AIM: To analyze the mechanism of Usher syndrome(USH)caused by Adgrv1 gene variation through the Hedgehog(Hh)signaling pathway.METHODS: Based on Adgrv1 gene variant mice(Adgrv1-/-), taking wild type(WT)C57BL/6 mice as controls, the expression of Adgrv1 gene and the structure of retina and cell cilia were analyzed by qRT-PCR, HE, transmission electron microscopy, and immunofluorescence. Additionally, the changes of key factors in the Hh signaling pathway caused by Adgrv1 gene variation were observed.RESULTS: The Adgrv1 gene was expressed in both the retina and primary cultured lung fibroblasts of Adgrv1-/- mice, but the expression levels were significantly decreased. The Adgrv1 gene variation can cause dissolution of the outer disc membrane of the retinal photoreceptors and significantly shorten the cilia length in primary lung fibroblasts. In the Hh signaling pathway, the expression of Ptch1 and Gli genes of Adgrv1-/- was significantly reduced, while the expression of PKA genes was increased.CONCLUSION:The Adgrv1 gene variation leads to shortened cell cilia and dissolution of the outer disc membrane of the retinal photoreceptors, resulting in retinitis pigmentosa, which is related to decreased expression of PTCH1 and GLI1 proteins in the Hh pathway.

Humans ; COVID-19 ; Epidemics ; Respiratory Tract Diseases ; Hospitalization

ObjectiveTo analyze changes of the chemical composition in Euodiae Fructus before and after processing with Coptidis Rhizoma decoction， so as to provide scientific basis for elucidating the processing mechanism of this decoction pieces. MethodUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF/MS） was performed on a Titank C₁₈ column （2.1 mm×100 mm， 1.8 μm）， the mobile phase was 0.1% formic acid aqueous solution-acetonitrile for gradient elution， the column temperature was set at 40 ℃， the flow rate was 0.25 mL·min^-1. Electrospray ionization （ESI） was used to scan in positive and negative ion modes， and the scanning range was m/z 50-1 250. The chemical constituents in Euodiae Fructus were identified before and after processing by reference substance comparison， database matching and literature reference， and MarkerView™ 1.2.1 software was used to normalize the obtained data， SIMCA-P 14.1 software was employed to perform principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） on MS data of raw and processed products to screen the differential components before and after processing. ResultA total of 50 compounds were identified， including 48 kinds of stir-fried products with Coptidis Rhizoma decoction and 44 kinds of raw products. After processing， six compounds were added， including danshensu， noroxyhydrastinine， oxyberberine， 13-methylberberrubine， protopine and canadine. However， two kinds of compounds， including （S）-7-hydroxysecorutaecarpine and wuchuyuamide Ⅱ， were not detected after processing. In general， after processing， the overall contents of phenolic acids and flavonoids decreased significantly， the overall content of limonoids increased， and the overall content of alkaloids did not decrease insignificantly. The results of PCA and OPLS-DA showed that there were significant differences in the composition and content of the chemical components of Euodiae Fructus before and after processing， and a total of 12 variables such as quercetin， dihydrorutaecarpine and dehydroevodiamine were obtained by screening. ConclusionEuodiae Fructus stir-fried with Coptidis Rhizoma decoction mainly contains phenolic acids， flavonoids， limonoids and alkaloids. The composition and content of the chemical components have some changes before and after processing. The addition of processing excipients and hot water immersion are the main reasons for the difference， which can provide experimental basis for interpretation of the processing mechanism of this characteristic processed products of Euodiae Fructus.

ObjectiveTo quickly analyze and identify the components in raw and rice-washed water products of Atractylodes lancea rhizoma （ALD） by ultra-high performance liquid chromatography quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF-MS）， and then find out the differential components before and after processing. MethodTitanK C₁₈ column （2.1 mm×100 mm， 1.8 μm） was used with 0.1% formic acid aqueous solution （A）-acetonitrile （B） for gradient elution （0-0.01 min， 10%B； 0.01-12 min， 10%-25%B； 12-18 min， 25%-55%B； 18-30 min， 55%-70%B； 30-35 min， 70%-95%B； 35-37 min， 95%B； 37-37.1 min， 95%-10%B under negative ion mode and 0-0.01 min， 10%B； 0.01-10 min， 10%-56%B； 10-30 min， 56%-75%B； 30-35 min， 75%-95%B； 35-37 min， 95%B； 37-37.1 min， 95%-10%B under positive ion mode）. Electrospray ionization was selected for collection and detection in positive and negative ion modes with the scanning range of m/z 100-1 250. Combining the reference substances， databases and related literature information， PeakView 1.2 software was used to identify the chemical components of ALD and its rice-washed water products. After normalized treatment by MarkerView™ 1.2.1， the MS data of each sample were analyzed with principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） in SICMA 14.1， and then the differential components before and after processing were screened according to the principle of variable importance in the projection （VIP） value>1 and P<0.01 in t-test. ResultA total of 56 components were identified from the raw and rice-washed water products of ALD， including 17 terpenoids， 8 polyacetylenes， 12 organic acids， 4 glycosides， 4 flavonoids and 11 others. There were 43 components in both， and 7 and 6 specific components respectively. The results of PCA and OPLS-DA showed that there were significant differences in the contents of the chemical components of ALD before and after processing， and 23 differential components such as atractylodin， atractylenolide Ⅰ， atractylenolide Ⅱ and wogonin were screened. ConclusionALD mainly contains sesquiterpenoids， polyacetylenes and organic acids. The components of ALD are hydrolyzed before and after processing， and the content of active ingredients such as atractylodin increased. According to this， it can provide reference for the research on material basis of processing of ALD.

ObjectiveTo identify the chemical constituents of Alismatis Rhizoma before and after processing with salt-water by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF-MS）， and to investigate the changes of terpenoids in Alismatis Rhizoma before and after processing with salt-water. MethodUPLC-Q-TOF-MS was used to detect with 0.1% formic acid aqueous solution （A）-acetonitrile （B）as mobile phase for gradient elution （0-0.01 min， 20%B； 0.01-5 min， 20%-40%B； 5-40 min， 40%-95%B； 40-42 min， 95%B； 42-42.1 min， 95%-20%B； 42.1-45 min， 20%B）， electrospray ionization （ESI） was selected for collection and detection in positive ion mode with the scanning range of m/z 100-1 250 and ion source temperature at 500 ℃. The data were analyzed by PeakView 1.2.0.3， the components were identified according to the primary and secondary MS data， and combined with the reference substance and literature. After normalized treatment by MarkerView 1.2.1， the MS data were analyzed by principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA）， and then the differential components before and after processing were screened. The content changes of differential components were analyzed according to the relative peak area. ResultA total of 30 components were identified under positive ion mode， including 28 prototerpene triterpenes and 2 sesquiterpenes. The results of PCA and OPLS-DA showed that there were significant differences in components from Alismatis Rhizoma before and after processing with salt-water， and 10 differential components （alisol B 23-acetate， alisol I， alismol， 11-deoxy-alisol B 23-acetate， alisol B， alisol C， 11-deoxy-alisol B， alisol G， 11-deoxy-alisol C and alisol A） were screened， and the contents of alisol G and alisol A decreased significantly after processing. ConclusionUPLC-Q-TOF-MS can comprehensively and accurately identify the chemical constituents in raw and salt-processed products of Alismatis Rhizoma. It takes a great difference in the contents of chemical constituents before and after processing， and the difference of substituents is the main reason for this differences， which can provide reference for determining the material basis of efficacy changes of Alismatis Rhizoma before and after processing with salt-water.

ObjectiveBy comparing the composition and content changes of the volatile components in Atractylodis Rhizoma before and after processing with rice-washed water， the effect of rice-washed water processing on volatile components in Atractylodis Rhizoma was investigated. MethodHeadspace-gas chromatography-mass spectrometry （HS-GC-MS） was used to detect the volatile components in rhizomes of Atractylodes chinensis and A. lancea， and their processed products of rice-washed water. Chromatographic conditions were programmed temperature （starting temperature of 50 ℃ for 2 min， rising to 120 ℃ with the speed of 10 ℃·min^-1， then rising to 170 ℃ at 2.5 ℃·min^-1， and rising to 240 ℃ at 10 ℃·min^-1 for 3 min）， the inlet temperature was 280 ℃， the split ratio was 10∶1， and the solvent delay time was 3 min. The conditions of mass spectrometry were electron bombardment ionization （EI） with ionization temperature at 230 ℃ and detection range of m/z 20-650. Then the relative content of each component was determined by the peak area normalization method. SIMCA 14.1 software was used to perform unsupervised principal component analysis （PCA） and supervised orthogonal partial least squares-discriminant analysis （OPLS-DA） on each sample data， the differential components of Atractylodis Rhizoma and its processed products were screened by the principle of variable importance in the projection （VIP） value>1. ResultA total of 60 components were identified， among which 40 were rhizomes of A. chinensis and 38 were its processed products， 46 were rhizomes of A. lancea and 47 were its processed products. PCA and OPLS-DA showed that the 4 kinds of Atractylodis Rhizoma samples were clustered into one category respectively， indicating that the volatile components of the two kinds of Atractylodis Rhizoma were significantly changed after processing with rice-washed water， and there were also significant differences in the volatile components of rhizomes of A. lancea and A. chinensis. The compound composition of Atractylodis Rhizoma and its processed products was basically the same， but the content of the compounds was significantly different. The differential components were mainly concentrated in monoterpenoids and sesquiterpenoids， and the content of monoterpenoids mostly showed a decreasing trend. ConclusionAfter processing with rice-washed water， the contents of volatile components in rhizomes of A. lancea and A. chinensis are significantly changed， and pinene， 3-carene， p-cymene， ocimene， terpinolene， atractylon， acetic acid and furfural can be used as difference markers before and after processing.

Objective:To observe the effect of combining scalp acupuncture with feedback training on muscle tone, motor ability, plantar pressure distribution and joint range of motion of stroke survivors with lower limb spastic paralysis.Methods:A total of 212 stroke survivors were randomly divided into a combination group ( n=70), an exercise group ( n=70) and a scalp acupuncture group ( n=72) according to a random number table. All of the patients received routine medication and 120 minutes of rehabilitation training six days a week for 8 consecutive weeks. The rehabilitation training included guidance on good posture, posture change training, balance training and gait training. The scalp acupuncture and exercise groups were additionally provided with 40 minutes of scalp acupuncture and lower limb intelligent feedback training, while the combination group was given both. Muscle tension, balance and lower extremity movement were quantified before and after the training, and a gait evaluation system was used to detect the plantar pressure distribution on the affected side and the range of motion range of the lower limb joints during walking. Results:After the treatment, significant differences were observed in the average modified Ashworth scores, modified Berg scale scores, Fugl-Meyer lower extremity ratings and modified Barthel Index scores compared with before the treatment. The average scores of the combination group were then significantly better than those of the other two groups. The average load bearing ratios of the affected toes, metatarsal bones Ⅰ-V, medial arch, external arch, medial heel and external heel had improved significantly in all of the groups, with the improvement of the combination group again significantly greater than those of the other groups. The same pattern of improvement was observed in the groups′ average pelvic rotation angles, hip flexion angles, knee flexion angles and ankle dorsiflexion angles.Conclusion:Combining scalp acupuncture with intelligent feedback can significantly improve lower extremity functioning after a stroke. That should improve performance in the activities of daily living of stroke survivors.

Objective:To explore the influence of multidimensional integration and 360° support on the function of family and marriage, and quality of life in women patients with systemic lupus erythematosus.Methods:Totally 196 patients with systemic lupus erythematosus from Department of Rheumatology and Immunology, The Second Affiliated Hospital of the Air Force Medical University from August 2016 to November 2017 were included. According to random number table method, these patients were divided into observation group and control group as 98 cases each. Conventional care and hospital discharge were used for control group. On the basis of this, multidimensional integration and 360° support were used for patients of observation group. The function of family and marriage, quality of life in patients were assessed before and after 3 months of the intervention. The treatment adherence was evaluated in 3 months and 6 months after intervention.Results:Before intervention, the marriage family function score, marital satisfaction, conflict resolution methods and the relationship with friends and family, husband and wife exchange scores of the observation group were (2.3 ± 0.5), (24.6 ± 6.1), (25.7 ± 7.1), (28.2 ± 6.9), (28.8 ± 6.9) points, respectively. Three months after intervention, these scores were (2.5 ± 0.7), (31.6 ± 5.0), (31.7 ± 5.3), (28.1 ± 6.8), (29.0 ± 7.1) points, respectively. There was statistically significant difference between before and after the intervention ( t values were -2.371 - 8.631, P < 0.01). These scores of control group before the intervention were (2.3 ± 0.6), (24.5 ± 6.2), (25.2 ± 7.2), (32.5 ± 6.0), (33.9 ± 6.3) points, respectively. Three months after intervention, these scores were (2.3 ± 0.4), (24.5 ± 6.2), (26.1 ± 6.9), (29.1± 4.8), (28.5 ± 7.2) points. Significant differeces were found between before and after the intervention in control group ( t values were -3.878-6.323, P < 0.05 or 0.01). There was statistically significant difference between the two groups after the intervention ( t values were 2.675-8.631, P<0.01). As for observation group, planning (62.8 ± 27.2 vs. 75.5 ± 25.4) and intimate relationship (62.8 ± 25.2 vs. 78.2± 24.9) in quality of life were obviously difference before and after 3 months of intervention ( t values were 3.050, 3.639, P < 0.01). As for control group, planning (62.5 ± 27.6 vs. 65.7 ± 24.9) and intimate relationship (65.8 ±25.2 vs. 63.5 ± 23.8) in quality of life were obviously difference before and after 3 months of intervention ( t values were 2.375, 3.132, P < 0.01). There was statistically significant difference between the two groups after the intervention ( t values were 3.050, 3.639, P < 0.01). The treatment adherence of observation group was significant better than control group. After 6 months intervention, the treatment adherece of observation group was 83.67% (82/98), while the treatment adherece of control group was 44.89% (44/98), significant differences were found btween the two groups ( χ2 value was 0.511, P < 0.01). Conclusion:Multidimensional integration and 360° support obviously improved function of family and marriage, improved the understanding of disease, and self-management ability of patients. Therefore, it can increase the treatment adherence and improve quality of life in SLE patients.

In the nucleus, chromatin is folded into hierarchical architecture that is tightly linked to various nuclear functions. However, the underlying molecular mechanisms that confer these archi-tectures remain incompletely understood. Here, we investigated the functional roles of H3 lysine 9 dimethylation (H3K9me2), one of the abundant histone modifications, in three-dimensional (3D) genome organization. Unlike in mouse embryonic stem cells, inhibition of methyltransferases G9a and GLP in differentiated cells eliminated H3K9me2 predominantly at A-type (active) genomic compartments, and the level of residual H3K9me2 modifications was strongly associated with B-type (inactive) genomic compartments. Furthermore, chemical inhibition of G9a/GLP in mouse hepatocytes led to decreased chromatin-nuclear lamina interactions mainly at G9a/GLP-sensitive regions, increased degree of genomic compartmentalization, and up-regulation of hundreds of genes that were associated with alterations of the 3D chromatin. Collectively, our data demonstrated essential roles of H3K9me2 in 3D genome organization.