Contemporary Prestroke Dual Antiplatelet Use and Symptomatic Intracerebral Hemorrhage Risk After Thrombolysis.

Importance: Intravenous alteplase (IV-tPA) can be administered to patients with acute ischemic stroke but is associated with symptomatic intracerebral hemorrhage (sICH). It is unclear if patients taking prestroke dual antiplatelet therapy (DAPT) are at higher risk of sICH. Objective: To determine the associated risk of sICH in patients taking prestroke dual antiplatelet therapy receiving alteplase for acute ischemic stroke using propensity score matching analysis. Design, Setting, and Participants: This cohort study used data from the American Heart Association and American Stroke Association Get With The Guidelines-Stroke (GWTG-Stroke) registry between 2013 and 2021. Data were obtained from hospitals in the GWTG-Stroke registry. This study included patients hospitalized with acute ischemic stroke and treated with IV-tPA. Data were analyzed from January 2013 to December 2021. Exposures: Prestroke DAPT before treatment with IV-tPA for acute ischemic stroke. Main Outcome Measures: sICH, In-hospital death, discharge modified Rankin scale score, and other life-threatening systemic hemorrhages. Results: Of 409 673 participants, 321 819 patients (mean [SD] age, 68.6 [15.1] years; 164 587 female [51.1%]) who were hospitalized with acute ischemic stroke and treated with IV-tPA were included in the analysis. The rate of sICH was 2.9% (5200 of 182 344), 3.8% (4457 of 117 670), and 4.1% (893 of 21 805) among patients treated with no antiplatelet therapy, single antiplatelet therapy (SAPT), and DAPT, respectively (P < .001). In adjusted analyses after propensity score subclassification, both SAPT (odds ratio [OR], 1.13; 95% CI, 1.07-1.19) and DAPT (OR, 1.28; 95% CI, 1.14-1.42) were associated with increased risks of sICH. Prestroke antiplatelet medications were associated with lower odds of discharge mRS score of 2 or less compared with no medication (SAPT OR, 0.92; 95% CI, 0.90-0.95; DAPT OR, 0.94; 95% CI, 0.88-0.98). Results of a subgroup analysis of patients taking DAPT exposed to aspirin-clopidogrel vs aspirin-ticagrelor combination therapy were not significant (OR, 1.35; 95% CI, 0.84-1.86). Conclusions and Relevance: Prestroke DAPT was associated with a significantly elevated risk of sICH among patients with ischemic stroke who were treated with thrombolysis; however, the absolute increase in risk was small. Patients exposed to antiplatelet medications did not have excess sICH compared with landmark trials, which demonstrated overall clinical benefit of thrombolysis therapy for acute ischemic stroke.

In Vivo Pharmacokinetic Study of Polygonatum cyrtonema Polysaccharide DPC1 after Oral and Intraperitoneal Administration.

(1) Background: Polygonatum cyrtonema is a medicinal plant, and its polysaccharides are used for immunomodulation and the treatment of hyperglycemia. Investigation of the tissue distribution and pharmacokinetics of P. cyrtonema polysaccharide can further elucidate its pharmacological mechanisms. (2) Methods: A fluorescence-labeling approach using rhodamine B (RhB) as a fluorescent molecular probe was used for the quantitative assessment of the polysaccharide from dried P. cyrtonema (DPC1) samples, and the pharmacokinetics and tissue distribution of DPC1 were evaluated in mice after intraperitoneal or oral administration. (3) Results: DPC1 was successfully labeled with RhB, showing degrees of fluorescence labeling at 0.453% and 0.568% as determined by the ultraviolet and enzyme marker methods, respectively. DPC1-RhB was rapidly absorbed into the bloodstream after oral and intraperitoneal administration. Pharmacokinetic characteristics showed that oral administration and intraperitoneal administration were consistent with the features of a two-compartment model. (4) Conclusion: After administration, DPC1-RhB was primarily distributed in the tissues of the heart, spleen, and lung, indicating that the drug has a targeted effect on these tissues. Overall, the findings provide a comprehensive reference for the in vivo distribution of DPC1, together with a foundation for further elucidation of its pharmacological mechanisms and the development and application of DPC1 formulations.

Curative effect analysis of PVP combined with Zoledronic acid in the treatment of postmenopausal osteoporotic vertebral fracture (with video) / 中华内分泌外科杂志

Objective:To explore the efficacy of PVP combined with zoledronic acid in the treatment of postmenopausal osteoporotic vertebral fractures.Method:90 patients with postmenopausal osteoporotic vertebral fractures treated in our hospital from Jul. 2018 to Aug. 2020 were selected. According to different treatment methods, the patients were divided into observation group and control group. The patients in both groups were treated with PVP. The patients in the control group were given oral alendronate, calcitriol capsules and calcium, and the patients in the observation group were given zoledronic acid injection, calcitriol capsules and calcium were taken orally for 1 year. BMD of lumbar spine, femoral neck, greater trochanter and ward triangle, lumbar ODI index and VAS score, serum BGP and β-CTX, PINP levels and adverse reactions during treatment. Results:One year after operation, the lumbar ODI index and VAS score of the observation group were significantly lower than those of the control group ( P<0.05), and the BMD of lumbar spine, femoral neck, greater trochanter and ward triangle were higher than those of the control group ( P<0.05). The levels of serum BGP, β-CTX and PINP levels in the two groups were significantly higher than those in the control group ( P<0.05) . Conclusion:Zoledronic acid can significantly improve bone metabolism, accelerate bone formation, increase BMD, reduce low back pain and improve lumbar function in patients with osteoporotic vertebral compression fracture after PVP.

Transcriptional profiling of uterine leiomyoma rats treated by a traditional herb pair, Curcumae rhizoma and Sparganii rhizoma

The aim of this study was to elucidate the concise effects of a traditional herb pair, Curcumae rhizoma-Sparganii rhizoma (CRSR), on uterine leiomyoma (UL) by analyzing transcriptional profiling. The UL rat model was made by intramuscular injection of progesterone and gavage administration of diethylstilbestrol. From 11 weeks of the establishment of the model, rats of the UL+CRSR group were gavaged daily with CRSR (6.67 g/kg). The serum concentrations of progesterone (P) and estradiol (E2) were determined by radioimmunoassay, the uterine index was measured by caliper measurement, and the pathological status was observed by hematoxylin and eosin stain. Gene expression profiling was checked by NimbleGen Rat Gene Expression Microarrays. The results indicated that the uterine mass of UL+CRSR rats was significantly shrunk and serum P and E2 levels significantly reduced compared to UL animals and nearly to the level of normal rats. Results of microarrays displayed the extensive inhibition of CRSR upon the expression of proliferation and deposition of extracellular matrix (ECM)-related genes, and significantly regulated a wide range of metabolism disorders. Furthermore, CRSR extensively regulated key pathways of the UL process, such as MAPK, PPAR, Notch, and TGF-β/Smad. Regulation of the crucial pathways for the UL process and ECM metabolism may be the underlying mechanisms of CRSR treatment. Further studies will provide clear clues for effectively treating UL with CRSR.

AATYK is a Novel Regulator of Oligodendrocyte Differentiation and Myelination / 神经科学通报·英文版

Oligodendrocytes (OLs) are myelinating glial cells that form myelin sheaths around axons to ensure rapid and focal conduction of action potentials. Here, we found that an axonal outgrowth regulatory molecule, AATYK (apoptosis-associated tyrosine kinase), was up-regulated with OL differentiation and remyelination. We therefore studied its role in OL differentiation. The results showed that AATYK knockdown inhibited OL differentiation and the expression of myelin genes in vitro. Moreover, AATYK-deficiency maintained the proliferation status of OLs but did not affect their survival. Thus, AATYK is essential for the differentiation of OLs.

Molecular imaging of epidermal growth factor receptor in glioma-bearing rats / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the value of 11C-PD153035 as an EGFR imaging agent in C6 tumor-bearing rat.</p><p><b>METHODS</b>The tumor-bearing rats were generated by subcutaneous injection of glioma C6 cells. Positron emission tomography/computer tomography (PET/CT) scans started as soon as intravenous injection of 11C-PD153035 (15-20 MBq/0.3 ml) was completed, images were collected continuously. The region of interest (ROI) was used to study the percentage of radioactivity in major organs and implanted tumors in the rats. The accumulation and blocking study in vitro was completed.</p><p><b>RESULTS</b>There were significant differences in 11C-PD153035 uptake among major organs. The maximum uptake in the organs ranked in the following order: liver > gastrointestinal tract > kidney > lung > brain > muscle. Radioactivity could be also observed in the tumors. The radioactivity ratio (T/NT, target/non-target) peaked (4.15) at 40 - 50 min post injection. The in vitro blocking study showed that 11C-PD153035 uptaken by C6 cells could be blocked by PD153035.</p><p><b>CONCLUSION</b>The results of this study show that 11C-PD153035 can be uptaken by EGFR-expressing tumors. 11C-PD153035 has a potential as a bioprobe to yield useful information for both diagnosis and therapy of tumors. However, the high concentration of 11C-PD153035 in the gastrointestinal tract is unfavorably affecting the tumor detection in these organs.</p>