基于美国研究生培养模式探讨中医药院校创新型研究生的培养

研究生教育是我国培养高层次人才的主要方式,也是创新型人才培养的主要途径。文章通过分析美国研究生培养模式,结合我国中医院校研究生培养的特点,从研究生质量问题、研究生课程和教学以及研究生导师情况等方面为切入点来解决培养创新型研究生的问题,改善我国创新型研究生培养模式,提高研究生培养质量。

肠道菌群代谢产物与胰岛素抵抗相关衰老疾病的研究进展

2型糖尿病(T2DM)和阿尔茨海默病(AD)都是与年龄相关的衰老性疾病,二者存在多种共同危险因素。肠道微生物通过多种代谢产物参与胰岛素生理机能的调控过程,在胰岛素抵抗(IR)发生发展中发挥重要的作用。该文从IR的角度,对肠道菌群代谢产物与T2DM及AD发病机制的内在联系作一综述。

双氢青蒿素对犬乳腺肿瘤细胞生物学特性的影响

犬乳腺肿瘤是犬类的一种常见肿瘤性疾病,目前治疗多为手术结合放、化疗法,但结果多易转移复发。双氢青蒿素(dihydroartemisinin,DHA)是中药提取物,近年来其抗肿瘤作用越来越受到重视。为探求双氢青蒿素是否影响犬乳腺肿瘤细胞的侵袭及其影响机制,本试验取对数增长期状态相同的犬乳腺肿瘤细胞CHMm,使用低(5μM)、中(10μM)、高(20μM)浓度DHA处理并分别培养24,48,72h。收集各组细胞,使用CCK-8法检测细胞活性;利用细胞划痕试验检测细胞迁移性;利用transwell检测细胞侵袭性;利用CCK-8检测细胞毒性。结果表明:DHA对CHMm细胞抑制率呈明显药物浓度依赖性。细胞划痕试验检测细胞迁移速率结果表明,相同培养时间,与空白对照组相比,低、中、高试验组对CHMm细胞迁移性抑制作用效果极显著(p<0.01)。各组组间比较,DHA对细胞迁移性抑制影响差异极显著(p<0.01)。DHA对CHMm细胞迁移性抑制呈明显的药物时间、浓度依赖性。细胞侵袭试验检测细胞侵袭性结果表明,相同培养时间,与空白对照组相比,低、中、高试验组穿透基底膜着色细胞个数显著增多,说明DHA对CHMm细胞侵袭性抑制效果极显著(p<0.01),组间比较,不同DHA作用浓度效果差异显著(p<0.05)。相同DHA作用浓度,随着培养时间的增加,细胞侵袭性降低,效果显著(p<0.05)。细胞毒性结果表明,相同培养时间,与空白对照组相比,低、中、高试验组对CHMm细胞抑制性影响效果极显著(p<0.01)。各组组间比较,DHA对细胞抑制性影响差异极显著(p<0.01)。综上所述,DHA对犬乳腺肿瘤细胞增殖、迁移和侵袭作用具有显著抑制作用,且随着DHA作用浓度增加和时间增长,抑制作用增强,呈浓度时间依赖性。

基于图像相减和随机森林的AST3巡天暂现源及变源搜寻方法

AST3-2(Antarctic Survey Telescopes)光学巡天望远镜位于南极大陆最高点冰穹A,其产生的大量观测数据对数据处理的效率提出了较高要求.同时南极通信不便,数据回传有诸多困难,有必要在南极本地实现自动处理AST3-2观测数据,进行变源和暂现源观测的数据处理,但是受到低功耗计算机的限制,数据的快速自动处理的实现存在诸多困难.将已有的图像相减方案同机器学习算法相结合,并利用AST3-22016年观测数据作为测试样本,发展一套的暂现源及变源的筛选方法成为可行的选择.该筛选方法使用图像相减法初步筛选出可能的变源,再用主成分分析法抽取候选源的特征,并选择随机森林作为机器学习分类器,在测试中对正样本的召回率达到了97%,验证了这种方法的可行性,并最终在2016年观测数据中探测出一批变星候选体.

The interaction between the Wnt/β-catenin signaling cascade and PKG activation in cancer

The activation of the Wnt/β-catenin signaling cascade has been well studied and documented in colorectal cancer（CRC）.The long-term use of non-steroidal anti-inflammatory drugs（NSAIDs） has been shown to reduce the incidence and risk of death from CRC in numerous epidemiological studies.The NSA1 D sulindac has also been reported to cause regression of precancerous adenomas in individuals with familial adenomatous polyposis who are at high risk of developing CRC.The mechanism responsible for cancer chemopreventive activity of NSAIDs is not well understood but may be unrelated to their cyclooxygenase inhibitory activity.Emerging evidence suggests that sulindac inhibits the growth of colon tumor cells by suppressing the activity of certain phosphodiesterase isozymes to activate cGMβ-dependent protein kinase,PKG,through the elevation of the second messenger cyclic guanosine monophosphote,cGMP.PKG activation has been shown to inhibit the nuclear translocation of β-catenin,reduce β-catenin mRNA and protein levels,and suppress the transcriptional activity of β-catenin.This review describes the relationship between the Wnt/β-catenin signaling cascade and the activation of PKG through PDE inhibition and elevation of intracellular cGMP levels.

Sulindac sulfide selectively increases sensitivity of ABCC1 expressing tumor cells to doxorubicin and glutathione depletion

ATP-binding cassette（ABC） transporters ABCC1（MRP1）,ABCB1（P-gp）,and ABCG2（BCRP） contribute to chemotherapy failure.The primary goals of this study were to characterize the efficacy and mechanism of the nonsteroidal anti-inflammatory drug（NSAID）,sulindac sulfide,to reverse ABCC1 mediated resistance to chemotherapeutic drugs and to determine if sulindac sulfide can influence sensitivity to chemotherapeutic drugs independently of drug efflux.Cytotoxicity assays were performed to measure resistance of ABC-expressing cell lines to doxorubicin and other chemotherapeutic drugs.NSAIDs were tested for the ability to restore sensitivity to resistance selected tumor cell lines,as well as a large panel of standard tumor cell lines.Other experiments characterized the mechanism by which sulindac sulfide inhibits ABCC1 substrate and co-substrate（GSH） transport in isolated membrane vesicles and intact cells.Selective reversal of multi-drug resistance（MDR）,decreased efflux of doxorubicin,and fluorescent substrates were demonstrated by sulindac sulfide and a related NSAID,indomethacin,in resistance selected and engineered cell lines expressing ABCC 1,but not ABCB 1 or ABCG2.Sulindac sulfide also inhibited transport of leukotriene C_4 into membrane vesicles.Sulindac sulfide enhanced the sensitivity to doxorubicin in 24 of 47 tumor cell lines,including all melanoma lines tested（7-7）.Sulindac sulfide also decreased intracellular GSH in ABCC1 expressing cells,while the glutathione synthesis inhibitor,BSO,selectively increased sensitivity to sulindac sulfide induced cytotoxicity.Sulindac sulfide potently and selectively reverses ABCC1-mediated MDR at clinically achievable concentrations.ABCC1 expressing tumors may be highly sensitive to the direct cytotoxicity of sulindac sulfide,and in combination with chemotherapeutic drugs that induce oxidative stress.

New Immunological Approaches in Hepatocellular Carcinoma: Glypican-3 (GPC-3) Opportunities and Challenges

Immunotherapy is one of the strategies to boost natural defenses to fight cancer. Immuno-oncology is an artificial stimulation of the human immune system to recognize and kill selectively neoplastic cells at different stage of transformation. Cancer cells have tumor antigens and the antibody of the immune system, binding them, can detect molecules on their extracellular side of cell membrane. Among these proteins, it is rising in interest and used for early detection of hepatocellular carcinoma (HCC) Glypican-3 (GPC-3) protein. It is a heparan sulfate proteoglycan (HSPG), anchored to the cell membrane of transformed hepatocytes. We investigated its function as key regulator of hepatocytes neoplastic transformation. Noteworthy, GPC-3 protein has been implicated in different pathways from cell growth to cell motility and migration. More recently, GPC-3 has been evaluated as a useful marker for HCC due to its increased expression in the liver during tumorigenesis and its absence in normal liver. Immunotherapy that targets GPC-3 domains and its connected proteins are currently under investigation. These new biomarkers may hold potential for the detection and treatment of HCC and other diseases in which GPC-3 may be overexpressed and/or play a crucial role. This review will summarize the current knowledge regarding the active immunotherapy developed to treat HCC and it will evaluate aspects of GPC-3 (structure and biology) as advantages and potential pitfalls for considering it as a valuable immunotherapeutic target. We also elaborated the current literature with the aim to better understand its biological interactions at a molecular and cellular level to identify alternative or combined targets, due to the existing gap in the literature surrounding GPC-3. The role GPC-3 plays in the hepatocellular carcinoma phenotype can be targeted for a novel immunotherapy strategy that can specify cell-mediated destruction of neoplastic cell that spares normal liver tissue, and it can be exploited as a new serum marker to trend for diagnosis and disease progression measurements. We believe further investigation of its functions and structure, including alternative cellular localizations, is necessary to evaluate GPC-3 as valuable target to cure this cancer.

Consequences of Non-Uniformity in the Stoichiometry of Component Fractions within One and Two Loops Models of α-Helical Peptides

A 3-D electrostatic density map generated using the Wavefront Topology System and Finite Element Method clearly demonstrates the non-uniformity and periodicity present in even a single loop of an α-helix. The four dihedral angles (N-C*-C-N, C*-C-N-C*, and C-N-C*-C) fully define a helical shape independent of its length: the three dihedral angles, φ = -33.5°, ω = 177.3°, and Ψ = -69.4°, generate the precise (and identical) redundancy in a one loop (or longer) α-helical shape (pitch = 1.59 /residue;r = 2.25 ). Nevertheless the pattern of dihedral angles within an 11 and a 22-peptide backbone atom sequence cannot be distributed evenly because the stoichiometry in fraction of four atoms never divides evenly into 11 or 22 backbone atoms. Thus, three sequential sets of 11 backbone atoms in an α-helix will have a discretely different chemical formula and correspondingly different combinations of molecular forces depending upon the assigned starting atom in an 11-step sequence. We propose that the unit cell of one loop of an α-helix occurs in the peptide backbone sequence C-(N-C*-C)3-N which contains an odd number of C* plus even number of amide groups. A two-loop pattern (C*-C-N)7-C* contains an even number of C* atoms plus an odd number of amide groups. Dividing the two-loop pattern into two equal lengths, one fraction will have an extra half amide (N-H) and the other fraction will have an extra half amide C=O, i.e., the stoichiometry of each half will be different. Also, since the length of N-C*-C-N, C*-C-N-C*, and C-N-C*-C are unequal, the summation of the number of each in any fraction of n loops of an α-helix in sequence will always have unequal length, depending upon the starting atom (N, C*, or C).

高等技术师范院校加强学生职业道德教育的探索

本文就高等技术师范院校开展职业道德教育的必要性及其内容、途径和方法进行了初步探索。

随机对照试验:综合医疗中应用一种治疗小儿哮喘的临床途径效果

Aims: To evaluate the effect of the implementation of an asthma clinical path way on asthma in children in general practice. Methods: A randomized, controlled trial involving 270 general practitioners. One group of general practitioners i mplemented the asthma clinical pathway for children (intervention group)- and t he control group continued with their usual asthma medical care management. The main outcome measures were admissions to hospital for asthma and attendance at t he Children’s Emergency Department. Compliance with the guidelines was assesse d by examining asthma drug prescriptions. Results: Admissions to hospital for as thma dropped 40% in the intervention group, by 33% in the control group and by 22% in general practitioners not participating in the trial. The difference s between the intervention and control and between the intervention and non- pa rticipating general practitioners were not statistically significant. The decrea se in attendance at the Children’s Emergency Department decreased by 25% , 30 % and 19% , respectively, but this was not statistically signifi- cant. Ther e was a significant decrease in prescriptions for oral relievers, dry powder rel ievers in the under 6s, mast cell stabilizers and methylxanthines in both contro l and intervention groups. However, only for oral relievers was there a signific ant difference between the intervention group and control, with the decrease lar ger in the intervention group (p < 0.001). Conclusions: Admissions to hospital f or asthma decreased, as did attendance at the Children’s Emergency Department. Prescriptions for asthma medication changed in the direction anticipated with c ompliance with the asthma clinical pathway. However, we found no evidence within the study that implementation of the asthma clinical pathway by general practit ioners resulted in lower morbidity than those general practitioners who did not implement the pathway. Possible explanations are that these general practitioner s were already providing care according to the recommendations of the pathway, o r that there was contamination of the control group by the intervention, or that the guidelines, although based on currently accepted recommendations, are ineff ective.

The dusty and extremely red progenitor of the typeⅡsupernova 2023ixf in Messier 101

Stars with initial masses in the range of 8-25 solar masses are thought to end their lives as hydrogen-rich supernovae(SNeⅡ).Based on the pre-explosion images of Hubble space telescope(HST)and Spitzer space telescope,we place tight constraints on the progenitor candidate of type IIP SN 2023ixf in Messier 101.Fitting of the spectral energy distribution(SED)of its progenitor with dusty stellar spectral models results in an estimation of the effective temperature as 3091+422-258K.The luminosity is estimated as lg(L/L⊙)~4.83,consistent with a red supergiant(RSG)star with an initial mass of 12-1+2M⊙.The derived mass loss rate(6×10^(-6)-9×10^(-6)M⊙yr^(-1))is much lower than that inferred from the flash spectroscopy of the SN,suggesting that the progenitor experienced a sudden increase in mass loss when approaching the final explosion.In the infrared bands,significant deviation from the range of regular RSGs in the color-magnitude diagram and period-luminosity space of the progenitor star indicates enhanced mass loss and dust formation.Combined with new evidence of polarization at the early phases of SN 2023ixf,such a violent mass loss is likely a result of binary interaction.

Crosstalk of the Wnt/b-catenin pathway with other pathways in cancer cells

Many cancers have similar aberrations in various signaling cascades with crucial roles in cellular proliferation,differentiation,and morphogenesis.Dysregulation of signal cascades that play integral roles during early cellular development is well known to be a central feature of many malignancies.One such signaling cascade is the Wnt/b-catenin pathway,which has a profound effect on stem cell proliferation,migration,and differentiation.This pathway is dysregulated in numerous cell types,underscoring its global oncogenetic potential.This review highlights regulators and downstream effectors of this receptor cascade and addresses the increasingly apparent crosstalk of Wnt with other tumorigenic signaling pathways.As understanding of the genetic and epigenetic changes unique to these malignancies increases,identifying the regulatory mechanisms unique to the Wnt/b-catenin pathway and similarly aberrant receptor pathways will be imperative.

美国的替代性纠纷解决

调解一般分为促进型调解、评估型调解和转变型调解三种基本类型。仲裁具有裁决结果的约束性、程序上的非公开性、时间上的快捷性等特点。仲裁裁决只有在非常有限的情况下才可以被撤销,因此,我们必须慎重选择仲裁员。其他替代性纠纷解决方式还包括仲裁外的其他裁决方式、评估式方式、调查和报告方式、混合方式等。行政裁决作为一种替代性的解决方式,和调解与仲裁相比具有自身的特点,证据和程序规则被适用,法官会进行较正式的听审。行政法庭有别于司法法庭,但其作出的裁决一般来说可以上诉到司法法庭。集体谈判对争议解决至关重要,但由于工会会员人数的持续下降,这样的争议解决方式能否维持下去值得关注。

正畸矫治的长期稳定性

1944年MiloHellman医生曾经这样阐述“保持正畸治疗后的长期稳定性是非常困难的，至今为止对于导致矫治复发的因素尚不十分明了。”至上周为止我开业已经30年了，在此期间治疗过各种错袷畸形，正畸患者多达11，000人次，积累了大量宝贵的临床资料。我本人对正畸矫治后长期稳定性的研究表明，正畸矫治后可以保持其矫治效果的长期稳定性。

Image guidance in endoscopic sinus surgery and skull base surgery

Objective The objective of this study was to review the current clinical applications and impact of intraoperative imaging on endoscopic sinonasal and skull base procedures in adult and pediatric patients.Methods The PubMed database was searched for articles related to the use of image guidance in otolaryngology using the search terms "image guidance otolaryngology".This was supplemented by the authors′ experience utilizing image guidance in nearly 3000 endoscopic sinus and skull base procedures.Results The literature demonstrates that intraoperative image guidance has utility in primary and revision endoscopic sinus surgery,as well as endoscopic surgery of the skull base.Image guidance also has applications in pediatric endoscopic surgery,such as pediatric sinus surgery and repair of choanal atresia.Conclusions Intraoperative image guidance,when combined with a thorough knowledge of paranasal sinus and skull base anatomy and technical proficiency,can provide improved safety when performing otolaryngologic procedures from endoscopic sinus surgery to endoscopic skull base surgery.While not a substitute for knowledge of anatomy,the increased availability and usability of image guidance systems make them a useful tool in the armamentarium of the otolaryngologist/head and neck surgeon and neurosurgeon.

Optical observations of LIGO source GW 170817 by the Antarctic Survey Telescopes at Dome A,Antarctica

The LIGO detection of gravitational waves(GW) from merging black holes in 2015 marked the beginning of a new era in observational astronomy. The detection of an electromagnetic signal from a GW source is the critical next step to explore in detail the physics involved. The Antarctic Survey Telescopes(AST3),located at Dome A, Antarctica, is uniquely situated for rapid response time-domain astronomy with its continuous night-time coverage during the austral winter. We report optical observations of the GW source(GW 170817) in the nearby galaxy NGC 4993 using AST3. The data show a rapidly fading transient at around 1 day after the GW trigger, with the i-band magnitude declining from 17:23 ± 0:13 magnitude to 17:72 ± 0:09 magnitude in ~1:8 h. The brightness and time evolution of the optical transient associated with GW 170817 are broadly consistent with the predictions of models involving merging binary neutron stars. We infer from our data that the merging process ejected about ~10^(-2) solar mass of radioactive material at a speed of up to 30% the speed of light.

EGFR signaling promotes resistance to CHK1 inhibitor prexasertib in triple negative breast cancer

Aim:Innate resistance to the CHK1 inhibitor prexasertib has been described,but resistance mechanisms are not understood.We aimed to determine the role epidermal growth factor receptor(EGFR)plays in innate resistance to prexasertib in triple negative breast cancer(TNBC).Methods:Using a panel of pre-clinical TNBC cell lines,we measured the sensitivity to prexasertib.We examined the effect activation of EGFR had on prexasertib sensitivity.We measured the synergy of dual blockade of EGFR with erlotinib and CHK1 with prexasertib in TNBC cell lines and xenografts.Results:EGFR overexpression and activation increased resistance to CHK1 inhibition by prexasertib.EGFR promoted the phosphorylation of BCL2-associated agonist of cell death(BAD),inactivating its pro-apoptotic functions.Inhibition of EGFR reversed BAD phosphorylation,increasing sensitivity to prexasertib.Conclusion:The use of prexasertib as a monotherapy in TNBC has been limited due to modest clinical responses.We demonstrated that EGFR activation contributes to innate resistance to prexasertib in TNBC and potentially other cancers.EGFR expression status should be considered in clinical trials examining prexasertib’s use as a monotherapy or combination therapy.

BRD7 plays an anti-inflammatory role during early acute inflammation by inhibiting activation of the NF-кB signaling pathway

Increasing evidence has shown a strong association between tumor-suppressor genes and inflammation.However,the role of BRD7 as a novel tumor suppressor in inflammation remains unknown.In this study,by observing BRD7 knockout mice for 6–12 months,we discovered that compared with BRD7+/+mice,BRD7^(−/−)mice were more prone to inflammation,such as external inflammation and abdominal abscess.By using mouse embryo fibroblast(MEF)cells from the BRD7 knockout mouse,an in vitro lipopolysaccharide(LPS)-stimulated MEF cell line was established.The mRNA levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),chemokine(C-X-C motif)ligand 1(CXCL-1)and inducible nitric oxide synthase(iNOS)were significantly increased in BRD7^(−/−)MEF cells compared with BRD7+/+MEF cells after LPS stimulation for 1 or 6 h.In addition,the cytoplasm-to-nucleus translocation of nuclear factor kappa-B(NF-κB;p65)and an increased NF-κB reporter activity were observed in BRD7^(−/−)MEF cells at the 1 h time point but not at the 6 h time point.Furthermore,an in vivo dextran sodium sulfate(DSS)-induced acute colitis model was created.As expected,the disease activity index(DAI)value was significantly increased in the BRD7^(−/−)mice after DSS treatment for 1–5 days,which was demonstrated by the presence of a significantly shorter colon,splenomegaly and tissue damage.Moreover,higher expression levels of IL-6,TNF-α,p65,CXCL-1 and iNOS,and an increased level of NF-κB(p65)nuclear translocation were also found in the DSS-treated BRD7^(−/−)mice.These findings suggest that BRD7 has an anti-inflammatory role during early acute inflammation by inhibiting activation of the NF-кB signaling pathway,which provides evidence to aid in understanding the therapeutic effects of BRD7 on inflammatory diseases.

Plant growth in a fragmented forest is a consequence of top-down and bottom-up processes, but not their interaction

Aims Habitat loss and fragmentation are the leading causes of global biodiversity decline.How fragmentation(leading to edge effects,increased isolation and declining habitat size)interacts with top-down processes like vertebrate herbivory,an important driver of vegetation structure and composition in many ecosystems,is poorly quantified.Interactions between fragmentation and changes in her-bivory may exacerbate their individual influences on plant growth,with implications for management of native plant communities within fragmented landscapes.We examined the effects of habitat fragmentation on herbivore activity,and also how both fragmen-tation and mammalian herbivory influence growth of understorey plant species.Methods This study was conducted at the Wog Wog habitat fragmentation experiment,located in south-eastern New South Wales,Australia.We use herbivore exclusion plots across an experimentally frag-mented landscape to assess the interactive effects of fragmenta-tion and herbivory on the growth of four plant species that vary in growth form and rarity in the landscape.Important Findings We observed species-specific responses to both herbivory and fragmentation,but no additive or interactive effects between these drivers.We show that a reduction in herbivore activity within frag-ments does not correspond with an increase in plant growth,even for the most palatable species.Rather,top-down processes continue to operate across the fragmented landscape.Although changes in habitat conditions within fragments appear to negatively influence both plant growth and mammalian herbivore activity,it is likely that alterations to bottom-up effects(i.e.fragmentation)may be more important than top-down effects(i.e.herbivores)for the spe-cies under investigation.The species-specific response of plants to herbivory or fragmentation may have implications for temporal and spatial population persistence in fragmented landscapes and ulti-mately fragment vegetation structure.

EGFR signaling promotes resistance to CHK1 inhibitor prexasertib in triple negative breast cancer

Aim:Innate resistance to the CHK1 inhibitor prexasertib has been described,but resistance mechanisms are not understood.We aimed to determine the role epidermal growth factor receptor(EGFR)plays in innate resistance to prexasertib in triple negative breast cancer(TNBC).Methods:Using a panel of pre-clinical TNBC cell lines,we measured the sensitivity to prexasertib.We examined the effect activation of EGFR had on prexasertib sensitivity.We measured the synergy of dual blockade of EGFR with erlotinib and CHK1 with prexasertib in TNBC cell lines and xenografts.Results:EGFR overexpression and activation increased resistance to CHK1 inhibition by prexasertib.EGFR promoted the phosphorylation of BCL2-associated agonist of cell death(BAD),inactivating its pro-apoptotic functions.Inhibition of EGFR reversed BAD phosphorylation,increasing sensitivity to prexasertib.Conclusion:The use of prexasertib as a monotherapy in TNBC has been limited due to modest clinical responses.We demonstrated that EGFR activation contributes to innate resistance to prexasertib in TNBC and potentially other cancers.EGFR expression status should be considered in clinical trials examining prexasertib’s use as a monotherapy or combination therapy.