This study establishes an integrated research paradigm based on traditional Chinese medicine （TCM） theory， guided by pathological characteristics， centered on formula compatibility principles， and supported by multidisciplinary technologies， to systematically analyze the mechanisms of hepatotoxicity induced by toxic Chinese herbal medicinals and strategies for reducing toxicity through compatibility. The findings revealed that the pathomechanism aligns closely with the "liver aversion to acute irritation" theory from Inner Canon of Yellow Emperor （《黄帝内经》）. The core pathology involves an imbalance between liver's form and function， which is characterized by malnourishment of liver form due to yin-blood depletion and dysfunction in ascending-dispersing and free-flowing activities， and closely linked to modern pathological mechanisms such as microcirculatory disturbances， oxidative stress， inflammatory response， metabolic disorder and gut-liver axis dysregulation. Based on this， a multi-layered compatibility strategy for toxicity reduction is put forward， which involves using sweet medicinals to alleviate urgency， balancing the liver form and its function， and pre-regulating other organs. This provides a theoretical basis for the safe application of toxic Chinese herbal medicinals.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.

The present study delves into the cellular mechanisms underlying the antiviral effects of dehydrodiisoeugenol(DEH) by focusing on the transcription factor EB(TFEB)/autophagy-lysosome pathway. The cell counting kit-8(CCK-8) was utilized to assess the impact of DEH on the viability of human non-small cell lung cancer cells(A549). The inhibitory effect of DEH on the replication of influenza A virus(H1N1) was determined by real-time quantitative polymerase chain reaction(RT-qPCR). Western blot was employed to evaluate the influence of DEH on the expression level of the H1N1 virus nucleoprotein(NP). The effect of DEH on the fluorescence intensity of NP was examined by the immunofluorescence assay. A mouse model of H1N1 virus infection was established via nasal inhalation to evaluate the therapeutic efficacy of 30 mg·kg~(-1) DEH on H1N1 virus infection. RNA sequencing(RNA-seq) was performed for the transcriptional profiling of mouse embryonic fibroblasts(MEFs) in response to DEH. The fluorescent protein-tagged microtubule-associated protein 1 light chain 3(LC3) was used to assess the autophagy induced by DEH. Western blot was employed to determine the effect of DEH on the autophagy flux of LC3Ⅱ/LC3Ⅰ under viral infection conditions. Lastly, the role of TFEB expression in the inhibition of DEH against H1N1 infection was evaluated in immortalized bone marrow-derived macrophage(iBMDM), both wild-type and TFEB knockout. The results revealed that the half-maximal inhibitory concentration(IC_(50)) of DEH for A549 cells was(87.17±0.247)μmol·L~(-1), and DEH inhibited H1N1 virus replication in a dose-dependent manner in vitro. Compared with the H1N1 virus-infected mouse model, the treatment with DEH significantly improved the body weights and survival time of mice. DEH induced LC3 aggregation, and the absence of TFEB expression in iBMDM markedly limited the ability of DEH to counteract H1N1 virus replication. In conclusion, DEH exerts its inhibitory activity against H1N1 infection by activating the TFEB/autophagy-lysosome pathway.
Influenza A Virus, H1N1 Subtype/genetics* ; Animals ; Autophagy/drug effects* ; Humans ; Mice ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics* ; Influenza, Human/metabolism* ; Lysosomes/metabolism* ; Orthomyxoviridae Infections/genetics* ; Eugenol/pharmacology* ; Antiviral Agents/pharmacology* ; Virus Replication/drug effects* ; A549 Cells ; Male

This study aims to investigate the molecular mechanism by which naringin alleviates cerebral ischemia/reperfusion(CI/R) injury through DRP1/LRRK2/MCU signaling axis. A total of 60 SD rats were randomly divided into the sham group, the model group, the sodium Danshensu group, and low-, medium-, and high-dose(50, 100, and 200 mg·kg~(-1)) naringin groups, with 10 rats in each group. Except for the sham group, a transient middle cerebral artery occlusion/reperfusion(tMCAO/R) model was established in SD rats using the suture method. Longa 5-point scale was used to assess neurological deficits. 2,3,5-Triphenyl tetrazolium chloride(TTC) staining was used to detect the volume percentage of cerebral infarction in rats. Hematoxylin-eosin(HE) staining and Nissl staining were employed to assess neuronal structural alterations and the number of Nissl bodies in cortex, respectively. Western blot was used to determine the protein expression levels of B-cell lymphoma-2 gene(Bcl-2), Bcl-2-associated X protein(Bax), cleaved cysteine-aspartate protease-3(cleaved caspase-3), mitochondrial calcium uniporter(MCU), microtubule-associated protein 1 light chain 3(LC3), and P62. Mitochondrial structure and autophagy in cortical neurons were observed by transmission electron microscopy. Immunofluorescence assay was used to quantify the fluorescence intensities of MCU and mitochondrial calcium ion, as well as the co-localization of dynamin-related protein 1(DRP1) with leucine-rich repeat kinase 2(LRRK2) and translocase of outer mitochondrial membrane 20(TOMM20) with LC3 in cortical mitochondria. The results showed that compared with the model group, naringin significantly decreased the volume percentage of cerebral infarction and neurological deficit score in tMCAO/R rats, alleviated the structural damage and Nissl body loss of cortical neurons in tMCAO/R rats, inhibited autophagosomes in cortical neurons, and increased the average diameter of cortical mitochondria. The Western blot results showed that compared to the sham group, the model group exhibited increased levels of cleaved caspase-3, Bax, MCU, and the LC3Ⅱ/LC3Ⅰ ratio in the cortex and reduced protein levels of Bcl-2 and P62. However, naringin down-regulated the protein expression of cleaved caspase-3, Bax, MCU and the ratio of LC3Ⅱ/LC3Ⅰ ratio and up-regulated the expression of Bcl-2 and P62 proteins in cortical area. In addition, immunofluorescence analysis showed that compared with the model group, naringin and positive drug treatments significantly decreased the fluorescence intensities of MCU and mitochondrial calcium ion. Meanwhile, the co-localization of DRP1 with LRRK2 and TOMM20 with LC3 in cortical mitochondria was also decreased significantly after the intervention. These findings suggest that naringin can alleviate cortical neuronal damage in tMCAO/R rats by inhibiting DRP1/LRRK2/MCU-mediated mitochondrial fragmentation and the resultant excessive mitophagy.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/genetics* ; Flavanones/administration & dosage* ; Rats ; Dynamins/genetics* ; Male ; Brain Ischemia/genetics* ; Protein Serine-Threonine Kinases/genetics* ; Signal Transduction/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage*

The AP2/ERF transcription factor family is a class of transcription factors widely present in plants, playing a crucial role in regulating flowering, flower development, flower opening, and flower senescence. Based on transcriptome data from flower, leaf, and stem samples of two Lonicera macranthoides varieties, 117 L. macranthoides AP2/ERF family members were identified, including 14 AP2 subfamily members, 61 ERF subfamily members, 40 DREB subfamily members, and 2 RAV subfamily members. Bioinformatics and differential gene expression analyses were performed using NCBI, ExPASy, SOMPA, and other platforms, and the expression patterns of L. macranthoides AP2/ERF transcription factors were validated via qRT-PCR. The results indicated that the 117 LmAP2/ERF members exhibited both similarities and variations in protein physicochemical properties, AP2 domains, family evolution, and protein functions. Differential gene expression analysis revealed that AP2/ERF transcription factors were primarily differentially expressed in the flowers of the two L. macranthoides varieties, with the differentially expressed genes mainly belonging to the ERF and DREB subfamilies. Further analysis identified three AP2 subfamily genes and two ERF subfamily genes as potential regulators of flower development, two ERF subfamily genes involved in flower opening, and two ERF subfamily genes along with one DREB subfamily gene involved in flower senescence. Based on family evolution and expression analyses, it is speculated that AP2/ERF transcription factors can regulate flower development, opening, and senescence in L. macranthoides, with ERF subfamily genes potentially serving as key regulators of flowering duration. These findings provide a theoretical foundation for further research into the specific functions of the AP2/ERF transcription factor family in L. macranthoides and offer important theoretical insights into the molecular mechanisms underlying floral phenotypic differences among its varieties.
Plant Proteins/chemistry* ; Gene Expression Regulation, Plant ; Transcription Factors/chemistry* ; Lonicera/classification* ; Flowers/metabolism* ; Phylogeny ; Gene Expression Profiling ; Multigene Family

Background and Aims:Chronic skin ulcers are a significant disease affecting patients'daily lives and psychological well-being.Abnormalities in the cells and extracellular matrix within the tissue may disrupt the balance of the microenvironment,hindering the normal skin repair process and leading to delayed healing of the ulcer.There is currently a lack of research on the mechanisms underlying the development of chronic ulcers and their diagnostic biomarkers.Single-cell sequencing,a newly developed high-throughput sequencing method in recent years,uses gene sequencing at the single-cell resolution to precisely reveal disease mechanisms and has been applied in various diseases.This study used single-cell transcriptome sequencing(scRNA-Seq)to investigate the cellular heterogeneity in chronic skin ulcer tissue to elucidate the potential molecular mechanisms behind delayed healing and provide new insights for clinical treatment.Methods:The scRNA-Seq technology was used to compare the differences in cell subpopulations and gene expression between chronic ulcer tissue and normal skin tissue.Single cells were sorted using a microfluidic platform,and cDNA libraries were constructed for subsequent differential gene analysis and functional enrichment analysis.Results:scRNA-Seq analysis revealed significant immune-metabolic remodeling features in chronic ulcer tissue:the number of B cells,monocytes,and macrophages in ulcer tissue increased by 2.1 to 3.5 times compared to the normal tissue control.This was accompanied by widespread activation of collagen synthesis genes(COL1A1/COL3A1)and synergistic suppression of immune regulators(e.g.,granzyme family GZMA/GZMB/H).Cross-cell subpopulation functional network analysis showed that hypoxia response mediated by the HIF-1 signaling pathway and PI3K/Akt pathway abnormalities formed a positive feedback loop,exacerbating the imbalance in the secretion of inflammatory factors(CXCL3/8,TGFBI)and compensatory upregulation of mitochondrial oxidative phosphorylation.Conclusion:Chronic skin ulcers exhibit significant differences in cellular heterogeneity and gene expression,suggesting that chronic ulcers are not simply tissue defects but a complex pathological process dominated by chronic inflammation and immune dysregulation.The coordinated dysregulation of multiple cell subpopulations in the ulcer microenvironment,along with persistent inflammatory responses and metabolic abnormalities,is interconnected through the HIF-1/TNF/MAPK pathway network.Downregulation of granzyme gene family members and abnormal histone modifications may contribute to immune clearance defects,providing a theoretical basis for developing novel therapies targeting epigenetic regulation or mitochondrial function.

Fetal ultrasound standard plane detection was introduced in terms of its importance and problems encountered.The deep learning techniques applied in fetal standard plane detection were reviewed,including transfer learning,modified basic network,hybrid network and multi-task network.The problems encountered by the deep learning techniques during the application were analyzed,and the future research directions were envisioned.[Chinese Medical Equipment Journal,2025,46(5):91-101]

Objective To explore the feasibility and safety of ultrasound-guided percutaneous microwave ablation for unresectable pancreatic cancer.Methods Totally 84 patients who underwent ultrasound-guided percutaneous microwave ablation for unresectable pancreatic cancer were enrolled,and the technical success rate,complete ablation rate,complication rate,pain relief rate and survival time,etc.were observed.Results The median age of 84 cases was 61.5 years.Totally 86 tumors,including 44.19％(38/86)at the head/neck and 55.81％(48/86)at the body/tail of pancreas were detected,and a total of 85 ablation sessions were performed with the median ablation energy applied per tumor of 9.90(1.08,21.60)kJ and the complete ablation rate of 42.86％(36/84).The technical success rate was 100％(85/85).Thirty-nine complication events occurred in 25 cases,no ablation-related death.Among 34 patients underwent ablation mainly for pain symptoms,the pain score decreased from(6.22±1.12)points before treatment to(1.94±1.64)points after treatment(P＜0.001).During 6.8(3.3,12.9)months' follow-up,the mean survival time was(8.5±6.7)months,and all 47 patients died due to tumor progression.Conclusion Ultrasound-guided percutaneous microwave ablation was safe and feasible for unresectable pancreatic cancer.

Objective:To evaluate the effect of acupuncture on postoperative delirium (POD) in diabetic patients undergoing surgery under general anesthesia.Methods:In this randomized controlled trial, 92 diabetic patients of either sex, aged 30-80 yr, with a body mass index of 18-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective surgery under general anesthesia, were divided into 2 groups ( n=46 each) using a table of random numbers: control group (group C) and acupuncture group (group A). Group A received acupuncture at the Baihui (GV20), Shenting (GV24) and Sishencong (EX-HN1) acupoints before anesthesia. The needles were retained for 30 min, with manual stimulation applied every 10 min for 10 s each time. After 4 stimulations, routine anesthesia was carried out. Group C received routine anesthesia only. Regional cerebral oxygen saturation was recorded on admission to the operating room (T 0), after anesthesia induction (T 1), at the start of surgery (T 2), at the end of surgery (T 3), and immediately after tracheal extubation (T 4). The POD developed within 3 days after surgery was assessed. The occurrence of needle-related adverse effects such as fainting, subcutaneous bleeding, and local paresthesia was recorded. Results:Compared with group C, the incidence of POD was significantly reduced, and the regional cerebral oxygen saturation was increased at T 1, 4 in group A ( P<0.05). Conclusions:Acupuncture can decrease the development of POD in diabetic patients undergoing surgery under general anesthesia, which is related to an increase in regional cerebral oxygen saturation.