Relationship between macrophage infiltration in the coronary plaque and downstream myocardial perfusion in mice / 中华超声影像学杂志

Objective:To explore the relationship between macrophage infiltration in the coronary plaque and downstream myocardial perfusion in mice.Methods:The experimental group consisted of 20 ApoE knockout mice models of the coronary plaque established by feeding with cholesterol-rich diets, and the control group consisted of 20 sex- and age-matched C57BL/6 mice with the same genetic background as ApoE mice.Adenosine stress myocardial contrast echocardiography was performed on all experimental animals to obtain the values of A, β and A×β of the left ventricular myocardium in anteroseptal and posterior walls both in the resting status and during adenosine stress. Concentrations of serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were determined using mouse enzyme-linked immunosorbent assay kits according to the manufacturer′s instructions. The degree of macrophage infiltration in the coronary plaque was evaluated by pathological immunohistochemistry staining and the correlations with the above indicators were analyzed.Results:There were no statistically significant differences in heart rate and left ventricular structural parameters between two groups (all P>0.05). The experimental group had a lower left ventricular ejection fraction( P=0.021), and higher weight and serum levels of triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, IL-6, and TNF-α than the control group (all P<0.05). The values of A, β and A × β of the left ventricular myocardium in anteroseptal and posterior walls in the experimental group were significantly lower than those in the control group during adenosine stress (all P<0.05). In the experimental group, the value of the macrophage infiltration found in the plaque of the left main coronary artery correlated positively with the level of serum TNF-α ( r=0.63, P=0.003) and negatively correlated with the values of A×β of the left ventricular myocardium in anteroseptal and posterior walls during adenosine stress ( r=-0.74, P<0.001; r=-0.72, P<0.001; respectively). Conclusions:Myocardial perfusion in ApoE knockout mice models of the coronary atherosclerosis was related with degree of macrophage infiltration in the coronary plaque, and macrophages may play a role by releasing inflammatory mediator TNF-α.

Efficacy of rTMS and CBT-I on patients with chronic insomnia disorder： a randomized controlled study / 四川精神卫生

BackgroundTo date， pharmacologic therapy is considered the standard first-line treatment for insomnia disorder， but there are still some concerns over the adverse reactions. Repetitive transcranial magnetic stimulation （rTMS） and cognitive behavioral therapy for insomnia （CBT-I） as an alternative to pharmacologic therapy have the advantages of fewer side effects and better patient tolerance in the treatment of chronic insomnia disorder. ObjectiveTo explore the clinical efficacy of rTMS and CBT-I on chronic insomnia disorder， so as to provide a novel therapeutic option for the treatment of chronic insomnia disorder. MethodsA total of 50 patients with chronic insomnia disorder attending the outpatient clinic of Inner Mongolia Autonomous Region Mental Health Center or community hospital from September 21， 2020 to December 16， 2021 and fulfilling the International Classification of Sleep Disorders， third edition （ICSD-3） diagnostic criteria were enrolled. Additionally， 16 age- and sex-matched healthy controls recruited from the community were set as control group. Patients were randomly divided into rTMS group and CBT-I group， 25 cases in each group， and received rTMS or CBT-I intervention for 6 weeks respectively. At enrollment and completion of intervention， patients were subjected to Polysomnography （PSG）， Pittsburgh Sleep Quality Index （PSQI）， Insomnia Severity Index （ISI） and Repeatable Battery for the Assessment of Neuropsychological Status （RBANS）. All participants underwent resting-state functional magnetic resonance imaging （rs-fMRI） scans， and amplitude of low-frequency fluctuation （ALFF） was calculated. The brain regions with statistically different ALFF values between patient group and control group were chosen as regions of interest （ROIs）， and whole-brain seed-based functional connectivity analyses were conducted. ResultsAfter a 6-week intervention in the two groups， the main effect of time was significant for PSQI （F=41.160， P<0.05）， ISI （F=69.615， P<0.05） and RBANS immediate memory （F=47.923， P<0.05）， language （F=12.090， P<0.05） and delayed memory indices （F=28.193， P<0.05）. A significant main effect of time for total sleep time （F=8.995， P<0.05）， a significant main effect of time for sleep efficiency （F=12.414， P<0.05）， a significant main effect of group for sleep efficiency （F=4.342， P<0.05） and a significant main effect of time for N1% （F=7.806， P<0.05） were observed. Sleep efficacy in CBT-I group improved significantly from pre- to post-test （t=-2.785， P<0.05）. Patients in rTMS group showed increased functional connectivity between the orbital superior frontal gyrus and other regions including left lentiform nucleus putamen （t=4.991， P<0.05）， right median cingulate and paracingulate gyri （t=4.471， P<0.05） and right postcentral gyrus （t=4.922， P<0.05）， and increased functional connectivity between the orbital superior frontal gyrus and left middle frontal gyrus was found in CBT-I group （t=6.586， P<0.05）. ConclusionrTMS and CBT-I may help alleviate insomnia and improve cognitive function of patients with chronic insomnia disorder. [Funded by Science and Technology Planning Projects in Inner Mongolia Autonomous Region （number， 201802142）］

Evaluation of left atrial structure and function by three-dimensional echocardiography in paitents with apical hypertrophic cardiomyopathy / 中华超声影像学杂志

Objective:To investigate the changes of left atrial structure and function in patients with apical hypertrophic cardiomyopathy (ApHCM) by three-dimensional (3D) echocardiography.Methods:From September 2020 to December 2022, 112 patients with ApHCM(ApHCM group) diagnosed at Tongji Hospital Tongji Medical College, Huazhong University of Science and Technology and 41 age- and sex-matched normal controls(control group) were finally enrolled. In 'pure’ ApHCM patients, cardiac hypertrophy was confined to the apical segment below the papillary muscle. The wall thickness of apical and intermediate segments in 'mixed’ ApHCM patients increased, but the wall thickness of apical segment was the largest. Two-dimensional(2D) and 3D volume and strain parameters of left atrium were compared between control group and ApHCM group, 'pure’ and 'mixed’ ApHCM patients.The correlations between 2D and 3D volume and strain parameters of left atrium and intraclass correlation coefficient (ICC) of those parameters were analyzed. The ROC curve was performed to determine the cutoff values of 3D left atrial volume abnormalities in all subjects. Logistics regression analysis was performed to analyze the impact factors of the left atrial enlargement in patients with ApHCM.Results:Compared with the control group, 2D left atrial maximum volume index (2D LAVimax), 2D left atrial minimum volume index (2D LAVimin), 3D left atrial maximum volume index (3D LAVimax), 3D left atrial minimum volume index (3D LAVimin), and 3D left atrial presystolic volume index (3D LAVipreA) significantly increased in ApHCM group( Z=-6.54, -6.38, -6.98, -7.40, -6.96; all P<0.001). However, 2D left atrial ejection fraction (2D LAEF) ( Z=-3.75, P<0.001), 2D left atrial expansion index (2D LAEI) ( t=-4.15, P<0.001), 3D left atrial ejection fraction (3D LAEF) ( Z=-5.09, P<0.001), 3D left atrial expansion index (3D LAEI) ( t=-5.49, P<0.001), 2D left atrial reservoir strain (2D LASr) ( t=-12.03, P<0.001), 2D left atrial conduit strain (2D LAScd) ( t=7.91, P<0.001), 2D left atrial contractile strain (2D LASct) ( t=6.06, P<0.001), 3D left atrial reservoir strain (3D LASr) ( t=-9.23, P<0.001), 3D left atrial conduit strain (3D LAScd) ( t=7.12, P<0.001) and 3D left atrial contractile strain (3D LASct) ( t=4.78, P<0.001) significantly decreased in ApHCM group. Compared with the 'pure’ ApHCM group, 2D LAVimax, 3D LAVimax, 2D LAVimin, 3D LAVimin, 3D LAVipreA in patients with mixed ApHCM increased more significantly, while 2D LAEF, 2D LAEI and 2D LASr decreased more significantly. The measurements of left atrial volume and strain by 3D echocardiography were significantly correlated with 2D measurements ( P<0.05). The correlations between 2D LAVimax and 3D LAVimax, 2D LAVimin and 3D LAVimin, 2D LAEF and 3D LAEF, 2D LASr and 3D LASr, 2D LAEI and 3D LAEI ( r=0.91, 0.93, 0.72, 0.76, 0.57; all P<0.05) were more than moderate. The repeatability of 3D left atrial strain was lower than 2D results, while the repeatability of 3D left atrial volume was higher than 2D results. ROC curve analysis showed that 3D echocardiography parameters could identify left atrial volume abnormality in all subjects. The cutoff values of 3D LAVimax, 3D LAVimin, 3D LAVipreA in all subjects were 36 ml/m 2, 18 ml/m 2 and 27 ml/m 2, respectively. Multivariate binary logistic regression analyses showed that ratio of LV systolic obliteration to cavity was independent factor affecting left atrial enlargement in ApHCM patients( OR=1.20, P<0.001). Conclusions:Three-dimensional echocardiography is significant for the accurate evaluation of left atrial structural changes in patients with ApHCM. Ratio of left ventricular systolic obliteration to cavity was an independent impact factor of left atrial enlargement in ApHCM patients.

Transapical beating interventricular septal resection under the navigation of three-dimensional transesophageal echocardiography for the treatment of hypertrophic obstructive cardiomyopathy / 中华超声影像学杂志

Objective:To evaluate the efficacy and safety of immediate intraoperative transapical beating-heart septal myectomy (TA-BSM) in patients with hypertrophic obstructive cardiomyopathy (HOCM) and explored the clinical value of three-dimensional transesophageal echocardiography (3D-TEE) during the procedure of TA-BSM.Methods:One hundred and thirty-seven HOCM patients who underwent TA-BSM surgery in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from April 2022 to March 2023 were selected.During the operation, 3D-TEE was used to locate the position of the myocardial circumcision system and navigate the range of myocardial circumcision. The interventricular septal thickness( IVST) and peak pressure gradient of the left ventricular outflow tract (LVOT-PG) were measured, and the degree of mitral systolic anterior motion (SAM) and mitral regurgitation (MR) were evaluated in HOCM patients before and after the operation. The range of the incisal margin was measured, and the number of resection knives and the weight of the removed myocardium were recorded.Results:TA-BSM under 3D-TEE navigation was successfully performed in 137 HOCM patients. The number of resection was 7(5, 9), and the weight of the removed myocardium was 5.6(3.4, 8.9)g. During the operation, there were no adverse events such as death, aortic valve injury, and iatrogenic interventricular septal perforation. Compared with those before the operation, the wall thickness of basal and middle segments of the anterior and posterior interventricular septum decreased significantly (all P<0.001), and LVOT-PG decreased significantly ( P<0.001). After TA-BSM, the number of patients with SAM≥3 decreased from 94 cases (68.6%) to 2 cases (1.5%), and the number of patients with MR≥3+ decreased from 86 cases (62.8%) to 9 cases (6.6%)(all P<0.001). For the patients with different degrees of ventricular septal hypertrophy (mild, moderate, and severe), the postoperative IVST and LVOT-PG were significantly lower than the preoperative values, and the degree of MR and SAM signs was relieved considerably. The length of the incisal margin, the weight of excised myocardium, and the number of resection in the group with extensive septal hypertrophy in all three regions were significantly higher than those in the group with localized interventricular septal hypertrophy in single or two areas (all P<0.05). Conclusions:3D-TEE can guide and monitor the process of TA-BSM myocardial resection in real-time. By accurately evaluating the IVST and the range and hemodynamic characteristics of HOCM patients, it can effectively relieve LVOTO and significantly reduce MR to ensure the safety and effectiveness of TA-BSM in HOCM patients with different degrees and ranges of hypertrophy.

Discussion on the performance reform of administrative and logistics personnel in a large public hospital / 中华医院管理杂志

Because the work of administrative and logistics personnel in public hospitals is difficult to quantify and evaluate, its performance reform is difficult. A large public hospital in Wuhan has explored and established a distribution incentive mechanism that combines department performance appraisal, individual classification and grading, and secondary distribution within the department. Taking into account the completion of performance appraisal indicators of the national tertiary public hospital in the department, the results of the institutional " Excellent Management Team Ranking" , personal job grades, working years and other factors, a relatively mature and operable system has been formed, which could provide reference for the performance reform of other hospitals.

The relationship between vulnerability of coronary atherosclerotic plaque and downstream myocardial perfusion and myocardial strain in mice / 中华超声影像学杂志

Objective:To investigate the relationship between vulnerability of mouse coronary artery plaque and downstream myocardial perfusion and myocardial strain.Methods:Thirteen ApoE knockout mice with stable coronary plaques (stable plaque group)and 13 ApoE knockout mice with vulnerable coronary plaques(vulnerable plaque group) were selected as the experimental group, and 15 sex- and age-matched C57BL/6 mice with the same genetic background as ApoE mice were chosed as the control group. Myocardial contrast echocardiography (MCE) was carried out to quantify regional myocardial perfusion at rest and during adenosine stress using a Vevo 2100 system (Visual sonics). Replenishment curves of myocardial contrast were obtained, and rates of signal rise (β) and plateau intensity (A) were recorded. MBF was estimated by the product of A and β. Speckle tracking imaging combined with adenosine stress test was used to evaluate the longitudinal strain of left ventricular myocardium in mice. The vulnerability of the plaque was assessed by histopathology in serial tissue sections of proximal and middle left coronary artery according to the previously reported method.Results:There were no significant differences in body weight, heart rate, left ventricular end diastolic volume, left ventricular end systolic volume, left ventricular mass and ejection fraction among the three groups( P>0.05). The levels of serum triglyceride, total cholesterol, high density lipoprotein and low density lipoprotein in stable plaque group and vulnerable plaque group were significantly increased when compared with those in control group (all P<0.05). The pathological results showed that the coronary luminal stenosis rates in the stable plaque group and the vulnerable plaque group were (74.3±4.9)% and (75.5±7.1)% respectively, with no significant difference between the two groups( P>0.05). MBF of the middle anterior septum and left ventricular posterior wall in the experimental groups were significantly decreased when compared with that in the control group both in the resting status and during adenosine stress(all P<0.05). There were no significant differences in the MCE parameters between the stable plaque group and the vulnerable plaque group at rest( P>0.05). However, during adenosine stress, MBF of the vulnerable plaque group was decreased more significantly than that of the stable plaque group ( P<0.05). Compared with the control group, the values of longitudinal strain of the left ventricle in both experimental groups were decreased during resting status, without statistical significance (all P>0.05), but decreased significantly during adenosine stress and with more decrease in the vulnerable plaque group (all P<0.05). Conclusions:For the same degree of coronary artery stenosis in mice, the coronary artery vulnerable plaque group has less downstream myocardial perfusion and myocardial strain than the stable plaque group during adenosine stress. That is, the plaque vulnerability can affect the downstream myocardial perfusion and myocardial strain in the mouse model.

Genotype and clinical phenotype analysis of a five-generation Ningxia family with autosomal dominant retinitis pigmentosa pedigree / 中华实验眼科杂志

Objective:To identify the pathogenic mutation in a five-generation Ningxia family with autosomal dominant retinitis pigmentsoa (adRP) and to analyze its associated clinical phenotype.Methods:One adRP pedigree was recruited for this study.All the patients and family members received complete ophthalmic examinations.DNA was abstracted from peripheral blood of three patients, one normal family member and 300 normal controls.Using whole exome sequencing (WES) chip and bioinformatics analysis to screen the candidate disease-causing mutations.PCR and direct sequencing were used to confirm the disease-causing mutations.Genotype-phenotype correlation was also analyzed.This study followed the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of People's Hospital of Ningxia Hui Autonomous Region (No.20160204).Results:PRPF31 c. C1048T (p.Q350X) nonsense mutation was identified as the disease-causing mutation for this family by WES chip, PCR and direct sequencing.This family demonstrated early onset of the disease by presenting nyctalopia from 5 to 6 years, performed rapid disease progression, severely impaired visual function and posterior subcapsular cataract.The fundus presentations and electroretinogram (ERG) results showed typical RP progressions. Conclusions:PRPF31 c. C1048T (p.Q350X) nonsense mutation is the disease-causing mutation of this family.This mutation is first reported in Chinese with distinct phenotypes in the present family, including early onset of the disease, rapid disease progression, severely impaired visual function and posterior subcapsular cataract.

Contrast enhanced ultrasound molecular imaging of platelets in the inflammatory procession of atherosclerosis / 中华超声影像学杂志

Objective To assess the role of activated platelets in the inflammatory procession of atherosclerosis(AS)by ultrasound molecular imaging.Methods Sixty ApoE-/-mice were fed with high fat diet to establish AS model as experimental group,and 40 C57BL/6J mice were fed with normal diet as control group.Biotin-avidin bridging method was used to construct platelet-targeted microbubbles with recombinant vWF-A1 domain (Mb-A1),microbubbles carrying monoclonal antibodies to VCAM-1 (Mb-VCAM1)and microbubbles carrying IgG monoclonal antibody(Mb-ctrl).In vitro and in vivo experiments were carried out to evaluate the ability of Mb-A1 to target platelets on vascular endothelial surface.Contrast enhanced ultrasound molecular imaging of proximal ascending aorta was performed with Mb-A1 ,Mb-VCAM1 and Mb-ctrl.The expression and distribution of platelets and monocytes/macrophages on the endothelium of ascending aorta of AS mice were observed and analyzed by immunofluorescence staining. Results ①A large number of Mb-A1 adhering to the surface of activated platelets coated in Petri dishes were observed under fluoresce.②After platelet immune-depletion in 30-week AS mice,the signal intensity of Mb-A1 decreased significantly in ascending aorta,while that of Mb-ctrl has no obvious change(P <0.05).③In ApoE-/-mice,signals from platelet targeted microbubbles increased from 8 to 32 weeks of age in ApoE-/-mice,which coincided with the increase of signals from VCAM-1 targeted microbubbles(P <0.05).④Activated platelets on the endothelial surface of ascending aorta increased progressively with age from 8 weeks,and partly overlapped with the distribution of monocytes/macrophages.Conclusions Platelets contribute to the initiation and progression of atherosclerosis as an inflammatory mediator through the interaction with vascular endothelium.

Effects of adenosine stress on myocardial perfusion in healthy mice / 中华超声影像学杂志

Objective To explore the effects of adenosine stress on myocardial perfusion in healthy mice by myocardial contrast echocardiography ( MCE) . Methods MCE was carried out to quantify regional myocardial perfusion at rest and during adenosine stress using a VEVO 2100 system in 26 C57BL/6 mice . Echocardiography images from standardized parasternal long axis and short axis at papillary muscle level were consecutively acquired in real‐time . All dynamic images were recorded for off‐line analysis . Left ventricular myocardial perfusion quantitative parameters were acquired both under resting status and during adenosine stress . Replenishment curves of myocardial contrast were obtained and myocardial blood flow ( MBF) was calculated . Results Twenty‐six experimental animals successfully underwent MCE before and during adenosine stress . T here was no significant difference in heart rate ,left ventricular structure and functional parameters before and during adenosine stress ( all P ＞0 .05) . Rates of signal rise β values which were used to estimate blood velocity of middle anterior septum and posterior wall in left ventricular long‐axis view and anterior wall ,lateral wall ,inferior wall and septal wall in short‐axis view at papillary muscle increased significantly during stress compared with those at rest ( all P ＜0 .05 ) . T here was no significant difference in the plateau intensity A values( all P ＞0 .05 ) . T he MBF in each segment of the myocardium increased significantly during stress compared with those in resting state ( all P ＜0 .05) . Conclusions T he physiological characteristics of myocardial perfusion in mice before and during adenosine stress were preliminarily obtained ,w hich provided a basis for the application of adenosine stress echocardiography in cardiovascular disease models such as coronary heart disease in mice .

Contrast enhanced ultrasound molecular imaging of platelets in the inflammatory procession of atherosclerosis / 中华超声影像学杂志

Objective@#To assess the role of activated platelets in the inflammatory procession of atherosclerosis(AS) by ultrasound molecular imaging.@*Methods@#Sixty ApoE-/- mice were fed with high fat diet to establish AS model as experimental group, and 40 C57BL/6J mice were fed with normal diet as control group. Biotin-avidin bridging method was used to construct platelet-targeted microbubbles with recombinant vWF-A1 domain (Mb-A1), microbubbles carrying monoclonal antibodies to VCAM-1 (Mb-VCAM1) and microbubbles carrying IgG monoclonal antibody (Mb-ctrl). In vitro and in vivo experiments were carried out to evaluate the ability of Mb-A1 to target platelets on vascular endothelial surface. Contrast enhanced ultrasound molecular imaging of proximal ascending aorta was performed with Mb-A1, Mb-VCAM1 and Mb-ctrl. The expression and distribution of platelets and monocytes/macrophages on the endothelium of ascending aorta of AS mice were observed and analyzed by immunofluorescence staining.@*Results@#①A large number of Mb-A1 adhering to the surface of activated platelets coated in Petri dishes were observed under fluoresce. ②After platelet immune-depletion in 30-week AS mice, the signal intensity of Mb-A1 decreased significantly in ascending aorta, while that of Mb-ctrl has no obvious change(P<0.05). ③In ApoE-/- mice, signals from platelet targeted microbubbles increased from 8 to 32 weeks of age in ApoE-/- mice, which coincided with the increase of signals from VCAM-1 targeted microbubbles(P<0.05). ④Activated platelets on the endothelial surface of ascending aorta increased progressively with age from 8 weeks, and partly overlapped with the distribution of monocytes/macrophages.@*Conclusions@#Platelets contribute to the initiation and progression of atherosclerosis as an inflammatory mediator through the interaction with vascular endothelium.

Effects of adenosine stress on myocardial strain in healthy mice / 中华超声影像学杂志

Objective To explore the effects of adenosine stress on myocardial strain in healthy mice by speckle tracking imaging (STI).Methods A high-resolution rodent ultrasound machine Vevo 2100 was used to perform conventional transthoracic echocardiography at baseline and after intravenous infusion of adenosine in 34 C57BL/6 mice.Echocardiography images from standardized parasternal long axis and short axis at papillary muscle level were consecutively acquired in real-time.All dynamic images were recorded for off-line analysis.Left ventricular myocardial mechanical strain parameters were acquired both under resting status and during adenosine stress.Results Thirty-four experimental animals successfully underwent STI before and during adenosine stress. There was no significant difference in heart rate,left ventricular structure and functional parameters between before and after the adenosine stress ( P >0.05).Global peak longitudinal strain value in left ventricular long-axis view was significantly increased during stress compared with those at resting status ( P < 0.05);while there was no significant increase in the global peak circumferential strain and global peak radial strain values in short-axis view at papillary muscle ( P >0.05).Conclusions Myocardial strain is obtained in healthy mice before and after adenosine stress.This provides an evidence to the application of stress echocardiography in mice with coronary heart disease or other cardiovascular disease in the future.

Simultaneous Determination and Clinical Application of Individual Thioguanine Nucleotides in Red Blood Cells by an HPLC-fluorescence Method / 中国药师

Objective: To establish an HPLC-fluorescence detection method for the determination of thioguanosine-monophosphate (TGMP), thioguanosine-diphosphate (TGDP) and thioguanosine-triphosphate (TGTP) in red blood cells (RBC), as well as quantify the individual thioguanine nucleotides metabolites in kidney transplant recipients with azathioprine (AZA) therapy.Methods: The individual thioguanosine phosphates were extracted from RBC by dichloromethane and subsequently oxidized by potassium permanganate.The separation was achieved on a Nucleosil C18 column (150 mm×4.6 mm,5 μm) with an ion pairing reagent and detected by a fluorescence detector (excitation at 315 nm, emission at 390 nm).The mobile phase consisted of 20 mmol·L-1 potassium phosphate buffer (pH was adjusted to 6.8 by 5 mmol·L-1 tetrabutylammonium hydrogensulfate)-acetonitril (80:20) with the flow rate of 1.0 ml·min-1.Results: TGMP, TGDP and TGTP were quantified from RBC within the range of 50-500, 50-1000 and 100-5 000 pmol·ml-1, respectively.The limit of quantification (LOQ) was 50, 50 and 100 pmol·ml-1 RBC for TGMP, TGDP and TGTP, respectively.The intra-and inter-day RSDs were below 7.0% with the method recovery between 95.0% and 103.6%.The mean extraction recovery was above 90%.The assay was applied in the blood samples of 30 kidney transplant recipients with AZA therapy, and the results indicated that TGTP was the predominant phosphate metabolite in RBC.Conclusion: The method is simple, rapid, sensitive and specific, and it can quantitatively determine the individual thioguanosine phosphates in RBC of kidney transplant recipients with AZA therapy.

Research Progress in β-Glucuronidase / 中国药师

Objective:To summarize the structure, properties and biological functions ofβ-glucuronidase. Methods:By referring to the relevant literatures at home and abroad onβ-glucuronidase in recent years, this paper induced, analyzed and drew conclusions. Results:The crystal structure of humanβ-glucuronidase is comprised of three distinct structural domains. The most common mutation of β-glucuronidase is missense mutation, which results in the change of enzyme activity, and then induces a series of pathological chan-ges like MPSⅦ. The researches on β-glucuronidase used in antibody-directed enzyme prodrug drug therapy and enzyme replacement therapy are becoming deeper and deeper. Conclusion:β-Glucuronidase as an important acid hydrolytic enzyme in human has a variety of genetic mutations, and plays an important role in the fields of medicine and disease diagnosis, which has become one of research hotspots.

Research Progress in β-Glucuronidase / 中国药师

Objective:To summarize the structure, properties and biological functions ofβ-glucuronidase. Methods:By referring to the relevant literatures at home and abroad onβ-glucuronidase in recent years, this paper induced, analyzed and drew conclusions. Results:The crystal structure of humanβ-glucuronidase is comprised of three distinct structural domains. The most common mutation of β-glucuronidase is missense mutation, which results in the change of enzyme activity, and then induces a series of pathological chan-ges like MPSⅦ. The researches on β-glucuronidase used in antibody-directed enzyme prodrug drug therapy and enzyme replacement therapy are becoming deeper and deeper. Conclusion:β-Glucuronidase as an important acid hydrolytic enzyme in human has a variety of genetic mutations, and plays an important role in the fields of medicine and disease diagnosis, which has become one of research hotspots.

Rapid identification of pathogenic mutations in sporadic hereditary retinal dystrophies using targeted next-generation sequencing / 中华实验眼科杂志

Background Hereditary retinal diseases (HRDs) are a group of retinal degenerative diseases with significant genetic and clinical heterogeneities.Traditional techniques are challenging for detection of pathogenic mutations.Objective This study was to identify the diseasing-causal genes in 20 Chinese families with a variety of HRDs.Methods Family histories and ophthalmic examinations were obtained from all participants in 20 sporadic families.Targeted sequence capture array technique with next-generation sequencing (NGS) was performed to detect pathogenic mutations in 232 identified genes associated with HRDs.Variants detected by NGS were filtered by bioinformatic analysis HRDs.Genotype-phenotype correlation was also assessed.Results We identified 11 patients with pathogenic mutations,including 8 compound heterozygous mutations and 3 homozygous mutations,which were not yet reported.These findings showed genetic diagnoses in 11 of 20 patients,with the positive rate of 55％.Among them,6 patients were autosomal recessive inheritance and 5 were unspecific.Identification of different mutations and divergent phenotypes revealed 5 patients were affected with cone-rod dystrophy,3 patients with Leber congenital amaurosis,1 patient with congenital stationary night blindness,1 patient with Best vitelliform macular dystrophy and 1 patient with Stargardt disease.Conclusions Targeted NGS is an effective approach for the genetic diagnoses of HRDs.These findings provide insights into understanding the genotype-phenotype correlations in HRDs.

Advances in the Modulation of Quercetin on Drug Metabolizing Enzymes / 中国药师

Objective: To summarize the recent research progress in the influence of quercetin on drug metabolizing enzymes. Methods:By referring to the relevant literatures at home and abroad in recent years, the paper summarized, analyzed and concluded the the influence of quercetin on drug metabolizing enzymes. Results: Quercetin could modulate the phase Ⅰmetabolic enzyme cyto-chrome P450 ( CYP) and the phase Ⅱ metabolic enzymes uridine diphosphate - glucuronosyltransferase enzyme ( UGTs) , sulfotrans-ferase ( SULTs) and glutathione S-transferase ( GSTs) to influence the in vitro and in vivo metabolism of a lot of drugs. Meanwhile, the modulation of quercetin on the metabolic enzymes demanded the participation of various nuclear receptors. Conclusion:Quercetin shows the inhibitory or inducing effect on a variety of drug-metabolizing enzymes, therefore, it can interact with other drugs.

Influence of RAC1 gene polymorphisms on Rac1-GTP expression levels / 中国免疫学杂志

Objective:To study the association of RAC1 gene polymorphisms with protein expression levels of Rac1-GTP. Methods:A total of 182 healthy Hans population in Hubei were recruited. The 4 tag-SNPs in RAC1 gene were genotyped by Real time TaqMan-MGB genotyping assay. And the Rac1-GTP protein levels in plasma samples from all participants were determined by enzyme linked immunosorbent assays ( ELISA ) . The distribution characteristics of Rac1-GTP expression levels were also analyzed. Furthermore,the expression levels of Rac1-GTP were compared among different genotypes of the 4 tag-SNPs in RAC1 gene. Results:The distribution of Rac1-GTP expression levels was positive skewed in healthy Chinese Hans population. The expression levels were significantly higher in females than in males (P0. 05). Different expression levels of Rac1-GTP were observed in different genotypes for rs702482 and rs10951982 (P0. 05). Conclusion:RAC1 genetic polymorphisms can potentially affect the expression levels of Rac1-GTP protein in healthy Chinese Hans population.

Effect of Qi-ming granule on multifocal ERG(mfERG) of patients with mild, moderate non-prolif-erative diabetic retinopathy (NPDR) / 中国医师杂志

Objective To evaluate effect of Qi-ming granule on vision function of patients with mild, moderate non-proliferative diabetic retinopathy ( NPDR ) .Methods Using the randomized double blind and placebo-controlled clinical trial method.From Oct.2012 to Jun.2014, 36 patients with 68 eyes who included in the standard were randomly divided into treatment group,control group,given Qi-ming gran-ule and placebo respectively for 6 months, exam with mfERG before treatment and after treatment, evaluate the curative effect.Results After 6 months treatment of Qi-ming granule, the implicit time of the 4th ring of the N1 wave about the mfERG was shorter than that of preoperative( P <0.05), the amplitude density was more than both that of preoperative and control group( P <0.01), the amplitude density of the 5th ring increased compared to that of control group;The peak latency of 3 rd ring of P1 wave was shorter than that of control group( P <0.01), the amplitude density of 1st,3rd,5th ring restored compared with that of preopera-tive and control group( P <0.01), the amplitude density of 4th ring improve than that of control group( P<0.01).Conclusions Qi-ming granule can improve the multifocal ERG of patients with mild, moderate non-proliferative diabetic retinopathy, restore the vision function.

Distribution of Nm23 gene polymorphism in healthy Chinese Hans population in Hubei,China / 中国免疫学杂志

Objective:To develop a method for the detection of 10 single nucleotide polymorphisms(SNPs) of Nm23 gene,and to explore the genotypic and allelic distributions of the 10 SNPs in Chinese Hans population in Wuhan.Methods: Two hundreds healthy subjects ,115 men and 85 women included ,were enrolled as DNA sample donors.The real time TaqMan-MGB genotyping assay was used for the determination of the 10 SNPs selected ,and the results were validated by direct gene sequencing.Results:The method established could accurately and quickly screen the genotypes of the 10 SNPs of Nm23/NDPK gene.Distribution frequencies of the 10 SNPs were similar to these in other researches as well as these of HCB.All the loci follow the Hardy-Weinberg equilibrium.Highly linkage disequilibriums were found between rs 16949649 and rs7207370 , rs16949649 and rs34214448 , rs2159359 and rs2302254 , rs2159359 and rs8075231 ,rs2159359 and rs2041296 ,as well as rs2159359 and rs8071647 ,respectively.Four Tag SNPs:rs34214448 , rs2302254 ,rs11868380 and rs2318785 were initially selected by Heploview software.Conclusion:The method established for SNP gen-otyping can meet the needs for rapid analysis of Nm 23 gene polymorphisms ,and may have great values in investigating the association between gene polymorphisms and diseases as well as adverse drug reactions.