Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

Objective:To discuss the risk factors for postoperative venous thromboembolism (VTE) in patients undergoing pancreatic surgery.Methods:The clinical data of 488 patients who underwent pancreatectomy at the First Affiliated Hospital of Harbin Medical University from Jan 2016 to Sep 2024 was retrospectively analyzed.Results:One hundred and sixteen patients (23.8%) developed VTE after pancreatic surgery. Logistic analysis showed that advanced age, abdominal surgery history, high preoperative white blood cell count, high platelet lymphocyte ratio (PLR), distal pancreatectomy with splenectomy, open surgery, conversion to open surgery, and long surgery duration were risk factors.Nomogram prediction model based on the above risk factors was constructed and the area under the ROC curve was subsequently measured to be 0.781 (95% CI: 0.731-0.830). Conclusion:The prevention and control of VTE should be strengthened for patients undergoing pancreatic surgery with advanced age, abdominal surgery history, high preoperative white blood cell count, high PLR, distal pancreatectomy with splenectomy, open surgery, conversion to open surgery, and long surgery duration.

Objective To develop a predictive model for postoperative mortality risk in patients with acute aortic dissection(AAD)using the Extreme Gradient Boosting(XGBoost)algorithm combined with Shapley Additive Explanation(SHAP),and to establish a prediction website to serve as a diagnostic and therapeutic support platform for clinicians and patients.Methods A retrospective cohort study design was adopted.Data from 782 AAD patients who underwent surgical treatment at the Fourth Hospital of Hebei Medical University from January 2013 to December 2023 were collected,including basic information and initial serum biomarker test results.Patients were randomly divided into training and test sets at a 7:3 ratio.An external validation set consisting of 313 AAD patients admitted to the Second Hospital of Hebei Medical University from January 2020 to December 2023 was also established for further model validation.Variables were screened using LASSO regression,and an XGBoost machine learning model was constructed and interpreted using SHAP.The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curve analysis.Using the Shiny package,the XGBoost model was deployed to shinyapps.io to create a prediction website for postoperative mortality risk in AAD patients.One patient was selected by simple random sampling from the test set and the external validation set respectively for the prediction example on the Shiny webpage.Results The XGBoost model demonstrated high predictive performance for postoperative mortality in AAD patients,with area under the ROC curve(AUC)values of 0.928(95%CI 0.901-0.956)in the training set,0.919(95%CI 0.891-0.949)in the test set,and 0.941(95%CI 0.915-0.967)in the external validation set.SHAP values indicated the following order of variable importance in the model(from highest to lowest):"lactate dehydrogenase""blood chlorine""multiple organ injury""carbon dioxide combining power""prothrombin time""α-hydroxybutyric acid""creatine kinase isoenzyme""Stanford classification""combined use of bedside blood purification""gender""acute kidney injury""gastrointestinal bleeding""brain injury"and"shock".A risk prediction website for adverse postoperative outcomes in AAD patients was developed using XGBoost-SHAP method(https://dun-dunxiaolu.shinyapps.io/document/)and validated with examples.One randomly selected patient from each of the test and external validation sets was applied:the predicted mortality risk value for patient 1(who died postoperatively)was 0.9539,and that for patient 2(who survived postoperatively)was 0.0206.Conclusions The XGBoost-SHAP model demonstrates high accuracy in predicting postoperative mortality risk for AAD patients.The online prediction tool established based on this model enhances the identification efficiency of high-risk postoperative mortality patients.

In a healthy human, the airway mucus forms a thin, protective liquid layer covering the surface of the respiratory tract. It comprises a complex blend of mucin, multiple antibacterial proteins, metabolic substances, water, and electrolytes. This mucus plays a pivotal role in the lungs' innate immune system by maintaining airway hydration and capturing airborne particles and pathogens. However, heightened mucus secretion in the airway can compromise ciliary clearance, obstruct the respiratory tract, and increase the risk of pathogen colonization and recurrent infections. Consequently, a thorough exploration of the mechanisms driving excessive airway mucus secretion is crucial for establishing a theoretical foundation for the eventual development of targeted drugs designed to reduce mucus production. Across a range of lung diseases, excessive airway mucus secretion manifests with unique characteristics and regulatory mechanisms, all intricately linked to mucin. This article provides a comprehensive overview of the characteristics and regulatory mechanisms associated with excessive airway mucus secretion in several prevalent lung diseases.
Humans ; Mucus/metabolism* ; Mucins/physiology* ; Lung Diseases/metabolism* ; Respiratory Mucosa/metabolism* ; Pulmonary Disease, Chronic Obstructive/physiopathology* ; Asthma/physiopathology* ; Cystic Fibrosis/physiopathology* ; Mucociliary Clearance/physiology*

The aim of this study was to qualitatively and quantitatively detect coronavirus(CoV)in the feces of bats from Qinghua Cave,Yunnan Province,China.CoV was qualitatively tested with reverse transcription polymerase chain reaction(RT-PCR),and homology and genetic evolution were analyzed with bioinformatics software.The established reverse transcription real-time fluores-cence quantitative PCR(qRT-PCR)method was applied to CoV quantification in bat feces.The positivity rate of CoV in 306 fecal samples collected from the fulvous fruit bat(Rousettus leschenaultia)was 7.8%(24/306)according to RT-PCR.All 24 strains of CoV belonged to β-CoV,and showed a similarity of 86.8%-100.0%at the nucleotide level and 95.2%-100.0%at the amino acid level,with respect to other β-CoV sequences in the NCBI database.The positivity rate of CoV was 18.6%(57/306)according to qRT-PCR,a value higher than that according to RT-PCR(χ2=25.3,P<0.05).The mean β-CoV load was 1.3×103 copies/μL.In conclusion,the bats in Qinghua Cave,Yunnan Province,carried CoV belonging to β-CoV.The established qRT-PCR method achieved good sensitiv-ity,accuracy,reproducibility,and a higher detection rate than that of RT-PCR,and can be used for rapid detection of β-CoV in bats.

The aim of this study was to qualitatively and quantitatively detect coronavirus(CoV)in the feces of bats from Qinghua Cave,Yunnan Province,China.CoV was qualitatively tested with reverse transcription polymerase chain reaction(RT-PCR),and homology and genetic evolution were analyzed with bioinformatics software.The established reverse transcription real-time fluores-cence quantitative PCR(qRT-PCR)method was applied to CoV quantification in bat feces.The positivity rate of CoV in 306 fecal samples collected from the fulvous fruit bat(Rousettus leschenaultia)was 7.8%(24/306)according to RT-PCR.All 24 strains of CoV belonged to β-CoV,and showed a similarity of 86.8%-100.0%at the nucleotide level and 95.2%-100.0%at the amino acid level,with respect to other β-CoV sequences in the NCBI database.The positivity rate of CoV was 18.6%(57/306)according to qRT-PCR,a value higher than that according to RT-PCR(χ2=25.3,P<0.05).The mean β-CoV load was 1.3×103 copies/μL.In conclusion,the bats in Qinghua Cave,Yunnan Province,carried CoV belonging to β-CoV.The established qRT-PCR method achieved good sensitiv-ity,accuracy,reproducibility,and a higher detection rate than that of RT-PCR,and can be used for rapid detection of β-CoV in bats.

Objective:To analyze the MYH9 gene sequence of a patient with hereditary thrombocytopenia and diffuse large B-cell lymphoma and his family members,and to explore the relationship between MYH9 gene and tumors.Methods:Peripheral blood samples were collected from the patients and their family members for complete blood count analysis.The platelet morphology was observed under microscope.The MYH9 gene sequence was analyzed by Whole Exon Sequencing and Sanger Sequencing.Results:The mutation site c.279C＞A:p.(Asn93Lys)in exon 2 of the MYH9 gene were found in patient and his family members,both presenting as thrombocytopenia.The platelet count was significantly increased after the administration of Avatrombopag.Conclusion:A novel mutation of MYH9 was found in this study,and the case was sensitive to Avatrombopag,by exploring the relationship between the MYH9 gene and tumors,suggesting that the MYH9 gene may be associated with the development of diffuse large B-cell lymphoma.

Objective:To discuss the risk factors for postoperative venous thromboembolism (VTE) in patients undergoing pancreatic surgery.Methods:The clinical data of 488 patients who underwent pancreatectomy at the First Affiliated Hospital of Harbin Medical University from Jan 2016 to Sep 2024 was retrospectively analyzed.Results:One hundred and sixteen patients (23.8%) developed VTE after pancreatic surgery. Logistic analysis showed that advanced age, abdominal surgery history, high preoperative white blood cell count, high platelet lymphocyte ratio (PLR), distal pancreatectomy with splenectomy, open surgery, conversion to open surgery, and long surgery duration were risk factors.Nomogram prediction model based on the above risk factors was constructed and the area under the ROC curve was subsequently measured to be 0.781 (95% CI: 0.731-0.830). Conclusion:The prevention and control of VTE should be strengthened for patients undergoing pancreatic surgery with advanced age, abdominal surgery history, high preoperative white blood cell count, high PLR, distal pancreatectomy with splenectomy, open surgery, conversion to open surgery, and long surgery duration.

This study investigated the mechanism by which kaempferol(KAE) affected intervertebral disc degeneration(IDD) through the p38 mitogen-activated protein kinase(p38 MAPK) signaling pathway. Rats were randomly divided into five groups: control group, model group, low-dose KAE group, medium-dose KAE group, and high-dose KAE group. An IDD model was established by needle puncture of the caudal intervertebral discs. Four weeks post-surgery, the rats were administered KAE via gavage for 8 consecutive weeks. Magnetic resonance imaging(MRI) was performed, and samples were collected. In vitro, an inflammation model of nucleus pulposus cells(NPCs) induced by tumor necrosis factor-alpha(TNF-α) was constructed. Anisomycin was used to activate the p38 MAPK signaling pathway. NPCs were divided into blank, model, KAE, agonist, and KAE + agonist groups. After 1 day of treatment, cell proliferation activity was assessed using the CCK-8. Protein expression levels were determined by Western blot, and mRNA expression was measured by real-time quantitative polymerase chain reaction. Cell apoptosis was detected by TUNEL staining, and immunofluorescence staining was used to detect type Ⅱ collagen and matrix metalloproteinase 3(MMP3). In vivo results indicated significant improvement in the degree of IDD in the treatment groups compared to the model group, with the medium-dose group showing more pronounced therapeutic effects than the low-and high-dose groups. In vitro results demonstrated that KAE treatment significantly enhanced NPC proliferation activity, down-regulated the expression levels of Bcl-2-associated X protein(Bax), interleukin-6(IL-6), interleukin-17A(IL-17A), MMP3, and a disintegrin and metalloproteinase with thrombospondin motifs 5, and inhibited the phosphorylation of p38 MAPK pathway-related proteins. Activation of the p38 MAPK signaling pathway by anisomycin reduced the therapeutic effects of KAE. The study concluded that KAE could improve the proliferation activity of degenerated NPCs, reduce inflammation levels, and slow the progression of IDD in rats, and the mechanism was likely related to the regulation of the p38 MAPK signaling pathway.
Animals ; p38 Mitogen-Activated Protein Kinases/genetics* ; Kaempferols/pharmacology* ; Intervertebral Disc Degeneration/genetics* ; Rats ; Rats, Sprague-Dawley ; Male ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Nucleus Pulposus/drug effects* ; Signal Transduction/drug effects* ; Humans ; MAP Kinase Signaling System/drug effects*

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis