This paper aims to evaluate the pharmacodynamic effect and mechanism of Zhifuxin in the prevention and treatment of vascular dementia(VD), providing a theoretical basis for later development. Bilateral common carotid artery ligation in male Wistar rats was conducted to replicate the long-term hypoperfused VD model, and the drug was given to groups after one month. The rats were fed daily with nimodipine of 20 mg·kg~(-1), Zhifuxin of 50, 100, and 200 mg·kg~(-1), or the same volume of solvent for four weeks. 24 hours after the last dose, Morris water maze experiments were performed to detect the learning and memory abilities of rats. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in the brain tissue of rats; the immunohistochemical method was used to detect the expression of muscarinic acetylcholine receptors M1 and M4 in rats and determine the content of acetyl choline(Ach), acetylcholin esterase(AchE), malondialdehyde(MDA), choline acetyl transferase(ChAT), and dimethyl arginine hydrolase 1(DDAH1) in the cerebral cortex of rats. Western blot was employed to detect protein expression of endothelial nitric oxide synthase(eNOS), caveolin-1, monoamine oxidase A(MAO-A), and monoamine oxidase B(MAO-B). RT-qPCR was utilized to detect mRNA expression of eNOS, caveolin-1, MAO-A, and MAO-B. The results showed that compared with the model group, the different doses of Zhifuxin were able to shorten the latency of VD rats in the water maze positioning navigation test, increase the number of crossing platforms in the space exploration test, and alleviate cone cell contracture in the hippocampus of VD rats. The expression of biochemical indicators related to the cholinergic system in the cerebral cortex: M1 and M4 receptors increased, as well as ChAT activity, and AchE activity significantly decreased. The protein and mRNA expression of indicators related to the eNOS/NO pathway: DDAH1 content, eNOS, and caveolin-1 increased, and that of indicators related to monoamine oxidase(MAO): MAO-A and MAO-B significantly decreased. The results show that Zhifuxin can improve cognition ability in long-term hypoperfused VD rats, and its mechanism of action may be related to its ability to modulate the cholinergic system and the eNOS/NO pathway and inhibit MAO expression.
Animals ; Dementia, Vascular/metabolism* ; Male ; Rats, Wistar ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Maze Learning/drug effects* ; Nitric Oxide Synthase Type III/genetics* ; Acetylcholinesterase/metabolism* ; Humans ; Choline O-Acetyltransferase/genetics* ; Disease Models, Animal

This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/chemistry*

Objective To explore the risk factors for medium-and long-term mortality in patients with severe community-acquired pneumonia(SCAP)based on the Medical Information Mart for Intensive Care Ⅳ(MIMIC-Ⅳ),construct a prognostic model and evaluate its predictive efficacy.Methods In this retrospective cohort study,1943 SCAP patients from the U.S.MIMIC-Ⅳdatabase(2008-2019)were randomly divided into training(n=1363)and validation(n=580)sets(7:3 ratio).Primary and secondary endpoints were 1-year and 30-/90-day all-cause mortality,respectively.Prognostic factors were selected using LASSO regression and multivariable Cox proportional hazards modeling,and a visual nomogram model was built.Model performance was assessed via C-index,receiver operator characteristic(ROC)curves,and calibration curves,and compared with the CURB-65 score.Risk stratification was validated using Kaplan-Meier analysis.Results The 30-day,90-day,and 1-year all-cause mortality rates for SCAP patients were 25.9％,34.5％,and 42.6％,respectively.Seven independent risk factors were identified:age(HR=1.037),heart rate(HR=1.007),red blood cell distribution width(RDW,HR=1.092),Acute Physiology Score Ⅲ(APS-Ⅲ,HR=1.013),cerebrovascular disease(HR=1.453),liver disease(HR=1.272),and malignancy(HR=2.007).Based on these factors,Cox regression model was constructed and nomogram was drawn,C-indices of training set and validation set were 0.710 and 0.688,respectively.For 1-year mortality prediction,the model achieved superior area under the ROC curve(AUC)values(training set:0.768;validation set:0.738)compared with CURB-65 score(training set:0.648;validation set:0.616).Kaplan-Meier survival analysis revealed significantly worse survival in high-risk group than low-risk group(P<0.0001).Conclusions Age,heart rate,RDW,APS-Ⅲ,cerebrovascular disease,liver disease,and malignant tumor were medium-and long-term mortality risk factors in SCAP patients.The prognostic model constructed based on these factors has high predictive power and provides an important clinical diagnosis and treatment reference.

Objective:To investigate the association of serum levels of myoglobin(Myo)and reticulocyte(Ret)with cardiac function class in patients with chronic heart failure(CHF).Methods:A total of 106 CHF patients treated in First Rongjun Special Care Hospital of Hebei Province between February 2020 and February 2024 were retrospec-tively selected as the observation group.According to New York Heart Association(NYHA)cardiac function class,patients were divided into class Ⅱ group(n=61)and class Ⅲ～Ⅳ group(n=45),and 107 healthy people with nor-mal physical examination results were selected from our hospital simultaneously as control group.The Myo and Ret levels were compared between control group and observation group,class Ⅱ group and class Ⅲ～Ⅳ group.Spearman correlation analysis was used to analyze the association of Myo and Ret levels with NYHA class in CHF patients.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of Myo,Ret and their combined detection for NYHA class Ⅲ～Ⅳ in CHF patients.Results:Compared to participants in the control group,those in the observation group had significant higher Myo level[(50.42±9.98)μg/ml vs.(35.22±5.36)μg/ml]and significant lower Ret level[(2.24±0.68)％vs.(2.91±0.61)％](P＜0.001 all).Compared to those in class Ⅱ group,those in class Ⅲ～Ⅳ group had significant higher Myo level[(60.77±5.94)μg/ml vs.(42.79±2.97)μg/ml]and significant lower Ret level[(1.73±0.31)％vs.(2.62±0.62)％](P＜0.001 all).Spearman correlation analysis showed that Myo(r=0.654)was positively correlated with NYHA cardiac function class in CHF patients,while Ret(r=-0.589)was inversely correlated with it(P＜0.001 all).ROC analysis showed that a combination of Myo and Ret had significant higher predictive efficacy(AUC=0.926,95％CI 0.858～0.968)for NYH A class Ⅲ～Ⅳ in CHF patients than Myo(AUC=0.804,95％CI 0.716～0.875)and Ret(AUC=0.701,95％CI 0.604～0.786)alone(Z=2.745,4.183,P＜0.01 both).Conclusion:Our study showed that Myo and Ret levels were significantly correlated with NYHA class in CHF patients.Moreover,a combination of Myo and Ret levels showed better diagnostic value for NYHA class Ⅲ～Ⅳ in this population.

Neonatal sepsis is a global health problem that seriously affects the body health and life safety of newborns. It has a higher incidence in preterm infants,especially for early-onset sepsis (EOS) within 72 hours of birth. The diagnosis of neonatal EOS requires a series of examinations,and early and accurate diagnosis can improve clinical outcomes and reduce antibiotic overuse in a timely manner. At present,the commonly used biomarkers and traditional blood culture methods for EOS diagnosis have certain shortcomings,so it is urgent to find new molecular diagnostic methods. This article summarizes and compares the early and novel diagnostic methods of neonatal EOS,in order to provide a reference for clinical practice.

Objective:To investigate the association of serum levels of myoglobin(Myo)and reticulocyte(Ret)with cardiac function class in patients with chronic heart failure(CHF).Methods:A total of 106 CHF patients treated in First Rongjun Special Care Hospital of Hebei Province between February 2020 and February 2024 were retrospec-tively selected as the observation group.According to New York Heart Association(NYHA)cardiac function class,patients were divided into class Ⅱ group(n=61)and class Ⅲ～Ⅳ group(n=45),and 107 healthy people with nor-mal physical examination results were selected from our hospital simultaneously as control group.The Myo and Ret levels were compared between control group and observation group,class Ⅱ group and class Ⅲ～Ⅳ group.Spearman correlation analysis was used to analyze the association of Myo and Ret levels with NYHA class in CHF patients.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of Myo,Ret and their combined detection for NYHA class Ⅲ～Ⅳ in CHF patients.Results:Compared to participants in the control group,those in the observation group had significant higher Myo level[(50.42±9.98)μg/ml vs.(35.22±5.36)μg/ml]and significant lower Ret level[(2.24±0.68)％vs.(2.91±0.61)％](P＜0.001 all).Compared to those in class Ⅱ group,those in class Ⅲ～Ⅳ group had significant higher Myo level[(60.77±5.94)μg/ml vs.(42.79±2.97)μg/ml]and significant lower Ret level[(1.73±0.31)％vs.(2.62±0.62)％](P＜0.001 all).Spearman correlation analysis showed that Myo(r=0.654)was positively correlated with NYHA cardiac function class in CHF patients,while Ret(r=-0.589)was inversely correlated with it(P＜0.001 all).ROC analysis showed that a combination of Myo and Ret had significant higher predictive efficacy(AUC=0.926,95％CI 0.858～0.968)for NYH A class Ⅲ～Ⅳ in CHF patients than Myo(AUC=0.804,95％CI 0.716～0.875)and Ret(AUC=0.701,95％CI 0.604～0.786)alone(Z=2.745,4.183,P＜0.01 both).Conclusion:Our study showed that Myo and Ret levels were significantly correlated with NYHA class in CHF patients.Moreover,a combination of Myo and Ret levels showed better diagnostic value for NYHA class Ⅲ～Ⅳ in this population.

Neonatal sepsis is a global health problem that seriously affects the body health and life safety of newborns. It has a higher incidence in preterm infants,especially for early-onset sepsis (EOS) within 72 hours of birth. The diagnosis of neonatal EOS requires a series of examinations,and early and accurate diagnosis can improve clinical outcomes and reduce antibiotic overuse in a timely manner. At present,the commonly used biomarkers and traditional blood culture methods for EOS diagnosis have certain shortcomings,so it is urgent to find new molecular diagnostic methods. This article summarizes and compares the early and novel diagnostic methods of neonatal EOS,in order to provide a reference for clinical practice.

Objective:To investigate the effect of lipopolysaccharide(LPS)on the crawling ability of fibroblasts derived from the scrotal skin under hypoxic conditions,its impact on vascular regeneration during wound healing,and the potential mechanism un-derlying chronic non-healing scrotal wound caused by gram-negative bacterial infection.Methods:We extracted peripheral blood buffy coats from healthy donors after venous blood centrifugation,divided them into four groups(normoxia,normoxia+LPS,hypoxia,and hypoxia+LPS)for pretreatment,and isolated the corresponding cultured supernatant.Then we measured the levels of VEGF-A,FGF and IL-8 secreted using enzyme-linked immunosorbent assay(ELISA),determined the cytotoxicity of different pretreated superna-tants by lactate dehydrogenase(LDH)release assay,and detected the cell migration ability and vascular formation in human-umbical vein endothelial cells(HUVEC).Results:Under hypoxic conditions,the expression of HIF-1 α was significantly lower in the fibro-blasts from the chronic scrotal wound than in the normal fibroblasts(0.09±0.00 vs 0.48±0.01,P＜0.05),the viability of the cells showed no statistically significant difference from that under normoxic conditions(P＞0.05),and the proliferation and migration abilities of the cells were markedly improved([83.09±2.56]％vs[17.84±1.12]％,P＜0.05).The viability of the scrotal fibroblasts was significantly lower in the normoxia+LPS than in the hypoxia+LPS group([20.15±1.19]％vs[32.54±1.57]％,P＜0.05).The cells treated with LPS,compared with those in the non-LPS groups,exhibited remarkably decreased endo-thelial cell tubes formed(5.20±0.15 va 55.30±1.15,P＜0.05),down-regulated expression of VEGF(OD value:0.59±0.07 vs 1.25±0.11,P＜0.05)and up-regulated expression of IL-8(OD value:2.42±0.07 vs 0.87±0.11,P＜0.05).Conclusion:The supernatant derived from the peripheral blood buffy coats treated with LPS has a stronger cytotoxicity and weaker an-giogenesis than that untreated under hypoxic or normoxic conditions,which may be one of the critical factors for difficult healing of scrotal wound.

Chlamydia psittaci is a worldwide distributed zoonotic pathogen that infects a variety of birds.In order to char-acterization of the duck originated C.psittaci strains,lung samples were collected from suspected infection ducks and was de-tected by real-time PCR.The positive samples were homogenized in phosphate buffered saline with kanamycin and streptomy-cin,and then inoculated onto L929 cells monolayer.After several sets of passages,chlamydial inclusions of the isolate in cul-tured cells were observed after Giemsa staining or by electron microscope.For species identification,16S rRNA,16-23S IGS gene fragments were sequenced and analyzed.Genotyping of the isolate was performed by comparative analysis of the obtained ompA gene sequence with that of different genotype of C.psittaci strains.A C.psittaci strain was successfully isolated from the lung sample of duck by cell culture and was identified as genotype A.This study expanded our understanding of the host range of genotype A C.psittaci strain,and provided basis for further research on the pathogenicity,transmission,and public health risk of this pathogen.

Objective To develop a deep learning model for automated age estimation based on 3D CT reconstructed images of Han population in western China,and evaluate its feasibility and reliability.Methods The retrospective pelvic CT imaging data of 1 200 samples(600 males and 600 females)aged 20.0 to 80.0 years in western China were collected and reconstructed into 3D virtual bone models.The images of the ischial tuberosity feature region were extracted to create sex-specific and left/right site-specific sample libraries.Using the ResNet34 model,500 samples of different sexes were randomly selected as training and verification set,the remaining samples were used as testing set.Initialization and transfer learning were used to train images that distinguish sex and left/right site.Mean absolute error(MAE)and root mean square error(RMSE)were used as primary indicators to evaluate the model.Results Prediction results varied between sexes,with bilateral models outperformed left/right unilateral ones,and transfer learning models showed superior performance over initial models.In the prediction results of bilateral transfer learning models,the male MAE was 7.74 years and RMSE was 9.73 years,the female MAE was 6.27 years and RMSE was 7.82 years,and the mixed sexes MAE was 6.64 years and RMSE was 8.43 years.Conclusion The skeletal age estimation model,utilizing is-chial tuberosity images of Han population in western China and employing the ResNet34 combined with transfer learning,can effectively estimate adult ischium age.