ObjectiveThis paper aims to clarify the material basis of Gualou Niubangtang and establish a quantitative analysis method for its main constituents， providing a reference for the overall quality control of this preparation. MethodsThe constituents in the formula were systematically characterized based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry （UPLC-Q-TOF-MS/MS）. Identification was performed by matching with the UNIFI 9.6 software and utilizing database platforms such as PubChem， ChemicalBook， and ChemSpider， combined with relevant literature reports. A quantitative analysis method for the seven main constituents in Gualou Niubangtang was established by using high performance liquid chromatography （HPLC）. ResultsUPLC-Q-TOF-MS/MS analysis identified 155 constituents， including 69 flavonoids， 36 terpenoids， 23 phenylpropanoids， 8 phenylethanoid glycosides， and 19 other types of constituents. In the established quantitative analysis method， the seven main constituents showed good linearity within their respective linear ranges. The precision， repeatability， stability， and spike recovery all met the required standards. The results showed that the content ranges of geniposide， liquiritin， hesperidin， arctiin， baicalin， oroxylin A-7-O-β-D-glucuronide， and wogonoside in 15 batches of Gualou Niubangtang were 13.67-21.25， 1.20-7.64， 5.45-7.45， 22.97-33.51， 29.95-39.07， 2.58-4.80， and 6.56-9.31 mg·g^-1， respectively. ConclusionThis study successfully characterizes and attributes multi-category constituents in Gualou Niubangtang， clarifying that its material basis is primarily composed of flavonoids， terpenoids， phenylethanoid glycosides， and phenylpropanoids. Furthermore， it enables the quantification of seven constituents within the formula. This work lays a foundation for research on the quality control， action mechanism， and clinical application of this formula.

Myasthenia gravis is an autoimmune disorder characterized by impaired neuromuscular transmission. Thymectomy is one of the therapeutic options for acetylcholine receptor antibody-positive myasthenia gravis patients. The quality of perioperative care is directly associated with surgical safety and patient outcomes. However, there is currently a lack of specialized nursing consensus or guidelines specifically addressing the care of these patients domestically or internationally. To promote the standardization and normalization of perioperative nursing care for myasthenia gravis patients undergoing thymectomy and to ensure treatment efficacy, a panel of 57 experts from relevant fields was convened. Based on evidence-based medicine and clinical practice experience, discussions were held on various aspects including condition assessment, nutritional support, medication management, and airway care, resulting in a consensus with 18 final recommendations by using the Delphi method through two rounds of expert consultation. This consensus aims to provide a scientific reference for the perioperative nursing care of myasthenia gravis patients undergoing thymectomy.

ObjectiveTo explore the structural characteristics， biocompatibility， anti-inflammatory and antioxidant properties of hyaluronic acid （HA）/silk fibroin （SF） composite hydrogel scaffolds loaded with epigallocatechin gallate （EGCG）， and to provide a new material basis for the treatment of periodontitis. MethodsThe composite hydrogel scaffolds were constructed by cross-linking HA and SF and loaded with EGCG. The water absorption rate， degradation property and material characteristics were detected by scanning electron microscopy. The cytocompatibility and anti-inflammatory and antioxidant properties were evaluated by in vitro experiments. ResultsThe EGCG-loaded scaffolds exhibited a porous network structure and desirable swelling properties. In vitro experiments demonstrated that the scaffolds possessed good biocompatibility， along with the ability to inhibit the expression of inflammatory factors and scavenge reactive oxygen species. ConclusionThe HA/SF-EGCG composite scaffolds have excellent biocompatibility and dual functional activities of anti-inflammatory and antioxidant， providing a new strategy for improving the clinical treatment effect of periodontitis.

ObjectiveTo construct a nomogram prediction model for non-valvular persistent atrial fibrillation （PeAF） patients with left ventricular hypertrophy （LVH） ， followed by prognostic analysis through follow-up. MethodsThis study retrospectively enrolled 949 patients with newly diagnosed and hospitalized non-valvular PeAF. Among them， 403 patients presented with LVH. The cohort was randomly stratified into a training set （n=665） and a validation set （n=284）. Univariate and multivariate Logistic regression analyses were employed to identify independent risk factors for PeAF complicated by LVH. A nomogram prediction model was subsequently constructed and evaluated for discriminative ability， calibration， and clinical utility using receiver operating characteristic （ROC） curve analysis， calibration plots， and decision curve analysis （DCA）. ResultsSeven independent risk factors were ultimately identified and included in the prediction model： female sex， hypertension， diabetes， red blood cell distribution width-SD （RDW-SD）， body mass index （BMI）， left atrial diameter （LAD）， and left ventricular ejection fraction （LVEF）. The area under the ROC curve （AUC） in the training set was 0.862 （95% CI： 0.834-0.890）， and in the validation set， it was 0.870 （95% CI： 0.829-0.911）， demonstrating excellent predictive performance. ConclusionIndependent risk factors for LVH in PeAF patients include female， hypertension， diabetes， RDW-SD， BMI， LAD， and LVEF. The prediction model built based on this can help early identification of PeAF patients with high risk of LVH. At the same time， the incidence of major adverse cardiovascular events （MACE） is higher in PeAF patients with LVH. Patients with atrial fibrillation combined with LVH may benefit from catheter ablation.

The JAK2 V617F mutation is a key molecular event in myeloproliferative neoplasms and is strongly associated with an increased risk of thrombosis. This review aims to summarize the underlying mechanisms, clinical manifestations, and management strategies for thrombosis driven by the JAK2 V617F mutation. Relevant recent studies are analyzed to evaluate the effect of the mutation on molecular signaling, hematopoietic cell function, inflammatory activation, endothelial injury, and coagulation imbalance. Findings indicate that the JAK2 V617F mutation induces the persistent activation of the JAK-STAT pathway, leading to erythroid clonal expansion, platelet hyperreactivity, and enhanced neutrophil chemotaxis, along with excessive inflammatory cytokine release, NET formation, and platelet-leukocyte aggregation. These processes collectively promote endothelial dysfunction and hypercoagulation, ultimately contributing to arterial and venous thrombosis. Clinically, affected patients may present with coronary artery events deep vein thrombosis, and portal vein thrombosis, often accompanied by high recurrence rates and poor outcomes. In conclusion, the JAK2 V617F mutation drives thrombosis via multiple intertwined mechanisms, suggesting that future therapeutic strategies should integrate anticoagulation, anti-inflammation therapy, NET inhibition, and targeted JAK-STAT pathway blockade to improve patient survival.

Objective: To investigate the effects of platelet-derived PD-L1 released during storage on T cell proliferation, apoptosis, and cytokine expression. Methods: Apheresis platelets were stored with agitation at 22℃. Platelet supernatant was collected on days 1, 3, 5, and 7 of storage, and then co-cultured with human CD4 and CD8 mixed T cells isolated by magnetic bead sorting. CCK8 assay was used to detect T cell proliferation; flow cytometry was applied to determine T cell apoptosis as well as the expression levels of IFN-γ and GZMB. Additionally, Western blot was employed to examine alterations in downstream signaling molecules of the PD-1 receptor. Results: With the prolongation of platelet storage time, the inhibitory effect of platelet storage medium on T cell proliferation was gradually enhanced, accompanied by suppressed expression of IFN-γ and GZMB, whereas the apoptosis level of T cells increased progressively. Treatment with PD-1 antibody or PD-L1 antibody partially blocked the regulatory effects of platelet storage medium on T cell proliferation, apoptosis, and the expression of IFN-γ and GZMB. Western blot results showed that the phosphorylation levels of p-SHP1 and p-SHP2 were significantly upregulated, whereas p-AKT expression was downregulated in T cells co-cultured with platelet storage medium. Intervention with PD-1 or PD-L1 antibody could partially reverse the above changes in protein expression. Conclusion: During platelet storage, platelet-derived PD-L1 in the storage medium promotes T cell apoptosis and inhibits T cell proliferation as well as the expression of related cytokines in a time-dependent manner. Therefore, platelet-derived PD-L1, as an important immune regulatory mediator, may be involved in transfusion-related immunomodulation (TRIM).

BACKGROUND:Research has demonstrated a close association between ferroptosis and vascular dementia.Tongmai Kaiqiao Pill has a certain effect on improving the cognitive function of vascular dementia patients,but its mechanism is unclear. OBJECTIVE:To explore the interventional effects and molecular mechanisms of Tongmai Kaiqiao Pill for vascular dementia based on the regulation of ferroptosis by the nuclear factor erythroid-2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4)signaling pathway. METHODS:Among eighty-four SD male rats,12 rats were used as the sham-operated group,and the rest of them were prepared as a model of vascular dementia by the modified 2-VO method,and then randomly divided into the model group,the Tongmai Kaiqiao Pills high-,moderate-,and low-dosage(27.6,13.8,and 6.9 g/kg)groups,the combined group(Tongmai Kaiqiao Pill high-dosage+ML385,20 mg/kg),and the donepezil hydrochloride group(0.45 mg/kg).The drug was given once a day by intragastric administration.The combined group was also intraperitoneally injected Nrf2 inhibitor ML385,once a day,for 4 weeks.Morris water maze was used to detect the learning memory ability of rats.Hematoxylin-eosin staining was used to observe the histopathological changes in the hippocampus of rats in each group.Colorimetric assay was used to detect the content of reduced glutathione,ferrous ion(Fe2+),and malondialdehyde in the serum of rats.Prussian blue staining was used to detect the iron deposition in the hippocampal tissue of rats.Transmission electron microscopy was used to observe the ultrastructural changes of mitochondria in rat hippocampal tissues.Western blot assay was used to detect the protein expression levels of Nrf2,HO-1,GPX4,XCT,and ferritin heavy chain 1(FTH1)in rat hippocampal tissues. RESULTS AND CONCLUSION:(1)In comparison to the sham operation,rats in the model group exhibited a significantly prolonged latency period(P<0.05)and a reduced number of platform crossings(P<0.05).Additionally,the hippocampal tissues of these rats displayed loosely organized structure,deeply stained cell nuclei,and solidified or lysed chromatin.Ferri ions aggregated in CA1 region.There were atrophied mitochondria with dissolved cristae and thickened mitochondrial membranes.Fe2+,malondialdehyde,and reduced glutathione levels in rat serum were found to be elevated(P<0.05).A significant reduction in the expression of GPX4,HO-1,XCT,Nrf2,and FTH1 proteins was detected in the hippocampus(P<0.05).(2)Compared to the model group,the average escape latency of the rats was significantly reduced following intervention with Tongmai Kaiqiao Pills and donepezil hydrochloride(P<0.05),with an increased number of platform crossings(P<0.05).Hippocampal neurons showed significant recovery.Notably,iron aggregation in the CA1 region was significantly reduced,and mitochondrial structure and function were improved.There were significant reductions in Fe2+and malondialdehyde levels,while the levels of GPX4,HO-1,XCT,Nrf2,and FTH1 in rat hippocampal tissues,and reduced glutathione in serum were significantly increased(P<0.05).(3)The high-dose Tongmai Kaiqiao Pills exhibited a treatment effect comparable to that of donepezil hydrochloride(P>0.05),with a significant prolongation of water maze escape latency(P<0.05),a reduced number of platform crossings(P<0.05),and insignificant neuronal pathological changes in the CA1 area.However,the combined group showed increased iron deposition,elevated malondialdehyde and Fe2+levels in blood serum(P<0.05),reduced glutathione content(P<0.05),hippocampal tissue mitochondrial atrophy,and reduced expression of Nrf2,XCT,HO-1,GPX4,and FTH1 proteins(P<0.05).Within a certain range,higher doses of Tongmai Kaiqiao Pills demonstrated a more pronounced effect,comparable to the efficacy of high-dose donepezil hydrochloride.(4)It is concluded that Tongmai Kaiqiao Pills have been shown to mitigate histopathological changes in the rat hippocampus and enhance cognitive function in rats with vascular dementia.The mechanism of action is likely associated with the suppression of ferroptosis through the activation of the Nrf2/HO-1/GPX4 signaling pathway.

BACKGROUND:Studies have reported that alendronate intake significantly increases bone mineral density in patients with osteoporosis. OBJECTIVE:To analyze and compare the changes in metabolites before and after alendronate intervention in ovariectomized rats by chromatography-mass spectrometry,and to further explore the specific mechanism and target of alendronate in the treatment of osteoporosis. METHODS:A total of 36 female Sprague-Dawley rats were randomly divided into model group,alendronate sodium group and sham operation group.The osteoporosis model was established by ovariectomy in the first two groups.Four weeks after modeling,the rats in the alendronate group were intragastrically given alendronate sodium,while those in the sham operation group and model group were given equal volume of normal saline.After 12 weeks of continuous gavage,the metabolites of the lumbar spine were analyzed by chromatography-mass spectrometry,and the common differential metabolites were obtained,which were analyzed by bioinformatics such as Kyoto Gene and Genome Encyclopedia pathway. RESULTS AND CONCLUSION:Totally 17 different metabolites were obtained in the three groups.The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes showed that alendronate sodium could regulate unsaturated fatty acid biosynthesis,linoleic acid metabolism and other pathways to protect ovariectomized rats.These results indicate that alendronate sodium may exert its anti-osteoporosis effect by interfering with unsaturated fatty acid bioanabolism and linoleic acid metabolism,so as to achieve the purpose of preventing osteoporosis

Objective To explore the accuracy of artificial intelligence-based diagnosis of ovarian malignant tumors and the identification of benign and malignant tumors under transabdominal scanning and transvaginal scanning methods. Methods A dataset of transabdominal and transvaginal two-dimensional ultrasound images was used and the images were preprocessed to enhance quality. The region of interest was segmented and divided into a training set and a test set. A convolutional neural network (CNN) was trained on the images in the training set, and the accuracy of the model on the test set was calculated. Results Transvaginal scanning was 14% more accurate in diagnosing malignant ovarian tumors than transabdo-minal scanning on the test set. For identifying the benign and malignant ovarian tumors containing cystic components, a mixture of transvaginal and transabdominal scanning increased the accuracy by 9.7% over transabdominal scanning alone. Conclusion CNN can identify ovarian malignant tumors under both scanning methods, but the accuracy of transvaginal scanning is higher than that of transabdominal scanning, and the CNN model has a higher accuracy in identifying benign and malignant ovarian tumors under transvaginal scanning.

Objective To investigate the value of enhanced magnetic resonance imaging(MRI)radiomics based on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)in predicting the histopathological grading of hepatocellular carcinoma(HCC)before surgery.Methods A total of 101 patients with HCC who were treated in the Second Affiliated Hospital of Kunming Medical University from January 2021 to June 2024 were selected as study subjects and randomly assigned to the training set(n=70)and the test set(n=31)in a ratio of 7∶3.Radiomics features were extracted from portal venous phase(PVP)and hepatobiliary phase(HBP)images,and support vector machine(SVM)image omics model was constructed after dimensionality reduction by least absolute shrinkage and selection operator logistic regression.Model performance was assessed by area under the curve(AUC),accuracy,sensitivity,and specificity.Results After feature screening,the SVM model was constructed by retaining the best image omics features of 2 HBP,5 PVP and 11 combined models.The AUC of PVP,HBP and PVP+HBP combined models were 0.870,0.914 and 0.952,respectively,showing a good ability to distinguish between high and low grade HCC.Conclusion Compared with the independent model,PVP+HBP combined model has better performance in predicting HCC histopathological grading,and can be used as a non-invasive auxiliary tool to help distinguish between high-grade and low-grade HCC before surgery.