A 91-year-old male patient was admitted with a history of mitral valve prolapse diagnosed by physical examination ten years prior and recent onset of exertional chest discomfort persisting for over one month. Transthoracic echocardiography showed that the anterior leaflet of mitral valve was thickened and prolapsed with severe regurgitation, and transesophageal echocardiography further confirmed that the anterior and posterior leaflets of mitral valve were prolapsed with massive regurgitation (A1, A2, A3, P1 and P2 were all prolapsed). Thus, the diagnosis of Barlow syndrome was considered. Transcatheter edge-to-edge mitral repair was performed with two MitraClip^TM G4 XTWs. After a 10 months follow-up, the patient's cardiac function was significantly improved, and the degree of mitral regurgitation was mild.
Humans ; Male ; Aged, 80 and over ; Mitral Valve Insufficiency/surgery* ; Mitral Valve Prolapse/diagnostic imaging* ; Cardiac Catheterization/methods* ; Mitral Valve/surgery* ; Heart Valve Prosthesis Implantation/methods*

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

Objective: To investigate the brain volume alterations in patients with hyposmia using voxel-based morphometry (VBM) and to correlate these alterations with the degree and duration of hyposmia. Methods: Forty patients with hyposmia from Department of Otorhinolaryngology Head and Neck Surgery, Beijing Anzhen Hospital since 2013 to 2016 and forty age and sex matched normal subjects were recruited in this study. Sniffin′ Sticks olfactory test was performed to evaluate the olfactory function of all subjects. We acquired T1-weighted magnetic resonance images from all subject on a 3T scanner. VBM was performed using VBM8 toolbox and SPM8 in a Matlab environment. Independent sample t test analysis was used to compare the volume of gray and white matter between the controls and patients. In addition, the Pearson or Spearman correlation analysis was used for the correlation between the voxel value of cerebral volume alterations area and the degree and duration of hyposmia on patients (threshold discrimination identification, TDI). Results: Compared with the controls, patients showed significantly decreased volume in the gray matter of right orbitofrontal cortex (number of voxel in clusters was 226, t=-4.46, P<0.001, uncorrected). There was negative correlation between decreased gray matter volume of the right orbitofrontal cortex with significantly decreased area and the TDI results (r=-0.40, P=0.01), but positive correlation with duration of hyposmia (r=0.37, P=0.02). Conclusions The patients with hyposmia show gray matter atrophy of the right orbitofrontal cortex. The duration may be an important risk factor for decreased gray matter in patients with hyposmia.

Objective: To investigate the white matter integrity in patients with olfactory dysfunction using diffusion tensor imaging (DTI). Methods: Twenty-one patients with olfactory dysfunction and sixteen age, sex and level of education matched normal subjects were recruited in this study. Sniffin′ Sticks olfactory test was performed to evaluate the olfactory function of all subjects. We acquired diffusion tensor images with a echo planar imaging (EPI) sequence from all subjects on a 3T scanner. The fractional anisotropy (FA) images were performed using DTI-studio, and bilateral piriform cortex, orbitofrontal cortex, hippocampus and insula cortex adjacent white matter as well as capsula interna were delineated from the FA images as the region of interest associated with olfactory (ROI_awo) manually. Independent sample t test analysis was used to compare the FA value of all ROI_awo between the controls and patients. Results: In olfactory dysfunction group, the FA value of adjacent white matter of right piriform cortex and orbitofrontal cortex were significantly lower than those of control group (0.42±0.05 (±s) vs 0.45±0.05, 0.43±0.06 vs 0.49±0.07, t value was 2.32, 2.79, respectively, all P<0.05). The FA value of adjacent white matter of left piriform cortex and orbitofrontal cortex had no significant difference compared with those of control group (0.43±0.05 vs 0.45±0.04, 0.44±0.04 vs 0.47±0.06, t value was 1.65, 1.37, respectively, all P>0.05). The FA value of the adjacent white matter of bilateral hippocampus, insula cortex and capsula interna had no significant difference compared with those of control group, neither (0.45±0.08 vs 0.44±0.08, 0.45±0.09 vs 0.44±0.10, 0.41±0.08 vs 0.39±0.07, 0.41±0.07 vs 0.38±0.05, 0.64±0.08 vs 0.63±0.08, 0.64±0.07 vs 0.63±0.07, t value was 0.30, 0.15, 0.88, 1.34, 0.14, 0.35, respectively, all P>0.05). Conclusions The patients with olfactory dysfunction showed abnormal white matter connection in the major primary and secondary olfactory cortex. The reduced white matter integrity in ROI_awo might contribute to the pathogenesis of olfactory dysfunction.

Objective: Using ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) and microPET-CT to test the feasibility of ¹⁸F-FDG PET-CT for validation of olfactory function of rats with standard phenethyl alcohol (PEA) and isovaleric acid (IVA) odors stimulation. To verify the possibility of ¹⁸F-FDG PET-CT as a new objective examination method for olfactory function. Methods: Six healthy Sprague-Dawley (SD) male rats were selected with a weight of 250-300 g. First of all, buried food pellet test (BFT) was used to confirm the normal olfactory function of rats. Then in the next 3 days, after the intravenous injection of ¹⁸F-FDG (18 MBq/100 g), awaken rats were placed in a ventilated plexiglas cage for 30 min. Subsequently, pure air (the first day), PEA (the second day) and IVA (the third day) were delivered. After odor stimulation for 30 min, rats were performed by a static PET-CT under anesthesia. Images reconstructed were assessed by SPM method and analyzed by VBM method. Data was analysied by paired t test. Results: Activation regions of rat′s brain after PEA stimulation included bed nucleus and insula. Activation regions of rat′s brain after IVA stimulation included olfactory bulb, anterior olfactory nucleus, amygdala, entorhinal cortex, olfactory cortex, piriform cortex, insula, prefrontal cortex, cingulate cortex and bed nucleus (P<0.005, Ke>20 voxels). Conclusions Through microPET-CT, we can observe that olfactory stimulation with different odors can induce metabolic activation in different regions of rat′s brain, which was in concordance with olfactory regions. The olfactory related brain regions of rats have strong responses to odor stimulation of IVA.

Objective: To explore the clinical effects and the influence factors of olfactory training in the treatment of olfactory dysfunction. Methods: A total of 86 patients with olfactory dysfunction (49 post-infectious and 37 post-traumatic) in Beijing Anzhen Hospital during Dec 2016 to May 2017 were recruited in this prospective study. The clinical data of patients were analyzed, including gender, age, body mass index (BMI), course of disease, smoking history, drinking history, diabetes history, hypertension history, hyperlipidemia history, and anxiety visual analogue score (VAS). All patients were treated with olfactory training for 16 weeks, and all of them underwent Sniffin′ Sticks olfactory test before and after treatment, which was evaluated by composite threshold-discrimination-identification score (TDI). SPSS 23.0 software, paired t test and univariate and multivariate Logistic regression analysis were used to analyze the data. Results: Eighty patients received treatment, including 46 post-infectious olfactory dysfunction and 34 post-traumatic olfactory dysfunction. After olfactory training, the total scores of TDI increased with statistically significant (18.3±8.6 vs 13.6±7.4, t=-6.158, P<0.05). The overall efficacy was 40% (32/80). The effective rate were 45.7% (21/46) in post-infectious olfactory dysfunction and 32.4% (11/34) in post-traumatic olfactory dysfunction respectively, with no statistically significant difference (χ²=1.441, P=0.230). Logistic regression analysis showed that the course of disease was an influence factor in the clinical curative effect (OR=0.881, 95%CI: 0.799-0.973, P=0.012). In patients with less than a year of olfactory dysfunction, the olfactory function improved obviously with the efficiency of 50.9% (29/57). Conclusion Sixteen weeks of olfactory training provides a significant therapeutic effect on the post-infectious and post-traumatic olfactory dysfunction, and the olfactory training can achieve better therapeutic effects at the early stage.

Objective To improve the orotracheal intubation verifying technique and reduce the complication of backflow in rat experiment.Methods A new position evaluation of anti-backflow device was designed and made of safety IV catheter and closed IV catheter system.60 adult male Sprague Dawley rats 216±20 g were randomly assigned to two groups: group A (n=40) for verifying placement, group B (n=20) for anti-backflow test.Group A was further divided into group A1 using self-designed positioning device, group A2 using aerosol, group A3 taking cotton fiber for positioning judgment.The group B was divided into two subgroups, B1 and B2, counting escaped bubbles as a means of positioning observation, the difference is that group B1 using frustum of a cone shape anti-backflow device, while the group B2 using common airway tube.Routine endotracheal intubation was performed to observe and record the time of positioning, the location of exhalation phase, and the length of inspiratory phase countercurrent water column.The group A1 further performed tracheotomy under direct vision clearly to confirm the anatomic positioning status.Results During the exhalation cycle,three or more bubbles were observed to escape continuously, indicating that the intubation tube was properly placed and open in the airway.Positioning time: It took 1.75±1.02 respiratory cycles in group A1,3.30±0.95 respiratory cycles in group A2 and 4.10±0.99 respiratory cycles in group A3 to complete the assessment the positioning status.There was no statistically significant difference between groups A2 and A3 (P> 0.05).The time needed for group A1 was significantly shorter than that of groups A2 and A3 (P < 0.01).The longest countercurrent water column length in group B1 was 3.23±0.53 cm, and 8.48±1.01 cm in the group B2.Conclusions The new designed anti-backflow positioning evaluation device is a simple and convenient appliance to evaluate the location of orotracheal intubation in rat experiment.It can effectively improve the positioning efficiency and has practical application value.

We transformed the fip-fve gene into Pichia pastoris GS115 for inducible and constitutive expression to obtain feasible bioactvie recombinant Fip-fve. The fip-fve gene was cloned from Flammulina velutipes fruting body by PCR and ligated to pPIC9 to construct inducible expression vector pPIC9-FIP-fve, and promotor pgap was used to replace the paox1 to construct constitutive expression vector pPIC9-PGAP-FIP-fve. These two vectors were used to transform P. pastoris by PEG method. The fip-fve was expressed after histamine-absence screening and yeast colony PCR. The inducible expression level reached 158.2 mg/L at the fourth day and the constitutive expression level was 46.3 mg/L and 29.5 mg/L using glucose and glycerol, respectively. The SDS-PAGE and Western blotting both proved the correctness of rFip-fve, and the hemagglutination test indicats the rFip-fve's bioactivity.
Electrophoresis, Polyacrylamide Gel ; Flammulina ; chemistry ; Fungal Proteins ; biosynthesis ; Genetic Vectors ; Pichia ; metabolism ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; Recombinant Proteins ; biosynthesis

Objective To observe the changes of urine microalbumin (mAlb), renal function and intima-media thickness(IMT) of the carotid artery in prehypertensive patients and investigate whether there are related target organ damage. Methods From August 2009 to May 2010,one hundred and eighty patients were recruited into the study and divided into 3 groups according to the 2005 revised edition of guideline for prevention and treatment of hypertension in China: Sixty normotensive subjects ( NT group,41 males, 19 females,mean age [54. 6 ± 12. 3] years old) ;Sixty prehypertensive patients( PH group,32 males,28 females,mean age [57.0 ± 12.7] years old) and 60 hypertensive patients ( EH group, 28 males, 32 females, mean age [65.0 ±12. 1] years old). Urine mAlb, serum creatinine(Cr) and IMT of the carotid artery were measured and compared among the three groups. The relationships between prehypertension and urine mAlb,serum Cr, IMT of the carotid artery were analyzed. Results In the NT group, PH group and EH group, the urine mAlb concentrations were ( 15.3 ± 7.5 ) mg/L, ( 24. 6 ± 10. 7 ) mg/L and ( 37.3 ± 20. 4) mg/L respectively ;serum Cr were ( 68.0 ± 16. 5 )μmol/L, (81.9 ± 14.9)μmol/L and (95.8 ± 22.5)μmol/L respectively; IMT of the carotid artery were ( 1.46 ± 0. 67 ) mm, ( 1.79 ± 0. 74 ) mm and( 2. 34 ± 0. 78 ) mm respectively. Urine mAlb, serum Cr and IMT of the carotid artery were significantly higher in the PH group and EH group when compared to NT group ( P ＜0. 05 or 0. 01 ); and in the EH group these indices were also significantly higher than those in the PH group( P ＜0. 01 ). Multiple linear regression analysis showed that after adjusted age, body mass index (BMI), blood pressure( BP), serum lipid and serum glucose, in the PH group,the standard partial regression coefficients of correlation between urine mAlb and systolic blood pressure (SBP), diastolic blood pressure(DBP) and serum glucose were 0. 279,0. 259 and 0. 360 respectively ( P = 0. 012, 0. 043 and ＜ 0. 001 ); the standard partial regression coefficients of correlation between serum Cr and SBP, DBP and serum glucose were 0. 317,0. 257 and 0. 377 respectively ( P = 0. 006,0. 049 and ＜ 0. 001 ). The standard partial regression coefficients of correlation between IMT of the carotid artery and age, SBP, DBP, total cholesterol and serum glucose were 0. 381,0. 375,0. 263,0. 265 and 0. 372 respectively( P ＜ 0. 001, ＜ 0. 001, = 0. 033,0. 021 and ＜ 0. 001 ). In the EH group, the standard partial regression coefficients of correlation between urine mAlb and SBP, DBP and serum glucose were 0. 378,0. 258 and 0. 283 respectively( P ＜ 0. 001, = 0. 046, and 0. 009); the standard partial regression coefficients of correlation between serum Cr and SBP, DBP and serum glucose were 0. 294,0. 261 and 0. 464respectively (P =0. 008,0. 042 and ＜0. 001 ) ;the standard partial regression coefficients of correlation between IMT of the carotid artery and age, SBP, high density lipoprotein cholesterol and serum glucose were 0. 262,0. 264, -0. 374 and 0. 306 respectively ( P = 0. 035,0. 023, ＜ 0. 001 and 0. 007 ). We found that both urine mAlb and serum Cr were significantly associated with BP and serum glucose; IMT of the carotid artery was significantly associated with age, BP, serum lipid and serum glucose. Conclusion Urine mAlb, serum Cr andIMT of the carotid artery increased in prehypertensive patients, and these indices were significantly associatedwith the level of the BP. These data indicated there were related target organ damage occurred in prehypertensive patients,the BP level was the risk factor that increased urine mAlb,serum Cr and IMT of the carotid artery.