Guide to assembling a successful K99/R00 application.

The National Institutes of Health's (NIH) K99/R00 Pathway to Independence Award offers promising postdoctoral researchers and clinician-scientists an opportunity to receive research support at both the mentored and the independent levels with the goal of facilitating a timely transition to a tenure-track faculty position. This transitional program has been generally successful, with most K99/R00 awardees successfully securing R01-equivalent funding by the end of the R00 period. However, often highly promising proposals fail because of poor grantsmanship. This overview provides guidance from the perspective of long-standing members of the National Heart, Lung, and Blood Institute's Mentored Transition to Independence study section for the purpose of helping mentors and trainees regarding how best to assemble competitive K99/R00 applications.

MOBILE Intervention Pilot Study in College Students With Elevated Blood Pressure.

BACKGROUND: Hypertension is typically recognized in middle-aged and older adults but often overlooked in younger populations. OBJECTIVE: We evaluated a mobile intervention for reducing blood pressure (BP) in college-age students for 28 days. METHODS: Students with elevated BP or undiagnosed hypertension were assigned to an intervention or control group. All subjects completed baseline questionnaires and attended an educational session. For 28 days, intervention subjects sent their BP and motivation levels to the research team and completed assigned BP-reducing tasks. After 28 days, all subjects completed an exit interview. RESULTS: We found a statistically significant decrease in BP in the intervention group only ( P = .001) but no statistical difference in sodium intake for either group. Mean hypertension knowledge increased in both groups but was only significant for the control group ( P = .001). CONCLUSIONS: The results provide preliminary data on BP reduction with greater impact on the intervention group.

(Pro)renin Receptor and Blood Pressure Regulation: A Focus on the Central Nervous System.

The renin-angiotensin system (RAS) is classically described as a hormonal system in which angiotensin II (Ang II) is one of the main active peptides. The action of circulating Ang II on its cognate Ang II type-1 receptor (AT1R) in circumventricular organs has important roles in regulating the autonomic nervous system, blood pressure (BP) and body fluid homeostasis, and has more recently been implicated in cardiovascular metabolism. The presence of a local or tissue RAS in various tissues, including the central nervous system (CNS), is well established. However, because the level of renin, the rate-limiting enzyme in the systemic RAS, is very low in the brain, how endogenous angiotensin peptides are generated in the CNS-the focus of this review-has been the subject of considerable debate. Notable in this context is the identification of the (pro)renin receptor (PRR) as a key component of the brain RAS in the production of Ang II in the CNS. In this review, we highlight cellular and anatomical locations of the PRR in the CNS. We also summarize studies using gain- and loss-of function approaches to elucidate the functional importance of brain PRR-mediated Ang II formation and brain RAS activation, as well as PRR-mediated Ang II-independent signaling pathways, in regulating BP. We further discuss recent developments in PRR involvement in cardiovascular and metabolic diseases and present perspectives for future directions.

Effects of age and gender on anti-inflammatory, anti-oxidative and anti-apoptosis functions of high-density lipoprotein / 中华老年医学杂志

Objective To investigate the effects of age and gender on anti-oxidative,antiinflammatory and anti-apoptosis functions of high-density lipoprotein (HDL).Methods Totally 120 healthy subjects aged from 20 to 60 years were randomly divided into young and middle-aged male (n=60) group and female (n =60) group,and the 120 healthy elderly aged from 60 to 78 years divided into elderly male (n =60) and elderly female (n =60) groups.Serum levels of high-and low-density lipoprotein cholesterol (HDL-C,LDL-C),total cholesterol (TC),and triacylglycerol (TG) were detected.Content of malonaldehyde (MDA) was detected to determine anti-oxidative function of HDL.Adhesion assay of endothelial cells and monocytes (THP1) was adopted to test the protective effects of HDL on endothelial cells.The expressions of endothelial cell adhesion molecules,VCAM-1 and ICAM-1,were analyzed by Western blot.MTT and flow cytometry assays were used to detect the viability and apoptosis of the cells to test anti-apoptosis function of HDL.Results The levels of low-density lipoprotein,triglycerides and total cholesterol were higher in elder female group than in other three groups (all P＜0.05).The level of HDL-C was higher in young and middle-aged females than in other three groups(all P＜0.05).The level of MDA was higher in elder female group than in other three groups(all P＜0.05).The level of MDA was higher in elder male group than in the young and middle-aged male and female groups(all P＜0.05).After protection of HDL,the number of monocytes adhesion and expression levels of VCAM-1 and ICAM-1 were higher in elder groups than in young and middle-aged male and female groups(all P＜ 0.05).Relative survival and viability rates of endothelial cells were higher in young and middle-aged groups than in elder groups (all P＜0.05).Conclusions Ageing in both male and female induces impairments of anti-oxidative,anti-inflammatory and anti-apoptosis functions of HDL,with more evident decrease in anti-oxidative function in females.

Effect of arterial blood collection from different spots in infants / 现代临床护理

ObjectiveTo investigate effects of the arterial blood collection from radial artery,brachial artery,femoral artery and orsalis pedis artery for gas analysis of infants.Methods Three hundred and fifty two infants receiving blood collection were divided into four groups radial artery (n=92),brachial artery (n=94),femoral artery (n=73) and dorsal artery (n=53).Comparisons were done between them in terms of one-time success rate of puncturing and rate of complications from puncturing.Result The radial artery group had lowest rates of hematoma and mistaken puncturing into veins (P<0.05) and higher rate of one-time successful puncturing (P<0.001).Conclusion The radial artery is the first choice for infants undergoing arterial puncturing.

Effects of phospholipid transfer protein overexpression on content of sphingosine-1-phosphate in mouse lipoprotein / 中国病理生理杂志

[ABSTRACT]AIM:Toinvestigatetheinteractionandthemechanismofsphingosine-1-phosphate(S1P)and phospholipid transfer protein (PLTP) in lipoprotein.METHODS:The S1P content in the plasma and lipoprotein from 10-week-old PLTP transgenic (PLTP-Tg) mice and wild-type (WT) mice (n=8 each) was assayed.The transport of S1P by PLTP was determined by S1P transfer assay.The content of specific S1P carrier, apolipoprotein M, was detected by West-ern blotting.RESULTS:Plasma S1P contents were decreased by 21.1%in PLTP-Tg mice compared with WT mice.S1P content in high-density lipoprotein ( HDL) fraction ( HDL-S1P) from PLTP-Tg mice was decreased by 35.1% compared with WT mice, whereas the S1P in low-density lipoprotein (LDL) fraction (LDL-S1P) was increased by 127.4%.The re-sults of S1P transfer assay indicated that PLTP facilitated S 1P transport from erythrocyte to recombinant liposome at 37℃in D-Hanks buffer solution .The plasma content of apolipoprotein M was not changed in PLTP-Tg mice compared with WT mice.CONCLUSION:PLTP is a key factor to maintain plasma HDL-S1P under physical condition .Overexpression of PLTP decreases the HDL-S1P but increases LDL-S1P.The mechanism might be related to the capability of PLTP on trans-ferring S1P from erythrocyte to lipoprotein.

Effect of herbs on preventing diarrhea caused by irinotecan and its correlation with gene polymorphism of UGT1A1*28 / 中国肿瘤临床

Objective:This study aimed to determine the function of herbs in preventing diarrhea after irinotecan chemotherapy and analyze the efficacy of the herbs based on UGT1A1*28 gene polymorphism. Methods:A total of 200 patients admitted to the De-partment of Synergistic Chinese and Western Medicine, Tianjin Medical University Cancer Institute and Hospital between October 2011 and May 2013 were randomly divided into the control (chemotherapy alone) and herb (chemotherapy combined with herbs) groups. All patients consented to UGT1A1*28 gene polymorphism detection prior to chemotherapy. Herbs were administered from 2 d prior to chemotherapy to 5 d post chemotherapy, with or without the regimen of fluorouracil, folinic acid, and irinotecan. Adverse reac-tions were recorded, and short-term effect was evaluated regularly. Results:A total of 144 patients had TA6/6 wild genotype, and anoth-er 56 patients had non-wild genotype (12 of the 56 cases were TA7/7 homozygous, and the other 44 cases were TA6/7 hybrid). A total of 58 patients experienced grades 2 to 4 diarrhea. A 14%decrease in the incidence of diarrhea was observed in the herb group compared with that of the control group (22%vs. 36%, P=0.029). In addition to diarrhea, grades 2 to 4 vomiting was significantly lower in the herb group than in the control group (15% vs. 27%, P=0.037). The overall response rate was 37.5%. No significant difference was found between the two groups (40% vs. 35%, P=0.465). The incidences of grades 2 to 4 diarrhea (22.9% vs. 44.6%, P=0.002) and grades 2 to 4 vomiting (23.2%vs. 16.7%, P=0.016) were lower in patients with the UGT1A1*28 wild genotype than in those with the non-wild genotype. However, in the herb group, the incidences of grades 2 to 4 diarrhea (22.2% vs. 21.9%, P=0.974) and vomiting (18.5% vs. 13.7%, P=0.777) were not significant between the non-wild-and wild-type groups. Conclusion:Herbs can effectively pre-vent the late diarrhea caused by irinotecan, which is also applicable in UGT1A1*28 non-wild genotype patients. Incidence of diarrhea was obviously higher in the cases with UGT1A1*28 non-wild type than in those with wild genotype. Hence, the UGT1A1*28 gene type should be detected prior to chemotherapy with irinotecan.

Progress of research on predicting breast cancer prognosis based on multi-gene expression levels / 中国肿瘤临床

Breast cancer is one of the most common cancers in women. Current clinical prognostic indicators and practice guide-lines show that almost 70% of node-negative and 30% of lymph node-positive breast cancer patients can survive 5-10 years without dis-tant metastasis after surgery. Patients also unnecessarily suffer the side effects of chemotherapy. Assays on multi-gene expression levels as prognosis prediction indicators have been successfully used to predict the prognosis of breast cancer patients because of the abnor-mal expression levels of a series of metastasis-related genes in cancer cells with high metastatic potential. In this review, we highlight the progress of research on predicting breast cancer prognosis based on multi-gene expression levels detected by microarray and qRT-PCR methods.

Clinical Value of Growth Factors and Their Receptors for the Metastasis and Prognosis of Breast Cancer / 中国肿瘤临床

Through its high affinity with membrane receptors, growth factors promote tumor growth, metastasis and an-giogenesis, induce the change of tumor microenvironment and regulate immune response. It has been demonstrated that the serum protein levels of epidermal growth factor and its receptor, transforming growth factors and their receptors, insu-lin-like growth factors, and angiogenesis factors may have predictive value for metastasis and prognosis of breast cancer. Detecting serum levels of growth factors and their receptors which have synergistic effect or interaction with each other may be helpful for predicting the metastasis and progression of breast cancer.