Objective: To explore the early effects of birth weight at different gestational ages on blood pressure trajectory among primary school students, so as to provide evidence for incorporating gestational age birth weight into individualized early warning and intervention strategies for childhood hypertension. Methods: From May to November 2023, a purposeful sampling method was used to recruit 1 676 students in grade 1-3 from three primary schools in a certain urban district of Chongqing. Follow up assessments were conducted in May 2024(T1), November 2024(T2), and May 2025(T3). General demographic and birth related information were collected via self administered questionnaires, while height, weight and blood pressure were obtained through physical examinations. Linear mixed effects model was used to analyze the associations between birth weight at different gestational ages and blood pressure trajectories. Results: During the T1-T3 period, the systolic blood pressure of boys were 98.5 (93.0, 104.5 ),98.5 (93.5, 105.0), and 97.5 (92.5, 103.5)mmHg, respectively, while the diastolic blood pressure were 60.5 (56.5, 65.0), 61.5 ( 57.0 , 65.5), and 60.0 (56.0, 64.0)mmHg, respectively. For girls, the systolic blood pressure were 95.5 (90.0, 102.0),95.5 (90.5, 101.5), and 96.0 (90.5, 101.5)mmHg, respectively, and the diastolic blood pressure were 60.5 (56.0, 64.5 ),61.5 (57.5, 65.5), and 59.5 (56.0, 63.0)mmHg, respectively. Through Friedman test within both boys and girls, diostolic blood pressure were statistically significant across three measurements( χ 2=48.85，81.54，both P <0.01). The proportion of normal blood pressure increased , and the proportion of prehypertension and hypertension decreased with time( χ 2=39.72，25.62，both P < 0.01 ). Linear mixed effects model analysis revealed that after adjusting for age, sex, household income monthly, parental education, family history of hypertension and maternal pregnancy complications, large for gestational age had significantly higher trajectories of systolic ( β = 1.50) and diastolic( β =0.94) blood pressure compared to appropriate for gestational age(both P <0.01). Conclusion Large for gestational age is associated with elevated blood pressure trajectories during school age, and it may be considered as an early indicator for individualized screening and intervention for childhood hypertension.

ObjectiveTo evaluate the impact of yang-reinforcing and blood-activating therapy on the long-term prognosis for patients with dilated cardiomyopathy （DCM） of yang deficiency and blood stasis syndrome. MethodsA retrospective cohort study was conducted involving 371 DCM patients with yang deficiency and blood stasis syndrome. The yang-reinforcing and blood-activating therapy was defined as the exposure factor. Patients were categorized into exposure group （186 cases） and non-exposure group （185 cases） according to whether they received yang-reinforcing and blood-activating therapy combined with conventional western medicine for 6 months or longer. The follow-up period was set at 48 months， and the Kaplan-Meier survival analysis was used to assess the cumulative incidence of major adverse cardiovascular events （MACE） in both groups. Cox regression analysis was used to explore the impact of yang-reinforcing and blood-activating therapy on the risk of MACE， and subgroup analysis was performed. Changes in traditional Chinese medicine （TCM） syndrome score， left ventricular ejection fraction （LVEF）， left ventricular fractional shortening （LVFS）， left ventricular end-diastolic diameter （LVEDD）， and Minnesota Living with Heart Failure Questionnaire （MLHFQ） score were compared between groups at the time of first combined use of yang-reinforcing and blood-activating therapy （before treatment） and 1 year after receiving the therapy （after treatment）. ResultsMACE occurred in 31 cases （16.67%） in the exposure group and 47 cases （25.41%） in the non-exposure group. The cumulative incidence of MACE in the exposure group was significantly lower than that in the non-exposure group ［HR=0.559， 95%CI（0.361，0.895）， P=0.014］. Cox regression analysis showed that yang-reinforcing and blood-activating therapy was an independent factor for reducing the risk of MACE in DCM patients ［HR=0.623， 95%CI（0.396，0.980）， P=0.041］， and consistent results were observed in different subgroups. Compared with pre-treatment， the exposure group showed decreased TCM syndrome score and MLHFQ score， reduced LVEDD， and increased LVEF and LVFS after treatment （P＜0.05）； in the non-exposure group， TCM syndrome score decreased， LVEF and LVFS increased， and LVEDD reduced after treatment （P＜0.05）. After treatment， the exposure group had higher LVEF and LVFS， smaller LVEDD， and lower TCM syndrome score and MLHFQ score compared with the non-exposure group （P＜0.05）. ConclusionCombining yang-reinforcing and blood-activating therapy with conventional western medicine can reduce the risk of MACE in DCM patients with yang deficiency and blood stasis syndrome， meanwhile improving their clinical symptoms， cardiac function， and quality of life.

ObjectiveThis paper aims to clarify the material basis of Gualou Niubangtang and establish a quantitative analysis method for its main constituents， providing a reference for the overall quality control of this preparation. MethodsThe constituents in the formula were systematically characterized based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry （UPLC-Q-TOF-MS/MS）. Identification was performed by matching with the UNIFI 9.6 software and utilizing database platforms such as PubChem， ChemicalBook， and ChemSpider， combined with relevant literature reports. A quantitative analysis method for the seven main constituents in Gualou Niubangtang was established by using high performance liquid chromatography （HPLC）. ResultsUPLC-Q-TOF-MS/MS analysis identified 155 constituents， including 69 flavonoids， 36 terpenoids， 23 phenylpropanoids， 8 phenylethanoid glycosides， and 19 other types of constituents. In the established quantitative analysis method， the seven main constituents showed good linearity within their respective linear ranges. The precision， repeatability， stability， and spike recovery all met the required standards. The results showed that the content ranges of geniposide， liquiritin， hesperidin， arctiin， baicalin， oroxylin A-7-O-β-D-glucuronide， and wogonoside in 15 batches of Gualou Niubangtang were 13.67-21.25， 1.20-7.64， 5.45-7.45， 22.97-33.51， 29.95-39.07， 2.58-4.80， and 6.56-9.31 mg·g^-1， respectively. ConclusionThis study successfully characterizes and attributes multi-category constituents in Gualou Niubangtang， clarifying that its material basis is primarily composed of flavonoids， terpenoids， phenylethanoid glycosides， and phenylpropanoids. Furthermore， it enables the quantification of seven constituents within the formula. This work lays a foundation for research on the quality control， action mechanism， and clinical application of this formula.

Objective To investigate the role and mechanism of paeoniflorin(PF)in sepsis-associated acute kidney injury(SA-AKI)in mice.Methods Mouse SA-AKI model was constructed by intraperitoneal injection of 15 mg/kg LPS.Twenty-four male C57BL/6J mice(6～8 weeks old,weighing 20～25 g)were randomly divided into Control group,model group,PF group(intraperitoneally injected with 50 mg/kg PF 30 min before LPS administration),and β-catenin specific agonist BML284 group(10 mg/kg BML284 by intraperitoneal injection after 50 mg/kg PF administration).The renal histopathological changes were observed by HE staining and Paller scoring.ELISA was used to determine the contents of serum creatinine(Scr),neutrophil gelatinase-associated lipocalin(NGAL)and lactate,and renal contents of hexokinase 2(HK2),lactate dehydrogenase A(LDHA),IL-1β and IL-18.Western blotting was performed to detect the expression of total β-catenin,p-β-cateninY654,nucleus β-catenin and c-Myc.Results Compared with the Control group,the LPS group showed obviously damaged renal tissue,higher Paller score(P＜0.05),increased serum Scr and NGAL levels(P＜0.05),elevated renal contents of aerobic glycolytic indexes such as HK2,LDHA and serum lactate,as well as contents of IL-1β and IL-18(P＜0.05),and enhanced expression of total β-catenin,p-β-cateninY654,nucleus β-catenin and c-Myc in the renal tissue(P＜0.05).PF treatment attenuated the renal tissue damage,decreased Paller score(P＜0.05),reduced serum Scr and NGAL levels(P＜0.05),HK2,LDHA and serum lactate levels,and contents of IL-1 β and IL-18 in renal tissues(P＜0.05),and down-regulated the renal expression of total β-catenin,p-β-cateninY654,nucleusβ-catenin and c-Myc when compared with the levels in the model group(P＜0.05).While,addition of BML284 reversed above effects of PF treatment with significant differences(P＜0.05).Conclusion PF can alleviate SA-AKI,and its mechanism may be through its inhibiting the β-catenin/c-Myc pathway,thus reducing the aerobic glycolysis level and inflammatory response in renal tissue.

Objective To investigate the effects of paeoniflorin(PF)on lipopolysaccharide(LPS)-induced aerobic glycolysis in renal tubular epithelial cell line HK-2 and its underlying mechanism of action.Methods This study consists of a preliminary experiment and a formal experiment.Preliminary experiment:CCK-8 assay and RT-qPCR were used respectively to measure cell viability and mRNA expression levels of inflammatory factors in HK-2 cells after LPS stimulation to determine the optimal LPS concentration for modeling as well as to evaluate the toxicity of PF and screen for its appropriate concentration.Formal experiment:HK-2 cells were divided into control group(CON group),LPS group,LPS+PF group and LPS+PF+740Y-P group.LPS was used to establish a cell model of sepsis associated-acute kidney injury(SA-AKI)in HK-2 cells,and then the cell model was treated with PF and PI3K activator 740Y-P,correspondingly for 24 h.CCK-8 assay was employed to detect cell viability,and Extracellular Acidification Rate(ECAR)Kit was utilized to measure the rate.The contents of IL-1β,IL-18,lactic acid(Lac)and lactate dehydrogenase A(LDHA)were determined with ELISA.Western blotting was applied to detect the expression of p-PI3K,p-AKT,HIF-1α,pyruvate kinase 2(PKM2,a key enzyme in aerobic glycolysis)and NOD-like receptor thermal protein domain associated protein 3(NLRP3),and immunofluorescence assay was performed to observe the expression and distribution of PKM2.Results ① Our preliminary experiment identified that the optimal concentration of LPS for modeling was 20.0 μg/mL,a safe dosage range of PF was 0～100.0 μmol/L,and its optimal therapeutic concentration was 25.0 μmol/L.② Compared with the CON group,LPS stimulation resulted in significantly decreased cell viability(P<0.05),increased ECAR(P<0.05),elevated contents of IL-1β,IL-18,Lac and LDHA(P<0.05),up-regulated protein levels of p-PI3K,p-AKT,HIF-1α,p-PKM2 and NLRP3(P<0.05),and enhanced fluorescence intensity of PKM2 in the nucleus of cells(P<0.05).Compared with the model group,PF treatment reversed all above effects induced by LPS stimulation(all P<0.05).Compared with the LPS+PF group,in the LPS+PF+740Y-P group,ECAR was elevated(P<0.05),the contents of IL-1β,IL-18,Lac and LDHA were increased(P<0.05),and the relative expression levels of p-PI3K,p-AKT,HIF-1α,p-PKM2 and NLRP3 were increased(P<0.05),and the fluorescence intensity of PKM2 was strengthened(P<0.05)and enhanced in the nucleus(P<0.05).Conclusion PF reduces aerobic glycolysis in HK-2 cells and alleviates the inflammatory response by inhibiting the PI3K/AKT/HIF-1α signaling pathway.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

BackgroundIn recent years， the incidence of non-suicidal self-injury （NSSI） behaviors among adolescents has been increasing annually. Self-esteem and alexithymia are strongly associated with NSSI behaviors， and alienation is closely linked to both self-esteem and alexithymia. However， there is limited research on the relationship between alienation and NSSI behaviors among adolescents in China. ObjectiveTo analyze the relationship between alienation and NSSI behaviors among adolescents， and to explore the factors influencing NSSI behaviors in this population， so as to provide insights for the prevention and treatment of NSSI behaviors in adolescents. MethodsAdolescents admitted to the Department of Psychiatry and Psychology at the 923^rd Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army from September 1， 2021 to March 1， 2023， who met the diagnostic criteria for NSSI in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）， were selected as the study group （n=60）. Concurrently， middle school students from Nanning were recruited as the control group （n=60）. Participants were assessed using Adolescent Self Harm Scale （ASHS）， Rosenberg Self-Esteem Scale （RSES）， Toronto Alexithymia Scale （TAS） and Adolescent Students′ Alienation Scale （ASAS）. Pearson correlation analysis was employed to examine the relationships between scale scores in the study group， and Logistic regression analysis was used to identify the influencing factors of NSSI behaviors among adolescents. ResultsThe RSES score of the study group was significantly lower than that of the control group （t=-7.033， P<0.01）. The TAS and ASAS scores of the study group were significantly higher than those of the control group （t=5.591， 8.124， P<0.01）. The ASHS score was negatively correlated with RSES score （r=-0.410， P<0.01） and positively correlated with ASAS score （r=0.555， P<0.01）. The RSES scores of the study group were negatively correlated with TAS and ASAS scores （r=-0.317， -0.590， P<0.05 or 0.01）. Logistic regression analysis showed that being female （OR=0.714， 95% CI： 0.042~0.709） was a protective factor for NSSI behaviors among adolescents， while high alienation （OR=1.028， 95% CI： 1.013~1.043） and residing in rural areas （OR=6.692， 95% CI： 2.038~21.967） were risk factors for NSSI behaviors among adolescents. ConclusionAlienation was positively correlated with NSSI behaviors in adolescents. Female adolescents had a lower risk of NSSI behaviors， while those with higher levels of alienation or residing in rural areas were more prone to NSSI behaviors. ［Funded by Self-financed Scientific Research Project of the Health Commission of Guangxi Zhuang Autonomous Region （number， Z20210656）； Self-financed Scientific Research Project of the Health Commission of Guangxi Zhuang Autonomous Region （number， Z-A20231057）］

Objective To screen long non-coding RNA(lncRNA)associated with lymph node metasta-sis in papillary thyroid carcinoma(PTC)and verify its function in vitro,so as to provide a theoretical basis for elucidating the molecular mechanism of lymph node metastasis in PTC.Methods lncRNA+mRNA microar-ray was used to detect the differential expression of lncRNA and mRNA in PTC cancer tissues with and with-out lymph node metastasis.Real time fluorescence quantitative PCR(qPCR)verified target differential lncR-NAs.Lentivirus was used as vector to construct high and low lncRNA expression PTC cell lines.Cell counting kit-8(CCK-8),cell scratches assay,Transwell assay,cell clone formation assay were used to detect the effects of target lncRNA on proliferation,migration,invasion,clonal formation of PTC cells.Results Compared with 5 cases of PTC tissues without lymph node metastasis,gene chips detected 119 lncRNA and 53 mRNA expres-sion levels upregulated,while 263 lncRNA and 198 mRNA expression levels down regulated in 5 cases of PTC tissues with lymph node metastasis.Furthermore,21 lncRNAs were selected for validation in the original 10 PTC samples,and the results showed that,compared with PTC tissues without lymph node metastasis,lncR-NAs FLJ20444,DPP10-AS1 and ENST00000567197 were highly expressed in PTC tissues with lymph node metastasis,while uc021thd.1,LNC00944,ENST00000429730 and BLNK were lowly expressed(P＜0.05).In addition,qPCR results of another 30 fresh PTC tissues showed that compared with PTC tissues without lymph node metastasis,DPP10-AS1 was highly expressed and LNC00944 was lowly expressed in PTC tissues with lymph node metastasis(P＜0.05).Cell function experiments showed that the proliferation,migration,invasion,and colony formation abilities of PTC cells in the DPP10-AS1 high expression group were higher than those in the DPP10-AS1 low expression group,and the differences were statistically significant(P＜0.05).Conclusion lncRNA DPP10-AS1 may play a role in PTC metastasis through certain signaling pathways.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Sexual dimorphism in the brain underlies behavioral differences between sexes. The bed nucleus of the stria terminalis (BNST) is a complex nucleus that differs between males and females, but the sexual dimorphism in cytoarchitecture and the connectome of its oval subdivision (ovBNST) remains largely unexplored. By combining snRNA-seq and transgenic labeling, we found a higher density of ovBNST proenkephalin (ovBNST^PENK) neurons in male than female mice. Anatomically, we virally mapped the efferents and afferents of ovBNST^PENK neurons, finding reciprocally dimorphic connections with the hypothalamus and striatum. Gene enrichment analysis suggests that ovBNST^PENK neurons are modulated by the upstream dopamine pathway. Functionally, by applying caspase-3-mediated depletion of ovBNST^PENK neurons, we found that loss of these neurons enhanced locomotor activity in male but not female mice, without altering the anxiety-like phenotypes in either sex. Our study may pave the way for a better understanding of the anatomical and functional profiles of ovBNST^PENK neurons from a sexually dimorphic perspective.
Animals ; Male ; Female ; Septal Nuclei/physiology* ; Sex Characteristics ; Neurons/physiology* ; Enkephalins/metabolism* ; Mice ; Mice, Transgenic ; Protein Precursors/metabolism* ; Mice, Inbred C57BL ; Neural Pathways/physiology*