Evaluation of key production processes of Schizonepetae Herba formula granules based on characteristic chromatogram and quantitative transfer relationship / 中国中药杂志

The aim of this paper was to evaluate the key production processes of Schizonepetae Herba formula granules based on the new model of combining characteristic chromatogram with quantitative transfer relationship. The rationality of production process design was evaluated by studying the intermediates in different processes of formula granules, analyzing the loss of index component pulegone in each step, and establishing the characteristic chromatogram. The content of pulegone in 10 batches of standard decoction ranged between 0.067% and 0.124%(70%-130% of the average value), and the transfer rate of pulegone was 44.58%-93.97%. After the improvement of the production process, the content of pulegone in Schizonepetae Herba formula granules was 0.093%, and the transfer rate of pulegone was 68.38%, which was consistent with the parameters range of standard decoction. This study emphasized the integrality of the research process of traditional Chinese medicine(TCM) formula granules, and provided a new idea for the quality control of TCM with content determination as the main evaluation index for a long time.

Effect of lncRNA HULC knockdown on rat secreting pituitary adenoma GH3 cells

Pituitary adenoma is one of the most common tumors in the neuroendocrine system. This study investigated the effects of long non-coding RNAs (lncRNAs) highly up-regulated in liver cancer (HULC) on rat secreting pituitary adenoma GH3 cell viability, migration, invasion, apoptosis, and hormone secretion, as well as the underlying potential mechanisms. Cell transfection and qRT-PCR were used to change and measure the expression levels of HULC, miR-130b, and FOXM1. Cell viability, migration, invasion, and apoptosis were assessed using trypan blue staining assay, MTT assay, two-chamber transwell assay, Guava Nexin assay, and western blotting. The concentrations of prolactin (PRL) and growth hormone (GH) in culture supernatant of GH3 cells were assessed using ELISA. The targeting relationship between miR-130b and FOXM1 was verified using dual luciferase activity. Finally, the expression levels of key factors involved in PI3K/AKT/mTOR and JAK1/STAT3 pathways were evaluated using western blotting. We found that HULC was highly expressed in GH3 cells. Overexpression of HULC promoted GH3 cell viability, migration, invasion, PRL and GH secretion, as well as activated PI3K/AKT/mTOR and JAK1/STAT3 pathways. Knockdown of HULC had opposite effects and induced cell apoptosis. HULC negatively regulated the expression of miR-130b, and miR-130b participated in the effects of HULC on GH3 cells. FOXM1 was a target gene of miR-130b, which was involved in the regulation of GH3 cell viability, migration, invasion, and apoptosis, as well as PI3K/AKT/mTOR and JAK1/STAT3 pathways. In conclusion, HULC tumor-promoting roles in secreting pituitary adenoma might be via down-regulating miR-130b, up-regulating FOXM1, and activating PI3K/AKT/mTOR and JAK1/STAT3 pathways.

Research progress of PD-1/PD-L1 inhibitors in the treatment of acute myeloid leukemia / 中国肿瘤生物治疗杂志

@# 对急性髓细胞性白血病（acute myeloid leukemia，AML）的治疗，在过去的40年除了传统的化疗和异基因造血干细胞 移植外尚未有很大的进展。而近些年来，随着分子生物学、免疫学等学科的不断发展，免疫检查点抑制剂、过继性免疫效应细胞 治疗、肿瘤疫苗等免疫疗法在治疗AML上初现锋芒。程序性死亡受体（programmed death-1, PD-1）和程序性死亡配体（programmed death-1 ligands, PD-L1）抑制剂是一种免疫检查点抑制剂，是目前最受瞩目的研究热点之一，其在治疗AML方面也取得 了一些令人鼓舞的进展。本文综述了PD-1/PD-L1抑制剂治疗AML的机制，其单药应用以及与其他化疗药物或免疫疗法联合应 用的研究进展，并分析了这些治疗方法存在的问题。

The effect of Connexin43 downregulation on biological functions of HUVEC / 药学学报

Connexin43 has been shown to play a pivotal role in wound healing process. Wound repair is enhanced by acute downregulation of connexin43, by increasing proliferation and migration of keratinocyte and fibroblast. Angiogenesis is also a central feature of wound repair, but little is known about the effects of connexin43 modulation on functions of endothelial cells. We used connexin43 specific small interference RNA (siRNA) to reduce the expression of connexin43 in human umbilical vein endothelial cell (HUVEC), and investigated the effects of connexin43 downregulation on intercellular communication, viability, proliferation, migration and angiogenic activity of HUVEC. Treatment of siRNA markedly reduced the expression of connexin43 by -80% in HUVEC (P < 0.05), and decreased the intercellular communication by -65% (P < 0.05). The viability, proliferation, migration and angiogenic activity of HUVEC decreased significantly (P < 0.05), compared with that of the normal cells. The results suggest that temporally downregulation of connexin43 expression at early stage of wound to inhibit the abnormal angiogenesis characterized with leaky and inflamed blood vessels, maybe a prerequisite for coordinated normal healing process.

Targeting angiogenesis and vascular remodeling as a novel therapeutic approach to liver fibrosis / 药学学报

Development of liver fibrosis is closely associated with angiogenesis and abnormal vascular remodeling. Recent studies have highlighted the importance of angiogenesis and vascular remodeling in fibrogenesis, the results that inhibition of angiogenesis is effective in suppression of liver fibrosis demonstrate that therapies with several molecular targets against angiogenesis, inflammation and fibrosis might be beneficial for the treatment of cirrhosis. However, there is some evidence that inhibition of angiogenesis can even worsen fibrosis. This article outlines recent advances regarding the interplay between inflammation, angiogenesis and fibrogenesis in terms of cellular and molecular mechanisms, and suggests a requirement of greater understanding to intervene in these key processes, such as liver sinusoidal endothelial cell fenestration and impact distinct chemokine actions driving monocyte migration and differentiation, for therapeutic benefit in the future.

Multi-mode MRI-based intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) reduces hemorrhagic transformation in ischemic stroke patients / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To compare the safety of intravenous thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) in ischemic patients under the guidance of CT and multi-mode MRI.</p><p><b>METHODS</b>The clinical, laboratory, and radiologic data from 113 consecutive hyperacute ischemic patients who received intravenous rtPA therapy from June 2009 to October 2011 was retrospectively reviewed. The rate of hemorrhagic transformation (HT) and the clinical outcome between CT and multi-mode MRI was compared. Etiological subgroups were classified according to Chinese ischemic stroke subclassification (CISS).</p><p><b>RESULTS</b>Among 113 patients treated with intravenous rtPA, the mean age was 66 ±12 years, 74(65.5%) were man, the pretreatment National Institutes of Health Stroke Scale score (NIHSS) was 12.4 ±6.5, and time from symptom onset to therapy was 259.7 ±131.7 min. Postlytic radiological HT was found in 34 patients (30.1%). Symptomatic ICH occurred in 9 patients (8%). Logistic regression analysis suggested that multi-mode MRI was an independent predictor of reduced risk of HT.</p><p><b>CONCLUSION</b>The risk of hemorrhagic complications is lower in patients receiving intravenous thrombolytic therapy with rtPA guided by multi-mode MRI than those guided by CT scan.</p>