[Cluster Analysis and Ablation Success Rate in Atrial Fibrillation Patients Undergoing Catheter Ablation]. / æˆ¿é¢¤å°„é¢‘æ¶ˆèžæ‚£è€ çš„èšç±»åˆ†æžåŠæ¶ˆèžæˆåŠŸçŽ‡è¯„ä»·.

Objective: Atrial fibrillation (AF) is a disease of high heterogeneity, and the association between AF phenotypes and the outcome of different catheter ablation strategies remains unclear. Conventional classification of AF (e.g. according to duration, atrial size, and thromboembolism risk) fails to provide reference for the optimal stratification of the prognostic risks or to guide individualized treatment plan. In recent years, research on machine learning has found that cluster analysis, an unsupervised data-driven approach, can uncover the intrinsic structure of data and identify clusters of patients with pathophysiological similarity. It has been demonstrated that cluster analysis helps improve the characterization of AF phenotypes and provide valuable prognostic information. In our cohort of AF inpatients undergoing radiofrequency catheter ablation, we used unsupervised cluster analysis to identify patient subgroups, to compare them with previous studies, and to evaluate their association with different suitable ablation patterns and outcomes. Methods: The participants were AF patients undergoing radiofrequency catheter ablation at West China Hospital between October 2015 and December 2017. All participants were aged 18 years or older. They underwent radiofrequency catheter ablation during their hospitalization. They completed the follow-up process under explicit informed consent. Patients with AF of a reversible cause, severe mitral stenosis or prosthetic heart valve, congenital heart disease, new-onset acute coronary syndrome within three months prior to the surgery, or a life expectancy less than 12 months were excluded according to the exclusion criteria. The cohort consisted of 1102 participants with paroxysmal or persistent/long-standing persistent AF. Data on 59 variables representing demographics, AF type, comorbidities, therapeutic history, vital signs, electrocardiographic and echocardiographic findings, and laboratory findings were collected. Overall, data for the variables were rarely missing (<5%), and multiple imputation was used for correction of missing data. Follow-up surveys were conducted through outpatient clinic visits or by telephone. Patients were scheduled for follow-up with 12-lead resting electrocardiography and 24-hours Holter monitoring at 3 months and 6 months after the ablation procedure. Early ablation success was defined as the absence of documented AF, atrial flutter, or atrial tachycardia >30 seconds at 6-month follow-up. Hierarchical clustering was performed on the 59 baseline variables. All characteristic variables were standardized to have a mean of zero and a standard deviation of one. Initially, each patient was regarded as a separate cluster, and the distance between these clusters was calculated. Then, the Ward minimum variance method of clustering was used to merge the pair of clusters with the minimum total variance. This process continued until all patients formed one whole cluster. The "NbClust" package in R software, capable of calculating various statistical indices, including pseudo t2 index, cubic clustering criterion, silhouette index etc, was applied to determine the optimal number of clusters. The most frequently chosen number of clusters by these indices was selected. A heatmap was generated to illustrate the clinical features of clusters, while a tree diagram was used to depict the clustering process and the heterogeneity among clusters. Ablation strategies were compared within each cluster regarding ablation efficacy. Results: Five statistically driven clusters were identified: 1) the younger age cluster (n=404), characterized by the lowest prevalence of cardiovascular and cerebrovascular comorbidities but the highest prevalence of obstructive sleep apnea syndrome (14.4%); 2) a cluster of elderly adults with chronic diseases (n=438), the largest cluster, showing relatively higher rates of hypertension, diabetes, stroke, and chronic obstructive pulmonary disease; 3) a cluster with high prevalence of sinus node dysfunction (n=160), with patients showing the highest prevalence of sick sinus syndrome and pacemaker implantation; 4) the heart failure cluster (n=80), with the highest prevalence of heart failure (58.8%) and persistent/long-standing persistent AF (73.7%); 5) prior coronary artery revascularization cluster (n=20), with patients of the most advanced age (median: 69.0 years old) and predominantly male patients, all of whom had prior myocardial infarction and coronary artery revascularization. Patients in cluster 2 achieved higher early ablation success with pulmonary veins isolation alone compared to extensive ablation strategies (79.6% vs. 66.5%; odds ratio [OR]=1.97, 95% confidence interval [CI]: 1.28-3.03). Although extensive ablation strategies had a slightly higher success rate in the heart failure group, the difference was not statistically significant. Conclusions: This study provided a unique classification of AF patients undergoing catheter ablation by cluster analysis. Age, chronic disease, sinus node dysfunction, heart failure and history of coronary artery revascularization contributed to the formation of the five clinically relevant subtypes. These subtypes showed differences in ablation success rates, highlighting the potential of cluster analysis in guiding individualized risk stratification and treatment decisions for AF patients.

Suicidal ideation and suicide attempts among students aged 12 to 24 after the lifting of COVID-19 restrictions in China: prevalence and associated factors.

Objective: To investigate the prevalence and associated factors of suicidal ideation and suicide attempts among adolescent and young adults in China from December 14, 2022 to February 28, 2023, when COVID-19 restrictions were lifted. Methods: Students in middle and high schools and colleges and universities in the province of Sichuan, China were asked to complete on-line cross-sectional surveys. Information was collected about sociodemographics, experiences related to the COVID-19 pandemic, suicidal ideation and suicide attempts. Participants also filled out the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 and the Social Support Rate Scale surveys. Factors associated with suicidal ideation or suicide attempts were explored using logistic regression. Results: Of the 82,873 respondents (aged 12 to 24 years), 21,292 (25.7%) reported having thought of suicide at least once in their lifetime, 10,382 (12.5%) reported having thought about suicide within the previous 12 months, and 1,123 (1.4%) reported having attempted it within the previous 12 months. Risk of lifetime suicidal ideation was higher among middle school students than among older students. Risk of suicidal ideation and risk of suicide attempts correlated directly with severity of symptoms of depression and anxiety, and inversely with level of social support. Greater risk of suicidal ideation and suicidal attempts was associated with: being female, living in an urban environment, attending a boarding school, currently being in love, having parents who divorced or remarried, having parents who exhibit non-authoritative parenting behavior, having higher family income, having been COVID-19 infected, having been quarantined for a long time, and being dissatisfied with one's education. Conclusions: Suicidal ideation and suicide attempts remain prevalent among young people in China. The potential associated factors identified in our study may be useful for targeting appropriate psychosocial interventions and developing mental health policies.

[Value of different endoscopic scoring methods in assessing disease activity in pediatric Crohn's disease]. / ä¸åŒå† é•œè¯„åˆ†æ³•è¯„ä¼°å„¿ç«¥å ‹ç½—æ©ç— ç–¾ç— æ´»åŠ¨åº¦çš„ä»·å€¼.

OBJECTIVES: To explore the value of different endoscopic scoring methods in assessing disease activity in pediatric Crohn's disease (CD). METHODS: A total of 70 children diagnosed with CD at the Children's Hospital of Chongqing Medical University from January 2018 to January 2023 were included. Clinical disease activity was assessed using the Pediatric Crohn's Disease Activity Index (PCDAI), while different endoscopic scores were assigned based on endoscopic findings. Spearman rank correlation analysis was used to evaluate the correlation between each endoscopic scoring method and PCDAI as well as laboratory indicators. Kappa test was used to assess the consistency between colonoscopy/capsule endoscopy scoring methods and PCDAI in determining CD activity. Receiver operating characteristic curve analysis was performed to assess the diagnostic efficacy of laboratory indicators in predicting endoscopic activity. RESULTS: The PCDAI score showed a moderate positive correlation with the scores of Crohn's Disease Endoscopic Index of Severity (CDEIS) (rs=0.696, P<0.01), Simple Endoscopic Score for Crohn's Disease (SES-CD) (rs=0.680, P<0.01), Lewis Score (rs=0.540, P<0.01), and Capsule Endoscopy-Crohn's Disease Index (CE-CD) (rs=0.502, P<0.01). The consistency between all endoscopic scoring methods and PCDAI in determining CD activity was poor (Kappa=0.069-0.226). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hematocrit (HCT), and serum albumin (ALB) levels showed a moderate correlation with the PCDAI score and the scores of colonoscopy scoring methods (CDEIS and SES-CD) (|rs|=0.581-0.725, P<0.01), but a weak correlation with the scores of capsule scoring methods (P<0.05). ESR and CRP had higher area under the curve (AUC) values in predicting disease activity based on PCDAI, CDEIS, SES-CD, and Lewis Score compared to HCT and ALB (P<0.05). CONCLUSIONS: CDEIS, SES-CD, Lewis Score, and CE-CD can be used to evaluate disease activity in pediatric CD, but they do not fully correspond with disease activity assessed by PCDAI. Elevated levels of ESR and CRP can predict clinical and endoscopic disease activity in children with CD.

Deep learning model for the prediction of all-cause mortality among long term care people in China: a prospective cohort study.

This study aimed to develop a deep learning model to predict the risk stratification of all-cause death for older people with disability, providing guidance for long-term care plans. Based on the government-led long-term care insurance program in a pilot city of China from 2017 and followed up to 2021, the study included 42,353 disabled adults aged over 65, with 25,071 assigned to the training set and 17,282 to the validation set. The administrative data (including baseline characteristics, underlying medical conditions, and all-cause mortality) were collected to develop a deep learning model by least absolute shrinkage and selection operator. After a median follow-up time of 14 months, 17,565 (41.5%) deaths were recorded. Thirty predictors were identified and included in the final models for disability-related deaths. Physical disability (mobility, incontinence, feeding), adverse events (pressure ulcers and falls from bed), and cancer were related to poor prognosis. A total of 10,127, 25,140 and 7086 individuals were classified into low-, medium-, and high-risk groups, with actual risk probabilities of death of 9.5%, 45.8%, and 85.5%, respectively. This deep learning model could facilitate the prevention of risk factors and provide guidance for long-term care model planning based on risk stratification.

Transmission of human-pet antibiotic resistance via aerosols in pet hospitals of Changchun.

In recent years, aerosols have been recognized as a prominent medium for the transmission of antibiotic-resistant bacteria and genes. Among these, particles with a particle size of 2 µm (PM2.5) can directly penetrate the alveoli. However, the presence of antibiotic-resistant genes in aerosols from pet hospitals and the potential risks posed by antibiotic-resistant bacteria in these aerosols to humans and animals need to be investigated. In this study, cefotaxime-resistant bacteria were collected from 5 representative pet hospitals in Changchun using a Six-Stage Andersen Cascade Impactor. The distribution of bacteria in each stage was analyzed, and bacteria from stage 5 and 6 were isolated and identified. Minimal inhibitory concentrations of isolates against 12 antimicrobials were determined using broth microdilution method. Quantitative Polymerase Chain Reaction was employed to detect resistance genes and mobile genetic elements that could facilitate resistance spread. The results indicated that ARBs were enriched in stage 5 (1.1-2.1 µm) and stage 3 (3.3-4.7 µm) of the sampler. A total of 159 isolates were collected from stage 5 and 6. Among these isolates, the genera Enterococcus spp. (51%), Staphylococcus spp. (19%), and Bacillus spp. (14%) were the most prevalent. The isolates exhibited the highest resistance to tetracycline and the lowest resistance to cefquinome. Furthermore, 56 (73%) isolates were multidrug-resistant. Quantitative PCR revealed the expression of 165 genes in these isolates, with mobile genetic elements showing the highest expression levels. In conclusion, PM2.5 from pet hospitals harbor a significant number of antibiotic-resistant bacteria and carry mobile genetic elements, posing a potential risk for alveolar infections and the dissemination of antibiotic resistance genes.

Lower plasma linoleic acids as a risk factor for gout: an integrated analysis of population-based cohort and genetic data.

Background: Gout is a nutrition-related, highly prevalent inflammatory arthritis with undesirable effects on the quality of life. The relationships between circulating fatty acids (FAs) and gout remain poorly understood. Method: We included 268 174 participants with plasma FAs measured using nuclear magnetic resonance at the baseline (2006-2010) from the UK Biobank, of which 15 194 participants had repeated measures of FAs between 2012 and 2013. Cox proportional hazards models were used to assess the association of the baseline and longitudinal changes in relative levels of plasma FAs (% total FAs) with incident gout. Mendelian randomization (MR) analyses were conducted to assess the potential causality of the examined association. Results: Over a median follow-up of 12.8 years, 5160 incident cases of gout occurred. Baseline polyunsaturated fatty acids (PUFAs), n-6 PUFAs, and linoleic acids (LAs) were inversely associated with incident gout (all P-trend values < 0.0001). Baseline monounsaturated fatty acids (MUFAs), n-3 PUFAs, and docosahexaenoic acids (DHAs) were positively associated with incident gout (all P-trend values < 0.0001). Longitudinal increments of n-6 PUFAs and LAs were associated with a lower risk of subsequent gout, whereas an increment of n-3 PUFAs was associated with a higher risk. In two-sample MR analyses, genetically determined higher levels of PUFAs, n-6 PUFAs, and LAs were associated with a decreased risk of gout (all P values < 0.05). Conclusions: Our findings consistently indicate a causal relationship of elevated levels of n-6 PUFAs, especially LAs, with a reduced risk of gout.

The roles of nitric oxide in improving postharvest fruits quality: Crosstalk with phytohormones.

Nowadays, improving the quality of postharvest fruits has become a hot research topic. Nitric oxide (NO) is often regarded as a signaling molecule that delays the postharvest senescence of fruits. Moreover, phytohormones affect the postharvest senescence of fruits. This review mainly describes how NO improves the postharvest quality of fruits by delaying postharvest fruit senescence, mitigating fruit cold damage and controlling postharvest diseases. Furthermore, the crosstalk of NO and multiple plant hormones effectively delays the postharvest senescence of fruits, and the major crosstalk mechanisms include (1) mediating phytohormone signaling. (2) inhibiting ETH production. (3) stimulating antioxidant enzyme activity. (4) decreasing membrane lipid peroxidation. (5) maintaining membrane integrity. (6) inhibiting respiration rate. (7) regulating gene expression related to fruit senescence. This review concluded the roles and mechanisms of NO in delaying postharvest fruit senescence. In addition, the crosstalk mechanisms between NO and various phytohormones on the regulation of postharvest fruit quality are also highlighted, which provides new ideas for the subsequent research.

Children with developmental coordination disorders: a review of approaches to assessment and intervention.

Developmental Coordination Disorder (DCD) is a neurodevelopmental disorder characterized by deficits in motor skills, with gross and fine motor dysfunction being the main symptom. This condition greatly impairs children's daily life, learning, and social interaction. Symptoms typically appear during preschool or school age, and if left untreated, they can persist into adulthood. Thus, early assessment and intervention are crucial to improve the prognosis. This study aims to review the existing literature on DCD, providing a comprehensive overview of the assessment for children with DCD in terms of body functions and structures, activities and participation, and environmental factors within the framework of the International Classification of Functioning, Disability, and Health - Children and Youth (ICF-CY). Additionally, specific rehabilitation interventions will be described, offering valuable insights for the clinical assessment and intervention of children with DCD.

A Bis-Cyclopentadienyl Ligand-Supported Di-Iron Trihydride Motif as a Synthon for Access to Heterobimetallic Trinuclear Complexes.

Herein, we report the synthesis of a flexible bis-cyclopentadienyl ligand L (the doubly deprotonated form of H2L (1,3-bis(2,4-di-tert-butylcyclopentadienyldimethylsilyl)benzene)), demonstrating its ability to stabilize a series of di-iron hydrido complexes. Notably, this ligand facilitates the isolation of an unprecedented anionic cyclopentadienyl ligand-supported di-iron trihydride complex, LFe2(µ-H)3Li(THF) (2), functioning as a synthon for the [Fe2(µ-H)3]- core and providing access to heterobimetallic complexes 4-6 with coinage metals.

The role of the "gut microbiota-mitochondria" crosstalk in the pathogenesis of multiple sclerosis.

Multiple Sclerosis (MS) is a neurologic autoimmune disease whose exact pathophysiologic mechanisms remain to be elucidated. Recent studies have shown that the onset and progression of MS are associated with dysbiosis of the gut microbiota. Similarly, a large body of evidence suggests that mitochondrial dysfunction may also have a significant impact on the development of MS. Endosymbiotic theory has found that human mitochondria are microbial in origin and share similar biological characteristics with the gut microbiota. Therefore, gut microbiota and mitochondrial function crosstalk are relevant in the development of MS. However, the relationship between gut microbiota and mitochondrial function in the development of MS is not fully understood. Therefore, by synthesizing previous relevant literature, this paper focuses on the changes in gut microbiota and metabolite composition in the development of MS and the possible mechanisms of the crosstalk between gut microbiota and mitochondrial function in the progression of MS, to provide new therapeutic approaches for the prevention or reduction of MS based on this crosstalk.

The ratio of high aspartate aminotransferase to alanine aminotransferase: an independent risk factor associated with poor prognosis in IgA nephropathy.

OBJECTIVE: To investigate the relationship between the aspartate aminotransferase to alanine aminotransferase ratio (AAR) and the prognosis of IgA nephropathy (IgAN). METHODS: Clinical, pathological and follow-up data of 271 patients with IgAN from January 1, 2013, to July 31, 2023, were collected. A 50% decrease in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD) was used as renal composite end point events. A receiver operating characteristic (ROC) curve was plotted to predict the composite end point events by AAR. The optimal cutoff value of 1.24 was determined, and patients were allocated to high AAR and low AAR groups. Kaplan‒Meier (K‒M) curves and Cox proportional hazard models were used to evaluate the predictive effect of AAR on renal composite end point events. RESULTS: After a mean follow-up of 29 months, 39 patients achieved renal composite end point events. Among them, 9 and 30 patients in the low and high AAR groups achieved renal composite end point events, respectively, with a significant difference (P < 0.001). After adjustment for confounding factors, AAR was found to be an independent prognostic factor for renal composite end point events (HR = 3.283, 95% CI: 1.489-7.238, P = 0.003). Kaplan‒Meier analysis showed that high AAR was associated with achieving renal composite end point events in patients with IgAN. Moreover, the clinical features in the high AAR group were more severe. Further subgroup analysis showed that high AAR had a better predictive effect in patients with more severe clinicopathological manifestations. CONCLUSION: AAR is an independent prognostic factor in patients with IgAN.

Disability level's impact on blood pressure-mortality association in older long-term care adults: evidence from a large Chinese cohort study.

BACKGROUND: Evidence of the optimal blood pressure (BP) target for older adults with disability in long-term care is limited. We aim to analyze the associations of BP with mortality in older adults in long-term care setting with different levels of disability. METHODS: This prospective cohort study was based on the government-led long-term care programme in Chengdu, China, including 41,004 consecutive disabled adults aged ≥ 60 years. BP was measured during the baseline survey by trained medical personnel using electronic sphygmomanometers. Disability profile was assessed using the Barthel index. The association between blood pressure and mortality was analyzed with doubly robust estimation, which combined exposure model by inverse probability weighting and outcome model fitted with Cox regression. The non-linearity was examined by restricted cubic spline. The primary endpoint was all-cause mortality, and the secondary endpoints were cardiovascular and non-cardiovascular mortality. RESULTS: The associations between systolic blood pressure (SBP) and all-cause mortality were close to a U-shaped curve in mild-moderate disability group (Barthel index ≥ 40), and a reversed J-shaped in severe disability group (Barthel index < 40). In mild-moderate disability group, SBP < 135 mmHg was associated with elevated all-cause mortality risks (HR 1.21, 95% CI, 1.10-1.33), compared to SBP between 135 and 150 mmHg. In severe disability group, SBP < 150 mmHg increased all-cause mortality risks (HR 1.21, 95% CI, 1.16-1.27), compared to SBP between 150 and 170 mmHg. The associations were robust in subgroup analyses in terms of age, gender, cardiovascular comorbidity and antihypertensive treatment. Diastolic blood pressure (DBP) < 67 mmHg (HR 1.29, 95% CI, 1.18-1.42) in mild-moderate disability group and < 79 mmHg (HR 1.15, 95% CI, 1.11-1.20) in severe disability group both demonstrated an increased all-cause mortality risk. CONCLUSION: The optimal SBP range was found to be higher in older individuals in long-term care with severe disability (150-170mmHg) compared to those with mild to moderate disability (135-150mmHg). This study provides new evidence that antihypertensive treatment should be administered cautiously in severe disability group in long-term care setting. Additionally, assessment of disability using the Barthel index can serve as a valuable tool in customizing the optimal BP management strategy. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Registration Number: ChiCTR2100049973).

The role of microRNA-142a in Toxoplasma gondii infection-induced downregulation of Foxp3: implications for adverse pregnancy outcomes.

BACKGROUND: Toxoplasma gondii (T. gondii) is capable of infecting nearly all warm-blooded animals and approximately 30% of the global population. Though most infections are subclinical in immunocompetent individuals, congenital contraction can lead to severe consequences such as spontaneous abortion, stillbirth, and a range of cranio-cerebral and/or ocular abnormalities. Previous studies reported that T. gondii-infected pregnancy mice unveiled a deficit in both the amount and suppressive functions of regulatory T (Treg) cells, accompanied with reduced levels of forkhead box p3 (Foxp3). Recently, accumulative studies have demonstrated that microRNAs (miRNAs) are, to some extent, relevant to T. gondii infection. However, the link between alterations in miRNAs and downregulation of Foxp3 triggered by T. gondii has been only sporadically studied. METHODS: Quantitative reverse transcription polymerase chain reaction (RT-qPCR), protein blotting and immunofluorescence were employed to evaluate the impact of T. gondii infection and antigens on miRNA transcription and Foxp3 expression. Dual-luciferase reporter gene assays were performed to examine the fluorescence activity in EL4 cells, which were transfected with recombinant plasmids containing full-length/truncated/mutant microRNA-142a-3p (miR-142a) promoter sequence or wild type/mutant of Foxp3 3' untranslated region (3' UTR). RESULTS: We found a pronounced increase in miR-142a transcription, concurrent with a decrease in Foxp3 expression in T. gondii-infected mouse placental tissue. Similarly, comparable findings have been experimentally confirmed through the treatment of EL4 cells with T. gondii antigens (TgAg) in vitro. Simultaneously, miR-142a mimics attenuated Foxp3 expression, whereas its inhibitors markedly augmented Foxp3 expression. miR-142a promoter activity was elevated upon the stimulation of T. gondii antigens, which mitigated co-transfection of mutant miR-142a promoter lacking P53 target sites. miR-142a mimics deceased the fluorescence activity of Foxp3 3' untranslated region (3' UTR), but it did not affect the fluorescence activity upon the co-transfection of mutant Foxp3 3' UTR lacking miR-142a target site. CONCLUSION: In both in vivo and in vitro studies, a negative correlation was discovered between Foxp3 expression and miR-142a transcription. TgAg enhanced miR-142a promoter activity to facilitate miR-142a transcription through a P53-dependent mechanism. Furthermore, miR-142a directly targeted Foxp3 3' UTR, resulting in the downregulation of Foxp3 expression. Therefore, harnessing miR-142a may be a possible therapeutic approach for adverse pregnancy caused by immune imbalances, particularly those induced by T. gondii infection.

P2X7 receptor is essential for ST36-attenuated cardiac fibrosis upon beta-adrenergic insult.

P2X7 receptor (P2X7R) plays an important role in modulating inflammation and fibrosis, but information is limited whether Zusanli (ST36) can inhibit inflammation and fibrosis by regulating P2X7R. Isoprenaline at 5 mg/kg was subcutaneously injected to wild-type and P2X7R knockout mice for 7 days, while treatment groups received electroacupuncture (EA) stimulation at ST36 for 7 sessions. Following 7-session treatment, Masson's trichrome staining was performed to assess the fibrosis. Morphology, electrocardiogram, and echocardiography were carried out to evaluate the cardiac function and structure. Western blotting, hematoxylin and eosin staining, immunohistochemistry, and biochemical analysis of inflammatory cytokine and transmission electron microscopy were carried out to characterize the effect of ST36 on inflammation. P2X7R was overexpressed in ISO-treated mice. EA at ST36, but not at non-points, reduced ISO-induced cardiac fibrosis, increases in HW/BW, R+S wave relative to mice in ISO groups. In addition, EA at ST36 downregulated ISO-upregulated P2X7R and NLRP3 in ventricle. Moreover, EA reduced cytokines of IL-1ß, IL-6, and IL-18 in serum, and inhibited foam cell gathering, inflammatory cell infiltration, and autophagy. However, EA at ST36 failed to attenuate the cardiac fibrosis and hypertrophy in P2X7R knockout mice. In conclusion, EA at ST36 attenuated ISO-induced fibrosis possibly via P2X7R.

Inhibition of Foxp3 expression in the placenta of mice infected intraperitoneally by toxoplasma gondii tachyzoites: insights into the PPARγ/miR-7b-5p/Sp1 signaling pathway.

BACKGROUND: Toxoplasma gondii, an obligate intracellular parasitic protozoa, infects approximately 30% of the global population. Contracting T. gondii at the primary infection of the mother can result in neonatal microcephaly, chorioretinitis, hydrocephalus, or mortality. Our previous study indicated that pregnant mice infected with T. gondii displayed a decrease in both the number and the suppressive ability of regulatory T cells, accompanied by the reduced Forkhead box P3 (Foxp3). Numerous studies have proved that microRNAs (miRNAs) are implicated in T. gondii infection, but there is meager evidence on the relationship between alterations of miRNAs and downregulation of Foxp3 induced by T. gondii. METHODS: Quantitative reverse transcription polymerase chain reaction was utilized to detect the transcriptions of miRNAs and Foxp3. Protein blotting and immunofluorescence were used to detect the expressions of Foxp3 and related transcription factors. The structure of mouse placenta was observed by hematoxylin and eosin (HE) staining. To examine the activity of miR-7b promoter and whether miR-7b-5p targets Sp1 to suppress Foxp3 expression, we constructed recombinant plasmids containing the full-length/truncated/mutant miR-7b promoter sequence or wildtype/mutant of Sp1 3' untranslated region (3' UTR) to detect the fluorescence activity in EL4 cells. RESULTS: In T. gondii-infected mice, miR-7b transcription was significantly elevated, while Foxp3 expression was decreased in the placenta. In vitro, miR-7b mimics downregulated Foxp3 expression, whereas its inhibitors significantly upregulated Foxp3 expression. miR-7b promoter activity was elevated upon the stimulation of T. gondii antigens, which was mitigated by co-transfection of mutant miR-7b promoter lacking peroxisome proliferator-activated receptor γ (PPARγ) target sites. Additionally, miR-7b mimics diminished Sp1 expression, while miR-7b inhibitors elevated its expression. miR-7b mimics deceased the fluorescence activity of Sp1 3' untranslated region (3' UTR), but it failed to impact the fluorescence activity upon the co-transfection of mutant Sp1 3' UTR lacking miR-7b target site. CONCLUSIONS: T. gondii infection and antigens promote miR-7b transcription but inhibit Foxp3 protein and gene levels. T. gondii antigens promote miR-7b promoter activity by a PPARγ-dependent mechanism. miR-7b directly binds to Sp1 3' UTR to repress Sp1 expression. Understanding the regulatory functions by which T. gondii-induced miR-7b suppresses Foxp3 expression can provide new perspectives for the possible therapeutic avenue of T. gondii-induced adverse pregnancy outcomes.

A bibliometric analysis of research on pediatric preoperative anxiety (2007-2022).

Objective: This study aimed to analyze the current state of research on preoperative anxiety in children through CiteSpace, VOSviewer, and the identification of hot spots and frontiers. Method: Relevant data were retrieved from the Web of Science Core Collection using the search terms children and preoperative anxiety. Data were analyzed using VOSviewer (version 1.6.18), CiteSpace (5.7. R5) software, and Scimago Graphica. Results: A total of 622 articles were published between 2007 and 2022, with an increasing trend over time. Kain, Zeev N. (13; 2.09%) and Dalhousie University (15; 2.41%) were the most influential authors and most prolific institutions, respectively. The United States (121; 19.45%) was the country with the most publications. Pediatric anesthesia (55; 8.84%) had the most publications. High-frequency keywords were categorized into three themes, including nonpharmacologic interventions for preoperative anxiety in children, preoperative medications, and risk factors for anxiety; of these, "predictor" (38; 2016) and "sedative premedication" (20; 2016) were the most studied keywords over the past 6 years. "Distraction" (67; 2019) and "dexmedetomidine" (65; 2019) have been the main areas of interest in recent years. Conclusion: Research on preoperative anxiety in children has been the focus of increasing attention over the past fifteen years, with the majority of publications from high-income countries. This review provides a useful perspective for understanding research trends, hot topics, and research gaps in this expanding field.

Effect of Preoperative immune-enhancing Enteral Nutrition on the Outcomes of Laparoscopic Surgery for Colon Cancer in elderly Patients: A Randomized Controlled Trial.

Objective: This study aims to explore the impact of immune-enhanced enteral nutrition on postoperative outcomes, focusing on inflammatory response, intestinal mucosal barrier integrity, and immune function following laparoscopic colon cancer surgery in elderly patients. Methods: In this single-center, randomized controlled trial, ninety-six elderly patients undergoing laparoscopic resection of colon tumors were enrolled and equally divided into two groups by random allocation. The control group (n=48) received standard enteral nutrition, while the experimental group (n=46) was administered immune-enhancing enteral nutrition. We assessed and compared specific metrics such as nutritional status (e.g., albumin levels), cellular immune status (CD4+ and CD8+ T-cell counts), inflammatory markers (e.g., C-reactive protein), and indicators of intestinal mucosal barrier function (e.g., D-lactate levels) before and after the intervention in both groups. Results: Initial comparison of baseline characteristics between the two groups showed no significant differences (P > .05). Postoperatively, the experimental group demonstrated significantly lower levels of inflammatory markers and an improved ratio of CD4+/CD8+ T-cells compared to the control group at day 7 (P < .05). Furthermore, nutritional status and markers indicative of intestinal mucosal barrier integrity were notably better in the experimental group at this time point. Conclusion: Immune-enhanced enteral nutrition is effective in enhancing intestinal mucosal barrier function, boosting immune response, and improving nutritional status in elderly patients post-laparoscopic colon cancer surgery. It also contributes to mitigating the inflammatory response, proving its safety and tolerability for clinical use.

Human amniotic mesenchymal stem cells inhibit immune rejection injury from allogeneic mouse heart transplantation: A preliminary study on the microRNA expression.

BACKGROUND: Mesenchymal stem cell therapy is a new treatment for immune rejection in heart transplantation. The aim of this paper is to investigate the effect of human amniotic mesenchymal stem cells (hAMSCs) on alleviating immune rejection of allogeneic heart transplantation in mice and its possible underlying mechanism. METHODS: We injected hAMSCs into cervical ectopic heart transplantation model mice via tail vein to observe the survival time, the pathological changes of donor myocardium, and the fluorescent distribution of hAMSCs after the transplantation. MicroRNAs (miRs) with significantly differential expression were obtained by RNA sequencing and bioinformatic analysis, and a dual luciferase reporter gene assay together with real-time quantitative PCR (qRT-PCR) was performed to verify the relationship between miRs and their targeting genes. RESULTS: The intervention of hAMSCs prolonged the graft survival time and alleviated the pathological damage of the donor heart. The injected hAMSCs were distributed mainly in the liver, spleen, and kidney, only a very small portion in the donor and recipient hearts. In the allogeneic transplantation models, the expression of miR-34b-5p significantly increased after hAMSC treatment. MiR-34b-5p showed a knockdown effect on gene Fc gamma receptor 2B (FCGR2B). CONCLUSIONS: hAMSCs can reduce the immune rejection injury after allogeneic heart transplantation. This effect may be associated with the upregulation of miR-34b-5p expression to knock down its targeting gene FCGR2B.

Rapid diagnosis of acute myocardial infarction through integrated microfluidic chips for detection of characteristic targets.

Myoglobin (Myo), creatine kinase-MB (CKMB), and cardiac troponin I (cTnI) are crucial biomarkers for diagnosing acute myocardial infarction (AMI) The accurate and rapid detection of these three targets can greatly improve the prognosis of AMI patients. Herein, this study developed a microfluidic immunofluorescence method that can detect all three targets in 10-15 min. Ultrasonic atomization and spray technology are used to modify the surface of the injection-molded microfluidic chip (MFC), which effectively solves the problem of biological cross-linking and antibody immobilization on the MFC surface. In addition, it improves the hydrophilicity of the chip surface, thus enhancing fluid self-driving effect. The linear response towards Myo, CKMB and cTnI range from 5 ng/mL to 500 ng/mL, 1 ng/mL to 70 ng/mL, and 0.05 ng/mL to 30 ng/mL, respectively. The intra-batch precision is ≤ 10%, and the inter-batch precision is ≤ 15%. Furthermore, this method shows good consistency compared with the BECKMAN ACCESS2 chemiluminescent immunoanalyzer. The present work provides an AMI diagnostic method with high sensitivity, good repeatability, high accuracy and simple operation, which can satisfy the needs of clinical diagnosis, and shows promising application prospects.