Otto Piening推出水基液压系统调距螺旋桨

DEUTSCHE YACHTEN集团旗下公司Otto Piening近日首次开发出可以用水基液压系统运行的可调螺距螺旋桨。该水基液压系统调距桨目前正在申请专利,将于今年9月6~9日在汉堡海事会展上展出。该系统是世界上第一台水基液压系统可调螺距螺旋桨,已经通过DNV、GL船级社认证,并且被巨型游艇市场认可,作为海军和海岸警卫队舰船使用也非常环保。

片仔癀通过调节小鼠的肠道菌群和代谢物抑制非酒精性脂肪性肝炎

Non-alcoholic steatohepatitis(NASH)is a severe form of non-alcoholic fatty liver disease without effective treatment.The traditional Chinese medicine formulation Pien Tze Huang(PTH)can suppress inflammatory diseases.Here,we evaluate the effects of PTH on the evolution of NASH and its underlying mechanisms.We found that PTH prevented the development of steatohepatitis induced by various dietary models,including a high-fat high-cholesterol(HFHC)diet,choline-deficient high-fat diet(CD-HFD),and methionine-and choline-deficient(MCD)diet,along with significant suppression of liver injury,hepatic triglyceride,and lipid peroxidation.Moreover,ten days of PTH treatment after the onset of NASH significantly ameliorated MCD diet-induced steatosis and liver injury in mice.Through the metagenomic sequencing of stool samples,we found that PTH administration restored the gut microbiota with enrichment of probiotics including Lactobacillus acidophilus(L.acidophilus),Lactobacillus plantarum,Lactococcus lactis,and Bacillus subtilis.The enriched L.acidophilus prevented MCD diet-induced steatohepatitis.In addition,PTH restored the gut barrier function in mice with steatohepatitis,as evidenced by reduced intestinal permeability,decreased serum lipopolysaccharides(LPS)level,and increased epithelial tightjunction protein E-cadherin expression.Our metabolomic analysis via liquid chromatography-mass spectrometry profiling identified the alteration in the metabolism of bile acids in the portal vein of PTHtreated mice.We further confirmed that an intact gut microbiota is necessary for PTH to exhibit antisteatohepatitis effects.In conclusion,PTH protects against steatohepatitis development by modulating the gut microbiota and metabolites.PTH is a potential promising prophylactic and therapeutic option for patients with NASH.

Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling

Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is unknown.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphorylation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

PTEN在肝细胞癌中的表达及其与VEGF的关系研究

目的研究PTEN在人类肝细胞癌中的异常表达及其临床意义,探讨PTEN及VEGF在肝细胞癌中表达的相互关系。方法采用免疫组织化学S-P法对67例人类肝细胞癌和36例癌旁肝组织、10例正常肝组织中的PTEN蛋白产物及VEGF的表达情况进行检测、分析。结果肝细胞癌组、癌旁肝组织组、正常肝组织组PTEN表达蛋白的阳性表达率分别为53.73%、83.33%及100%。PTEN的表达与肿瘤组织分化、有无门静脉侵犯及区域淋巴结转移、肿瘤包膜是否完整相关,而与患者的年龄、性别、肿瘤的大小、是否携带乙肝表面抗原均无明显关系。在同一肝细胞癌组织中,PTEN与VEGF的表达呈一定程度的负相关关系。结论PTEN的表达与肝细胞癌的发生发展有关,PTEN与VEGF在肝细胞癌的发生、发展过程中可能起协同作用.

胃癌中PTEN、p27^(kip1)及cyclinE蛋白表达及其意义

目的探讨PTEN、p27kip1及cyclinE蛋白表达与胃癌发生、发展的关系。方法应用免疫组化S-P法分别检测59例胃癌及癌旁组织中PTEN、p27kip1及cyclinE蛋白表达情况。结果PTEN在癌旁组织阳性率96.61%(51/59)显著高于胃癌组织中阳性率50.85%(30/59)(P<0.05),胃癌组织中高中分化腺癌PTEN阳性率78.75%(15/19)显著高于低分化腺癌37.5%(9/24)与胃黏液癌37.5%(6/16)(P<0.05),而后两者间无显著性差异(P>0.05)。p27kip1在癌旁组织阳性率84.75%(50/59)显著高于胃癌组织中阳性率47.46%(28/59)(P<0.05),胃癌组织中高中分化腺癌p27kip1阳性率73.68%(14/19),显著高于低分化腺癌37.5%(9/24)与胃黏液癌31.25%(5/16)(P<0.05),后两者间无显著性差异(P>0.05)。cyclinE在胃癌组织中阳性率55.93%(33/59)明显高于癌旁组织40.68%(24/59)(P<0.05),胃癌组织中黏液癌阳性率68.75%(11/16)和胃低分化腺癌阳性率66.67%(16/24)显著高于胃高中分化腺癌阳性率31.58%(6/19)(P<0.05),前两者间无显著性差异(P>0.05)。结论PTEN、p27kip1在胃癌组织中表达下降、cyclinE表达升高,随着病理分化程度降低PTEN、p27kip1表达降低,cyclinE表达升高,提示PTEN、p27kip1、cyclinE可能与胃癌的发生、发展及生物学行为有关。

PTEN蛋白表达与胃癌临床病理生物学行为的关系

目的观察PTEN蛋白在胃癌中的表达,探讨其与胃癌临床病理因素的关系。方法采用免疫组化方法检测PTEN蛋白在58例胃癌,23例异型增生和25例正常胃黏膜中的表达。结果PTEN在正常胃黏膜,胃异型增生和胃癌中阳性率分别为100%,69.57%和44.83%。PTEN在胃癌中的阳性率明显低于胃异型增生,正常胃黏膜。进展期胃癌PTEN阳性率低于早期胃癌,两者之间有显著差异;淋巴结转移和低分化腺癌的PTEN阳性率明显低于淋巴结未转移和高中分化腺癌;随着浸润深度的加深,PTEN的阳性率依次降低。结论PTEN的下调在胃癌的发生中起着重要的作用,PTEN表达可能对胃癌的浸润和转移具有抑制作用,可作为胃癌临床病理学行为有效的客观指标。

人脑胶质瘤中p57KIP2蛋白和PTEN蛋白的表达及意义

目的探讨p57KIP2蛋白和PTEN蛋白在人脑胶质瘤中的表达及意义。方法采用S-P法免疫组织化学技术检测54例人脑胶质瘤和15例正常脑组织中p57KIP2蛋白和PTEN蛋白的表达。结果p57KIP2蛋白在胶质瘤和正常脑组织中的阳性表达率分别为40.74%、80%,两者有显著性差异(P<0.01);其在胶质瘤低度恶性组(WHOⅠ-Ⅱ级)和高度恶性组(WHOⅢ-Ⅳ级)中的阳性表达率分别为66.67%、14.81%,两者有显著性差异(P<0.001)。PTEN蛋白在胶质瘤和正常脑组织中的阳性表达率分别为50%、93.33%,两者有显著性差异(P<0.005);其在胶质瘤低度恶性组和高度恶性组中的阳性表达率分别为77.78%、22.22%,两者有显著性差异(P<0.001)。在胶质瘤中,PTEN蛋白和p57KIP2蛋白表达和PTEN蛋白表达呈显著正相关(γs=0.904,P<0.001)。多分类Logistic回归分析显示p57KIP2蛋白和PTEN蛋白在胶质瘤中的表达与肿瘤恶性程度有关(P<0.01),与患者的性别和年龄无显著性关系(P>0.1)。结论p57KIP2蛋白、PTEN蛋白在人脑胶质瘤中的阳性表达率随肿瘤恶性程度的增高而降低,与患者的年龄和性别无关。两者可能有协同抑制人脑胶质瘤发生和恶性进展的作用。

结直肠癌中PTEN的缺失表达及临床意义

目的:研究PTEN在结直肠癌中的表达及其与结直肠癌病理特征的关系．方法:应用免疫组化SP法分别检测65例癌组织和癌旁组织及13例腺瘤组织PTEN蛋白的表达．结果:PTEN主要在细胞核或细胞质中表达,在结直肠癌组织中阳性表达率显著低于癌旁组织阳性表达率(56．92% vs 86．15％,P<0．01)．中、高分化腺癌阳性表达率显著高于低、未分化腺癌阳性表达率(75．76% vs 37．50％, P<0．01)．Dukes A、B期阳性表达率显著高于Dukes C、D期阳性表达率(73．33％vs 42．86％, P<0．05)．此外,PTEN的表达与淋巴转移有关(P<0．01),而与性别、年龄、同期的肿瘤大小无关．结论:PTEN在结直肠癌组织中的表达下调,其表达水平可作为反映结直肠癌进展和预后的生物学指标之一．

PINK1/Parkin介导的线粒体自噬在缺血性脑卒中的作用研究进展

PTEN诱导推定激酶1(PINK1)/人帕金森蛋白2(Parkin)介导的线粒体自噬过程作为线粒体质量控制的关键机制之一,与缺血性脑卒中的凋亡、氧化应激及炎症反应等病理机制密切相关,极大地影响着该病的发生发展过程。本文将对PINK1、Parkin蛋白的结构与功能、该通路介导的线粒体自噬在缺血性脑卒中的作用展开综述,并分析其作为治疗缺血性脑卒中新靶点的优势。

抑癌基因PTEN与口腔肿瘤

PTEN基因是第一个具有双特异性磷酸酶活性的抑癌基因，具有调控细胞的生长发育和细胞凋亡的作用，并能影响肿瘤细胞的浸润、转移过程。该基因与口腔癌发生、发展及预后有相关性，从而为口腔癌基因治疗提供一种新途径。

Pien Tze Huang alleviates Concanavalin A-induced autoimmune hepatitis by regulating intestinal microbiota and memory regulatory T cells

BACKGROUND Traditional Chinese medicine has used the drug Pien Tze Huang(PTH),a classic prescription,to treat autoimmune hepatitis(AIH).However,the precise mode of action is still unknown.AIM To investigate the mechanism of PTH in an AIH mouse model by determining the changes in gut microbiota structure and memory regulatory T(mTreg)cells functional levels.METHODS Following induction of the AIH mouse model induced by Concanavalin A(Con A),prophylactic administration of PTH was given for 10 d.The levels of mTreg cells were measured by flow cytometry,and intestinal microbiota was analyzed by 16S rRNA analysis,while western blotting was used to identify activation of the toll-like receptor(TLR)2,TLR4/nuclear factor-κB(NF-κB),and CXCL16/CXCR6 signaling pathways.RESULTS In the liver of mice with AIH,PTH relieved the pathological damage and reduced the numbers of T helper type 17 cells and interferon-γ,tumor necrosis factor-alpha,interleukin(IL)-1β,IL-2,IL-6,and IL-21 expression.Simultaneously,PTH stimulated the abundance of helpful bacteria,promoted activation of the TLR2 signal,which may enhance Treg/mTreg cells quantity to produce IL-10,and suppressed activation of the TLR4/NF-κB and CXCL16/CXCR6 signaling pathways.CONCLUSION PTH regulates intestinal microbiota balance and restores mTreg cells to alleviate experimental AIH,which is closely related to the TLR/CXCL16/CXCR6/NF-κB signaling pathway.

An Important Acupuncture Demonstration in the History of Legalization of Acupuncture in the United States

This article details a public acupuncture demonstration that took place on May 9,1972,in San Francisco,California.It was conducted by two traditional Chinese medicine doctors Pien Bae Chi(卞伯岐)and Leung Kok Yuen(梁觉玄),and was observed by 500 American medical doctors.This was an important public acupuncture demonstration in the early history of acupunccture in the United States(US).It directly promoted the passage of the first acupuncture bill by California government and had a significant impact on the legalization of acupuncture in California.

Establishment of the First Professional Organization of Traditional Chinese Medicine and Acupuncture in California

The California Chinese Medicine and Acupuncture Research Association,founded on March 25,1974,is the first Chinese medicine organization registered with the state government in California.It was established after more than a year of arduous preparation and had 15 founding members.Over time,it evolved into the biggest organization of Chinese medicine and acupuncture in California.And in 2015,it became the American Association of Chinese Medicine and Acupuncture with more than 500 members.

Skin rash caused by EGFR-TKI could be treated successfully by Pien Tze Huang Unguentum Compositum: a case report

Epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)plays an important role in cancer therapy.However,EGFR is highly expressed in the skin and gives rise to one of the most concerning issues for the EGFR-TKI treatment,namely skin toxicity.Antibiotics and corticosteroids are usually used to treat the EGFR inhibitor-associated skin rash,with prominent side effects over long-time use.Pien Tze Huang(PZH)Unguentum Compositum is a traditional product for external application which is made of traditional Chinese medicine and oil base.Herein,we reported the case of a 50-year-old man who presented with skin rash on the face,head,and back induced by an EGFR-TKI named erlotinib.By using PZH Unguentum Compositum,we observed that the skin rash was mitigated and eventually disappeared.This case report suggests that PZH Unguentum Compositum may be an effective therapy in treating skin rash caused by EGFR-TKI with fewer side effects.

Immunomodulatory Function of Pien Tze Huang in T Cell-Mediated Anti-tumor Activity against B16-F10,MC38 and Hep1-6 Tumor Models

Objective To investigate the anti-tumor effects of Pien Tze Huang(PZH)in mouse models of B16–F10 melanoma,MC38 colorectal cancer,Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model.Methods Various tumor models,including B16–F10,MC38 and Hep1-6 tumor hypodermic inoculation models,B16–F10 and Hep1-6 pulmonary metastasis models,Hep1-6 orthotopic implantation model,and chemically induced hepatocellular carcinoma model,were utilized to evaluate the anti-tumor function of PZH.Tumor growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 mice.For cell proliferation and death of tumor cells in vitro,as well as T cell activation markers,cytokine production and immune checkpoints analysis,single-cell suspensions were prepared from mouse spleen,lymph nodes,and tumors after PZH treatment.Results PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth(P<0.01).Treatment with PZH resulted in a reduction in tumor size in subcutaneous MC38 colon adenocarcinoma and B16–F10 melanoma models,and decreased pulmonary metastasis of B16–F10 melanoma and Hep1-6 hepatoma(P<0.01).However,in vitro experiments showed that PZH only had slight impact on the cell proliferation and survival of tumor cells(P>0.05).Nevertheless,PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma,tumor necrosis factor alpha,and interleukin 2 in CD4^(+)T cells in vitro(P<0.01 or P<0.05).Importantly,PZH substantially inhibited T cell exhaustion and boosted cytokine production by tumor-infiltrating CD8^(+)T cells(P<0.01 or P<0.05).Conclusion This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity,indicating that PZH holds promise as a potential therapeutic agent for cancer treatment.

Pien Tze Huang Inhibits Proliferation of Colorectal Cancer Cells through Suppressing PNO1 Expression and Activating p53/p21 Signaling Pathway

ObjectiveTo explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it’s down-stream mediators in colorectal cancer (CRC) cells.MethodsQuantitative polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in tissues.ResultsPZH treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05).ConclusionThe mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.

PTEN和磷酸化Akt在婴幼儿血管瘤中的表达及意义

目的检测PTEN和磷酸化Akt在婴幼儿血管瘤不同时期的表达情况,分析二者的表达相关性,探讨其在婴幼儿血管瘤发生发展过程中的作用及意义。方法应用免疫组化SP法检测婴幼儿血管瘤增生期、消退期,血管畸形及正常皮肤中的PTEN和磷酸化Akt蛋白表达情况,利用计算机图像分析技术测量其平均光密度。结果PTEN在增生期血管瘤内皮细胞的表达低于消退期、血管畸形及正常皮肤(P<0.01);磷酸化Akt在增生期血管瘤内皮细胞的表达高于消退期、血管畸形及正常皮肤(P<0.05);消退期血管瘤、血管畸形与正常皮肤间PTEN、磷酸化Akt的表达差异无统计学意义(P>0.05);PTEN与磷酸化Akt在婴幼儿血管瘤组织中的表达呈负相关(r=-0.7192,P<0.05)。结论PTEN与磷酸化Akt可能在婴幼儿血管瘤增生过程中起了一定的作用。

Pien Tze Huang(片仔癀)-Induced Apoptosis in Human Colon Cancer HT-29 Cells Is Associated with Regulation of the Bcl-2 Family and Activation of Caspase 3

Objective：To investigate the cellular effects of Pien Tze Huang（片仔癀,PZH） in the HT-29 human colon carcinoma cell line.Methods：The viability of HT-29 cells was determined by MTT assay.A fluorescence-activated cell sorting（FACS） analysis with annexin-V/propidium iodide（PI） and JC-1 staining were performed to determine cell apoptosis and the loss of mitochondrial membrane potential,respectively.Activation of caspase 3 was evaluated by a colorimetric assay.The mRNA expression levels of Bcl-2 and Bax were measured by reverse transcription polymerase chain reaction（RT-PCR）.Results：PZH,in a dose- and time-dependent manner,reduced viability and induced apoptosis of HT-29 cells.Moreover,PZH treatment resulted in the collapse of the mitochondrial membrane potential,activation of caspase 3,and an increase in the Bax/Bcl-2 ratio.Conclusion：PZH inhibits the growth of HT-29 cells by inducing cancer cell apoptosis via regulation of the Bcl-2 family and activation of caspase 3,which may,in part,explain its anticancer activity.

Effects of Pien Tze Huang(片仔癀) on Angiogenesis in vivo and in vitro

Objective： TO investigate the anti-angiogenic effects of Pien Tze Huang （片仔癀, PZH） in vivo and in vitro. Me.otis： Human umbilical vein endothelial cells （HUVECs） were treated with 0 mg/mL, 0.25 mg/mL, 0.5 mg/mL, and 1 mg/mL of PZH for 24 h, 48 h and 72 h, respectively. Chicken embryo chorioallantoic membrane （CAM） model was used to evaluate in vivo angiogenesis. An ECMatrix gel system was used to evaluate in vitro angiogenesis by examining the tube formation of HUVECs. 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide assay was performed to determine HUVEC viability. Cell density of HUVECs was observed by phase- contrast microscopy. HUVEC migration was determined by wound healing method. The mRNA and protein expression of vascular endothelial growth factor A （VEGF-A） and basic fibroblast growth factor （bFGF） in both HUVEC and human colon adenocaminoma cells （HT-29） was examined by reverse transcription polymerase chain reaction （RT-PCR） and enzyme linked immune sorbent assay （ELISA）, respectively. Results： PZH treatment significantly reduced the total number of blood vessels compared with the untreated control in the chicken embryos and resulted in a significant decrease in capillary tube formation and cell density of HUVECs （P〈0.05）. In addition, treatment with 0.25-1 mg/mL of PZH for 24 h, 48 h, and 72 h respectively reduced cell viability by 9%-52%, 24%-87% or 25%-87%, compared with the untreated control cells （P〈0.05）. Moreover, PZH treatment decreased the migration of HUVECs. Furthermore, PZH close-dependently suppressed the expression of VEGF-A and bFGF on both mRNA and protein levels （P〈0.05）. Conclusion： PZH could inhibit angiogenesis in vivo in CAM model and in vitro on HUVECs, suggesting that inhibiting tumor angiogenesis might be one of the mechanisms by which PZH treats cancer.

Pien Tze Huang(片仔癀) Overcomes Doxorubicin Resistance and Inhibits Epithelial-Mesenchymal Transition in MCF-7/ADR Cells

Objective: To evaluate the effect of Pien Tze Huang (片仔癀, PZH) on breast cancer chemo resistance and related epithelial-mesenchymal transition (EMT) and investigate the underlying mechanisms. Methods: 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to determine the cell viability. Adriamycin (ADR) staining observed by fluorescence microscope was performed to detect the accumulation of ADR. Transwell assay was used to analyze the cell migration and invasion. Western-blot was performed to detect the protein expression of related genes. Results: MCF-7/ADR cells were resistant to ADR treatment, and PZH treatment inhibited the viability of MCF-7/ADR cells in a dose-dependent manner. PZH treatment also increased the intercellular accumulation of ADR and down-regulated the expression of ABCG2 and ABCB1 in MCF-7/ADR cells (P<0.05). In addition, PZH treatment inhibited EMT, migration and invasion of MCF-7/ADR cells (P<0.05). Moreover, PZH suppressed activation of transforming growth factor β 1 (TGF-β) signaling in MCF-7/ADR cells (P<0.05). Conclusion: PZH treatment can effectively overcome chemoresistance via down-regulating ABCG2, ABCB1 and inhibit EMT in ADR resistant human breast cancer cells via suppression of the TGF-β 1 pathway.