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Growth hormone deficiency (GHD) has become a serious healthcare burden, and presents a huge impact on the physical and mental health of patients. Here, we developed an actively separated microneedle patch (PAA/NaHCO3-Silk MN) based on silk protein for sustained release of recombinant human growth hormone (rhGH). Silk protein, as a friendly carrier material for proteins, could be constructed in mild full-water conditions and ensure the activity of rhGH. After manually pressing PAA/NaHCO3-Silk MN patch to skin for 1 min, active separation is achieved by absorbing the interstitial fluid (ISF) to trigger HCO3 ‒ in the active backing layer to produce carbon dioxide gas (CO2). In rats, the MN patch could maintain the sustained release of rhGH for more than 7 days, and produce similar effects as daily subcutaneous (S.C.) injections of rhGH in promoting height and weight with well tolerated. Moreover, the PAA/NaHCO3-Silk MN patch with the potential of painless self-administration, does not require cold chain transportation and storage possess great economic benefits. Overall, the PAA/NaHCO3-Silk MN patch can significantly improve patient compliance and increase the availability of drugs, meet current unmet clinical needs, improve clinical treatment effects of GHD patients.
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Liver is the central hub regulating energy metabolism during feeding-fasting transition. Evidence suggests that fasting and refeeding induce dynamic changes in liver size, but the underlying mechanisms remain unclear. Yes-associated protein (YAP) is a key regulator of organ size. This study aims to explore the role of YAP in fasting- and refeeding-induced changes in liver size. Here, fasting significantly reduced liver size, which was recovered to the normal level after refeeding. Moreover, hepatocyte size was decreased and hepatocyte proliferation was inhibited after fasting. Conversely, refeeding promoted hepatocyte enlargement and proliferation compared to fasted state. Mechanistically, fasting or refeeding regulated the expression of YAP and its downstream targets, as well as the proliferation-related protein cyclin D1 (CCND1). Furthermore, fasting significantly reduced the liver size in AAV-control mice, which was mitigated in AAV Yap (5SA) mice. Yap overexpression also prevented the effect of fasting on hepatocyte size and proliferation. Besides, the recovery of liver size after refeeding was delayed in AAV Yap shRNA mice. Yap knockdown attenuated refeeding-induced hepatocyte enlargement and proliferation. In summary, this study demonstrated that YAP plays an important role in dynamic changes of liver size during fasting-refeeding transition, which provides new evidence for YAP in regulating liver size under energy stress.
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Objective:To investigate the immunoregulatory effects of Glycyrrhiza uralensis ethanol extract(GUEE) on the maturation of dendritic cells (DCs) and the adjuvant effect of GUEE on OVA in na?ve BALB/c mice and an ovalbumin (OVA)-induced asthma mouse model. Methods:GUEE was prepared, and the effects of different concentrations of GUEE on the maturation of DCs and the secreted cytokines as well as the effects of GUEE on bacterial lipopolysaccharide (LPS)-induced DC maturation were examined in vitro. The effect of GUEE on the morphology of mouse bone marrow derived DCs was observed using microscopy. Molecular expression levels on the surface of DCs were detected using flow cytometry. The levels of interleukin-1β (IL-1β), IL-6, IL-12, and tumor necrosis factor-α (TNF-α) in the supernatant of DCs cultures were measured by enzyme-linked immunosorbent assay (ELISA). The maturation status of DCs was detected by flow cytometry by injecting different concentrations of GUEE into the paws of mice and isolating the draining lymph nodes 24 h later. The naive BALB/c mice were co-immunized with OVA, and the changes in regulatory T cells (Treg) were detected by flow cytometry. An OVA-protein-induced mouse asthma model was established to investigate whether GUEE as a tolerogenic adjuvant has an antigen-specific therapeutic effect on asthmatic mice. Pulmonary pathological changes were analyzed by hematoxylin-eosin staining (HE) and PAS staining. OVA-specific antibodies in serum and the frequencies of Tregs, CD4 + IFN-γ + and CD4 + IL-4 + T cells in the spleen were detected by ELISA and flow cytometry, respectively. Results:GUEE suppressed DCs maturation induced by LPS both in vitro and in vivo (all P<0.05), and reduced proinflammatory cytokine production, including IL-1β, IL-6, IL-12 and TNF-α in the absence or presence of LPS (all P<0.05). Moreover, co-immunization with OVA and GUEE increased the amount of Tregs in na?ve BALB/c mice ( P<0.05). In OVA-induced asthmatic mice, OVA and GUEE co-immunization and GUEE alone treatment substantially ameliorated the inflammation of lung tissues, decreased the levels of IgG 1 and the amount of CD4 + IL-4 + T cells, and increased the amount of Tregs (all P<0.05). Conclusions:GUEE alone or as the tolerogenic adjuvant can ameliorate allergic diseases through inhibition of DC maturation and type 2 helper T cell responses and induction of Tregs.
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Objective:To investigate the value of 18F-fluorodeoxyglucose (FDG) PET imaging in evaluating the 18F-FDG influx rate of lungs and its relationship with parameters of pulmonary hemodynamics in patients with pulmonary arterial hypertension related to congenital heart disease (PAH-CHD). Methods:From January 2018 to June 2019, a total of 16 PAH-CHD patients (6 males, 10 females, age (29.2±10.6) years) and 22 health controls who received physical examinations (8 males, 14 females, age (45.4±3.8) years) in Fuwai Hospital were respectively enrolled. All cases underwent dynamic 18F-FDG PET imaging for whole lung 18F-FDG influx rate (presented as Ki). Right heart catheterization was performed to evaluate pulmonary hemodynamic parameters such as pulmonary vascular resistance (PVR), mean pulmonary vascular pressure (mPAP) in PAH-CHD patients after imaging within one week. Independent-sample t test was used to compare Ki of 2 groups, and Pearson correlation analysis was used to analyze the relationship between Ki and PVR, mPAP in PAH-CHD patients. Results:Ki of the lungs was significantly higher in PAH-CHD patients than that in controls ((0.000 6±0.000 3) vs (0.000 4±0.000 3) ml·g -1·min -1; t=2.15, P=0.038). Ki was not correlated with PVR ((10.86±4.45) Wood units) or mPAP ((69.75±18.93) mmHg; 1 mmHg=0.133 kPa) in PAH-CHD patients ( r values: 0.202 and 0.006, both P>0.05). Conclusions:Pulmonary vascular remodeling can lead the increasing lung 18F-FDG uptake in patients with PAH-CHD. 18F-FDG PET may have the ability in monitoring and evaluating pulmonary vascular remodeling in PAH-CHD.
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Background/Aims@#Studies have shown that nucleos(t)ide analogue (NA) treatment can reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients, but it is unclear which NA is most effective. We performed a meta-analysis and systematic review comparing the efficacies of NAs in CHB patients. @*Methods@#We searched literature databases for randomized controlled trials (RCTs) and observational studies that analyzed the hepatic biochemical response, virological response, seroconversion rate, drug resistance rate, and HCC incidence rate in CHB patients treated with NAs. Meta-analyses were performed with RevMan and Stata/SE software. @*Results@#Twelve cohort studies and one RCT were selected, in which entecavir (ETV), lamivudine (LAM), telbivudine (LdT), and/or tenofovir disoproxil fumarate (TDF) were evaluated in CHB patients. The meta-analysis showed that ETV was superior to LAM with regard to the HCC incidence (p<0.001), biochemical response (p=0.001), virological response (p=0.02), and drug resistance (p<0.001), and ETV was superior to LdT with regard to the virological response (p<0.001) and drug resistance (p<0.001). We found no significant difference between ETV and TDF with regard to the HCC incidence (p=0.08), biochemical response (p=0.39), virological response (p=0.31), serological conversion (p=0.38), or drug resistance (p=0.95). NA-treated patients with pre-existing cirrhosis had a 5.49 times greater incidence of HCC than those without cirrhosis (p<0.001). @*Conclusions@#ETV or TDF should be used for long-term first-line monotherapy in CHB patients according to the current guidelines. Standardized protocols are needed for future studies of ETV and TDF to facilitate conclusive comparisons. Patients with cirrhosis are at significantly elevated risk for HCC, despite the benefits of NA treatment.
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Objective:To establish SPECT quantitative method for assessment of right ventricular myocardial blood flow (MBF) and investigate the relationship between right ventricular MBF and pulmonary hemodynamics in patients with pulmonary arterial hypertension.Methods:From January 2018 to June 2019, 14 patients (13 females, 1 male; age: (30.9±13.5) years) in Fuwai Hospital with pulmonary arterial hypertension related to congenital heart disease (PAH-CHD), whose right ventricular function were preserved, were retrospectively analyzed in this study. All subjects underwent dynamic SPECT myocardial perfusion imaging using cadmium-zine-telluride (CZT) SPECT. Full physical correction was applied for imaging reconstruction. One-tissue two compartmental model was used for kinetic analysis and the spill-over effect from right ventricular blood pool to right ventricular myocardium was considered into the correction, thus right ventricular MBF and left ventricular MBF was calculated. Right heart catheterization was performed within one week after SPECT imaging to evaluate the pulmonary hemodynamic parameters, and the right ventricular end-diastolic dimension (EDD) was measured by transthoracic echocardiography. Correlations between the MBF and other parameters were analyzed with Pearson correlation analysis.Results:The right ventricular MBF was (0.70±0.19) ml·min -1·g -1, which was significantly correlated with mean pulmonary artery pressure ((68.64±18.18) mmHg (1 mmHg=0.133 kPa); r=0.716, P<0.05) and pulmonary vascular resistance ((14.10±7.81) Wood units; r=0.768, P<0.05). The right ventricular MBF was also significantly correlated with right ventricular EDD ((32.00±7.75) mm; r=-0.624, P<0.05). Meanwhile, there was no significant relationship between left ventricular MBF and hemodynamic parameters ( r values: from -0.350 to 0.310, all P>0.05). Conclusions:A method using SPECT to quantitively measure right ventricular MBF in patients with PAH-CHD is preliminarily established. Right ventricular MBF is increased with the increased pulmonary arterial pressure and pulmonary vascular resistance in patients with PAH-CHD.
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Objective@#To investigate the impact of comprehensive geriatric assessment(CGA)on treatment outcomes of chronic heart failure(CHF)complicated with emotional disorders in the elderly.@*Methods@#A total of 216 CHF patients with emotional disorders at Henan Provincial People’s Hospital were recruited from September 2017 to March 2019 and were randomly divided into a CGA group and a control group with 108 cases in each group.The control group was given standard drug treatment and psychological counseling, whereas individualized treatment was given to participants in the CGA group in compliance with CGA guidelines.The clinical effects after intervention for 8 weeks in the two groups were examined, using measures such as Hamilton Depression Rating Scale for Depression(HAMD)-24, Hamilton Anxiety Scale(HAMA)-14, amino-terminal pro-brain natriuretic peptide(NT-proBNP), the 6 minute walk test(6MWT)and left ventricular ejection fraction(LVEF). The changes of cognitive status, nutritional status, fall risk and other indicators in patients were comprehensively assessed and statistically analyzed.@*Results@#Compared with pre-treatment data, 8 weeks of treatment for both the control group and the CGA group resulted in decreased HAMD-24 scores(Control group: 31.78±9.08, 23.69±10.16; CGA group: 32.09±8.98, 15.35±7.91; P<0.05), HAMA-14 scores(Control group: 22.38±7.09, 15.28±6.54; CGA group: 21.99±8.12, 10.48±6.82; P<0.05)and NT-proBNP levels[Control group: (4672±392)ng/L, (3279±282)ng/L; CGA group: (4861±378)ng/L, (2387±215)ng/L; P<0.05], and increased LVEF(%)[Control group(34.5±6.2)%, (39.8±7.5)%; CGA group(35.1±3.9)%, (42.5±6.1)%; P<0.05]and 6MWT scores[Control group(298±79±7.5)m, (358±102)m; CGA group(305±98)m, (402±178)m; P<0.05], with more marked changes in all the measures in the CGA group than in the control group(P<0.05).@*Conclusions@#The early application of CGA can improve the condition and prognosis in elderly heart failure patients complicated with emotional disorders.
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Objective To investigate the impact of comprehensive geriatric assessment(CGA)on treatment outcomes of chronic heart failure(CHF)complicated with emotional disorders in the elderly.Methods A total of 216 CHF patients with emotional disorders at Henan Provincial People's Hospital were recruited from September 2017 to March 2019 and were randomly divided into a CGA group and a control group with 108 cases in each group.The control group was given standard drug treatment and psychological counseling,whereas individualized treatment was given to participants in the CGA group in compliance with CGA guidelines.The clinical effects after intervention for 8 weeks in the two groups were examined,using measures such as Hamilton Depression Rating Scale for Depression(HAMD)-24,Hamilton Anxiety Scale (HAMA)-14,amino-terminal pro-brain natriuretic peptide(NT-proBNP),the 6 minute walk test(6MWT)and left ventricular ejection fraction(LVEF).The changes of cognitive status,nutritional status,fall risk and other indicators in patients were comprehensively assessed and statistically analyzed.Results Compared with pre-treatment data,8 weeks of treatment for both the control group and the CGA group resulted in decreased HAMD-24 scores(Control group:31.78± 9.08,23.69± 10.16;CGA group:32.09 ± 8.98,15.35 ± 7.91;P＜0.05),HAMA-14 scores(Control group:22.38±7.09,15.28±6.54;CGA group:21.99±8.12,10.48±6.82;P＜0.05)and NT-proBNP levels[Control group:(4672±392)ng/L,(3279±282)ng/L;CGA group:(4861 ± 378) ng/L,(2387 ± 215) ng/L;P ＜ 0.05],and increased LVEF (％) [Control group(34.5±6.2)％,(39.8 ± 7.5)％;CGA group(35.1 ± 3.9)％,(42.5 ± 6.1)％;P＜0.05]and 6MWT scores[Control group (298 ± 79 ± 7.5) m,(358 ± 102) m;CGA group (305 ± 98) m,(402±178) m;P＜0.05],with more marked changes in all the measures in the CGA group than in the control group(P＜0.05).Conclusions The early application of CGA can improve the condition and prognosis in elderly heart failure patients complicated with emotional disorders.
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Zinc levels are high in pancreatic β-cells, and zinc is involved in the synthesis, processing and secretion of insulin in these cells. However, precisely how cellular zinc homeostasis is regulated in pancreatic β-cells is poorly understood. By screening the expression of 14 Slc39a metal importer family member genes, we found that the zinc transporter Slc39a5 is significantly down-regulated in pancreatic β-cells in diabetic db/db mice, obese ob/ob mice and high-fat diet-fed mice. Moreover, β-cell-specific Slc39a5 knockout mice have impaired insulin secretion. In addition, Slc39a5-deficient pancreatic islets have reduced glucose tolerance accompanied by reduced expression of Pgc-1α and its downstream target gene Glut2. The down-regulation of Glut2 in Slc39a5-deficient islets was rescued using agonists of Sirt1, Pgc-1α and Ppar-γ. At the mechanistic level, we found that Slc39a5-mediated zinc influx induces Glut2 expression via Sirt1-mediated Pgc-1α activation. These findings suggest that Slc39a5 may serve as a possible therapeutic target for diabetes-related conditions.
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OBJECTIVE:To evaluate the effectiveness and safety of repaglinide combined with metformin versus glimepiride combined with metformin in the treatment of type 2 diabetes mellitus (T2DM),and to provide evidence-based reference for the clinic. METHODS:Retrieved from CJFD, VIP, Wanfang database, PubMed, Embase, Medline and Cochrane Library, randomized controlled trials (RCTs) about therapeutic efficacy (HbA1c, FPG, 2 hPG) and safety (the incidence of ADR,hypoglycemia and gastrointestinal reaction)of repaglinide combined with metformin(trial group)versus glimepiride combined with metformin(control group)in the treatment of T2DM were collected. Meta-analysis was performed by using Rev Man 5.2 statistical software after data extraction and quality evaluation with Cochrane systematic evaluation manual. RESULTS:A total of 12 RCTs were included,involving 957 patients. Results of Meta-analysis showed that the decrease of 2 hPG in trial group was significantly better than control group,with statistical significance [MD=-0.70,95％CI(-1.02,-0.38),P<0.001]. There was no statistical significance in the decrease of HbA1c [MD=0.00,95％CI(-0.24,0.25),P=0.98] or FPG [MD=0.10,95％CI(-0.17,0.36),P=0.47],the incidence of ADR [OR=0.54,95％CI(0.28,1.06),P=0.07],hypoglycemia [OR=0.52,95％CI(0.13,2.06),P=0.35] or gastrointestinal reactions [OR=0.60,95％CI(0.15,2.41),P=0.47] between 2 groups. CONCLUSIONS:Repaglinide combined with metformin is better than glimepiride combined with metformin in reducing 2 hPG,but both of them have similar safety.
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Objective To investigate the effects of crude extract of Capparis spinosa L. fruit alka-loids (CSFA) on the maturation of murine bone marrow-derived dendritic cells (DCs). Methods CSFA was prepared and the contents were determined by high performance liquid chromatography. DCs were trea-ted with different doses (1, 2, 3 mg/ml) of CSFA. The viability of DCs, the expression of surface mole-cules and the ability of phagocytosis were detected by flow cytometry. The secretion of cytokines was meas-ured by ELISA. Western blot assay was performed to analyze the activation of key molecules in mitogen-acti-vated protein kinases ( MAPK) and nuclear factor-kappa B ( NF-κB) signaling pathways. Results The re-sults showed that CSFA alone had no significant influence on the expression of surface molecules and cyto-kines in DCs. However, it significantly decreased the expression of CD40, CD80, CD86 and MHC Ⅱ as well as the secretion of IL-12p40 and TNF-αthat were induced by lipopolysaccharides (LPS), but increased IL-10 secretion and the ability of phagocytosis after treating DCs with both CSFA and LPS. Further, the phosphorylation of p38, extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) and the nuclear translocation of NF-κBp65 induced by LPS were inhibited by CSFA. Conclusion CSFA could inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines induced by LPS while in-creasing the secretion of the anti-inflammatory cytokine IL-10 and the ability of phagocytosis, which might in-volve MAPK and NF-κB signaling pathways. This study suggests that CSFA could be used as a potential im-munosuppressant.
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Objective@#To understand the histopathological and ultrastructural pathology changes of great gerbils in the Junggar Basin to Yersinia pestis infection.@*Methods@#Forty captured great gerbils from the Junggar Basin that tested negative for anti-F1 antibodies were infected. The Y. pestis strain 2504, isolated from a live great gerbil in the natural plague foci of the Junggar Basin in 2005 with a median lethal dose (LD50) of <10 CFU/ml, was used in this study. Forty great gerbils were divided into seven infection groups and were subcutaneously infected with 7.4×105, 7.4×106, 7.4×107, 7.4×108, 7.4×109, 7.4×1010, or 3.0×1011 CFU/ml of 2504. One milliliter of physiological saline was injected in the noninfected group as a control. We collected the liver, spleen, heart, and lung from all animals for histopathologic and ultrastructural pathology examination.@*Results@#Great gerbils in the 7.4×108-3.0×1011 CFU/ml groups did not survive and exhibited pathological changes and altered ultrastructural pathology. The liver tissue of infected great gerbils showed spotty necrosis and fatty degeneration, intranuclear canaliculi with increased hepatocytes, and uneven distribution of organelles. Additionally, reactive proliferation of lymphoid tissue in the spleen, blood sinusoid lacunae with neutrophil infiltration, and phagocytosed bacteria in phagocyte cells were observed. Myocardial fiber hypertrophy and interstitial indistinction, nuclear matrices decreased in cardiac myocytes, and loose arrangement of myogenic fibers in myocardial cells were also observed. Angiectasia, capillary congestion, and tissue necrosis were found in the lung. No significant difference in histopathological and ultrastructural pathology in the parenchymal organ was observed between the 7.4×105-7.4×107 CFU/ml groups and the 7.4×108-3.0×1011 CFU/ml groups, and no specific death caused by Y. pestis infection was apparent in the 7.4×105-7.4×107 CFU/ml groups.@*Conclusion@#Y. pestis infection altered tissue and ultrastructural pathology in the parenchyma apparatus of great gerbils. In particular, the liver and spleen appeared to be the primary site of Y. pestis infection in great gerbils.
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Objective@#To observe the dynamics of antibody response in great gerbils infected with Yersinia pestis in experiment.@*Method@#A total of 211 great gerbils were captured in the southern margin of plague natural focus of Junggar Basin of the Xinjiang Uygur Autonomous Region in 2011. Among them, there were 167 great gerbils without infection of Y. pestis and 44 great gerbils infected by Y.pestis. Y.pestis No. 2504 was employed for this experimental strain, which was strong toxic strain with negativity in the reduction experiment of nitrate. 35 great gerbils without the infection of Y. pestis were divided randomly and averagely into 7 groups including 6 experimental groups and 1 control group. Great gerbils in the 1st to 6th experimental groups were exposed first with 1 × 106-1 × 1011 CFU/ml of bacterial fluid with 10 times of gradient dilution; groin areas of great gerbils in the control group were injected subcutaneously with physiological saline; and the amount of infection was all 1 ml. 17 great gerbils infected with Y. pestis and the first detection of F1-antibody titer in 1∶256-1∶4 096 were grouped according to F1-antibody titer: group 1∶4 096 (n=4), group 1∶2 048 (n=4), group 1∶1 024 (n=3), group 1∶512 (n=3) and group 1∶256 (n=3); and blood in caudal regions was collected in asepsis for the detection of F1-antibody, with a total of 5 times. 9 great gerbils which were selected from the remaining great gerbils infected with Y. pestis and detected F1-antibody negative 2 times were exposed 1×106 CFU/ml of bacterial fluid for the second infection, with the amount of infection being 1 ml. Blood in caudal regions of great gerbils after the first and second infection were collected for the detection of plague F1-antibody on the 3rd, 5th, 7th, 15th, 30th, 60th, 90th and 120th day after infection. Declined regression models for great gerbils' antibodies were established with unary linear regression equation; declined change diagrams for the antibodies were drawn to observe the declined F1-antibody after great gerbils were exposed to Y. pestis.@*Results@#In great gerbils with the first infection of Y. pestis, antibodies were detected in the 1 × 106-1 × 108 CFU/ml of group on the 30th, 15th and 15th day, respectively; the positive rates of antibody were 1/4, 3/4 and 4/5, respectively; the group 1×107 and 1× 108 CFU/ml reached to the highest antibody titer with 1∶256 on the 120th day; antibodies were revealed in the group 1×109, 1×1010 and 1×1011 CFU/ml from the 5th to 7th day when the seroconversion of all antibodies was observed; group 1×1011 CFU/ml reached to the highest antibody titer on the 120th day with 1∶4 096. In the great gerbils with the second exposure to Y.pestis, positive antibodies were detected on the 3rd day with the positive rate being 2/9; and the highest antibody titer with 1∶2 048 was noted on the 90th day. Unary linear regression equation of declined F1 antibody of great gerbils was y=0.045x- 0.321 (F=115.40, P< 0.001), and the shortest duration for F1-antibody titer declining from 1∶4 096 to 0 was 140 d and the longest duration 200 d.@*Conclusion@#Great gerbils infected with the high concentration of Y. pestis fluid show shorter duration in producing F1-antibody, the antibody positive rate is also higher, and the highest antibody titer can reach 1∶4 096. The great gerbils could hold the plague F1 antibodies for a long time which was about 140 to 200 days from the highest titer.
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Objective To investigate the value of ADC and FA of diffusion tensor imaging(DTI)and T2 value of T2 mapping for assessing lumbar intervertebral disc degeneration.Methods 12 cases of healthy volunteers(8 males and 4 females),28 cases of patients with chronic low back pain(15 males and 13 females,19-70 years old)were performed lumbar spine MRI,DTI and T2 mapping to obtain ADC,FA and T2 value.Intervertebral discs were classified according to the Pfirrmann grading.The correlations of different degeneration grade with ADC,FA and T2 value were analyzed.The diagnostic value of ADC,FA and T2 values of lumbar intervertebral disc degeneration were compared. Results Both ADC value and T2 value were significantly negative correlated with lumbar intervertebral disc degeneratic Pfirrminn grading(r=-0.779,r=-0.708,P<0.001).FA value were positively correlated with Pfirrminn grading(r=0.474,P<0.001), the correlation was not closely.Conclusion DTI and T2 mapping can be effectively used to quantitatively evaluate the degeneration degree of lumbar intervertebral disc,the diagnostic value of ADC was the highest,followed by T2 ,and FA was the worst.
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Objective To observe the dynamics of F1 antibody and immunoglobulin M (IgM) in cats after vaccinated Yersinia pestis,to discuss the significance of detection of F1 antibody and IgM in surveillance of animal plague.Methods The 3 cats were vaccinated Yersinia pestis on their backs with muhipoint hypodermic injection and blood samples were collected via femoral vein on 3rd to 521st days after injection.F1 antibody was detected by sandwich Enzyme-linked immunosorbent assay (ELISA),and IgM of F1 antibody was determined with a capture antibody.Results After vaccinated Yersinia pestis for 3rd days,F1 antibody and IgM appeared slightly positive,with the titer of 1 ∶ 22.00 and 1 ∶ 20.33,respectively.The titer of F1 antibody increased to 1 ∶ 25.33 on the 4th day,and reached the peak of 1 ∶ 29.67 on the 97th day,kept 1 ∶ 25.33 on the 521st day.While the titer of IgM reached peak of 1 ∶ 212.00 on the 7th to 10th days,and decreased rapidly to below the positive standard on the 30th day.Conclusions Detection of F1 antibody in cats with plague by sandwich ELISA can trace plague prevalence in animals back to a long time,which may be applied for investigation of plague foci.A single serum sample can determine early animal plague with a capture antibody to detect IgM of F1 antibody in cat with the plague,and a single serum sample tested with the two methods at the same time for detection of F1 antibody and IgM can precisely verify the infection time of plague in animals for 3 to 7 days.
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<p><b>OBJECTIVE</b>To explore the spatial and temporal distributions of animal plague in Junggar Basin natural plague focus.</p><p><b>METHODS</b>Data regarding plague antibody (F1) in serum of Great Gerbil (Rhombomys opimus, R. opimus) which were collected from 2005 to 2012 in Junggar Basin and analyzed. The changing rates on the positivity of F1 that appeared spatially and temporally were also analyzed.</p><p><b>RESULTS</b>A total of 4 825 R. opimus serum samples were collected in 13 administrative regions in Junggar Basin.</p><p><b>RESULTS</b>showed that plague R. opimus existed in two areas-Gurbantonggut desert in the eastern-center and the clay desert of western Junggar Basin. However, in these two areas, the intensity of animal plague prevalence was different. In the former region where Yesinia pestis positive serum was detected from R. opimus, the detected rate of R. opimus was 8.39%. However, in the latter areas, the average positive rate was 1.56%. The changing trends of R. opimus plague prevalence were also varied annually. In the western Junggar Basin, the trend showed a slowly downward profile. The serum positive rate of R. opimus for Yesinia pestis decreased, from 7.59% in 2005 to 0.61% in 2008, and appeared as a resting state that none of the positive sample could be found since then. However, in the eastern-center Junggar Basin area-also named as Gurbantonggut desert which had been divided into 3 segments(western, central and eastern, according to related geographical characteristics), the changing trends of animal plague seemed quite complex. In the western segment, the animal plague had two epidemic peaks-in 2006 and 2010, with the interval of 4 years, with the higher peak of all the three geographic segments as 45.65% in 2010 and the positive serum of R. opimus for plague could be detected each year from 2006 to 2012. However, there were 3 epidemic peaks in the same period in the central and eastern segments. In the central segment, the peaks appeared in 2006, 2009 and 2011, with the intervals as 2.5 years and the average positive rate 8.92% was seen the lowest in Gurbantonggut desert. In the eastern segment, the first 2 peaks appeared the same season as in the central segment, but the third peak appeared in 2012, with the peak interval as 3 years. The positive rate of R. opimus for plague was also different in seasons, with the positive rate higher in autumn than in spring. These findings showed that the animal plague could be continuously prevalent from spring to autumn in the natural foci of plague in the Junggar Basin.</p><p><b>CONCLUSION</b>Both geographical and temporal fluctuations of animal plague existed in the natural foci of Junggar Basin which was also named as geographical heterogeneity. Consequently, animal plague could be divided into two areas-the clay plains desert in the western and the Gurbantonggut desert in the eastern-center Junggar Basin.</p>
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Animals , Gerbillinae , Plague , Epidemiology , Time , Yersinia pestisABSTRACT
Objective To construct a recombinant Ientiviral vector of mFVII/Fc and investigate its transfective efficiency into human bone mesenchymal stem cells (hBMSCs),and to detect the expression of mFVII/Fc fusion gene in vitro. Methods Coagulation factor VII (FVII) was cloned in vitro,with a point mutation from Lys to Ala in the position of 341 in the gene level.The cDNA fragments of mutational FVII (mFVII) and those of IgG1Fc were fused together with DNA ligase.After digestion,integration and sequencing,the fusion DNA was identified and transfected human embryonic kidney 293T cell packaging for re-mFVII/Fc lentiviral vector.After successful identification of vectors,detect the Ientiviral titer determination,bulk transfer after the determination of best MOI value of the third generation of hBMSCs,obseve the GFP expression with fluorescence microscope,have relative quantitative analyse of mRNA and protein expression of mFVII/Fc with RT-PCR and ELISA at different time points. Results In contrast with GenBank ID: AF 272774,the fusion gene matches exactly except the synonymous mutation,and the titer of packaging lentivirus was 2×108 TU/ml.Analyzed by Flow cytometry, indentification results of hBMSCs were as follows,CD+29(98.08%),CD+44 (97.63%),CD+34(0.31%) and CD+45(0.58%),respectively.The transfection efficiency of hBMSCs after 72 hours was (84±3)%,and the hBMSCs with mFVII/FC transfcetion have a large number of mRNA transcription and protein expression levels. Conclusions In this experiment we obtained a stable genetic vector with hBMSCs fusion gene expression successfully,which lay a foundation for the tissue factor study of prostate cancer targeting therapy and cancer gene therapy research.
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Objective To investigate the effect of lacosamide on expression of Nav1 .8 in dorsal root ganglia (DRG) in a rat model of chronic neuropathic pain.Methods Thirty-six female specific-pathogen-free (SPF)SD rats were randomly assigned into 3 groups ( n = 12 each): sham operation group (group S), model group (group M) and lacosamide group (group L) . Chronic neuropathic pain was produced by insertion of a small stainless steel rod (4.00 mm in length and 0.63 mm in diameter) into the L, intervertebral foramen in the rat, producing a chronic steady compression of the DRG in M and L groups. The mechanical threshold was measured 2 days before operation and on the 2, 4, 6, 7, 8, 9 and 10 days after operation (T0-7 ) . Intraperitoneal lacosamide 20mg/kg (in normal saline 0.5 ml) was injected at T4-7, twice a day in S and L groups. In group M, normal saline 0.5 ml was injected at T4-7 twice a day and the mechanical threshold was measured after the last administration everyday . The L, DRG on the operated side was removed after measurement of pain threshold to detect the expression of Na, 1.8 mRNA and protein by RT-PCR and immuno-histochemistry respectively. Results Compared with group S, the mechanical pain threshold was significantly decreased at T1-7 and the expression of Navl .8 mRNA and protein was up-regulated in M and L groups ( P < 0.05) . Compared with group M, the mechanical pain threshold was significantly increased at T4-7 and the expression of Nav 1.8 mRNA and protein was down-regulated in group L ( P < 0.05) . Conclusion The mechanism by which lacosamide reduces chronic neuropathic pain is related to the down-regulation of the expression of Nav 1.8 in rat DRG.
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Objective:To investigate the dynamic changes of glycine (Gly) and taurine (Tau) in corpus striatum of rats with ischemia-reperfusion injury (IRI),and the regulation effect of electroacupuncture on them.Methods:Thirty SD rats were randomly divided into sham surgery group,model group,and treatment group.Rats in the sham surgery group were operated without ischemia.Rats in the model group and treatment group were operated to make model of cerebral IRI.The ischemia status lasts 1.5 h,and reperfusion was performed for 3.75 h.Rats in the treatment group were treated with electroacupuncture at Fengchi (GB 20).Neurologic deficit score (NDS) was used to evaluate the rats functions.Microdialysis and High Performance Liquid Chromatography technique were used to detect the changes of Gly and Tau in corpus striatum of rats.Results:Contents of Gly and Tau increased at 1.5 h after ischemia.Them decreased to level as same as those rats in the sham surgery group after reperfusion.The content of Gly in the model and treatment group increased again at 2-2.5 h after reperfusion,and then decreased to the same level of the sham surgery group.There was a third increase of Gly content in the treatment group at 2.75 h after reperfusion.Electroacupuncture treatment could delay the decrease of Tau content after reperfusion,and make it increase at 1.5,2 and 2.75 h after reperfusion.The peak appeared in the last time.NDS in the model and treatment group were more than that in the sham surgery group,and lowered at 5.25 h after surgery.Effects in treatment group was better than that in the model group (P＜0.05).Conclusion:IRI makes contents of Gly and Tau in corpus striatum increase at a special time.Electroacupuncture treatment could increase contents of Gly and Tau at a special time after reperfusion,which maybe an important mechanism of protecting effects of electroacupuncture on the brain.
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Objective To investigate the type of plasmid map of Y. pestis in the R. opimas natural plague loci in Junggar Basin. Methods A total of 39 plasmid DNA of Y. pestis which were isolated from the natural plague loci of Junggar Basin, Tianshan Mountain, Kunlun Mountain, Qinghai-Tibet Plateau and In-ner Mongolia were extracted by the methods of Kado and Liu. The plasmid map was analyzed by the methods of agarose gel eleetrophoretogram. Results Two types of plasmid map were found in 26 Y. pestis which were isolated from Junggar Basin. Of them 23 were 6 × 106, 45 × 106 and 65 × 106 type of plasmid map, and 3 were 6 × 106, 45 × 106 and 72 × 106 type. Conclusion There are two types of plasmid map in the R. opi-mus natural plague loci in Junggar Basin. One type, which is the dominant type in this area, is 6 × 106, 45 × 106 and 65 × 106 type. This type is also similar to the dominant plasmid map type of the nature plague loci of Tianshan Mountain, Kunlun Mountain, Qinghai-Tibet Plateau and Inner Mongolia. The other type is 6 × 106, 45 × 106 and 72 × 106 type, and this type is new plasmid map type of Y. pestis in our country.