How does biomedicine interact with complementary and alternative medicines (CAMs)? Existing studies emphasize boundary work and epistemological distinctions, but give limited attention to the professional contexts shaping biomedical responses. Adopting a social space perspective, this study argues that variation in biomedical responses to CAMs arises from healthcare space structures-specifically, the social distance between biomedicine and CAMs and physicians' social positions. Drawing on a comparative study of Hong Kong and Chinese mainland, we show that biomedical physicians adopt two distinct professional norms toward traditional Chinese medicine (TCM): an exclusive norm in Hong Kong and an integrative norm in Chinese mainland. Evidence from in-depth interviews with physicians indicates that these norms reflect differing patterns of social distance between biomedicine and TCM and the stratified social positions of physicians in the two regions. By foregrounding professional context, this study offers a spatial framework for understanding variation in biomedical responses to CAMs across sociocultural settings.
Prostate cancer treatment increasingly emphasizes quality-of-life maintenance alongside oncological control. Integrative Traditional East Asian Medicine (TEAM), including traditional Chinese medicine, traditional Korean medicine, and Kampo medicine, has been used as an adjunctive approach for symptom management during cancer treatment. However, evidence regarding its effectiveness and safety across different disease stages remains heterogeneous and has not been comprehensively synthesized. This systematic review and meta-analysis aims to evaluate the clinical effectiveness, safety, and quality-of-life benefits of TEAM-based adjunctive therapies combined with standard conventional treatments in patients with prostate cancer. Randomized controlled trials will be identified through comprehensive multilingual searches of PubMed, Embase, China National Knowledge Infrastructure, Oriental Medicine Advanced Searching Integrated System, Research Information Sharing Service, and other databases from inception to January 2026. Two reviewers will independently screen studies, extract data, and assess risk of bias using the Cochrane risk of bias 2 tool. Primary outcomes will consist of tumor-related outcomes (prostate-specific antigen levels and Response Evaluation Criteria in Solid Tumors-evaluated tumor response rates) and survival outcomes (overall survival and progression-free survival). Secondary outcomes will include clinical symptoms (International Prostate Symptom Score), pain scores (visual analog scale or numeric rating scale), quality of life, and treatment-related adverse events. Potential herb-drug interactions reported in primary trials will also be systematically assessed. Meta-analyses will be performed using random effects models in RevMan (version 5.4). In cases of substantial heterogeneity (I²≥50%), sensitivity and subgroup analyses will be conducted. The certainty of evidence will be assessed with the Grading of Recommendations Assessment, Development, and Evaluation approach. The study selection process will be illustrated using a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram. Where appropriate, pooled effect estimates will be presented using forest plots. This review will provide comprehensive evidence on the role of TEAM-based adjunctive therapies in prostate cancer care across disease stages and will inform the development of integrative oncology guidelines. PROSPERO CRD420251275137; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251275137. PRR1-10.2196/94053.
Nausea and vomiting of pregnancy (NVP) are common symptoms during early pregnancy that significantly impact maternal quality of life and fetal development. Given concerns about the safety of pharmacological treatments, non-pharmaceutical Chinese medical therapies (NPCT) have been new topics of great interest due to their minimal side effects. To evaluate the efficacy and safety of NPCT for the management of NVP through an umbrella review of systematic reviews and meta-analyses of randomized controlled trials. Eligible data were retrieved from online databases up to August 31, 2024 for subsequent analyses. The quality of included reviews and the certainty of evidence were evaluated using the AMSTAR-2 tool and the GRADE criteria, respectively. Subgroup analyses were performed based on intervention types, treatment methods, and control conditions to explore potential sources of heterogeneity. Primary outcomes included the severity of NVP, treatment effectiveness, and safety. This study included a total of 22 systematic reviews or meta-analyses on various NPCT interventions. The AMSTAR-2 assessment rated 6 studies as high quality, 2 as moderate, and 14 as low or very low quality. The GRADE evaluation categorized evidence as moderate for 5 comparisons, low for 15, and very low for 5 out of the 25 outcome measures. Further analyses revealed the superior effects of acupuncture in decreasing the Pregnancy-Unique Quantification of Emesis score (MD, -1.32; 95% CI, -1.69 to -0.95; moderate evidence), increasing the rate of negative urinary ketone bodies (RR, 1.32; 95% CI, 1.14 to 1.53; moderate evidence); as well as reducing anxiety (MD, 0.78; 95% CI, -1.13 to 2.6; moderate evidence) and depression scores (MD, 0.20; 95% CI, -2.05 to 2.46; moderate evidence). NPCT, particularly acupuncture, may have potential benefits in alleviating NVP. However, due to limited overall quality and certainty of evidence, studies with more rigorous designs and larger sample sizes should be included to produce higher-quality evidence, thereby better informing clinical practice. (PROSPERO registration No. CRD42024590714).
To compare the efficacy and safety of Yinhua Miyanling Tablets (YMT) versus levofloxacin in the treatment of female patients with uncomplicated urinary tract infections (uUTIs). A multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority clinical trial was conducted from August 2022 to August 2023 in 9 tertiary hospitals across China. By using a block randomization method, 480 female patients with uUTI were randomized in a 1:1 ratio to receive either YMT 2 g, 4 times daily for 7 consecutive days (plus levofloxacin-matching placebo) or levofloxacin tablets 0.5 g, once daily for 3 consecutive days (plus YMT-matching placebo). The primary outcome was the proportion of patients requiring additional antimicrobial therapy for uUTIs between day 1 and days 38-42 of treatment, while the secondary outcomes included the Acute Cystitis Symptom Score (ACSS) and urinalysis after 42-d treatment. Safety assessments were conducted based on all adverse events (AEs) and abnormal laboratory test results. A total of 458 women with uUTIs were enrolled in the modified intention-to-treat analysis. Between day 1 and days 38-42 of treatment, the proportion of patients requiring additional antimicrobial therapy was 20.8% (47/226) in the YMT group and 9.9% (23/232) in the levofloxacin group (P<0.01). The non-inferiority criterion (margin 8 = 20%) was met. YMT treatment improved ACSS typical symptoms and quality-of-life scores and urinalysis results compared with levofloxacin, although the differences between groups were not statistically significant (P>0.05). The incidence of treatment-emergent AEs was 7.7% (17/226) in the YMT group and 7.0% (16/232) in the levofloxacin group (P=0.775). YMT is non-inferior to levofloxacin in the proportion of patients requiring additional antimicrobial therapy during treatment of uUTIs in women. YMT treatment is as effective as levofloxacin in terms of improving uUTI symptoms and quality-of-life scores. YMT may be used as a promising adjunctive therapy for uUTIs in women. (Trial registration No. ChiCTR2200066312).
To investigate the pharmacodynamic and pharmacokinetic interactions between Shenqi Oral Liquid (SQ) and atorvastatin (ATV) in hyperlipidemic rats, explore the impact of SQ on ATV-related transporters and metabolic enzymes, the potential implications for the safety and rationality of their combined administration based on pharmacodynamic, pharmacokinetic, transporter, and metabolic enzyme data. Hyperlipidemic rats were induced using a high-fat diet and randomized according to serum total cholesterol levels using a randomized block design into model, ATV (10 mg/kg), SQ (0.68, 1.68, 3.38 g/kg), and combination groups, and treated for 4 weeks. Serum lipid profiles, liver histopathological changes, pharmacokinetic parameters of ATV, mRNA expression levels of transporters (including Bcrp, Mrp2, etc.) and metabolic enzymes (CYP2C11, CYP3A2), enzyme activities, as well as the effects of SQ's active ingredients were assessed using quantitative PCR, cocktail probe assays, and primary hepatocyte studies. The combination therapy significantly reduced serum lipid levels and improved liver histology, as evidenced by a more organized cellular structure and reduced accumulation of lipid droplets. SQ significantly increased systemic exposure of ATV metabolites, elevating the maximum plasma concentration (Cmax) and area under the curve from time 0 to time t (AUC0-t) of o-ATV by 97.02% and 119.01%, and of p-ATV by 73.22% and 63.39%, respectively (all P<0.05). SQ downregulated the expressions of Bcrp and Mrp2 in the jejunum and Oatp2b1, Bcrp, and Mrp2 in the ileum, while upregulating Oatp1b2 and CYP3A2 in the liver (all P<0.05). Additionally, it enhanced the enzymatic activities of CYP2C11 and CYP3A2, as shown by significantly reduced AUC0-∞ of omeprazole (P<0.01) and AUC0-t of midazolam (P<0.05). Notably, tangshenoside I, lobetyolin, and ononin were found to promote CYP3A2 mRNA expression (P<0.05). SQ synergizes with ATV in lipid regulation and hepatoprotection through modulation of drug transporters and metabolic enzymes. These findings suggest that dose adjustment of ATV may be necessary during combination therapy, thereby providing a scientific basis for the rational co-administration of these agents.
Cancer-related fatigue(CRF) is one of the most distressing symptoms in patients with malignant tumors, characterized by persistent physical and mental exhaustion that is not alleviated by rest, significantly impairing patients' quality of life. The pathogenesis of CRF involves complex multi-system interactions, which can be summarized as neuro-immune dysregulation and skeletal muscle and mitochondrial dysfunction. Currently, modern medicine faces significant challenges in the clinical management of CRF, including unclear mechanisms of pharmacological interventions, insufficient evidence-based support, and notable side effects. Although non-pharmacological interventions(such as exercise therapy, cognitive behavioral therapy, and light therapy) have been proven effective, they are limited by inadequate standardization of implementation protocols, low patient adherence, and difficulties in sustaining long-term therapeutic effects. In contrast, traditional medicine, especially TCM, demonstrates unique advantages in the holistic regulation of CRF. Chinese herbal medicine offers distinct strengths through multi-target modulation(such as immune regulation, HPA axis modulation, and energy metabolism). The strategy of treatment based on syndrome differentiation(such as replenishing Qi and nourishing blood, strengthening the spleen, and tonifying the kidney) has achieved remarkable clinical outcomes. Non-pharmacological TCM therapies(such as moxibustion and Tuina) have also been shown to alleviate CRF symptoms. This article systematically reviews the multi-system interactive mechanisms underlying CRF and the challenges in modern medical interventions, with a focused discussion on the integrative application prospects of TCM in CRF treatment. It aims to provide a theoretical foundation and research directions for establishing a new comprehensive treatment model that integrates TCM and western medicine, emphasizing individualized and precision-based approaches.
Emerging evidence has demonstrated that lung cancer patients with brain oligometastases (oligo-BMs) could benefit from local radical therapies. Despite rapid advancements in the treatment of oligometastatic disease, the molecular determinants governing the oligometastatic phenotype in the central nervous system remain elusive. We performed 1021-panel sequencing, transcriptome profiling, DNA methylation mapping, and multiplex immunohistochemistry on 20 paired primary lung adenocarcinoma and oligo-BMs specimens to delineate their evolutionary dynamics and microenvironmental characteristics. A pronounced intertumor heterogeneity was observed between primary tumors (PTs) and oligo-BMs, while intratumoral heterogeneity was conserved across lesions. Subclonal analysis and phylogenetic reconstruction demonstrated that oligo-BMs exhibited predominant polyclonal seeding patterns and parallel progression trajectories. Moreover, oligo-BMs displayed a more immunosuppressed microenvironment compared to PTs, characterized by attenuated immunogenic cell death signatures, downregulation of immune-activated pathways, and diminished infiltration of activated immune cells (including B cells, NK cells, and Th1 cells). The methylation levels at functional genomic regions were highly concordant between PTs and oligo-BMs. Notably, we identified NLGN1 as a potential regulator of oligo-BM, where the hypermethylation at its genebody regions was mechanistically associated with transcriptional upregulation. Clinical validation revealed that NLGN1 was specifically overexpressed in BMs compared to PTs and extracranial metastases, correlating with advanced pathological stages and poor prognosis. In vivo studies further confirmed NLGN1 promotes BM in mice. Our findings provide novel insights into the evolutionary trajectory, immune landscape and methylation pattern of oligo-BMs, potentially paving the way for the development of innovative therapeutic strategies for lung cancer patients with oligo-BMs.
暂无摘要（点击查看详情）
Lung adenocarcinoma (LUAD) is a prevalent and lethal malignancy. The three-dimensional (3D) chromatin architecture significantly influences tumor progression, yet the contribution of 3D chromatin structure-related genes (3DCRGs) in LUAD remains unclear. This study was designed to explore the role of 3DCRGs in postoperative recurrence of early-stage LUAD, response to Sorafenib therapy in advanced LUAD, tumor progression, and the regulation of the tumor microenvironment (TME). Based on prior studies of chromatin 3D architecture, we curated 49 3DCRGs. Differential expression analysis in the TCGA-LUAD cohort identified 21 3D differentially expressed genes (3DDEGs) between tumor and adjacent normal tissues. Seven GEO datasets (GSE31210, GSE30219, GSE33072, GSE27389, GSE115002, GSE83836 and GSE31428) were used to screen key genes associated with early recurrence, Sorafenib response, and LUAD stage progression through integrated machine learning approaches, and the selected genes were validated in independent datasets. TME characteristics in high-risk early-stage LUAD patients were assessed using IOBR 2.0. Single-cell transcriptomic analysis (GSE200972) was utilized to identify cell populations enriched with the core genes, while spatial transcriptomics was employed to validate their spatial localization. Virtual single-gene perturbation analysis was performed using scTenifoldKnk to assess the functional convergence of core 3DCRGs in tumor proliferating cells. We identified 21 3DDEGs (|log2FC|≥ 0.5, q < 0.05). Machine-learning integration consistently highlighted SMC3, RAD21, FOXM1, MYBL2, and MTA3 as key regulators in postoperative recurrence in early-stage LUAD, response to Sorafenib treatment in advanced LUAD, and tumor progression across different stages of LUAD. Models constructed using these genes demonstrated robust performance and were validated in independent cohorts. IOBR analysis revealed that patients with high recurrence risk exhibited co-activation of glycolysis and oxidative phosphorylation, along with significantly increased infiltration of myeloid-derived suppressor cells (MDSCs) (P = 0.0001). Single-cell transcriptomic analysis demonstrated a significant enrichment of these genes within tumor proliferating cells (TPCs), and spatial transcriptomics confirmed their robust expression in epithelial hotspots regions. Virtual single-gene perturbation analysis using scTenifoldKnk revealed that all five core genes convergently regulate cell cycle, DNA replication, and mismatch repair pathways in tumor proliferating cells. Immunohistochemistry results confirmed that SMC3 protein expression was significantly higher in tumor tissues compared to adjacent normal tissues. This study identified five 3DCRGs (SMC3, RAD21, FOXM1, MYBL2 and MTA3) that significantly influence postoperative recurrence in early-stage LUAD, Sorafenib treatment response in advanced tumors, and clinical staging. These genes are enriched in TPCs and may promote tumor evolution and therapeutic resistance by coordinating stemness maintenance and metabolic-immune crosstalk. Our findings highlight the significance of chromatin 3D architecture in LUAD and provide a theoretical foundation for its application in cancer precision medicine and therapeutic intervention.
暂无摘要（点击查看详情）
To compare the effectiveness of electroacupuncture (EA) combined with omeprazole (Ome) and Ome alone on indomethacin-induced gastric injury mice and reveal the underlying mechanism of this combination. Fourty-eight male C57BL/6J mice were randomly divided into 6 groups by a simple random method (n=8), including control, model, Ome, Ome + EA, Ome + sham EA, and Ome + EA + ML385 groups. A gastric ulcer mouse model was constructed by intragastrically administering indomethacin at a dose of 30 mg/kg. EA and Ome treatment were performed twice daily with each session of EA treatment lasting 20 min. Gastric injury severity was determined by measuring the ulcer index. Sixteen mice with gastric ulcers underwent left cervical vagotomy (CV) were further divided into model + CV and Ome + EA + CV groups. Eight mice with gastric ulcers underwent sham vagotomy and EA combined with Ome treatment were included in the Ome + EA + SCV group. Following respective treatments, the gastric mucosal ulcer tissues were collected and pathologic scores were evaluated by HE staining. Oxygenase-1/tumor necrosis factor-α levels in gastric tissue were measured using ELISA. Colorimetric assay was conducted to measure oxidative stress levels. Real-time polymerase chain reaction was applied to detect the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in gastric tissue. Immunofluorescence staining was performed to observe the locations and expressions of F4-80 and Nrf2 in the gastric mucosa. CV was conducted to evaluate the role of the vagus nerve in EA-mediated gastric injury improvement. EA combined with Ome alleviated gastric ulcers and decreased gastric pathologic scores (both P<0.01). Furthermore, it decreased gastric oxidative stress levels and inhibited macrophages activation (all P<0.01). However, vagotomy abolished the antioxidant function of EA. Meanwhile, we observed that Nrf2 plays a critical role in inducing the therapeutic effect of EA combined with Ome on gastric injury. In mice with gastric ulcers, EA combined with Ome can better repair indomethacin-induced gastric injury via inactivation of macrophages and Nrf2-mediated antioxidant signaling pathway, which is primarily mediated by vagus nerve.
Patients with acute decompensated ischemic heart failure (ADIHF) often present with severe clinical symptoms and poor quality of life. In China, Yiqi Fumai lyophilized injection (YQFM) is widely used in the treatment of ADIHF. However, high-quality evidence is still needed to support its efficacy and safety. This study aims to assess the therapeutic efficacy and safety of YQFM in patients with ADIHF. By conducting a multicenter, open-label, blinded-outcome, randomized controlled trial, we recruited patients with ADIHF from 37 hospitals in 20 regions of China from October 2015 to October 2018. Patients were allocated in a 1:1 ratio to either the YQFM group or the control group. Both groups received guideline-directed medical therapy (GDMT), with the YQFM group additionally receiving YQFM for 7 days. The primary outcome included the proportion of patients with a decrease from baseline B-type natriuretic peptide (BNP) value ≥ 30% on day 8 post-randomization. We evaluated the left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) functional class, Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, and composite endpoints. A total of 666 patients with ADIHF (332 in the YQFM group and 334 in the control group) were enrolled. The full analysis set (FAS) analysis revealed that the proportion of patients in the YQFM group with a reduction of at least 30% in BNP value on day 8 was higher than that in the control group (175 [55.21%] vs. 135 [41.93%], one-sided p < 0.001, two-sided p < 0.001; RR, 1.32 [95% CI, 1.12-1.56]). The YQFM group showed statistically significant improvements in LVEF, NYHA functional class, and MLHFQ scores compared to controls. There was no statistically significant difference between the two groups regarding composite endpoint events and adverse events during the follow-up period. Based on GDMT, the combined use of YQFM was associated with further reductions in BNP levels, improve quality of life and cardiac function in patients with ADIHF, without increasing safety risks. However, no significant differences were observed in clinical events, such as mortality or hospitalization, during the follow-up period.
Cardiometabolic disease (CMD) is a widespread public health concern. Few studies have investigated the association of intrinsic capacity (IC) with a range of specific CMD outcomes from an international perspective. We examined the association between IC and CMD along with the joint effect of social isolation. This prospective, multi-regional cohort study integrated individual-level data from three studies conducted between 2006 and 2020: the Chinese Health and Retirement Longitudinal Study (CHARLS); the English Longitudinal Study of Aging (ELSA); and the Korean Longitudinal Study of Aging (KLoSA). Individuals aged 45 years or more without CMD at baseline and with complete follow-up were included. Cox proportional hazards models were used to assess the IC-CMD association. Whether social isolation modified the IC-CMD association was also investigated. In total, 12,792 participants were included. During a median follow-up of 7 years, 4735 participants developed CMD. After adjusting for confounders, "impaired" IC participants (CHARLS: hazard ratio [HR] 1.25, 95% confidence interval [CI] 1.12-1.39) and "pre-impaired" IC participants (ELSA: HR 1.26, 95% CI 1.08-1.46) had significantly elevated risks of incident CMD than "robust" participants. These relationships were most significant for stroke (CHARLS: HR 1.78, 95% CI 1.28-2.46; KLoSA: HR 1.51, 95% CI 1.05-2.19; ELSA: HR 2.23, 95% CI 1.22-4.09; pooled: HR 1.85, 95% CI 1.48-2.32; I2 = 0.0%, p = 0.740). Compared with participants with robust IC and social non-isolation, those with impaired IC and social isolation had a higher risk of CMD (CHARLS: HR 1.37, 95% CI 1.08-1.73; pooled: HR 1.34, 95% CI 1.13-1.59; I2 = 49.6%, p = 0.132), especially diabetes (pooled HR 1.91, 95% CI 1.37-2.66; I2 = 0.0%, p = 0.531). Impaired IC was associated with an increased risk of CMD. The strength of this association varied with the CMD subtypes and across countries. Moreover, IC and social isolation exhibited a joint effect in this relationship.
To study the anti-proliferative and anti-angiogenic mechanism of oridonin in psoriatic keratinocytes by blocking phosphatidylinositol 3-kinase (PI3K/Akt) signaling pathway based on system pharmacology. Protein targets of oridonin and psoriasis-related genes were predicted and their overlap was determined using the Venny package in R. The DAVID database was used for enrichment analysis. The oridonin-psoriasis-target and oridonin-target-pathway (OTP) networks associated with psoriasis, as well as a protein-protein interaction, were constructed using Cytoscape. Molecular docking with AutoDock was used to verify the relationships between oridonin and core targets, and ZDOCK was used to assess interactions between core proteins. All bioinformatics results were verified empirically. The mRNA levels of core targets in oridonin-treated cells were measured using real-time q-PCR. The HaCaT keratinocytes were divided to 4 groups: control, low-, medium- and high-concentration groups and treated with different concentrations of oridonin (1, 5 and 10 µmol/L) for 18 h, and then stimulated with tumor necrosis factor (TNF)-α (20 ng/mL) for 6 h. Western blot was used to detect PI3K/Akt pathway protein levels. Seventy-three targets were found to be strongly associated with the effects of oridonin on psoriasis. The Cluster ONE algorithm was used to extract 6 kernel clusters from the PPI network, and 9 PPI interaction pairs comprising 13 targets showed combined scores ⩾0.999. The OTP network, molecular docking, and protein interaction simulations indicated that oridonin targeted Sirtuin 1 (SIRT1), cyclin dependent kinase 2 (CDK2), Src tyrosine protein kinase (SRC), proteintyrosine phosphatase, nonreceptor-type (PTPN), and SIRT1-tumor protein p53 (TP53), with the CDK2-TP53, SRC-heat shock protein 90 alpha family class a member 1 (HSP90AA1), and PTPN1-epidermal growth factor receptor (EGFR) interaction pairs regulating the PI3K-Akt signaling pathway. Oridonin was observed to block hyperplasia in HaCaT keratinocytes, accompanied by reduced levels of TNF-α, interleukin (IL-)-6, and IL-1 β (P<0.05 or P<0.01). qPCR measurements showed that oridonin significantly inhibited the expression of angiogenesis-related genes, including C-X-C chemokine receptor type 7, C-X-C motif chemokine ligand 12, and vascular endothelial growth factor (P<0.05 or P<0.01). In addition, the qPCR results showed significant changes in the mRNA levels of SIRT1, CDK2, SRC, PTPN1, TP53, HSP90AA1, and EGFR, and Western blot indicated marked changes in the protein levels of cleaved caspase-3, BAD, Bcl-2, p-ERK1/2, and p-p38 after oridonin treatment (P<0.05 or P<0.01). The study identified the primary oridonin targets during psoriasis treatment using network pharmacology. Bioinformatics analysis with empirical verification demonstrated strong associations between SIRT1, CDK2, SRC, PTPN1, TP53, HSP90AA1, and EGFR and oridonin. These interactions were positively correlated with an inhibition of proliferation and angiogenesis mediated by blocking PI3K-Akt signaling pathway.
Solid pseudopapillary neoplasm of pancreas (SPN) is a rare low-grade malignant pancreatic tumor. The morphology of SPN exhibits considerable diversity. Accurate diagnosis is crucial due to the morphological similarity of SPN to other pancreatic tumors, including pancreatic neuroendocrine tumors (NETs), acinar cell carcinoma (ACC) and pancreatoblastoma (PB), especially in the preoperative biopsy specimen. Image-guided biopsy techniques are essential for preoperative diagnosis, but the limited tissue in biopsy samples can complicate the diagnosis of SPN from other tumors. In this study, we evaluate the diagnostic utility of ATP Binding Cassette Subfamily D Member 1 (ABCD1), a novel immunohistochemical (IHC) marker previously identified in surgically resected SPN specimens, for distinguishing SPN in biopsy samples. We analyzed biopsy samples from a cohort of 55 SPN patients (55 biopsy samples and 6 paired surgical resected samples) and compared them with samples from 61 pancreatic ductal adenocarcinoma (PDAC), 90 NET, 13 intraductal papillary mucinous neoplasm (IPMN), 7 ACC and 3 PB patients from four institutions. Our findings show that ABCD1 positively marks SPN biopsy samples consistently as surgical resected samples, with 100% overall positivity and 96.37% exhibiting moderate to strong expression. In contrast, moderate to strong ABCD1 expression was significantly lower in PDAC (3.28%) and NET (6.66%). However, strong expression was observed in 57.14% of acinar cell carcinomas (ACC). Furthermore, ABCD1 complements β-catenin in cases where nuclear β-catenin staining is ambiguous (100% ABCD1 positivity). ROC curve analysis revealed that ABCD1 exhibits excellent diagnostic performance for distinguishing SPN from other pancreatic tumors, achieving a sensitivity of 96.36% and a specificity of 93.10%, establishing it a reliable complementary diagnostic marker in biopsy samples. These results suggest that ABCD1 could serve as a valuable tool for the accurate preoperative diagnosis of SPN, thereby improving clinical management and patient outcomes.
To evaluate active components of Tianma Gouteng Yin (TMGTY) and its mechanisms in treating hypertension-associated vascular cognitive impairment (VCI). Network pharmacology and molecular docking were used to identify major active ingredients and potential targets of TMGTY in treating hypertension-associated VCI. An in vivo model was established using spontaneously hypertensive rats subjected to unilateral common carotid artery occlusion and a high-salt diet. Rats were randomly divided into 7 groups by a simple randomization method: control, model, sham, low-, medium-, and high-dose TMGTY, and nimodipine groups (n=6). After 28 days of oral administration, blood pressure, behavioral studies, pathological staining, and molecular mechanisms were assessed via tail artery blood pressure monitoring, the morris water maze test, HE staining, immunofluorescence staining, ELISA, and Western blotting. Network analysis identified quercetin, kaempferol, beta-sitosterol, and stigmasterol as key ingredients. Pathway enrichment analysis identified the NF-κB signaling pathway as a key pathway through which TMGTY antagonizes the development of hypertension combined with VCI. Core targets included glyceraldehyde-3-phosphate dehydrogenase (GAPDH), interleukin 6 (IL-6), insulin (INS), tumor necrosis factor (TNF), and tumor protein p53 (TP53), and molecular docking confirmed stable binding to TNF and INS. In vivo experiments demonstrated that TMGTY significantly enhanced cognitive performance and reduced blood pressure. Furthermore, it lowered the levels of pro-inflammatory factors (IL-1β, IL-6, TNF-α, Ang-II) and malondialdehyde (MDA), while elevating superoxide dismutase (SOD) expression (P<0.05 or P<0.01). Immunofluorescence staining further revealed that TMGTY treatment reduced the number of Iba1- and CD16-labeled microglia in the hippocampal CA1 region, thereby alleviating neuroinflammation. Additionally, TMGTY inhibited the expression levels of p-NF-κB p65/NF-κB p65 proteins and attenuated neuroinflammation. TMGTY exerts multi-component, multi-target effects on hypertension-associated VCI, mitigating neuroinflammation and oxidative stress via modulation of NF-κB signaling pathway.
Integrative multiomics analysis offers valuable insights into complex biological systems, yet conventional stepwise extraction methods are often limited by tissue spatial heterogeneity and technical biases introduced through repeated processing, which may compromise cross-omics comparability. To address this, we evaluated a coextraction strategy for multiomics profiling of mouse brain tissue. This approach increased RNA yield per milligram of tissue by 32.55% compared with traditional methods while maintaining comparable sequence coverage (88.14%) and reproducibility (r > 0.98). At the proteome level, approximately 7100 proteins were identified, comparable to conventional protocols, with consistent representation of neural functional protein categories, including membrane proteins, kinases, ubiquitin ligase complexes, and transcription factors. Phosphoproteomic analysis revealed increased coverage with 4347 additional high-confidence phosphosites identified, enabling enhanced resolution of regulatory signaling pathways. Integrated multiomics analysis further showed higher RNA-protein correlations (median r value from 0.25 to 0.56) and strengthened enrichment of neural pathways such as synaptic transmission and nervous system development. Overall, this coextraction strategy provides a practical workflow for multiomics integration and may facilitate studies of complex molecular regulation in brain systems.
Ankylosing spondylitis (AS) and SAPHO syndrome both involve the spine and sacroiliac joints with bone marrow edema (BME) on MRI, which can lead to spinal structural damage. No previous study has compared BME characteristics between the two diseases. 42 SAPHO and 60 AS patients with spinal or sacroiliac involvement underwent whole-spine and sacroiliac MRI. SPARCC scores for each spinal segment and sacroiliac joints, vertebral unit involvement frequency, and BME range, intensity, depth were compared. Correlation between SPARCC scores of the whole spine and sacroiliac joints and clinical indicators were analyzed in the two groups of patients. SPARCC scores for all spinal segments and sacroiliac joints in AS patients were significantly higher than those in SAPHO syndrome patients (P < 0.01). Defining bone marrow edema as SPARCC score > 0, the positive rate of vertebral units in spinal segments and sacroiliac joints was higher in AS than in SAPHO syndrome (P < 0.05). The incidence of BME in the cervical, thoracic, and sacroiliac joints was higher in AS than in SAPHO syndrome (P<0.001), with no significant difference in the incidence of lumbar spine BME (P > 0.05); the incidence of bilateral sacroiliac joint edema also showed no intergroup difference (P > 0.05). Further analysis of the score composition in SPARCC-positive cases revealed: the extent scores for each spinal segment in AS patients were higher than those in the SAPHO group (P < 0.001), while there were no significant differences in intensity and depth scores between the two groups; in the sacroiliac joints, the extent score was higher in the AS group (P < 0.05), but the intensity score was higher in the SAPHO group (P < 0.05). Correlation analysis in AS and SAPHO patients showed: spinal SPARCC scores in AS patients were positively correlated with ESR, CRP, and ASDAS-CRP; spinal SPARCC scores in SAPHO patients were positively correlated with BASFI and BASMI. In subgroup analysis, AS patients showed positive correlations between spinal SPARCC scores and ASDAS-CRP at both thresholds (≥2, ≥3), and sacroiliac joint SPARCC scores were positively correlated with BASDAI at both thresholds; at threshold ≥3, sacroiliac joint SPARCC scores were also positively correlated with ASDAS-CRP. In SAPHO patients, at threshold ≥2, spinal SPARCC scores were positively correlated with VAS, BASFI, and BASMI; at threshold ≥3, spinal SPARCC scores were only positively correlated with BASFI, and sacroiliac joint SPARCC scores were positively correlated with ASDAS-CRP (all P < 0.05). SAPHO and AS show similar BME characteristics on MRI. SAPHO patients have a smaller extent of BME in spine and sacroiliac joints, whereas spinal BME may have a stronger correlation with their physical function. In SAPHO patients with axial involvement, the treatment experience of SPA may have certain reference value.
A smartphone-integrated ratiometric fluorescent platform was developed for on-site quantitative and visual detection of ethephon (ETH) using a UiO-66-NH2/red carbon dots (R-CD) hybrid probe. The R-CDs were synthesized from green tea via an environmentally friendly route. Upon hydrolysis, ETH releases phosphate ions that competitively coordinate with the Zr clusters of UiO-66-NH2, thereby inhibiting ligand-metal charge transfer (LMCT) and enhancing the blue fluorescence at 456 nm. Meanwhile, the red emission of R-CDs at 674 nm remains constant as an internal reference. The intensity ratio (F456/F674) exhibited a linear response to ETH concentrations ranging from 12.5 to 500 µM (R2 = 0.997), with a limit of detection (LOD) of 3.5 µM. The probe displayed a distinct red-to-blue fluorescence transition for visual semi-quantification. Quantitative analysis using smartphone RGB imaging exhibited a linear range of 50-500 µM and a LOD of 15 µM. The probe exhibited excellent selectivity against interfering ions and pesticides. It also demonstrated good reproducibility, as evidenced by intra- and inter-day RSDs of 5.11% and 3.94%, respectively. When applied to Coltsfoot flower samples, the method achieved spiked recoveries ranging from 92.71% to 112.14% by fluorometry and from 89.1% to 110.6% by visual detection, both of which agreed well with HPLC-MS/MS results. This platform demonstrated great potential for food safety monitoring.
Diabetic foot ulcers (DFUs) are devastating complications of diabetes, defined by impaired healing, high amputation rates, and substantial mortality, with pathogenesis rooted in interconnected metabolic, immune, and vascular dysregulation. Serum metabolomic profiling identifies elevated branched-chain amino acid (BCAA) levels in DFU patients, yet the metabolic mechanisms linking BCAA dysregulation to DFU remain unexplored. This review systematically presents a causal framework: impairment of the BCAA metabolic process (downregulation of BCKDH in skeletal muscle/fat tissue), dysbiosis of the intestinal microbiota leading to systemic accumulation of BCAA, and subsequent activation of the mTORC1/NF-κB signaling cascade. This triggers insulin resistance, mitochondrial dysfunction, and oxidative stress, causing macrophages to polarize to the pro-inflammatory M1 phenotype, disrupting the functions of NK cells and neutrophils, and inhibiting angiogenesis mediated by HIF-1α/VEGF forming a self-perpetuating metabolic-immune-vascular vicious cycle, thereby delaying the wound healing process. This review aims to provide a metabolism-centered framework for understanding the pathogenesis of DFU and for informing future diagnostic and therapeutic research.