Synthesis, anti-leukemia activity, and molecular docking of novel 3,16-androstenedione derivatives.

In this study, we synthesized androsta-4,14-diene-3,16-dione, 12ß-hydroxyandrosta-4,14-diene-3,16-dione, and other 3,16-androstenedione derivatives from commercially available dehydroepiandrosterone as a starting material in 9-13 steps with high yields. The bioactivity of the obtained compounds was evaluated. Compounds 14a and 23a were shown to have high antitumor activity against acute lymphoblastic leukemia cell lines Nalm-6 and BALL-1, respectively. Network pharmacology analysis showed that the anti-leukemia activity of compounds 14a and 23a might be related to the JAK2, ABL1 protein, and PI3K/Akt signaling pathways. The molecular docking of compounds 14a and 23a identified possible active sites, with the lowest docking scores for PTGS2 and MAPK14, respectively. In addition, the absorption, distribution, metabolism, and excretion prediction results revealed the drug-likeness of the two compounds. Therefore, compounds 14a and 23a should be considered anti-leukemia candidates in future studies.

Clinical safety and possible efficacy of tirofiban in combination with intravenous thrombolysis by recombinant tissue plasminogen activator for early treatment of capsular warning syndrome (CWS).

The purpose of this study was to assess the efficacy and safety of the combination of tirofiban with intravenous thrombolysis (IVT) in treating patients with capsular warning syndrome (CWS) who failed to respond to the treatment of intravenous thrombolysis alone. Tirofiban was approved for the treatment of CWS patients with fluctuating symptoms or no substantial improvement after intravenous thrombolysis within 24 h in our hospital from October 2019 to June 2021. Patients were evaluated with the National Institutes of Health Stroke Scale (NIHSS) at admission, at 72 h post-thrombolysis, at 1-week, and at 3-months with the modified Rankin Scales (MRS) score. A total of 12 patients received tirofiban and eight patients received control treatment with a history of CWS in our cohort. Among the patients, 13 patients smoked more than one pack of cigarettes a day, 17 had hypertension, 17 had hypercholesterolemia, 7 had diabetes, 1 had the history of cerebral infarction, 2 had atrial fibrillation, 7 had mild big vascular stenosis, 13 had lesions of the perforating branch by imaging, and 19 had acute capsular infarction. In both the tirofiban and control groups, NIHSS scores were significantly reduced after intravenous thrombolysis or 1-week after onset compared with before intravenous thrombolysis (P < 0.001). Before and after intravenous thrombolysis, there were no differences between the tirofiban group and control group (P = 0.970, P = 0.384, respectively). The tirofiban group, however, showed remarkably lower scores in both 1-week NIHSS and 3-month MRS than the control (P = 0.012, P = 0.003, respectively). Our study revealed that tirofiban did not increase the risk of hemorrhage and had favorable clinical efficacy as a remedial treatment for CWS patients with poor prognosis for intravenous thrombolysis, therefore indicating great potential for broader use.

Clinical Characteristics of 254 COVID-19 Inpatients in Yichang, Hubei, China, and Efficacy of Integrated Chinese and Western Medicine Treatment.

Introduction: There is no effective treatment plan for coronavirus disease 2019 (COVID-19). We employed a combination of Chinese and Western medicine treatment for some COVID-19 inpatients. Methods: This study was a prospective cohort study that observed non-critical COVID-19 inpatients. The differences will be observed in the time from admission to two consecutive 2019-nCoV nucleic acid test negatives and the Visual Analog Scale (VAS) score between the two groups. Results: A total of 254 confirmed COVID-19 patients were included in this study. The median time from the admission to two consecutive negative nucleic acid tests was 14 days for the integrated Chinese and Western Medicine (ICWM) group, while the Western Medicine (WM) group was 16 days. Besides, the median VAS score of the ICWM group was 0, which was an average decrease of 2 points compared to the time of admission. Conclusion: For non-critical COVID-19 patients, it was safe and have more benefits to add traditional Chinese medicine decoction based on WM treatment.

Liuwei Dihuang Pills Enhance the Effect of Western Medicine in Treating Diabetic Nephropathy: A Meta-Analysis of Randomized Controlled Trials.

Objectives. To assess the effectiveness and adverse effects of adding Liuwei Dihuang Pills (LDP) to Western medicine for treating diabetic nephropathy. Methods. Studies were retrieved from seven electronic databases, including PubMed, Embase, The Cochrane Library, CBM, CNKI, Chinese Scientific Journal Database (VIP), and Wanfang Data until November 2015. Study selection, data extraction, quality assessment, and data analyses were conducted according to Cochrane standards. Meta-analysis was performed on the overall therapeutic efficacy of hyperglycemia and renal functions, and the study also analyzed adverse events. Results. A total of 1,275 patients from 18 studies were included. The methodological quality of these included trials was generally low. We found that adding LDP can lower patients' FBG (MD: -0.36 [-0.46, -0.25], P < 0.00001), PBG (MD: -1.10 [-1.35, -0.85], P < 0.00001), and HbA1c (MD: -0.14 [-0.49, 0.21], P = 0.43). There were also improvements in lowering patients' BUN (MD: -0.67 [-0.89, -0.45], P < 0.00001), SCr (MD: -0.96 [-1.53, -0.39], P < 0.00001), 24 h UTP (SMD: -1.26 [-2.38, -0.15], P < 0.00001), UAER (MD: -26.18 [-27.51, -24.85], P < 0.00001), and UmAlb (SMD: -1.72 [-2.67, -0.77], P < 0.00001). Conclusion. There is encouraging evidence that adding LDP to Western medicine might improve treatment outcomes of diabetic nephropathy, including hyperglycemia and renal functions. However, the evidence remains weak. More rigorous high-quality trials are warranted to substantiate or refute the results.