miR-155 promotes Th17 differentiation by targeting FOXP3 to aggravate inflammation in MRSA pneumonia.

BACKGROUND: Previous researches have clarified that miR-155 is increased in methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, and modulates Th9 differentiation. Like Th9 cells, Th17 cells were also a subset of CD4+ T cells and involved in MRSA pneumonia progression. This work aimed to investigate the role and mechanism of miR-155 in Th17 differentiation. METHODS: Bronchoalveolar lavage fluid (BALF) was collected from children with MRSA pneumonia and bronchial foreign bodies. MRSA-infected murine model was established followed by collecting BALF and lung tissues. qRT-PCR, ELISA and flow cytometry were performed to examine the mRNA expression and concentration of IL-17 and the number of Th17 cells in above samples. HE and ELISA were used to evaluate inflammatory responses in lung. Furthermore, CD4+ T cells were isolated from BALF of children for in vitro experiments. After treatments with miR-155 mimic/inhibitor, the roles of miR-155 in Th17/IL-17 regulation were determined. The downstream of miR-155 was explored by qRT-PCR, western blotting, dual luciferase reporter analysis and RIP assay. RESULTS: The levels of IL-17 and the proportion of Th17 cells were increased in children with MRSA pneumonia. A similar pattern was observed in MRSA-infected mice. On the contrary, IL-17 neutralization abolished the activation of Th17/IL-17 induced by MRSA infection. Furthermore, IL-17 blockade diminished the inflammation caused by MRSA. In vitro experiments demonstrated miR-155 positively regulated IL-17 expression and Th17 differentiation. Mechanistically, FOXP3 was a direct target of miR-155. miR-155 inhibited FOXP3 level via binding between FOXP3 and Argonaute 2 (AGO2), the key component of RNA-induced silencing complex (RISC). FOXP3 overexpression reversed elevated IL-17 levels and Th17 differentiation induced by miR-155. CONCLUSIONS: miR-155 facilitates Th17 differentiation by reducing FOXP3 through interaction of AGO2 and FOXP3 to promote the pathogenesis of MRSA pneumonia. IL-17 blockade weakens the inflammation due to MRSA, which provides a nonantibiotic treatment strategy for MRSA pneumonia.

Clinical characteristics of post-stroke basal ganglia aphasia and the study of language-related white matter tracts based on diffusion spectrum imaging.

BACKGROUND: Stroke often damages the basal ganglia, leading to atypical and transient aphasia, indicating that post-stroke basal ganglia aphasia (PSBGA) may be related to different anatomical structural damage and functional remodeling rehabilitation mechanisms. The basal ganglia contain dense white matter tracts (WMTs). Hence, damage to the functional tract may be an essential anatomical structural basis for the development of PSBGA. METHODS: We first analyzed the clinical characteristics of PSBGA in 28 patients and 15 healthy controls (HCs) using the Western Aphasia Battery and neuropsychological test batteries. Moreover, we investigated white matter injury during the acute stage using diffusion magnetic resonance imaging scans for differential tractography. Finally, we used multiple regression models in correlation tractography to analyze the relationship between various language functions and quantitative anisotropy (QA) of WMTs. RESULTS: Compared with HCs, patients with PSBGA showed lower scores for fluency, comprehension (auditory word recognition and sequential commands), naming (object naming and word fluency), reading comprehension of sentences, Mini-Mental State Examination, and Montreal Cognitive Assessment, along with increased scores in Hamilton Anxiety Scale-17 and Hamilton Depression Scale-17 within 7 days after stroke onset (P < 0.05). Differential tractography revealed that patients with PSBGA had damaged fibers, including in the body fibers of the corpus callosum, left cingulum bundles, left parietal aslant tracts, bilateral superior longitudinal fasciculus II, bilateral thalamic radiation tracts, left fornix, corpus callosum tapetum, and forceps major, compared with HCs (FDR < 0.02). Correlation tractography highlighted that better comprehension was correlated with a higher QA of the left inferior fronto-occipital fasciculus (IFOF), corpus callosum forceps minor, and left extreme capsule (FDR < 0.0083). Naming was positively associated with the QA of the left IFOF, forceps minor, left arcuate fasciculus, and uncinate fasciculus (UF) (FDR < 0.0083). Word fluency of naming was also positively associated with the QA of the forceps minor, left IFOF, and thalamic radiation tracts (FDR < 0.0083). Furthermore, reading was positively correlated with the QA of the forceps minor, left IFOF, and UF (FDR < 0.0083). CONCLUSION: PSBGA is primarily characterized by significantly impaired word fluency of naming and preserved repetition abilities, as well as emotional and cognitive dysfunction. Damaged limbic pathways, dorsally located tracts in the left hemisphere, and left basal ganglia pathways are involved in PSBGA pathogenesis. The results of connectometry analysis further refine the current functional localization model of higher-order neural networks associated with language functions.

Early Rituximab as an Add-On Therapy in Children With the Initial Episode of Nephrotic Syndrome.

Introduction: The approximately 70% 12-month relapse in children experiencing the initial episode of steroid-sensitive nephrotic syndrome (SSNS) is a significant concern, with over 50% developing frequent relapses or steroid-dependent nephrotic syndrome (FRNS/SDNS). There is a lack of strategies to reduce relapse after the onset. Whether early administration of rituximab, which effectively reduces relapses in FRNS/SDNS, may be a solution has not been evaluated. Methods: A prospective, multicenter, open-label, single-arm trial was conducted in China, with a 12-month follow-up. Children aged 1 to 18 years with the first episode of nephrotic syndrome (NS) were screened for eligibility. Proteinuria was evaluated daily using dipsticks. A dose of 375 mg/m2 of rituximab was intravenously infused within 1 week after achieving corticosteroid-induced remission. The main outcome was 12-month relapse-free survival. Results: Out of the initially 66 children screened, 44 were enrolled and received rituximab, with all but 1 participant completing the 12-month follow-up. The median age at diagnosis was 4.3 years (interquartile range [IQR]: 3.4-5.9), and 33 (77%) of the participants were male. In the rituximab group, the 12-month relapse-free survival was significantly higher compared to historical controls (32 of 43 [74.4%] vs. 10 of 33 [30.3%]; P < 0.001; hazard ratio [HR], 3.76; 95% confidence interval [CI], 1.80-7.81). The post hoc analysis revealed a higher 24-month relapse-free survival and a lower incidence of FRNS/SDNS at the 12-month follow-up. Treatment with rituximab was well-tolerated. Conclusion: Our findings support that early administration of rituximab may be associated with a higher 12-month relapse-free survival and a reduced incidence of FRNS/SDNS in children experiencing the initial episode of SSNS.

Gender Differences in Prevalence and Associated Factors of Dyslipidemia in Initial-Treatment and Drug-Naïve Schizophrenia Patients.

Background: Dyslipidemia is frequently comorbid with schizophrenia (SCZ), and both conditions often demonstrate significant gender differences in their clinical features. This study specifically focuses on investigating the prevalence of dyslipidemia and the factors that contribute to it in initial-treatment and drug-naïve (ITDN) SCZ patients, specifically focusing on gender differences. Methods: A total of 224 male ITDN SCZ patients and 424 female ITDN SCZ patients were included in this study. Socio-demographic and general clinical data of the patients were collected, and routine biochemical parameters, such as lipid levels, fasting blood glucose, thyroid function, renal function, and blood cell counts, were measured. Patients were also assessed for psychopathology and disease severity using the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Scale - Severity of Illness (CGI-SI), respectively. In addition, a lipids score was calculated for assessing the severity of dyslipidemia. Results: The study revealed that the prevalence of dyslipidemia in male patients was 34.02% (83/224), whereas 33.25% (141/424) in females, indicating no statistically significant difference (χ2 = 0.04, p = 0.841). For males, the risk factors for dyslipidemia were high education levels and diastolic blood pressure (DBP), while red blood cell count (RBC) as a protective factor. Additionally, DBP was identified as a risk factor for dyslipidemia score. In females, systolic blood pressure (SBP) was identified as a risk factor for dyslipidemia, while being married and creatinine (CRE) levels were found to be protective factors. Moreover, SBP was revealed as a risk factor for dyslipidemia score. Conclusion: No significant gender differences were observed in the prevalence of dyslipidemia among the ITDN SCZ patients. However, notable gender differences were identified in the factors influencing dyslipidemia and its severity within this group. These findings suggest the necessity of implementing gender-specific interventions to address the potential risk factors associated with dyslipidemia.

Relationship between age and remimazolam dose required for inducing loss of consciousness in older surgical patients.

Background: Remimazolam is a new ultra-short-acting benzodiazepine for procedural sedation and general anaesthesia, characterised by rapid onset of action, quick recovery, and organ-independent metabolism. Older patients tend to sustain more treatment-emergent adverse events (TEAEs) and worse perioperative prognoses after receiving remimazolam. However, few studies have investigated the appropriate dose of remimazolam for loss of consciousness (LOC) in geriatric patients. We designed this study to provide evidence for dose references and elucidate the relationship between age and remimazolam requirement for inducing LOC during anaesthesia induction. Methods: Exactly 120 patients scheduled for general surgery under general anaesthesia were included and divided into two groups: Group A (60 patients, 18-64 years) and Group B (60 patients, ≥ 65 years). LOC, defined as a Modified Observer's Assessment of Alertness and Sedation score at 1 had been reached, emerged after all participants received a continuous infusion of remimazolam at a rate of 0.05 mg/kg/min. Results: The remimazolam required for inducing LOC was 0.26 and 0.19 mg/kg in groups A and B, respectively, and the remimazolam dose in group B decreased by 26.9% compared to group A. According to the bivariate linear correlation analysis, remimazolam requirement was negatively correlated with age. Multivariable linear regression models and further adjustments for potential impact factors indicated that age was an independent factor for the remimazolam dose required for LOC. Conclusion: This study demonstrated that age was significantly and independently correlated with the remimazolam requirement for inducing LOC. To obtain haemodynamic stability during the induction of general anaesthesia, appropriately reducing the remimazolam dose is recommended for geriatric patients.

Hematospermia in a Transgender Woman with Evidence for Endometrial Tissue in the Prostate.

Background/Objective: The frequency of hematospermia in transgender women is unknown. This report aimed to describe the development of hematospermia in a transgender woman. Case Report: A 35-year-old transgender woman treated with estradiol valerate and leuprolide presented with painless rust-tinged ejaculate, urethral bleeding after ejaculation, and intermittent hematuria. Her medical history included gastroesophageal reflux disease, internal hemorrhoids, and attention deficit hyperactivity disorder with negative tobacco smoking and urologic history. Additional medications included emtricitabine-tenofovir disoproxil fumarate and fexofenadine. Physical examination did not reveal constitutional or genitourinary abnormalities. Urinalysis and culture disclosed rare white blood cells with gram-variable bacilli. The chlamydia, gonorrhea, and human immunodeficiency virus test results were negative. Abdominal computed tomography did not reveal bladder or prostate cancer, calcifications, inflammation, or cysts. She continued to have symptoms after this initial workup. One year after the initial symptom onset, transrectal ultrasound disclosed a 1.7-cm midline posterior prostatic cyst with hemorrhagic products, later revealed by magnetic resonance imaging as communicating with the left seminal vesicle. Two ultrasound-guided transperineal biopsy samples revealed benign prostatic tissue with a small focus of Müllerian or endometrial-type tissue, evidenced by immunopositivity for paired-box gene 8 and estrogen receptor in epithelium and cluster of differentiation 10 immunopositivity in stroma. After medical consultation, the patient underwent prostatic cyst aspiration, resection of the transurethral ejaculatory ducts, and orchiectomy. She did not experience any complications after these procedures. Discussion: The etiology of hematospermia may be idiopathic, iatrogenic, anatomic, or pathologic. Conclusion: Occult endometriosis or ectopic Müllerian epithelial tissue growth may occur in transgender women taking feminizing gender-affirming hormone therapy.

Comparison of diagnostic criteria for sepsis-associated acute kidney injury in the pediatric intensive care unit: a retrospective cohort study.

Background: pRIFLE (Pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease), KDIGO (Kidney Disease Improving Global Outcomes) and pROCK (Pediatric Reference Change Value Optimized for AKI) are diagnostic criteria used for acute kidney injury (AKI) incidence evaluation. The aim of this study was to explore the diagnostic consistency, incidence and mortality rate, clinical signs, and influencing factors of renal injury related to sepsis in children diagnosed by three different AKI diagnostic criteria, and then evaluate which one was more valuable. Methods: A retrospective analysis was performed on the clinical data of children with severe sepsis. The patients were diagnosed and staged according to the 2007 pRIFLE standard, the 2012 KDIGO standard, and the 2018 pROCK standard. The clinical characteristics and prognosis of children with different stages of sepsis were compared between the three diagnostic standards. Results: A total of 62 patients with sepsis were included. Blood stream infection is common (11 cases, 17.74%). According to pRIFLE, KDIGO, and pROCK standards, the incidence of sepsis-associated AKI (SA-AKI) was 74.2%, 67.7%, and 56.5%, respectively. The pRIFLE had the highest diagnostic rate of early detection of SA-AKI. There was no statistical difference in SA-AKI incidence or staging consistency between the pRIFLE and KDIGO groups (κ=0.0671; κ>0.60); the consistency of SA-AKI diagnoses across the three standards was good (all P values <0.05), and pROCK demonstrated a higher specificity. A high Pediatric Risk of Mortality (PRISM) score and high procalcitonin level were independent risk factors. Shock and renal replacement therapy were independent risk factors for SA-AKI death. Death from admission to 28 days after admission was used as an endpoint to draw a survival graph, which revealed that the AKI group had a significantly higher risk of death than did the non-AKI group. Conclusions: The consistency of diagnosing SA-AKI across the three classification criteria was similar, and mortality rate increased with increased SA-AKI staging. The pRIFLE criteria were more sensitive in the early detection of SA-AKI, while the pROCK had higher specificity. There was no significant difference between the pRIFLE and KDIGO in terms of incidence, diagnosis, or staging of SA-AKI.

Parent material influences soil properties to shape bacterial community assembly processes, diversity, and enzyme-related functions.

Soil parent material is the second most influential factor in pedogenesis, influencing soil properties and microbial communities. Different assembly processes shape diverse functional microbial communities. The question remains unresolved regarding how these ecological assembly processes affect microbial communities and soil functionality within soils on different parent materials. We collected soil samples developed from typical parent materials, including basalt, granite, metamorphic rock, and marine sediments across soil profiles at depths of 0-20, 20-40, 40-80, and 80-100 cm, within rubber plantations on Hainan Island, China. We determined bacterial community characteristics, community assembly processes, and soil enzyme-related functions using 16S rRNA high-throughput sequencing and enzyme activity analyses. We found homogeneous selection, dispersal limitation, and drift processes were the dominant drivers of bacterial community assembly across soils on different parent materials. In soils on basalt, lower pH and higher moisture triggered a homogeneous selection-dominated assembly process, leading to a less diverse community but otherwise higher carbon and nitrogen cycling enzyme activities. As deterministic process decreased, bacterial community diversity increased with stochastic process. In soils on marine sediments, lower water, carbon, and nutrient content limited the dispersal of bacterial communities, resulting in higher community diversity and an increased capacity to utilize relative recalcitrant substrates by releasing more oxidases. The r-strategy Bacteroidetes and genera Sphingomonas, Bacillus, Vibrionimonas, Ochrobactrum positively correlated with enzyme-related function, whereas k-strategy Acidobacteria, Verrucomicrobia and genera Acidothermus, Burkholderia-Caballeronia-Paraburkholderia, HSB OF53-F07 showed negative correlations. Our study suggests that parent material could influence bacterial community assembly processes, diversity, and soil enzyme-related functions via soil properties.

Are children with IgA nephropathy different from adult patients?

BACKGROUND: Previously, several studies have indicated that pediatric IgA nephropathy (IgAN) might be different from adult IgAN, and treatment strategies might be also different between pediatric IgAN and adult IgAN. METHODS: We analyzed two prospective cohorts established by pediatric and adult nephrologists, respectively. A comprehensive analysis was performed investigating the difference in clinical and pathological characteristics, treatment, and prognosis between children and adults with IgAN. RESULTS: A total of 1015 children and 1911 adults with IgAN were eligible for analysis. More frequent gross hematuria (88% vs. 20%, p < 0.0001) and higher proteinuria (1.8 vs. 1.3 g/d, p < 0.0001) were seen in children compared to adults. In comparison, the estimated glomerular filtration rate (eGFR) was lower in adults (80.4 vs. 163 ml/min/1.73 m2, p < 0.0001). Hypertension was more prevalent in adult patients. Pathologically, a higher proportion of M1 was revealed (62% vs. 39%, p < 0.0001) in children than in adults. S1 (62% vs. 28%, p < 0.0001) and T1-2 (34% vs. 8%, p < 0.0001) were more frequent in adults. Adjusted by proteinuria, eGFR, and hypertension, children were more likely to be treated with glucocorticoids than adults (87% vs. 45%, p < 0.0001). After propensity score matching, in IgAN with proteinuria > 1 g/d, children treated with steroids were 1.87 (95% CI 1.16-3.02, p = 0.01) times more likely to reach complete remission of proteinuria compared with adults treated with steroids. CONCLUSIONS: Children present significantly differently from adults with IgAN in clinical and pathological manifestations and disease progression. Steroid response might be better in children.

The role of language-related functional brain regions and white matter tracts in network plasticity of post-stroke aphasia.

The neural mechanisms underlying language recovery after a stroke remain controversial. This review aimed to summarize the plasticity and reorganization mechanisms of the language network through neuroimaging studies. Initially, we discussed the involvement of right language homologues, perilesional tissue, and domain-general networks. Subsequently, we summarized the white matter functional mapping and remodeling mechanisms associated with language subskills. Finally, we explored how non-invasive brain stimulation (NIBS) promoted language recovery by inducing neural network plasticity. It was observed that the recruitment of right hemisphere language area homologues played a pivotal role in the early stages of frontal post-stroke aphasia (PSA), particularly in patients with larger lesions. Perilesional plasticity correlated with improved speech performance and prognosis. The domain-general networks could respond to increased "effort" in a task-dependent manner from the top-down when the downstream language network was impaired. Fluency, repetition, comprehension, naming, and reading skills exhibited overlapping and unique dual-pathway functional mapping models. In the acute phase, the structural remodeling of white matter tracts became challenging, with recovery predominantly dependent on cortical activation. Similar to the pattern of cortical activation, during the subacute and chronic phases, improvements in language functions depended, respectively, on the remodeling of right white matter tracts and the restoration of left-lateralized language structural network patterns. Moreover, the midline superior frontal gyrus/dorsal anterior cingulate cortex emerged as a promising target for NIBS. These findings offered theoretical insights for the early personalized treatment of aphasia after stroke.

Assessing the causal link between liver function and acute pancreatitis: A Mendelian randomisation study.

A correlation has been reported to exist between exposure factors (e.g. liver function) and acute pancreatitis. However, the specific causal relationship remains unclear. This study aimed to infer the causal relationship between liver function and acute pancreatitis using the Mendelian randomisation method. We employed summary data from a genome-wide association study involving individuals of European ancestry from the UK Biobank and FinnGen. Single-nucleotide polymorphisms (SCNPs), closely associated with liver function, served as instrumental variables. We used five regression models for causality assessment: MR-Egger regression, the random-effect inverse variance weighting method (IVW), the weighted median method (WME), the weighted model, and the simple model. We assessed the heterogeneity of the SNPs using Cochran's Q test. Multi-effect analysis was performed using the intercept term of the MR-Egger method and leave-one-out detection. Odds ratios (ORs) were used to evaluate the causal relationship between liver function and acute pancreatitis risk. A total of 641 SNPs were incorporated as instrumental variables. The MR-IVW method indicated a causal effect of gamma-glutamyltransferase (GGT) on acute pancreatitis (OR = 1.180, 95%CI [confidence interval]: 1.021-1.365, P = 0.025), suggesting that GGT may influence the incidence of acute pancreatitis. Conversely, the results for alkaline phosphatase (ALP) (OR = 0.997, 95%CI: 0.992-1.002, P = 0.197) and aspartate aminotransferase (AST) (OR = 0.939, 95%CI: 0.794-1.111, P = 0.464) did not show a causal effect on acute pancreatitis. Additionally, neither the intercept term nor the zero difference in the MR-Egger regression attained statistical significance (P = 0.257), and there were no observable gene effects. This study suggests that GGT levels are a potential risk factor for acute pancreatitis and may increase the associated risk. In contrast, ALP and AST levels did not affect the risk of acute pancreatitis.

Construction of a nomogram risk prediction model for prolonged mechanical ventilation in patients following surgery for acute type A aortic dissection.

Background: This study aims to analyze the risk factors associated with prolonged mechanical ventilation (PMV) in patients following surgical treatment for acute type A aortic dissection (ATAAD). The objectives include constructing a predictive model for risk assessment and validating its predictive efficacy. Methods: A total of 452 patients diagnosed with ATAAD and undergoing surgical procedures at a tertiary hospital in Nanjing between January 2021 and April 2023 were selected using a convenience sampling method. Patients were categorized into two groups: PMV group (n = 132) and non-PMV group (n = 320) based on the occurrence of prolonged mechanical ventilation (PMV), and their clinical data were compared. The data were randomly divided into a modeling set and a validation set in a 7:3 ratio. Risk factors for PMV were identified in the modeling group using logistic regression analysis. A risk prediction model was constructed using R 4.1.3 software, visualized via a column chart. Receiver Operating Characteristic (ROC) curves were generated using the validation set to assess model differentiation. Calibration curves were plotted to evaluate accuracy and consistency, and Decision Curve Analysis (DCA) was applied to evaluate clinical utility. Results: The logistic regression analysis identified age, body mass index, preoperative white blood cell count, preoperative creatinine, preoperative cerebral hypoperfusion, and cardiopulmonary bypass time as significant risk factors for postoperative PMV in patients with ATAAD. The area under the curve (AUC) for the validation set ROC curve was 0.856, 95% confidence interval (0.805-0.907), indicating good discrimination. Calibration curves revealed strong alignment with the ideal curve, and the Hosmer-Lemeshow goodness-of-fit test indicated a well-fitted model (P = 0.892). The DCA curve demonstrated a high net benefit value, highlighting the model's strong clinical utility. Conclusions: The risk prediction model developed in this study for PMV in patients undergoing surgery for ATAAD exhibits robust predictive performance. It provides valuable insights for healthcare practitioners in predicting the likelihood of PMV and devising timely and personalized intervention strategies.

Semi-permeable membrane-covered high-temperature aerobic composting: A review.

Semi-permeable membrane-covered high-temperature aerobic composting (SMHC) is a suitable technology for the safe treatment and disposal of organic solid waste as well as for improving the quality of the final compost. This paper presents a comprehensive summary of the impact of semi-permeable membranes centered on expanded polytetrafluoroethylene (e-PTFE) on compost physicochemical properties, carbon and nitrogen transformations, greenhouse gas emission reduction, microbial community succession, antibiotic removal, and antibiotic resistance genes migration. It is worth noting that the semi-permeable membrane can form a micro-positive pressure environment under the membrane, promote the uniform distribution of air in the heap, reduce the proportion of anaerobic area in the heap, improve the decomposition rate of organic matter, accelerate the decomposition of compost and improve the quality of compost. In addition, this paper presents several recommendations for future research areas in the SMHC. This investigation aims to guide for implementation of semi-permeable membranes in high-temperature aerobic fermentation processes by systematically compiling the latest research progress on SMHC.

H-ferritin-nanocaged gadolinium nanoparticles for ultra-sensitive MR molecular imaging.

Rationale: Magnetic resonance imaging (MRI) is a powerful diagnostic technology by providing high-resolution imaging. Although MRI is sufficiently valued in its resolving morphology, it has poor sensitivity for tracking biomarkers. Therefore, contrast agents are often used to improve MRI diagnostic sensitivity. However, the clinically used Gd chelates are limited in improving MRI sensitivity owing to their low relaxivity. The objective of this study is to develop a novel contrast agent to achieve a highly sensitive tracking of biomarkers in vivo. Methods: A Gd-based nanoprobe composed of a gadolinium nanoparticle encapsulated within a human H-ferritin nanocage (Gd-HFn) has been developed. The specificity and sensitivity of Gd-HFn were evaluated in vivo in tumor-bearing mice and apolipoprotein E-deficient mice (Apoe-/-) by MRI. Results: The Gd-HFn probe shows extremely high relaxivity values (r1 = 549 s-1mM-1, r2 = 1555 s-1mM-1 under a 1.5-T magnetic field; and r1 = 428 s-1mM-1 and r2 = 1286 s-1mM-1 under a 3.0-T magnetic field), which is 175-fold higher than that of the clinically standard Dotarem (Gd-DOTA, r1 =3.13 s-1mM-1) under a 1.5-T magnetic field, and 150-fold higher under a 3.0-T magnetic field. Owing to the substantially enhanced relaxivity values, Gd-HFn achieved a highly sensitive tracking for the tumor targeting receptor of TfR1 and enabled the in vivo MRI visualization of tumors approaching the angiogenic switch. Conclusions: The developed Gd-HFn contrast agent makes MRI a more powerful tool by simultaneously providing functional and morphological imaging information, which paves the way for a new perspective in molecular imaging.

Clinical significance of measuring MP-DNA, C-reactive protein, and inflammatory cytokines in children with mycoplasma pneumoniae pneumonia.

OBJECTIVE: To explore the clinical significance of detecting mycoplasma pneumoniae (MP)-DNA, C-reactive protein (CRP), interleukin-6 (IL-6), IL-8, and IL-10 in children with mycoplasma pneumoniae pneumonia (MPP). METHODS: The data from 106 children who received treatment or underwent health examination in the Children's Medical Center of Anhui Medical University from January 2021 to October 2022 were collected and analyzed retrospectively. The observation group (OG) consisted of 64 children with MPP, while the control group (CG) consisted of 42 healthy children. The levels of IL-6, IL-8, IL-10, CRP, and MP-DNA were compared between the two groups. The diagnostic value of MP-DNA in patients with MPP and its correlation with the levels of IL-6, IL-8, IL-10 and CRP were analyzed. RESULTS: The level of MP-DNA in the OG was notably higher than that in the CG (P<0.05). Additionally, the levels of IL-6, IL-8, IL-10, and CRP in the OG were significantly higher than those in the CG (P<0.05). MP-DNA was positively correlated with the levels of IL-6, IL-8, IL-10, and CRP (P<0.05). The area under the curve of MP-DNA in diagnosing MPP was 0.979, with a specificity of 92.19% and a sensitivity of 97.62%. CONCLUSION: Indicators such as MP-DAN, IL-6, IL-8 are crucial in the development and progression of MPP, playing an important role in diagnosing and treating patients with MPP.

Associations of MSK1 Methylation and Executive Function With Suicidal Ideation in Adolescents With Major Depressive Disorder: A Prospective Cohort Study.

Objective: Adolescent suicide is a major public health problem, and risk of suicide is higher among those with major depressive disorder (MDD), which may be linked to alterations in mitogen- and stress-activated kinase 1 (MSK1) and to defects in executive function. Here, we aimed to investigate the potential impacts of executive function and MSK1 methylation on suicidal ideation in adolescents with MDD.Methods: The study enrolled 66 drug-naive adolescents who were experiencing their first episode of MDD from February 2019 until October 2020. After 6 weeks of receiving antidepressant treatment, 65 participants remained in the study. Suicidal ideation and depressive severity were assessed using the Hamilton Depression Rating Scale, while executive function was evaluated using the Cambridge Neuropsychological Test Automated Battery. MSK1 methylation was measured using bisulfite DNA analysis.Results: Among the 66 adolescents with MDD, 43 (65.15%) reported suicidal ideation, while 23 (34.85%) did not. Individuals with suicidal ideation had worse executive function and higher MSK1 methylation than those without suicidal ideation. The MSK1 methylation percentage may predict suicidal ideation in adolescents with MDD (odds ratio [OR] 1.227, 95% CI [1.031 to 1.461]). Improvement in executive function was significantly associated with reduced suicidal ideation during antidepressant treatment (ß = -0.200, 95% CI [-0.877 to -0.085]).Conclusions: Our results strengthen the evidence for a link among MSK1 methylation, executive function, and suicidal ideation in adolescent MDD.Trial Registration: Chinese Clinical Trial Registry identifier: ChiCTR2000033402.

Chemical Vapor Deposition Synthesis of Intrinsic High-Temperature Ferroelectric 2D CuCrSe2.

Ultrathin 2D ferroelectrics with high Curie temperature are critical for multifunctional ferroelectric devices. However, the ferroelectric spontaneous polarization is consistently broken by the strong thermal fluctuations at high temperature, resulting in the rare discovery of high-temperature ferroelectricity in 2D materials. Here, a chemical vapor deposition method is reported to synthesize 2D CuCrSe2 nanosheets. The crystal structure is confirmed by scanning transmission electron microscopy characterization. The measured ferroelectric phase transition temperature of ultrathin CuCrSe2 is about ≈800 K. Significantly, the switchable ferroelectric polarization is observed in ≈5.2 nm nanosheet. Moreover, the in-plane and out-of-plane ferroelectric response are modulated by different maximum bias voltage. This work provides a new insight into the construction of 2D ferroelectrics with high Curie temperature.

A Phase 1/2 multicenter trial of DKN-01 as monotherapy or in combination with docetaxel for the treatment of metastatic castration-resistant prostate cancer (mCRPC).

BACKGROUND: Dickkopf-related protein 1 (DKK1) is a Wingless-related integrate site (Wnt) signaling modulator that is upregulated in prostate cancers (PCa) with low androgen receptor expression. DKN-01, an IgG4 that neutralizes DKK1, delays PCa growth in pre-clinical DKK1-expressing models. These data provided the rationale for a clinical trial testing DKN-01 in patients with metastatic castration-resistant PCa (mCRPC). METHODS: This was an investigator-initiated parallel-arm phase 1/2 clinical trial testing DKN-01 alone (monotherapy) or in combination with docetaxel 75 mg/m2 (combination) for men with mCRPC who progressed on ≥1 AR signaling inhibitors. DKK1 status was determined by RNA in-situ expression. The primary endpoint of the phase 1 dose escalation cohorts was the determination of the recommended phase 2 dose (RP2D). The primary endpoint of the phase 2 expansion cohorts was objective response rate by iRECIST criteria in patients treated with the combination. RESULTS: 18 pts were enrolled into the study-10 patients in the monotherapy cohorts and 8 patients in the combination cohorts. No DLTs were observed and DKN-01 600 mg was determined as the RP2D. A best overall response of stable disease occurred in two out of seven (29%) evaluable patients in the monotherapy cohort. In the combination cohort, five out of seven (71%) evaluable patients had a partial response (PR). A median rPFS of 5.7 months was observed in the combination cohort. In the combination cohort, the median tumoral DKK1 expression H-score was 0.75 and the rPFS observed was similar between patients with DKK1 H-score ≥1 versus H-score = 0. CONCLUSION: DKN-01 600 mg was well tolerated. DKK1 blockade has modest anti-tumor activity as a monotherapy for mCRPC. Anti-tumor activity was observed in the combination cohorts, but the response duration was limited. DKK1 expression in the majority of mCRPC is low and did not clearly correlate with anti-tumor activity of DKN-01 plus docetaxel.

Timing theory integrated nursing combined behavior change integrated theory of nursing on primiparous influence.

BACKGROUND: The comprehension and utilization of timing theory and behavior change can offer a more extensive and individualized provision of support and treatment alternatives for primipara. This has the potential to enhance the psychological well-being and overall quality of life for primipara, while also furnishing healthcare providers with efficacious interventions to tackle the psychological and physiological obstacles encountered during the stages of pregnancy and postpartum. AIM: To explore the effect of timing theory combined with behavior change on self-efficacy, negative emotions and quality of life in patients with primipara. METHODS: A total of 80 primipara cases were selected and admitted to our hospital between August 2020 and May 2022. These cases were divided into two groups, namely the observation group and the control group, with 40 cases in each group. The nursing interventions differed between the two groups, with the control group receiving routine nursing and the observation group receiving integrated nursing based on the timing theory and behavior change. The study aimed to compare the pre- and post-nursing scores of Chinese Perceived Stress Scale (CPSS), Edinburgh Postpartum Depression Scale (EPDS), Self-rating Anxiety Scale (SAS), breast milk knowledge, self-efficacy, and SF-36 quality of life in both groups. RESULTS: After nursing, the CPSS, EPDS, and SAS scores of the two groups was significantly lower than that before nursing, and the CPSS, EPDS, and SAS scores of the observation group was significantly lower than that of the control group (P = 0.002, P = 0.011, and P = 0.001 respectively). After nursing, the breastfeeding knowledge mastery, self-efficacy, and SF-36 quality of life scores was significantly higher than that before nursing, and the breastfeeding knowledge mastery (P = 0.013), self-efficacy (P = 0.008), and SF-36 quality of life (P = 0.011) scores of the observation group was significantly higher than that of the control group. CONCLUSION: The integration of timing theory and behavior change integrated theory has been found to be an effective approach in alleviating negative mood and stress experienced by primipara individuals, while also enhancing their self-efficacy and overall quality of life. This study focuses on the key concepts of timing theory, behavior change, primipara individuals, negative mood, and quality of life.