ObjectiveTo construct a multifunctional liposomal delivery system by replacing cholesterol（Chol） in conventional liposomes with saikosaponin D（SSD） and modifying with poloxamer 407（P407） for co-delivery of curcumin（Cur）. The system was evaluated for in vivo tumor targeting and inhibitory effects on mouse subcutaneous solid tumors. MethodsSingle-factor and orthogonal tests combined with information entropy weighting were used to optimize the formulation process of the liposome with encapsulation efficiency and absolute Zeta potential as indexes， and validation studies and liposomal characterization were performed. A subcutaneous solid tumor model was established by injecting H22 hepatocellular carcinoma cells subcutaneously into the dorsal surface of the right forelimb of mice. DiR-loaded traditional Chol liposomes（P407-DiR-Chol-LPs， PDCL） and novel SSD-based liposomes（P407-DiR-SSD-LPs， PDSL） were prepared by the optimized formulation process， and tail vein injection was performed to investigate the impact of SSD on liposome tumor targeting with small animal in vivo imaging. Mice were randomly divided into eight groups， including blank group， model group， free doxorubicin（DOX） group（2 mg·kg^-1）， free Cur group（8 mg·kg^-1）， free SSD group（10 mg·kg^-1）， P407-Cur-Chol-LPs（PCCL） group， P407-SSD-LPs（PSL） group， and P407-Cur-SSD-Lps（PCSL） group. Treatments were administered intraperitoneally every other day for seven doses. Antitumor efficacy and biocompatibility were evaluated by monitoring body weight change， organ indices， tumor volume and mass， relative tumor proliferation rate（T/C）， and tumor growth inhibition rate（TGI）. Histopathological analysis of liver， kidney， and tumor tissues was performed using hematoxylin-eosin（HE） staining. Serum levels of aspartate aminotransferase（AST）， alanine aminotransferase （ALT）， blood urea nitrogen（BUN）， and creatinine（Crea）in mice were quantified by fully automated biochemical analyzer. ResultsOrthogonal test yielded optimal ratios of Cur， SSD， and P407 to soybean phosphatidylcholine（SPC） as 1∶25， 1∶20， and 1∶4. The optimized PCSL exhibited spherical morphology with a particle size of 179.15 nm， a Zeta potential of -47.25 mV， and an encapsulation efficiency of 96.40%. Its in vitro release profile conformed to first-order kinetics， demonstrating excellent storage stability and hemocompatibility. In vivo imaging revealed that the fluorescence signal in tumor tissues and the fluorescence intensity ratio between tumors and organs were significantly higher in the PDSL group than in the PDCL group（P<0.05， P<0.01）. Among the treatment groups， PCSL group showed superior efficacy over free Cur group， free SSD group， PCCL group， and PSL group， with TGI>40% and T/C<60%， indicating pronounced anti-hepatocellular carcinoma effects（P<0.05， P<0.01）. Histopathology and serum biochemistry indicated minimal hepatorenal toxicity and improved hepatic and renal function in PCSL-treated mice. ConclusionReplacing Chol with SSD in preparing multifunctional drug delivery systems not only stabilizes liposomes but also yields superior anti-hepatocellular carcinoma efficacy， achieving the effect of drug-excipient integration. Co-delivery of Cur via this system can be used for treating subcutaneous solid tumors in hepatocellular carcinoma， providing new insights and technical approaches for anti-hepatocellular carcinoma research and the meridian-guiding and messenger-directing theory in traditional Chinese medicine.

Traditional Chinese medicine （TCM） diagnostics is a discipline that studies the basic theories and fundamental skills of diagnostic methods， disease diagnosis， and differentiation in accordance with the theories of TCM. The artificial intelligence （AI） technology has gained remarkable achievements in the intelligentization of the four diagnostic methods in TCM and the standardization of differentiation and diagnosis. However， it still faces many challenges. The standardization of clinical data collection is difficult， and the data quality is uneven， which affects the usability of the data. The integration of the four diagnostic information is insufficient. Most instruments can only collect data from a single diagnostic method， lacking overall integrity. The scientific nature of the diagnostic model needs to be improved. The existing models lack dynamics and the reasoning logic of TCM differentiation. The accuracy of intelligent methods needs to be improved， and the existing evaluation indicators cannot fully reflect the practical application effect of the model. Furthermore， the relevant laws and regulations are still not perfect， and data security and patient privacy lack guarantees. The cultivation of compound talents is insufficient， and there is a lack of interdisciplinary talents who are proficient in both TCM and AI. On this basis， this paper expounded on the current development status， difficulties， and bottlenecks of AI in TCM diagnosis and then explored the development trend of AI in the field of TCM diagnosis. It proposed solutions such as optimizing the data collection process， constructing multimodal diagnostic models， facilitating multi-disciplinary exchanges and cooperation， improving laws and regulations， and cultivating compound talents. It is hoped that modern， standardized， normalized， and intelligent TCM diagnosis can be further promoted， thereby providing new impetus and methods for the inheritance and innovation of TCM.

Community-acquired pneumonia （CAP） refers to an infectious inflammation of the lung parenchyma （including the alveolar wall，that is，the broad pulmonary interstitium） acquired outside the hospital. Its common pathogens include streptococcus pneumoniae，respiratory viruses， mycoplasma pneumoniae， and so on. The related factors for the occurrence and development of CAP include patient characteristics （immune function，mucus production and clearance function，coagulation function，physical condition， and comorbidity） and pathogen characteristics （susceptibility，virulence，and antibiotic resistance）. The pathogenesis of CAP lies in immune deficiency，pathogen invasion，inflammatory response disorder，mucus production and clearance disorder， coagulation disorder， and so on. The pathogenesis of CAP in traditional Chinese medicine can be described as "vital Qi deficiency and toxic stasis". Vital Qi deficiency （lack of immunity） is the potential pathogenesis of the disease and easy to be invaded by external pathogens （respiratory pathogens）. Toxic stasis （inflammatory disorder，mucus production and clearance disorder，and coagulation dysfunction） is the key pathogenic factor. Vital Qi deficiency and toxic stasis are intermingled in a state of deficiency and excess，which suggests that the treatment of CAP lies in strengthening vital Qi and eliminating pathogenic factors. This involves strengthening vital Qi in the whole process to consolidate body resistance and nourish promordial Qi. It also involves clearing heat，eliminating phlegm，removing dampness，and dispelling stasis to dispel pathogenic toxins based on the syndrome differentiation. Its action mechanism is to regulate immune and inflammatory responses，resist pathogens，and improve mucus production and clearance， as well as coagulation disorders. Starting from the key pathogenesis of CAP，"vital Qi deficiency and toxic stasis"， this paper discussed the pathogenesis of CAP and summarized the action mechanism of vital Qi strengthening for detoxification in its treatment. It is intended to complement the theoretical system by identifying "vital Qi deficiency and toxic stasis" as the key pathogenesis underlying CAP and the scientific connotation of treating CAP with vital Qi strengthening for detoxification，thereby providing insights for its clinical application.

The principle of treating different diseases with the same therapy is the essence of syndrome differentiation and treatment in traditional Chinese medicine （TCM）. It means that when the same pathogenic changes or the same symptoms appear in the development of different diseases， the same principles or methods can be used for treatment. Due to the complexity and high variability of viral pathogenicity， the precise and effective treatment of different types of viral pneumonia （VP） has always been a research focus and difficulty in modern medicine. VP belongs to the category of external-contraction febrile disease， warm disease， and epidemic in TCM. Haoqin Qingdantang （HQQDD） is a representative formula for clearing heat and dispelling dampness in warm diseases， and its intervention in VP caused by various viral infections has significant effects. This study， guided by the theory of treating different diseases with the same therapy， links the related studies on using HQQDD to treat different types of VP and finds that influenza virus pneumonia （IVP）， severe acute respiratory syndrome （SARS）， and COVID-19 all have a common pathogenic mechanism of dampness-heat at different stages of respective diseases. When these diseases are dominated by damp-heat factors， the use of HQQDD yields remarkable therapeutic effects. Modern pharmacological studies have confirmed that HQQDD can inhibit virus replication， reduce fever reactions， inhibit the expression of inflammatory mediators， and regulate immune balance. Moreover， the sovereign medicine in this formula has excellent antiviral activity， and the formula reflects rich scientific connotations of treating VP. According to the theory of treating different diseases with the same therapy and based on the effective treatment practice and modern pharmacological research of HQQDD for different types of VP， this paper mines the underlying TCM theory of treatment with the same therapy， explores the syndrome differentiation and treatment strategy and effect mechanism of this formula for different types of VP， and analyzes the treatment mechanism and characteristics， with the aim of providing evidence and reference for the clinical application and modern research of HQQDD.

Pneumonia is an infectious disease with high morbidity and mortality worldwide， and its damage to the body is not limited to the acute phase. The theory of combination of pathogenic factors emphasizes that the combination of new pathogens and residual pathogens in the body leads to the occurrence of diseases， which generalizes the causes of recurrence during pneumonia recovery. During the recovery stage of pneumonia， pathological changes such as disturbance of immune homeostasis， persistent low-grade inflammation， and microvascular damage continue to affect the body function， impair the health and quality of life of patients， and increase the risk of secondary infection. According to the theory of traditional Chinese medicine （TCM）， pneumonia is caused by deficiency， and Qi deficiency and blood stasis is the core pathogenesis in the recovery stage. At this time， the body is not full of healthy qi and still has residual pathogens， and thus it is susceptible to external pathogenic factors that lead to disease recurrence. As an important part of the TCM philosophy of treating disease before its onset， prevention of recurrence after recovery emphasizes the need for aftercare in the recovery stage to prevent disease recurrence. Based on the pathogenesis theory of combination of pathogenic factors and the pathogenesis of Qi deficiency and blood stasis， this paper discusses the effect and connotation of TCM in regulating immune inflammation and microvascular damage in preventing recurrence of pneumonia during the recovery stage， aiming to develop new ideas for effective prevention and treatment of pneumonia at this stage.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Neuropathic pain is a chronic condition caused by damage or dysfunction in the nervous system. While the spleen may influence neuropathic pain, its role has been poorly understood. This study demonstrates that the spleen plays a crucial role in regulating neuropathic pain through the bed nucleus of the stria terminalis (BNST) - paraventricular nucleus of the hypothalamus (PVN) neural circuit in a chronic constriction injury (CCI) mouse model. Splenectomy, splenic denervation, or splenic sympathectomy significantly increased the mechanical withdrawal threshold (MWT) and reduced macrophage infiltration in the dorsal root ganglia (DRG) of CCI mice. Pseudorabies virus injections into the spleen revealed connections to the BNST and PVN in the brain. Chemogenetic inhibition of the BNST-PVN circuit increased macrophage infiltration in the DRG and decreased the MWT; these effects were reversed by splenectomy, splenic denervation, or sympathectomy. These findings underscore the critical role of the spleen, regulated by the BNST-PVN circuit, in neuropathic pain.
Animals ; Neuralgia/pathology* ; Septal Nuclei/physiopathology* ; Male ; Spleen/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiopathology* ; Mice, Inbred C57BL ; Splenectomy ; Mice ; Neural Pathways/physiopathology* ; Disease Models, Animal ; Ganglia, Spinal/physiopathology* ; Sympathectomy ; Macrophages

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

OBJECTIVE: To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD). METHODS: The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4⁺ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis. RESULTS: POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA. CONCLUSION Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy* ; Animals ; Humans ; Cell Differentiation/drug effects* ; Phosphorylation/drug effects* ; Mice ; Th2 Cells/drug effects* ; Keratinocytes/drug effects* ; Disease Models, Animal ; Mice, Inbred BALB C ; Calcitriol/analogs & derivatives*

Objective:To analyze the cost-effectiveness of high-flux hemodialysis compared to low-flux hemodialysis in the treat-ment of End-Stage Renal Disease(ESRD)patients.Methods:Based on a literature review,a cost-effectiveness analysis model was established,using the Incremental Cost-Effectiveness Ratio(ICER)as the outcome indicator to evaluate the economic value of high-flux versus low-flux hemodialysis.One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to further assess the robustness of the results.Results:In the treatment of ESRD patients,compared to low-flux hemodialysis,the ICER of high-flux hemodialysis was 234 882 yuan per QALY.The key factors influencing the model results were the cost discount rate,ef-fect discount rate,utility value of high-flux hemodialysis,and treatment costs.Conclusion:Compared to low-flux hemodialysis,high-flux hemodialysis demonstrates a cost-effectiveness advantage at a willingness-to-pay threshold of three times GDP per capita.