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.

Objective To investigate dynamic changes in myocardial protein phosphorylation during the acute phase of myocardial infarction (MI) in mice. Methods Six 8-week-old C57BL/6J mice were randomly assigned to MI model (n＝3) or sham-operated control (n＝3) groups. Cardiac tissues were harvested 72 hours post-intervention for proteomic analysis. Phosphorylation modifications were systematically characterized using liquid chromatography-mass spectrometry (LC-MS). Bioinformatics analyses included differential phosphorylation screening, functional enrichment, hierarchical clustering, and protein-protein interaction network. Results LC-MS identified 1 921 differentially phosphorylated sites (20 tyrosine and 1 901 serine/threonine sites) across 851 proteins. Compared with controls, MI hearts exhibited significant phosphorylation upregulation at 1 545 sites and downregulation at 376 sites (P＜0.05). Conclusions This study delineates MI-associated phosphorylation dynamics, providing mechanistic insights and potential therapeutic targets for acute MI intervention.

Objective:This study aims to investigate the differences in emotional status and cognitive function among patients with vestibular migraine (VM), Meniere′s disease (MD), and their comorbidity (VMMD), and to analyze key factors influencing cognitive function.Methods:This cross-sectional study included 96 outpatients (32 males, 64 females, aged 21-73 years) from the Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, between December 2022 and December 2023. The study population consisted of 31 VM patients (VM group), 36 MD patients (MD group), and 29 VMMD patients (VMMD group), along with 32 healthy controls (16 males, 16 females, aged 19-74 years). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), while emotional status and somatization symptoms were evaluated through the Generalized Anxiety Disorder scale, Patient Health Questionnaire Depression scale, Symptom Checklist-90, and the Self-rating Somatization Symptom scale. Multiple linear regression analysis was conducted to explore the influence of different variables on cognitive function.Results:The total MoCA score in the VMMD group (26.0 [24.5, 28.0]) was significantly lower than that in the control group (28.0 [27.0, 29.0]) and the MD group (28.0 [26.0, 30.0]) ( P=0.006). VMMD patients exhibited significant impairments in specific cognitive domains, including visuospatial/executive function, delayed recall, and orientation ( P<0.05). Patients with VM, MD, and VMMD showed higher rates of anxiety, depression, and somatization symptoms compared to the control group ( P<0.05), with the VMMD group experiencing the most severe emotional distress. Multiple linear regression analysis identified education level and vestibular disease type as key factors affecting cognitive function, with a university-level education predicting higher MoCA scores ( P<0.001), while VMMD was associated with cognitive decline ( P<0.01). Conclusions:Patients with VM and MD, particularly those with comorbid VMMD, exhibit significant emotional distress. Cognitive impairments are present in VM and VMMD patients, affecting different cognitive domains. These factors should be comprehensively considered in clinical assessments to develop more effective treatment strategies.

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.

Abstract Ring finger protein 183(RNF183) is an E3 ubiquitin ligase that catalyzes the covalent attachment of ubiquitin molecules to substrate proteins. RNF183 is expressed in tissues such as kidney and testis, and it is mainly localized to the endoplasmic reticulum, Golgi apparatus, and lysosomes in cells. As one of the components of the endoplasmic reticulum membrane, it participates in the endoplasmic reticulum stress-responsive pathway that affects cellular and protein ubiquitination. In recent years, the study of E3 ubiquitin ligase member-RNF183 with various diseases such as colorectal cancer, endometrial cancer and bladder cancer has gradually increased. In this review, the role of RNF183 in colorectal cancer, inflammatory bowel disease and other diseases, as well as biological functions such as endoplasmic reticulum stress are summarized, aiming to provide reference ideas for the study of related diseases.

ObjectiveTo investigate the effects of Chaihu and Longgu Mulitang （CLMT） on hippocampal neural damage in the mouse model of depression via the extracellular signal-regulated protein kinase （ERK）/cAMP-response element-binding protein （CREB） signaling pathway. MethodsSeventy-eight male C57BL/6 mice were randomly allocated into normal control， model， low/medium/high-dose （2.89， 5.78， and 11.56 g·kg^-1， respectively） CLMT， and paroxetine （10 mg·kg^-1） groups. A depression model was established by chronic unpredictable mild stress （CUMS） combined with social isolation. Behavioral tests were carried out to evaluate depressive-like behaviors. Hematoxylin-eosin staining and Nissl staining were performed to assess hippocampal morphology and neuronal damage. Immunofluorescence was employed to detect glial fibrillary acidic protein （GFAP） and ionized calcium-binding adapter molecule 1 （Iba1）. Real-time PCR was employed to measure the mRNA levels of ERK and CREB. Western blot was employed to determine the expression of ERK/CREB pathway proteins and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. Molecular Operating Environment （MOE） software was used for molecular docking to evaluate the interactions between CLMT components and target proteins. ResultsCompared with the normal control group， the model group showed decreased sucrose preference （P0.01）， increased tail-suspension immobility time （P0.01）， decreased activity in the central region of the open field test （P0.01）， and decreased activity in the middle and open-arm region of the elevated plus maze test （P0.01）. The hippocampal area in the model group showed wrinkled cells and a reduction in the number of cells， neurons with reduced sizes and Nissl bodies， enhanced fluorescence intensity of GFAP and Iba1 （P0.01）， and down-regulated expression of phosphorylated （p）-ERK， p-CREB， and BDNF （P0.05， P0.01） and mRNA levels of ERK and CREB （P0.01）. Compared with the model group， the CLMT group showed increased body weight （P0.05， P0.01）， restored cell morphology， with only a small number of ruptured cells， normal neuronal structure and morphology with obvious nuclei and abundant Nissl bodies， weakened fluorescence intensity of GFAP and Iba1 （P0.05， P0.01）， up-regulated mRNA levels of ERK and CREB （P0.05， P0.01） and protein levels of phosphorylated （p）-ERK， p-CREB， and BDNF in the hippocampal tissue （P0.05， P0.01）. The results of molecular docking indicated that nine active ingredients in CLMT had good binding affinity with ERK and CREB. ConclusionCLMT may ameliorate the hippocampal nerve injury in the mouse model of depression by regulating the ERK/CREB pathway.

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

Chronic hepatitis B（CHB）is one of the major challenges in the global public health field. As of 2022，approximately 254 million people worldwide were infected with the hepatitis B virus（HBV）. CHB is one of the main causes of liver cirrhosis and hepatocellular carcinoma（HCC）. Nucleos（t）ide analogs（NAs）and interferon therapy can delay the progression of liver fibrosis by inhibiting viral replication，but they cannot completely avoid the problem of heterogeneous treatment responses. Some patients are in a state of low-level viremia（LLV）during treatment. The persistent LLV state can induce chronic inflammation and the progression of liver fibrosis，ultimately increase the risk of HCC. In patients with poor treatment responses，the continuous active viral replication can induce immune disorders，accelerate the evolution of fibrosis to the decompensated stage of liver cirrhosis，and increase the risk of patient death. This article aims to review the definition，mechanisms，and impact on treatment outcomes of LLV and suboptimal response based on the latest research，provide a basis for optimizing antiviral therapy for CHB.

The cellular and molecular components of the tumor immune microenvironment (TIME) and their information exchange processes significantly influence the trends of anti-tumor immunity. In recent years, numerous studies have begun to evaluate TIME in the context of previous cancer treatment strategies. This review will systematically summarize the compositional characteristics of TIME and, based on this foundation, explore the impact of current cancer therapies on the remodeling of TIME, aiming to provide new insights for the development of innovative immune combination therapies that can convert TIME into an anti-tumor profile.
Tumor Microenvironment/immunology* ; Humans ; Neoplasms/therapy* ; Immunotherapy/methods* ; Animals

Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C₂P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn²⁺ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C₂P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.