BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

Artificial blood is a type of liquid preparation with oxygen-loading capacity and can temporarily substitute some function of blood.The developed artificial blood can be divided into four categories:artificial synthetic hemo-globin,artificial red blood cells made from natural hemoglobin,perfluorocarbons,and stem cell-differentiated red blood cells.This review focuses on the domestic and foreign research progress of artificial blood in recent years,and discusses its clinical application value,development trend,and future research,in order to provide new ideas to the development the artificial blood products and promote clinical application.

Background and objective Lung cancer is the most common type of cancer,accounting for more than half of all cancer cases,with lung adenocarcinoma(LUAD)representing over half of lung cancer patients.Currently,the 5-year survival rate for metastatic LUAD patients remains low and there is an urgent need for new biomarkers as targets for targeted therapy.Go-Ichi-Ni-San 1(GINS1),an important member of the GINS family,is closely related to the occurrence and devel-opment of human malignant tumors.This study aims to explore the role of GINS1 in glycolysis,proliferation,and metastasis of LUAD cells and the related molecular mechanisms.Methods The expression of GINS1 was analysed using bioinformatics between LUAD patients and healthy controls.The expression levels of GINS1 in LUAD and adjacent tissues were detected by immunohistochemistry and Western blot.Western blot and real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)were used to detect the expression of GINS1 in LUAD cell lines A549,SK-LU-1,Calu-3,H1299 and BEAS-2B.Stably knockdown GINS1 in A549 cells and its negative control cell line,as well as stably overexpress GINS1 in H1299 cells and its negative control cell line,were constructed by lentiviral transduction.Colony formation test was used to detect cell proliferation.Scratch test was used to detect cell migration.Transwell test was used to detect cell invasion,and the test kits were used to detect glucose consumption and lactate production.The expression levels of glycolysis-related proteins,Notch signaling pathway proteins and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)signaling pathway proteins were detected by Western blot.The Notch receptor agonist Jagged1 was added to cells from the shGINS1-A549 group and the Notch receptor inhibitor LY3039478 was added to cells from the GINS1-OE-H1299 group for the regression assay.Results The expression of GINS1 was up-regulated in LUAD patients,tissues and cell lines,and corre-lated with overall survival(P＜0.05).Knockdown of GINS1 significantly inhibited the proliferation,migration and invasion of A549 cells(P＜0.05),while overexpression of GINS1 significantly enhanced the proliferation,migration and invasion of H1299 cells(P＜0.05).Furthermore,knockdown of GINS1 resulted in reduced glucose consumption,reduced lactate production,and reduced expression levels of glycolytic-related proteins in A549 cells(P＜0.05);overexpression of GINS1 enhanced glycolytic level in H1299 cells(P＜0.05).The expression levels of Notch1,Notch3,phosphorylated-PI3K(p-PI3K),phosphorylated-AKT(p-AKT)and phosphorylated-mTORC1(Ser2448)[p-mTORC1(Ser2448)]in A549 cells were significantly decreased by GINS1 knockdown(P＜0.05),while the expression levels of P13K,AKT,mTOR and p-mTORC2(Ser2481)were not significantly changed(P＞0.05).Overexpression of GINS1 increased the levels of Notch1,Notch3 and PI3K/AKT/mTORC1 pathway phosphorylated proteins in H1299 cells(P＜0.05).Jagged1 significantly reversed the inhibition of glycolysis,prolif-eration and metastasis induced by GINS1 knockdown in A549 cells(P＜0.05),and LY3039478 significantly inhibited the en-hancement of glycolysis,proliferation and metastasis induced by GINS1 overexpression in H1299 cells(P＜0.05).Conclusion The expression of GINS1 enhances the expression of Notch1 and Notch3 receptors,and then phosphorylates and activates the downstream PI3K/AKT/mTORC1 signaling pathway to enhance the glycolysis,proliferation and metastasis of LUAD cells.

Objective To evaluate the role of clinical pharmacists on the pharmacological monitoring and management of diabetic patients. Methods 406 adult outpatients with diabetes in outpatient were selected as research object. The patients were given the questionnaire and intervened with diabetes education and management by the clinical pharmacist regularly. The patient’s knowledge of the diabetes medication before and after intervention, blood glucose and glycosylated hemoglobin values, treatment compliance, non-reserved outpatient visit, emergency, hospitalization, etc. were compared and statistically analyzed. Results After pharmacy intervention, the patients' knowledge of diabetes and drug-related information, treatment compliance, blood glucose and glycosylated hemoglobin were better than before intervention, P<0.01. Non-reserved outpatient visits and emergency cases were better than before intervention, P<0.05. There are significant differences. Conclusion Clinical pharmacists carry out diabetes chronic disease management and build a clinical pharmacist-led chronic disease management model, which helps to promote standardized treatment, improve patient compliance, promote rationalized medication, achieve the goal of controlling blood sugar and reduce complications.

Objective To investigate the effect of 1α, 25-dihydroxyvitamin D3 [1α,25-(OH)2 D3] on tumor necrosis factor-α ( TNF-α) induced activation of human umbilical vein endothelial cells ( HUVECs ) . The mechanism involved in this process was also studied. Methods HUVECs were cultured and treated with TNF-α( 40 ng/ml), 1α,25-(OH)2D3(10-8 mol/L), and SN50 as indicated. Vascular cell adhesion molecule (VCAM) and E-selectin were used as markers of endothelial activation, which were detected by Western blotting and realtime PCR (RT-PCR). NF-κB signaling pathway was investigated to study the mechanism. Western blotting, RT-PCR, immunofluorescence assay, and chromatin immunoprecipitation ( ChIP ) method were used to evaluate the effects of 1α,25-( OH) 2 D3 on its early activation, nuclear transport, and binding to VCAM and E-selectin promoters. Results (1) Western blotting and RT-PCR showed that TNF-α could significantly up-regulate the expression of VCAM and E-selectin in HUVECs, which can be inhibited by specific NF-κB blocker SN50. 1α,25-( OH) 2 D3 down-regulated the expression of VCAM and E-selectin induced by TNF-α. ( 2 ) Western blotting showed that TNF-α induces I-κBαphosphorylation, thereby activating NF-κB p65 subunit. Immunofluorescence showed that 1α, 25-( OH ) 2 D3 significantly inhibited the nuclear translocation of NF-κB p65 subunit. ChIP analysis revealed that 1α,25-( OH) 2 D3 inhibited the binding of NF-κB p65 to VCAM and E-selectin promoters and thus affected gene expression. Conclusions TNF-αenhanced the expression of E-selectin and VCAM in HUVECs via NF-κB signaling pathway. 1α,25-( OH) 2 D3 may inhibit NF-κB early activation, nuclear transport and the binding of NF-κB p65 to VCAM and E-selectin promoters, thereby inhibiting TNF-α-induced endothelial cell activation.

Objective To investigate the application value of procalcitonin(PCT) in fever of the patients with malignant tumor.Methods A total of 254 patients with malignant tumor complicating fever from January to October 2016 were collected and grouped after clearly diagnosing the causes of body temperature increase according to the clinical manifestations,laboratory examination and imaging examination results.The difference of PCT level was compared among various groups.Results Compared with tumor thermal group,the PCT level in the sepsis and non-sepsis groups was significantly increased(P<0.001).Moreover no matter which was bacterial infection,fungal infection or both mixed infection,the PCT level was significantly higher than that in the tumor thermal group;compared with the fungal infection group,the PCT level in the bacterial infection group was increased significantly(P<0.01).The PCT level distribution difference among the tumor thermal group,fungal infection group and bacterial infection group was statistically significant(P<0.01).The critical values of PCT for diagnosing fungal and bacterial infectious fever were 0.575,0.945 ng/mL respectively.The areas under ROC curve were 0.812(95%CI:0.805-0.934);0.951(95%CI:0.917-0.985).Conclusion It is priliminarily considered that PCT can serve as an effective clinical auxiliary diagnostic indicator for differentiating the fever cause in the patients with malignant tumor.