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.

ObjectiveThrough qualitatively and quantitatively analysis of the differences in chemical composition between the combined decoction and single decoction of Huaganjian and comparison of their core efficacy， to explore the rationality of the flexible clinical application of Huaganjian compound preparations and single-flavored dispensing granules. MethodsUltra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to qualitatively analyze the combined decoction and single decoction samples of Huaganjian， and meanwhile， the contents of four index components（geniposide， paeoniflorin， hesperidin and paeonol） were quantitatively analyzed by high performance liquid chromatography（HPLC）. Nonalcoholic fatty liver disease（NAFLD） rat model induced by high-fat diet was applied to compare the efficacy of combined decoction and single decoction of Huaganjian. A total of 30 male SD rats were randomly divided into the control group， model group， lovastatin group（1.8 mg·kg^-1）， combined decoction group（1.26 g·kg^-1） and single decoction group（1.18 g·kg^-1）. After successful modeling， lovastatin group， combined decoction group and single decoction group were given corresponding doses of drugs by intragastric administration every day， and the control group and model group were given equal amounts of normal saline by intragastric administration， after 4 weeks of administration， the serum and liver tissues were collected， and the contents of alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， total cholesterol（TC）， triglyceride（TG）， low-density lipoprotein cholesterol（LDL-C） and high-density lipoprotein cholesterol（HDL-C） in serum of rats were detected， and the liver pathological examination was carried out by hematoxylin-eosin（HE） staining and oil red O staining， so as to compare differences of their efficacy. ResultsSeventy chemical components were initially identified and attributed from the lyophilized powder of the combined decoction and single decoction samples of Huaganjian， and there was no obvious difference in composition between the two. Further quantitative analysis showed that the contents of geniposide， paeoniflorin， hesperidin and paeonol in the combined decoction samples were significantly increased when compared with those of the single decoction samples（P<0.01）. The pharmacodynamic results showed that compared with the model group， both the combined and single decoction groups of Huaganjian could improve the liver index of NAFLD rats， reduce the serum levels of AST， ALT， TC， TG and LDL-C， increase the serum level of HDL-C， and ameliorate the pathological changes of liver cell steatosis and fat accumulation. However， there was no significant difference in pharmacodynamic effects between the combined decoction group and the single decoction group. ConclusionThere is no significant difference between the combined decoction and single decoction of Huaganjian in terms of chemical composition， but the contents of the four index components show significantly difference. Both of them can significantly improve the fat accumulation and liver function in NAFLD rats. This study provides a reference basis for the rational clinical application and evaluation of famous classical formula compound preparations and single-flavored dispensing granules.

This study aims to explore the protective effect of Chaihu Jia Longgu Muli Decoction on rats with heart failure after myocardial infarction, and to clarify its possible mechanisms, providing a new basis for basic research on the mechanism of classic Chinese medicinal formula-mediated inflammatory response in preventing and treating heart failure induced by apoptosis after myocardial infarction. A heart failure model after myocardial infarction was established in rats by coronary artery ligation. The rats were divided into sham group, model group, and low, medium, and high-dose groups of Chaihu Jia Longgu Muli Decoction, with 10 rats in each group. The low-dose, medium-dose, and high-dose groups of Chaihu Jia Longgu Muli Decoction were given 6.3, 12.6, and 25.2 g·kg~(-1) doses by gavage, respectively. The sham group and model group were given an equal volume of distilled water by gavage once daily for four consecutive weeks. Cardiac function was assessed using color Doppler echocardiography. Myocardial pathology was detected by hematoxylin-eosin(HE) staining, apoptosis was measured by TUNEL assay, and mitophagy was observed by transmission electron microscopy. The levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, and N-terminal pro-B-type natriuretic peptide(NT-proBNP) in serum were detected by enzyme-linked immunosorbent assay(ELISA). The expression of apoptosis-related proteins B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), and cleaved caspase-3 was detected by Western blot. Additionally, the expression of phosphorylated nuclear transcription factor-κB(NF-κB) p65(p-NF-κB p65)(upstream) and nuclear factor kappa B inhibitor alpha(IκBα)(downstream) in the NF-κB signaling pathway was assessed by Western blot. The results showed that compared with the sham group, left ventricular ejection fraction(LVEF) and left ventricular short axis shortening(LVFS) in the model group were significantly reduced, while left ventricular end diastolic diameter(LVEDD) and left ventricular end systolic diameter(LVESD) increased significantly. Myocardial tissue damage was severe, with widened intercellular spaces and disorganized cell arrangement. The apoptosis rate was increased, and mitochondria were enlarged with increased vacuoles. Levels of TNF-α, IL-1β, and NT-proBNP were elevated, indicating an obvious inflammatory response. The expression of pro-apoptotic factors Bax and cleaved caspase-3 increased, while the anti-apoptotic factor Bcl-2 decreased. The expression of p-NF-κB p65 was upregulated, and the expression of IκBα was downregulated. In contrast, the Chaihu Jia Longgu Muli Decoction groups showed significantly improved of LVEF, LVFS and decreased LVEDD, LVESD compared to the model group. Myocardial tissue damage was alleviated, and intercellular spaces were reduced. The apoptosis rate decreased, mitochondrial volume decreased, and the levels of TNF-α, IL-1β, and NT-proBNP were lower. The expression of pro-apoptotic factors Bax and cleaved caspase-3 decreased, while the expression of the anti-apoptotic factor Bcl-2 increased. Additionally, the expression of p-NF-κB p65 decreased, while IκBα expression increased. In summary, this experimental study shows that Chaihu Jia Longgu Muli Decoction can reduce the inflammatory response and apoptosis rate in rats with heart failure after myocardial infarction, which may be related to the regulation of the IκBα/NF-κB signaling pathway.
Animals ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Myocardial Infarction/physiopathology* ; Male ; NF-kappa B/genetics* ; Heart Failure/etiology* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; NF-KappaB Inhibitor alpha/genetics* ; Humans ; Tumor Necrosis Factor-alpha/genetics*

OBJECTIVE: To assess the cardioprotective effect and impact of Qishen Granules (QSG) on different ischemic areas of the myocardium in heart failure (HF) rats by evaluating its metabolic pattern, substrate utilization, and mechanistic modulation. METHODS: In vivo, echocardiography and histology were used to assess rat cardiac function; positron emission tomography was performed to assess the abundance of glucose metabolism in the ischemic border and remote areas of the heart; fatty acid metabolism and ATP production levels were assessed by hematologic and biochemical analyses. The above experiments evaluated the cardioprotective effect of QSG on left anterior descending ligation-induced HF in rats and the mode of energy metabolism modulation. In vitro, a hypoxia-induced H9C2 model was established, mitochondrial damage was evaluated by flow cytometry, and nuclear translocation of hypoxia-inducible factor-1 α (HIF-1 α) was observed by immunofluorescence to assess the mechanism of energy metabolism regulation by QSG in hypoxic and normoxia conditions. RESULTS: QSG regulated the pattern of glucose and fatty acid metabolism in the border and remote areas of the heart via the HIF-1 α pathway, and improved cardiac function in HF rats. Specifically, QSG promoted HIF-1 α expression and entry into the nucleus at high levels of hypoxia (P<0.05), thereby promoting increased compensatory glucose metabolism; while reducing nuclear accumulation of HIF-1 α at relatively low levels of hypoxia (P<0.05), promoting the increased lipid metabolism. CONCLUSIONS QSG regulates the protein stability of HIF-1 α, thereby coordinating energy supply balance between the ischemic border and remote areas of the myocardium. This alleviates the energy metabolism disorder caused by ischemic injury.
Animals ; Myocardial Infarction/physiopathology* ; Male ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Rats, Sprague-Dawley ; Glucose/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Energy Metabolism/drug effects* ; Rats ; Fatty Acids/metabolism* ; Myocardium/pathology*

Objective To observe the value of T1WI deep learning models for evaluating brain injury of neonatal hyperbilirubinemia(NHB).Methods Totally 106 NHB(defined as newborns with neonatal behavioral neurological assessment≤37,NHB group)and 119 non-NHB newborns(control group)in center A,as well as 34 NHB and 18 non-NHB newborns in center B were collected.ROI was delineated based on bilateral globus pallidus on T1WI.A total of 690 slices were obtained by preprocessing data of center A and then were divided into training set(n=552)and test set(n=138)at a ratio of 8∶2.ResNet18,DenseNet121 and EfficientNetB0 models was established,respectively.External validation was performed based on data of center B.Receiver operating characteristic curves were drawn,area under the curves(AUC)were calculated to evaluate the performance of models for assessing NHB brain injuries compared with traditional visual analysis.Results The AUC of ResNet18 model for evaluating NHB brain injury was 0.910-0.990,significantly higher than that of DenseNet121 model(0.710-0.820)and EfficientNetB0 model(0.640-0.740)(all P＜0.001).The accuracy,sensitivity and precision of ResNet18 model for evaluating NHB brain injury were all higher than those of visual analysis(all P＜0.05),while no significant difference of specificity was found between the above two(P＞0.05).Conclusion T1WI ResNet18 model showed excellent performance and generalization ability for evaluating NHB brain injury.

Objective To construct a dynamic framework for bidirectional transitions of mild cognitive impairment(MCI),quantifying both rare reversion and high-risk progression trajectories in cognitive dynamics.Methods Patients diagnosed with MCI at baseline from 2005 to 2022 and completed at least two follow-up visits were selected from the Alzheimer's Disease Neuroimaging Initiative(ADNI),and a retrospective cohort was constructed.Demographic information,APOEε4 genotype,and neuropsychological scales data were collected.Longitudinal cognitive assessments were functionally reconstructed using multivariate functional principal component analysis(MFPCA),with functional principal components(FPCs)extracted based on cumulative variance contribution rate(PVE＞90％).Functional multi-state Markov models were developed to estimate inter-state transition intensities,year to year transition probabilities,and covariate effects.Results Among 1,019 MCI patients(4,657 follow-up visits),93(9.1％)reverted to normal cognition,while 359(35.2％)progressed to Alzheimer's disease(AD).Longitudinal trajectory analysis revealed significant heterogeneity:progressive MCI＞stable MCI＞reverted MCI in the first functional principal component(MFPC1)scores.The transition intensity for MCI reversion(0.020)was approximately one-fourth of the AD progression risk(0.086),but the post-reversion cognitive re-impairment intensity was 0.138.Reduced MFPC1(HR=0.993,95％Cl:0.991,0.995)and elevated MFPC2(HR=1.004,95％Cl:1.001,1.007)were closely associated with MCI reversion.Conclusion MCI exhibits marked heterogeneity in longitudinal cognitive trajectories.Although reversion is rare,reversed patients remain at high risk of cognitive re-impairment.

Objective To observe the value of T1WI deep learning models for evaluating brain injury of neonatal hyperbilirubinemia(NHB).Methods Totally 106 NHB(defined as newborns with neonatal behavioral neurological assessment≤37,NHB group)and 119 non-NHB newborns(control group)in center A,as well as 34 NHB and 18 non-NHB newborns in center B were collected.ROI was delineated based on bilateral globus pallidus on T1WI.A total of 690 slices were obtained by preprocessing data of center A and then were divided into training set(n=552)and test set(n=138)at a ratio of 8∶2.ResNet18,DenseNet121 and EfficientNetB0 models was established,respectively.External validation was performed based on data of center B.Receiver operating characteristic curves were drawn,area under the curves(AUC)were calculated to evaluate the performance of models for assessing NHB brain injuries compared with traditional visual analysis.Results The AUC of ResNet18 model for evaluating NHB brain injury was 0.910-0.990,significantly higher than that of DenseNet121 model(0.710-0.820)and EfficientNetB0 model(0.640-0.740)(all P＜0.001).The accuracy,sensitivity and precision of ResNet18 model for evaluating NHB brain injury were all higher than those of visual analysis(all P＜0.05),while no significant difference of specificity was found between the above two(P＞0.05).Conclusion T1WI ResNet18 model showed excellent performance and generalization ability for evaluating NHB brain injury.

Objective To construct a dynamic framework for bidirectional transitions of mild cognitive impairment(MCI),quantifying both rare reversion and high-risk progression trajectories in cognitive dynamics.Methods Patients diagnosed with MCI at baseline from 2005 to 2022 and completed at least two follow-up visits were selected from the Alzheimer's Disease Neuroimaging Initiative(ADNI),and a retrospective cohort was constructed.Demographic information,APOEε4 genotype,and neuropsychological scales data were collected.Longitudinal cognitive assessments were functionally reconstructed using multivariate functional principal component analysis(MFPCA),with functional principal components(FPCs)extracted based on cumulative variance contribution rate(PVE＞90％).Functional multi-state Markov models were developed to estimate inter-state transition intensities,year to year transition probabilities,and covariate effects.Results Among 1,019 MCI patients(4,657 follow-up visits),93(9.1％)reverted to normal cognition,while 359(35.2％)progressed to Alzheimer's disease(AD).Longitudinal trajectory analysis revealed significant heterogeneity:progressive MCI＞stable MCI＞reverted MCI in the first functional principal component(MFPC1)scores.The transition intensity for MCI reversion(0.020)was approximately one-fourth of the AD progression risk(0.086),but the post-reversion cognitive re-impairment intensity was 0.138.Reduced MFPC1(HR=0.993,95％Cl:0.991,0.995)and elevated MFPC2(HR=1.004,95％Cl:1.001,1.007)were closely associated with MCI reversion.Conclusion MCI exhibits marked heterogeneity in longitudinal cognitive trajectories.Although reversion is rare,reversed patients remain at high risk of cognitive re-impairment.

OBJECTIVES: To investigate the correlation of serum levels of bridging integrating factor 1 (BIN1) with acute myocardial infarction (AMI) and Killip class of the patients. METHODS: We retrospectively collected the data from 94 patients with AMI and 30 healthy individuals for analysis of the correlations of serum BIN1 levels with Killip class, TIMI scores, and neutrophil-to-lymphocyte ratio (NLR). We also assessed the diagnostic value of BIN1 combined with NLR for AMI. RESULTS: Serum BIN1 levels were significantly lower in AMI patients than in the healthy individuals (P=0.032). The AMI patients with Killip class I had significantly lower serum BIN1 levels than the healthy individuals (P=0.008). Serum BIN1 level was an independent predictor of AMI with a predictive value of 0.630 (95% CI: 0.513-0.748) at the optimal cutoff level of 0.341 ng/mL, a specificity of 50%, and a sensitivity of 78.5%. Serum BIN1 level was also an independent predictor for Killip class I group in the AMI patients with a predictive value of 0.672 (95% CI: 0.548-0.797) at the optimal cutoff level of 0.287 ng/mL, a specificity of 74.1%, and a sensitivity of 60%. For AMI diagnosis, the combination of NLR and serum BIN1 level had a predictive value of 0.811 (95% CI: 0.727-0.895) at the optimal cutoff level of 0.548 ng/mL, with a specificity of 92.6% and a sensitivity of 62.2%. There was a positive correlation between serum BIN1 level and TIMI score in AMI patients (r=0.186, P=0.003). CONCLUSIONS BIN1 is correlated with AMI and can be helpful for predicting short-term prognosis of the patients, and BIN1 combined with NLR has a high diagnostic value for AMI.
Humans ; Myocardial Infarction/diagnosis* ; Tumor Suppressor Proteins/blood* ; Adaptor Proteins, Signal Transducing/blood* ; Retrospective Studies ; Nuclear Proteins/blood* ; Lymphocytes/cytology* ; Neutrophils/cytology* ; Female ; Male ; Prognosis ; Middle Aged

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.