Individualized and Biomarker-Based Prognosis of Longitudinal Cognitive Decline in Early Symptomatic Alzheimer's Disease.

Background: Although individualized models using demographic, MRI, and biological markers have recently been applied in mild cognitive impairment (MCI), a similar study is lacking for patients with early Alzheimer's disease (AD) with biomarker evidence of abnormal amyloid in the brain. Objective: We aimed to develop prognostic models for individualized prediction of cognitive change in early AD. Methods: A total of 421 individuals with early AD (MCI or mild dementia due to AD) having biomarker evidence of abnormal amyloid in the brain were included in the current study. The primary cognitive outcome was the slope of change in Alzheimer's Disease Assessment Scale-cognitive subscale-13 (ADAS-Cog-13) over a period of up to 5 years. Results: A model combining demographics, baseline cognition, neurodegenerative markers, and CSF AD biomarkers provided the best predictive performance, achieving an overfitting-corrected R2 of 0.59 (bootstrapping validation). A nomogram was created to enable clinicians or trialists to easily and visually estimate the individualized magnitude of cognitive change in the context of patient characteristics. Simulated clinical trials suggested that the inclusion of our nomogram into the enrichment strategy would lead to a substantial reduction of sample size in a trial of early AD. Conclusions: Our findings may be of great clinical relevance to identify individuals with early AD who are likely to experience fast cognitive deterioration in clinical practice and in clinical trials.

Adolescent suicidal ideation: dissecting the role of sex in depression and NSSI predictors.

BACKGROUND: Suicidal ideation (SI) is increasingly prevalent among adolescents, often arising from depression and linked with non-suicidal self-injury (NSSI). Previous studies have noted significant sex differences in the manifestation and predictors of SI, depression, and NSSI. AIM: This study aims to analyze and compare the relationships between SI, depression, and NSSI among male and female adolescents, examining whether these associations differ based on sex. METHODS: A total of 368 adolescents (M = 15.43, SD = 1.22, about 56.2% female participants), both from clinical and school settings, were assessed for SI, depression, NSSI, and other related variables. Network analysis was utilized to explore the interconnections among these variables, focusing on identifying sex-specific patterns. Logistic regression was used to confirm the findings from the network analysis. RESULTS: The network analysis revealed significant sex differences in the relationships between SI, depression, and NSSI. In the female network, the edge weights between SI and NSSI (0.93) and between SI and depression (0.31) were much higher compared to the male network (0.29 and 0, respectively). Centrality indices (strength, betweenness, closeness, and expected influence) for SI, NSSI, and depression were also higher in the female network. Logistic regression confirmed these findings, with depression being a potential predictor of SI only in females (OR = 1.349, p = 0.001) and NSSI having a stronger influence on SI in females (OR = 13.673, p < 0.001) than in males (OR = 2.752, p = 0.037). CONCLUSION: The findings underscore the necessity of considering sex differences when predicting suicidal ideation from depression and NSSI in adolescents. Intervention and prevention strategies should be tailored to address these distinct patterns in male and female adolescents.

Latent profile analysis of Eysenck's personality dimensions and psychological constructs in university students.

Background: The exploration of personality traits in relation to psychological constructs has become increasingly relevant in understanding the mental health of university students (the emerging adulthood). Studies have focused on how dimensions intersect with various psychological parameters. Aim: The study aims to identify distinct personality profiles among university students based on Eysenck's personality dimensions and investigate how these profiles differ across psychological constructs. Method: A quantitative methodology was utilized, involving 708 university students from Wenzhou and Nanjing in China as participants. The research employed the Eysenck Personality Questionnaire along with other psychological measures. Latent Profile Analysis was applied to categorize the participants into distinct personality profiles. Results: Four distinct personality profiles emerged: 'The Reserved Analyst,' 'The Social Diplomat,' 'The Unconventional Pragmatist,' and 'The Impulsive Truth-Teller.' Significant differences were found among these profiles on various psychological constructs. 'The Social Diplomat' exhibited the most adaptive psychological profile, with higher cognitive reappraisal (F = 45.818, p < 0.001, η2 = 0.163), meaning in life (F = 17.764, p < 0.001, η2 = 0.070), and positive coping (F = 40.765, p < 0.001, η2 = 0.148) compared to other profiles. Conversely, 'The Reserved Analyst' showed higher intolerance of uncertainty (F = 13.854, p < 0.001, η2 = 0.056) and state anxiety (F = 26.279, p < 0.001, η2 = 0.101). Conclusion: This study enriches the understanding of personality traits in relation to psychological constructs within the context of university student populations. By identifying distinct personality profiles, it lays the groundwork for developing tailored mental health strategies that cater to the specific needs of different student groups.

Four-year variation in pathogen distribution and antimicrobial susceptibility of urosepsis: a single-center retrospective analysis.

Background: Urosepsis is a common disease in urology, which is characterized by high treatment costs and high mortality. In the treatment of sepsis, anti-infection therapy is the most important means. However, the effect of empirical anti-infection therapy is often not ideal. Therefore, it is necessary to continuously monitor the prevalence of bacterial isolates in the blood culture of patients with urinary sepsis and their sensitivity to antibacterial drugs. This is of great significance to improve the efficacy of empirical antibiotic therapy for urosepsis. Objective: To elucidate the landscape of prevailing bacterial profiles and their antimicrobial susceptibilities in urosepsis cases, and to furnish robust clinical evidence to underpin the timely initiation of empirical antibiotic treatment. Methods: Collect the basic information and blood culture results of patients with urosepsis hospitalized from 2017 to 2020. Retrospective analysis of bacterial species and antimicrobial susceptibility in urosepsis and changes over 4 years. Results: Gram-negative bacteria (178 isolates, 75.11%) constituted the main pathogens causing urosepsis, followed by Gram-positive bacteria (46 isolates, 19.41%) and fungus (13 isolates, 5.48%). The sensitivity of ertapenem, meropenem, amikacin, and imipenem to Gram-negative bacteria all exceeded 85%. The sensitivity rates of levofloxacin, gentamicin, and ciprofloxacin are decreasing every year (p < 0.05). Tigecycline, vancomycin, and linezolid exhibited excellent sensitivity against Gram-positive bacteria. Among fungi, fluconazole demonstrated universal sensitivity, while itraconazole-resistant isolates have been found, and amphotericin B is still effective. Conclusion: Analysis of blood culture results of patients more accurately reflected the etiology of urosepsis, mainly Escherichia coli, Enterococcus, and Klebsiella pneumoniae. If there are no definitive blood culture results, empiric treatment of urosepsis should not include fluoroquinolone antibiotics. Cefepime, cefoxitin, and ceftazidime are the most sensitive antibiotics to Gram-negative bacteria besides carbapenem antibiotics. In addition, the current situation regarding extended-spectrum ß-lactamase-producing bacteria and carbapenem-resistant Enterobacteriaceae bacteria resistance is extremely concerning with limited therapeutic options available. Strengthening antibiotic management practices and exploring novel antibacterial agents can help mitigate this issue.

Mental toughness in adolescents: bridging family relationships and depression across personality traits.

BACKGROUND: Adolescence is a pivotal stage vulnerable to mental health issues like anxiety and depression. While family relationships, mental toughness, and personality traits are known to impact adolescent mental health, their interactive and moderating roles are not fully understood. AIM: This study aims to investigate the mediating role of mental toughness in the relationship between family relationships and depression among high school students, and to examine the varying impacts of personality traits on this mediation. METHOD: A cross-sectional study was conducted on a sample of 734 adolescents. Participants completed measures assessing family relationships, mental toughness, personality traits, and mental health outcomes (depression). Latent Profile Analysis, Multiple Regression Analysis, and Structural Equation Modeling, to investigate these relationships. RESULTS: The study found that mental toughness significantly mediates the relationship between family relationships and depression. Notably, this mediating effect varied between personality type; it was more pronounced in the moderate-reserved type compared to the proactive-engaged type. LPA identified two distinct personality types of students based on their personality traits, with differential patterns of family relationships, mental toughness, and depression. Multiple regression analysis indicated that character and adaptability, components of mental toughness, were significant negative predictors of depression. CONCLUSION: The study contributes to understanding the dynamics of adolescent mental health, particularly in the context of Chinese high school students. It underscores the importance of considering family dynamics, personality traits, and mental toughness in developing effective mental health interventions for adolescents.

Identification of key pathways and mRNAs in interstitial cystitis/bladder pain syndrome treatment with quercetin through bioinformatics analysis of mRNA-sequence data.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition with painful bladder. At present, the pathogenesis of IC/BPS is still unknown. Quercetin (QCT) is a kind of natural flavonoid with wide sources and multiple biological activities. The purpose of this study was to explore the effects of QCT on mRNA expression and related regulatory signal pathways in IC model rats. METHODS: LL-37 was used to induce the IC/BPS model rats. 20 mg/kg QCT was injected intraperitoneally into IC/BPS rats. ELISA, HE, Masson and TB staining were used to evaluate the level of inflammation and pathology. The concentration of QCT in rats was detected by HPLC. The mRNA sequencing was used to detect the differentially expressed (DE) mRNA in each group. The over-expression experiment of Lpl was carried out in IC/BPS model rats. RESULTS: QCT treatment significantly decreased the level of MPO, IL-1ß, IL-6 and TNF-α induced by LL-37 in rats, and alleviated bladder injury and mast cell degranulation. There were significant differences in mRNA sequencing data between groups, and the hub gene Lpl were screened by Cytohubba. The expression of Lpl was downregulated in IC/BPS rats. QCT intervention promoted Lpl expression. Overexpression of Lpl reduced the bladder injury induced by LL-37, increased GAG level and decreased the expression of MPO, IL-1ß, IL-6 and TNF-α. CONCLUSION: In this study, we provided the DE mRNA in IC/BPS rats treated with QCT, the signaling pathways for DE enrichment, screened out the hub genes, and revealed that Lpl overexpression alleviated IC/BPS model rats.

Cognitive control in honesty and dishonesty under different conflict scenarios: insights from reaction time.

This study investigated the role of cognitive control in moral decision-making, focusing on conflicts between financial temptations and the integrity of honesty. We employed a perceptual task by asking participants to identify which side of the diagonal contained more red dots within a square to provoke both honest and dishonest behaviors, tracking their reaction times (RTs). Participants encountered situations with no conflict, ambiguous conflict, and clear conflict. Their behaviors in the clear conflict condition categorized them as either "honest" or "dishonest." Our findings suggested that, in ambiguous conflict situations, honest individuals had significantly longer RTs and fewer self-interest responses than their dishonest counterparts, suggesting a greater need for cognitive control to resolve conflicts and a lesser tendency toward self-interest. Moreover, a negative correlation was found between participants' number of self-interest responses and RTs in ambiguous conflict situations (r = -0.27 in study 1 and r = -0.66 in study 2), and a positive correlation with cheating numbers in clear conflict situations (r = 0.36 in study 1 and r = 0.82 in study 2). This suggests less cognitive control was required for self-interest and cheating responses, bolstering the "Will" hypothesis. We also found that a person's self-interest tendency could predict their dishonest behavior. These insights extend our understanding of the role of cognitive control plays in honesty and dishonesty, with potential applications in education, policy-making, and business ethics.

Succinate Dehydrogenase Defects Giant Renal Cell Carcinoma.

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a new subtype of RCC included in the 2016 edition of the WHO classification in RCC. SDH-defective RCC accounts for 0.05-0.2%, and preoperative diagnosis is difficult. We report a severe adherent RCC of inferior vena cava that underwent open radical nephrectomy after preoperative renal artery embolization. Postoperative histopathological examination diagnosed SDH-defective RCC; the clinicopathological stage was pT2b. After 10 months of follow-up, the patient had no evidence of disease recurrence. For patients with large RCC, interventional embolization can be selected to reduce intraoperative bleeding and blood transfusion, and it is recommended to complete interventional surgery within 3-4 h before surgery. SDH-deficient RCC is difficult to distinguish from other renal tumors in imaging, so immunohistochemical examination of SDHB is recommended for young and middle-aged patients, especially those under 45.

Diagnostic and therapeutic value of biomarkers in urosepsis.

Urosepsis is sepsis caused by urogenital tract infection and is one of the most common critical illnesses in urology. If urosepsis is not diagnosed early, it can rapidly progress and worsen, leading to increased mortality. In recent years, with the increase of urinary tract surgery, the incidence of urosepsis continues to rise, posing a serious threat to patients. Early diagnosis of urosepsis, timely and effective treatment can greatly reduce the mortality of patients. Biomarkers such as WBC, NLR, PCT, IL-6, CRP, lactate, and LncRNA all play specific roles in the early diagnosis or prognosis of urosepsis. In addition to the abnormal increase of WBC, we should be more alert to the rapid decline of WBC. NLR values were superior to WBC counts alone in predicting infection severity. Compared with several other biomarkers, PCT values can differentiate between bacterial and non-bacterial sepsis. IL-6 always has high sensitivity and specificity for the diagnosis of sepsis, and CRP also has high sensitivity and specificity for the diagnosis of urosepsis. Lactic acid is closely related to the prognosis of patients with urosepsis. LncRNAs may be potential biomarkers of urosepsis. This article summarizes the main biomarkers, hoping to provide a reference for the timely diagnosis and evaluation of urosepsis.

Comparison of Transperitoneal and Retroperitoneal Laparoscopic Ureterolithotomy: A Meta-Analysis.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of transperitoneal and retroperitoneal laparoscopic ureterolithotomy (TLU and RLU). MATERIALS AND METHODS: We undertook a literature search PubMed, Embase, and the Cochrane Library. Search date will range from inception to January 1, 2020. The final article results will be analyzed using StataSE 12 software. This meta-analysis was reported according to PRISMA guidelines, and a protocol was registered in PROSPERO (CRD42020160906). RESULTS: Eleven articles eventually met the requirements, involving a total of 609 patients. The final result shows the operative time (Std. Mean Difference [SMD] = 0.58; 95% CI 0.36-0.80; p < 0.01), hospital stay (SMD = 0.26; 95% CI 0.02-0.49; p = 0.031), and the complication of paralytic ileus (risk difference = 0.11; 95% CI 0.05-0.17; p < 0.01) are significant difference between TLU and RLU, and TLU are higher or longer. CONCLUSIONS: Our meta-analysis suggests that if there are no other constraints, it is better to choose RLU. And more clinical trial data are needed to confirm this conclusion.

N6-methyladenosine-related lncRNAs in combination with computational histopathology and radiomics predict the prognosis of bladder cancer.

OBJECTIVES: Identification of m6A- related lncRNAs associated with BC diagnosis and prognosis. METHODS: From the TCGA database, we obtained transcriptome data and corresponding clinical information (including histopathological and CT imaging data) for 408 patients. And bioinformatics, computational histopathology, and radiomics were used to identify and analyze diagnostic and prognostic biomarkers of m6A-related lncRNAs in BC. RESULTS: 3 significantly high-expressed m6A-related lncRNAs were significantly associated with the prognosis of BC. The BC samples were divided into two subgroups based on the expression of the 3 lncRNAs. The overall survival of patients in cluster 2 was significantly lower than that in cluster 1. The immune landscape results showed that the expression of PD-L1, T cells follicular helper, NK cells resting, and mast cells activated in cluster 2 were significantly higher, and naive B cells, plasma cells, T cells regulatory (Tregs), and mast cells resting were significantly lower. Computational histopathology results showed a significantly higher percentage of tumor-infiltrating lymphocytes (TILs) in cluster 2. The radiomics results show that the 3 eigenvalues of diagnostics image-original minimum, diagnostics image-original maximum, and original GLCM inverse variance are significantly higher in cluster 2. High expression of 2 bridge genes in the PPI network of 30 key immune genes predicts poorer disease-free survival, while immunohistochemistry showed that their expression levels were significantly higher in high-grade BC than in low-grade BC and normal tissue. CONCLUSION: Based on the results of immune landscape, computational histopathology, and radiomics, these 3 m6A-related lncRNAs may be diagnostic and prognostic biomarkers for BC.

Osteopontin: An important protein in the formation of kidney stones.

The incidence of kidney stones averages 10%, and the recurrence rate of kidney stones is approximately 10% at 1 year, 35% at 5 years, 50% at 10 years, and 75% at 20 years. However, there is currently a lack of good medicines for the prevention and treatment of kidney stones. Osteopontin (OPN) is an important protein in kidney stone formation, but its role is controversial, with some studies suggesting that it inhibits stone formation, while other studies suggest that it can promote stone formation. OPN is a highly phosphorylated protein, and with the deepening of research, there is growing evidence that it promotes stone formation, and the phosphorylated protein is believed to have adhesion effect, promote stone aggregation and nucleation. In addition, OPN is closely related to immune cell infiltration, such as OPN as a pro-inflammatory factor, which can activate mast cells (degranulate to release various inflammatory factors), macrophages (differentiated into M1 macrophages), and T cells (differentiated into T1 cells) etc., and these inflammatory cells play a role in kidney damage and stone formation. In short, OPN mainly exists in the phosphorylated form in kidney stones, plays an important role in the formation of stones, and may be an important target for drug therapy of kidney stones.

Bruton tyrosine kinase (BTK) may be a potential therapeutic target for interstitial cystitis/bladder pain syndrome.

AIMS: To determine the potential diagnostic and therapeutic targets of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). METHODS: We selected the GSE11783, GSE57560 and GSE621 datasets from the GEO database and merged them. R software was used to screen differentially expressed genes (DEGs) between IC/BPS and normal bladder tissues. The "String" online tool is used to analyze DEGs interaction and functional protein enrichment. CIBERSORT online tool was used to analyze the infiltration of immune cells. In addition, we verified the function of BTK in IC/BPS at the clinical samples and cells level. RESULTS: Bioinformatics analysis revealed that 5 genes were significantly overexpressed in IC/BPS, and the protein-protein interaction diagram showed that BTK was a critical link between these five proteins. At the same time, functional enrichment showed that they were significantly related to innate immunity. Immunoinfiltration showed that mast cell resting in IC/BPS was significantly higher. IHC staining of clinical samples showed that the mast cell markers Tryptase and BTK were highly expressed in IC/BPS tissues. At the cell level, knockdown of BTK inhibited proliferation, migration, invasion, and degranulation of mast cells. CONCLUSIONS: This study provides a new perspective for understanding the molecular mechanisms involved in IC/BPS and suggests that BTK may be a target for treating IC/BPS.

Mechanism of ketotifen fumarate inhibiting renal calcium oxalate stone formation in SD rats.

OBJECTIVES: To investigate the inhibitory effect of ketotifen fumarate (KFA), a mast cell membrane stabilizer, on renal calcium oxalate stone (CaOx) formation and its possible molecular mechanism. METHODS: We used the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database for functional and pathway enrichment analyses of osteopontin (OPN), CD44 and fibronectin (FN). Blood biochemistry, reactive oxygen species ratio (ROS), mast cells, proteins (CD44, OPN and FN) and OPN receptor integrin family genes were detected by ELISA, flow cytometry, immunohistochemistry and RT-QPCR, respectively. RESULTS: The crystal area of CaOx in the KFA and Control group was significantly smaller than that in the Model group. The number of activated mast cells, the expression levels of OPN and CD44 in the Control and KFA groups were significantly lower than those in the Model group, and the percentage of ROS in the KFA group was also significantly lower than that in the Model group. The mRNA expression levels of ITGB1, ITGA9, ITGAV and ITGA4 genes in the prominent OPN receptor integrin family increased significantly in the Model group. CONCLUSIONS: Ketotifen can effectively inhibit the crystal formation of CaOx and reduce the inflammatory response of tissue in SD rats. The mechanism may be to reduce the infiltration and activation of mast cells in renal tissue and down-regulate the expression of OPN, CD44 and FN in renal tubules and renal interstitium. And affect the synthesis of integrins (ITGA9, ITGA4, ITGAV, ITGB1, ITGB3 and ITGB5) and ROS.

Comparison of Vacuum Suction Sheath and Non-Vacuum Suction Sheath in Minimally Invasive Percutaneous Nephrolithotomy: A Meta-Analysis.

Objective To evaluate the clinical efficacy of minimally invasive percutaneous nephrolithotomy (mPCNL) with vacuum suction sheath in the treatment of renal calculi. Methods: We collected relevant studies of vacuum suction sheath and non-vacuum sheath mPCNL from PubMed, Embase, and Cochrane databases for a meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Results: 7 studies were included (4 randomized controlled studies, 3 retrospective studies involving 1803 patients). The final meta-analysis results showed that the operative time (Standardised Mean Difference [SMD] = -0.84, 95% CI [-1.20; -0.48], P < 0.001), auxiliary procedures (Odds Ratio [OR] = 0.61, 95% CI [0.46; 0.81], P < 0.001) and complications in the vacuum suction sheath group were significantly lower than those in the non-vacuum sheath group. The immediate and final stone-free rates (OR = 1.69, 95% CI [1.30; 2.18], P < 0.001; OR = 1.44, 95% CI [0.98; 2.13], P = 0.039) were also significantly lower in the vacuum suction sheath group. Conclusion: This study indicates that the application of vacuum suction sheath in mPCNL can significantly shorten the operative time and patient hospitalization, reduce auxiliary procedures and complications (especially fever, urinary tract infection, and pain).

Role of protein phosphatase 2A in kidney disease (Review).

Kidney disease affects millions of people worldwide and is a financial burden on the healthcare system. Protein phosphatase 2A (PP2A), which is involved in renal development and the function of ion-transport proteins, aquaporin-2 and podocytes, is likely to serve an important role in renal processes. PP2A is associated with the pathogenesis of a variety of different kidney diseases including podocyte injury, inflammation, tumors and chronic kidney disease. The current review aimed to discuss the structure and function of PP2A subunits in the context of kidney diseases. How dysregulation of PP2A in the kidneys causes podocyte death and the inactivation of PP2A in renal carcinoma tissues is discussed. Inhibition of PP2A activity prevents epithelial-mesenchymal transition and attenuates renal fibrosis, creating a favorable inflammatory microenvironment and promoting the initiation and progression of tumor pathogenesis. The current review also indicates that PP2A serves an important role in protection against renal inflammation. Understanding the detailed mechanisms of PP2A provides information that can be utilized in the design and application of novel therapeutics for the treatment and prevention of renal diseases.

The current status of preventive measures for urinary calculi in children.

Urological calculus is a common disease in urology. Urological calculi are generally more common in adults but have become more common in children in recent years. Most existing studies focus on the prevention of urinary calculi in adults; there are relatively few articles on calculi in children. Reported preventive measures are not comprehensive enough, while the latest research progress has not been updated. The pathogenesis and preventive measures associated with urinary calculi have been the focus of research, but many preventive measures still need further clarification. This article reviews the progress on preventive measures for urinary calculi in children.