To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

ObjectiveTo investigate the effects of salidroside （SAL） on the impaired bioactivity of endothelial progenitor cells （EPCs） in atherosclerotic （As） mice and the potential mechanisms regarding AMP-activated protein kinase （AMPK）. MethodsAtherosclerosis was induced in 8-week-old male ApoE^-/- mice with high-fat diet. Intragastric administration of SAL was given to one mice group to investigate the effects of SAL on aortic plaque burden， plasma NO level， the migration and angiogenic capabilities of bone marrow-derived EPCs （BM-EPCs）. The proliferation， migration and vasculogenic properties of EPCs isolated from As mice were investigated in vitro. AMPK-sh-RNA or the AMPK inhibitor Compound C was used to investigate the role of AMPK/Akt/eNOS pathway in the regulatory effects of SAL. ResultsCompared with As group， NO level was significantly elevated in SAL group. The sizes of atherosclerotic plaques at the aortic root were reduced with smaller lipid cores in SAL group compared with As group. Moreover， the migration and angiogenesis capacity of EPCs markedly decreased in As mice， while SAL treatment reversed these impairments. Incubation with SAL at concentrations of 20， 40， and 80 μmol/L for 48 hours significantly promoted the proliferation， migration， and angiogenesis of EPCs. AMPK-sh-RNA transfection abrogated the 20 μmol/L SAL improvement in EPC biological activities. Western blot analysis further demonstrated that treatment with Compound C blocked the activation of AMPK/Akt/eNOS signaling pathway induced by SAL. ConclusionSAL upregulates the biological functions of EPCs through activating the AMPK/Akt/eNOS signaling pathway， thereby ameliorating EPC dysfunction during the pathological progression of atherosclerosis.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

ObjectiveTo analyze the volatile components in raw Coptidis Rhizoma， Euodiae Fructus juice-processed Coptidis Rhizoma （Yuhuanglian）， and the processing adjuvant Euodiae Fructus juice， identify marker volatile components in the processed product， and elucidate the material basis changes during the processing with Euodiae Fructus juice. MethodsHeadspace solid-phase microextraction coupled with gas chromatography-quadrupole-time-of-flight mass spectrometry （HS-SPME-GC-Q-TOF-MS） was employed to analyze the volatile components in raw Coptidis Rhizoma， Yuhuanglian， and Euodiae Fructus juice. Chemometric analysis was performed to compare volatile components among samples and screen the marker components. Finally， the relative odor activity value （ROAV） was calculated to investigate odor characteristics. ResultsA total of 127 components were detected， with 27， 75， 84 volatile components identified in Euodiae Fructus juice， raw Coptidis Rhizoma， and Yuhuanglian， respectively. Processing with Euodiae Fructus juice significantly increased the number and content of volatile components. Chemometric analysis revealed significant changes in volatile components among the three sample types， allowing clear discrimination. After processing， 39 components such as methyl octanoate and allyl propionate were introduced， while 34 components including furfural and hexanoic acid increased in content， and 11 components including butyric acid and octanal decreased. Additionally， eight components， including zingiberene， 6-methyl-6-hepten-2-one， and 5-methyl-2-hexanone， were screened as marker components of Yuhuanglian. Moreover， processing enhanced the ROAV values of 2，5-dimethylpyrazine （roasted， nutty， coffee-like aroma）， 3-ethylphenol， and guaiacol （smoky， woody aroma）. Additionally， it incorporated 1-hepten-3-one from Euodiae Fructus juice and the newly generated 1-hexen-3-one， contributing mushroom and cucumber-like odors. The sensory profile of Yuhuanglian integrated nutty， roasted， smoky， and woody notes with the citrus and fruity aroma originally contributed by octanal. ConclusionThe processing with Euodiae Fructus juice introduced components from adjuvant， significantly altering the volatile component profile and enhancing the sensory odor characteristics of Yuhuanglian. This study provides a valuable reference for exploring the material basis of volatile components and establishing processing specifications for Yuhuanglian.

ObjectiveTo analyze the volatile components in raw Coptidis Rhizoma， Euodiae Fructus juice-processed Coptidis Rhizoma （Yuhuanglian）， and the processing adjuvant Euodiae Fructus juice， identify marker volatile components in the processed product， and elucidate the material basis changes during the processing with Euodiae Fructus juice. MethodsHeadspace solid-phase microextraction coupled with gas chromatography-quadrupole-time-of-flight mass spectrometry （HS-SPME-GC-Q-TOF-MS） was employed to analyze the volatile components in raw Coptidis Rhizoma， Yuhuanglian， and Euodiae Fructus juice. Chemometric analysis was performed to compare volatile components among samples and screen the marker components. Finally， the relative odor activity value （ROAV） was calculated to investigate odor characteristics. ResultsA total of 127 components were detected， with 27， 75， 84 volatile components identified in Euodiae Fructus juice， raw Coptidis Rhizoma， and Yuhuanglian， respectively. Processing with Euodiae Fructus juice significantly increased the number and content of volatile components. Chemometric analysis revealed significant changes in volatile components among the three sample types， allowing clear discrimination. After processing， 39 components such as methyl octanoate and allyl propionate were introduced， while 34 components including furfural and hexanoic acid increased in content， and 11 components including butyric acid and octanal decreased. Additionally， eight components， including zingiberene， 6-methyl-6-hepten-2-one， and 5-methyl-2-hexanone， were screened as marker components of Yuhuanglian. Moreover， processing enhanced the ROAV values of 2，5-dimethylpyrazine （roasted， nutty， coffee-like aroma）， 3-ethylphenol， and guaiacol （smoky， woody aroma）. Additionally， it incorporated 1-hepten-3-one from Euodiae Fructus juice and the newly generated 1-hexen-3-one， contributing mushroom and cucumber-like odors. The sensory profile of Yuhuanglian integrated nutty， roasted， smoky， and woody notes with the citrus and fruity aroma originally contributed by octanal. ConclusionThe processing with Euodiae Fructus juice introduced components from adjuvant， significantly altering the volatile component profile and enhancing the sensory odor characteristics of Yuhuanglian. This study provides a valuable reference for exploring the material basis of volatile components and establishing processing specifications for Yuhuanglian.

Jianghuanglian is one of the representative processed products of Coptidis Rhizoma for treating cold syndrome with drugs of heat nature， and ginger is used to restrict the bitter cold of Coptidis Rhizoma， which can be traced back to Bojifang， and it is suitable for stagnation of damp-heat in middle-jiao， cold-heat mutual knots and other symptoms. Jianghuanglian retains the alkaloids， phenylpropanoids and flavonoids of Coptidis Rhizoma， and also introduces gingerol components such as 6-gingerol in ginger， which has pharmacological activities such as anti-inflammatory， antibacterial， anti-tumor， and improving gastrointestinal function. The 2020 edition of Chinese Pharmacopoeia and many local processing specifications have included the traditional processing process and quality standards of Jianghuanglian， but the specific process parameters and quality standards are incomplete， which limits the production and clinical application of this processed product. By summarizing the processing history， process research， quality evaluation， pharmacodynamic and medicinal property changes and application of Jianghuanglian in the past 20 years， there are differences in the processing methods and standards in various provinces and cities， which are mainly reflected in the preparation method， dosage， processing process and quantitative standards of ginger juice. In addition， there are also certain differences in the changes of the main components of Jianghuanglian prepared from ginger or dried ginger， as well as their efficacy and medicinal properties. The research on the processing process of Jianghuanglian plays an important role in improving its quality standards， and this review can provide a reference for improving the quality evaluation system of Jianghuanglian.

Objective To develop a predictive model for postoperative mortality risk in patients with acute aortic dissection(AAD)using the Extreme Gradient Boosting(XGBoost)algorithm combined with Shapley Additive Explanation(SHAP),and to establish a prediction website to serve as a diagnostic and therapeutic support platform for clinicians and patients.Methods A retrospective cohort study design was adopted.Data from 782 AAD patients who underwent surgical treatment at the Fourth Hospital of Hebei Medical University from January 2013 to December 2023 were collected,including basic information and initial serum biomarker test results.Patients were randomly divided into training and test sets at a 7:3 ratio.An external validation set consisting of 313 AAD patients admitted to the Second Hospital of Hebei Medical University from January 2020 to December 2023 was also established for further model validation.Variables were screened using LASSO regression,and an XGBoost machine learning model was constructed and interpreted using SHAP.The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curve analysis.Using the Shiny package,the XGBoost model was deployed to shinyapps.io to create a prediction website for postoperative mortality risk in AAD patients.One patient was selected by simple random sampling from the test set and the external validation set respectively for the prediction example on the Shiny webpage.Results The XGBoost model demonstrated high predictive performance for postoperative mortality in AAD patients,with area under the ROC curve(AUC)values of 0.928(95%CI 0.901-0.956)in the training set,0.919(95%CI 0.891-0.949)in the test set,and 0.941(95%CI 0.915-0.967)in the external validation set.SHAP values indicated the following order of variable importance in the model(from highest to lowest):"lactate dehydrogenase""blood chlorine""multiple organ injury""carbon dioxide combining power""prothrombin time""α-hydroxybutyric acid""creatine kinase isoenzyme""Stanford classification""combined use of bedside blood purification""gender""acute kidney injury""gastrointestinal bleeding""brain injury"and"shock".A risk prediction website for adverse postoperative outcomes in AAD patients was developed using XGBoost-SHAP method(https://dun-dunxiaolu.shinyapps.io/document/)and validated with examples.One randomly selected patient from each of the test and external validation sets was applied:the predicted mortality risk value for patient 1(who died postoperatively)was 0.9539,and that for patient 2(who survived postoperatively)was 0.0206.Conclusions The XGBoost-SHAP model demonstrates high accuracy in predicting postoperative mortality risk for AAD patients.The online prediction tool established based on this model enhances the identification efficiency of high-risk postoperative mortality patients.

The study aimed to investigate the effect of the CD200R1 gene deletion on microglia activation and nigrostriatal dopamine neuron loss in the Parkinson's disease (PD) process. The CRISPR-Cas9 technology was applied to construct the CD200R1^-/- mice. The primary microglia cells of wild-type and CD200R1^-/- mice were cultured and treated with bacterial lipopolysaccharide (LPS). Microglia phagocytosis level was assessed by a fluorescent microsphere phagocytosis assay. PD mouse model was prepared by nigral stereotaxic injection of recombinant adeno-associated virus vector carrying human α-synuclein (α-syn). The changes in the motor behavior of the mice with both genotypes were evaluated by cylinder test, open field test, and rotarod test. Immunohistochemical staining was used to assess the loss of dopamine neurons in substantia nigra. Immunofluorescence staining was used to detect the expression level of CD68 (a key molecule involved in phagocytosis) in microglia. The results showed that CD200R1 deletion markedly enhanced LPS-induced phagocytosis in vitro by the microglial cells. In the mouse model of PD, CD200R1 deletion exacerbated motor behavior impairment and dopamine neuron loss in substantia nigra. Fluorescence intensity analysis results revealed a significant increase in CD68 expression in microglia located in the substantia nigra of CD200R1^-/- mice. The above results suggest that CD200R1 deletion may further activates microglia by promoting microglial phagocytosis, leading to increased loss of the nigrostriatal dopamine neurons in the PD model mice. Therefore, targeting CD200R1 could potentially serve as a novel therapeutic target for the treatment of early-stage PD.
Animals ; Microglia/physiology* ; Mice ; Phagocytosis ; Parkinson Disease/genetics* ; Disease Models, Animal ; Receptors, Cell Surface/physiology* ; Dopaminergic Neurons/pathology* ; Antigens, CD/metabolism* ; Gene Deletion ; Substantia Nigra ; Mice, Inbred C57BL ; Mice, Knockout ; Cells, Cultured ; Male ; alpha-Synuclein ; CD68 Molecule ; Orexin Receptors

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy of the digestive tract that poses a significant threat to human health, with an incidence rate that continues to rise globally. Increasing research highlights the crucial role of non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in regulating ferroptosis and contributing to the malignant progression of ESCC. These ncRNAs influence the proliferation, apoptosis, and invasion capabilities of ESCC cells by modulating iron metabolism and redox balance. miRNAs can regulate cellular iron accumulation and oxidative stress by targeting ferroptosis-related genes; lncRNAs may indirectly affect iron metabolic pathways by competitively binding to miRNAs; circRNAs, through a sponge effect, may regulate the activity of miRNAs. This review systematically summarizes the mechanisms of ncRNAs-mediated regulation of ferroptosis in ESCC, focusing on molecular mechanisms, regulatory networks, and their specific roles in the ferroptosis process. Additionally, the potential of ncRNAs in ESCC diagnosis, prognosis assessment, and therapeutic intervention is discussed, aiming to provide new insights and targets for ferroptosis-based tumor therapy.
Ferroptosis/genetics* ; Humans ; Esophageal Neoplasms/physiopathology* ; Esophageal Squamous Cell Carcinoma ; MicroRNAs/physiology* ; RNA, Long Noncoding/physiology* ; RNA, Circular ; RNA, Untranslated/physiology*