Affiliated Hospital of Shandong University of Traditional Chinese Medicine

Abstract Background: Abnormally elevated intra-abdominal pressure (IAP) predisposes critically ill patients to multiple organ dysfunction. Although guidelines recommend routine IAP monitoring, the relative prognostic value of baseline IAP versus dynamic changes in IAP (ΔIAP) remains controversial. In complex critical care settings, medical interventions frequently introduce confounding by indication into ΔIAP measurements. Thus, identifying stable and independent IAP predictors of adverse outcomes is essential for optimizing early risk stratification. This study aimed to determine the independent predictive value of baseline IAP and ΔIAP for mortality across various time points and overall prognosis in critically ill patients, and to assess the incremental prognostic and clinical utility of adding baseline IAP to the standard SOFA score. Methods: We included 1,440 adult critically ill patients with documented baseline IAP from the MIMIC-IV database. Patients were stratified into three groups according to baseline IAP. Kaplan-Meier analysis and multivariable Cox proportional hazards models were used to assess the independent associations of baseline IAP and ΔIAP with 7-, 28-, 90-, and 365-day all-cause mortality. Optimal prognostic cutoffs were determined using receiver operating characteristic (ROC) curves and the maximum Youden index. Subgroup analyses were performed with interaction testing, and the likelihood ratio test (LRT), C-index, and net reclassification improvement (NRI) were calculated to quantify the incremental predictive value. Results: Multivariable Cox regression analysis identified high baseline IAP (> 20 mmHg) as an independent risk factor for 7-day mortality (HR:1.378). When treated as a continuous variable, each 1-mmHg increase in baseline IAP was independently associated with a 2.6% higher risk of 7-day mortality. Conversely, ΔIAP showed no independent predictive value for early mortality. Optimal cutoff analysis demonstrated that as the observation period extended from the early (7 days) to the medium- and long-term (28–365 days), the prognostic IAP threshold for mortality shifted from 19.5 mmHg to a stable 22.5 mmHg. Subgroup analyses verified the robust predictive performance of baseline IAP across diverse clinical subgroups. Furthermore, incorporating baseline IAP into the SOFA score significantly improved model goodness-of-fit (LRT P = 0.028) and risk reclassification capacity (NRI = 0.127). Conclusions: Baseline IAP is significantly associated with time‑dependent mortality risk in critically ill patients, with early predictive utility superior to that of ΔIAP. Thus, it serves as a simple and robust predictor for early risk stratification in this population.

This study seeks to characterize the clinicopathological features of a cohort of breast apocrine carcinomas (AC) in the Chinese population, investigate their biological properties through immunohistochemistry and proteomics, and conduct a preliminary exploration of their biologically relevant molecules. Specimens from 12 female patients (median age 52 years) with AC of the breast were obtained from the Department of Pathology of Shandong University of Traditional Chinese Medicine Affiliated Hospital from 2019 to 2024. Clinical pathological features were observed, and relevant immunohistochemical staining and KEGG pathway enrichment analysis were performed. Additionally, three cases each of triple-negative apocrine carcinoma (TNAC) and luminal androgen receptor triple-negative breast cancer (LAR-TNBC) were included for comparative analysis. Proteomic profiling and assessment of TRPS1 gene amplification were performed to elucidate the differences between these entities. In 75% of patients (9/12), the tumours were located in the upper outer quadrant; 50% (6/12) exhibited invasive apocrine carcinoma (IAC) with apocrine-type ductal carcinoma in situ (ADCIS). All cases exhibited an apocrine morphology and were AR/GCDFP-15 positive and ER/PR-negative. CD10 was expressed in a patchy pattern in the marginal zone of the breast in IAC and was highly expressed in ADCIS but not expressed in apocrine metaplasia. The linear development pattern of breast AC (6 cases) was significantly associated with Her-2 positivity (66.7% vs. 33.3%). Hypoxia-inducible factor-1α(HIF-1α) expression was significantly higher in IAC than in ADCIS (p < 0.01) and was associated with invasion. IL-10 was continuously highly expressed in the tumour microenvironment. KEGG analysis revealed AR-Cyclin D1 pathway enrichment; the proteomic analysis revealed significant differences between the TNAC and LAR-TNBC groups (more than 200 differentially expressed proteins (DEPs)).TRPS1 amplification was significantly greater in the LAR-TNBC group (100%, 3/3) than in the AC group. The median follow-up was 6–39 months, with no recurrence or metastasis (100% disease-free survival). AC exhibits unique AR-driven characteristics and an apocrine morphological lineage. CD10, Cyclin D1, and HIF-1α are potential biologically relevant markers. TNAC significantly differs from LAR-TNBC in terms of its proteomic and TRPS1 amplification characteristics, supporting its classification as an independent disease type.

The physiological roles of prolactin extend beyond its classical functions in reproductive regulation. Emerging evidence indicates that prolactin is involved in energy homeostasis and may interact pathophysiologically with obesity; this has attracted increasing attention in endocrinology and metabolic research. Hyperprolactinemia (HPRL) is frequently observed in obese individuals. Observational studies have reported that weight-loss interventions are associated with reduced circulating prolactin levels, whereas dopamine agonists, which suppress prolactin secretion, improve metabolic and endocrine abnormalities in patients with established hyperprolactinemia. Accumulating evidence suggests an association between hyperprolactinemia and obesity. However, the directionality and causality of this relationship remain unclear. Experimental and translational studies suggest that elevated prolactin levels contribute to obesity-related phenotypes through multiple pathways, including altered central appetite regulation, modulation of adipocyte differentiation and lipid storage, impairment of insulin sensitivity, and disruption of the hypothalamic–pituitary–gonadal (HPG) axis. In contrast, obesity may be associated with increased circulating prolactin levels, which are potentially mediated by adipose tissue expansion, enhanced aromatase-dependent estrogen production, and chronic low-grade systemic inflammation. This review aimed to provide a systematic synthesis of current evidence regarding the mechanistic links between hyperprolactinemia and obesity, with an emphasis on the biological properties of prolactin, clinical characteristics of obesity complicated by HPRL, and molecular and physiological pathways underlying their reciprocal interactions. In addition, we critically evaluate current clinical management strategies, including dopamine agonist therapy and lifestyle-based weight-loss interventions, highlighting existing uncertainties and future directions aimed at improving the diagnosis and integrated management of these frequently coexisting conditions.

Integrin α2β1, a major collagen-binding receptor, functions as a key mediator of cell-extracellular matrix (ECM) communication, mechanosensing, and adhesion-dependent signaling. As a core molecular switch in cancer biology, integrin α2 profoundly influences the metastatic cascade-from local invasion, intravasation, survival in circulation, and pre-metastatic niche formation to dormancy and colonization. Although extensive studies indicate that integrin α2β1 regulates tumor proliferation, migration, ECM remodeling, angiogenesis, and immune modulation, its mechanochemical activation mechanisms and context-dependent functions across different stages of metastasis remain incompletely defined. This review systematically summarizes the structural characteristics, activation mechanisms, regulatory networks, and functional roles of integrin α2β1 in the cancer metastatic cascade. We first describe the domain architecture of integrin α2, emphasizing the structural determinants underlying ligand specificity and metal ion-dependent adhesion. We then outline multi-level regulatory mechanisms that drive variable integrin α2 expression across tumor types. The dual biochemical and mechanical modes of integrin α2β1 activation are discussed, with emphasis on nanocluster formation, focal adhesion maturation, force-dependent conformational changes, and key downstream signaling pathways. We further dissect the stage-specific contributions of integrin α2β1 at each stage of metastasis, including its contributions to epithelial-mesenchymal transition, matrix metalloproteinase - mediated ECM degradation, vascular remodeling, circulating tumor cell survival, immune evasion, pre-metastatic niche formation, tumor dormancy, and organotropic colonization. Finally, we review current progress in integrin α2-targeted therapies-including small-molecule inhibitors, monoclonal antibodies, natural compounds, and nanomedicine-based delivery systems-and discuss future directions that leverage mechanobiology, integrin-targeted biomaterials, and computational drug design. Integrin α2β1 is a central mechanochemical regulator of the metastatic cascade, coordinating tumor cell responses to extracellular and intracellular cues. Its functions span critical metastatic processes, making integrin α2 and its downstream pathways promising therapeutic targets. Continued advances in mechanobiology and multi-omics technologies will be essential to refine integrin-centered strategies and improve interventions against metastatic cancer.

Growing evidence suggests that the stimulator of interferon genes (STING)-dependent inflammatory pathway is crucial in the progression of non-alcoholic fatty liver disease (NAFLD). Diosgenin (DG), a natural steroidal saponin, has demonstrated multi-pharmacological potential, such as anti-inflammatory and lipid-lowering capacities. Our previous study confirmed the protective role of DG in rat models of NAFLD. Our present study sought to further explore the protective effects of DG in NAFLD and to determine whether its mechanism involves the STING-dependent inflammatory pathway. In this research, we developed experimental models for both high-fat diet (HFD)-induced NAFLD in rats and steatosis induced by free fatty acids (FFAs) in HepG2 cells. The results revealed that DG treatment significantly reduced body weight, liver index, serum lipid levels, hepatic lipid accumulation, and liver injury in HFD-fed rats. Additionally, DG markedly alleviated mitochondrial dysfunction and suppressed the protein expression of the STING-dependent inflammatory pathway in both in vivo and in vitro NAFLD models. In contrast, administration of cGAMP, a STING agonist, upregulated the STING-dependent inflammatory pathway and exacerbated lipid accumulation and mitochondrial dysfunction in FFAs-induced HepG2 cells. In conclusion, our findings suggested that DG protects against NAFLD by mitigating lipid accumulation and mitochondrial dysfunction, with its mechanism related to the inhibition of the STING-dependent inflammatory pathway.

BackgroundThis study employed a Bayesian network meta-analysis (NMA) to systematically evaluate the efficacy and safety of various acupuncture therapies compared to conventional medication, sham acupuncture, and other interventions for primary insomnia.MethodsPubMed, Embase, Cochrane Library, Web of Science, CNKI, VIP Chinese Scientific Journals, Wanfang, and China Biology Medicine were searched from inception to July 16, 2025. Literature quality was assessed using the Cochrane Risk of Bias Tool v 2.0 (RoB 2.0). Statistical analyses were performed using Stata 18 and R 4.5.1.ResultsIn total, 80 studies involving 7,791 patients were included. Among these, 60.0% were rated as low RoB, 26.3% as unclear RoB, and 13.8% as high RoB. Statistical analysis showed that, compared with conventional medication, abdominal acupuncture (Weighted Mean Difference (MD) −3.73; 95% Credible Interval (95% CrI) [−6.88, −0.55]), acupuncture (MD −1.96; 95% CrI [−2.64, −1.27]), and catgut embedding (MD −3.08; 95% CrI [−5.18, −0.93]) significantly reduced the short-term Pittsburgh sleep quality index (PSQI) scores. Compared with acupuncture, warm acupuncture (MD −2.55; 95% CrI [−4.88, −0.21]) significantly reduced the long-term PSQI scores. Compared with sham acupuncture, abdominal acupuncture (Standardized Mean Difference (SMD) −3.06; 95% CrI [−6.08, −0.09]) and acupuncture (SMD −2; 95% CrI [−3.05, −0.98]) significantly reduced anxiety scores; meanwhile, acupuncture (SMD −1.52; 95% CrI [−2.79, −0.26]) significantly reduced depression scores. Compared with conventional medication, acupuncture (Relative Risk (RR) 1.19; 95% CrI [1.12, 1.27]) and catgut embedding (RR 1.25; 95% CrI [1.05, 1.52]) significantly improved clinical efficacy rates. However, no significant differences were observed in the relative effectiveness among different acupuncture therapies. The cumulative sample size included in the safety analysis was 1,772, from which 99 adverse events were reported (5.59%). No significant differences were detected across interventions; based on the surface under the cumulative ranking curve (SUCRA), wrist-ankle needle may show higher potential safety.ConclusionCurrently, no single intervention has emerged as optimal across all outcomes. Abdominal acupuncture, catgut embedding, electroacupuncture, and wrist-ankle needle ranked relatively high for certain outcomes based on SUCRA and showed potential advantages. However, given the potential publication bias, variations in acupuncture protocols, and insufficient long-term follow-up data, further validation is required.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251040450, Identifier: CRD420251040450.

Tic disorder (TD) frequently co-occurs with attention-deficit/hyperactivity disorder (ADHD) and is associated with greater symptom severity and limited treatment options. Qiangzhi Fang is a Traditional Chinese Medicine (TCM) herbal formula that has been clinically used for neurobehavioral disorders, but its experimental evidence and mechanisms remain insufficiently characterized. To evaluate the behavioral effects of Qiangzhi Fang in a drug-induced rat model of TD comorbid with ADHD and to explore potential striatal molecular mechanisms. A drug-induced TD+ADHD rat model was established in male Sprague-Dawley rats. Animals were assigned to control, model, and Qiangzhi Fang treatment groups (low, medium, and high doses). Behavioral assessments included stereotypic behavior scoring (tic-like behaviors), locomotor activity (hyperactivity), anxiety-related behavior, and spatial learning and memory. Striatal expression of tyrosine hydroxylase (TH) and phosphorylated Ca2⁺/calmodulin-dependent protein kinase II (p-CaMKII) was examined using Western blotting and real-time PCR. Qiangzhi Fang treatment ameliorated TD- and ADHD-like behavioral abnormalities, including reduced stereotypic movements, decreased hyperactivity, and improved spatial learning and memory performance, with the most pronounced effects observed at higher doses. At the molecular level, treatment was associated with downregulation of striatal TH and p-CaMKII expression. These markers reflect alterations in dopamine synthesis and synaptic signaling; however, dopamine levels, receptor subtypes, and neural circuitry were not directly assessed. Qiangzhi Fang improved behavioral phenotypes in a preclinical rat model of TD comorbid ADHD and was associated with changes in striatal TH and p-CaMKII expression. These findings suggest a possible neuromodulatory role of Qiangzhi Fang, although the mechanistic evidence remains preliminary. This study may provide an experimental basis for further investigation of herbal formulations in TD and ADHD.