ObjectiveTo investigate the influencing factors for traditional Chinese medicine （TCM） syndromes of primary liver cancer， and to provide a theoretical basis for the TCM syndrome differentiation and standardized treatment of liver cancer. MethodsTCM syndrome differentiation was performed for 415 patients who were admitted to Shanxi Institute of Traditional Chinese Medicine and were diagnosed with primary liver cancer based on pathological or clinical examinations from January 2019 to December 2023. The chi-square test was used for comparison of categorical data between groups， and the unordered polytomous logistic regression model was used to investigate the influencing factors for TCM syndromes of liver cancer. ResultsThe common initial symptoms of the 415 patients with primary liver cancer included pain in the liver area （31.81%）， abdominal distension （25.30%）， abdominal pain （15.18%）， and weakness （13.98%）， and the main clinical symptoms included poor appetite （70.84%）， fatigue （69.16%）， pain in the liver area （67.47%）， poor sleep （59.04%）， abdominal distension （53.01%）， and constipation （52.53%）. There were significant differences in TCM syndromes between patients with different sexes， courses of the disease， clinical stages， Child-Pugh classes， presence or absence of intrahepatic and extrahepatic metastasis， and presence or absence of transcatheter arterial chemoembolization （TACE） and radiofrequency ablation （all P<0.05）. The logistic regression analysis showed that male sex was a risk factor for damp-heat accumulation （odds ratio ［OR］=2.036， P=0.048） and the syndrome of spleen-kidney Yang deficiency （OR=5.240， P<0.001）； a course of disease of<1 year was a risk factor for damp-heat accumulation （OR=2.837， P=0.004） and syndrome of Qi stagnation and blood stasis （OR=2.317， P=0.021）， but it was a protective factor against syndrome of spleen-kidney Yang deficiency （OR=0.385， P=0.005）； Child-Pugh class A/B was a protective factor against liver-kidney Yin deficiency （OR=0.079， P<0.001）； intrahepatic metastasis was a risk factor for liver-kidney Yin deficiency （OR=5.117， P=0.003） and syndrome of spleen-kidney Yang deficiency （OR=3.303， P=0.010）； TACE was a protective factor against liver-kidney Yin deficiency （OR=0.171， P<0.001） and syndrome of spleen-kidney Yang deficiency （OR=0.138， P<0.001）； radiofrequency ablation was a risk factor for damp-heat accumulation （OR=4.408， P<0.001） and liver-kidney Yin deficiency （OR=32.036， P<0.001）. ConclusionSex， course of disease， Child-Pugh class， intrahepatic metastasis， TACE， and radiofrequency ablation are the main influencing factors for TCM syndromes of liver cancer.

ObjectiveTo investigate the influencing factors for traditional Chinese medicine （TCM） syndromes in pancreatic cancer by analyzing 608 cases， and to provide a theoretical reference for TCM syndrome differentiation and standardized treatment of pancreatic cancer. MethodsA total of 608 patients with a pathological or clinical diagnosis of pancreatic cancer who were admitted to Shanxi Institute of Traditional Chinese Medicine， The Affiliated Hospital of Shanxi University of Chinese Medicine， and Shanxi Provincial Hospital of Integrated Traditional Chinese and Western Medicine from January 2019 to December 2023 were enrolled， and TCM syndrome differentiation was performed. The chi-square test was used for comparison of categorical data between groups. The clinical data with statistical significance between groups were included in the regression analysis， and the unordered polytomous logistic regression model was used to investigate the influencing factors for the TCM syndrome of pancreatic cancer. ResultsFor the 608 patients with pancreatic cancer， common initial symptoms included abdominal pain （32.40%）， abdominal distension （23.85%）， fatigue （16.12%）， and emaciation （10.03%）， and the main clinical symptoms included poor appetite （75.97%）， abdominal pain （67.27%）， fatigue （61.84%）， abdominal distension （57.40%）， and emaciation （53.62%）. There were significant differences between the patients with different TCM syndromes of pancreatic cancer in sex （χ²=62.823， P<0.001）， disease duration （χ²=14.868， P=0.011）， clinical stage （χ²=21.006， P<0.001）， lymph node metastasis （χ²=2.205， P=0.032）， surgery （χ²=38.008， P<0.001）， chemotherapy （χ²=21.384， P<0.001）， radiotherapy （χ²=17.510， P=0.004）， and immunotherapy （χ²=18.573， P=0.002）. The logistic regression analysis showed that male sex was a protective factor against Qi and blood deficiency syndrome （odds ratio ［OR］=0.081， 95% confidence interval ［CI］： 0.031‍ ‍—‍ ‍0.213， P<0.001）， Qi stagnation and blood stasis syndrome （OR=0.100， 95%CI： 0.041‍ ‍—‍ ‍0.247， P<0.001）， and syndrome of Yin deficiency with internal heat （OR=0.158， 95%CI： 0.057‍ ‍—‍ ‍0.444， P<0.001）， while it was a risk factor for the syndrome of damp-heat accumulation （OR=2.378， 95%CI： 1.074‍ ‍—‍ ‍5.266， P=0.033）； the course of the disease of<1 year was a protective factor against Qi and blood deficiency syndrome （OR=0.167， 95%CI： 0.073‍ ‍—‍ ‍0.383， P<0.001）， syndrome of spleen-kidney Yang deficiency （OR=0.183， 95%CI： 0.089‍ ‍—‍ ‍0.378， P<0.001）， and syndrome of Yin deficiency and internal heat （OR=0.164， 95%CI： 0.070‍ ‍—‍ ‍0.385， P<0.001）； clinical stage Ⅰ/Ⅱ/Ⅲ was a risk factor for damp-heat accumulation （OR=2.793， 95%CI： 1.259‍ ‍—‍ ‍6.196， P=0.012） and Qi stagnation and blood stasis syndrome （OR=7.863， 95%CI： 2.808‍ ‍—‍ ‍22.020， P<0.001）； lymph node metastasis was a risk factor for Qi and blood deficiency syndrome （OR=4.005， 95%CI： 1.477‍ ‍—‍ ‍10.861， P=0.006）； surgical treatment was a risk factor for Qi and blood deficiency syndrome （OR=4.151， 95%CI： 1.916‍ ‍—‍ ‍8.995， P<0.001）， syndrome of spleen-kidney yang deficiency （OR=5.352， 95%CI： 2.436‍ ‍—‍ ‍11.759， P<0.001）， Qi stagnation and blood stasis syndrome （OR=2.334， 95%CI： 1.071‍ ‍—‍ ‍5.088， P=0.033）， and syndrome of Yin deficiency and internal heat （OR=4.167， 95%CI： 1.789‍ ‍—‍ ‍9.707， P<0.001）； chemotherapy was a protective factor against damp-heat accumulation （OR=0.188， 95%CI： 0.082‍ ‍—‍ ‍0.428， P<0.001）； radiotherapy was a risk factor for damp-heat accumulation （OR=2.571， 95%CI： 1.151‍ ‍—‍ ‍5.746， P=0.021） and syndrome of Yin deficiency with internal heat （OR=8.384， 95%CI： 3.348‍ ‍—‍ ‍20.997， P<0.001）； immunotherapy was a risk factor for Qi and blood deficiency syndrome （OR=2.114， 95%CI： 1.021‍ ‍—‍ ‍4.379， P=0.044）. ConclusionSex， course of the disease， clinical stage， presence or absence of lymph node metastasis， surgery， chemotherapy， radiotherapy， and immunotherapy are the main influencing factors for the TCM syndrome of pancreatic cancer.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

As a common clinical Chinese medicine, Prunellae Spica has the effects of clearing liver-fire, improving eyesight, resolving massesand detumescence, and has strong anti-tumor effects against thyroid cancer, breast cancer, liver cancer and other cancers. Extracts of Prunellae Spica and its active components can play an anti-tumor role in a variety of ways, including cell apoptosis, inhibiting cell invasion and metastasis, inhibiting cell proliferation, inducing autophagy, anti tumor angiogenesis, reversing tumor multidrug resistance and regulating immune function, by regulating miRNA and Wnt/β-catenin, PI3/AKT, AMPK/mTOR/ULK1, RANKL/RANK/OPG and other signal pathways . In this paper, the anti-tumor mechanism of Prunellae Spica extract was reviewed, in order to provide reference for further research and application.

Angelicae Sinensis Radix, drived from a medicinal and edible plant Angelica sinensis, with the reputation of "nine Angelica recipes out of ten". The volatile oils from Angelicae Sinensis Radix was the main medicinal component of Angelicae Sinensis Radix, mainly including benzene phthalides, terpenoids and alkanes, its chemical composition was complex. Such factors as growth environment, concoction process, extraction methods and other factors all can trigger changes in volatile oil constituents and content from Angelicae Sinensis Radix. Angelicae Sinensis Radix essential oil has diverse pharmacological activities such as anti-hypotension, protection of ischemia-reperfusion injury, asthma, anti-inflammatory and anti-cancer, etc., implying its high clinical application value. This paper reviewed the literature on the volatile oil of Angelicae Sinensis Radix in the past ten years, the chemical components of Angelicae Sinensis Radix were sorted out and the factors affecting the chemical components were summarized, focusing on its anti-hypotensive, ischemia-reperfusion injury protection, asthma and other active effects, in order to provide reference for the further development and utilization of the volatile oil of Angelicae Sinensis Radix.

Objective:To explore the potent effects of denatonium benzoate(DB)on Mas-related G protein-coupled receptor-B2(MrgprB2)-mediated rat mast cell degranulation.Methods:RBL-2H3 cells were treated with DB overnight,before challenged with MrgprB2 ligands substance P(SP).The release of β-hex from MrgprB2-activated RBL-2H3 was detected by substrate method.Detec-tion of LTC4,IL-6,TNF-α and cPLA2 activity were performed by ELISA.The Ca2+influx and the expression of RBL-2H3 MrgprB2 re-ceptors were measured by fluorescence assay.Results:The results showed 10 μmol/L,50 μmol/L,80 μmol/L,100 μmol/L DB treat-ments promoted β-hex and LTC4 releases from activated RBL-2H3,accompanied by increased Ca2+mobilization and cPLA2 activa-tion.DB treatments did not affect IL-6 and TNF-α LTC4 releases in MrgprB2-activated RBL-2H3,as well as the levels of MrgprB2 ex-pression in mast cells.Conclusion:Taken together,DB enhanced the MrgprB2-mediated RBL-2H3 degranulation in vitro,probably by up-regulating Ca2+mobilization in activated cells.

Background: Total knee arthroplasty (TKA) is a common surgical procedure for patients with knee osteoarthritis. The patellar component plays a crucial role in knee biomechanics and can influence postoperative outcomes. This study aimed to investigate the relationship between radiological indices of patellar height and patient outcomes following TKA. Methods: A retrospective analysis was conducted on patients who underwent TKA for osteoarthritis. Radiographic measurements of patellar height, including the Insall-Salvati (IS) ratio, modified Blackburne-Peel (mBP) ratio, Caton-Deschamps ratio, and plateaupatellar angle (PPA), were obtained. Clinical outcomes were assessed using the Knee Society Score (KSS) and the Forgotten Joint Score-12 (FJS-12). Patient satisfaction and postoperative complications were also evaluated. Statistical analyses, including correlation analysis and multiple regression models, were performed to determine the association between radiological indices and patient outcomes. Results: The study included 330 cases that met the inclusion criteria. The analysis revealed significant correlations between different radiological indices of patellar height and patient outcomes. Lower postoperative PPA was correlated with worse KSS and range of motion scores. A decreased mBP ratio was associated with poorer FJS-12 responses and higher risks of dissatisfaction and patellar clunk or crepitus. Increased IS ratio was linked to a lower likelihood of incidental giving way of the knee. Advanced age was associated with reduced dissatisfaction and incidental giving way probabilities. Conclusions The findings of this study demonstrate that radiological indices of patellar height can predict patient outcomes following TKA. Assessing patellar height using various radiographic measurements provides valuable information for surgical planning and prognostic evaluation. Understanding the impact of patellar height on clinical outcomes can aid in optimizing TKA procedures and improving patient satisfaction. These findings emphasize the importance of considering patellar height as a predictive factor in TKA and highlight its potential role in guiding postoperative management and rehabilitation strategies.

ObjectiveTo reveal the targets and molecular mechanisms of the action of Qiangxin Decoction （强心汤） for the treatment of chronic heart failure based on the combination of network pharmacology and molecular docking. MethodsThe active ingredients of Qiangxin Decoction were retrieved from TCMSP database， and the targets of chronic heart failure were screened by searching GeneCards， OMIM， TTD， PharmGkb， and DrugBank databases， and the intersections were taken to obtain the intersecting targets of Qiangxin Decoction for the treatment of chronic heart failure. STRING platform was used to construct the protein-protein interaction network （PPI）， Cytoscape 3.8.0 software was used to calculate the network topology to screen the core targets， and R 4.2.3 was used to construct the “active ingredient-target” network by analyzing the GO enrichment analysis and KEGG pathway enrichment analysis. AutoDock 1.5.7 was used for molecular docking to predict the binding performance of active ingredients and core targets. ResultsSeventy-five intersecting targets were identified for the treatment of chronic heart failure with Qiangxin Decoction， among which the core targets were estrogen receptor 1 （ESR1， degree value=7）， nuclear receptor coactivator 1 （NCOA1， degree value=8）， glucocorticoid receptor （NR3C1， degree value=7）， and nuclear receptor coactivator 2 （NCOA2， degree value=7）. GO enrichment analysis showed that the top 3 items with the smallest P value in molecular function were G protein-coupled amine receptor activity， postsynaptic neurotransmitter receptor activity， and neurotransmitter receptor activity （P＜0.01）； the top 3 items with the smallest P value in biological process were adenylyl cyclase-activated adrenergic receptor signaling pathway， adrenergic receptor signaling pathway， and adenylyl cyclase-regulated G protein-coupled receptor signaling pathway （P＜0.01）； the top 3 items with the smallest P values in cellular composition were components of the postsynaptic membrane， synaptic membrane， and presynaptic membrane （P＜0.01）. KEGG enrichment analysis showed that the top 5 key signaling pathways were neuroactive ligand-receptor interactions， calcium signaling pathway， dopaminergic synapses， cocaine addiction， and cyclic guanosine monophosphate-protein kinase G （cGMP-PKG） signaling pathway. The molecular docking results showed that lignans and isoflavones had lower binding energies and more structural stability with the four core targets （ESR1， NCOA1， NR3C1， NCOA2）. ConclusionThe treatment of chronic heart failure by Qiangxin Decoction was associated with neuroactive ligand-receptor interactions， calcium signaling pathway， dopaminergic synapses， chemoattractant-receptor activation， cGMP-PKG signaling pathway， lipids and atherosclerosis， and cAMP signaling pathway， and lignans and isoflavones may be the core active compounds in its treatment of chronic heart failure.

Oxidative Phosphorylation ; Acetylglucosamine ; Uridine Diphosphate N-Acetylglucosamine/metabolism*

Hepatic stellate cells (HSCs) represent a significant component of hepatocellular carcinoma (HCC) microenvironments which play a critical role in tumor progression and drug resistance. Tumor-on-a-chip technology has provided a powerful in vitro platform to investigate the crosstalk between activated HSCs and HCC cells by mimicking physiological architecture with precise spatiotemporal control. Here we developed a tri-cell culture microfluidic chip to evaluate the impact of HSCs on HCC progression. On-chip analysis revealed activated HSCs contributed to endothelial invasion, HCC drug resistance and natural killer (NK) cell exhaustion. Cytokine array and RNA sequencing analysis were combined to indicate the iron-binding protein LIPOCALIN-2 (LCN-2) as a key factor in remodeling tumor microenvironments in the HCC-on-a-chip. LCN-2 targeted therapy demonstrated robust anti-tumor effects both in vitro 3D biomimetic chip and in vivo mouse model, including angiogenesis inhibition, sorafenib sensitivity promotion and NK-cell cytotoxicity enhancement. Taken together, the microfluidic platform exhibited obvious advantages in mimicking functional characteristics of tumor microenvironments and developing targeted therapies.