In recent years, gastrointestinal stromal tumors (GIST) have increased incidence and mortality, and most GIST is caused by the activation mutation of the c-KIT gene. Therefore, c-KIT has become a promising therapeutic target of GIST. At present, the drugs approved for the treatment of GIST including imatinib, sunitinib, regorafenib and ripretinib, are mostly prone to developing resistance and accompanied by various degrees of adverse reactions. Therefore, there is an urgent need to develop new c-KIT inhibitors to solve the problem of resistance. In this study, we investigated the anti-tumor effect of a novel c-KIT inhibitor PN17-1 on gastrointestinal stromal tumor GIST-882 cells in vitro. We found that PN17-1 significantly inhibited the proliferation, colony formation and migration ability of GIST-882 cells, and significantly downregulated the protein expression levels of p-c-KIT and its downstream signals p-AKT, p-STAT5 and p-ERK in GIST-882 cells. In addition, PN17-1 induced apoptosis in GIST-882 cells, and the apoptosis may be mainly related to the mitochondrial-dependent endogenous pathway. In conclusion, the novel c-KIT inhibitor PN17-1 is a promising anti-GIST drug, and this study provides new ideas for further development of c-KIT inhibitors in the future.

Improving the reproducibility of biomedical research results is a major challenge. Transparent and accurate reporting of the research process enables readers to evaluate the reliability of the research results and further explore the experiment by repeating it or building upon its findings. The ARRIVE 2.0 guidelines, released in 2019 by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), provide a checklist that is applicable to any in vivo animal research report. These guidelines aim to improve the standardization of experimental design, implementation, and reporting, as well as enhance the reliability, repeatability, and clinical translation of animal experimental results. The use of the ARRIVE 2.0 guidelines not only enriches the details of animal experimental research reports, ensuring that information on animal experimental results is fully evaluated and utilized, but also enables readers to understand the content expressed by the author accurately and clearly, promoting the transparency and completeness of the fundamental research review process. At present, the ARRIVE 2.0 guidelines have been widely adopted by international biomedical journals. This article is based on the best practices following the ARRIVE 2.0 guidelines in international journals, and it interprets, explains, and elaborates in Chinese the fifth part of the comprehensive version of the ARRIVE 2.0 guidelines published in PLoS Biology in 2020 (the original text can be found at https://arriveguidelines.org). This section includes the items 6-11 of Recommended 11 section, covering "Animal Care and Monitoring", "Interpretation/Scientific Implications", "Generalisability/Translation", "Protocol Registration", "Data Access" and "Declaration of Interests". Its aim is to promote a comprehensive understanding and use of the ARRIVE 2.0 guidelines among domestic researchers, to enhance the standardization of experimental animal research and reporting, and to promote high-quality development of experimental animal sciences and comparative medicine research in China.

Compared with conventional radiotherapy fields, small field has unique dosimetry characteristics such as high dose gradient, charged particle imbalance, and dose effect caused by source occlusion. These characteristics increase the difficulty of dose measurement and thus the uncertainty of clinical dose measurement, far exceeding the requirement of < 5% measurement error in ICRU 24 report. In recent years, with the development of new radiotherapy technologies, the minimum radiotherapy field can reach the millimeter level, and the single irradiation dose of hypofractionated radiotherapy can exceed 6 Gy. The larger dose gradient at the edge of radiotherapy field requires higher accuracy of dose measurement, and accurate small field dosimetry technologies have gradually become a research hotspot in the field of precision radiotherapy. In order to ensure the high accuracy of measurement, this paper reviews the research on small field dosimetry worldwide, and summarizes the key points of small field dosimetry. In this paper, the characteristics of small field dosimetry are introduced, and the current small field dosimetry technologies and optimization methods are summarized, including the optimization of detector selection and detector sensitive volume. The field output correction factor technologies are analyzed. In view of the difficulty in small field dosimetry, this paper provides suggestions on dosimetry based on clinical needs and the characteristics of medical linear accelerators. Our suggestions provide a scientific reference for small field dosimetry in clinical practice in radiotherapy institutions, and facilitate the development of radiotherapy dose verification.

Objective To investigate the clinical effect of metal supported multi-sided versus ordinary ultra-fine drainage tube in the uniportal video-assisted thoracic surgery (VATS) lower pulmonary lobectomy. Methods From January 2021 to June 2022, the clinical data of patients who underwent uniportal VATS lower lobectomy in our hospital were retrospectively analyzed. According to the different types of ultra-fine drainage tubes used in the surgery, the patients were divided into an experimental group (using multi-sided hole 10F ultra-fine drainage tubes with metal support) and a control group (using ordinary 12F ultra-fine drainage tubes). The clinical data of the two groups were compared. Results A total of 190 patients were enrolled, including 108 males and 82 females. There were 90 patients in the experimental group aged 56.60±10.14 years; and 100 patients in the control group aged 57.07±11.04 years. The incidences of postoperative lung infection and pleural effusion in the experimental group were lower than those in the control group, with statistically significant differences (P<0.05). The postoperative visual analogue scale score, the need to adjust the chest drainage tube after the surgery, the need for chest puncture after the surgery, the time of postoperative chest tube removal, and the hospitalization cost were statistically different (P<0.05). There was no statistical difference in the length of postoperative hospital stay or the incidences of postoperative lung leakage, arrhythmia, and atelectasis complications (P>0.05). Conclusion Compared with the ordinary ultra-fine drainage tubes, multi-sided hole ultra-fine drainage tubes with metal support can reduce the incidences of lung infection and pleural effusion complications after the uniportal VATS lower lobectomy, reduce the pain and economic burden, which can be applied in the uniportal VATS lower lobectomy.

Seven triterpenoids were isolated and purified from the 95% aqueous EtOH extract whole plants of P. villosa by various chromatographic techniques, such as silica gel, ODS, Sephadex LH-20 gel column chromatography and preparative high performance liquid chromatography. Based on physicochemical properties and spectral analyses, the structures of the seven compounds were identified as 29-acetoxyoleanolic acid-3-O-α-L-arabinopyranoside (1), oleanolic acid (2), 3β-hydroxy-24-norursa-4(23),12,20(30)-trien-28-oic acid (3), 3β-hydroxy-24-nor-urs-4(23),12-dien-28-oic acid (4), ursolic acid (5), hederagenin (6), oleanolic acid 3-O-arabinoside (7). Compound 1 is a new compound. Compounds 3, 4, 6, and 7 are isolated from P. villosa for the first time. All compounds were assayed for their anti-inflammatory activity by the prodution of NO in lipopolysaccharide-stimulated RAW 264.7 cells. The results showed that compounds 1, 2, 3, 4, 6, and 7 significantly inhibited the NO release.

The traditional commodity specifications of Chinese medicinal materials are mainly divided into different grades based on macroscopic characteristics. As the basis for high quality and good price, there is still a lack of systematic evaluation on whether they are consistent with the current standards and whether they can reflect the internal quality of medicinal material. Panax notoginseng is a commonly used, large consumption of Chinese medicinal material. At present, it is divided into 8 grades in the market based on "Tou" (the number of crude drug /500 g), but it is not related to the standard of total saponins of Panax notoginseng (the sum of three saponins) in Chinese Pharmacopoeia. In this study, ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) coupled with mass spectrometry molecular network were used for the rapid identification of saponins of Panax notoginseng with different "Tou" and a total of 64 saponins were identified. Seventeen saponins related to "Tou" were screened by orthogonal partial least squares discriminant analysis (OPLS-DA). The content of five saponins R₁, Rb₁, Rg₁, Rd, and Re in Panax notoginseng with different "Tou" was determined by high performance liquid chromatography (HPLC). The results of correlation analysis showed that Rd and R₁ with the largest VIP values among the differential saponins, which significantly negatively correlated with "Tou" (P < 0.05). Based on the determination results of 36 batches of samples, using Rd/Total Panax notoginseng saponins (TPNS) ratio ( > 0.08) as the index, Panax notoginseng can be divided into two grades: 20-60 "Tou" (superior) and 80-200 "Tou" (qualified). Based on the concept of "macroscopic characteristics and chemical profiling", this study integrates the non-targeted analysis and quantitative determination methods to provide a new strategy for quality evaluation of Panax notoginseng.

In order to study the compounds from Glechoma longituba (Nakai) Kupr. and explore the substance bases of its dissipating blood stasis, MCI, silica gel, Sephadex LH-20, ODS column chromatography and preparative thin layer chromatography were used to isolate and purify the compounds. The structures were identified by MS, 1D NMR, and 2D NMR spectra analysis, etc. Eight triterpenoids were isolated from dichloromethane fraction of ethanol extract from G. longituba and identified as 2α,3α,16β-trihydroxy-13α,27-cyclours-11-en-28-oic acid (1), 28-norurs-12-ene-3β,17β-diol (2), 28-norolean-12-ene-3β,17β-diol (3), oleanonic acid (4), 3β,13β-dihydroxyurs-11-en-28-oic acid (5), uvaol (6), oleanolic acid (7), ursolic acid (8). Compound 1 is a new hexacyclic triterpene with 13α,27-cyclopropane structure, named euscaphic acid H; compounds 2 and 3 were isolated from Lamiaceae for the first time while compounds 4 and 5 were isolated from this genus. The in vitro anticoagulant activity of triterpenoids was evaluated by four coagulation indexes (activated partial thromboplastin time, APTT; thrombin time, TT; prothrombin time, PT; fibrinogen, FIB). Among them, compounds 1 and 6 showed obvious anticoagulant effects.

INTRODUCTION

Aspiration is a major risk factor for the development of pneumonia. Critically ill patients are at higher risk due to several factors. Many physicians routinely hold feeding prior to extubation due to usual practice, but evidence is scarce that continuing feeding increases the risk of aspiration. This study was designed to determine whether continuing enteral feeding prior to a scheduled extubation is associated with a higher risk of aspiration.

This is a prospective, cohort study done in the critical units of Chong Hua Hospital. All intubated patients, (18 years and above) started on enteral feeding via nasogastric tube for at least 24 hours prior to planned extubation, were included. Patients were grouped into either Continuous or Withold Group (feeding withheld for at least 3 hours before and 2 hours after extubation). The following events were observed: aspiration of gastric contents during and after extubation, vomiting within 2 hours after extubation, and reintubation within 24 hours from extubation. In the event of reintubation, vomiting and aspiration of gastric content during the process of reintubation was documented.

Seventy patients were included in the study. There was no documented aspiration in both groups. In the Withhold group, feeding was withheld with a mean average of 7.11 + 2.35 hours and the amount of calories withheld ranged from as low as 166 calories to as high as 800 calories (320 + 144.28).

Continuing nasogastric feeding during the peri-extubation period does not increase the risk of aspiration and allows for delivery of optimal nutrition to critically ill patient.

[摘 要] 目的：探讨解偶联蛋白2（UCP2）抑制剂京尼平（GEN）对人下咽癌FaDu细胞增殖及线粒体功能的影响。方法：使用不同浓度的GEN作用于FaDu细胞24 h，实验分为GEN 0（对照）、50、100、200和400 μmol/L组。采用CCK-8法检测各组细胞增殖能力，DCFH-DA探针及JC-1染色联合流式细胞术检测GEN对FaDu细胞活性氧（ROS）含量及线粒体膜电位的影响，激光共聚焦显微镜观察GEN对FaDu细胞线粒体膜通透性转换孔的影响，可见分光光度法检测细胞中乳酸的含量，WB法检测细胞中UCP2蛋白的表达变化。结果：与对照组相比，GEN可显著抑制FaDu细胞的增殖活力（P<0.05或P<0.01）、细胞中UCP2蛋白的表达（P<0.05），降低线粒体膜电位（P<0.05或P<0.01）、乳酸含量（P<0.000 1），改变细胞线粒体膜孔道通透性，提高细胞中ROS水平（P<0.05或P<0.01）。结论：GEN通过调节细胞中UCP2的表达水平进而影响细胞的氧化还原能力及线粒体功能，从而发挥抑制人下咽癌FaDu细胞增殖并诱导细胞凋亡的作用。

Breast cancer is the most common cancer in women and one of the deadliest cancers worldwide.According to the distribution of tumor tissue,breast cancer can be divided into invasive and non-invasive forms.The cancer cells in invasive breast cancer pass through the breast and through the immune system or systemic circulation to different parts of the body,forming metastatic breast cancer.Drug resistance and distant metastasis are the main causes of death from breast cancer.Research on breast cancer has attracted extensive attention from researchers.In vitro construction of tumor models by tissue engineering methods is a common tool for studying cancer mechanisms and anticancer drug screening.The tumor microenvironment consists of cancer cells and various types of stromal cells,including fibroblasts,endothelial cells,mesenchymal cells,and immune cells embedded in the extracellular matrix.The extracellular matrix contains fibrin proteins(such as types Ⅰ,Ⅱ,Ⅲ,Ⅳ,Ⅵ,and Ⅹcollagen and elastin)and glycoproteins(such as proteoglycan,laminin,and fibronectin),which are involved in cell signaling and binding of growth factors.The current traditional two-dimensional(2D)tumor models are limited by the growth environment and often cannot accurately reproduce the heterogeneity and complexity of tumor tissues in vivo.Therefore,in recent years,research on three-dimensional(3D)tumor models has gradually increased,especially 3D bioprinting models with high precision and repeatability.Compared with a 2D model,the 3D environment can better simulate the complex extracellular matrix components and structures in the tumor microenvironment.Three-dimensional models are often used as a bridge between 2D cellular level experiments and animal experiments.Acellular matrix,gelatin,sodium alginate,and other natural materials are widely used in the construction of tumor models because of their excellent biocompatibility and non-immune rejection.Here,we review various natural scaffold materials and construction methods involved in 3D tissue-engineered tumor models,as a reference for research in the field of breast cancer.