Objectives The use of anticoagulants in patients increases the risk of intracranial hemorrhage (ICH). Our aim was to identify factors associated with cerebral hemorrhage in patients using anticoagulants and to develop a predictive model that would provide an effective tool for the clinical assessment of cerebral hemorrhage. Methods In our study, indications for patients receiving anticoagulation included AF, VTE, stroke/TIA, arteriosclerosis, peripheral vascular diseases (PVD), prosthetic mechanical valve replacement, etc. Data were obtained from the patient record hospitalization system. Logistic regression, area under the curve (AUC), and bar graphs were used to build predictive models in the development cohort. The models were internally validated, analytically characterized, and calibrated using AUC, calibration curves, and the Hosmer-Lemeshow test. Results This single-center retrospective study included 617 patients treated with anticoagulants. Multifactorial analysis showed that male, leukoaraiosis, high risk of falls, APTT ≥ 45.4 s, and FIB ≥ 4.2 g/L were independent risk factors for cerebral hemorrhage, and β -blockers were protective factors. The model was constructed using these six factors with an AUC value of 0.883. In the validation cohort, the model had good discriminatory power (AUC = 0.801) and calibration power. Five-fold cross-validation showed Kappa of 0.483. Conclusion Predictive models based on a patient’s medical record hospitalization system can be used to identify patients at risk for cerebral hemorrhage. Identifying people at risk can provide proactive interventions for patients.
Quality evaluation of phytomedicines is limited to small molecules as quality markers, even for herbs with high sugar contents. We established a high-resolution method for distinguishing similar medicinal materials using sugar as quality marker, taking Schisandrae Chinensis Fructus (SCF) and Schisandrae Sphenantherae Fructus (SSF) as an example. High performance liquid chromatography with an evaporative light-scattering detector (HPLC-ELSD), high performance size exclusion chromatography coupled with multi-angle laser light scattering detector and refractive index detector (HPSEC-MALLS-RID) and high performance liquid chromatography with photo-diode array (HPLC-PDA) after 1-phenyl-3-methyl-5-pyrazolone (PMP) pre-column derivatization were used respectively to determine monosaccharide contents, molecular weights and monosaccharide compositions of polysaccharides in this study. The differences of SCF and SSF from ten producing areas were compared by principal component analysis (PCA) and hierarchical cluster analysis (HCA). Results showed that contents of fructose and glucose were similar between SCF and SSF. Molecular weight (Mw) of SCF polysaccharides was ranging from 1.561 × 102 to 6.599 × 102 kDa, and that of SSF polysaccharides was ranging from 8.524 × 102 to 1.7416 × 103 kDa. Schisandra polysaccharides were mainly composed of mannose, galacturonic acid, glucose, galactose and arabinose. Based on PCA and HCA, SCF and SSF from ten different areas were classified into three categories. With great accuracy, sensitivity and stability, the methods established in this study had important reference value for quality evaluation, development and utilization of saccharide components in medicinal materials.
Abstract Background Impaired thyroid hormone sensitivity has been associated with type 2 diabetes (T2D), obesity, and metabolic syndrome, which can lead to alterations of body composition. However, impaired thyroid sensitivity to exacerbate alterations of body composition remains unconfirmed. This study aimed to ascertain impaired thyroid hormone sensitivity association with body composition in euthyroid T2D. Methods A total of 634 individuals with normothyroid T2D were enrolled. Each participant underwent a dual-energy X-ray absorptiometry (DXA) scan to assess body composition, including measurements of body fat percentage (B-FAT), trunk fat percentage (T-FAT), appendicular skeletal muscle index (ASMI), lumbar spine bone mineral density (BMD) (LS-BMD), femoral neck BMD (FN-BMD), hip BMD (H-BMD), and total BMD (T-BMD). Thyroid hormone resistance indices were assessed by calculating serum thyrotropin (TSH) index (TSHI), thyrotrophin T4 resistance index (TT4RI), thyroid feedback quantile-based index (TFQI), and parametric TFQI (PTFQI). Relevant clinical data was also collected. Results Among the recruited patients, females (n = 265) had higher indicators of thyroid hormone resistance and fat distribution than males (n = 369) (all P < 0.05). Across the entire population, indicators of thyroid hormone resistance exhibited positive correlations with fat distribution (all P < 0.01), while most indicators displayed negative associations with skeletal muscle mass. These findings were consistent solely among male participants. Furthermore, even after adjusting for basic characteristics, linear regression analysis revealed that these correlations remained statistically significant (all P < 0.05). Conclusions In males with euthyroid T2D, impaired thyroid hormone sensitivity correlates with fat distribution independent of conventional risk factors.
To observe the protective effect of electroacupuncture (EA) intervention on the expression of brain-derived-neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) proteins and genes in the hippocampus areas in myocardial ischemia (MI) rats, so as to reveal its underlying mechanisms in protecting hippocampal cells under MI.Eighty healthy male SD rats were randomized into sham-operation (sham), MI model, Shenmen (HT 7), HT 7-Zhizheng (SI 7) and HT 7-Xinshu (BL 15) groups (n = 15 in each group). The MI model was established by occlusion of the anterior descending branch of the left coronary artery. EA (2 Hz, 2 mA) was applied to bilateral HT 7, HT 7-SI 7, and HT 7-BL 15, respectively for 15 min, once per day for a week. The number of BDNF and its receptor TrkB positive cells in the left hippocampus and that of mRNAs in the right hippocampus tissue were determined by immunohistochemistry and real-time fluorescence quantitative PCR, respectively.In comparison with the sham group, the numbers of both BDNF and TrkB positive cells in the left hippocampus and the expression levels of BDNF mRNA and TrkB mRNA in the right hippocampus were increased slightly (P > 0.05). After EA intervention, the numbers of hippocampal BDNF and TrkB positive cells and the expression levels of BDNF mRNA and TrkB mRNA were evidently up-regulated (P < 0.05, P < 0.01), and the effects of HT 7-SI 7 and HT 7-BL 15 were obviously superior to those of simple HT 7 in up-regulating BDNF and TrkB expression (P < 0.01, P < 0.05). No significant differences were found between the HT 7-SI 7 and HT 7-BL 15 groups in increasing the number of hippocampal BDNF and TrkB positive cells and in up-regulating expression of both BDNF mRNA and TrkB mRNA (P > 0.05).EA intervention is effective in increasing the expression of hippocampal BDNF and TrkB in MI rats, which may contribute to its effect in protecting hippocampal cells from injury under MI condition. The effect of EA stimulation of HT 7-SI 7 and HT 7-BL 15 was obviously superior to that of simple HT 7 in up-regulating BDNF and TrkB expression.
Homogeneous core–shell structured cuprous oxide (Cu2O) is fabricated through a facile reduction reaction at room temperature (20–25 °C). Ostwald ripening processes are proposed to explain the growth mechanism of the homogeneous Cu2O core–shell structure. The electrochemical impedance spectrum (EIS), cyclic voltammetry (CV) and differential pulse voltammetry (DPV) show that the modified electrodes with the obtained homogeneous core–shell Cu2O exhibit high efficiency and convenience toward the detection of dopamine (DA). The anodic peak current increases linearly with the concentration of dopamine in the range of 3.0 × 10−7 to 5 × 10−4 M. The detection limit has been estimated to be 1.0 × 10−7 M. The high sensitivity of the determination of dopamine by using the modified electrode implies that homogeneous core–shell Cu2O may be of great potential in the field of biosensors.
In the present study, the protective effect and the potential underlying mechanism of rutaecarpine (Ru) on renal ischemia reperfusion injury (IRI) in rats were investigated. A renal ischemia reperfusion mouse model was established. Ru at 30, 60 mg/kg administered intraperitoneally prior to reperfusion led to attenuated renal injury. The results demonstrated that Ru treatment significantly reduced the content of serum creatinine, urea nitrogen and neutrophil gelatinase‑associated lipocalin in rats with renal IRI. In addition, Ru treatment improved the degree of renal proximal tubular necrosis, decreased the content of inflammatory cytokines in reperfused renal tissue and increased serum superoxide dismutase levels to protect the kidney. The associated underlying mechanism may involve the inhibition of p38 kinase phosphorylation and c‑Jun N‑terminal kinase, anti‑lipid peroxidation, elimination of free radicals, and a reduction in the degree of apoptotic damage and oxidative stress injury induced by renal IRI. Therefore, Ru may be a suitable compound for the prevention and treatment of renal IRI.
Bioactivity-guided fractionation was used to determine the cytotoxic alkaloids from the toxic plant Peganum harmala. Two novel indole alkaloids, together with ten known ones, were isolated and identified. The novel alkaloids were elucidated to be 2-(indol-3-yl)ethyl-α-L-rhamnopyranosyl-(1 → 6)-β-D-glucopyranoside (2) and 3-hydroxy-3-(N-acetyl-2-aminoethyl)-6-methoxyindol-2-one (3). The cytotoxicity against human leukemia cells was assayed for the alkaloids and some of them showed potent activity. Harmalacidine (compound 8, HMC) exhibited the highest cytotoxicity against U-937 cells with IC50 value of 3.1 ± 0.2 μmol/L. The cytotoxic mechanism of HMC was targeting the mitochondrial and protein tyrosine kinase signaling pathways (PTKs-Ras/Raf/ERK). The results strongly demonstrated that the alkaloids from Peganum harmala could be a promising candidate for the therapy of leukemia.
Taurochenodeoxycholic acid (TCDCA) is the principal ingredient of Compound Shougong Powder. Despite traditional Chinese medicine (TCM) research demonstrates that Compound Shougong Powder can restrict tumor growth, whether TCDCA exerts a role in suppressing cancer as the major ingredient of Compound Shougong Powder remains unknown. This study aims to clarify the regulatory mechanism of TCDCA on gastric cancer. Gastric cancer cells SGC-7901 were cultured to investigate the effects of TCDCA on proliferation and apoptosis. Furthermore, a subcutaneously implanted tumor model was established using SGC-7901 cells in BALB/C nude mice and tumor volume was measured under low and high dose treatment of TCDCA. Cell proliferation, apoptosis, and invasion were subjected to 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, flow cytometry, and transwell assay. Differentially expressed genes were screened by transcriptome sequencing. Nude mouse tumorigenicity assay was initiated to identify the effect of TCDCA on both tumor volume and weight, and the expression of candidate genes screened by transcriptome sequencing was determined by real-time fluorescence quantification (qPCR) and Western blot. The experiments revealed that TCDCA could significantly inhibit the proliferation and invasion of gastric cancer cells and induce apoptosis of these cells. Meanwhile, test findings via in vivo indicated that TCDCA severely diminished the volume and weight of tumors. This study first demonstrated that TCDCA inhibited the proliferation and invasion of gastric cancer and induced apoptosis, which is expected to serve as an experimental basis for the application of TCM in tumor therapeutic options. PRACTICAL APPLICATIONS: Through this study, the inhibitory effect of Taurochenodeoxycholic acid on gastric cancer can be clarified, which provides a new research basis for the application of traditional Chinese medicine (TCM) and TCM monomer in cancer. In addition, this study can further promote the research and application of Chinese traditional medicine, which has important application value and economic benefits.
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