ObjectiveTo investigate the effects of Tianma Goutengyin on the tumor necrosis factor-α （TNF-α）/signal transducer and activator of transcription 3 （STAT3）/α1-antichymotrypsin C-terminal tail fragment （α1ACT） signaling pathway and A1-type astrocytes in a rat model of vascular dementia. MethodsSeventy-two male Sprague-Dawley rats were randomly divided into six groups （n=12 per group）： Sham-operated group， model group， Tianma Goutengyin high-， medium-， and low-dose groups （5.13， 10.26， and 20.52 g·kg^-1）， and a nimodipine group （8.1 mg·kg^-1）. The vascular dementia model was established by permanent bilateral common carotid artery occlusion， followed by 4 weeks of intervention. Learning and memory ability were evaluated using the novel object recognition test， and behavioral performance was assessed using the forced swimming test. Levels of interleukin-6 （IL-6） and C-C motif chemokine ligand 2 （CCL2） in hippocampal tissue were measured by enzyme-linked immunosorbent assay （ELISA）. Hippocampal neuronal morphology was observed by Nissl staining， and apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Immunohistochemistry was used to detect positive expression of brain-derived neurotrophic factor （BDNF）， glial fibrillary acidic protein （GFAP）， and myelin basic protein （MBP）. Western blot analysis was performed to measure the protein expression levels of TNF-α， TNF receptor 1 （TNFR1）， phosphorylated STAT3 （p-STAT3）， α1ACT， IL-6， complement component 3 （C3）， BDNF， S100 calcium-binding protein A10 （S100A10）， and GFAP in hippocampal tissue. ResultsCompared with the sham-operated group， the model group showed a significantly reduced relative recognition index in the novel object recognition test （P<0.01）， prolonged immobility time and increased immobility frequency in the forced swimming test （P<0.01）. Hippocampal IL-6 and CCL2 levels were significantly increased （P<0.01）. Nissl staining revealed a marked reduction in neuronal number and loss of Nissl bodies （P<0.01）. MBP-positive expression was significantly decreased （P<0.01）， apoptosis was significantly increased （P<0.01）， BDNF-positive expression was significantly reduced （P<0.05）， and GFAP-positive expression was significantly increased （P<0.01）. In addition， the protein expression levels of TNF-α， TNFR1， p-STAT3， α1ACT， IL-6， and C3 were significantly elevated （P<0.01）， while BDNF and S100A10 expression levels were significantly decreased （P<0.01）. Compared with the model group， all Tianma Gouteng yin dose groups exhibited a significant increase in the relative recognition index （P<0.05）， shortened immobility time and reduced immobility frequency （P<0.05， P<0.01）. IL-6 and CCL2 levels were significantly decreased （P<0.01）， neuronal number was significantly increased （P<0.05， P<0.01）， and MBP-positive expression was significantly enhanced （P<0.01）. Apoptosis was significantly reduced （P<0.01）， BDNF-positive expression was significantly increased （P<0.05）， and GFAP-positive expression was significantly decreased （P<0.01）. Moreover， the protein expression levels of TNF-α， TNFR1， p-STAT3， α1ACT， IL-6， and C3 were significantly decreased （P<0.01）， while BDNF and S100A10 protein expression levels were significantly increased （P<0.01）. ConclusionTianma Goutengyin may inhibit A1-type astrocyte activation in rats with vascular dementia through the TNF-α/STAT3/α1ACT signaling pathway， thereby reducing neuronal apoptosis and improving learning and memory function.

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.

OBJECTIVE To formulate the Hazardous Drug List in China， and provide a scientific basis for standardizing the management of hazardous drugs， preventing and controlling occupational exposure risks in medical institutions at all levels in China. METHODS Under the joint organization of the Intravenous Medication Admixture Management Professional Committee of the Chinese Pharmaceutical Association and the National Medical Quality Control Center for Pharmaceutical Management， based on literature research and international hazardous drug lists and their development procedures， the scope of hazardous drug selection， selection principles， and evidence confirmation criteria were determined through expert panel seminars and expert questionnaire survey method （Delphi method）. Chemical drugs， biological agents， and Chinese patent medicines marketed in China that met the selecti on principles were screened to form the Chinese Expert Consensus on the Hazardous Drug List . RESULTS Five principles for selecting hazardous drugs were established （including protective labeling in package inserts， carcinogenicity， reproductive toxicity， genotoxicity， and organ toxicity at low doses）， along with the corresponding evidence confirmation criteria. The Hazardous Drug List containing 210 drugs was formulated， covering anti-tumor drugs， endocrine system drugs， nervous system drugs， immunomodulators， anti-infective drugs， cardiovascular system drugs， hematological system drugs， urinary system drugs， obstetrics and gynecology drugs， dermatological drugs and other categories. Compared with international hazardous drug lists， 25 newly included hazardous drugs were added， including 15 anti-tumor drugs， 6 Chinese patent medicines and 4 biological agents. In addition， 88 Chinese patent medicines that may have potential occupational exposure risks are listed in the appendix for reference by medical institutions in management. CONCLUSIONS The development of this consensus closely aligns with the actual clinical drug use in China， with a scientific and rigorous methodology， and can serve as a reference for medical institutions at all levels to standardize the management of hazardous drugs and prevent and control occupational exposure risks.

ObjectiveColorectal cancer (CRC) is a highly heterogeneous malignancy, and traditional Chinese medicine (TCM) syndrome differentiation is widely used in its clinical management. However, the biological basis underlying different TCM syndromes remains insufficiently understood. This study aimed to investigate the proteomic differences between qi-blood deficiency syndrome (QBDS) and damp-heat syndrome (DHS) in CRC patients and to establish a “syndrome-differential protein-herbal component” network for exploring potential molecular mechanisms and therapeutic targets associated with syndrome-specific treatment strategies. MethodsTumor tissue samples were collected from 10 patients with pathologically confirmed CRC, including 5 patients diagnosed with QBDS and 5 with DHS according to standardized TCM syndrome differentiation criteria. Tandem mass tag (TMT)-based quantitative proteomics was employed to identify differentially expressed proteins (DEPs) between the two syndrome groups. Functional enrichment analyses, including Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, were performed to characterize the biological functions and signaling pathways associated with the identified DEPs. Least absolute shrinkage and selection operator (LASSO) regression analysis was further applied to screen key syndrome-related proteins and construct a core protein prediction model. Subsequently, molecular docking was conducted to evaluate the binding affinities between representative herbal compounds, astragaloside IV and berberine, and the identified core proteins. Finally, cell counting kit-8 (CCK-8) assays were performed in HCT 116 and HT-29 colorectal cancer cell lines to validate the anti-proliferative activities of these compounds in vitro. ResultsA total of 44 DEPs were identified between QBDS and DHS tissues, including 21 upregulated and 23 downregulated proteins in the QBDS group relative to the DHS group. Functional enrichment analyses revealed that these proteins were primarily associated with antiviral immune responses, regulation of inflammatory signaling, NF‑κB signaling pathways, cholesterol metabolism, and other biological processes relevant to tumor progression and host immune regulation. LASSO regression analysis identified eight core proteins with potential syndrome-specific significance. Among them, ST7, GPCPD1, and PODXL were closely associated with QBDS, whereas FAT1, GRB7, KRT7, MAFF, and MMP8 were associated with DHS. Molecular docking demonstrated favorable interactions between astragaloside IV and QBDS-related proteins, with binding energies lower than -5 kcal/mol, indicating stable binding activity. Berberine exhibited even lower binding energies and stronger binding specificity toward DHS-related core proteins. In vitro experiments further confirmed that both compounds inhibited CRC cell proliferation, while berberine displayed significantly greater anti-proliferative efficacy. The lowest 48 h IC₅₀ value of berberine reached 15.21 mg/L in CRC cells, indicating a stronger growth-inhibitory effect than astragaloside IV. ConclusionCRC patients with QBDS and DHS exhibit distinct proteomic characteristics, suggesting that different TCM syndromes possess unique molecular signatures. The identified core proteins may serve as potential biomarkers for syndrome differentiation, while astragaloside IV and berberine may exert therapeutic effects through targeting syndrome-specific molecular networks. These findings provide preliminary proteomic evidence supporting syndrome-guided precision integrative medicine in CRC and offer new insights into the biological basis of TCM syndrome differentiation and individualized therapeutic strategies.

The sensitive scalp is a complex syndrome characterised by abnormal nerve sensations, such as stinging, itching, burning, and tightness, and diminished tolerance to physical or chemical stimuli that would not typically cause such unpleasant responses, with its pathology involving physical barrier destruction at the stratum corneum level, neural hyperreactivity and sensory nerve sensitization, and local immunological dysregulation and chronic low‑grade inflammation. The homeostasis of the scalp microenvironment plays a crucial regulatory role in maintaining the hair follicle growth cycle, yet this “soil” factor has long been underappreciated in hair loss research, which has traditionally centered on intrinsic follicular defects, such as genetic predisposition or androgen-driven mechanisms. In this review, we summarized the potential mechanisms underlying the imbalance in the “barrier-neural-immune” network in sensitive scalps. Sensitive scalp is further manifested as impaired skin barrier, including increased transepidermal water loss and abnormal lipid secretion. These alterations are accompanied by increased surface pH, excessive secretion of sebum rich in free fatty acids, reduced microbial diversity, and dysbiosis characterized by a reduction in Cutibacterium and an increase in Staphylococcus colonization. Mechanistically, we also analyzed how neurogenic inflammation, mediated by substances such as substance P (SP) and calcitonin gene-related peptide (CGRP), along with persistent low-grade inflammation, disrupts the microenvironment of the hair follicle stem cell niche through mechanisms involving mechanosensitive ion channels (e.g., Piezo1), oxidative stress, and cytokine cascades. When the barrier is compromised, the weakened stratum corneum may facilitate the penetration of external stimuli, sensitizing cutaneous nerve endings. Those hyperresponsive nerves then fire off neuropeptides like substance P and CGRP. These peptides activate mast cells and other immune cells via the MrgprB2 receptor, prompting degranulation and a wave of pro-inflammatory mediators that kick off neurogenic inflammation. At the same time, oxidative stress and inflammatory cytokines drive a persistent low-grade inflammation that directly damages the hair follicle stem cell niche. Physical compression from shrinking hair shafts activates Piezo1 channels, setting off calcium influx and Caspase‑3‑dependent apoptotic signaling. We primarily considered the interactions between inflammatory signaling and the sensitization of the androgen receptor (AR) pathway, as well as the inhibition of the Wnt/β‑catenin pathway, which may subsequently contribute to hair follicle miniaturization and disruption of the growth cycle. The inflammatory microenvironment appears to boost AR expression in dermal papilla cells, making them more sensitive to dihydrotestosterone (DHT). This heightened sensitivity may promote the expression of transforming growth factor-β1 (TGF-β1), TGF-β2, and Dickkopf-1 (DKK1), which suppress the Wnt/β‑catenin pathway—essential for follicle growth and regeneration—potentially accelerating follicular miniaturization and stalling the growth cycle. Coupled with direct inflammatory apoptosis, oxidative stress, and circadian disruption, these routes may collectively speed up hair follicle stem cell depletion and diffuse hair thinning. These findings point to the need for more mechanistic and translational research to test the proposed pathways and explore therapies that target the microenvironment in sensitive scalp-related hair loss. Ultimately, we hope to provide theoretical support for the intervention of hair loss by restoring the steady state of the scalp microenvironment and combining with new precision delivery technologies such as microneedles.

BACKGROUND:At present,osteoarthritis has become a major disease affecting the quality of life of the elderly,and the therapeutic effect is poor,often focusing on preventing the disease process,and the pathogenesis of osteoarthritis is still not fully understood.Bioinformatics analysis was carried out to explore the main pathogenesis of osteoarthritis and related mechanisms of gene coding regulation. OBJECTIVE:To screen core differential genes with a major role in osteoarthritis by gene expression profiling. METHODS:Datasets were downloaded from the Gene Expression Omnibus(GEO):GSE114007,GSE117999,and GSE129147.Differential genes in the GSE114007 and GSE117999 data collections were screened using R software,performing differential genes to weighted gene co-expression network analysis.The module genes most relevant to osteoarthritis were selected to perform protein interaction analysis.Candidate core genes were selected using the cytocape software.The candidate core genes were subsequently subjected to least absolute shrinkage and selection operator regression and COX analysis to identify the core genes with a key role in osteoarthritis.The accuracy of the core genes was validated using an external dataset,GSE129147. RESULTS AND CONCLUSION:(1)A total of 477 differential genes were identified,265 differential genes associated with osteoarthritis were obtained by weighted gene co-expression network analysis,and 8 candidate core genes were identified.The least absolute shrinkage and selection operator regression analysis finally yielded a differential gene ASPM with core value that was externally validated.(2)It is concluded that abnormal gene ASPM expression screened by bioinformatics plays a key central role in osteoarthritis.

Background: The transvenous approach to the treatment of cerebral arteriovenous malformation (AVM) is difficult and requires strict blood pressure and blood flow control; however, the cure rate is very high. Appropriate blood pressure control techniques can greatly benefit these patients.Case: A 55-year-old male patient was found to have an aneurysm complicated with a cerebral AVM (length: 2.0 cm, width: 1.6 cm, height: 1.2 cm). Aneurysm embolization was considered for the first-stage surgery and transvenous AVM embolization for the second-stage surgery. Rapid ventricular pacing (RVP) provided a stable blood flow environment for the surgery, which was completed successfully. Conclusion RVP can thus provide an ideal condition for the embolization of cerebral AVM through the transvenous approach and can be a viable surgical option.

Objective To explore the application effect of 3D printed individualized model in the treatment of complex ankle fractures(AF).Methods Patients with complex AF admitted to our hospital from July 2021 to October 2022 were selected and divided into the control group and the observation group using a random number table method,with 50 cases in each group.Patients in the control group were received minimally invasive reduction and internal fixation,while these in the observation group were given minimally invasive reduction and internal fixation under the guidance of 3D printed individualized model.The surgical conditions,ankle joint reduction,stress indicators[norepinephrine(NE)and angiotensin Ⅱ(AngⅡ)],ankle function and postoperative complications were compared between the two groups.Results There were 2 patients in the observation group and 3 patients in the control group were lost to follow-up 12 months after surgery.Compared with the control group,the observation group showed a decrease in the intraoperative blood loss,shortened surgical time,hospitalization time,and weight-bearing activity time,and an increase in the anatomical reduction rate(P<0.05).The observation group had lower serum levels of NE and AngⅡ 1 and 3 days after surgery(P<0.05)and higher Kofoed score and American Orthopedic Foot and Ankle Society(AOFAS)scores 1,6,and 12 months after surgery(P<0.05),as well as lower incidence of postoperative complications(P<0.05)than those in the control group.Conclusion For the treatment of complex AF,3D printed individualized model assisted the formulation of minimally invasive reduction and fixation surgical plans before surgery can shorten surgical time,reduce stress injury,decrease the risk of complications,and simultaneously increase the anatomical reduction rate and improve ankle joint function,thereby accelerating postoperative recovery of patients.

Objectives:To explore the feasibility of zero-ray radiofrequency catheter ablation for paroxymal atrial fibrillation under the guidance of transthoracic echocardiography combined with three-dimensional mapping system.Methods:This is a single-center prospective observational study.A total of 12 patients with paroxysmal atrial fibrillation who underwent radiofrequency catheter ablation in Fuwai Hospital,Chinese Academy of Medical Sciences from June 1,2024 to September 30,2024 were included.All patients underwent successful percutaneous puncture,atrial septal puncture under the guidance of transthoracic echocardiography,and all patients underwent left atrial modeling and discharge ablation under the guidance of transthoracic echocardiography combined with three-dimensional mapping system.The disappearance of pulmonary vein potential was confirmed after the ablation operation and as the ablation endpoint and successful ablation marker.The operation results and 1-month and 3-month follow-up results of the patients were observed.Results:There were 12 patients with paroxysmal atrial fibrillation,9 males and 3 females,aged(56.8±11.2)years,with a history of paroxysmal atrial fibrillation(4.2±2.3)years.The mean left atrial diameter was(36.5±2.5)mm,the left ventricular end-diastolic diameter was(47.8±4.1)mm,and the left ventricular ejection fraction was 55%-65%.The mean overall operation time was(102.25±14.51)min,the ultrasound operation time was(29.58±6.23)min,and the catheter operation time was(33.08±4.10)min.All patients completed circumferential pulmonary vein isolation without intraoperative complications.The hospitalization time was 2-6 days.At the 1-month follow-up after ablation,all patients showed sinus rhythm on 24-hour ambulatory electrocardiogram,and 2 patients had occasional atrial premature contractions without recurrence of atrial fibrillation.At the 3-month follow-up,two patients had occasional premature atrial contractions,and no recurrence of atrial fibrillation was recorded on the electrocardiogram of all patients.Conclusions:It is feasible to complete radiofrequency catheter ablation of paroxysmal atrial fibrillation under the guidance of transthoracic echocardiography combined with three-dimensional mapping system.

SARS-CoV-2 and its emerging variants continue to pose a significant global public health threat. The SARS-CoV-2 main protease (M^pro) is a critical target for the development of antiviral agents that can inhibit viral replication and transcription. In this study, we identified chebulagic acid (CHLA), isolated from Terminalia chebula Retz., as a potent non-peptidomimetic and non-covalent M^pro inhibitor. CHLA exhibited intermolecular interactions and provided significant protection to Vero E6 cells against a range of SARS-CoV-2 variants, including the wild-type, Delta, Omicron BA.1.1, BA.2.3, BA.4, and BA.5, with EC₅₀ values below 2 μmol/L. Moreover, in vivo studies confirmed the antiviral efficacy of CHLA in K18-hACE2 mice. Notably, CHLA bound to a unique groove at the interface between M^pro domains I and II, which was revealed by the high-resolution crystal structure (1.4 Å) of the M^pro-CHLA complex, shrinking the substrate binding pocket of M^pro and inducing M^pro aggregation. CHLA was proposed to act as an allosteric inhibitor. Pharmacokinetic profiling and safety assessments underscore CHLA's potential as a promising broad-spectrum antiviral candidate. These findings report a novel binding site on M^pro and identify antiviral activity of CHLA, providing a robust framework for lead compounds discovery and elucidating the underlying molecular mechanisms of inhibition.