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ObjectiveTo observe the effect of Banxia Xiexintang on the autophagy of interstitial cells of Cajal （ICCs） in the gastric antrum of rats with gastric electric dysrhythmia， and explore the protective effect and regulatory mechanism. MethodThirty-two SD rats were randomly assigned into a normal group， a model group， a Banxia Xiexintang （24.68 g·kg-1） group， and a positive drug （2.7 mg·kg-1） group. The rat model of gastric electric dysrhythmia was established by the method of dieting every other day and drinking dilute hydrochloric acid， and Banxia Xiexintang and the positive drug were administrated for intervention. The body weight of each rat was recorded weekly. The gastric electric activity was recorded by the biological function experimental system. The ultrastructural changes of the gastric antrum tissue were observed by a transmission electron microscope. The co-expression of receptor tyrosine kinase （c-kit）/mammalian homolog of yeast Atg6 （Beclin1） in the gastric antrum tissue was detected by double immunofluorescence labeling method. The expression of microtubule-associated protein 1 light chain 3B （LC3B） and p62 protein in the gastric antrum tissue was determined by Western blot， and the LC3BⅡ/Ⅰ ratio was calculated. ResultCompared with the normal group， the modeling reduced the body weight （P<0.01） and decreased the dominant frequency and dominant power of gastric electricity （P<0.01）. In addition， the modeling caused ultrastructural damage of ICCs in gastric antrum， degeneration and necrosis of organelles， and appearance of a small number of autophagic vesicles. The results of double immunofluorescence labeling showed that the modeling inhibited the positive expression of c-kit and promoted the positive expression of Beclin1 in gastric antrum tissue. Western blot results showed that the modeling increased the ratio of LC3BⅡ/Ⅰ （P<0.01） and down-regulated the expression of p62 protein （P<0.01） in the gastric antrum tissue. Compared with the model group， Banxia Xiexintang and the positive drug increased the body weight （P<0.01） and the dominant frequency and dominant power of gastric electricity （P<0.01）， repaired the ultrastructural damage of ICCs in gastric antrum tissue， promoted the positive expression of c-kit and inhibited the positive expression of Beclin1 in the gastric antrum tissue. Furthermore， Banxia Xiexintang up-regulated the expression of p62 （P<0.05） and inhibited the transformation of LC3BⅠ into LC3BⅡ in gastric antrum tissue （P<0.05）. ConclusionBy regulating the expression of autophagy-related proteins， Banxia Xiexintang can reduce the autophagy and regulate the number and structure of ICCs and thus improve the gastric electric rhythm of rats， which preliminarily explains the mechanism of Banxia Xiexintang in the treatment of epigastric stuffiness.
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BACKGROUND@#Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent. This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules.@*METHODS@#Multiple databases with relevant studies were searched with an end date of October 31, 2021, and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31, 2022. Randomized controlled trials (RCTs) that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed. Primary outcomes included neutralizing antibodies against the original strain and serious adverse events (SAEs). A network meta-analysis (NMA) was conducted using a random-effects model.@*RESULTS@#In all, 11 RCTs were included in the systematic review, and nine were ultimately included in the NMA. Among participants who received two doses of CoronaVac, another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit (SU); a dose of BNT162b2 induced the highest geometric mean ratio (GMR) of 15.24, 95% confidence interval [CI]: 9.53-24.39. Following one dose of BNT162b2 vaccination, a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone (GMR = 1.32; 95% CI: 1.06-1.64), NVX-CoV2373 (GMR = 1.60; 95% CI: 1.16-2.21), or ChAdOx1 (GMR = 1.80; 95% CI: 1.25-2.59). Following one dose of ChAdOx1, a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1 (GMR = 11.09; 95% CI: 8.36-14.71) or NVX-CoV2373 (GMR = 2.87; 95% CI: 1.08-3.91). No significant difference in the risk for SAEs was found in any comparisons.@*CONCLUSIONS@#Relative to vaccination with two doses of CoronaVac, a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines. For primary vaccination, schedules including mRNA vaccines induce a greater immune response. However, the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted.@*REGISTRATION@#PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42021278149.
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Adult , Humans , BNT162 Vaccine , 2019-nCoV Vaccine mRNA-1273 , Network Meta-Analysis , Immunization Schedule , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Viral Vaccines , mRNA Vaccines , Antibodies, Neutralizing , Antibodies, ViralABSTRACT
Objective:To analyze the current situation and effect of mobile applications for physical activity management in China.Methods:In this systematic review, search terms such as “exercise”, “sports”, “exercise”, “physical activity” and “mobile health” were used to retrieve the applications for physical activity management in the IOS Application Store developed in mainland of China. Then the Mobile Application Rating Scale (MARS) and the Behavior Change Technology (BCT) were used to evaluate the quality of the applications and analyze the behavior change technologies that applications adopted. Moreover, a systematic review of relevant experimental studies was applied to summarize the effectiveness of the applications in promoting physical activity.Results:Total of 141 applications were included in this analysis, and 58 behavior change techniques in 16 categories were applied. The most frequently used 4 categories of BCT were behavior comparison (67.4%), repetition and substitution (67.4%), knowledge construction (67.4%), feedback and monitoring (58.2%). The overall objective quality score of MARS was 3.17±0.42, of which, the score of engagements, functionality, aesthetic design and information quality was 2.67±0.73, 3.75±0.54, 3.44±0.59 and 2.83±0.55, respectively. The number of BCT adopted in each application had a linear relationship with the application′s objective quality score in MARS ( B=0.023, 95% CI: 0.018-0.029) and user rating ( B=0.040, 95% CI: 0.019-0.060) (both P<0.001). A total of 4 articles were included to test the effects of techniques (i.e., physical activity behavior monitoring, physical activity planning and physical activity guidance) in 4 applications. The overall quality of the literatures was good. The main outcomes were physical activity duration (3 articles) and step count (1 article). Compared with those who did not use the application or only used the accelerometer to monitor physical activity, subjects who used the application to monitor physical activity had significant longer physical activity durations and step count (both P<0.05). Conclusions:The number, function and technology of physical activity management applications in China are abundant, but the quality of the applications is moderate. The number of BCT is an important factor in evaluating application′s quality, but its effect on behavior change is still not clear.
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The competitive sports are beneficial to cardiovascular system and brain health. However, physical exercise is accompanied with risks. Severe trauma is possible in competitive sports that may impact on the head and body. In recent years, more interests are aroused in sports-related traumatic brain injury(TBI), especially the mild TBI(mTBI). Repetitive mTBI can cause persistent cognitive, behavioral and mental problems, leading to chronic traumatic encephalopathy(CTE) and eventually resulting in neurodegeneration. In this study, the authors summarize the pathological characteristics and mechanism of CTE induced by mTBI due to competitive exercise so as to reveal the pathogenesis of CTE and provide valuable information for early diagnosis, development of disease biomarkers and explore effective therapeutic targets.
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Objective@#To explore the application value of interferon gamma release assay (IGRA) combined with tuberculin skin test (TST) in diagnosis of intraocular tuberculosis and latent tuberculosis infection.@*Methods@#One hundred and ten patients with pulmonary tuberculosis (observation group) and 80 healthy persons (control group) in Hebei Chest Hospital from January 2016 to December 2018 were selected. Among the 110 patients with pulmonary tuberculosis, intraocular tuberculosis was in 35 cases, and latent tuberculosis infection was in 75 cases. All the patients were examined by ocular secretions IGRA and TST.@*Results@#The positive rates of IGRA and TST in observation group were significantly higher than those in control group: 88.18% (97/110) vs. 11.25% (9/80) and 83.64% (92/110) vs. 41.25% (33/80), and there were statistical differences (χ2 = 113.138 and 36.971, P<0.01). The positive rate of IGRA in patients with intraocular tuberculosis was significantly higher than that in latent tuberculosis infection: 97.14% (34/35) vs. 84.00% (63/75), and there was statistical difference (χ2 = 3.955, P<0.05). There was no statistical difference in the positive rate of TST between the patients with intraocular tuberculosis and patients with latent tuberculosis infection: 91.43% (32/35) vs. 80.00% (60/75), χ2 = 2.277, P>0.05. The consistency rate of IGRA and TST was 89.90% (Kappa = 0.867, P>0.05). The sensitivity of IGRA combined with TST was significantly higher than the single detection of IGRA and TST (97.83% vs. 88.18% and 83.64%), while the specificity of IGRA combined with TST was significantly lower than the single detection of IGRA and TST (61.11% vs. 92.31% and 83.33%), and there were statistical differences (P<0.05). The receiver operating characteristic curve analysis result showed that the area under curve of IGRA in diagnosis of intraocular tuberculosis and latent tuberculosis infection was 0.781, area under curve of TST was 0.604, and area under curve of IGRA combined with TST was 0.679.@*Conclusions@#IGRA has high value in the diagnosis of intraocular tuberculosis and latent tuberculosis infection, and can be used as a diagnostic means of intraocular tuberculosis.
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Objective To explore the application value of interferon gamma release assay (IGRA) combined with tuberculin skin test (TST) in diagnosis of intraocular tuberculosis and latent tuberculosis infection. Methods One hundred and ten patients with pulmonary tuberculosis (observation group) and 80 healthy persons (control group) in Hebei Chest Hospital from January 2016 to December 2018 were selected. Among the 110 patients with pulmonary tuberculosis, intraocular tuberculosis was in 35 cases, and latent tuberculosis infection was in 75 cases. All the patients were examined by ocular secretions IGRA and TST. Results The positive rates of IGRA and TST in observation group were significantly higher than those in control group: 88.18% (97/110) vs. 11.25% (9/80) and 83.64% (92/110) vs. 41.25% (33/80), and there were statistical differences (χ2=113.138 and 36.971, P﹤0.01). The positive rate of IGRA in patients with intraocular tuberculosis was significantly higher than that in latent tuberculosis infection: 97.14% (34/35) vs. 84.00% (63/75), and there was statistical difference (χ2=3.955, P﹤0.05). There was no statistical difference in the positive rate of TST between the patients with intraocular tuberculosis and patients with latent tuberculosis infection: 91.43% (32/35) vs. 80.00% (60/75), χ2 = 2.277, P＞0.05. The consistency rate of IGRA and TST was 89.90% (Kappa=0.867, P＞0.05). The sensitivity of IGRA combined with TST was significantly higher than the single detection of IGRA and TST (97.83% vs. 88.18% and 83.64% ), while the specificity of IGRA combined with TST was significantly lower than the single detection of IGRA and TST (61.11% vs. 92.31% and 83.33% ), and there were statistical differences (P﹤0.05). The receiver operating characteristic curve analysis result showed that the area under curve of IGRA in diagnosis of intraocular tuberculosis and latent tuberculosis infection was 0.781, area under curve of TST was 0.604, and area under curve of IGRA combined with TST was 0.679. Conclusions IGRA has high value in the diagnosis of intraocular tuberculosis and latent tuberculosis infection, and can be used as a diagnostic means of intraocular tuberculosis.
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This article collects related literatures which is about the Chinese medicine adjuvant treatment of bladder urothelial carcinoma, and sums up the etiology, pathogenesis and TCM auxiliary treatment methods of this disease. Through the analysis, it is believed that the pathogeny of the disease is mainly concentrated in the aspects of damp, heat, blood stasis and poison. The literature on the adjuvant treatment of bladder urothelial carcinoma mainly focuses on the treatment of syndrome differentiation, postoperative recovery, postoperative perfusion, adjuvant chemotherapy and palliative therapy. The progress of its research is summarized as follows.
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Objective To explore the structure changes of white matter in the first-episode schizo-phrenic patients with never-medicated(FESZ)and the relationship between facial emotion perception and white matter(WM)integrity.Methods Sixty-three schizophrenic patients and thirty health control subjects underwent diffusion tensor imaging(DTI)scans.Voxel-based analysis was used to compared fractional ani-sotropy(FA)map between the two groups.Correlations were analyzed with pearson relative analysis between impaired facial emotion perception tested by facial emotion categorization(FEC)and severity of symptoms measured by the Positive and Negative Syndrome Scale(PANSS).Results (1)Compared with controls, FESZ patients showed overall decreased FA in WM of the body of left ventral frontal lobe((MNI(x,y,z):-18,26,-4;t=4.43)),right supramarginal gyrus((MNI(x,y,z):32,-50,26;t=4.27)),left middle oc-cipital gyral((MNI(x,y,z):-26,-60,0;t=4.89)),right middle occipital gyral((MNI(x,y,z):28,-70, 14;t=4.18)),left fusiform gyrus((MNI(x,y,z):-40,-50,0;t=3.92)),left cerebellum anterior lobe ((MNI(x,y,z):-32,-56,-28;t=4.57)),right parahippocampa gyrus1((MNI(x,y,z):32,-10,-14;t=4.16)),right parahippocampa gyrus2((MNI(x,y,z):16,-6,-14;t=4.56)),left anterior cingulate ((MNI(x,y,z):-2,4,-6;t=4.41)),left extra-nuclear((MNI(x,y,z):-2,-10,-6;t=4.44)),right thalamus((MNI(x,y,z):10,-10,2;t=4.20)),left thalamus((MNI(x,y,z):-22,-28,12;t=4.01)), and right caudate((MNI(x,y,z):14,12,8;t=4.87)).(2)Compared with controls,the patients with schizo-phrenia showed a higher shift point and a steeper slope than control subjects in FEC.Correlational analysis re-vealed that the negative correlations were found between the slope and negative factor(r=-0.298,P=0.036),between positive factor and the FA value in WM of the right middle occipital gyral(r=-0.322,P=0.023)and the left middle occipital gyral(r=-0.288,P=0.043),and between the FA value in the left cere-bellum anterior lobe and shift point(r=-0.393,P=0.005),but the positive correlation was found between disorganized/concrete factor and the FA value in the right parahippocampal gyrus(r=0.429,P=0.002).Con-clusions There are extensive microstructural abnormalities in WM of patients with FESZ.Disrupted WM in-tegrity in these regions may constitute a potential neural pathological basis for the facial emotion perception impairments in schizophrenia.
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Objective To investigate the induction and regulatory mechanism of placental trophoblast cell autophagy in women with preeclampsia (PE).Methods Twenty gravidas with severe PE who underwent cesarean section in the Department of Obstetrics and Gynecology of Changzhou Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University from August 2016 to November 2016 were enrolled in PE group.An equal number of normotensive gravidas without proteinuria who also underwent cesarean section during the same period were randomly selected as control group.Placental tissue samples were collected from all gravidas.Ultrastructure of placental trophoblast cells and changes in autophagosome formation were observed by transmission electron microscope.Expressions ofmicrotubule associated protein 1 light chain 3B (MAP1LC3B,or LC3B) and Beclin 1 in placental tissue samples were detected by quantitative real-time polymerase chain reaction (PCR) and Western blot.Activities of protein kinase B (PKB,also known as Akt)/mammalian target of rapamycin (mTOR) pathway in placental tissue samples were detected by Western blot.Two independent samples t-test or Mann-Whitney U test was used for statistical analysis.Results Sparse and disordered villi and many typical autophagosomes were observed in placental trophoblast cells from patients with severe PE.Significantly enhanced expression of LC3B at mRNA and protein levels and increased ratio of LC3-Ⅱ/LC3-Ⅰ were observed in the PE group as compared with the control group [3.37 (2.37-6.11) vs 0.62 (0.25-4.15),1.40±0.17 vs 1.00±0.13,1.57±0.25 vs 1.00±0.31,Zor t=--4.440,3.274 and 3.113,all P＜0.05].No significant difference in the expression ofBeclin 1 at mRNA or protein level in placental tissues was found between the two groups (both P＞0.05).Furthermore,Akt and mTOR phosphorylation in the PE group was significantly suppressed as compared with that in the control group (1.00±0.29 vs 0.64±0.21,1.00±0.32 vs 0.60±0.22,t=--3.672 and-2.895,both P＜0.05).However,the two groups showed no significant difference in the expression of Akt or mTOR protein (both P＞0.05).Conclusions Suppressed activity of Akt/mTOR pathway and enhanced induction of trophoblast cell autophagy are detected in placental tissues of patients with severe PE,indicating that excessive trophoblast cell autophagy,induced by decreased activity of Akt/mTOR pathway,may be the pathogenesis for PE.
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Breast cancer resistance to therapy can result from expression of antiapoptotic genes. Survivin is an antiapoptotic gene that is over expressed in most human tumors. RNA interference using short interfering RNA [siRNA] can be used to specifically inhibit survivin expression. A novel siRNA targeting survivin was used to process MCF-7 cells. Cellular survivin mRNA and protein levels were determined by real-time qRT-PCR and Western blot, respectively. Cellular morphology and cell cycle were determined by fluorescence microscopy and flow cytometry. Cell proliferation was measured by MTT assay. Our data showed that the novel survivin-targeted siRNA could efficiently knockdown the expression of survivin, inhibit cell proliferation and cell cycle, especially at the G2/M checkpoint. These data suggest that the siRNA has potential for therapeutic applications
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Objective During pregnancy , exosomes can be released from the placenta into maternal circulation and play im-portant roles in normal pregnancy or placenta-related diseases .We aimed to establish a simple and efficient method for isolating and i-dentifying placental exosomes from maternal serum and lay a foundation for the studies of pregnancy -related diseases . Methods Using sucrose gradient centrifugation with 8% PEG6000 precipitation twice , we isolated and purified placenta-derived exosomes from normal maternal serum and detected their molecular markers CD 63 , CD81 and PLAP by Western blot , followed by silver staining anal-ysis of the protein profile of the exosome pellet .We identified the morphology of the placenta-derived exosomes by transmission electron microscopy ( TEM) and measured the size and distribution of the particles by dynamic light scattering ( DLS) . Results Silver stai-ning of the protein profiles of the exosomes after sucrose gradient centrifugation clearly revealed the bands of the protein molecules . Western blot showed the expressions of CD 63, CD81, and PLAP in the 21-34%density layer, which demonstrated the presence of serum placental exosomes mainly in the 1.09-1.16 g/mL density layer.TEM exhibited that the placenta-derived exosomes were round or oval cup-shaped, specifically expressing PLAP, and the particles were uniform in size, with a mean diameter of (41.79 ±11.94) nm. Conclusion A simple, fast, and efficient method was successfully established for isolating placenta-derived exosomes from ma-ternal serum, which provides a basis for studying the roles of placental exosomes in normal pregnancy and placenta -related diseases.
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Genome editing tools such as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated system (Cas) have been widely used to modify genes in model systems including animal zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious knowledge gap remains in our understanding of DNA repair mechanisms in human early embryos, and in the efficiency and potential off-target effects of using technologies such as CRISPR/Cas9 in human pre-implantation embryos. In this report, we used tripronuclear (3PN) zygotes to further investigate CRISPR/Cas9-mediated gene editing in human cells. We found that CRISPR/Cas9 could effectively cleave the endogenous β-globin gene (HBB). However, the efficiency of homologous recombination directed repair (HDR) of HBB was low and the edited embryos were mosaic. Off-target cleavage was also apparent in these 3PN zygotes as revealed by the T7E1 assay and whole-exome sequencing. Furthermore, the endogenous delta-globin gene (HBD), which is homologous to HBB, competed with exogenous donor oligos to act as the repair template, leading to untoward mutations. Our data also indicated that repair of the HBB locus in these embryos occurred preferentially through the non-crossover HDR pathway. Taken together, our work highlights the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform, a prerequisite for any clinical applications of CRSIPR/Cas9-mediated editing.
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Humans , Blastocyst , CRISPR-Cas Systems , Hemoglobins, Abnormal , Genetics , Metabolism , ZygoteABSTRACT
ObjectiveTo investigate the significance of cerebrospinal fluid(CSF) S-100B protein and vascular endothelial growth factor (VEGF) levels in the pathogenesis of brain injury of viral encephalitis.MethodsForty-two patients with viral encephalitis (viral encephalitis group) and 40 patients with other disease at the corresponding time period(control group) were involved in this study.CSF (routine,biochemistry and cytology) was detected,and the levels of S-100B protein and VEGF in CSF were detected by ABC-ELISA method.ResultsWhite blood cell count was (0-584) × 106/L in viral encephalitis group,and (0-200) × 106/L in control group.The levels of protein and glucose in CSF had no significant difference between two groups (P＞ 0.05),and the level of chloride in CSF in viral encephalitis group was significantly lower than that in control group[ ( 110.10 ± 31.22 ) mmol/L vs.( 123.80 ± 6.32 ) mmol/L ] (P =0.006).In viral encephalitis group,cytological examination showed that mixed type cytological reaction was in 6 cases (14.3％,6/42).The level of S-100B protein in viral encephalitis group [25.04-47.97 (28.37 ± 6.09) ng/L] was significantly higher than that in control group[ 25.04-29.64(26.03 ± 0.90) ng/L ] (t =2.462,P =0.018).The level of VEGF in viral encephalitis group[88.84～143.77(96.24 ± 13.38) ng/L] was significantly higher than that in control group [89.15～96.18 (90.67 ± 1.71 ) ng/L] (t =2.673,P =0.011 ).ConclusionsThe high levels of S-100B protein and VEGF in CSF could support the viral encephalitis diagnosis.Tracking the levels of S-100B protein and VEGF in CSF dynamically have noticeable effect on checking the condition of viral encephalitis patients.
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Objective To build three-dimensional (3-D) finite element models for local advancement skin flap, by which the post-operative local strain and local stress of skin were figured out to assist in the design of skin flap in clinic. Methods The biomechanical parameters of human forehead skin were obtained in vitro from biomechanical experiments. The 3-D finite element model of local advancement skin flap was set up by MSC Marc/Mentat 2005 (3-D finite element software). Six models were built with the same flap but different skin defects, to simulate post-operative local strain of skin and local stress of skin in different models. Results Post-operative local stress of skin increased with the skin flaps stretching, but the relationship between increase and stretching did not meet the linear rule. Skin flap was able to stretch to 40 % of its initial length in theory if we did not consider blood supply of it. When the skin flap stretched over 40 % of its initial length, the maximal stress could exceed the yield limit. Conclusion It is an effective and workable way to simulate local advancement skin flap using 3-Dfinite element model and biomechanical parameters of human skin. The stretch ratio of local advancement skin flap should be not over 40% for safety.
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Production of wear debris following artificial joint replacement contributes to joint loosening and useful life shortening of the prosthesis.This paper summarized the mechanism of prosthesis loosening and prevention methods,so as to provide evidence for delay or prevent prosthesis loosening.
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Histology and Embryology is a very important basic curriculum of medicine. It is directly related to the freshmen’s interest in learning medicine continually. New teaching model pays close attention not only to knowledge and phenomena but also to the essence and the design idea of the structure of human body. New teaching model attempts to arouse the students’strong desire for exploration and interests in medical sciences.
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0.05). Conclusion: 100 g/L(NH 4) 2MoO 2F 4 solution may arres t root lesion progress as effectively as 380 g/L Ag(NH 4) 2F 4 solution and preferably to 20 g/L NaF solu tion.
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Objective: To evaluate the diagnostic efficacy of the bitewing radiograph(BWR),clinic examination(CE) and laser fluorescence examination (LF) for detection of initial posterior approximal caries . Methods:A total of 162 approximal surfaces from 81 extracted posterior teeth were examined by BWR, CE and LF. The histological diagnosis of sectioned teeth was used as the validating criterion (gold standard) to assess the sensitivity, specificity, accuracy and reproducibility. Results: The sensitivity and accuracy of BWR was higher than those of CE or LF at the level of enamel caries. Conclusions: BWR is an accurate diagnostic method for initial posterior approximal caries in present clinic practice. The inferior efficacy of LF is mainly due to its poor reproducibility of approximal surfaces.