Cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic disorders are the 3 major chronic diseases threatening human health, which are closely related and often coexist, significantly increasing the difficulty of disease management. In response, the American Heart Association (AHA) proposed a novel disease concept of “cardiovascular-kidney-metabolic (CKM) syndrome” in October 2023, which has triggered widespread concern about the co-treatment of heart and kidney diseases and the prevention and treatment of metabolic disorders around the world. This review posits that effectively managing CKM syndrome requires a new and multidimensional paradigm for diagnosis and risk prediction that integrates biological insights, advanced technology and social determinants of health (SDoH). We argue that the core pathological driver is a “metabolic toxic environment”, fueled by adipose tissue dysfunction and characterized by a vicious cycle of systemic inflammation and oxidative stress, which forms a common pathway to multi-organ injury. The at-risk population is defined not only by biological characteristics but also significantly impacted by adverse SDoH, which can elevate the risk of advanced CKM by a factor of 1.18 to 3.50, underscoring the critical need for equity in screening and care strategies. This review systematically charts the progression of diagnostic technologies. In diagnostics, we highlight a crucial shift from single-marker assessments to comprehensive multi-marker panels. The synergistic application of traditional biomarkers like NT-proBNP (reflecting cardiac stress) and UACR (indicating kidney damage) with emerging indicators such as systemic immune-inflammation index (SII) and Klotho protein facilitates a holistic evaluation of multi-organ health. Furthermore, this paper explores the pivotal role of non-invasive monitoring technologies in detecting subclinical disease. Techniques like multi-wavelength photoplethysmography (PPG) and impedance cardiography (ICG) provide a real-time window into microcirculatory and hemodynamic status, enabling the identification of early, often asymptomatic, functional abnormalities that precede overt organ failure. In imaging, progress is marked by a move towards precise, quantitative evaluation, exemplified by artificial intelligence-powered quantitative computed tomography (AI-QCT). By integrating AI-QCT with clinical risk factors, the predictive accuracy for cardiovascular events within 6 months significantly improves, with the area under the curve (AUC) increasing from 0.637 to 0.688, demonstrating its potential for reclassifying risk in CKM stage 3. In the domain of risk prediction, we trace the evolution from traditional statistical tools to next-generation models. The new PREVENT equation represents a major advancement by incorporating key kidney function markers (eGFR, UACR), which can enhance the detection rate of CKD in primary care by 20%-30%. However, we contend that the future lies in dynamic, machine learning-based models. Algorithms such as XGBoost have achieved an AUC of 0.82 for predicting 365-day cardiovascular events, while deep learning models like KFDeep have demonstrated exceptional performance in predicting kidney failure risk with an AUC of 0.946. Unlike static calculators, these AI-driven tools can process complex, multimodal data and continuously update risk profiles, paving the way for truly personalized and proactive medicine. In conclusion, this review advocates for a paradigm shift toward a holistic and technologically advanced framework for CKM management. Future efforts must focus on the deep integration of multimodal data, the development of novel AI-driven biomarkers, the implementation of refined SDoH-informed interventions, and the promotion of interdisciplinary collaboration to construct an efficient, equitable, and effective system for CKM screening and intervention.

Objective To analyze the pathogenic characteristics and drug sensitivity of candidaemia,and construct a short-term mortality risk prediction scoring model.Methods The clinical data of patients with candidaemia admitted to the 909 Hospital of Joint Logistics Support Force from January 2011 to December 2020 were retrospectively analyzed,and the composition of pathogen composition,drug sensitivity test results and incidence of hospitalized patients were analyzed.324 cases of candidaemia were randomly divided into modeling group(190 cases)and validation group(134 cases),and the risk factors were screened by binary logistic regression.According to the odds ratio(OR)score,the 30 day mortality risk prediction scoring model was constructed,and the predictive performance of the model was verified both in modeling and validation groups.Results 356 strains of Candida including 126 strains of C.albicans(35.39%),79 strains of C.tropicalis(22.19%),74 strains of C.parapsilosis(20.79%),48 strains of C.glabrata(13.48%),14 strains of C.guilliermondii(3.93%),8 strains of C.krusei(2.25%),and 7 strains of other Candida(1.97%)were detected in 336 patients with candidemia.The incidence of candidaemia among hospitalized patients increased from 0.20 ‰ in 2011 to 0.48 ‰ in 2020.The resistance rate of candida to amphotericin B was significantly lower than that of fluconazole,voriconazole and itraconazole(P＜0.05).Among the 324 cases included in the model,95 patients died in 30 days after diagnosis,and the mortality rate was 29.32%.The proportion of males,fever,and parenteral nutrition in modeling group was significantly higher than that in validation group(P＜0.05),while the proportion of chronic lung disease and surgical history within one month were lower than those in validation group(P＜0.05).Logistic regression analysis showed that chronic renal failure,mechanical ventilation,severe neutropenia,failure to receive anti-fungal treatment within 72 hours,and APACHE Ⅱ≥20 were risk factors for short-term death of candidaemia,the OR values were 3.179,1.970,2.979,2.080,and 2.399,and the risk scores were 6,4,6,4,and 5,respectively.The area under the curve(AUC)of the risk scoring model for modeling group was 0.792(95%CI 0.721-0.862),and the result of Hosmer-Lemeshow(H-L)test was P=0.305;The AUC of validation group was 0.796(95%CI 0.735-0.898),and the H-L test result was P=0.329.A risk score≤8 indicated a low risk group for short-term mortality,a score of 9-15 indicated a medium risk group,and a score≥16 indicated a high risk group.Conclusions The incidence of candidemia in hospitalized patients is increasing and the mortality is high.The risk prediction score model can effectively predict the short-term prognosis and facilitate the early identification of the prognosis.

Objective To investigate the association between auditory processing and problem behaviors in preschool children,as well as the mediating role of executive function.Methods A total of 2 342 preschool children were selected from 7 kindergartens in Nanjing,China from June to August 2021.They were evaluated using Preschool Auditory Processing Assessment Scale,Conners Parent Symptom Questionnaire,and Behavior Rating Inventory of Executive Functioning-Preschool version.Children with different demographic features were compared in the scores and the abnormality rates of auditory processing,problem behaviors,and executive function.The influencing factors of the total scores of auditory processing,problem behaviors,and executive function were evaluated using multiple linear regression analysis.Whether executive function was a mediating factor between auditory processing and executive function was examined.Results Sex and grade were the main influencing factors for the total score of auditory processing(P<0.05),and sex,grade,parental education level,and family economic status were the main influencing factors for the total scores of problem behaviors and executive function(P<0.05).The auditory processing score(rs= 0.458,P<0.05)and problem behavior score(rs=0.185,P<0.05)were significantly positively correlated with the executive function score,and the auditory processing score was significantly positively correlated with the problem behavior score(rs=0.423,P<0.05).Executive function played a partial mediating role between auditory processing and problem behaviors,and the mediating effect accounted for 33.44% of the total effect.Conclusions Auditory processing can directly affect the problem behaviors of preschool children and indirectly affect problem behaviors through executive function.[Chinese Journal of Contemporary Pediatrics,2024,26(2):174-180]

Heart failure with preserved ejection fraction(HFpEF)is a highly heterogeneous systemic condition and represents the predominant form of heart heart failure(HF)worldwide.Current pharmacotherapies for HFpEF are limited and lack specific targeted drugs.Recent studies suggest that non-pharmacological strategies serve as adjuncts to conventional pharmacological treatment,offering improvements in symptoms,quality of life,and reducing the risk of rehospitalization for HF in patients with HFpEF.These strategies include CD34 stem cell transplantation,the greater splanchnic nerve ablation,atrial septal shunting,atrial pacing,myocardial contractility modulation,left ventricular expander,baroreceptor stimulation,and others.This review comprehensively summarizes the latest clinical evidence on non-pharmacological treatments for HFpEF,with the aim of advancing the understanding of treatment strategies for this condition.

OBJECTIVE: To investigate the mechanism of self-efficacy between self-management ability and self-management behavior and its differences among patients with different disease courses through mediation tests. METHODS: In the study, 489 patients with type 2 diabetes who attended the endocrinology departments of four hospitals in Shanxi Province and Inner Mongolia Autonomous Region from July to September 2022 were enrolled as the study population. They were investigated by General Information Questionnaire, Diabetes Self-Management Scale, Chinese version of Diabetes Empowerment Simplified Scale, and Diabetes Self-Efficacy Scale. Mediation analyses were performed using the linear regression model, Sobel test, and Bootstrap test in the software Stata version 15.0 and divided the patients into different disease course groups for subgroup analysis according to whether the disease course was > 5 years. RESULTS: In this study, the score of self-management behavior in the patients with type 2 diabetes was 6.16±1.41, the score of self-management ability was 3.99±0.74, and the score of self-efficacy was 7.05±1.90. The results of the study showed that self-efficacy was positively correlated with self-management ability (r=0.33) as well as self-management behavior (r=0.47) in the patients with type 2 diabetes (P < 0.01). The mediating effect of self-efficacy accounted for 38.28% of the total effect of self-management ability on self-management behaviors and was higher in the behaviors of blood glucose monitoring (43.45%) and diet control (52.63%). The mediating effect of self-efficacy accounted for approximately 40.99% of the total effect for the patients with disease course ≤ 5 years, while for the patients with disease course > 5 years, the mediating effect accounted for 39.20% of the total effect. CONCLUSION Self-efficacy enhanced the effect of self-management ability on the behavior of the patients with type 2 diabetes, and this positive effect was more significant for the patients with shorter disease course. Targeted health education should be carried out to enhance patients' self-efficacy and self-management ability according to their disease characteristics, to stimulate their inner action, to promote the development of their self-management behaviors, and to form a more stable and long-term mechanism for disease management.
Humans ; Diabetes Mellitus, Type 2/therapy* ; Self Efficacy ; Self-Management ; Blood Glucose Self-Monitoring ; Blood Glucose ; Self Care

Objective: To investigate the impact of obstructive sleep apnea syndrome (OSAS) on pregnancy outcomes, especially the relationship between OSAS and hypertensive disorders in pregnancy (HDP). Methods: A total of 228 pregnant women with high risk of OSAS who underwent sleep monitoring during pregnancy in Peking University People's Hospital from January 2021 to April 2022 were collected by reviewing their medical records for retrospective analysis. According to the diagnosis of OSAS, the pregnant women were divided into OSAS group (105 cases) and non-OSAS group (123 cases). The non-parametric Mann-Whitney U test, χ² test or Fisher's exact test were used to compare the general data and maternal and fetal outcomes between the two groups, and the occurrence of each type of HDP was further compared. Results: (1) Compared with the non-OSAS group, the median pre-pregnancy body mass index (23.6 vs 27.6 kg/m²) and the proportion of snoring [28.9% (33/114) vs 59.2% (61/103)] in the OSAS group were higher, and the differences were both statistically significant (both P<0.001). (2) The incidence of HDP [67.6% (71/105) vs 39.0% (48/123)] and gestational diabetes mellitus [GDM; 40.0% (42/105) vs 26.8% (33/123)] of pregnant women in the OSAS group were higher than those in the non-OSAS group, and the median delivery week was shorter than that in the non-OSAS group (38.4 vs 39.0 weeks). The differences were all statistically significant (all P<0.05). Between-group differences for the delivery way, postpartum hemorrhage, the rate of intensive care unit admission, preterm birth, small for gestational age infants, neonatal asphyxia, the rate of neonatal intensive care unit admission, newborn birth weight and the proportion of umbilical artery blood pH<7.00 were not statistically significant (all P>0.05). (3) Compared with the non-OSAS group, the incidence of chronic hypertension [11.4% (14/123) vs 22.9% (24/105)] and chronic hypertension with superimposed pre-eclampsia [11.4% (14/123) vs 30.5% (32/105)] were higher in the OSAS group, and the differences were both statistically significant (both P<0.01). Conclusion: OSAS is related to HDP (especially chronic hypertension and chronic hypertension with superimposed pre-eclampsia) and GDM, which could provide a practical basis for the screening, diagnosis and treatment of OSAS in pregnant women at high risk.
Infant, Newborn ; Pregnancy ; Infant ; Humans ; Female ; Pre-Eclampsia/epidemiology* ; Hypertension, Pregnancy-Induced/epidemiology* ; Retrospective Studies ; Premature Birth ; Sleep Apnea, Obstructive/epidemiology* ; Diabetes, Gestational/epidemiology*

OBJECTIVES: To investigate the characteristics of auditory processing (AP) in preschool children with attention deficit hyperactivity disorder (ADHD) using Preschool Auditory Processing Assessment Scale (hereafter referred to as "auditory processing scale"). METHODS: A total of 41 children with ADHD and 41 typically developing (TD) children were assessed using the auditory processing scale, SNAP-IV rating scale, and Conners' Kiddie Continuous Performance Test (K-CPT). The auditory processing scale score was compared between the TD and ADHD groups. The correlations of the score with SNAP-IV and K-CPT scores were assessed. RESULTS: Compared with the TD group, the ADHD group had significantly higher total score of the auditory processing scale and scores of all dimensions except visual attention (P<0.05). In the children with ADHD, the attention deficit dimension score of the SNAP-IV rating scale was positively correlated with the total score of the auditory processing scale (r_s30=0.531, P<0.05; r_s27=0.627, P<0.05) as well as the scores of its subdimensions, including auditory decoding (r_s=0.628, P<0.05), auditory attention (r_s=0.492, P<0.05), and communication (r_s=0.399, P<0.05). The hyperactivity-impulsivity dimension score of the SNAP-IV rating scale was positively correlated with the hyperactivity-impulsivity dimension score of the auditory processing scale (r_s=0.429, P<0.05). In the children with ADHD, the attention deficit dimension score of the K-CPT was positively correlated with the total score (r_s30=0.574, P<0.05; r_s27=0.485, P<0.05) and the hyperactivity-impulsivity dimension score (r_s=0.602, P<0.05) of the auditory processing scale. CONCLUSIONS Preschool children with ADHD have the risk of AP abnormalities, and the auditory processing scale should be used early for the screening and evaluation of AP abnormalities in children.
Child, Preschool ; Humans ; Attention Deficit Disorder with Hyperactivity ; Schools ; Auditory Perception

Objective: To explore the effect of growth arrest-specific5 (GAS5) inhibition on the proliferation, colony formation, invasion, migration andepithelial-mesenchymal transition(EMT), cancer cell stem of HCT-116 and its mechanism. Methods: The colorectal carcinoma (CRC) cell HCT116 was divided into blank control, negative control (NC), si-GAS5 and si-GAS5+ miR-21 inhibitor groups. The quantitative real-time polymerase chain reaction (qRT-PCR) was used to test the expressions of miR-21 and GAS5 at 48 h after transfection. The binding site of GAS5 and miR-21 was determined by luciferase reporter array. Cell proliferation ability was detected by CCK-8 assay. Cell colony ability was detected by colony formation assay. Cell invasion and migration abilities were detected by Transwell assay. Cell cycle and apoptosis were examined by flow cytometer (FCM). The protein levels of EMT associated factors including Snail, N-cadherin, vimentin, E-cadherin, stem cell related factors including CD44, SOX2, Oct2, and PTEN/Akt signal pathway associated factors were examined by western blotting. Results: The expression levels of miR-21 in blank, NC, si-GAS5 group were 1.00±0.10, 1.00±0.10, 1.80±0.20, the absorbance values were 0.51±0.02, 0.50±0.01 and 0.65±0.01, the cell clones were 90±4, 91±5, 200±8, the invaded cells were 118±3, 119±3, 150±4, the migrated cells were 110±2, 108±2, 127±2, the cell ratios in G(1) phase were (49.3±2.1)%, (50.1±2.0)% and (42.2±1.1)%, the cell ratios in S phase were (19.2±1.2)%, (20.2±1.1)% and (28.3±2.2)%, the cell apoptotic ratios were (14.4±2.2)%, (14.5±2.1)% and (7.2±1.3)%. These results indicated that inhibition of GAS5 up regulated the expression level of miR-21, promoted cell proliferation, invasion and migration, decreased G(1)-phase cells and increased S-phase cells, and suppressed cell apoptosis (P<0.05). Moreover, inhibition of GAS5 up regulated the expressions of Snail, N-cadherin, vimentin, Sox2, CD44, Oct2 and p-Akt in HCT-116 cells (P<0.05), while down regulated the expressions of E-cadherin and PTEN (P<0.05). Inhibition of miR-21 reversed the impact of GAS5 knockdown on PTEN/Akt signaling pathway (P<0.05). Conclusion: GAS5 can act as a competing endogenous RNA for miR-21, and down regulation of GAS5 can promote the development of CRC by activating the miR-21/PTEN/Akt signaling pathway and promoting the acquisition of EMT and tumor cell stemness.
Humans ; Cadherins/metabolism* ; Cell Line, Tumor ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Colorectal Neoplasms/pathology* ; Epithelial-Mesenchymal Transition/genetics* ; Gene Expression Regulation, Neoplastic ; MicroRNAs/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; PTEN Phosphohydrolase/metabolism* ; Vimentin/metabolism*

OBJECTIVES: To study the early clinical efficacy of combined therapy of stage 4 neuroblastoma. METHODS: A retrospective analysis was performed on the medical data and follow-up data of 14 children with stage 4 neuroblastoma who were diagnosed in Hong Kong University-Shenzhen Hospital from January 2016 to June 2021. RESULTS: The median age of onset was 3 years and 7.5 months in these 14 children. Among these children, 9 had positive results of bone marrow biopsy, 4 had N-Myc gene amplification, 13 had an increase in neuron-specific enolase, and 7 had an increase in vanilmandelic acid in urine. Based on the results of pathological examination, differentiated type was observed in 6 children, undifferentiated type in one child, mixed type, in one child and poorly differentiated type in 6 children. Of all the children, 10 received chemotherapy with the N7 regimen (including 2 children receiving arsenic trioxide in addition) and 4 received chemotherapy with the Rapid COJEC regimen. Thirteen children underwent surgery, 14 received hematopoietic stem cell transplantation, and 10 received radiotherapy. A total of 8 children received Ch14.18/CHO immunotherapy, among whom 1 child discontinued due to anaphylactic shock during immunotherapy, and the other 7 children completed Ch14.18/CHO treatment without serious adverse events, among whom 1 child was treated with Lu177 Dotatate 3 times after recurrence and is still undergoing chemotherapy at present. The median follow-up time was 45 months for all the 14 children. Four children experienced recurrence within 2 years, and the 2-year overall survival rate was 100%; 4 children experienced recurrence within 3 years, and 7 achieved disease-free survival within 3 years. CONCLUSIONS Multidisciplinary combined therapy is recommended for children with stage 4 neuroblastoma and can help them achieve better survival and prognosis.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child ; Child, Preschool ; Combined Modality Therapy ; Humans ; Infant ; Neuroblastoma/drug therapy* ; Positron-Emission Tomography ; Radionuclide Imaging ; Retrospective Studies ; Treatment Outcome

ObjectiveTo establish a neuroinflammation-based obesity and depression comorbidity （COM） model in mice and explore the pharmacodynamics and preliminary pharmacological mechanism of tripterine on COM mice. MethodC57BL/6J mice were randomly divided into a normal group （Chow）， a diet-induced obesity group （DIO）， and a COM group. The mice in the COM group were fed on a high-fat diet and chronically stressed with moist litter for 12 weeks to establish the COM model. C57BL/6J mice were randomly divided into a Chow group， a COM group， and a tumor necrosis factor-α（TNF-α） knock-down group. In the TNF-α knock-down group， TNF-α shRNA adeno-associated virus was injected into the amygdala through brain stereotaxis， and the expression of TNF-α in the amygdala was down-regulated. C57BL/6J mice were randomly divided into a Chow group， a DIO group， a DIO + low-dose tripterine group （0.5 mg·kg^-1）， a DIO + high-dose tripterine group （1.0 mg·kg^-1）， a COM group， a COM + low-dose tripterine group （0.5 mg·kg^-1）， and a COM + high-dose tripterine group （1.0 mg·kg^-1）. The body weight， food intake， glucose tolerance， white/brown fat ratio， serum total cholesterol （TC）， triglyceride （TG）， and high-/low-density lipoprotein cholesterol （HDL-C and LDL-C） content were recorded， and obesity of mice in each group was evaluated. Forced swimming test （FST）， tail suspension test （TST）， and open field test were used to evaluate the degree of depression of mice in each group. Immunofluorescence staining was used to detect the protein expression levels of neuropeptide Y， tryptophan hydroxylase 2 （TPH2）， and brain-derived neurotrophic factor （BDNF） in various brain nuclei of mice. Correlation analysis was used to detect the correlation of obesity and depression indexes. ResultThe comparison of the Chow group and the DIO group indicated that COM mice showed obesity and depression. To be specific， obesity was manifested as increased body weight and food intake （P<0.05， P<0.01）， as well as increased NPY expression in the central amygdala， and depression was manifested as prolonged immobility time in FST and TST （P<0.01）， and reduced TPH2-positive 5-hydroxytryptamine neurons in the dorsal raphe nucleus （DRN） and basolateral nucleus of the amygdala （BLA）. The down-regulation of TNF-α protein in BLA of COM mice shortened the immobility time in FST and TST （P<0.05， P<0.01）， increased TPH2/BDNF-positive neurons in BLA， and showed no significant changes in obesity. In DIO mice， the administration of 0.5 mg·kg^-1 tripterine for 9 days significantly decreased the 60 min blood glucose in glucose tolerance （P<0.01） and food intake （P<0.05）. In COM mice， 1.0 mg·kg^-1 tripterine was administered for 14 days to significantly decrease 30 min blood glucose in glucose tolerance （P<0.01）， and food intake （P<0.05）， and immobility time in TST （P<0.01）， increase TPH2-BDNF double-labeled cells in BLA and DRN， and reduce the area of TMEM119-stained cells. ConclusionThe model of obesity and depression comorbidity can be properly induced in mice under the condition of dual stress of energy environment. Tripterine can effectively interfere with obesity-depression comorbidity， and its mechanism may be related to the inhibition of central nervous system inflammation.