The pathogenesis of metabolic dysfunction-associated steatotic liver disease （MASLD） is fundamentally rooted in spleen deficiency and is closely associated with phlegm turbidity， damp-heat and blood stasis. Clinically， liver constraint with spleen deficiency and internal retention of damp turbidity represent the predominant traditional Chinese medicine （TCM） syndrome patterns. Researches have indicated intrinsic connections between the syndrome patterns and biological indicators such as gut microbiota and metabolic profiles. Regarding treatment， classical famous formulas， modern empirical formulas， and newly developed TCM drugs show positive effects in regulating glucose and lipid metabolism， improving insulin resistance， and alleviating metabolic inflammation， exhibiting multi-target mechanisms of action； acupuncture and other external therapies also provide adjunctive value. Nevertheless， current researches still have limitations such as the lack of high-quality clinical evidence and insufficient systematic elucidation of the uncerlying mechanisms. Future efforts should focus on conducting high-quality TCM clinical trials with hard endpoint outcomes such as hepatic histology outcomes， and utilizing modern technologies like multi-omics to elucidate TCM's mechanisms of action， thereby advancing the position of TCM as a first-line therapeutic strategy for MASLD.

ObjectiveTo investigate the effects of Chaihu Jia Longgu Mulitang（CJLM） on depression-like behaviors and neuroinflammation in rats subjected to social isolation combined with chronic unpredictable mild stress（CUMS）， and to explore the potential underlying mechanisms. MethodsSixty male SD rats were randomly divided into a normal group， a model group， and low-， medium-， and high-dose CJLM groups（2.89， 5.78， 11.56 g·kg^-1）， as well as a fluoxetine group（10 mg·kg^-1）. Except for the normal group， all other groups were subjected to social isolation combined with CUMS for 63 d. During the first 35 d， depression models were established only， and from day 36 onward， modeling and drug administration were conducted simultaneously for a total intervention period of 28 d. Depression-like behaviors were evaluated using the sucrose preference test， open-field test， and forced swimming test. Hematoxylin-eosin（HE） staining was performed to observe hippocampal histomorphology. Immunohistochemistry（IHC） was used to detect the expression levels of ionized calcium-binding adapter molecule 1（Iba1） and gasdermin D（GSDMD） proteins in the hippocampus. Western blot analysis was employed to determine the protein expression levels of adenosine 5′-monophosphate（AMP）-activated protein kinase（AMPK） and phosphorylated（p）-AMPK， silent information regulator 1（SIRT1）， nuclear factor-κB（NF-κB） and p-NF-κB， NOD-like receptor protein 3（NLRP3）， and Caspase-1 in the hippocampus. Real-time quantitative polymerase chain reaction（Real-time PCR） was used to detect the mRNA expression levels of tumor necrosis factor-α（TNF-α）， interleukin（IL）-6， and IL-1β in the hippocampus. ResultsCompared with the normal group， the model group showed a decreased sucrose preference rate（P<0.01）， reduced total movement distance（P<0.01）， prolonged immobility time（P<0.01）， and decreased central zone residence time（P<0.01） in the open-field test， and increased immobility time in the forced swimming test（P<0.01）. Hippocampal neuronal structure was damaged. The contents of Iba1 and GSDMD in the hippocampus were significantly increased（P<0.01）. The protein expression levels of p-AMPK and SIRT1 in the hippocampus were significantly decreased（P<0.01）， whereas the protein expression levels of p-NF-κB， NLRP3， and Caspase-1 were significantly increased（P<0.01）. The mRNA expression levels of IL-1β， IL-6， and TNF-α in the hippocampus were significantly upregulated（P<0.01）. Compared with the model group， the low-， medium-， and high-dose CJLM groups and the fluoxetine group all were able to reverse depression-like behavioral changes， as evidenced by increased sucrose preference rate， increased total movement distance with shortened immobility time in the open-field test， prolonged central zone residence time， and reduced immobility time in the forced swimming test（P<0.05， P<0.01）. Meanwhile， hippocampal neuronal structural damage was alleviated. In the hippocampus， the expression levels of Iba1 and GSDMD were downregulated， the expression levels of p-AMPK and SIRT1 were upregulated， and the abnormal elevations of p-NF-κB， NLRP3， Caspase-1， as well as IL-1β， IL-6， and TNF-α mRNA were suppressed（P<0.05， P<0.01）. ConclusionCJLM can ameliorate depression-like behaviors in rats subjected to social isolation combined with CUMS and attenuate hippocampal neuroinflammation and pyroptosis， suggesting that its effects may be associated with the regulation of AMPK/SIRT1/NF-κB/NLRP3 signaling pathway.

Zoledronic acid (ZA), a nitrogen-containing bisphosphonate with established clinical utility in osteoporosis management, exhibits emerging antitumor potential in estrogen receptor-positive breast cancer. However, the molecular mechanisms underlying its nonapoptotic anticancer effects remain poorly characterized. This study revealed that ZA induced ferroptosis in ER+ breast cancer cells through dual suppression of cystine-glutamate antiporter SLC7A11 and glutathione peroxidase 4 (GPX4), key repressors of ferroptosis. Pharmacological inhibition of ferroptosis using Ferrostatin-1 significantly attenuated ZA-induced cytotoxicity, while combinatorial treatment with the GPX4 inhibitor RSL3 synergistically enhanced lipid peroxidation and cell death. Mechanistically, ZA activated the Hippo-YAP signaling pathway, promoting YAP phosphorylation, proteasomal degradation, and cytoplasmic retention, thereby silencing SLC7A11 and GPX4. We established a novel metabolic vulnerability in hormone-responsive malignancies.These findings position ZA as a bifunctional ferroptosis inducer in ER+ breast cancer, offering a promising strategy to overcome endocrine resistance.

Objective To investigate the expression characteristics of the transcription factor E2F2 in clear cell renal cell carcinoma (ccRCC), its impact on patient prognosis, and its potential role in the tumor immune microenvironment, with validation using clinical samples and functional assays. Methods RNA sequencing data and clinical information of ccRCC patients were obtained from the TCGA database; GSE53757 and GSE66272 datasets were downloaded from the GEO database as external validation cohorts. The expression difference of E2F2 between ccRCC tissue and normal tissue was compared, and the relationship between E2F2 expression and clinical pathological characteristics was analyzed. Kaplan-Meier (KM) survival analysis with log-rank test was performed to evaluate the effects of E2F2 on overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS). The prognostic efficacy of E2F2 in predicting 1-, 3- and 5-year survival was evaluated using receiver operating characteristic (ROC) curve. GSEA was performed to identify E2F2-related signaling pathways, and the ESTIMATE and CIBERSORT algorithms were used to assess the relationship between E2F2 expression level and tumor immune cell infiltration and immune microenvironment. Twenty pairs of surgically resected and pathologically confirmed ccRCC tissues and matched adjacent non-tumor tissues were collected from our hospital, and immunohistochemistry (IHC) was performed to detect the protein expression of E2F2. Human ccRCC cell line 786-O was used for functional assays;shRNA was used to knock down E2F2 expression (constructing stable shE2F2#1 and shE2F2#2 cell lines), and qRT-PCR and Western blot were performed to verify knockdown efficiency, followed by MTT, colony formation, and Transwell migration assays to evaluate the effects of E2F2 on the biological behaviors of ccRCC cells. Results E2F2 was significantly upregulated in ccRCC tissues (the same results in the verification set). Higher E2F2 expression was associated with advanced histological grade, clinical stage and higher TNM classification (P＜0.05). KM analysis showed that patients in the E2F2 high-expression group had worse OS, PFS, and DSS (P=0.019, 0.036, ＜0.001); the ROC curves showed area under the curve (AUC) of E2F2 of predicting 1-, 3- and 5- year survival of ccRCC patients were 0.844, 0.851 and 0.815, respectively. GSEA revealed that the E2F2 low-expression group was enriched in multiple metabolism-related pathways, whereas the E2F2 high-expression group was associated with immune-related pathways. Immune analysis demonstrated that high E2F2 expression was associated with increased immune scores, increased proportion of immune cells, higher tumor mutation burden, and potentially stronger immunotherapy response. IHC results showed that the E2F2 immunoreactivity score in ccRCC tissues was significantly higher than that in adjacent non-tumor tissues (P＜0.05). Functional assays indicated that E2F2 knockdown significantly inhibited the proliferation, colony formation, and migration of ccRCC cells. Conclusion E2F2 is highly expressed in ccRCC and may be involved in tumorigenesis and progression through modulation of the immune microenvironment. Its expression level is closely associated with patient prognosis, and E2F2 has the potential to serve as a prognostic biomarker and immunotherapeutic target in ccRCC.

Patients with lung cancer experience a heavy symptom burden during the perioperative period, which seriously affects their recovery and quality of life. Traditional symptom management models rely mainly on scheduled ward rounds during hospitalization and outpatient follow-up after discharge. However, they have limitations such as delayed symptom recognition, lack of post-discharge monitoring, and non-quantitative symptom assessment, which often lead to delayed interventions and low patient satisfaction. In recent years, the symptom management model based on electronic patient-reported outcomes (ePRO) has been increasingly valued in clinical practice. Existing high-level evidence from both domestic and international studies indicates that, through proactive monitoring, real-time alerts, and remote interventions, this model enables dynamic and continuous symptom management and helps improve patient recovery and healthcare experience. As a supplement to routine medical care, the ePRO-based symptom management model aims to enhance the quality of care rather than replace existing medical processes. To promote the standardized application of this model in perioperative lung cancer care, this consensus integrates domestic and international evidence. After multiple rounds of voting by more than 50 experts, it formulates 12 consensus statements covering the three core components, symptom monitoring, alerting, and intervention, to provide scientific and practical recommendations for clinical practice.

Objective: To investigate the efficacy, safety, and traditional Chinese medicine (TCM) medication patterns of rituximab (RTX) combined with TCM on treating children with steroid-dependent nephrotic syndrome (SDNS). Methods: One hundred and forty-three children with SDNS who visited the Pediatric Nephrology Department of the First Affiliated Hospital of Henan University of Chinese Medicine from January 2018 to December 2022 were enrolled. A cohort study design was adopted, with " RTX treatment" as the exposure factor. Children who met this exposure factor were assigned to the RTX cohort (RTX, glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment), whereas those who did not were assigned to the basic treatment cohort (glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment ), and followed up for 6 months. The frequency of urinary protein recurrences, urinary protein remission duration, proportion and duration of steroid reduction and cessation, cumulative usage of steroids, proportion of recurrence, recurrence amount of steroid used, efficacy of TCM syndrome, and laboratory and safety indicators after treatment, and height and CD19+ B cell count before and after treatment were compared between the two cohorts. The medication patterns of TCM in the two cohorts were analyzed using frequency statistics, association rule analysis, and systematic clustering analysis. Results: Compared with the basic treatment cohort, the RTX cohort showed a decrease in the frequency of urinary protein recurrence, extended sustained remission of urinary protein, an increase in the proportion of steroid reduction and cessation, a shorter duration of steroid reduction and cessation, a decrease in cumulative steroid dosage, a lower recurrence rate, a decrease in CD19+ B cell count, and a decrease in 24-h urinary total protein quantification and the level of cholesterol (P<0.05). No significant difference in the recurrence amount of steroid used, height, TCM syndrome efficacy, albumin, aspartate transaminase, blood urea nitrogen, platelet count, and safety indicators between the two cohorts. Children with SDNS were mostly characterized by qi and yin deficiency syndrome, followed by spleen and kidney yang deficiency syndrome. A total of 175 TCMs were included, including 28 high-frequency drugs such as Huangqi, Fuling, Gancao, Baizhu, Dangshen, and Jiuyurou. The primary use of medication is to nourish the qi and spleen, nourish the kidney, and warm yang. The analysis of association rules yielded eight binary associations and ten three-phase associations, with Huangqi, Baizhu, Fuling, and Dangshen, being the most closely related. Cluster analysis identified four TCM combinations, primarily focusing on tonifying kidney and replenishing essence, benefiting qi and nourishing yin, and removing blood stasis. Conclusion RTX combined with TCM syndrome differentiation treatment can reduce the recurrence frequency of SDNS, prolong the remission period, reduce the glucocorticoid dosage, and have no marked effect on height growth. No apparent adverse reactions were observed. TCM should focus on nourishing qi and yin while removing blood stasis.

PURPOSE: To analyze risk factors for severe trauma and establish a nomogram for early risk prediction, to improve the early identification of severe trauma. METHODS: This study was conducted on the patients treated in 81 trauma treatment institutions in Gansu province from 2020 to 2022. Patients were grouped by year, with 5364 patients from 2020 to 2021 as the training set and 1094 newly admitted patients in 2020 as the external validation set. Based on the injury severity score (ISS), patients in the training set were classified into 2 subgroups of the severe trauma group (n = 478, ISS scores ≥25) and the non-severe trauma group (n = 4886, ISS scores <25). Univariate and binary logistic regression analyses were employed to identify independent risk factors for severe trauma. Subsequently, a predictive model was developed using the R software environment. Furthermore, the model was subjected to internal and external validation via the Hosmer-Lemeshow test and receiver operating characteristic curve analysis. RESULTS: In total, 6458 trauma patients were included in this study. Initially, this study identified several independent risk factors for severe trauma, including multiple traumatic injuries (polytrauma), external hemorrhage, elevated shock index, elevated respiratory rate, decreased peripheral oxygen saturation, and decreased Glasgow coma scale score (all p < 0.05). For internal validation, the area under the receiver operating characteristic curve was 0.914, with the sensitivity and specificity of 88.4% and 87.6%, respectively; while for external validation, the area under the receiver operating characteristic curve was 0.936, with the sensitivity and specificity of 84.6% and 93.7%, respectively. In addition, a good model fitting was observed through the Hosmer-Lemeshow test and calibration curve analysis (p > 0.05). CONCLUSION This study establishes a nomogram for early risk prediction of severe trauma, which is suitable for primary healthcare institutions in underdeveloped western China. It facilitates early triage and quantitative assessment of trauma severity by clinicians prior to clinical interventions.
Humans ; Nomograms ; Male ; Female ; Wounds and Injuries/diagnosis* ; Risk Factors ; Middle Aged ; Adult ; Injury Severity Score ; Risk Assessment ; ROC Curve ; Aged ; Logistic Models ; China ; Glasgow Coma Scale

OBJECTIVES: To explore the predictive factors for non-response to intravenous immunoglobulin (IVIG) in children with Kawasaki disease (KD) and to establish an IVIG non-response prediction scoring model for the Sichuan region. METHODS: A retrospective study was conducted by collecting clinical data from children with KD admitted to four tertiary hospitals in Sichuan Province between 2019 and 2023. Among them, 940 children responded to IVIG, while 74 children did not respond. Multivariate logistic regression analysis was used to identify the predictive factors for non-response to IVIG and to establish a predictive scoring model. The model's effectiveness was assessed using the receiver operating characteristic curve (ROC) and validated with an independent dataset. RESULTS: Multivariate logistic regression analysis showed that the platelet-to-lymphocyte ratio (PLR), hemoglobin (Hb), serum creatinine, aspartate aminotransferase (AST), and platelet count (PLT) were closely related to non-response to IVIG in children with KD (P<0.05). Based on these indicators, a predictive scoring model was established: PLR > 199, 0.4 points; Hb ≤ 116 g/L, 4 points; AST > 58 U/L, 0.2 points; serum creatinine > 38 µmol/L, 3.9 points; PLT count ≤ 275 × 10⁹/L, 0.3 points. Using this model, children with KD were scored, and a total score greater than 4.3 was considered high risk of non-response to IVIG. The sensitivity of the model in predicting non-response to IVIG was 77.0%, specificity was 65.7%, and the area under the ROC curve was 0.746 (95%CI: 0.688-0.805). CONCLUSIONS The predictive scoring model based on PLR, Hb, serum creatinine, AST, and PLT demonstrates good predictive performance for non-response to IVIG in children with KD in the Sichuan region and can serve as a reference for clinical decision-making.
Humans ; Mucocutaneous Lymph Node Syndrome/blood* ; Immunoglobulins, Intravenous/therapeutic use* ; Male ; Female ; Retrospective Studies ; Child, Preschool ; Infant ; Logistic Models ; Child ; Platelet Count ; ROC Curve

OBJECTIVES: To investigate the clinical features and prognosis of children with non-Down-syndrome-related acute megakaryoblastic leukemia (non-DS-AMKL). METHODS: A retrospective analysis was conducted on the medical data of 17 children with non-DS-AMKL who were admitted to Children's Hospital of The First Affiliated Hospital of Zhengzhou University from January 2013 to December 2023, and their clinical features, treatment, and prognosis were summarized. RESULTS: Among the 17 children with non-DS-AMKL, there were 8 boys and 9 girls. Fourteen patients had an onset age of less than 36 months, with a median age of 21 months (range:13-145 months). Immunophenotyping results showed that 16 children were positive for CD61 and 13 were positive for CD41. The karyotype analysis was performed on 16 children, with normal karyotype in 6 children and abnormal karyotype in 9 children, among whom 5 had complex karyotype and 1 had no mitotic figure. Detected fusion genes included EVI1, NUP98-KDM5A, KDM5A-MIS18BP1, C22orf34-BRD1, WT1, and MLL-AF9. Genetic alterations included TET2, D7S486 deletion (suggesting 7q-), CSF1R deletion, and PIM1. All 17 children received chemotherapy, among whom 16 (94%) achieved complete remission after one course of induction therapy, and 1 child underwent hematopoietic stem cell transplantation (HSCT) and remained alive and disease-free. Of all children, 7 experienced recurrence, among whom 1 child received HSCT and died of graft-versus-host disease. At the last follow-up, six patients remained alive and disease-free. CONCLUSIONS Non-DS-AMKL primarily occurs in children between 1 and 3 years of age. The patients with this disorder have a high incidence rate of chromosomal abnormalities, with complex karyotypes in most patients. Some patients harbor fusion genes or gene mutations. Although the initial remission rate is high, the long-term survival rate remains low.
Humans ; Male ; Female ; Leukemia, Megakaryoblastic, Acute/etiology* ; Child, Preschool ; Infant ; Child ; Retrospective Studies ; Prognosis ; Down Syndrome/complications*