Objective:To investigate whether idebenone can improve behavioral disorders in mice with Parkinson disease (PD) by increasing PHB2 mediated mitophagy.Methods:In the first small experiment, thirty mice were randomly divided into normal control group, model group and treatment group according to the random number table method, with 10 animals in each group.The aim of this study was to observe the effect of idebenone on the behavior of Parkinson disease model mice. In the second experiment, 20 mice were randomly divided into blank control group, MPTP group, shRNA-PHB2 group and shRNA-PHB2+ MPTP group, with 5 mice in each group. The changes of tyrosine dehydrogenase (TH) in brain tissue were detected by immunofluorescence assay. In the third experiment, 30 mice were randomly divided into blank control group, shRNA-PHB2 group, MPTP+ idebenone group, shRNA-PHB2+ MPTP group, shRNA-PHB2+ idebenone group and shRNA-PHB2+ MPTP+ idebenone group, with 5 animals in each group. The aim of this study was to investigate the effect of idebenone on mitochondrial autophagy in mouse brain.C57BL-6 mice were intraperitoneally injected with MPTP to establish the animal model of chronic PD. Then 200 mg / kg idebenone was given by gavage for 21 days. And the expression of PHB2 in brain was inhibited by microinjection of adeno-associated virus 9 (AAV9) shRNA inhibin 2(PHB2) into lateral ventricle. The behavioral changes of the PD mice were detected by Morris water maze, and the changes of tyrosine dehydrogenase (TH) induced by inhibiting PHB2 were detected by immunohistochemistry. The protein expression of LC3 and PHB2 in substantia nigra of midbrain was detected by Western blot.The data were analyzed by GraphPad 7.0 and SPSS 22.0.Results:(1) In the water maze test data of the first small experiment, the repeated measurement ANOVA showed that the group-time interaction effects of latency of mice from 1 to 7 days were significant ( Ftime×group=20.51, P<0.05). Simple effect analysis showed that on the 5th, 6th and 7th day, the incubation period of the treatment group was significantly shortened (all P<0.05). Univariate analysis of variance showed that on the 7th day of the test, the differences between the control group and the model group, the model group and the treatment group, the control group and the treatment group were all statistically significant( t=-49.95, -21.81, 28.14; all P<0.01). In the third small experiment, repeated measurement analysis of variance showed that the interaction between time and group was significant ( Ftime×group=42.11, P<0.01). Simple effect analysis showed that compared with MPTP+ idebenone group, the latency of shRNA-PHB2+ MPTP+ idebenone group was significantly prolonged (all P<0.05). There were no significant difference between shRNA-PHB2+ MPTP+ idebenone group and shRNA-PHB2+ MPTP group except the 4th day ( P<0.05). On the 7th day, compared with MPTP+ idebenone group, the residence time of shRNA-PHB2+ MPTP+ idebenone group was significantly increased ( t=-34.36, P<0.001), but there was no significant difference between shRNA-PHB2+ MPTP group and shRNA-PHB2+ MPTP+ idebenone group ( t=2.94, P>0.05). (2)The results of immunofluorescence experiment showed that the relative expression of TH in the control group, model group, shRNA-PHB2 group and shRNA-PHB2+ MPTP group were (41.03±3.01), (24.20±4.18), (38.39±3.31) and (13.12±2.65), respectively. Compared with the control group, the expression of TH in the midbrain of the MPTP group was significantly down-regulated, the difference was statistically significant( t=7.98, P<0.01). Compared with the MPTP group, the expression of TH in shRNA-PHB2 group was down regulated ( t=-6.73, P<0.05). (3) Western blot results showed that the relative expression of LC3 in midbrain tissue of control group, shRNA-PHB2 group, MPTP+ idebenone group, shRNA-PHB2+ MPTP group, shRNA-PHB2+ idebenone group and shRNA-PHB2+ MPTP+ idebenone group were (0.86±0.07), (0.77±0.08), (0.42±0.05), (0.21±0.05), (0.66±0.09) and (0.27±0.07). The relative expression of PHB2 were (1.13±0.14), (0.56±0.11), (1.08±0.14), (0.27±0.07), (0.68±0.14) and (0.24±0.10). Compared with MPTP+ idebenone group, the relative expression of LC3 and PHB2 in shRNA-PHB2+ MPTP+ idebenone group was significantly decreased ( F=1.96, P<0.01). Conclusion:Idebenone can increase the level of mitophagy in PD mice through PHB2, thus improving the behavioral disorder.

Objective: Explore the function and regulatory mechanism of Annexin A1 (ANXA1) in bladder cancer cell proliferation, apoptosis and migration. Methods: From February 2018 to June 2019, we use T24 cells as the model and divide it into over-expression control group (ctrl), ANXA1 over-expression group (ANXA1), knockdown control group (shctrl), ANXA1 knockdown group 1 (shANXA1-1), ANXA1 knockdown group 2 (shANXA1-2) and ANXA1 knockdown group 3 (shANXA1-3). 24 hours after the culture, the cells were collected and the mRNA expression level of ANXA1 was detected by Real-Time quantitative PCR. The cell activity was detected by CCK-8; the cell apoptosis and cycle were detected by flow cytometry. The cell migration was detected by Transwell assay. Results: The Real-Time quantitative PCR showed that the expression of ANXA1 in the over expression group was significantly higher than that in the over expression control group (15 369.00±874.20 and 1.00±0.07, P<0.001). The expression of ANXA1 in the knockdown group 2 and 3 were significantly lower than that in the knockdown control group (0.51±0.04, 0.51±0.02 and 1.00±0.04, P<0.001). Compared with the over expression control group(1.61±0.01), the cell activity of the over expression group(2.04±0.02)was significantly increased (P<0.001), while the activity of the knockdown group 2 and 3 (1.40±0.002 and 1.31±0.003)were significantly decreased than the knockdown ctrl group (1.73±0.01)(P<0.001). The results of flow cytometry showed that the number of G₀/G₁ cells in the over-expression group was significantly lower than that in the over-expression control group (28.14±0.33 and 46.19±0.73, P<0.001), while that in the knockdown group 2 and 3 were significantly higher than that in the knockdown control group (58.670±0.49, 62.34±4.01 and 45.59± 0.19, P<0.001 and P<0.05). There was no significant difference in the number of apoptosis between the over-expression group and the over-expression control group (P>0.05), while the number of apoptosis in the knockdown group 2 and 3 were significantly higher than that in the knockdown control group (13.04%, 14.58% and 7.76%, P<0.001). Cell function analysis showed that the number of cells passing through the membrane of the over expression group was significantly higher than that of the over expression group (525.00±9.30 and 385.70±13.40, P<0.01), while that of the knockdown group 2 and 3 were significantly lower than that of the knockdown control group (214.70±6.40, 226.00±5.30 and 398.70±10.00, P<0.001). Conclusions Over-expression of ANXA1 significantly promoted the proliferation, cycle and migration of T24 cells and inhibited apoptosis. On the contrary, ANXA1 knockdown inhibited the proliferation, cycle and migration of T24 cells and promoted apoptosis.

In recent years, the incidence of single-gene nephrolithiasis has been increasing year by year. With the application of whole-genome analysis and whole-exome sequencing technology, the etiology of single-gene mutations leading to the development of urinary calculi has been extensively verified. Therefore, this article reviews the research on urinary calculi-related genetic diseases at home and abroad, and introduces transport proteins and channels; ions, protons and amino acids. The role of urinary calculi in the majority of clinicians realizes the significance of genetic testing in such diseases, thereby increasing the understanding of genetically related urinary calculi and improving the level of clinical diagnosis and treatment.

Objective:To investigate the etiological mechanism in single small subcortical infarction (SSSI) with different imaging features.Methods:The patients registered in a database of ischemic stroke in the Department of Neurology of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2019 were analyzed. According to the lowest slice (LS) and the total number of involved slices (TNS) on diffusion-weighted imaging, the SSSI was divided into 3 types: proximal SSSI (pSSSI; LS≤2), distal and large SSSI (dl-SSSI; LS>2, TNS>2) and distal and small SSSI (ds-SSSI; LS>2, TNS≤2). The clinical and imaging features among 3 different lesion patterns were compared by using χ 2 test, Kruskal-Wallis H test and multiple Logistic regression analysis, etc. Results:In the 3 groups of ds-SSSI ( n=205), dl-SSSI ( n=157) and pSSSI ( n=166), the prevalences of parent artery disease (PAD)[10.7% (22/205) , 19.1% (30/157) , 42.8% (71/166), respectively, χ 2=54.89, P<0.001], coronary artery disease [8.3% (17/205), 14.0% (22/157), 16.9%(28/166), respectively, χ 2=6.44, P=0.040] and severe white matter hyperintensities (sWMHs)[58.0% (119/205), 43.3% (68/157), 41.0% (68/166), respectively, χ 2=12.94, P<0.001], the level of serum homocysteine (Hcy)[18.01 (13.54, 25.56), 16.03 (12.50, 21.09), 14.72 (11.12, 19.14) μmol/L, respectively, H=19.36, P<0.001], and the National Institutes of Health Stroke Scale (NIHSS) score[2(1, 3), 3(1, 4), 3(2, 6), respectively, H=39.53, P<0.001] showed statistically significant differences. Multiple Logistic regression analysis showed that compared with dl-SSSI patients, the lesion pattern of patients with higher proportion of PAD ( OR=3.12, 95% CI 1.86-5.24, P<0.001) was closer to pSSSI; the lesion pattern of patients with higher serum Hcy level ( OR=1.02, 95% CI 1.00-1.04, P=0.046) or higher proportion of sWMHs ( OR=1.79, 95% CI 1.12-2.86, P=0.015) was closer to ds-SSSI, and the lesion pattern of patients with higher proportion of PAD ( OR=0.50, 95% CI 0.27-0.93, P=0.029) or higher NIHSS score ( OR=0.84, 95% CI 0.77-0.92, P<0.001) was closer to dl-SSSI. Conclusions:The pathogenesis of ds-SSSI tends to be cerebral small vessel disease. The pathogenesis of pSSSI is related to atherosclerosis. The patients with dl-SSSI have the intermediate characteristics of pSSSI and ds-SSSI and may be unstable.

Background It has been reported that orthokeratology has the effects of slowing down myopia progression and axial elongation.However,the affecting mechanism of orthokeratology wearing on ocular peripheral refraction is still not elucidated.Objective This study was to observe and compare the changes of ocular peripheral refraction and relative peripheral refraction (RPR) in low to moderate myopic eyes of children after wearing orthokeratology lens and spectacles for 6 months.Methods A randomized controlled clinical trial was carried out after approval of Ethic Committee of Beijing Tongren Hospital and informed consent of guardians of the children.One hundred myopic children aged (ll.0±1.9) years were recruited in Beijing Tongren Hospital from June 2014 to January 2015,with the diopter of-0.50 to-6.00 D.The subjects were randomized into orthokeratology group and spectacles group by the process PLAN PROC of software SAS 9.1.3,50 for each group.The subjects in the orthokeratology group wore orthokeratology lens for 6 months and those in the spectacles group wore spectacles for the same period.An infrared open-field autorefractor was employed to measure the refraction at central 0°,temporal 15°,temporal 30°,nasal 15°and nasal 30° radial lines before and after wearing lens for the assessment and comparison of the changes of peripheral refraction and RPR.Results There was no significant difference in spherical equivalent between the orthokeratology group and the spectacles group before wearing lens ([-3.35±1.31] D versus [-3.01± 1.15] D,P =0.20).The peripheral refraction values in the orthokeratology group were (-2.28 ± 1.60),(-3.28±1.41),(-3.40±1.23),(-3.38±1.12) and (-2.09±1.29)D at nasal 15°and nasal30°,central,temporal 15° and temporal 30°radial lines before wearing lens,and reduced by (0.29±1.67),(0.85±1.66),(0.92±1.76) and (0.66±1.66) D at nasal 30°,nasal 15°,central and temporal 15° after wearing lens,respectively,with significant differences at nasal 15°,central and temporal 15°(all at P＜0.05).The peripheral refraction values in the spectacles group were (-1.88±1.30),(-2.66±1.18),(-2.89±1.27) and (-1.94±1.31)D at nasal 15°,nasal 30°,temporal 15 ° and temporal 30°,radial lines before wearing lens and increased by (-0.25±0.80),(-0.43 ±0.67),(-0.32±0.64) and (-0.22±0.75)D after wearing lens,respectively,with significant differences between before and after wearing lens (all at P＜0.05).The RPR shifted from hyperopia defocus to myopia defocus before and after wearing lens in temporal 15° and 30° radial lines in the orthokeratology group,and at various radial lines in the spectacles group,the RPR showed gradually worsening of hyperopia defocus.Conclusions Long-term wearing of orthokeratology results in a hyperopia shifting in myopic children by exposing the peripheral retina towards relative myopia defocus,whereas wearing spectacles leads to a relative hyperopia defocus on retina.Thus,orthokeratology may slow down the myopia progression.

L-arginine (L-Arg) is an alkaline amino acid that possesses various function groups and acts as an important precursor for useful chemical synthesis. L-Arg derivatives are widely applied in pharmaceutical, food and cosmetic industries. Environment friendly and cost-effective production of L-Arg derivatives by enzymatic catalysis provides significant advantages over chemical synthesis and microbial fermentation. In this article, several typical L-Arg derivatives and their enzymatic production processes are highlighted. Furthermore, prospect is also addressed about enzymatic production of L-Arg derivatives.