Objective To clarify the signaling mechanisms underlying angiotensin Ⅱ biphasic regulation of renal proximal Na+-HCO3- transport. Methods Different concentration Ang Ⅱ to the responses of Na+-HCO3- cotransporter (NBC) activity in isolated proximal tubules, with or without ATR, MAPK, cPLA2α, P450 blockade was compared in wild-type and Ang Ⅱ type 1a receptor (AT1aR)-deficient mice. The phospholipase of ERK was examined by Western blotting. AT1aR mRNA was examined by RT-PCR from kidney proximal tubules. Results (1)In isolated wild-type mouse, renal proximal tubules showed biphasic effects of Ang Ⅱ on NBC activity. Low concentration Ang Ⅱ (10-10 mol/L) increased NBC activity, but high concentration Ang Ⅱ (10-6 mol/L) decreased NBC activity. Olmcsartan (AT1 antagonist) blocked both stimnlatory and inhibitory effects of Ang Ⅱ on NBC activity, but PD98059 (mitogen-activated protein kinase inhibitor) blocked only the stimulatory effect of low concentration Ang Ⅱ ( 10-10 mol/L). (2)In AT1aR-deficient mice, only the stimulatory effect by high concentration of Ang Ⅱ (10-6 mol/L) was observed, which was blocked by olmesartan and PD98059. (3)In wild-type mice, pharmacological blockade of cPLA2 or P450 converted the inhibition effect by high concentration Ang Ⅱ (10-6 mol/L) to the stimulation, which was blocked by olmesanan and PD98059. These results indicated that the extracellular sigual-regulated kinase (ERK) activation via AT1 mediated only the stimulatory effect of Ang Ⅱ, while the cPLA2α/P450 activation via AT1 mediated the inhibitory effect of Ang Ⅱ independently of ERK. The analysis of ERK phosphorylation by Ang Ⅱ also supported a view that the cPLA2α/P450 pathway worked to suppress the ERK activation. Conclusions Ang Ⅱ activates ERK and cPLA2α with different concentration dependency via AT1. The balance between ERK and cPLA2α activities determines the final responses to Ang Ⅱ in intact proximal tubules.

Objective To investigate the clinical characteristic of vernier acuity in age-related macular degeneration (AMD) patients. Methods The vernier acuity test soft wear system was developed to detect the 23 cases (39 eyes) of AMD patients. Tweenty-one eyes were atrophic type and 17 eyes were exudative type. Two fixed targets and a movable target are shown on the computer screen. The examinee was asked to adjust the position of the central target and the relationship between it and align them by using a track ball. The computer automatically recorded the deviations of distances between the movable target and the specific one, and then computed and analysed the results of average threshold and variance. Results Both the atrophic and exudative AMD had higher vernier acuity threshold and its variance than normal subjects, and the differences were significant (P

Ebola virus (EBOV) causes hemorrhagic fever, resulting in mortality rates as high as 90% among infected humans and non-human primates (NHPs). The 2014 Ebola epidemic in West Africa is the severest in history, leading to WHO taking all control measures to stop any possibility of cross-border outbreaks. Because no licensed vaccines or effective therapeutics against EBOV are available, the current outbreak management has been limited to palliative care and barrier methods to prevent transmission. Several promising experimental EBOV vaccines have demonstrated protection in NHPs against lethal EBOV challenge, and some progresses have been made through clinical trials of EBOV vaccine candidates. It is believed there will be some licensed vaccine available in the near future to control EBOV outbreaks. In this review we provide some insights for further development of EBOV vaccines.
Animals ; Ebola Vaccines ; Ebolavirus ; Hemorrhagic Fever, Ebola ; prevention & control ; Humans

Salt reduction is one of the effective strategy for chronic non-communicable disease control and prevention recommended by World Health Organization. Research evidences on salt reduction emerge recently and some issues remain controversial. With the aim of providing reference for the future salt reduction action, this article reviewed the current evidence and strategies on the source of salt intake, the relationship between salt and health, the cost-effectiveness of salt reduction, as well as the targets and strategies of salt reduction. It also elaborated the main controversial issues in salt reduction, including salt reduction in population, evaluation method of salt intake, substitute salt, iodine intake, and the effectiveness of salt reduction strategy. The international and internal salt reduction activities were introduced as well.

In medicine, it is the physician's obligation to promote and protect the patient's interest. In obstetrics, the ethical principles of beneficence and autonomy provide the fundamental framework which guides the management of all pregnant patients. As there is the need for consideration of the fetus, autonomy can become a complex issue giving rise to what is sometimes called "maternal-fetal conflict." In this paper, we aim to discuss some scenarios we encounter in our day-to-day obstetric practice such as pre-eclampsia, fetal growth restriction and labour induction when the best interests of the mother and fetus may be conflicted. We hope to illustrate that logical consideration for maternal and fetal best interests is only possible when there is adequate knowledge to support clinical practice. Certainly, with the rapid availability of newer knowledge and technology, it is the duty of the physician to be educated continuously so as to protect the patient from harm.
Beneficence ; Clinical Competence ; Conflict (Psychology) ; Ethics, Medical ; Female ; Fetal Growth Retardation ; Fetus ; Health Knowledge, Attitudes, Practice ; Humans ; Maternal Welfare ; Maternal-Fetal Relations ; Obstetrics ; ethics ; methods ; Patient Care ; ethics ; Patient Rights ; Personal Autonomy ; Physician-Patient Relations ; ethics ; Pregnancy ; Pregnancy Complications ; Prenatal Diagnosis

OBJECTIVEThis research project aimed to evaluate whether a simplified method for identifying high-risk individuals for cardiovascular diseases proposed by the China Rural Health Initiative (CRHI) was feasible in the rural areas in China.

METHODS2 036 adults, aged 20 years or older were stratified-randomly sampled from 12 villages in Luquan county and Anguo county (Hebei province) respectively, to receive physical examination and filling in administered questionnaires. "Gold Standard" was used on high risk in Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults to evaluate the CRHI standards:people with a history of coronary heart disease or stroke, or elderly as men ≥50 years or women ≥60 years with diabetes, or elderly with systolic blood pressure ≥160 mmHg. Sensitivity, specificity, positive and negative predictive values related to the identification of high-risk individuals for cardiovascular diseases were assessed.

RESULTSThe concordance rate between the CRHI standard and the gold standard was 92.9% , with sensitivity as 77.2%, specificity as 98.5%, Youden's Index as 0.76, positive predictive value as 94.7% and negative predictive value as 92.5%. Under CRHI standard, 21.3% of the adults were identified as high risk. The rate was increasing with age (P < 0.001), reaching 44% among those who were over 60 years old.

CONCLUSIONThe CRHI standard seemed simple and easy and was suitable for identifying high-risk individuals for cardiovascular diseases in the resource-constrained rural areas.

Cytotoxic T cells (CTLs) play a key role in the control of Hepatitis B virus (HBV) infection and viral clearance. However, most of identified CTL epitopes are derived from HBV of genotypes A and D, and few have been defined in virus of genotypes B and C which are more prevalent in Asia. As HBV core protein (HBc) is the most conservative and immunogenic component, in this study we used an overlapping 9-mer peptide pool covering HBc to screen and identify specific CTL epitopes. An unconventional HLA-A2-restricted epitope HBc141-149 was discovered and structurally characterized by crystallization analysis. The immunogenicity and anti-HBV activity were further determined in HBV and HLA-A2 transgenic mice. Finally, we show that mutations in HBc141-149 epitope are associated with viral parameters and disease progression in HBV infected patients. Our data therefore provide insights into the structure characteristics of this unconventional epitope binding to MHC-I molecules, as well as epitope specific CTL activity that orchestrate T cell response and immune evasion in HBV infected patients.
Adult ; Amino Acid Sequence ; Animals ; Binding Sites ; Epitopes ; chemistry ; immunology ; metabolism ; Female ; Genotype ; HEK293 Cells ; HLA-A2 Antigen ; metabolism ; Hepatitis B Core Antigens ; chemistry ; immunology ; metabolism ; Hepatitis B virus ; genetics ; metabolism ; Humans ; Hydrogen Bonding ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Middle Aged ; Molecular Dynamics Simulation ; Mutation ; Protein Binding ; Protein Structure, Tertiary ; T-Lymphocytes, Cytotoxic ; immunology ; metabolism

Animals ; China ; Humans ; Immunophenotyping ; Influenza A Virus, H7N9 Subtype ; classification ; genetics ; immunology ; Influenza A virus ; classification ; genetics ; immunology ; Phylogeny

For the first time ever, the scientists of J. Craig Venter team have created actual self-replicating synthetic life. The research was just published in the Journal of Science on May 20, 2010. Although this news immediately brings the worry about the possible potential threat to biosecurity and biosafety as well as the ethical disputes, it yet indicates that mankind have made a new step forward in synthetic biology. In the time of post-genome era, we believe the advancement of synthetic biology that might affect or change the future life of human being will be widely used in energy, environment, materials, medication and many other fields.
Biological Science Disciplines ; methods ; Cloning, Organism ; Genome, Human ; genetics ; Human Genome Project ; Humans ; Synthetic Biology ; trends

LZ-8 protein, isolated from a well known Chinese traditional medicinal fungus Ganoderma lucidum, is the first member of fungal immunomodulatory protein, members of which have been isolated from a variety of medicinal and edible mushrooms in the last two decades. The protein plays a multifunctional and important role in modulating immune system. In this report, in order to get LZ-8 protein crystals, the LZ-8 gene was expressed and purified by affinity chromatography, gel filtration chromatography and anion exchange chromatography subsequently. The protein was then crystallized using the hanging-drop vapour-diffusion method. The LZ-8 crystals were obtained and the phase information was calculated by X-ray diffraction. The resolution of LZ-8 crystals is 3.2A. This study will provide an insight into the structure of fungal immunomodulatory proteins.
Animals ; Crystallography ; Fungal Proteins ; biosynthesis ; genetics ; immunology ; Ganoderma ; genetics ; metabolism ; Genetic Vectors ; genetics ; Immunologic Factors ; biosynthesis ; genetics ; Mice ; Recombinant Proteins ; biosynthesis ; genetics ; immunology