The α4β2-nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel that is distributed throughout the nervous system. It is involved in the regulation of various neurotransmitters including acetylcholine, dopamine, γ-aminobutyric acid, and norepinephrine. α4β2-nAChR plays an important role in learning, memory, cognition, attention, inflammation, and pain. A large number of studies have shown that α4β2-nAChR is an important therapeutic target for neurological diseases such as Alzheimer's disease, Parkinson's disease, epilepsy, depression, nicotine dependence, pain, etc. It is an important target in the early diagnosis and curative effect detection of neurodegenerative diseases including Alzheimer's disease. This review summarizes the role, mechanisms and related drug research advances on α4β2-nAChR ligand drugs in neurological diseases, as well as providing a theoretical basis for identifying and developing more suitable α4β2-nAChR-related compounds.

OBJECTIVETo study the color reappearance effect of metal-ceram restoration and foundry-ceram restoration using Crystaleye spectrophotometer.

METHODS58 metal-ceram restorations and 58 foundry-ceram restorations according to the result of the Crystaleye spectrophotometer were made respectively. The deltaE between restorations and natural teeth as referenced were analyzed. And satisfaction of dentists and patients were evaluated.

RESULTSThe deltaE between metal-ceram restorations and natural teeth was 7.13 +/- 0.74. The deltaE between foundry-ceram restorations and teeth was 1.47 +/- 0.84. There were statistical differences between the deltaE (P < 0.01). The satisnatural faction of dentists and patients to the foundry-ceram restorations were higher than to the metal-ceram restorations (P < 0.05).

CONCLUSIONCrystaleye spectrophotometer can provide accurate reference for foundry-ceram restoration, but for metal-ceram restoration it is not accurate.

Color ; Humans ; Metals ; Spectrophotometry ; Tooth

Abstract: Objective　To investigate the drug demand and related influencing factors of AIDS non-occupational post-exposure prophylaxis (nPEP) among men who have sex with men (MSM) in Wuhan, and to provide a scientific basis for the development of subsequent intervention policies for MSM. Methods　With the assistance of social organizations in Wuhan, MSM was recruited by the snowball method to carry out an online questionnaire survey to collect information on demographics, AIDS-related knowledge, high-risk behaviors, and the need for nPEP medication. The χ2 test and unconditional Logistic regression were used to analyze the related factors of the demand for nPEP medication. Results　A total of 308 valid subjects were included in this study, with predominantly 18-29 years old (78.57%, 242/308). The self-reported sexual orientation was mainly homosexuality (82.47%, 254/308), and the awareness rate of AIDS knowledge was high (89.29%, 275/308). Among the survey respondents, 35.06% (108/308) did not know the situation of HIV infection among MSM population in Wuhan; 55.19% (170/308) had two or more same-sex sexual partners in the last six months; 90.91% (280/308) had heard of nPEP before participating in this survey. After passing nPEP and informing the protective effect of nPEP, 59.42% (183/308) of them needed nPEP. After HIV exposure, 73.38% (226/308) were willing to spend money to buy nPEP drugs, and 88.64% (273/308) were willing to take nPEP drugs because of the known side effects. Logistic regression analysis showed that in the last six months, the needs for taking nPEP medication in those who had 2 or more same-sex sexual partners (OR=2.121, 95%CI: 1.329-3.386) and who had received peer education (OR=1.740, 95%CI: 1.088-2.781) were higher than those of those who had a same-sex sexual partner in the last six months and who had not received peer education. Conclusions　The MSM population in Wuhan has a great demand for nPEP drugs, and peer education is an important way to carry out nPEP publicity and promotion. At the same time, we should continue to strengthen warning publicity and education and behavioral intervention to reduce MSM risky sexual behaviors and reduce new HIV infections.

OBJECTIVETo investigate the effect of Rongshi granule on osteopontin(OPN) expression.

METHODThe urlisthiasis rats were induced by ethylene glycol (EG) and ammonium chloride, the control group rats were non-treated, and the Rongshi granule groups (low-dose group, middle-dose group and high-dose group) were administered Rongshi granule in addition to EG and ammonium chloride in 21 days. Pooled 24 h urine samples from each group were collected weekly with the use of metabolic cages, the concentration of uric calcium and oxalic acid were respectively measured by EDTA and photoelectric colorimetric method. Eight animals from each group were killed at 0, 7, 14, and 21 days, kidneys were histologic examinaed and immunohistochemical staining.

RESULTThe expression of kidney osteopontin in model group was obviously higher than that of control group (P <0.01), and was up to the highest at 21 days with 1.4 times (0.281 3/0.201 8) of the control group. The expression of kidney osteopontin in all of the Rongshi granule groups were lower than those of model group (P < 0.05), with an obvious dose-dependent manner. The degree of the kidney calcium oxalate crystal of the rats in all the Rongshi granule groups was much lower than that of model group, and the uric calcium and oxalic acid were much lower than those of model group (P < 0.01).

CONCLUSIONThe Rongshi granule could inhibit the expression of osteopontin in rat urolithiasis model.

Ammonium Chloride ; Animals ; Calcium ; urine ; Calcium Oxalate ; metabolism ; Dose-Response Relationship, Drug ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Ethylene Glycol ; Female ; Kidney ; metabolism ; Kidney Calculi ; chemically induced ; metabolism ; Male ; Osteopontin ; metabolism ; Oxalic Acid ; urine ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Adult ; Aged ; Aged, 80 and over ; China ; epidemiology ; Female ; Hemorrhagic Fevers, Viral ; epidemiology ; Hospitalization ; Humans ; Male ; Middle Aged

Background/Aims: Oral EDP-514 is a potent core protein inhibitor of hepatitis B virus (HBV) replication, which produced a >4-log viral load reduction in HBV-infected chimeric mice with human liver cells. This study evaluated the safety, pharmacokinetics, and antiviral activity of three doses of EDP-514 in treatment-naive viremic patients with HBeAgpositive or -negative chronic HBV infection. Methods: Patients with HBsAg detectable at screening and at least 6 months previously were eligible. HBeAg-positive and -negative patients had a serum/plasma HBV DNA level ≥20,000 and ≥2,000 IU/mL, respectively. Twenty-five patients were randomized to EDP-514 200 (n=6), 400 (n=6) or 800 mg (n=7) or placebo (n=6) once daily for 28 days. Results: A dose-related increase in EDP-514 exposure (AUClast and Cmax) was observed across doses. At Day 28, mean reductions in HBV DNA were –2.9, –3.3, –3.5 and –0.2 log10 IU/mL with EDP-514 200 mg, 400 mg, 800 mg, and placebo groups, respectively. The corresponding mean change from baseline for HBV RNA levels was –2.9, –2.4, –2.0, and –0.02 log10 U/mL. No virologic failures were observed. No clinically meaningful changes from baseline were observed for HBsAg, HBeAg or HBcrAg. Nine patients reported treatment emergent adverse events of mild or moderate severity with no discontinuations, serious AEs or deaths. Conclusions In treatment-naïve viremic patients, oral EDP-514 was generally safe and well-tolerated, displayed PK profile supportive of once-daily dosing, and markedly reduced HBV DNA and HBV RNA.

OBJECTIVETo establish a novel model of lumbar disc degeneration on the early stage in the rhesus monkey using percutaneous needle puncture guided by CT.

METHODS(1) Thirteen rhesus monkeys aged from 4 to 7 years, female 7 and male 6 were selected for establishing a model of the early stage of lumbar disc degeneration. (2)13 monkeys, 91 discs were divided into 3 groups: 64 discs from L1/2 to L5/6 were percutaneous punctured with a needle 20G as experimental group and 1 disc with a needle 15G as puncture control group and 26 discs were not be punctured from L6,7 to L7-S1 as control group. (3) Lumbar disc localization for needle puncture was guided by CT. All discs were examined by MRI, the HE, Masson's trichrome, Safranine-O and immunohistochemical staining of type II collagen before disc puncture and after puncture at 4, 8 and 12 weeks.

RESULTSMRI: (1) Experimental group: Pfirmann's Grade I was shown at postoperation 4, 8 and 12 weeks; (2) Puncture control group: Grade III was shown at postoperation 4 weeks and Grade IV at 8 weeks; (3) CONTROL GROUP: Grade I was shown at postoperation 4, 8 and 12 weeks. Histological examination: (1) In experimental group, there was no any change at postoperation 4 weeks, and the cell population of the nucleus was decreased at 8 weeks and more decreased at 12 weeks in HE. (2) There was no any change at postoperation 4 weeks, the clefts among the lamellae of the annulus fibrosus (AF) were shown at 8 weeks and more wider of the clefts of AF at 12 weeks in Masson's trichrome. (3) No any change was shown at postoperation 4 weeks, proteoglycan were progressively decreased at 8 and 12 weeks in Safranine-O. (4) No statistically significant difference in positive rate was observed at 4 and 8 weeks compared with control group in immunohistochemical staining of type II collagen. There was statistical difference at 12 weeks compared with control group (P<0.05). In puncture control group postoperation 8 weeks, the morphology of cell of nucleus pulposus was not clear in HE. The wider clefts of lamellae of the AF were shown in Masson's trichrome. The proteoglycan was obviously decreased in Safranine-O. Immunohistochemical staining collagen II synthesized was decreased. In normal control group, no any change was shown at 4, 8 and 12 weeks.

CONCLUSIONSThe degeneration of lumbar intervertebral disc on the early stage could be induced by the percutaneous needle puncture (20G) to the annulus fibrosus. The assessment of disc degeneration on early stage is not shown on MRI and only confirmed by histological examination.

Animals ; Disease Models, Animal ; Female ; Intervertebral Disc ; metabolism ; pathology ; surgery ; Intervertebral Disc Displacement ; etiology ; metabolism ; pathology ; Lumbar Vertebrae ; surgery ; Macaca mulatta ; Male ; Minimally Invasive Surgical Procedures ; Random Allocation

Contraction of smooth muscle cells is triggered by an increase in cytosolic Ca(2+) upon agonist stimulation. Ca(2+) influx across the plasma membrane constitutes a major component of the agonist-induced response in smooth muscle cells. Traditionally, voltage-operated Ca(2+) channel (VOCC) is considered as the channel mediating the Ca(2+) entry. However, this view has been challenged by recent discoveries, which demonstrated that other types of ion channels, such as store-operated and/or receptor-operated Ca(2+) channels (SOCC and/or ROCC), also participate in Ca(2+) response induced by agonists in smooth muscle cells. SOCC is defined as the channel activated in response to the depletion of the internal Ca(2+) stores, an event secondary to G protein coupled receptor or receptor tyrosine kinase stimulation. The Ca(2+) flow mediated by SOCC is termed as capacitative Ca(2+) entry (CCE). Previous study from other group has demonstrated that VOCC played a predominant role in ACh-induced contraction of distal colon smooth muscle in guinea pig. However, whether SOCC participates in the agonist-induced contractile response in this particular tissue is unknown. The present study was performed to investigate the role of CCE in ACh-induced mechanical activity of distal colon smooth muscle in rats. The contractile function of the smooth muscle was assessed by measuring isometric force of isolated rat distal colon rings. We showed that both high extracellular K(+) (40 mmol/L) and ACh (5 mumol/L) evoked striking contraction of the smooth muscle. The contractile responses were almost abolished by removal of extracellular Ca(2+) with ethylene glycol-bis(2-aminoethylether)-N,N,N',N' tetraacetic acid (EGTA), suggesting a critical contribution of extracellular source of Ca(2+) to the contraction. Verapamil (5 mumol/L), an L-type VOCC blocker, significantly attenuated, but didn't completely eliminate the high K(+)- and ACh-induced contraction (74% and 41% for high K(+) and ACh, respectively), indicating that additional channels might be involved in the contractile mechanism. Furthermore, ACh only induced transient contractions in the absence of extracellular Ca(2+). Readmission of Ca(2+) into the extracellular compartment resulted in a significant and sustained increase in the tension of the smooth muscle. This response was not affected by verapamil (5 mumol/L) and Cd(2+) (5 mumol/L), both of which efficiently block VOCC at the doses. However, La(3+), a known inhibitor of SOCC, significantly suppressed the Ca(2+) readdition-induced contraction in a dose-dependent manner. On the basis of these results, we conclude that contraction of smooth muscle in the distal colon is regulated by multiple Ca(2+) channels. In addition to VOCC-mediated Ca(2+) influx, SOCC-mediated CCE participates in agonist-induced contractile response of distal colon smooth muscle in rats.
Acetylcholine ; physiology ; Animals ; Calcium ; metabolism ; Calcium Channels ; physiology ; Colon ; physiology ; Female ; Male ; Muscle Contraction ; physiology ; Muscle, Smooth ; physiology ; Myocytes, Smooth Muscle ; physiology ; Rats ; Rats, Sprague-Dawley ; Verapamil ; pharmacology

OBJECTIVETo clarify the genetic characteristics of N protein coding region of HRSV isolates from Beijing and GenBank downloaded sequences.

METHODSReverse transciption polymerase chain reaction (RT-PCR) was performed to amplify the N protein gene of 2 A and 2 B subgroups HRSV isolates from Beijing in the year 2004. The RT-PCR products were sequenced for N protein coding region. The sequences of N protein coding region of 4 Beijing isolates and those downloaded from GenBank were compared and analyzed.

RESULTSThe differences in number of nucleotide and deduced amino acid between 2 A Beijing 2004 isolates and prototype strain Long were 36-40 (3.1%-3.4%) and 4 (1.0%). The differences in number of nucleotide and deduced amino acid between 2 B Beijing 2004 isolates and prototype strain CH18537 were 17 (1.4%) and 1 (0.3%). The differences in number of nucleotide and deduced amino acid were 3-172 (0.25%-14.63%) and 0-18 (0-4.6%) respectively between 4 Beijing 2004 isolates and GenBank sequences.

CONCLUSIONN gene is the highly conservative gene in the HRSV genome. The variation between A and B subgroups were widely distributed in the entire gene of N protein, while the variation within the A or B subgroups HRSV was considerably lower.

Humans ; Molecular Sequence Data ; Nucleocapsid Proteins ; chemistry ; genetics ; Phylogeny ; Respiratory Syncytial Virus Infections ; virology ; Respiratory Syncytial Virus, Human ; chemistry ; classification ; genetics ; isolation & purification ; Sequence Homology, Amino Acid

OBJECTIVETo investigate the infection status and epidemiological characteristics of influenza virus and respiratory syncytial virus (RSV) in influenza-like illness (ILI) of children ( ≤ 14 years) in Wuhan area from 2008 to 2012.

METHODSA total of 2854 cases of ILI patients ( ≤ 14 years) in a hospital of Wuhan were recruited in the study from July 2008 to June 2012. The sample of pharyngeal swab was collected from each patient, to extract the virus nucleic acids. Real-time fluorescent quantitation reverse transcription PCR (RT-PCR) method was applied to detect the subtypes of influenza virus and RSV, and then analyzed the time and age characteristics.

RESULTSOut of the 2854 cases, 758 (26.6%) were positive for influenza virus,including 547 (19.2%) influenza A virus positive samples and 211 (7.4%) influenza B virus positive samples. Usually, there were two peaks present in the annual curve of influenza virus, namely summer peak and winter/spring peak. The positive rate of influenza virus in 6-14 years old children (48.0%, 275/573) was significantly higher than that in 3-5 years old children (26.6%, 213/801) and that under 3 years old children (18.3%, 270/1480). The difference showed statistical significance (χ(2) = 187.432, P < 0.01). A total of 219 (7.7%) cases were positive for RSV,including 108 RSV-A positive samples and 112 RSV-B positive samples (1 co-infection). The epidemic of RSV showed an obvious seasonal pattern with peaks in autumn,winter and spring,which accounted for 96.8% (212/219) of all the cases; however, the annual incidence of RSV fluctuated greatly. The predominant subtype shifted every 2 years. RSV-B predominated during September 2008 and May 2009, December 2009 and March 2010, accounting for 76.6% (36/47) and 96.9% (62/64) respectively. RSV-A predominated during November 2010 and March 2011, September 2011 and April 2012, accounting for 92.5% (37/40) and 100.0% (48/48) respectively. With the increase of the age, the positive rate of RSV-A and RSV-B decreased gradually (RSV-A: χ(2) = 36.223, P < 0.01; RSV-B: χ(2) = 36.281, P < 0.01). The positive rates of RSV-A in children < 1,1,2,3,4,5-9 and 10-14 years old were 7.0% (26/373), 5.9% (39/662), 4.0% (18/445), 3.2% (13/406), 1.3% (3/236), 1.4% (7/517) and 0.9% (2/215) respectively; while, the positive rates of RSV-B in each age group were 6.4% (24/373), 6.0% (40/662), 4.5% (20/445), 4.4% (18/406), 1.3% (3/236), 1.0% (5/517) and 0.9% (2/215) respectively. The children aged 0-3 years old were more susceptible for RSV infection,accounting for 90.0% (197/219) of the total positive samples. During the outbreak of influenza A H1N1 in November 2009, the positive rate of RSW was 3.0% (3/100), lower than that in the same month of 2008, 2010 and 2011,which were separately 18.2% (6/33), 10.8% (10/93) and 10.0% (4/40). The difference showed statistical significance (χ(2) = 8.450, P < 0.05). During the outbreak of influenza A (H1N1) in January 2011,the positive rate of RSV was 5.7% (3/53), lower than those in the same month of 2009, 2010 and 2012, which was separately 21.7% (5/23), 28.6% (22/77) and 16.0% (8/50). The difference showed statistical significance (χ(2) = 11.233,P < 0.05). During the period of less influenza happened in September 2011, the RSV positive rate was 25.0% (10/40), higher than those in the same month of 2008, 2009 and 2010, which was separately 11.4% (4/35), 1.7% (2/118) and 0.0% (0/109). The difference showed statistical significance (χ(2) = 32.521, P < 0.01).

CONCLUSIONBoth influenza virus and RSV were important etiological agents of ILI of children in Wuhan. The characteristics of seasonal and age distributions of the two viruses were notably different; meanwhile, a certain inhibitional effect of influenza virus on RSV could be observed.

Adolescent ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Influenza, Human ; epidemiology ; Male ; Orthomyxoviridae ; classification ; isolation & purification ; Respiratory Syncytial Virus Infections ; epidemiology ; Respiratory Syncytial Viruses ; classification ; isolation & purification