Advances in immunotherapy for neuroendocrine neoplasms / 中华胃肠外科杂志

Neuroendocrine neoplasms (NEN) is a rare and heterogeneous tumor. Different pathologic morphology, differentiation, grade and clinical stages of the tumors had various treatment and prognosis. Patients with recurrent or metastatic NEN have limited treatment options and poor prognosis. In recent years, PD-1 pathway blockade has become integral components of disease management for many cancers. Immunotherapy is being explored in NEN. Studies have shown that the efficacy of immune monotherapy in NEN is limited, and it can be considered for selected patients. Biomarkers for predicting efficacy of immunotherapy include PD-L1 expression, TMB-H, MSI-H/dMMR, etc. Combined regimens of anti-CTLA-4 and anti-PD-1/PD-L1 inhibitors, and immune checkpoint inhibitor combined with anti-angiogenic drugs or chemotherapy are promising in patients with NEN, and it is worthwhile to further explore of the responding populations.

Two new phenolic glycosides isolated from Ginkgo seeds / 中国天然药物

Two new phenolic glycosides, 7S, 8R-urolignoside-9'-O-β-D-glucoside (1) and scrophenoside G (2), were isolated and identified from the seeds of Ginkgo biloba L., a famous traditional medicine and functional food around the world. Their structures were elucidated by spectroscopic methods (1D and 2D NMR, HR-ESI-MS, and CD), and the comparisons of spectroscopic data with the reported values in the literature.

Two new phenolic glycosides isolated from Ginkgo seeds / 中国天然药物

Two new phenolic glycosides, 7S, 8R-urolignoside-9'-O-β-D-glucoside (1) and scrophenoside G (2), were isolated and identified from the seeds of Ginkgo biloba L., a famous traditional medicine and functional food around the world. Their structures were elucidated by spectroscopic methods (1D and 2D NMR, HR-ESI-MS, and CD), and the comparisons of spectroscopic data with the reported values in the literature.

In vitro anti-oxidant and hypoglycemic activity of acetonitrile-water extract of Origanum vulgare leaves harvested in different times / 中草药

Objective: By investigating the material composition, anti-oxidant and hypoglycemic activity of acetonitrile-water extracts of Origanum vulgare leaf (OL) in different harvest time, to acquire the scientific data for the utilization of OL. Methods: OL was extracted with acetonitrile and water (1: 1). The contents of total phenols and total flavonoid were measured by Foline-Phenol reagent method and AlCl3 colorimetry. The main compositional analysis was performed using LC-QTOF-MS technology. Meanwhile, the anti-oxidation of OL extracts in different harvest time was evaluated by total anti-oxidant capacity assay kit with ABTS method and ferric reducing anti-oxidant potential assay (FRAP). The methods of 2-NBDG glucose uptake and α-glycosides inhibition were applied to evaluate hypoglycemic activity of OL extracts. Results: The six main components in OL extract were identified to be origanoside I, luteolin 7-O-glucuronide, apigenin 7-O-glucuronide, rosmarinic acid, lithospermic acid and origanoside I derivative. The contents of total phenols and the total flavonoids were the highest in OL extracts harvested in July and September, respectively. There was good in vitro anti-oxidant and hypoglycemic activity for OL extracts harvested in different times. Among them, the best anti-oxidant activity was observed in OL extracts harvested in July, while the best hypoglycemic activity was observed in OL extracts harvested in October. Conclusion: OL has potential anti-oxidant and hypoglycemic activity, which is affected by the harvest time.

Effects of bevacizumab on morphology and apoptosis of human retinal pigment epithelial cells as well as the expression of apoptosis-related factors / 眼科新进展

Objective To investigate the effects of bevacizumab on cell morphology,apoptosis rate and apoptosis-related factors in human retinal pigment epitheliumcells.Methods Human retinal pigment epithelial cells (ARPE-19) were cultured in DMEM/F1 2 medium containing 0.25 g · L-1 bevacizumab and divided into 1-week dosing group and 2-week dosing group according to the different incubation time,respectively.Meanwhile,the control group was set up.Then,the cell morphology and apoptosis of each group were observed by light microscope and flow cytometry,accordingly.The expression levels of apoptosis-promoting genes P53,TP53INP1,Bax and apoptosisinducible gene Bcl-2 mRNA and protein were detected by RT-PCR and Western blot,respectively.Results Light microscopic observation revealed that the cells in the 1-week control group and the 2-week control group showed typical epithelial cell morphology,and were in stone-like,single-layer adherent-like growth.Compared with the control group,part of the cell morphology after bevacizumab treatment changed slightly,and the cells became rounded,the cell body was elongated and the boundary was poor.The apoptotic rates of the 1-week control group,l-week dosing group,2-weekcontrol group and 2-week dosing group were (5.57 ± 1.46) ％,(6.39 ± 1.25) ％,(6.88 ± 1.10)％ and (13.34 ± 1.94)％,respectively,and there was no significant difference in the apoptotic rate between 1-week control group,1-week dosing group and 2-week control group (both P ＞ 0.05),but the apoptotic rate of the 2-week dosing group was significantly higher than that of the 2-week control group,the 1-week dosing group and 1-week control group,and the differences were statistically significant (all P ＜0.01).RT-PCR and Western blot results showed that compared with the 1-week control group,the expression of P53,TP53INP1 and Bax mRNA was up-regulated in 1-week dosing group,but the expression of Bcl-2 mRNA was down-regulated,and the differences were statistically significant (all P ＜ 0.05).The expression levels of P53,TP53INP1 and Bax mRNA in 2-week dosing group were higher than those in 2-week control group and 1-week dosing group,while Bcl-2 mRNA expression was down-regulated,and the differences were statistically significant (all P ＜ 0.05).There was no significant difference in the expression of the above factors in 1-week control group and 2-week control group(all P ＞ 0.05).The protein expressions of above factors were similar to their mRNA expression.Conclusion Bevacizumab can alter the morphology of ARPE-19 ceils,increase the apoptotic rate and up-regulate the expression of apoptosis-promoting factors,but down-regulate the expression of apoptosis-suppression factors in ARPE-19 cells,which may be the reason for the loss of RPE layer in the macula after anti-VEGF therapy.

Characteristics of autophagy and its effect on cell proliferation in giant cell tumor of bone / 临床与实验病理学杂志

Purpose To investigate the autophagy characteristics of giant cell tumor of bone and its effect on cell proliferation. Methods Giant cell tumors of bone (GCT-0404 cells) were cultured in vitro and treated with serum-starvation, rapamycin and inhibitor chloroquine. Western blot analysis was performed to detect the autophagic markers LC3 and Beclin 1 expression. Immunofluorescence method was used to show intracellular autophagy formation. Inverted microscope was used to observe the cell morphology. CCK-8 assays were used to detect the cell viability. Results Green fluorescent spots that represented the transformation level of LC3-I to LC3-Ⅱ increased significantly (P＜0.05) by serum-starvation, rapamycin and inhibitor chloroquine respectively, but the expression level of Beclin 1 was not raised. In addition, the cell morphology changed significantly, and cell proliferation was inhibited after serum-starvation, and treatment with rapamycin and inhibitor chloroquine (P＜0.05), Conclusion The changes of autophagy caused by serum starvation, rapamycin and inhibitor chloroquine in GCT-0404 cells may be involved in the down-regulation of cell proliferation.

Analysis on medication rules of modern traditional Chinese medicines in treating palpitations based on traditional Chinese medicine inheritance support system / 中国中药杂志

To analyze the prescription and medication rules of Chinese medicines in the treatment of palpitations in the Chinese journal full text database(CNKI) by using traditional Chinese medicine inheritance system, and provide a reference for further research and development of modern traditional Chinese medicines(TCMs) in treatment of palpitations. In order to give better guidance for clinical mediation, prescriptions used for treatment of palpitations in CNKI were collected, and then were input to the TCM inheritance support system for establishing a Chinese medicine prescription database for palpitations. The software's revised mutual information, complex system entropy clustering and other data mining methods were adopted to analyze the prescriptions according to the frequencies of herbs, "four natures", "five flavors" and "meridians" of the high-frequency medicines in the database, identify the core herbs and application characteristics, and analyze the prescription rules and medication experience. Totally, 545 prescriptions used for palpitation were included in this study and involved 247 Chinese herbs. The analysis results showed that the herbs in prescriptions for palpitation mostly had the warm property, and the herbs in heart and spleen meridian accounted for a larger proportion, indicating that the treatment was mainly to nourish heart and strengthen spleen. The top 11 herbs in usage frequency were consistent with the high-frequency medicines in medication patterns of common herbal pairs; therefore, we considered that these 11 herbs were the core herbs; the core herbal combination included Cassia Twig, Licorice, fossil fragments, Ostreae decoction, and evolved into 9 new prescriptions for treating palpitation. Our results objectively presented the prescription and medication rules for treating palpitation and provided extremely effective guidance for the clinical therapy.

Quantification of (-)doxazosin at very low concentration in rat plasma samples by SPE-LC-MS/MS / 药学学报

Previous publications showed that the value of LLOQ (lowest limit of quantification) for doxazosin and its enantiomers in biological samples were above 0.1 ng·mL-1. The present study was designed to establish a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification at very low concentration of (-)doxazosin in rat plasma after intravenous administration of (-)doxazosin (3.0 mg·kg-1). The plasma samples containing prazosin as an internal standard were extracted by solid-phase extraction (SPE) and separated on Acquity BEH C18(50 mm×2.1 mm, 1.7 μm) column under alkaline conditions of the mobile phase. (-)Doxazosin was monitored under positive ionization condition by multiple reaction monitoring (MRM) with an ESI source. The good linear range of (-)doxazosin varied from 10.4 pg·mL-1 to 13 ng·mL-1(r=0.9922), and the lowest limit of quantification was 10.4 pg·mL-1. An assessment of the matrix effect using post-extraction spiking method and post-column infusion method demonstrated that co-eluting matrix components did not significantly influenced the ionization of (-)doxazosin and prazosin (IS). Using the new method, we accurately measured (-)doxazosin concentration at 48 h after intravenous administration in the rats, and the concentration was 0.0344±0.0102 ng·mL-1. The method is specific, sensitive, and suitable for determining (-)doxazosin at very low concentration in rat plasma samples.

Progress of Experimental Research on Differentiation of Muscle-Derived Stem Cells into Haematopoietic Lineages in Vitro -Review / 中国实验血液学杂志

Muscle-derived stem cells (MDSC) are a population of multipotent stem cells in the muscular tissue. It provide an excellent prospect of hemopathy treatment due to their superiorities, such as rich sources, convenient material resource and a high survival rate after transplantation and so on. However, there are great differences in sampling, separation, purification, and proliferation when MDSC were cultured in vitro. In addition, the proliferation conditions of the MDSC in vitro are yet unclear. The related regulatory mechanisms, which MDSC transformed into haematopoietic cells, need to be investigated. In this article, the experimental researches on the differentiation of MDSC into haematopoietic lineages are reviewed, the concrete problems discussed in this review are culture of MDSC in vitro, identification of MDSC, proleferation of MDSC, differention of MDSC in to hematopoietic lineages and so on.

The neuroprotective effects of grape seed proanthocyanidin on rat brain injury caused by chronic intermittent hypoxia

Chronic intermitted hypoxia including sleep breathing disorder leads to brain injury. This study explores the potential therapeutic effects of grape seed proanthocyanidin as a neuroprotective agent. A rat model of chronic intermittent hypoxia was employed, and the animals were given low or high doses of grape seed proanthocyanidin. The ultrastructure changes in the brain, the biochemical components, and the animal behavior were examined. The results showed that with hypoxia exposure, neuronal mitochondria exhibited injuries at ultrastructural level, with increased malondialdehyde (MDA) content and reduced superoxide dismutase (SOD) activity. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining revealed increased cell apoptosis in hippocampus. In Morris water maze the animals showed decreased learning abilities, when compared to normal control. The administration of grape seed proanthocyanidin treatment reversed all these observed changes, and improved the learning behavior. We concluded that grape seed proanthocyanidin could alleviate the brain injury caused by hypoxia from sleep breathing disorder.

A survey of occupational health among polyether-exposed workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the occupational health of the workers simultaneously exposed to acrylonitrile, epoxyethane, epoxypropane, and styrene.</p><p><b>METHODS</b>A questionnaire survey was conducted in 70 front-line workers simultaneously exposed to acrylonitrile, epoxyethane, epoxypropane, and styrene (exposure group) and 50 managers (control group) in a polyether manufacturer; in addition, air monitoring at workplace and occupational health examination were also performed. The obtained data were analyzed.</p><p><b>RESULTS</b>The female workers in exposure group and the spouses of male workers in exposure group had significantly higher spontaneous abortion rates than their counterparts in control group (P < 0.01). The exposure group had a significantly higher abnormal rate of blood urea nitrogen than the control group (P < 0.01). The workers with different polyether-exposed working years had significantly higher mean levels of DNA damage than the control group (P < 0.01); the workers with not less than 5 and less than 20 polyether-exposed working years and those with not less than 20 polyether-exposed working years had significantly higher mean micronucleus rates than the control group (P < 0.01); there were no significant differences in overall chromosome aberration rate and mean level of DNA damage between each two groups of workers with different polyether-exposed working years (P > 0.05); the workers with not less than 5 and less than 20 polyether-exposed working years and workers with not less than 20 polyether-exposed working years had significantly higher mean micronucleus rates than those with less than 5 polyether-exposed working years (P < 0.01).</p><p><b>CONCLUSION</b>Simultaneous exposure to acrylonitrile, epoxyethane, epoxypropane, and styrene causes occupational hazards among the workers in polyether manufacturer.</p>

Determination of aconitine, hypaconitine and mesaconitine in Shenfu injection / 中国中药杂志

To establish a method for the content determination of indexes for measuring aconitic compounds contained in Shenfu injection, in order to provide basis for the evaluation of the curative effect of monkshood in Shenfu injection. The sample were purified and enriched with HF-LPME. ACQUITY UPLC BEH C18 column (2.1 mm x 50 mm, 1.7 microm) was adopted and eluted with a gradient program, with acetonitrile-10 mmol x L(-1) NH4HCO3 (pH 10) as the mobile phases. The flow rate was 0.45 mL x min(-1). The content was determined with ESI and MRM. The results showed that aconitine, hypaconitine and mesaconitine showed a good linear relationship, with r > 0.999, within the range of 0.1-100 ng x L(-1). The recoveries were detected to be 100.1%, 97.4%, 97.5%, with RSD being 1.2%, 1.1%, 1.5%, respectively. This method was used to prove the safety of Shenfu injection, and provide scientific basis for correct evaluation of curative effect of monkshood, as well as a reliable, simple and practical means for quality control of monkshood-containing Chinese materia medica preparations.

Influence of different degrees of chronic intermittent hypoxia on c-fos protein and apoptosis in rats / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To establish different degrees and duration of animal hypoxia model of sleep apnea hypopnea syndrome according to the mechanism of intermittent hypoxia, to observe the effect of c-fos protein and apoptosis, and to explore the mechanism of nervous system injury.</p><p><b>METHODS</b>By using the model of chronic intermittent hypoxia in rats, male Wistar rats (n = 72) were randomly divided into three groups: 5% of chronic intermittent hypoxia group (the fraction of oxygen volume reduced to 5% under hypoxia), 10% of chronic intermittent hypoxia group (the fraction of oxygen volume reduced to 5% under hypoxia) and control group. The levels of on c-fos protein and apoptosis of hippocampal cell in three groups were detected at the 2nd, 4th, 6th and 8th week respectively. The expression of c-fos protein in hippocampal cell was detected by immunohistochemical method and the apoptosis of hippocampal cell was detected by TUNEL.</p><p><b>RESULTS</b>The relative quantity of c-fos protein and apoptotic index in CIH groups were significantly higher than that of the control group on the 2nd, 4th, 6th and 8th weeks (F were 44.52, 57.56, 24.20 and 13.18, P < 0.05), and these were higher obviously in 5% CIH group than that in 10% CIH group (P < 0.05). The expression of c-fos protein and apoptotic index in two CIH groups was different depending upon the different degree and duration of chronic intermittent hypoxia. With increased exposure time, the expression of c-fos protein and apoptotic index was high generally at first, peaked at 6th week, then down at 8th week (P < 0.05). While it in UC group was invariability in different time (P > 0.05). The correlation between the relative quantity of c-fos protein and apoptotic index in two CIH groups was positive (r were 0.816 and 0.701, P < 0.01).</p><p><b>CONCLUSION</b>Moderate and severe intermittent hypoxia induced the excessive expression of c-fos protein in hippocampus, caused nerve cell apoptosis, and may play an important role in the mechanism of early brain injury of intermittent hypoxia.</p>

Expression of periodontal ligament-associated protein-1 in normal periodontal tissues and cells in rat / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To examine the expression of periodontal ligament-associated protein-1 (PLAP-1) in the periodontal tissues and periodontal ligament cells (PDLC).</p><p><b>METHODS</b>The PLAP-1 expression in normal periodontal tissue was examined by immunohistochemistry. The protein expression and mRNA transcription of PLAP-1 in PDLC were investigated by immunocytochemistry and reverse transcription-polymerase chain reaction.</p><p><b>RESULTS</b>PLAP-1 was expressed in periodontium but not in cementum, alveolar bone and gingival tissues. PLAP-1 expression was observed in cell plasma, but not in nuclei. There was a 350 bp electrophoresis band representing PLAP-1 mRNA.</p><p><b>CONCLUSIONS</b>PLAP-1 may play a role in physiology of periodontal tissues and cells in normal adult rats.</p>