ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride（CRPV）， and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts， as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards， databases， and relevant literature were utilized for compound annotation， with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups， including the blank group， model group， diazepam group（2.5 mg·kg^-1）， raw CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， and vinegar-processed CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， with 10 mice per group. Except for the blank group， all other groups underwent chronic restraint stress（2 h·d^-1） for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling， with a total treatment duration of 10 d. Following model-based drug administration， mice underwent open-field， forced swimming， and elevated plus maze tests. After anesthesia with isoflurane， whole brains were collected from each group of mice， and hippocampi were dissected. Reactive oxygen species（ROS） level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay（ELISA）. Hematoxylin-eosin（HE） staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei（NeuN） and peroxisome proliferator-activated receptor alpha（PPARα） expressions in hippocampal tissue. Then， pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders， exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV， with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds， including 20 flavonoids， 20 flavonoid glycosides， 3 triterpenes， 3 phenolic acids， 1 alkaloid， and 6 other compounds. Twenty-one components were detected in blood（15 methoxyflavones， 4 flavonoid glycosides， and 2 phenolic acids）， with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues（all common to both forms）. In regulating emotional disorders， Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology， particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS（P<0.05）. ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing， but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway， thereby negatively regulating ROS generation in the hippocampus， reducing oxidative stress， and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards， pharmacodynamic material research， and active drug development of raw and vinegar-processed CRPV.

Objective To investigate the status and predictive factors of future acute exacerbation of asthma in adults. Methods Adult patients with asthma who were admitted to the hospital from March 2023 to July 2025 were selected. Based on the acute exacerbation status after follow-up, the patients were categorized into acute exacerbation group (n=107) and control group (n=245). The clinical data, pulmonary function [peak expiratory flow (PEF) and forced expiratory volume in the 1st second/forced vital capacity (FEV₁/FVC)] and health status [asthma control questionnaire (ACQ), Morisky medication adherence scale (MMAS-8), short form 36-item health survey (SF-36)] of the study subjects were collected. The correlation between the indicators and acute exacerbation was explored by logistic regression analysis, and the predictive efficiency was evaluated by ROC curve. Results The age, smoking history, asthma course, allergen exposure and ACQ in the acute exacerbation group were higher than those in the control group, while the average monthly family income, glucocorticoid treatment, PEF, FEV₁/FVC, MMAS-8 and SF-36 were lower (P<0.05). Multivariate logistic regression suggested that ACQ score, glucocorticoid treatment, MMAS-8 score, FEV₁/FVC, PEF and smoking history were the influencing factors of acute asthma exacerbation (P<0.05). ROC analysis revealed that the diagnostic efficiency of combined prediction was the highest (AUC=0.965), with sensitivity of 0.944 and specificity of 0.857 (P<0.05). Conclusion It is necessary to pay more attention to the medication compliance and asthma control level of patients, and integrate multi-dimensional information such as smoking history, pulmonary function and treatment conditions to accurately identify patients with high-risk acute exacerbation and implement targeted intervention measures.

AIM: To investigate the changes in ocular surface-related indicators and tear matrix metalloproteinase-9(MMP-9)levels in diabetic patients complicated with meibomian gland dysfunction(MGD), analyze the effects of diabetes mellitus on ocular surface status and tear MMP-9 levels in patients with MGD, and provide evidence for clinical diagnosis and treatment.METHODS: Prospective observational study.Patients with type 2 diabetes mellitus complicated with MGD who visited the Department of Ophthalmology of the hospital from June 2024 to December 2024 were enrolled(diabetes mellitus+MGD group), and patients diagnosed solely with MGD without a history of diabetes mellitus during the same period were recruited as the non-diabetic MGD group. Patients in the diabetes mellitus+MGD group were further subdivided into aglycosylated hemoglobin(HbA1c)<7.5% subgroup and an HbA1c≥7.5% subgroup based on HbA1c levels, and into a diabetes duration<10 y subgroup and a diabetes duration ≥10 y subgroup according to the duration of diabetes mellitus. Multiple ocular surface parameters, including the Ocular Surface Disease Index(OSDI)score and eyelid margin alteration score, as well as tear MMP-9 concentration, were measured in all participants, followed by between-group comparative analyses.RESULTS:Total of 101 patients(202 eyes)with type 2 diabetes mellitus combined with MGD were enrolled, including 56 males and 45 females with a mean age of 60.2±8.5 y. The non-diabetic MGD group consisted of 151 patients(302 eyes), with 82 males and 69 females and a mean age of 57.5±7.8 y.The HbA1c <7.5% group comprised 55 patients(110 eyes)aged 59.6±8.2 y; 31 males and 24 females. The HbA1c ≥7.5% group included 46 patients(92 eyes)aged 60.9±8.7 y; 25 males and 21 females.The subgroup with diabetes duration <10 y had 50 patients(100 eyes)aged 58.7±8.1 y; 28 males and 22 females, and the subgroup with duration ≥10 y consisted of 51 patients(102 eyes)aged 61.6±8.4 y; 27 males and 24 females. Patients in diabetes mellitus+MGD group exhibited higher OSDI scores, meibomian gland orifice scores, meibum expressibility scores, meibum quality scores, corneal fluorescein staining scores, and tear MMP-9 levels compared with non-diabetic MGD patients(all P<0.01), while tear film breakup time(BUT)and Schirmer test values were lower(all P<0.01).Among diabetic patients with MGD, the HbA1c≥7.5% subgroup had significantly higher OSDI score, meibomian gland orifice score, meibum expressibility scores, meibum quality scores, corneal fluorescein staining scores, and tear MMP-9 concentration than the HbA1c<7.5% subgroup(all P<0.05), accompanied by significantly shorter BUT and lower Schirmer I test results(all P<0.05). Similarly, the diabetes duration≥10 y subgroup showed significantly higher OSDI score, meibomian gland orifice score, meibum expressibility scores, meibum quality scores, corneal fluorescein staining scores, and tear MMP-9 concentration compared with the diabetes duration<10 y subgroup(all P<0.05), whereas BUT and Schirmer I values were significantly lower(all P<0.05).CONCLUSION: Diabetes mellitus may be associated with aggravated ocular surface damage in patients with MGD, accompanied by elevated tear MMP-9 levels. Poor glycemic control and longer disease duration are related to more severe ocular surface injury and higher tear MMP-9 levels. Tear MMP-9 may serve as a potential indicator for evaluating ocular surface inflammation and damage in diabetic patients with MGD, providing certain evidence for clinical treatment decision-making.

Objective To investigate the association between dietary patterns and adolescent development in girls in Pudong New Area，Shanghai. Methods Using a stratified cluster sampling method, a total of 998 girls were selected from the cohort of growth, development, and health of children and adolescents in Pudong New Area of Shanghai. Physical development examinations and dietary surveys were conducted on these girls. Principal component analysis was used to determine girls' dietary patterns, and their relationship with adolescent development was analyzed using logistic regression. Results Among the 998 participants, 770 (77.15%) were pubertal girls. The factor analysis identified three dietary patterns, fungi and algae~nuts~legumes pattern, meat-vegetables and fruits-cereals pattern, and milk-eggs pattern. Logistic regression analysis revealed that after adjusting for age, waist circumference, residential district, mother's education level, and father's education level, the Q2 level (OR=0.54, 95% CI: 0.30-0.99), Q3 level (OR=0.50, 95% CI: 0.27-0.91), and Q4 level (OR=0.49, 95% CI: 0.26-0.90) of the fungi and algae-nuts-legumes pattern were negatively correlated with adolescent development. The Q2 level (OR=0.48, 95% CI: 0.27-0.87) and Q3 level (OR=0.49, 95% CI: 0.27-0.88) of the milk-eggs pattern were also negatively correlated with adolescent development. Conclusion The fungi and algae~nuts~legumes pattern and milk-eggs patterns are inversely related to pubertal development.

ObjectiveTo screen and evaluate the antidepressant compounds of Curcumae Rhizoma， and explore its mechanism of regulating the nuclear factor erythroid 2-related factor 2（Nrf2）/glutathione（GSH） peroxidase 4（GPX4）/GSH pathway from an antioxidant perspective. MethodsThe antioxidant activities in vitro of 11 characteristic components from Curcumae Rhizoma， including curcumol， curgerenone， curdione， curzerene， curcumenol， curcumenone， dehydrocurdione， isocurcumenol， furanodienone， furanodiene and zederone， were detected using 1，1-diphenyl-2-picrylhydrazyl（DPPH） and 2，2'-azinobis-（3-ethylbenzothiazoline-6-sulphonic acid） diammonium salt（ABTS） radical scavenging assays. The depression in Drosophila melanogaster was induced by chronic unpredictable mild stress（CUMS）， and W1118 wild-type male D. melanogaster were randomly divided into blank group， model group， curcumol group， curgerenone group， curdione group， curzerene group， curcumenol group，curcumenone group， dehydrocurdione group， isocurcumenol group， furanodienone group， furanodiene group， zederone group and fluoxetine group（10 μmol·L^-1）. The treatment groups received a dose of 0.1 g·L^-1 of 11 characteristic components from Curcumae Rhizoma， while the blank and model groups were administered equivalent volumes of solvent. The sucrose preference test， climbing test and forced swimming test were used to evaluate the behavioral indicators of depression in D. melanogaster. Liquid chromatography-mass spectrometry（LC-MS） was used to detect the levels of 5-hydroxytryptamine（5-HT） and dopamine（DA） in the brain of D. melanogaster， and the entropy weight method was used to comprehensively evaluate neurobehavioral and neurotransmitter indicators， resulting in the identification of the antidepressant active components of Curcumae Rhizoma. In addition， a mouse depression model was established by CUMS， and C57BL/6J mice were randomly divided into blank group， model group， low and high dose groups of curzerene（0.5， 1 mg·kg^-1）， and fluoxetine group（10 mg·kg^-1） to confirm the antidepressant effect of the optimal active ingredient by behavioral analysis. Flow cytometry was used to detect the content of reactive oxygen species（ROS） in the hippocampus of mice from each group. Enzyme-linked immunosorbent assay was used to detect the contents of adenosine triphosphate（ATP）， superoxide dismutase（SOD）， catalase（CAT） and GSH. Transmission electron microscope（TEM） was used to observe the effect of curzerene on the ultrastructure of mitochondria in hippocampal tissue. Western blot was performed to determine the level of Nrf2 protein， and Nrf2 inhibitor（ML385） was used to verify the relationship between the antidepressant effect of curzerene and regulation of Nrf2. Real time fluorescence quantitative polymerase chain reaction（Real-time PCR） was employed to detect the effect of curzerene on the mRNA expression level of GPX. ResultsIn vitro antioxidant experiments showed that curzerene and curgerenone exhibited the most significant ability to scavenge free radicals， and comprehensive evaluation results of entropy weight method indicated that curzerene stood out as the most promising active component. Compared with the blank group， the model group exhibited a significant decrease in sucrose preference coefficient and the number of times entering the open field center（P<0.01）， as well as a significant increase in immobility time in the forced swimming and tail suspension tests（P<0.01）， and the ROS content in hippocampus significantly elevated（P<0.01）， while the ATP content significantly reduced（P<0.01）. In the hippocampal neurons of the model group， mitochondrial cristae were disordered， with vacuolation of the inner membrane and severe damage. Nrf2 protein expression level in the model group was significantly decreased（P<0.05）， and the antioxidant enzymes SOD， CAT and GSH contents were also significantly reduced（P<0.05， P<0.01）， and the gene expression levels of GPX1， GPX4 and GPX7 were significantly decreased（P<0.01）. Compared with the model group， the high-dose group of curzerene showed a significant increase in the sucrose preference coefficient and the number of times entering the open field center（P<0.05）， as well as a significant decrease in immobility time in the forced swimming and tail suspension tests（P<0.05， P<0.01）. The ROS content in the hippocampus of the high-dose group of curzerene was significantly reduced（P<0.01）， while the ATP content was significantly increased（P<0.05）. The neuronal mitochondrial damage in the hippocampus of the high-dose group of curzerene was alleviated， and the expression level of Nrf2 protein was significantly increased（P<0.05）. The Nrf2 inhibitor ML385 reversed the improvement of curzerene on depressive behaviors in CUMS mice. The GSH content in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.01）， while there were no significant differences in SOD and CAT contents. The expression level of GPX4 gene in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.05）， while there were no significant differences in other GPX genes. ConclusionCurzerene is the best component with antidepressant activity in Curcumae Rhizoma. It may improve mitochondrial dysfunction to exert its antidepressant effect by regulating Nrf2 and its downstream GPX4/GSH pathway rather than CAT or SOD pathways.

Objective:To analyze the research programs of clinical trials related to the TCM treatment of Hashimoto's thyroiditis (HT) at home and abroad; To provide references for the follow-up study of TCM treatment of HT.Methods:All clinical research registration plans for TCM prevention and treatment of HT were retrieved from the Chinese Clinical Trial Registry, the International Traditional Medicine Clinical Trial Registry, and the WHO International Clinical Trial Registration Platform from the establishment of the databases to December 31, 2024. Excel 2019 and GraphPad Prism 9.0 were used for data processing, and the basic characteristics, study types, randomized methods, interventions, outcome indicators and other registration information of registered trials with the frequency analysis.Results:A total of 31 clinical trials were included in this study, and the number of registered studies has gradually increased since 2018, which involving 23 clinical institutions in 9 provincial-level administrative regions until 2024. The region with the highest number of registrations is Shanghai (14 items). The funding sources were mainly local financial support and hospital funding. The research types were mostly intervention studies (30 items). The main research design type was randomized parallel controlled trials (27 items).Conclusions:At present, the overall number of registration studies on TCM prevention and treatment of HT is relatively small. However, in recent years, researchers have paid more attention to the registration of clinical trials in this field. The regional distribution of existing trial registration is not balanced, and the research design scheme needs to be improved.

Spinal cord injury(SCI)is a central nervous system disease that can lead to motor,sensory,and autonomic dysfunction.Depending on the state of immune microenvironment,macrophage polarization can differentiate into M1/M2 phenotypes.The regulation of macrophage polarization by stem cells in many pathophysiological processes of SCI has become a hot topic of research in recent years.This review summarizes the relationship between macrophage polarization and SCI,and how mesenchymal stem cells(MSCs)and neural stem cells(NSCs)regulate macrophage polarization to improve SCI through paracrine secretion,delivery molecules,derived exosomes,and metabolic reprogramming pathways.It also summarizes the mechanism by which stem cells regulate the macrophage polarization phenotypes to promote SCI recovery through signaling pathways such as Janus tyrosine kinase/signal transducer and activator of transcription(JAK/STAT),Notch,Toll-like receptor 4/nuclear factor kappa-B(TLR4/NF-κB),phosphatidylinositol 3 kinase/protein kinase B(PI3K/Akt).The aim is to provide theoretical support for the treatment of SCI by regulating macrophage polarization with stem cells and to offer new perspectives for exploring the mechanism of stem cell therapy for SCI.

Atherosclerosis(AS)is an inflammatory cardiovascular disease characterized by plaque accumulation in the arterial wall,leading to increased morbidity and mortality of related cardiovascular disorders.The main pathological mechanisms of AS include lipid deposition,oxidative stress,and chronic inflammation,with disease progression involving endothelial cell dysfunction,macrophage polarization,foam cell formation,and smooth muscle cell proliferation or apoptosis.Mitochondria are essential organelles that provide energy for cellular metabolism,and the mitochondrial quality control(MQC)system is the fundamental mechanism maintaining mitochondrial functional homeostasis.MQC dysfunction can induce vascular phenotype changes through pathways such as oxidative stress,apoptosis,and inflammation,thereby promoting the progression of AS.Therefore,targeting MQC to regulate mitochondrial function may become a new direction for the treatment of AS.This review summarizes the molecular mechanisms of MQC,including mitochondrial biogenesis,mitochondrial dynamics,and mitochondrial autophagy(mitophagy),and further elucidates the role of abnormal MQC in the pathological processes of AS,aiming to provide a scientific basis for identifying potential targets to delay the progression of AS and developing related drugs.

Objective To investigate the effects of remimazolam(REM)on cerebral ischemia-reperfusion injury(CIRI)rats and the AMP-activated protein kinase(AMPK)/NOD-like receptor protein 3(NLRP3)signaling pathway.Methods One hundred rats were selected to construct the CIRI rat model(Mod)and stochastically separated into a Mod group,low,medium,and high dose remifentanil groups(REM-L,REM-M,REM-H),and high dose remifentanil+pathway inhibitor Compound C group(REM-H+Compound C),with 20 rats in each group.Another 20 healthy rats were included as the control(Ctrl)group.All rats were subjected to neurobehavioral scoring.The water content,infarct area,and oxidative stress indicators of brain tissue were detected.The morphology and apoptosis of brain tissue were observed by HE and TUNEL staining.Western blotting was applied to detect protein expression related to the AMPK/NLRP3 signaling pathway.Results Compared with the Mod group,with the increase of REM dose,the movement disorders in rats were alleviated,the overall structure of brain tissue gradually recovered,pathological damage was reduced,the area of cerebral infarction,brain water content,and apoptosis rate of brain tissue cells decreased,reactive oxygen species(ROS)level,malondialdehyde(MDA)content,and NLRP3 and Caspase-1 protein expression levels decreased,superoxide dismutase the(SOD)content and AMPK protein expression level increased(P＜0.05).Compared with the REM-H group,the REM-H+Compound C group showed aggravated motor disorders,and more severe pathological damage to brain tissue,the area of cerebral infarction,cerebral water content and apoptosis rate of brain tissue cells increased,the ROS level,MDA content and the protein expression of NLRP3 and Caspase-1 increased,while the content of SOD and the protein expression decreased(P＜0.05).Conclusion Remimazolam can enhance the antioxidant function of the body,reduce brain cell apoptosis,alleviate brain tissue injury,and thus have a certain protective effect on ischemia-reperfusion brain injury in rats,the mechanism of which may be related to the activation of the AMPK/NLRP3 signaling pathway.

Objective:To investigate the prognostic value of the combined use of central venous-arterial carbon dioxide partial pressure difference/arterial-central venous oxygen content difference ratio (Pv-aCO 2/Ca-vO 2) combined with peripheral perfusion index (PI) for prognosis in middle-aged and elderly patients with acute heart failure (AHF) complicated by hypoperfusion. Methods:A case-control study was conducted, enrolling middle-aged and elderly AHF patients with tissue hypoperfusion admitted to the Emergency Intensive Care Unit of Nanjing First Hospital from May 2022 to May 2024. The primary endpoint was 28-day all-cause mortality. Patients were divided into survival and death groups based on prognosis. Baseline characteristics and clinical data were compared between groups. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive performance of risk factors. Stratified analysis based on optimal cutoff values was performed, and Kaplan-Meier survival curves were used to compare prognostic differences between subgroups.Results:A total of 70 patients with AHF and hypoperfusion were enrolled, with 36 deaths (28-day mortality rate: 51.43%). No significant differences were observed in baseline characteristics, N-terminal B-type natriuretic peptide precursor, creatine kinase, creatine kinase-myocardial band, cardiac troponin I,central venous pressure, or left ventricular ejection fraction between groups(all P>0.05). Compared with the survival group, the death group exhibited significantly higher APACHEⅡ scores, lactate levels, and Pv-aCO 2/Ca-vO 2 ratios, along with lower PI values (all P<0.05). The area under the ROC curve (AUCs) for PI, Pv-aCO 2/Ca-vO 2, and their combination in predicting 28-day mortality were 0.804 (95% CI: 0.701-0.908), 0.848 (95% CI: 0.758-0.938), and 0.922 (95% CI: 0.859-0.985), respectively. The optimal cutoff value for PI was 1.17 (sensitivity 83.3% and specificity 67.6%), and for Pv-aCO 2/Ca-vO 2 was 1.59 (sensitivity 77.8% and specificity 79.4%). Stratified analysis revealed that the PI≤1.17 group had a significantly higher 28-day mortality rate than the PI>1.17 group ( P<0.01), and the Pv-aCO 2/Ca-vO 2>1.59 group had a markedly higher mortality rate than the Pv-aCO 2/Ca-vO 2≤1.59 group ( P<0.01) ,consistent with Kaplan-Meier survival analysis. Conclusion:Early assessment of Pv-aCO 2/Ca-vO 2 combined with PI demonstrates superior predictive performance for prognosis in AHF patients with hypoperfusion.