Objective: To elucidate the biological basis of traditional Chinese medicine (TCM) syndromes from the perspective of “same syndrome, different diseases” in patients with chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC), thereby providing a complementary approach for the diagnosis and treatment of chronic liver diseases (CLD). Methods: To investigate the dynamic characteristics of TCM syndromes in CLD, transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) was performed from patients with CHB, LC, or HCC presenting with three TCM syndromes: liver gallbladder dampness heat syndrome (LGDHS), liver depression spleen deficiency syndrome (LDSDS), and liver kidney Yin deficiency syndrome (LKYDS). These participants were recruited at Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between August 1, 2018 and December 31, 2021. Differentially expressed genes (DEGs) were identified using the random variance model (RVM) F test with false discovery rate (FDR) correction. Principal component analysis (PCA) and unsupervised hierarchical clustering were applied to visualize sample grouping. Dynamic network biomarkers (DNB) analysis was employed to detect critical transition stages during syndrome evolution, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to characterize the functional roles and pathway involvement of the DNB members. Random forest (RF) analysis and the area under the receiver operating characteristic (ROC) curves (AUC) were used to rank the importance of candidate genes. External validation was performed using microarray data from an independent CLD cohort (GSE89377) and RNA-seq data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset. Additionally, reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed on an independent cohort of LC patients to validate the expression levels of the candidate genes. Results: The study included a total of 132 participants. DNB analysis identified LDSDS stage as a critical tipping point during TCM syndrome evolution across CHB, LC, and HCC. The phosphoinositide 3-kinase/protein kinase B (PI3K-AKT) signaling pathway was consistently enriched in the DNB analysis across all three types of CLD, suggesting its potential involvement in the critical transition of TCM syndromes. Among the 24 core DNB members of the PI3K-AKT pathway, four genes—integrin subunit beta 1 (ITGB1), collagen type IV alpha 1 chain (COL4A1), collagen type IV alpha 2 chain (COL4A2), and DNA damage inducible transcript 3 (DDIT3)—were identified by RF analysis (Gini score > 1) and ROC analysis. ROC analysis demonstrated high discriminative ability for distinguishing LGDHS from LKYDS in CHB patients, with AUC of 0.7891 for ITGB1, 0.7070 for COL4A1, 0.7148 for COL4A2, and 0.8945 for DDIT3. In the independent CLD cohort (GSE89377), all four genes showed significant stepwise upregulation from normal to CHB, LC, and HCC (all P < 0.05). In the TCGA-LIHC dataset, their expression progressively increased with tumor stage. RT-qPCR validation in an independent LC cohort (30 LGDHS vs. 30 LKYDS) confirmed that ITGB1, COL4A2, and DDIT3 were significantly upregulated in LKYDS compared with LGDHS (P = 0.0152, 0.0186, and 0.0247, respectively), whereas COL4A1 showed a non-significant upward trend (P = 0.1201). Conclusion This study introduces a novel approach to understanding the molecular features underlying TCM syndrome evolution in CLD. The PI3K-AKT pathway and four identified genes (ITGB1, COL4A1, COL4A2, and DDIT3) play crucial roles in the transition from excess (LGDHS) to deficiency (LKYDS) via the critical LDSDS stage. These findings offer potential quantitative biomarkers and therapeutic targets for TCM syndrome differentiation and may help arrest syndrome progression in CLD.

ObjectiveTo construct a risk prediction model for chronic atrophic gastritis （CAG） that combines disease and syndrome by integrating spleen deficiency and blood stasis syndrome scores， gastric stem cell marker analysis， and network pharmacology and to elucidate the mechanism link between spleen deficiency， blood stasis， and gastric stem cell dysregulation. MethodsA total of 60 patients were stratified into high-risk CAG， low-risk CAG， and non-atrophic groups based on the operative link for gastritis assessment （OLGA）/operative link for gastric intestinal metaplasia assessment （OLGIM） stages. General data and syndrome scores of the patients were collected. Immunohistochemistry was employed to measure the protein levels of leucine-rich repeat-containing G protein-coupled receptor 5 （LGR5）， trefoil factor 2 （TFF2）， and β-catenin in gastric mucosa across groups. Transcriptomic data （GSE130823） from the Gene Expression Omnibus （GEO） database were analyzed to validate the expression of these molecular markers at the gene level. A Firth penalized maximum likelihood logistic regression model was employed to integrate clinical， molecular， and TCM syndrome data to develop a CAG risk prediction model. Finally， network pharmacology analysis was conducted on spleen-invigorating herbs （Astragali Radix， Atractylodis Macrocephalae Rhizoma， and Dioscorea Rhizoma） and blood-activating herbs （Hedyotis diffusa， Salviae Miltiorrhizae Radix et Rhizoma， and Curcumae Rhizoma） to identify overlapping targets between these herbs and differentially expressed genes between low-grade intraepithelial neoplasia （LGIN） and gastritis， thereby clarifying the role of spleen deficiency and blood stasis in CAG progression from a pharmacological perspective. ResultsHigh-risk CAG patients exhibited higher blood stasis scores （4.60±1.50，2.62±1.32， P<0.01）， progressive nuclear accumulation of β-catenin （A 0.28-0.53， P<0.01）， and an increased LGR5⁺/TFF2⁺ ratio （A 1.02-1.92， P<0.01）. Blood stasis scores were correlated with LGR5/TFF2 imbalance （P=0.03） and activation of the Wnt/β-catenin signaling pathway （CTNNB1 increase， log₂=0.78）. The integrated prediction model （blood stasis score≥5 + β-catenin>0.38 + LGR5/TFF2>1.5） outperformed a pure biomarker approach ［Area Under the Curve （AUC） 0.92，0.89， ΔAUC=0.03， P=0.02］. Moreover， network pharmacology revealed 66 overlapping targets between spleen-invigorating/blood-activating herbs and LGIN， which were functionally enriched in mucosal repair and anti-oxidative stress， and negatively correlated with the Wnt/β-catenin signaling pathway （P<0.01）. ConclusionThis study developed an integrated risk prediction model for CAG by combining TCM spleen deficiency and blood stasis syndromes with gastric stem cell molecular markers. Furthermore， it proposed for the first time the "blood stasis-Wnt/β-catenin-stem cell axis" hypothesis， preliminarily elucidating that spleen deficiency and blood stasis may exacerbate gastric stem cell dysregulation and promote malignant transformation of CAG through hypoxia-induced Wnt activation. This provides a theoretical foundation and a translational tool for risk stratification and multi-target TCM intervention in CAG.

ObjectiveTo construct a risk prediction model for chronic atrophic gastritis （CAG） that combines disease and syndrome by integrating spleen deficiency and blood stasis syndrome scores， gastric stem cell marker analysis， and network pharmacology and to elucidate the mechanism link between spleen deficiency， blood stasis， and gastric stem cell dysregulation. MethodsA total of 60 patients were stratified into high-risk CAG， low-risk CAG， and non-atrophic groups based on the operative link for gastritis assessment （OLGA）/operative link for gastric intestinal metaplasia assessment （OLGIM） stages. General data and syndrome scores of the patients were collected. Immunohistochemistry was employed to measure the protein levels of leucine-rich repeat-containing G protein-coupled receptor 5 （LGR5）， trefoil factor 2 （TFF2）， and β-catenin in gastric mucosa across groups. Transcriptomic data （GSE130823） from the Gene Expression Omnibus （GEO） database were analyzed to validate the expression of these molecular markers at the gene level. A Firth penalized maximum likelihood logistic regression model was employed to integrate clinical， molecular， and TCM syndrome data to develop a CAG risk prediction model. Finally， network pharmacology analysis was conducted on spleen-invigorating herbs （Astragali Radix， Atractylodis Macrocephalae Rhizoma， and Dioscorea Rhizoma） and blood-activating herbs （Hedyotis diffusa， Salviae Miltiorrhizae Radix et Rhizoma， and Curcumae Rhizoma） to identify overlapping targets between these herbs and differentially expressed genes between low-grade intraepithelial neoplasia （LGIN） and gastritis， thereby clarifying the role of spleen deficiency and blood stasis in CAG progression from a pharmacological perspective. ResultsHigh-risk CAG patients exhibited higher blood stasis scores （4.60±1.50，2.62±1.32， P<0.01）， progressive nuclear accumulation of β-catenin （A 0.28-0.53， P<0.01）， and an increased LGR5⁺/TFF2⁺ ratio （A 1.02-1.92， P<0.01）. Blood stasis scores were correlated with LGR5/TFF2 imbalance （P=0.03） and activation of the Wnt/β-catenin signaling pathway （CTNNB1 increase， log₂=0.78）. The integrated prediction model （blood stasis score≥5 + β-catenin>0.38 + LGR5/TFF2>1.5） outperformed a pure biomarker approach ［Area Under the Curve （AUC） 0.92，0.89， ΔAUC=0.03， P=0.02］. Moreover， network pharmacology revealed 66 overlapping targets between spleen-invigorating/blood-activating herbs and LGIN， which were functionally enriched in mucosal repair and anti-oxidative stress， and negatively correlated with the Wnt/β-catenin signaling pathway （P<0.01）. ConclusionThis study developed an integrated risk prediction model for CAG by combining TCM spleen deficiency and blood stasis syndromes with gastric stem cell molecular markers. Furthermore， it proposed for the first time the "blood stasis-Wnt/β-catenin-stem cell axis" hypothesis， preliminarily elucidating that spleen deficiency and blood stasis may exacerbate gastric stem cell dysregulation and promote malignant transformation of CAG through hypoxia-induced Wnt activation. This provides a theoretical foundation and a translational tool for risk stratification and multi-target TCM intervention in CAG.

ObjectiveTo explore the relationship between triglyceride high-density cholesterol-glucose body index （TyHGB） and gestational diabetes mellitus （GDM）. MethodsThis single-center retrospective cohort study was conducted. A total of 723 singleton pregnant women who received prenatal care and delivered at Lingnan Hospital， the Third Affiliated Hospital of Sun Yat-sen University， from May 2024 to July 2024 were enrolled. Clinical baseline data and laboratory test results in the first trimester （before 13⁺⁶ weeks of gestation） were collected. Based on the tertiles of the TyHGB index were equally divided into 3 groups. Clinical baseline data， and GDM risk were compared among the three groups. ResultsCompared with the control group， the GDM group had older maternal age， higher Pre-pregnancy BMI， FPG， TG， and higher values of 75 g OGTT fasting plasma glucose， 1 h plasma glucose， and 2 h plasma glucose. The early-pregnancy TyHGB index， andincidence of macrosomiawere all higher in the GDM group than in the control group （ all P<0.05）， whereas gestational weight gain （GWG） was lower than that of the control group （P<0.05）. The individuals were divided into three groups according to the tertiles of the TyHGB index. Significantly differences were identified among TyHGB index tertiles in maternal age， parity， Pre-BMI， FPG， TC， TG， HDL-C， LDLL-C， Ur， 75 g OGTT fasting plasma glucose， 1 h plasma glucose， 2 h plasma glucose， GWG， neonatal birth weight， GDM， GH， macrosomia incidence， and cesarean section rate（all P<0.05）. Further trend test analysis found that matenal age， parity， Pre-BMI， FPG， TC， TG， LDL-C， 75 g OGTT_FPG， 75 g OGTT_1 h PG and 75 g OGTT_2 h PG level， neonatal birth weight， GDM， GH， incidence of macrosomia and cesarean section rate all showed an upward trend. The multivariate Logistic regression models revealed that there was an independent positive correlation between TyHGB index and the risk of GDM. Curve fitting by restricted cubic splines （RCS） were used to assess linearity between TyHGB and GDM， and there was a linear dose-response relationship between TyHGB and GDM （P _{nonlinear test} = 0.597）. The threshold value for early pregnancy TyHGB index to predict GDM was 6.449 ， with an area under the curve （AUC） of 0.644 （95% CI： 0.597-0.691）， sensitivity of 0.480 ， and specificity of 0.779. After adjusting for maternal age， Pre-BMI， family history of diabetes， and history of GDM， the AUC for the early pregnancy TyHGB index to predict GDM was 0.672 （95% CI： 0.626-0.718）. ConclusionThe early-pregnancy TyHGB index is independently associated with GDM risk， and exhibits a linear dose-response relationship with GDM. It may serve as an early screening and monitoring tool for pregnant women at high risk of GDM. However， its predictive value for GDM requires further validation.

Objective To observe the value of three-dimensional ultrasound combined with microvascular flow imaging for prenatal diagnosis of fetal intracranial anomalies.Methods Totally 118 fetuses with intracranial anomalies diagnosed through cranial MRI/induced labor specimen dissection who underwent prenatal ultrasound examination were retrospectively enrolled.Two-dimensional,three-dimensional ultrasound and microvascular flow imaging manifestations of fetal intracranial anomalies were observed,and the accuracy of three-dimensional ultrasound combined with microvascular flow imaging for prenatal diagnosis of fetal intracranial anomalies was analyzed.Results The accuracy of three-dimensional ultrasound combined with microvascular flow imaging for prenatal diagnosis of fetal intracranial anomalies was 93.22％(110/118),of isolated and non-isolated intracranial anomalies was 97.47％(77/79)and 84.62％(33/39),respectively.Six fetuses were missed diagnosis of malformations of cortical development(1 fetus of tuberous sclerosis,4 of abnormal morphology of the sulci gyrus and 1 of schizencephaly)and 1 fetus of intracranial softening lesion,while posterior fossa arachnoid cyst in 1 fetus was misdiagnosed as mega cisterna magna.Conclusion The accuracy of three-dimensional ultrasound combined with microvascular flow imaging for prenatal diagnosis of fetal intracranial anomalies was relatively high.

Objective To observe prenatal ultrasonic findings of fetal malformation of cortical development(MCD).Methods Totally 37 singleton fetuses with MCD diagnosed by fetal cranial MRI and/or genetic examination were retrospectively enrolled,and prenatal ultrasonic manifestations were observed.Results Among 37 fetuses,29(29/37,78.38％)were found with abnormal Sylvian fissure,26(26/37,70.27％)with widened/asymmetrical lateral ventricles,22(22/37,59.46％)with abnormal surface sulci,14(14/37,37.84％)with abnormal cavity of septum pellucidum(CSP)/corpus callosum(CC),11(11/37,29.73％)with midline deviation/curvature,11(11/37,29.73％)with widened subarachnoid space,10(10/37,27.03％)with head circumference＜2 standard deviation below mean value,9(9/37,24.32％)with abnormalities in the cerebellar hemisphere/vermis,7(7/37,18.92％)with abnormal echoes in the brain parenchyma,7(7/37,18.92％)with midline cysts and 2(2/37,5.41％)with enlarged ganglion eminence.Conclusion Fetal MCD mainly presented as abnormal Sylvian fissure,widened/asymmetrical lateral ventricles and abnormal surface sulci,which might accompanied by abnormal CSP/CC,midline deviation/curvature,widened subarachnoid space and abnormal head circumference in prenatal ultrasound.

Astragali Radix (AR), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use. While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy (DIC); however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action. Through network medicine analysis, astragaloside IV (AsIV) and formononetin (FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsIV-FMT combination (AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsIV and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
Animals ; Doxorubicin/adverse effects* ; Saponins/administration & dosage* ; Isoflavones/pharmacology* ; Rats ; Cardiomyopathies/prevention & control* ; Mice ; Fatty Acids/metabolism* ; Myocytes, Cardiac/metabolism* ; Triterpenes/administration & dosage* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Cardiotonic Agents/administration & dosage* ; Mice, Inbred C57BL ; Cell Line ; Astragalus Plant/chemistry* ; Astragalus propinquus

OBJECTIVE To analyze the risk factors for positive culture of carbapenem-resistant Enterobacteriaceae(CRE)in the intensive care unit(ICU)patients so as to provide scientific technical support for early identification of the patients at high-risk of CRE colonization/infection in clinical practice.METHODS The clinical data and bac-terial culture data were collected from the ICU patients who were hospitalized in Beijing Friendship Hospital from 2021 to 2023 so as to build up retrospective cohorts.The risk factors for positive culture of CRE in the ICU pa-tients were screened out with the use of multivariate logistic regression model,and the predictive effect of the model was evaluated by means of receiver operating characteristic(ROC)curves and Hosmer-Lemeshow test.RESULTS Gastric tube indwelling history(OR=3.992,95％CI:1.894 to 8.121),wards of patients detected with CRE within 7 days during the stay(OR=3.518,95％CI:1.492 to 8.294),renal disease history(OR=2.063,95％CI:1.128 to 3.775),history of isolation of multidrug-resistant organisms(OR=2.400,95％CI:1.240 to 4.647)and use of carbapenem antibiotics(OR=1.141,95％CI:1.088 to 1.196)were the independent risk fac-tors for the positive culture of CRE in the ICU patients.The prediction model that was established based on the risk factors showed favorable discrimination,and the area under the ROC curve(AUC)was 0.773.The actual probability was comparatively consistent with the ideal probability,with the Hosmer-Lemeshow test(x2=9.274,P=0.233).CONCLUSION The model shows remarkable effect on prediction of positive culture of CRE in the ICU patients,and it has high value in early identification of the patients at high risk of CRE colonization/infection in clinical practice.

Objective To explore the potential central mechanisms of functional electrical stimulation(FES)hand cycling in promot-ing upper limb motor recovery after stroke.Methods A total of 35 stroke patients hospitalized in the Rehabilitation Center of Changzhou De'an Hospital from May,2023 to December,2024 were enrolled.They sequentially completed 10-minute FES hand cycling and 10-minute sham stimulation(simple hand cycling)tasks.The task order was randomized via dice rolling.Functional near-in-frared spectroscopy(fNIRS)was used to monitor real-time cerebral hemodynamic changes during both tasks to calculate the overall functional connectivity(FC)strength and the FC strength within regions of interest.Results The overall FC strength was higher during the FES hand cycling task than during the sham task(t=2.591,P<0.05),as well as FC between the ipsilateral primary motor cortex(iM1)and ipsilateral somatosensory association cortex(iSAC),iM1 and contralateral somatosensory association cortex(cSAC),ipsilateral pre-motor and supple-mentary motor cortex(iPMC)and iSAC,iPMC and cSAC,iPMC and ipsilateral primary somatosensory cortex(iS1),iPMC and iM1,and contralateral pre-motor and supplementary motor cortex(cPMC)and iSAC(PFDR<0.05).Conclusion FES hand cycling can promote the cortical function remodeling between cerebral hemispheres and the af-fected hemisphere,to integrate sensory-motor function.

OBJECTIVE To establish a core competency evaluation system for drug clinical trial quality management personnel in China and validate its application. METHODS Based on the scope of work， responsibilities， and role positioning of quality management personnel in drug clinical trials， a preliminary draft of the core competency evaluation system was constructed through literature analysis and expert consultation. The draft was refined through a Delphi method involving 17 experts who provided feedback and revisions， ultimately forming a complete evaluation system. The developed system was applied to conduct electronic surveys from March to May 2024 among 110 quality management personnel from 38 drug clinical trial institutions， comparing their scores on indicator importance and self-assessed capabilities. RESULTS The response rate of both rounds of questionnaire survey was 100%， with Kendall’s W coefficients of 0.256 and 0.277 （P＜0.001 for both）， and an expert authority coefficient of 0.946. The finalized evaluation system for core competencies of clinical trial quality management personnel comprised 9 primary indicators， covering individual professional competence， communication skills， implementation condition verification， informed consent process review， clinical trial execution monitoring， adverse event disposal， reporting and documentation， trial record examination， trial report auditing， and inspection of other tasks， and 107 secondary indicators. Empirical research revealed significant discrepancies between importance scores and self-assessed competency scores across 70 indicators among 110 respondents （P＜0.05）. Indicators with relatively notable gaps between importance scores and self-assessed competency scores included in-depth understanding of Good Clinical Practice （GCP） requirements （0.34-point gap）， familiarity with national and institutional clinical trial inspection priorities （0.24-point gap），etc. CONCLUSIONS The indicator system constructed in this study has good scientificity and reliability. Clinical trial quality management personnel demonstrate deficiencies in multiple critical competencies， highlighting the urgent need for targeted training programs to enhance their overall professional capabilities.