Animals ; Chronic Disease ; Heart Failure ; drug therapy ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; adverse effects ; therapeutic use

Adult ; Altitude ; Female ; Heart ; physiology ; Humans ; Male ; Occupational Health ; Railroads ; Tibet

Chronic hepatitis B (CHB) is a major cause of liver-related morbidity and mortality. Functional cure of CHB, defined as sustainable hepatitis B surface antigen (HBsAg) seroclearance, is associated with improved clinical outcomes. However, functional cure is rarely attainable by current treatment modalities. RNA interference (RNAi) by small-interfering RNA (siRNA) and anti-sense oligonucleotide (ASO) has been studied as a novel treatment strategy for CHB. RNAi targets post-transcriptional messenger RNAs and pregenomic RNAs to reduce hepatitis B virus (HBV) antigen production and viral replication. By reducing viral antigens, host immune reconstitution against HBV may also be attained. Phase I/II trials on siRNAs have demonstrated them to be safe and well-tolerated. siRNA is effective when given in monthly doses with different total number of doses according to different trial design, and can lead to sustainable dose-dependent mean HBsAg reduction by 2–2.5 log. Incidences of HBsAg seroclearance after siRNA therapy have also been reported. ASOs have also been studied in early phase trials, and a phase Ib study using frequent dosing regimen within 4 weeks could achieve similar HBsAg reduction of 2 log from baseline. Given the established efficacy and safety of nucleos(t) ide analogues (NAs), future RNAi regimens will likely include NA backbone. While the current evidence on RNAi appears promising, it remains undetermined whether the potent HBsAg reduction by RNAi can result in a high rate of HBsAg seroclearance with durability. Data on RNAi from phase IIb/III trials are keenly anticipated.

Objective To develop a multiplex PCR-based reverse line blot(mPCR/RLB) hybridization assay to detect,simultaneously,seven genes encoding AR-erm(A/TR),erm(B),mef(A/ E),tet(M),tet(O),aphA-3,aad-6 and two AR-related genes,int-Tn and mreA in group B streptococcus.Methods Nine pairs of specific primers and Oligonucleotide probes targeting erm(A/TR), erm(B),mef(A/E),tet(M),tet(O),aphA-3,aad-6 int-Tn and mreA respectively were modified according to former studies or designed in this study.The primers and probes were labeled with biotin and amino,respectively.The nine genes were amplified simultaneously in the same tube.PCR product hybridized with the probes labeled in the BiodyneC nylon membrane to detect the nine genes.To detect the sensitivity and specificity of the method developed,PCR with single pair of primer targeting each gene were tested in 318 isolates tested and the results were compared with the one abtained by RLB.Results The nine resistance-related genes could be successfully detected by mPCR/RLB assay developed in this study.Based on sequencing,21 of 22 isolates with mef had mef(E)and eight of 353 with int-Tn had an atypical sequence.Except for the above 29 genes,all the others corresponded well with the results obtained by single pair primer PCR.Conclusion The mPCR/RLB assay developed in this study is simple,rapid and suitable for surveillance of antibiotic resistance in GBS.

Objective To explore the semitivity of ovarian cancer cell line SKOV3 to paclitaxel,oroteasome inhibitors,bortezomib,and their combination.Methods The methyl thiazolyl tetrazolitim (MTT)assay was applied to examine the cell viability after treatment.The annexin V-propidium iodide apoptosis detection kit was used to determine the apoptosis rate of different groups.Western blot assay was used to evaluate the expression levels of phosphorylated protein kinase B(AKT)and glycogen synthase kinase-3 beta(GSK-3β).Results In MTT assay,the cell viability ratios of the combination group at serial time points from 12,24,36,48 and 72 hours Were(65.2±5.8)%,(58.3±14.4)%,(35.3±5.0)%,(19.2±1.5)%,and(11.4 ±2.5)%,which were significantly lower than those of the paclitaxel group (P<0.05).After arug treatments,apoptosis rates of paclitaxel group,bortezomib group and the combination group were (14.7±0.5)%,(15.1±0.8)%and(20.5±0.7)%respectively.The rate of the combination group was significantly higher than that of non-treated group and paclitaxel group(P<0.05).Western blot assay showed the changes in expression levels of phosphorylated AKT and GSK-3β,which were decreased significantly after paclitaxd and bortezomib combination treatment [(3.2±0.8)%,(19.3±0.4)%;P<0.05].Conclusions The lethal effect of paclitaxel on tumor cells could be increased significantly by its combination with proteasome inhibitors,bertezomib.The AKT/GSK-3β signaling pathway plays an important role in the molecular mechanism of the combination treatment.

Objective To explore the sensitivity and the molecular mechanism of cisplatinresistance ovarian cancer cell line C13 to proteasome inhibitors and the combination with cisplatin. Methods After different treatments, methyl thiazolyl tetrazolium (MTT) assay was applied to examine the cell viability, annexin-V/propidium iodide(PI) apoptosis detection kit was used to determine the apoptosis rate of different groups, western blot assay was introduced to evaluate the expression levels of Fas-associated death domain-like interleukin-1 beta converting enzyme inhibitory protein (cFLIPs), and the activity of caspase-8 was examined. Results MTT assay shown that the cell viability ratios of combination group at serial time points from 12, 24, 36, 48, 60, 72 hours were ( 56.0 ± 8.4 ) %, (44.7 ± 7.3 ) %, ( 33.7 ±11.2) %, (27.6 ± 8.0) %, (27. 6 ± 7.6) % and (28.1 ± 2.4) %, which were much lower than those of cisplatin group (P <0.05). After treated for 24 hours, apoptosis rates of cisplatin group, bortezomib group and combination group were ( 16.7 ± 1.7) %, (23.4 ± 2.1 ) % and (26.9 ± 1.6) %, respectively. The rate of combination group was much higher than that of non-treated group and that of cisplatin group or bortezomib group ( P < 0.05 ). Western blot assay showed the changes of expression levels of cFLIPs, which were downregulated seriously after cisplatin, bortezomib or combination treatment [ (43.2 ± 2.3 )% vs( 75.7 ± 3.0)%vs (67.9 ± 2.1 ) %, P < 0.05 ]. The caspase-8 activity of combination group was (5.6 ± 1.6) folds than that of non-treated group, which was higher than those of other two groups [ ( 2.3 ± 1.0) and (4.2 ± 0.9 ) folds,P < 0.05 ]. Conclusions The tumor cell lethal effect of cisplatin could be increase significantly by the combination application of proteasome inhibitors, bortezomib. And the cFLIPs/caspase-8 signaling pathway may be play an important role in the molecular mechanism of the combination treatment.

OBJECTIVETo observe the preventive protection of Kangdu Bufei Decoction (KBD) on acute severe respiratory syndrome (SARS) in medical personnel of Hong Kong at the epidemic period.

METHODSAt the epidemic period of SARS in Hong Kong, there were 2,601 medical staffs administered with KBD distributed by the Center. It was confirmed that 1,063 persons had taken it for successive two weeks according to the request and returned the effective questionnaire, they were regarded as the TCM group. The control group was consisted of 15,374 subjects who didn't take Chinese herbal medicine. Contents of the questionnaire including the condition of testee in terms of quality of life (QOL), changes of influenza-like symptoms and Warm disease symptoms. Serum immunological examination had been conducted in 37 of the persons in the TCM group.

RESULTSNo one in the TCM group got SARS infection while in the control group, 64 (0.4%) had got. Self-control before and after treatment examination showed that significant improvement appeared in the TCM in aspects of influenza-like and Warm disease symptoms and QOL. The results of serum immunological examination showed that after administration of KBD, the immunity of organism was improved and elevated.

CONCLUSIONKBD could prevent the occurrence of SARS, it is possibly realized through improving symptoms, elevating QOL and enhancing immunity of organism.

Adjuvants, Immunologic ; therapeutic use ; Adult ; Cross Infection ; prevention & control ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Hong Kong ; Humans ; Infectious Disease Transmission, Patient-to-Professional ; prevention & control ; Male ; Middle Aged ; Phytotherapy ; Severe Acute Respiratory Syndrome ; prevention & control ; transmission ; Surveys and Questionnaires

Objective To summarize the characteristics and associated malformation of fetal isolate cleft palate in prenatal ultrasonography, and analyze the reason of ultrasound misdiagnosis and missed diagnosis in isolate fetal cleft palate prenatally. Methods Systemic screening was performed with two-and three-dimensional ultrasonography in 3 576 cases. The fetal lip and plane were observed especially in nasolabial coronary plane, axial plane through maxilla, median sagittal plane, oblique coronal plane through oral cleft. Meanwhile the accompanied deformity were also screened. And prenatal ultrasound results were compared with postpartum ifndings. Results Eleven in 3 598 cases (0.31%, 11/3 598) were diagnosed as fetal isolate cleft palate by prenatal ultrasonography. The ultrasonic characteristics of isolate cleft palate were:(1) One case ofⅠ° cleft palate, the ultrasonic manifestations:in median sagittal plane, the hyperecho line of median palatine suture was disappeared, and the mucous membranes above and below it were complete;in oblique coronal plane of soft palate through oral cleft, the soft palate was complete and continuous;uvula couldn′t be displayed. (2) Three cases ofⅡ° cleft palate, the ultrasonic manifestations:in median sagittal plane though jaw, the hyperecho line of median palatine suture was shorter;the latter half and the midline of soft palate was disappeared;in both paramedian sagittal plane, the arc-shaped hyperecho line of median palatine suture were displayed;and longer than the hyperecho of midline of palate;in oblique coronal plane of hard palate through oral cleft, the ifrst half hyperecho line of hard palate was continuous, the middle of the latter half hyperecho line was interrupted;in oblique coronal plane of soft palate through oral cleft, the midline of soft palate was interrupted. 3D volume data analysis showed that the ifrst half hard palate was complete, the midline of the latter half hard palate and soft palate was interrupted. (3) Seven cases ofⅢ° cleft palate, the ultrasonic manifestations:in median sagittal plane, the hyperecho line of median palatine suture was disappeared;in oblique coronal plane of hard palate through oral cleft, the middle part echoes of the hard palate was interrupted;in oblique coronal plane of soft palate through oral cleft, the midline of soft palate was interrupted;oral and nasal cavity were communicated;the hyperecho of the vomer at the lower edge of the nasal septum could be displayed though oral cavity. 3D volume data analysis showed that hard palate and soft palate were interrupted. The hyperecho of the vomer at the lower edge of the nasal septum could be displayed clearly though oral cavity. Prenatal ultrasonic diagnosis was conifrmed by postpartum ifndings. And 2 cases were misdiagnosed (0.06%, 2/3 598), 1 case was missed diagnosed (8.33%, 1/12). The incidence of isolate fetal cleft palate was 0.33%(12/3 598). In 12 cases of isolate fetal cleft palate, 11 cases were accompanied with other fetal deformities, including central nervous system malformations (6/12), small jaw (6/12), urinary tract malformation (5/12), hydramnios (2/12), and absence of amniotic lfuid (1/12). Conclusions Fetal secondary palate should be routinely included in the prenatal screening. When secondary palate planes weresuccessfully demonstrated, the isolate cleft palate could be detected. Prenatal diagnosis of the isolate cleft palate is contributive to prenatal counseling and risk assessment.

AIMTo evaluate the effects of beta3-adrenergic receptors (ARs) agonist (BRL-37344) on beating rate and cAMP levels and investigate the influence on the chronotropic action of beta3-ARs in cultured cardiomyocyte of rats.

METHODSCultured neonatal rat cardiomyocytes were divided randomly into eight groups, control group, ISO group, Nadolol + ISO group, BRL group, PIX + BRL group, L-NAME + BRL group, Nadolol + BRL group and Bupranolol + BRL group. Beating rate of culture neonatal rat cardiomyocytes was observed and cAMP measured by enzyme immunoassay kit. Expression levels of beta3-ARs mRNA in cardiomyocytes was evaluated by reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSISO, nonspecific beta-ARs agonist increased beating rate and intracellular cAMP production, antagonized by Nadolol, beta1, beta2-ARs antagonist. BRL37344 decreased beating rate and intracellular cAMP levels. FPTX, Gi protein inhibitor and Bupranolol, nonspecific beta-ARs antagonist totally blocked the effect and L-NAME, nitric oxide synthase (NOS) inhibitor partly blocked the effect, but Nadolol did not. There was the expression of beta3-AR mRNA in cardiomyocytes by RT-PCR.

CONCLUSIONSBeta3-ARs showed in cardiomyocytes and produced negative chronotropic effects. beta1, beta2-ARs antagonist did not affect it. It suggested beta3-ARs signal transduction was related with G1 protein. The negative inotropic effect of beta3-ARs stimulation was mediated by activation of the NOS pathway.

Adrenergic beta-Agonists ; pharmacology ; Animals ; Animals, Newborn ; Cells, Cultured ; Cyclic AMP ; metabolism ; Ethanolamines ; pharmacology ; Myocytes, Cardiac ; drug effects ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar ; Receptors, Adrenergic, beta-3 ; metabolism

Objective To compare the difference on health statistical survey system between China and United States of American.Methods Four aspects in statistical agencies,legislation,survey items and health statistics information were compared.Results The system in China has its own characteristics,but it also faced with many challenges,including the relatively slow transfer and exchange of statistical information,the lack of legislation on data dissemination and sharing,the insufficient diversification of survey items and survey content.Conclusion The statistics information center of Ministry of Health should strengthen the management and coordination to ensure the data collection timely and accurately.The policies should be strengthened to protect data privacy and improve data dissemination.