regulatory network was established. The CIBERSORT algorithm was utilized to investigate immune cell infiltration in AA. The correlation of hub IADEGs with infiltrating immunocytes was also evaluated. Lastly, wet laboratory experiments were carried out to confirm the expression of hub IADEGs. Results: 342 and 715 AA-related DEGs (ADEGs) recognized from GSE140947 and GSE7084 datasets were procured by intersecting the results of "Limma" and WGCNA analyses. After 83 IADEGs were obtained, PPI analysis and ML algorithms pinpointed 7 and 5 hub IADEGs candidates respectively, and 6 of them demonstrated a high diagnostic value. Immune cell infiltration outcomes unveiled immune dysregulation in AA. In the wet laboratory experiments, 3 hub IADEGs, including BLNK, HLA-DRA, and HLA-DQB1, finally exhibited an expression trend in line with the bioinformatics analysis result. Discussion: Our research identified three genes - BLNK, HLA-DRA, and HLA-DQB1- that play a significant role in promoting the development of AA through inflammaging, providing novel insights into the future understanding and therapeutic intervention of AA.

Laparoscopic common bile duct exploration with primary closure is preferred for selected elderly individuals with choledocholithiasis.

Background: Laparoscopic common bile duct exploration with primary closure (LCBDE-PC) exhibits more benefits than other surgeries for patients with choledocholithiasis. It remains unclear whether it is feasible for and beneficial to elderly individuals. This study aimed to clarify and stratify elderly patients who would benefit from LCBDE-PC. Methods: A retrospective study of 1240 patients with choledocholithiasis who underwent laparoscopic procedures between 2011 and 2019 was conducted. Patients were divided into the young group (<65 years old, n = 708) and the elderly group (≥65 years old, n = 532). Perioperative outcomes were compared between the two groups. Results: Laparoscopic common bile duct exploration with primary closure was successfully performed in 90.20% of the elderly and 94.20% of the young. No significant differences were observed between the two groups regarding reoperation, postoperative bile leakage, residual stones, drainage removal, and postoperative mortality. Compared with the young, the elderly had longer postoperative hospital stay (p = 0.035) and delayed postoperative eating time (p = 0.036) in the matched cohort. Independent risk factors for failed LCBDE-PC were preoperative pancreatitis (p = 0.018), year of the surgeon's experience (p = 0.008), preoperative C-reactive protein level (p = 0.034), preoperative total bilirubin (p = 0.021), impacted common bile duct (CBD) stones (p = 0.006), blood loss (p = 0.001), and edema of the CBD (p = 0.001). A novel nomogram for predicting failed LCBDE-PC in elderly individuals exhibited a sufficient discriminative ability according to the estimated area under the curve (AUC) of 0.869 (95% CI: 0.817-0.921, p < 0.01). Conclusion: Laparoscopic common bile duct exploration with primary closure is safe, feasible, and effective for elderly individuals with choledocholithiasis. Elderly patients with a high risk of failed LCBDE-PC should be cautious of undergoing LCBDE-PC.

The efficacy of virtual reality exposure therapy for the treatment of alcohol use disorder among adult males: a randomized controlled trial comparing with acceptance and commitment therapy and treatment as usual.

Background: This multicenter, three-armed, parallel, single-blind randomized controlled trial (RCT) primarily aims to compare the efficacy of virtual reality exposure therapy (VRET) with that of acceptance and commitment therapy (ACT) and treatment as usual (TAU) to depreciate the degree of alcohol craving among alcohol use disorder patients who have undergone in-patient detoxification across four timelines (t0 = baseline prior to intervention, t1 = 4 weeks after baseline, t2 = 12 weeks after baseline, and t3 = 24 weeks after baseline). The secondary aims of this RCT are to compare the efficacy of VRET with that of ACT and TAU to alleviate the severity of alcohol use disorder, dissipate comorbid depressive and anxiety symptoms, and normalize event-related potential (ERP) in electroencephalogram (EEG) monitoring across the four timelines. Methods: Initially, after 2 weeks of in-patient detoxification, 120 patients with alcohol use disorder will be randomized into three groups (VRET, ACT, and TAU control groups) via stratified permuted block randomization in a 1:1:1 ratio. Baseline assessment (t0) commences, whereby all the participants will be administered with sociodemographic, clinical, and alcohol use characteristics questionnaire, such as Alcohol Use Disorder Identification Test (AUDIT), Penn Alcohol Craving Scale (PACS), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HAM-D), while event-related potential (ERP) detection in electroencephalogram (EEG) will also be carried out. Then, 4 weeks of VRET, ACT, and non-therapeutic supportive activities will be conducted in the three respective groups. For the subsequent three assessment timelines (t1, t2, and t3), the alcohol use characteristic questionnaire, such as AUDIT, PACS, HAM-D, HAM-A, and ERP monitoring, will be re-administered to all participants. Discussion: As data on the effects of non-pharmacological interventions, such as VRET and ACT, on the treatment of alcohol craving and preventing relapse in alcohol use disorder are lacking, this RCT fills the research gap by providing these important data to treating clinicians. If proven efficacious, the efficacy of VRET and ACT for the treatment of other substance use disorders should also be investigated in future. Clinical trial registration: NCT05841823 (ClinicalTrials.gov).

Exploring the genetic association of allergic diseases with cardiovascular diseases: a bidirectional Mendelian randomization study.

Background: In observational and experimental studies, allergic diseases (AD) have been reported to be associated with some types of cardiovascular diseases (CVD), as both share common pathophysiological processes involving inflammation and metabolic disorders. However, the direction of the causal association between them remains unclear. This Mendelian randomization (MR) study aims to examine the bidirectional causality between AD and CVD. Methods: We utilized publicly available genome-wide association study (GWAS) summary statistics data from European participants in the UK Biobank and the IEU Open GWAS database. Genetic variants associated with AD, asthma, and CVD were identified and used as instrumental variables to investigate the genetically causal association between them. MR analyses were performed using various analytical methods, including inverse variance weighted-fixed effects (IVW-FE), inverse variance weighted-multiplicative random effects (IVW-RE), MR-Egger, weighted median, weighted mode, and maximum likelihood. Sensitivity tests were conducted to assess the validity of the causality. Results: The MR analysis with the IVW method revealed a genetically predicted association between AD and essential hypertension [odds ratio (OR)=0.9987, 95% confidence interval (CI): 0.9976-0.9998, P=0.024], as well as between asthma and atrial fibrillation (OR=1.001, 95% CI: 1.0004-1.0017, P=6.43E-05). In the reverse MR analyses, heart failure was associated with allergic diseases (OR=0.0045, 95% CI: 1.1890E-04 - 0.1695, P=0.004), while atherosclerosis (OR=8.7371E-08, 95% CI: 1.8794E-14 - 4.0617E-01, P=0.038) and aortic aneurysm and dissection (OR=1.7367E-07, 95% CI: 3.8390E-14 - 7.8567E-01, P=0.046) might be protective factors of asthma. However, after a Bonferroni correction, only the association between asthma and atrial fibrillation remained robust. Conclusion: The MR study revealed that asthma is a predominant risk of atrial fibrillation in European individuals, consistent with most experimental and observational studies. Whether AD affects other CVD and the causality between them needs further investigation.

[Early electroacupuncture intervention delays progression of disease in mice with amyotrophic lateral sclerosis by down-regulating TLR4/NF-κB signaling].

OBJECTIVE: To observe the effect of early electroacupuncture (EA) intervention on Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway in mice with amyotrophic lateral sclerosis (ALS), so as to explore its mechanisms underlying alleviation of ALS. METHODS: Fifty-four ALS (ALS-SOD1G93A) mice with SOD1G93A gene mutation identified by PCR were randomly divided into model group, 60 day(d) EA group and 90 d EA group(n=18 mice in each group), and other 18 ALS-SOD1G93A negative mice were used as the control group. At the age of 60 and 90 days, mice of the two EA groups received EA (2 Hz, 1 mA) stimulation of bilateral "Jiaji" (EX-B2) of L1-L2 and L5-L6 for 20 min, twice a week for 4 weeks,respectively. When being 60 days old, the mice in the model and control groups were subjected to the same binding as that in the two EA groups but without EA intervention. The tail suspension test was used to judge the onset time of disease and the survival period, and rotary rod fatigue test was used to evaluate the hind limb motor function. Nissl staining method was used to observe the content of Nissl bodies in the anterior horn of the lumbar spinal cord. Immunohistochemical staining was used to observe the expression of ionized calcium binding adaptor molecule-1 (Iba-1) in the anterior horn of the lumbar spinal cord, and Western blot was used to detect the relative expression of TLR4, NF-κB and tumor necrosis factor-α (TNF-α) in the lumbar spinal cord. RESULTS: The disease onset time apparently delayed in the 60 d EA group than in the model group (P<0.01). The survival time was apparently shorter in the model group than in the control group (P<0.01), and obviously prolonged in the 60 d EA and 90 d EA groups than in the model group (P<0.01). The rotatory rod time was obviously shorter in the model group than in the control group (P<0.05), and apparently longer in the 60 d EA group than in the model group and 90 d EA group (P<0.05). Compared with the control group, the model group had a decrease in the number of Nissl bodies in the anterior horn of the lumbar spinal cord (P<0.01), and an increase in the expression levels of Iba-1, TLR4, NF-κB and TNF-α in the lumbar spinal cord (P<0.01). In contrast to the model group, both 60 d EA and 90 d EA groups had an apparent increase in the number of Nissl bodies and a marked decrease in the expression levels of Iba-1, TLR4, NF-κB and TNF-α in the lumbar spinal cord (P<0.05, P<0.01). The therapeutic effects of 60 d EA group were evidently superior to those of 90 d EA group in delaying the onset time of disease, prolonging the survival time and rotatory rod time, increasing the number of Nissl bodies, and in down-regulating the expression of Iba-1, TLR4, NF-κB and TNF-α (P<0.05, P<0.01). CONCLUSION: The early intervention of EX-B2 EA is more effective in delaying the progression of ALS than post-onset intervention in ALS-SOD1G93A mice, which may be related to its functions in inhibiting the excessive activation of microglia, and down-regulating TLR4/NF-κB signaling.

Congo Red-Derived Carbon Dots: Simultaneously as Fluorescence Probe for Protein Aggregates, Inhibitor for Protein Aggregation, and Scavenger of Free Radicals.

The pathological aggregation of some proteins is claimed to be highly related to several human diseases, such as ß-amyloid 1-42 (Aß42 ) to Alzheimer's disease (AD), islet amyloid polypeptide, and insulin to type 2 diabetes mellitus. Therefore, it is in desperate need to develop effective methods for detection of protein aggregates and inhibition of abnormal aggregation. Herein, to construct all-in-one probe with both diagnosis and treatment potentials for protein aggregation diseases, Congo red (CR), a classical staining reagent with red fluorescence signal output for protein aggregates, is deliberately adopted to react with three different reductive carbon sources and ammonium persulfate to generate three CR-derived carbon dots (CDs). The obtained CDs exhibit the capabilities of turn-on red fluorescence imaging of protein aggregates, and/or inhibition of protein aggregation as well as scavenging of free radicals. Among them, CA-CDs, using citric acid as the reductive carbon source, demonstrate the superiority to the other two studied CDs in integrating all of these functions, and particularly exert excellent cytoprotection effect against toxic Aß42 species, possessing tremendous potential in diagnosis and treatment of AD for future study. The present study paves a new way to develop all-in-one CDs for the protein disease research.

Evaluationof compact air-induction flat fan nozzles for herbicide applications: Spray drift and biological efficacy.

Nozzles are the most critical component of a sprayer for pesticide applications. Recently, air-induction nozzles and twin flat-fan air-induction nozzles have started to be used for herbicide applications. In order to evaluate the potential of compact air-induction nozzles for herbicide spraying, this paper compares the effects of air-induction nozzles and standard flat-fan nozzles on spray atomization, deposition, drift, and weed control efficacy in maize and wheat. Droplet spectra were measured by a laser particle size analyzer, and drift potential values were determined using a drift test bench (ISO 22401). A field study was conducted to compare the spray drift and biological efficacy between Lechler standard flat-fan nozzles and compact air-induction nozzles including different nozzle sizes. In the range from 0.2 to 0.4 MPa, the droplet size classes of the LU and ST nozzles were very similar and ranged from fine to very fine, while the droplets of the air-induction nozzles IDK and IDKT were medium or coarse depending on the spray pressure and nozzle size. The drift potential trials showed that the droplet size characteristics, mainly V 100, are strongly linked with the drift reduction potential. Both drift potential and field results showed that the compact air-induction nozzles had a good performance in drift reduction. In terms of weed control biological efficacy, there were no significant differences between standard flat-fan nozzles and air-induction nozzles. In all cases, the efficacy values were above 80% both in maize and in wheat. In conclusion, air-induction nozzles are recommended for herbicide applications as they provide good biological efficacy while significantly reducing the amount of spray drift, which is of great significance for the protection of the environment and the surrounding sensitive crops.