Effects of methionine enkephalin on immune enhancement by reducing myeloid derived suppressor cells and reprogramming liver metabolism in colon cancer mice

OBJECTIVE To investigate enhanced immune function of methionine encephalin(MENK)and its anti-tumor mechanism in CT26 colon cancer mouse model.METHODS 3×10~6CT26 cells were implanted subcutaneously in BALB/c mice.Four days after,MENK was peritoneally administrated at the concentration of 20 mg·kg^(-1) for 14 d.The percentage of MDSCs in bone marrow,spleen,blood,tumor and liver were detected by flow cytometry.Non-esterified fatty acid(NEFA),triglycerides(TG)and total cholesterol(T-CHO)in liver homogenate were tested by a NEFA test kit,a TG test kit and a T-CHO test kit respectively.qRT-PCR and Western blot were used to measure m RNA and protein levels of inflammation-,glycometabolsim-and lipometabolsim-associated indexes in liver.RESULTS MENK decreased percentages of MDSCs in bone marrow,spleen,blood and tumor in colon cancer mice.MENK-treated mice displayed elevated ratio of CD4^+T and CD8^+T cells in spleen as well as increased T and B lymphocytes proliferation.Meanwhile,MENK also ameliorated liver damage reflected by lower levels of GPT and GOT in serum and reduced risks of cancer-associated index including inflammation,high lipid and high glucose.Furthermore,MENK lowered down the levels of NEFA,TG and T-CHO in liver homogenate.MENK treatment decreased expression of p-STAT3,increased expression of p-AKT,IRS1 and Glut4 at protein level as well as reduced lipogenesis-associated genes and elevated glycolysis-associated genes in liver of tumor bearing mice.Also,abated expression of genes associated with MDSCs generation(M-CSF,GM-CSF,IL-6,IL^(-1)β)and migration(S100A9,KC)was observed within shrunken subcutaneous tumor by MENK intervention.CONCLUSION MENK has the ability to strength immune function against colon cancer by reducing MDSCs and improving liver metabolism.

药学专业学生开设临床药学选修课程的教学情况调查

目的了解药学专业学生对临床药学选修课的需求,分析教学反馈,为进行教学改革、提升教学质量提供依据。方法以华中科技大学同济医学院409名4年制药学本科生为调查对象,在临床药学选修课程教学结束后采用问卷调查方法对选课目的、课程设置评价、教学形式等方面调查,评估课程设置需求。结果被调查对象中,44.99%的学生认为学校所学不能满足临床药学工作需要,91.20%的学生对本课程设置感到满意,90.46%的学生期待增加临床药学实践环节教学,90.95%的学生认为本课程有必要开设。结论临床药学选修课可满足药学专业学生的需求,今后还需在教学方法、课程结构等方面进行不断改进和完善。

Absorption Characteristics of Novel Compound Calcium Carbonate Granules:Effects of Gastric Acid Deficiency and Exogenous Weak Acids

Calcium carbonates are commonly administered as supplements for conditions of calcium deficiency.We report here pharmacokinetic characteristics of a novel formulation,calcium carbonate compound granules(CCCGs).forming complexes of calcium carbonate and calcium citrate in water.CCCGs were compared to a kind of commonly?used calcium carbonate preparation(CC)in the market in 5-week-old mice that had been treated with omeprazole,to suppress gastric acid secretion,and in untreated control mice.The results showed that:(1)CCCGs had better water solubility than CC in vitro;(2)In control mice,calcium absorption rates after CCCGs administration were comparable to those after CC administration;(3)Inhibition of gastric acid secretion did not affect calcium absorption after CCCGs,but moderately decreased it after CC;(4)The presence of phytic acid or tannin did not affect calcium absorption rates after CCCGs but did for CC;and(5)In nonnal mice,CCCGs did not inhibit gastric emptying and intestinal propulsion,and did not alter the gastrointestinal honnones.The results suggest that CCCGs may be therapeutically advantageous over more commonly used calcium supplement formulations,particularly for adolescents,because of their stable calcium absorption characteristics and their relatively favorable adverse effect profile.

Kinsenoside:A Promising Bioactive Compound from Anoectochilus Species

Kinsenoside is a main active component isolated from plants of the genus Anoectochilus,and exhibits many biological activities and pharmacological effects,including hepatoprotective,anti-hyperglycemic,anti-hyperliposis,anti-inflammatory,vascular protective and anti-osteoporosis effects and so on,which is contributing to its promising potency in disease treatments.This review aims to recapitulate the pharmacological functions of kinsenoside,as well as its source,extraction,identification,quantitative analysis,pharmacokinetics,synthesis and patent information.The data reported in this work can confirm the therapeutic potential of kinsenoside and provide useful information for further new drug development.

Notch1 Drives the Formation and Proliferation of Intrahepatic Cholangiocarcinoma

The molecular mechanisms underlying the development of intrahepatic cholangiocarcinoma(ICC)are not clear yet.In this study,we investigated the involvement of Notch1 in the development of ICC.The cDNA microarray analysis showed that Notch1 expression was higher in ICC tissues than in normal biliary epithelial cells.Stable transfection of Notchl receptor intracellular domain(NICD1)by hydrodynamic tail vein injection induced ICC formation in mice.Western blotting confirmed that Notchl signaling was activated in human ICC cell lines and mouse ICC tissues.Silencing Notchl with specific short interfering RNA(siRNA)inhibited the proliferation of ICC cells.Flow cytometry and Western blotting indicated that apoptosis was induced in Notchl-silenced ICC cells compared with controls.Additionally,Notchl silencing was associated with the inhibition of hairy and enhancer of split-1(Hes1)and activation of the phosphatase and tensin homolog(PTEN)/p53 pathway.Taken together,these data suggest that Notchl drives ICC formation and proliferation;downregulation of Notchl induces apoptosis in ICC cells;Notchl signaling may serve as a novel therapeutic target for the treatment of ICC.

The Role of CARD9 in Metabolic Diseases

Caspase recruitment domain containing protein 9(CARD9)is an adaptor protein that plays a critical role in pattern recognition receptors(PRRs)-mediated activation of NF-kB and mitogen-activated protein kinase(MAPK).This elicits initiation of the pro・inflammatory cytokines and leads to inflammatory responses,which has been recognized as a critical contributor to chronic inflammation.Current researches demonstrate that CARD9 is strongly associated with metabolic diseases,such as obesity,insulin resistance,atherosclerosis and so on.In this review,we summarize CARD9 signaling pathway and the role of CARD9 in metabolic diseases.

PID1,a new tumor-promoting gene in insulin resistance mediated acceleration of hepatocellular carcinoma development and progression

OBJECTIVE To investigate the effect of phosphotyrosine interaction domain containing 1(PID1,NYGGF4)on promotion of IR and HCC,and explore its underlying mechanisms.METHODS Lentivirus were used to mediate the knockdown of PID1 in HFD induced IR mouse model as well as ob/ob mice.Intraperitoneal glucose and insulin tolerance were performed 4 weeks after lentivirus injection.Hydrodynamics-based transfection was applied to inducethe liver specific overexpression of PID1.Flow cytometry was exerted to detect the proportion and function of immune cells.qR T-PCR and Western blot were used to detect the expression of downstream pathways of PID1.Immunoprecipitation was used to determine the receptor of PID1.Chromatin immunoprecipitation(ChI P)was operated to measure the modification of H3K4me3 of PID1 promoter.RESULTS PID1 restriction improved insulin resistance,hyperglycemia and fatty liver.Conversely,hepatic knockdown of PID1 attenuated liver xenografted tumor growth.Moreover,PID1 liver-specific protooncogenes via hydrodynamics-based transfection established a primary hepatocellular carcinoma mouse model,induced an immunosuppressive environment,with the reduction of CD3^+,CD4^+,CD8^+T cel s,retarded maturation of dendritic cel s(DCs),pronounced differentiation of regulatory T cells(Tregs),and recruitment of MDSC.In addition,PID1 overexpression activated proliferation related genes,promoted anti-inflammatory genes,suppressed pro-inflammatory genes,induced glycolysis and lipid metabolism genes to facilitate tumorigenesis in liver.Importantly,PID1 exerted its tumor-promoting function through binding to epidermal growth factor receptor(EGFR)and activation of downstream MAPK pathway.As such,PID1 exist trimethylation of histone H3 at lysine 4(H3K4me3)modification and IR up-regulated the expression of PID1 by activation the H3K4me3 modification.CONCLUSION PID1 is a new gene that exerts both liver cancer-promoting and insulin resistance inducing function.IR accelerates liver cancer development and progressionpartially dependent on the activation of PID1.

PID1 based connection of insulin resistance to hepatocellular carcinogenesis

OBJECTIVE To investigate the effect of phosphotyrosine interaction domain containing1(PID1,NYGGF4) onpromotion of IR and HCC,and explore its underlying mechanisms.METHODS Lentivirus were used to mediate the knockdown of PID1 in HFD induced IR mouse model as well as ob/ob mice.Intraperitoneal glucose and insulin tolerance were performed 4 weeks after lentivirus injection.Hydrodynamics-based transfection was applied to induce the liver specific overexpression of PID1.Flow cytometry was exerted to detect the proportion and function of immune cells.qRT-PCR and Western blot were used to detect the expression of downstream pathways of PID1.Liquid chromatographymass spectrometry(LC-MS) and co-immunoprecipitation(Co-IP) were conducted to identify proteins interacting with PID1.Chromatin immunoprecipitation(ChIP) was operated to measure the modification of H3K4me3 of PID1 promoter.RESULTS PID1 restriction improved insulin resistance,hyperglycemia and fatty liver.Conversely,hepatic knockdown of PID1 attenuated liver xenografted tumor growth.Moreover,PID1 liver-specific protooncogenes via hydrodynamics-based transfection established a primary hepatocellular carcinoma mouse model,induced an immunosuppressive environment,with the reduction of CD3+,CD4+,CD8+T cells,retarded maturation of dendritic cells(DCs),pronounced differentiation of regulatory T cells(Tregs),and recruitment of MDSC.In addition,PID1 overexpression activated prolifer.ation related genes,promoted anti-inflammatory genes,suppressed pro-inflammatory genes,induced glycolysis and lipid metabolism genes to facilitate tumorigenesis in liver.Importantly,PID1 exerted its tumor-promoting function through binding to epidermal growth factor receptor(EGFR) and activation of downstream KRAS/ERK pathway.As such,PID1 exist trimethylation of histone H3 at lysine 4(H3K4me3)modification and IR up-regulated the expression of PID1 by activation the H3K4me3 modification.CONCLUSION PID1 is a new gene that exerts both liver cancer-promoting and insulin resistance inducing function.IR accelerates liver cancer development and progression partially dependent on the activation of PID1.

Erratum to:The Role of CARD9 in Metabolic Diseases

The article“The Role of CARD9 in Metabolic Diseases”,written by Cheng TIAN,Ya-li TUO,Yi LU,Chuan-rui XU,Ming XIANG,was originally published electronically on the publisher’s internet portal on May 2020 without open access.With the author(s)’decision to opt for Open Choice,the copyright of the article is changed to©The Author(s)2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License(https://creativecommons.org/licenses/by/4.0/),which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons license,and indicate if changes were made.

巨大肩袖撕裂的可修复性评估及治疗选择

巨大肩袖撕裂的治疗仍具有挑战性,治疗方式分为修复性和非修复性两种,其选择的关键在于判断巨大肩袖撕裂的可修复性。本文重点在于明确巨大肩袖的概念、几个重点名词的定义;阐述肩袖撕裂后的生物力学改变,分析并筛选出影响肩袖撕裂可修复性和愈合的独立风险因素以及影响治疗选择的重要分型系统,有利于术前评估巨大肩袖撕裂的可修复性或不可修复性,制定出更加有针对性的治疗方案。修复性手术方式包括完全修复、部分修复、移植物加强和间置、上关节囊重建。

Progresses in Manufacturing Techniques of Lithium-Ion Battery Separators in China

What is the most favorite and original chemistry developed in your research group?We focus on high-performance and multi-functionality of polymer blends and nanocomposites obtained via processing.The physics and chemistry during polymer processing is our most favorite research topic,which is more complicated and challenging compared with that in state polymer physics and chemistry because it is a dynamic and non-equilibrium process.

Effect of Fumed SiO_2 on Pore Formation Mechanism and Various Performances of β-iPP Microporous Membrane Used for Lithium-ion Battery Separator

In this work, four samples containing different contents of fumed SiO_2 were prepared to improve the pore size distribution and various properties of b nucleated isotatic polypropylene（b-i PP） biaxial membrane used for lithium-ion battery separator. The wide-angle X-ray diffraction（WAXD） and differential scanning calorimetry（DSC） results show that the fumed SiO_2 promotes the formation of b-crystal slightly and narrows down the thickness distribution of b-lamellae; meanwhile, evenly distributed SiO_2 within b-i PP can be inspected by scanning electron microscopy（SEM）. Moreover, further detailed characterization of morphological evolutions during biaxial stretching by tensile testing and SEM manifests that SiO_2 can strengthen b-i PP and make the samples deform more homogeneously, resulting in a gradually elaborate and finer oriented microfibril structure after longitudinal stretching, in which more uniform defects distribute between fibrils and restrain the formation of coarse fibrils effectively. Therefore, more superior microporous structure emerges with the addition of SiO_2, accompanied by narrower pore size distribution and better connectivity between microvoids, which is confirmed by mercury porosimeter and diminished Gurley value. Moreover, the lower thermal shrinkage, decreased shrinkage rate and suppressed porosity reduction indicate that fumed SiO_2 improves thermal and dimensional stability of membrane dramatically. Furthermore, due to the excellent wettability of SiO_2 with electrolyte, the microporous membranes doped with SiO_2 have higher electrolyte uptake, even after heat treatment at elevated temperature.

Comparison of the Structural Evolution ofβPolypropylene during the Sequential and Simultaneous Biaxial Stretching Process

In this work,the lamellar structural evolution and microvoids variations of βpolypropylene(β-PP)during the processing of two different stretching methods,sequential biaxial stretching and simultaneous biaxial stretching,were investigated in detail.It was found that different stretching methods led to significantly different lamellae deformation modes,and the microporous membranes obtained from the simultaneous biaxial stretching exhibited better mechanical properties.For the sequential biaxial stretching,abundant coarse fibers originated from the tight accumulation of the lamellae parallel to the longitudinal stretching direction,whereas the lamellae perpendicular to the stretching direction were easily deformed and separated.Those coarse fibers were difficult to be separated to form micropores during the subsequent transverse stretching process,resulting in a poor micropores distribution.However,for the simultaneous biaxial stretching,theβcrystal had the same deformation mode,that is,the lamellae distributed in different directions were all destroyed,forming abundant microvoids and little coarse fibers.

Practicing the concept of “structuring” processing in the manufacture of polymer films

Polymer processing is a technology used to transfer raw materials into products with different shapes and functionalities and is a key step for polymer application.After years of development,the polymer processing task has changed from traditional processing,which mainly addresses the specific shapes of articles and focuses on the effect of processing on the structures and properties of polymers,to modern processing,which directly transforms a“designed structure”into commercial products via processing.It is the so-called“structuring”processing.Owing to the unique long-chain nature and slow topological relaxation,polymers are always driven and frozen into different nonequilibrium conformations,providing an effective way to design a given polymer material with desired structure and tunable performances via processing.Among the endless number of processing techniques,film casting is a prototypical pathway involving high supercooling or/and a strong flow field,based on which diverse thin polymer films have been successfully developed.In this review,taking isotactic polypropylene(i PP)film as an example,we highlight the strategy of“structuring”processing,in which we transform various crystalline structures of i PP into diverse commercial film products.

Fluorescent lamp promoted formaldehyde removal over CeO_(2) catalysts at ambient temperature

Exploring an alternative strategy with high efficiency and low cost to abate formaldehyde(HCHO)in indoor environment,is of increasing significance for people’s health.CeO_(2) catalysts prepared by hydrothermal,precipitation and calcination methods were investigated for HCHO removal at ambient temperature.It is found that indoor fluorescent light visibly boosts the catalytic performance of CeO_(2) catalysts for HCHO decomposition at ambient temperature.Among the CeO_(2) catalysts,CeO_(2) prepared from hydrothermal method(CeO_(2)-H)exhibits a superior catalytic performance and an excellent durability by eight recycle times.Based on the characterization and analysis,the excellent catalytic performance of CeO_(2)-H is mainly contributed by its abundance of surface oxygen vacancies,and photogenerated electrons and hole activated by fluorescent light.This work shows a potential practicability in HCHO pollution elimination by taking full advantage of the existing lighting in indoor environments.

肱骨距螺钉在肱骨近端骨折治疗中的研究进展

肱骨近端骨折是老年人常见的骨折之一,手术治疗是移位的肱骨近端骨折最主要的治疗方式,肱骨头内翻、内侧柱支撑不足是导致肱骨近端骨折内固定失败的主要原因之一,如何有效增强内侧柱支撑、维持复位是肱骨近端骨折内固定治疗中的难点。肱骨距螺钉在肱骨近端骨折的治疗中,能有效提供内侧支撑,起到对抗肱骨头移位和内翻畸形的作用。但在临床上,关于肱骨距螺钉的认识和使用仍有争议,包括肱骨距螺钉的适用范围、置钉技巧等。本文以肱骨近端骨折手术治疗中使用肱骨距螺钉加强内侧支撑、维持复位为核心,通过系统阐述肱骨距螺钉的概念、生物力学、置钉陷阱与技巧、置钉位置与数量,加强对肱骨距螺钉的认识与理解,以期进一步指导临床,提高临床疗效。

恩师功德言无尽 禅者风范映慈光——缅怀恩师佛源老和尚

恩师佛源老和尚,生前曾任中国佛教协会咨议委员会副主席,广东省佛教协会副会长,韶关市佛教协会会长,广东省人大代表、政协委员,乳源县政协副主席,韶关云门寺、南华寺、湖南南岳祝圣寺、益阳白鹿寺、栖霞寺、德山乾明寺方丈等职,他为弘扬佛法、绍隆佛种、利益众生,贡献了毕生精力,无愧于云门宗的一代传人、近代禅宗泰斗虚云老和尚的入室弟子。他老人家虽然于2009年农历正月廿九日20时36分,度生功德圆满示寂,但给我们留下了许多珍贵的精神财富,足以启迪后人。亲近恩师十余年,我对此感触良多。恩师一去,倏忽十年,谨以此文缅怀恩师,续沐慈光。

Broadband usage for rural communities in the North Island of Aotearoa New Zealand

New Zealand government’s Rural Broadband Initiative(RBI)aims to invest 400 million New Zealand dollar to provide 99%of New Zealanders with access to 50 Mbps peak broadband speed,with the remaining 1%at 10 Mbps by 2025.By 2017,stage 1 of the RBI has been completed,and research is needed to find out the level of usage,proficiency,and productivity achieved by then.Therefore,a survey was carried out to learn whether the rural residents and their communities are making good use of the new fast broadband connection.The survey collected data from 217 rural residents from North Island,and the results indicate that about half of the interview respondents are satisfied with the new broadband speed and the reliability which is offered by RBI stage 1.However,there is about 28%of the respondents disagreed with them.The majority of the Internet uses for rural residents are information searching,reading news,online entertainment,and online banking.Besides that,only a small proportion of respondents know how to utilize the Internet in their work/business and benefit/profit from it,e.g.,using cloud technology capabilities and online marketing campaigns,etc.by then.Therefore,we argue that information and communications technologies(ICT)adoption is not only the availability of the infrastructure but also the beneficial outcomes of Internet availability.In other words,Internet skills in-depth training and education need to catch up with the infrastructure deployment,which is useful to fuel the digital productivity and inclusion for booming rural economies.The survey data-driven findings presented in this paper could serve as a reference to inform government policymakers and those who wish to create,invest,and take actions to speed up the economic and social growth of rural communities in Aotearoa New Zealand through the Internet while shifting from the Internet speed and traffic volume-driven to a more effective Internet connectivity and value-added driven rural economy.