Clinical death refers to the permanent cessation of life functions. This article reviews the definition of clinical death and the various scenarios in which it occurs, classifies the process of clinical death, and discusses the criteria for determining uncontrollable cardiac death, controllable cardiac death and the criteria and workflow for determining brain death. It elaborates on the relationship between brain death and death, and proposes the areas to note when standardizing the medical documentation of death cases. Based on this, it introduces the content of the management system and workflow construction for death determination in medical institutions, including management structure, personnel qualifications, document norms, quality control system and training mechanism. Paying attention to the construction of the management system and workflow for death determination in medical institutions is of great significance for ensuring medical quality and safety, promoting the healthy development of organ donation, and maintaining the seriousness of legal and ethical practices.

Objective: To investigate the associations between childhood obesity and performance of six minute walk test (6MWT), providing evidence for exercise tolerance assessment and exercise intervention strategies for children and adolescents. Methods: From March 2021 to December 2023, a cohort study was conducted among students recruited from a primary and secondary school in Chongqing, a total of 709 valid samples were included. The 6MWT was used to assess exercise tolerance, with vital signs measured before and after the test. Anthropometric indicators, including height, weight, and waist circumference, were measured using standardized procedures. Generalized additive models (GAM) and restricted cubic spline (RCS) regression were employed to analyze the nonlinear relationships between obesity related indicators and six minute walk distance (6MWD). Results: The mean 6MWD of participants was (602.59±70.73)m. GAM showed that after adjusting for confounding factors, body mass index (BMI) and weight had non linear relationships with 6MWD [effective degrees of freedom were 1.55 and 7.13 respectively], and overweight/obesity was associated with a decrease in 6MWD ( β =-18.65) (all P <0.01). Further RCS regression analysis showed that both BMI and weight showed an "inverted U shaped" non linear relationship with 6MWD in the overall population and sex stratified subgroups; the 6MWD of females was lower than that of males, and it showed a significant downward trend with the increase of BMI or weight (all P <0.05). Conclusion Body weight and BMI in children and adolescents have an important impact on 6MWD, and obesity in children and adolescents is markedly associated with decline in exercise tolerance.

Objective: To investigate the association between body weight standardized vitamin B intakes and blood pressure among school aged children, so as to provide evidence for developing dietary guidance and intervention strategies of promoting healthy blood pressure in children. Methods: The data were derived from a pediatric health cohort established in both urban and rural areas of Chongqing. A total of 1 368 primary school students in grades one to three were recruited for the baseline survey between October and November 2014 by using a stratified cluster random sampling design. From February to March 2019, 1 283 participants completed the first follow up assessment. Dietary intake and sociodemographic characteristics were assessed using a food frequency questionnaire and a self administered questionnaire. Blood pressure, height, weight, and other anthropometric indicators were measured. Body weight standardized intakes of six B vitamins(B 1, B 2, B 3, B 6, B 9, and B 12 )were categorized into tertiles( T1-T 3). Linear mixed effects models were applied to examine the associations between body weight standardized vitamin B intakes and changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP). In addition, mixed effects Logistic regression models were used to assess the risk of elevated blood pressure. Results: Linear mixed effects model regression analyses showed that, after adjusting for potential confounders including age, sex, and family history of obesity, body weight standardized B vitamin intake was negatively associated with SBP, DBP, and MAP in school aged children ( β =-7.79 to -0.68, all P <0.05). Results from the mixed effects Logistic regression models showed that, compared with the T 1 group, children in the T 3 group had a lower risk of elevated blood pressure for vitamin B 1 ( OR=0.40, 95%CI =0.25-0.64), B 2 ( OR=0.36, 95%CI =0.23-0.58), B 3 ( OR=0.47, 95%CI =0.31-0.72, B 6 ( OR=0.37, 95%CI =0.22-0.60), B 9 ( OR=0.36, 95%CI =0.21-0.60), and B 12 ( OR= 0.56 , 95%CI =0.37-0.86)(all P <0.05). Conclusions Body weight standardized B vitamins were associated with changes in blood pressure levels and the risk of elevated blood pressure among school aged children. Ensuring sufficient dietary intakes of vitamin B may help prevent and control of abnormal blood pressure in children.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

OBJECTIVES: To explore the mechanism by which Pulsatilla saponin D (PSD) inhibits invasion and metastasis of triple-negative breast cancer (TNBC). METHODS: The public databases were used to identify the potential targets of PSD and the invasion and metastasis targets of TNBC to obtain the intersection targets between PSD and TNBC. The "PSD-target-disease" interaction network was constructed and protein-protein interaction (PPI) analysis was performed to obtain the core targets, which were analyzed for KEGG pathway and GO functional enrichment. Molecular docking study of the core targets and PSD was performed, and the therapeutic effect and mechanism of PSD were verified using Transwell assay and Western blotting in cultured TNBC cells. RESULTS: Network pharmacology analysis identified a total of 285 potential PSD targets and 26 drug-disease intersection core targets. GO analysis yielded 175 entries related to the binding of biomolecules (protein, DNA and RNA), enzyme activities, and regulation of gene transcription. KEGG analysis yielded 46 entries involving pathways in cancer, chemical carcinogenesis-receptor activation, microRNAs in cancer, chemical carcinogenesis-reactive oxygen species, PD-L1 expression and PD-1 checkpoint pathway in cancer. Molecular docking showed high binding affinities of PSD to MTOR, HDAC2, ABL1, CDK1, TLR4, TERT, PIK3R1, NFE2L2 and PTPN1. In cultured TNBC cells, treatment with PSD significantly inhibited cell invasion and migration and lowered the expressions of MMP2, MMP9, N-cadherin and the core proteins p-mTOR, ABL1, TERT, PTPN1, HDAC2, PIK3R1, CDK1, TLR4 as well as NFE2L2 expressionin the cell nuclei. CONCLUSIONS The inhibitory effects of PSD on TNBC invasion and metastasis are mediated by multiple targets and pathways.
Humans ; Triple Negative Breast Neoplasms/metabolism* ; Saponins/pharmacology* ; Pulsatilla/chemistry* ; Female ; Molecular Docking Simulation ; Cell Line, Tumor ; Neoplasm Invasiveness ; Protein Interaction Maps ; Neoplasm Metastasis ; Signal Transduction/drug effects* ; Cell Movement/drug effects*

OBJECTIVES: To explore the molecular mechanism by which lncRNA SNHG15 regulates proliferation, invasion and migration of lung adenocarcinoma cells. METHODS: The lncRNA microarray chip dataset GSE196584 and LncBase were used to predict the lncRNAs that interact with miR-30b-3p, and their association with patient prognosis were investigated using online databases, after which lncRNA nucleolar RNA host gene 15 (SNHG15) was selected for further analysis. The subcellular localization of lncRNA SNHG15 and its expression levels in normal human lung epithelial cells and lung adenocarcinoma cell lines were detected using fluorescence in situ hybridization and qRT-PCR. In cultured A549 cells, the changes in cell proliferation, migration, and invasion following transfection with a SNHG15 knockdown plasmid (sh-SNHG15), a miR-30b-3p inhibitor, or their co-transfection were assessed with EdU, wound healing, and Transwell assays. Bioinformatics analyses were used to predict the regulatory relationship between lncRNA SNHG15 and COX6B1, and the results were verified using Western blotting and rescue experiments in A549 cells transfected with sh-SNHG15, a COX6B1-overexpressing plasmid, or both. RESULTS: LncRNA SNHG15 was shown to target miR-30b-3p, and the former was highly expressed in lung adenocarcinoma, and associated with a poor patient prognosis. LncRNA SNHG15 was localized in the cytoplasm and expressed at higher levels in A549 and NCI-H1299 cells than in BEAS-2B cells. In A549 cells, lncRNA SNHG15 knockdown significantly inhibited cell migration, invasion and proliferation, and these changes were reversed by miR-30b-3p inhibitor. A regulatory relationship was found between lncRNA SNHG15 and COX6B1, and their expression levels were positively correlated (r=0.128, P=0.003). MiR-30b-3p knockdown obviously decreased COX6B1 expression in A549 cells, and COX6B1 overexpression rescued the cells from the inhibitory effects of lncRNA-SNHG15 knockdown. CONCLUSIONS LncRNA SNHG15 may compete with COX6B1 to bind miR-30b-3p through a ceRNA mechanism to affect proliferation, migration, and invasion of lung adenocarcinoma cells.
Humans ; MicroRNAs/metabolism* ; RNA, Long Noncoding/genetics* ; Cell Proliferation ; Cell Movement ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung ; Neoplasm Invasiveness ; A549 Cells ; Adenocarcinoma/genetics* ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor

Objective:To investigate the effects of a low-energy balanced diet combined with exercise intervention on glycolipid metabolism levels in children with simple obesity.Methods:A prospective randomized controlled trial was performed in this study. Forty children with simple obesity who attended the pediatric outpatient department of Tangshan Maternal and Child Health Care Hospital in Hebei Province from January 2022 to January 2024 were selected and randomly divided into two groups using a random number table: an observation group ( n=22) and a control group ( n=18). No weight-loss products were used by any children in either group. The control group received exercise intervention alone, while the observation group received a combined intervention of exercise and a low-energy balanced diet. The intervention lasted for 8 weeks for both groups. The differences in energy intake during the intervention, as well as body weight, body mass index (BMI), waist circumference, fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), total cholesterol (TC), and adiponectin levels before and after the intervention were compared between the two groups. Measurement data with normal distribution were expressed as Mean±SD, inter-group comparisons were performed by independent samples t-test, and within-group comparisons before and after treatment were performedby paired t-test. Counting data were expressed as case (%), and inter-group comparisons were performed by χ2 test. Results:The energy intake during the intervention was lower in the observation group than in the control group [(1 450±180) kcal/d vs. (1 780±205) kcal/d, t=-5.35, P<0.001]. Before the intervention, there were no statistically significant differences in body weight, BMI and waist circumference between the two groups (all P>0.05). After 8 weeks of intervention, body weight, BMI, and waist circumference decreased significantly compared to pre-intervention levels in both groups [Control group: (62±12) kg vs. (64±13) kg, (26.4±2.9) kg/m 2 vs. (27.9±3.4) kg/m 2, (85±7) cm vs. (91±7) cm, t=7.23, 9.07, 12.31, respectively, all P<0.001; Observation group: (59±16) kg vs. (65 ± 17) kg, (23.3±4.3) kg/m 2 vs. (28.5±4.1) kg/m 2, (82±9) cm vs. (92±10) cm, t=24.90, 17.93, 21.40, respectively, all P<0.001]. Furthermore, the post-intervention values for body weight, BMI, and waist circumference were significantly lower in the observation group than in the control group ( t=-10.89, -18.92, -5.16, respectively, all P<0.001). Before the intervention, there were no statistically significant differences in FBG, FINS, TG, TC, or adiponectin levels between the two groups (all P>0.05). After 8 weeks of intervention, FBG, FINS, TG, and TC levels decreased significantly compared to pre-intervention levels in both groups [Control group: (4.99±0.26) mmol/L vs. (5.22±0.27) mmol/L, (24±6) mU/L vs. (26±8) mU/L, (1.3±0.5) mmol/L vs. (1.5±0.4) mmol/L, (4.3±0.6) mmol/L vs. (4.5±0.6) mmol/L, t=19.75, 6.69, 7.64, 18.27, respectively, all P<0.001; Observation group: (4.64±0.34) mmol/L vs. (5.31±0.26) mmol/L, (16±5) mU/L vs. (21±10) mU/L, (1.0±0.3) mmol/L vs. (1.4±0.5) mmol/L, (4.0±0.8) mmol/L vs. (4.5±0.8) mmol/L, t=19.66, 8.82, 11.26, 22.68, respectively, all P<0.001]. Adiponectin levels increased significantly in both groups [Control group: (8.0±1.2) mg/L vs. (6.8±1.1) mg/L , t=8.38, P<0.001; Observation group: (8.8±1.1) mg/L vs. (6.8±1.2) mg/L, t=23.78, P<0.001], while the improvements in all these glycolipid metabolic parameters were significantly greater in the observation group than in the control group ( t=3.70, 2.76, 2.42, 2.22,2.14, P=0.001, 0.009, 0.020, 0.027, 0.039). Conclusion:The combined intervention of a low-energy balanced diet and exercise can reduce body weight, blood glucose, and blood lipid levels in obese children, thereby improving their glycolipid metabolism.

Objective:To explore the clinical phenotypes and genetic characteristics of a pedigree with Distal arthrogryposis type 5D (DA5D) caused by compound heterozygous variants in the ECEL1 gene. Methods:A child (proband) diagnosed with DA5D and his family members (proband′s parents and sister) who was admitted to the Department of Rehabilitation Medicine of Henan Children′s Hospital in July 2022 due to " multiplex distal arthrogryposis" were enrolled into this study. Clinical data of the proband were collected and peripheral blood samples were obtained from the proband and members of his family about 3 mL. Trio-whole genome sequencing (trio-WGS) was carried out to detected the genetic variations of the proband and his family members. The candidate′s pathogenic gene variants were screened and analyzed by Genome Aggregation Database (gnomAD) and other databases. The screened variants wer annotated for clinical phenotypes using databases like the Online Mendelian Inheritance in Man (OMIM). The pathogenicity of the candidate variants was predicted by bioinformatics tools such as Provean. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), pathogenicity ratings were conducted for variant sites. The protein conservation and mutation structure prediction of ECEL1 protein among species were carried out though MEGA-X and PyMOL. The research protocol of this study was reviewed by the Ethics Committee of Henan Provincial Children′s Hospital (Approval No. 2023-H-H01), and informed consent for clinical research was obtained from the guardians of the probands.Results:The proband had multiplex distal arthrogryposis involving hands, feet, knees, and ankles, and had right ptosis, micrognathia, low auricular position, and upturned nose. The parents and sister both had normal phenotypes. Trio-WGS and Sanger sequencing revealed that the child had compound heterozygous variants of paternal c. 1742_c.1743insT and maternal c. 2314T>G, for which the father and sister were carriers of the c. 1742_c.1743insT heterozygous variant and the mother was carrier of c. 2314T>A. Neither mutation site has been reported. According to guidelines of ACMG, the c. 1742_c.1743insT variant was classified as likely pathogenic (PSV1+ PM2_Supporting), and c. 2314T>G was classified as uncertain (PM2_Supporting+ PM3+ PP3). The results of conserved analysis of amino acid residue sequences of ECEL1 protein showed that the missense mutation of the maternal c. 2314T>G(p.Cys772Gly) was highly conserved among humans and other seven species. The protein structure prediction revealed that the c.1742_c.1743insT frameshift mutation led to the protein truncation, and the c. 2314T>G missense mutation resulted in the failure of forming 1 disulfide bond.Conclusion:The compound heterozygous variants of ECEL1 gene were considered to be pathogenic for this DA5D patient, which have expanded the mutational spectrum of the ECEL1 gene and provided a reference for clinical diagnosis as well as genetic counseling for this family.