Diseases of the central nervous system have become a growing global health concern. At present， there are many adverse reactions in the treatment with Western medicine. In contrast， traditional Chinese medicine has shown unique efficacy and rich clinical practice accumulation in diseases of the central nervous system. As a traditional Chinese medicine， Bupleuri Radix has played an important role in the treatment of neurological diseases through multi-target regulation， multi-pathway intervention， and multi-pathway mechanism of action. In recent years， with the in-depth study of the pharmacological effects of Bupleuri Radix， it has been found that the active ingredients such as saikosaponin， baicalin， quercetin， and kaempferol in Bupleuri Radix can be used as the main material basis for the treatment of neurological diseases. The results of this study showed that in neurodegenerative diseases， active ingredients of Bupleuri Radix can inhibit β-amyloid （Aβ） deposition and abnormal phosphorylation of microtubule-associated protein （Tau protein） in Alzheimer's disease， regulate the nuclear factor-κB/nuclear factor E₂ related factor 2 （NF-κB/Nrf2） pathway to play the anti-inflammatory role， and alleviate α-Synuclein （α-Syn） aggregation and mitochondrial damage in Parkinson's disease. In epilepsy， depression， and cerebral ischemia， they can improve symptoms by regulating neurotransmitters， oxidative stress， and apoptosis pathways， and inhibit brain glioma proliferation. However， the mechanism of action has not been fully elucidated， and the complexity of compound components and poor blood-brain barrier penetration limit their clinical application. In the future， it is necessary to integrate multi-omics， network pharmacology， and nano-delivery technologies， focus on the optimization of active ingredient group compounds and the precise guidance of biomarkers， accelerate the development of innovative therapies for Alzheimer's disease， Parkinson's disease， and other diseases for laying a solid theoretical foundation for further development and application and inspiring new research ideas.

ObjectiveTo conduct a theoretical study on the medical-rehabilitation integration. MethodsStarting from the background, objectives and content of the medical-rehabilitation integration, this study analyzed its innovative points from the dimensions of conceptual innovation, organizational innovation, model innovation and technological innovation. Results and ConclusionThe medical-rehabilitation integration is an innovation in medical services that takes conceptual innovation as the forerunner, organizational innovation as the foundation, model innovation as the carrier and technological innovation as the core.

ObjectiveAbnormal lipids in neurons can cause the accumulation of α-synuclein（α-syn）. This study aimed to explore the mechanism of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis extract （ASH） in treating Parkinson's disease （PD） mice using lipidomics combined with network pharmacology. MethodsMice were divided into the blank group， model group and ASH （45.5 mg·kg^-1） group. Motor ability was evaluated by pole climbing time and autonomous activity count； The oxidative stress indicators were detected by enzyme-linked immunosorbent assay （ELISA）. Lipid biomarkers in brain tissues were screened and identified by ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， and metabolic pathway analysis was conducted. The key targets of ASH for PD treatment were explored using network pharmacology. The Kyoto Encyclopedia of Genes and Genomes （KEGG） database was used for pathway enrichment analysis， and the "compound-reaction-enzyme-gene" network was constructed using the MetScape plugin. The protein expression levels of glutathione S-transferase P1 （GSTP1）， glutathione S-transferase Mu 2 （GSTM2）， prostaglandin peroxide synthase 1 （PTGS1）， prostaglandin peroxide synthase 2 （PTGS2）， and prostaglandin E synthase （PTGES） were validated by Western blot. ResultsCompared with the blank group， the model group showed significantly prolonged pole climbing time and reduced autonomous activity count （P<0.01）. Compared with the model group， the ASH group demonstrated significantly faster pole climbing and increased autonomous activity count （P<0.01）. The model group exhibited significantly decreased superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） levels， and increased malondialdehyde （MDA） level in brain tissues compared with the blank group （P<0.01）. The ASH group showed increased SOD and GSH-Px levels and decreased MDA level compared with the model group （P<0.05， P<0.01）. Lipidomics analysis identified 10 differential metabolites and 8 differential metabolic pathways. Network pharmacological analysis revealed 213 intersection targets between ASH components and PD， with KEGG enrichment involving the sphingolipid signaling pathway， lipid arteriosclerosis， phosphoinositide 3-kinase/protein kinase B（PI3K/Akt） signaling pathway， mitogen-activated protein kinase（MAPK） signaling pathway， and hypoxia inducible factor-1（HIF-1） signaling pathway. Integrated lipidomics and network pharmacology analysis highlighted the central role of the arachidonic acid metabolic pathway. The Western blot results showed that ASH effectively up-regulated GSTP1， GSTM2， and PTGS1 protein expression， and down-regulated PTGS2 and PTGES protein expression. ConclusionASH can ameliorate behavioral deficits， exert antioxidant effects， regulate lipid differential metabolites and the arachidonic acid metabolic pathway， thereby exerting therapeutic effects in PD model mice.

ObjectiveTo explore the improving effect of Huangqi Chifengtang（HCT） on atherosclerosis（AS）， and elucidate its mechanism in relation to adenosine monophosphate-activated protein kinase（AMPK）/peroxisome proliferator-activated receptor α（PPARα） signaling pathway and nucleotide-binding oligomerization domain（NOD）-like receptor thermal protein domain associated protein 3（NLRP3） inflammasome. MethodsEight C57BL/6J mice were set as the normal group， and 32 ApoE^-/- mice were randomly divided into the model group， the positive drug group（atorvastatin， 5 mg·kg^-1·d^-1）， HCT low- and high-dose groups（1.95， 3.90 g·kg^-1·d^-1）. ApoE^-/- mice were fed with high-fat and high-cholesterol feed to establish an AS mouse model. After modeling， they were orally administered corresponding dose of drugs for 28 days， while the normal and model groups received an equal volume of physiological saline via oral gavage. Hematoxylin-eosin（HE） staining was used to observe the pathological status of the aorta and liver in mice， Biochemical testing and enzyme-linked immunosorbent assay（ELISA） were used to detect the levels of total cholesterol（TC）， triglycerides（TG）， low-density lipoprotein cholesterol（LDL-C）， alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， C-reactive protein（CRP）， interleukin（IL）-1β， IL-18 in the serum， as well as superoxide dismutase（SOD）， malondialdehyde（MDA）， and reduced glutathione（GSH） in the liver. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to measure the mRNA expression levels of NLRP3， apoptosis-associated speck-like protein（ASC）， cysteinyl aspartate specific proteinase-1（Caspase-1）， Toll-like receptor 4（TLR4） in the aorta， and fatty acid synthase（FAS）， stearoyl-CoA desaturase 1（SCD1）， PPARα， and carnitine palmitoyltransferase 1A（CPT1A） in the liver. Immunohistochemistry was used to determine the protein expressions of NLRP3， Caspase-1， and ASC in the aorta， and Western blot was used to measure the protein expressions of AMPK， p-AMPK， sterol regulatory element binding protein-1c（SREBP-1c）， CPT1A， and FAS in the liver. ResultsCompared with the normal group， the model group showed a significant increase in lipid plaque deposition in the aorta and lipid accumulation in the liver， the levels of TC， TG， LDL-C， AST， ALT， IL-1β， IL-18 and CRP in the serum were significantly increased（P<0.01）， and the mRNA and protein expressions of aortic TLR4， NLRP3， Caspase-1 and ASC were significantly upregulated（P<0.01）. The levels of SOD and GSH in the liver were significantly reduced， while the level of MDA was significantly increased（P<0.01）. The mRNA expressions of FAS and SCD1 in the liver were significantly downregulated， while the mRNA expressions of PPARα and CPT1A were significantly upregulated. The protein expressions of p-AMPK/AMPK and CPT1A in the liver were significantly reduced， while the expressions of SREBP-1c and FAS proteins were significantly increased（P<0.01）. Compared with the model group， the low- and high-dose HCT groups showed significant improvements in aortic plaques and hepatic lipid deposition. The levels of TC， LDL-C， AST， IL-1β and IL-18 in the serum of the low-dose HCT group， as well as TC， TG， LDL-C， AST， ALT， IL-1β， IL-18 and CRP in the serum of the high-dose HCT group， were significantly reduced（P<0.01）. The mRNA expressions of TLR4， NLRP3 and Caspase-1 in the aorta of the low-dose HCT group， as well as TLR4， NLRP3， Caspase-1 and ASC in the aorta of the high-dose HCT group， were significantly downregulated（P<0.01）. The protein expressions of Caspase-1 and ASC in the aorta of the low-dose HCT group， as well as NLRP3， Caspase-1 and ASC in the high-dose HCT group， were significantly downregulated（P<0.01）. The levels of SOD and GSH in the liver of the low- and high-dose HCT groups were significantly increased， while the level of MDA in the high-dose HCT group was significantly decreased（P<0.05， P<0.01）. In the HCT-treated group， the mRNA expressions of FAS and SCD1 in the liver were significantly upregulated， while the mRNA expressions of PPARα and CPT1A were significantly downregulated， the protein expressions of p-AMPK/AMPK and CPT1A in the liver were significantly increased， while the protein expressions of SREBP-1c and FAS were significantly decreased（P<0.05， P<0.01）. ConclusionHCT can improve lipid metabolism by activating the AMPK/PPARα pathway and inhibit NLRP3 inflammasome-mediated inflammatory responses， thereby reducing hepatic lipid deposition and AS plaque formation.

BackgroundAdolescents with depressive disorder often engage in non-suicidal self-injury （NSSI） behaviors， which severely impacts their physical and mental health. Impulsivity and emotional regulation are key factors influencing NSSI behaviors. However， research on the mechanisms through which impulsivity and emotional regulation affect NSSI behaviors in adolescent depressive disorder patients with NSSI remains insufficient， limiting the development of effective intervention strategies. ObjectiveTo explore the differences in impulsivity and emotion regulation abilities between adolescent patients with depressive disorder accompanied by and without NSSI behaviors， and to analyze the association between NSSI behaviors and impulsivity and emotion regulation abilities in adolescent patients with depressive disorder accompanied by NSSI behaviors. MethodsA total of 184 adolescents hospitalized in the child and adolescent psychiatry department of Wuxi Mental Health Center from October 2023 to August 2024， who met the diagnostic criteria for depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）， were consecutively enrolled as study subjects. Based on the diagnostic criteria for NSSI in DSM-5， patients were divided into NSSI group （n=108） and non-NSSI group （n=76）. The Barratt Impulsiveness Scale-11 （BIS-11）， the Emotion Regulation Questionnaire （ERQ）， the Adolescent Self-Harm Questionnaire， and the Positive and Negative Suicide Ideation （PANSI） were used for assessment. Spearman correlation analysis was employed to explore the correlation between the scores of the Adolescent Self-Harm Questionnaire and the scores of BIS-11 and ERQ in the NSSI group. Multiple regression analysis was conducted to examine the effects of impulsivity and emotion regulation on NSSI behaviors in the NSSI group. ResultsCompared to the non-NSSI group， the NSSI group showed significantly higher scores in BIS-11 non-planned impulsivity （Z=-4.181， P<0.05）， action impulsivity （t=4.944， P<0.05）， cognitive impulsivity （Z=-3.392， P<0.05）， and total score （t=4.763， P<0.05）， and lower scores in the cognitive reappraisal of ERQ （t=-4.094， P<0.05） and total score （Z=-2.299， P<0.05）， and higher scores in the expression inhibition of ERQ （Z=-3.019， P<0.05）. The correlation analysis results showed that the score of the adolescent self-harm questionnaire in the NSSI group was positively correlated with the behavioral impulsivity factor score in the BIS-11 （r=0.434， P<0.05）. Multiple regression analysis indicated that action impulsivity factor was a significant correlate of self-injury behaviors in the NSSI group （B=0.855， P<0.05）， explaining 22.30% of the total variance. ConclusionAdolescent patients with depressive disorder accompanied by NSSI behaviors exhibit higher levels of impulsivity and poorer emotional regulation abilities. Action impulsivity may play a significant role in the mechanism of NSSI behaviors. ［Funded by Wuxi Municipal Health Commission Research Project （number， Q202320）］

Nervous system diseases， also known as neuropathies， encompass a wide range of conditions， primarily including Alzheimer's disease （AD）， Parkinson's disease （PD）， Huntington's disease， and other neurodegenerative disorders， as well as depression， subarachnoid hemorrhage， cerebral ischemia-reperfusion injury， vascular dementia， and other neurological diseases. These diseases pose serious threats to the health and lives of patients， bringing heavy burdens to society and families. The pathogenesis of nervous system diseases is highly complex， involving mechanisms such as neuroinflammation， oxidative stress， apoptosis， endoplasmic reticulum stress， mitochondrial dysfunction， brain-derived neurotrophic factor deficiency， reduced cholinergic activity， axonal injury， and demyelination. In recent years， the incidence and mortality of nervous system diseases have been rising annually. Currently， western medicine primarily focuses on symptomatic treatment， often accompanied by many adverse reactions， including lethargy， excessive sedation， dizziness， headaches， tachycardia， liver function damage， metabolic disorders， and incomplete recovery after surgery. As a traditional Chinese medicine， Salviae Miltiorrhizae Radix et Rhizoma has effects such as promoting blood circulation， removing blood stasis， cooling the blood， clearing the heart， nourishing the blood， and calming the nerves. It can play a role in the treatment and protection against nervous system diseases through multiple targets， pathways， and mechanisms. Studies have found that the water-soluble phenolic acids and fat-soluble diterpenoid quinones in Salviae Miltiorrhizae Radix et Rhizoma are the main active ingredients for the treatment of nervous system diseases. This paper summarized the effects of the active components and compounds of Salviae Miltiorrhizae Radix et Rhizoma on nervous system diseases over the past ten years， aiming to provide a theoretical basis and research ideas for the development and application of active components and compounds of Salviae Miltiorrhizae Radix et Rhizoma in nervous system diseases.

OBJECTIVE To explore the mechanism of improvement effect of Chanbao zhichuang suppository （CBZCS） on hemorrhoids in rats through network pharmacology and metabolomics. METHODS A hemorrhoid model was established by subcutaneous injection of rhododendron oil to induce anal swelling. SD rats were divided into blank group （NC group， 0.32 g/kg vaseline）， model group （Model group， 0.32 g/kg vaseline）， CBZCS low-， medium-， and high-dose groups （CBZCS-L， CBZCS- M， CBZCS-H groups， with dosages of 0.16， 0.32， and 0.64 g/kg respectively）， and Mayinglong musk hemorrhoids suppository group （Positive group， 0.32 g/kg）， with 9 rats in each group. Anal administration was performed at 6， 12， 24， 48， and 72 hours after modeling. After the last administration， the pathological changes of the anal tissues in rats were observed， and the serum levels of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in rats were detected. Differential metabolite analysis and enrichment analysis were conducted by metabolomics methods， and the target proteins of CBZCS in treating hemorrhoids were obtained by network pharmacology. The core metabolic pathways were screened by interaction and enrichment analysis of differential metabolites and proteins， and the core proteins were experimentally verified. RESULTS Compared with the NC group， the anal tissues of the Model group showed obvious lesions， and the levels of IL-6 and TNF- α in the serum were significantly increased （P＜0.05）； compared with the Model group， the pathological damage of the anal tissues in the treatment groups was alleviated to varying degrees， and serum levels of IL-6 in CBZCS-H group， CBZCS-M group， and Positive group as well as serum levels of TNF-α in CBZCS-H group were significantly reduced （P＜0.05）. The metabolomics results showed that 34 differential metabolites were screened from the anal tissues of rats， and 22 of them showed a return after CBZCS administration. The differential metabolites mainly enriched in arachidonic acid metabolism， histidine metabolism， and glycerophospholipid metabolism. Through the network pharmacology， 138 intersection genes of CBZCS against hemorrhoids were determined. The analysis results showed that differential metabolites and target proteins were mainly enriched in the arachidonic acid metabolism pathway， and the regulation of this pathway might be related to cyclooxygenase-2 （COX-2）， Myc proto-oncogene protein （c-MYC）， cytochrome P450 1B1 （CYP1B1）， interleukin-1β （IL-1β）， and IL-6 protein expression. The experimental verification results showed that the expression levels of key proteins （COX-2， c-MYC， CYP1B1， IL-6， IL-1β） in the anal tissues of the Model group were significantly higher than those in the NC group （P＜0.05）， and the levels of the above proteins in the anal tissues of CBZCS-H group and Positive group were significantly lower than those in the Model group （P＜0.05）. CONCLUSIONS The mechanism of CBZCS in treating hemorrhoids may be to inhibit the expression of COX-2， c-MYC and CYP1B1 proteins， thereby inhibiting arachidonic acid metabolism and reducing the release of inflammatory factors IL-6 and IL-1β.

This paper aimed to use non-targeted urine metabolomics to reveal the potential biomarkers of toxicity in rats with hepatic injury induced by aqueous extracts of Dictamni Cortex(ADC). Forty-eight SD rats were randomly assigned to a blank group and high-dose, medium-dose, and low-dose ADC groups, with 12 rats in each group(half male and half female), and they were administered orally for four weeks. The hepatic injury in SD rats was assessed by body weight, liver weight/index, biochemical index, L-glutathione(GSH), malondialdehyde(MDA), and pathological alterations. The qPCR was utilized to determine the expression of metabolic enzymes in the liver and inflammatory factors. Differential metabolites were screened using principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA), followed by a metabolic pathway analysis. The Mantel test was performed to assess differential metabolites and abnormally expressed biochemical indexes, obtaining potential biomarkers. The high-dose ADC group showed a decrease in body weight and an increase in liver weight and index, resulting in hepatic inflammatory cell infiltration and hepatic steatosis. In addition, this group showed elevated levels of MDA, cytochrome P450(CYP) 3A1, interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α), as well as lower levels of alanine transaminase(ALT) and GSH. A total of 76 differential metabolites were screened from the blank and high-dose ADC groups, which were mainly involved in the pentose phosphate pathway, tryptophan metabolism, purine metabolism, pentose and glucuronic acid interconversion, galactose metabolism, glutathione metabolism, and other pathways. The Mantel test identified biomarkers of hepatotoxicity induced by ADC in SD rats, including glycineamideribotide, dIDP, and galactosylglycerol. In summary, ADC induced hepatotoxicity by disrupting glucose metabolism, ferroptosis, purine metabolism, and other pathways in rats, and glycineamideribotide, dIDP, and galactosylglycerol could be employed as the biomarkers of its toxicity.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Metabolomics ; Biomarkers/metabolism* ; Liver/metabolism* ; Drugs, Chinese Herbal/adverse effects* ; Female ; Chemical and Drug Induced Liver Injury/metabolism* ; Glutathione/metabolism* ; Humans

This study developed a core outcome set(COS) for traditional Chinese medicine(TCM) interventions in diabetic peripheral neuropathy(DPN), standardizing evaluation metrics for TCM efficacy and providing a new framework for DPN treatment and management. A systematic search was conducted across databases, including CNKI, Wanfang, and PubMed, targeting clinical trial literature published between January 1, 2013, and January 1, 2023. The search focused on extracting outcome indicators and measurement tools used in TCM treatments for DPN. Retrospective data collection was performed from January 2018 to June 2023, involving 200 DPN patients hospitalized at the Department of Endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine. Additionally, semi-structured interviews were conducted with inpatients, outpatients, their families, and nursing staff to further refine and enhance the list of outcome indicators. After two rounds of Delphi questionnaire survey and consensus meeting, a consensus was reached. The study initially retrieved 3 421 publications, of which 170 met the inclusion criteria after review. These publications, combined with retrospective analysis and semi-structured interviews, supplemented the list of indicators. After two rounds of Delphi surveys, experts agreed on 24 indicators and 6 measurement tools. The final COS determined by expert consensus meeting included 5 domains and 13 outcome indicators: neurological function signs, quality of life, TCM syndrome score, nerve conduction velocity, current perception threshold test, fasting blood glucose, 2 h postprandial blood glucose, glycated hemoglobin, complete blood count, urinalysis, liver function test, kidney function test, and electrocardiogram.
Humans ; Diabetic Neuropathies/drug therapy* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Male ; Female

This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively. In the in vitro study, the authors subjected the NRK52E cells with or without knock-down Z-DNA binding protein 1(ZBP1) to a high-glucose(HG) environment and various treatments including TFA, EM, and TFA+EM. In the in vivo and in vitro studies, The authors investigated the relative characteristics of renal tubular injury and renal tubular epithelial cells damage induced by reactive oxygen species(ROS), analyzed the relative characteristics of renal tubular PANoptosis and ZBP1-mediatted PANoptosis in renal tubular epithelial cells, and compared the relative characteristics of the protein expression levels of marked molecules of mitochondrial fission in the kidneys and mitochondrial homeostasis in renal tubular epithelial cells, respectively. Furthermore, in the network pharmacology study, the authors predicted and screened targets of TFA and EM using HERB and SwissTargetPrediction databases; The screened chemical constituents and targets of TFA and EM were constructed the relative network using Cytoscape 3.7.2 network graphics software; The relative targets of DT were integrated using OMIM and GeneCards databases; The intersecting targets of TFA, EM, and DT were enriched and analyzed signaling pathways by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG) software using DAVID database. In vivo study results showed that TFA+EM could improve renal tubular injury, the protein expression levels and characteristics of key signaling molecules in PANoptosis pathway in the kidneys, and the protein expression levels of marked molecules of mitochondrial fission in the kidneys. And that, the ameliorative effects in vivo of TFA+EM were both superior to TFA or EM. Network pharmacology study results showed that TFA+EM treated DT by regulating the PANoptosis signaling pathway. In vitro study results showed that TFA+EM could improve ROS-induced cell injury, ZBP1-mediatted PANoptosis, and mitochondrial homeostasis in renal tubular epithelial cells under a state of HG, including the protein expression levels of marked molecules of mitochondrial fission, mitochondrial ultrastructure, and membrane potential level. And that, the ameliorative effects in vitro of TFA+EM were both superior to TFA or EM. More importantly, using the NRK52E cells with knock-down ZBP1, the authors found that, indeed, ZBP1 was mediated PANoptosis in renal tubular epithelial cells as an upstream factor. In addition, TFA+EM could regulate the protein expression levels of marked signaling molecules of PANoptosis by targeting ZBP1. In summary, this study clarified that TFA+EM, different from TFA or EM, could attenuate DT with multiple targets by ameliorating mitochondrial homeostasis and inhibiting ZBP1-mediated PANoptosis. These findings provide the clear pharmacological evidence for the clinical treatment of DT with a novel strategy of TFA+EM, which is named "coordinated traditional Chinese and western medicine".
Animals ; Rats ; Mitochondria/metabolism* ; Benzhydryl Compounds/administration & dosage* ; Glucosides/administration & dosage* ; Abelmoschus/chemistry* ; Male ; Homeostasis/drug effects* ; Flavones/administration & dosage* ; Rats, Sprague-Dawley ; Diabetic Nephropathies/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; DNA-Binding Proteins/genetics* ; Humans ; Apoptosis/drug effects*