1.Multimodal investigation of stress-induced RNA-brain covariance and its association with depression vulnerability
Yun LIU ; Xijuan XIA ; Kehan YAN ; Yang JI ; Yifeng LUO ; Zhihong CAO ; Yuefeng LI
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(9):790-797
Objective:To explore the RNA expression and alterations in brain structure in individuals who have experienced stressful life events (SLE), as well as the correlation patterns between them and their association with the occurrence of depression.Methods:Prospectively, a total of 80 SLE subjects were recruited from the psychiatry and psychology clinic of the Jiangsu University Affiliated Yixing Hospital between January 2021 and December 2022, with 16 normal controls (NC) enrolled concurrently. The 17 items Hamilton depression scale (HAMD-17) and social readjustment rating scale (SRRS) were used to assess depressive symptoms and stress levels. RNA sequencing information of peripheral blood and imaging data at baseline were collected. Based on whether depression occurred during the 2-year follow-up period, SLE subjects were divided into the SLE-depression group ( n=15) and the SLE-non-depression group ( n=65). Differentially expressed genes (DEGs) were screened using differential analysis and protein-protein interaction (PPI) networks. Fractional anisotropy (FA) of white matter tracts and gray matter volume (GMV) were extracted using tract-based spatial statistics and voxel-based morphometry.Using analysis of variance compared inter-group differences in gene expression, GMV and white matter FA values. Partial correlation analysis was used to explore correlations between DEGs, altered GMV and white matter microstructure. Gene set enrichment analysis (GSEA) was performed on key genes to identify potential biological pathways. Propensity score matching constructed sensitivity subgroups to verify result robustness. Results:The SLE-depression group showed significantly higher SRRS and HAMD-17 scores at baseline and at the end of follow-up compared to the SLE-non-depression group and the NC group ( H=47.773, 35.427, 41.114, all P<0.05). Expression levels of IL-10 (2.12±0.28, 2.43±0.44), EZH2 (2.11±0.43, 2.45±0.51), NCAM1 (3.60±0.30, 3.03±0.39), CD3E (4.95±0.37, 4.57±0.48), CCK (3.29±0.28, 3.02±0.42), and CX3CR1 (5.55±0.40, 5.91±0.34) were significantly different between the SLE-depression group and SLE-non-depression group( F=5.549~28.371, all P<0.05). Compared with the SLE-non-depression group, the SLE-depression group exhibited significantly lower FA values in the genu of the corpus callosum (0.29±0.04, 0.31±0.04) and the left uncinate fasciculus (0.31±0.02, 0.33±0.02), as well as significantly smaller GMV in the right hippocampus (0.29±0.07, 0.33±0.06), bilateral middle frontal gyrus (left: 0.27±0.05, 0.31±0.05; right: 0.28±0.06, 0.32±0.06), right insula (0.36±0.03, 0.38±0.04), and left precentral gyrus (0.19±0.04, 0.24±0.05) ( F=4.593-12.064, all P<0.05, FDR correction). GMV in the right anterior cingulate and paracingulate gyri was significantly larger than that in the SLE-non-depression group (0.34±0.05, 0.29±0.06) ( F=6.704, P=0.034, FDR correction). Partial correlation analysis revealed significantly stronger correlations between hub DEGs and altered brain regions in the SLE-depression group ( r=0.017-0.801) compared to the SLE-non-depression group ( r=0.002-0.382), with a statistically significant difference ( U=629, P<0.001; Cliff's Delta=0.454). GSEA indicated that the aforementioned genes were primarily involved in pathways including the ribosome, spliceosome, ribosome biogenesis in eukaryotes, and neuroactive ligand-receptor interaction. Sensitivity analysis confirmed that the above results remained statistically significant after balancing sample sizes (all P<0.05). Conclusion:The SLE-depression group showed specific RNA expression and brain structure alterations compared to the SLE-non-depression group, and the correlation between RNA and brain structure was significantly enhanced in the SLE-depression group. This suggests that the correlation between genes and brain structure in the SLE population may be related to their susceptibility to depression.
2.Multimodal investigation of stress-induced RNA-brain covariance and its association with depression vulnerability
Yun LIU ; Xijuan XIA ; Kehan YAN ; Yang JI ; Yifeng LUO ; Zhihong CAO ; Yuefeng LI
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(9):790-797
Objective:To explore the RNA expression and alterations in brain structure in individuals who have experienced stressful life events (SLE), as well as the correlation patterns between them and their association with the occurrence of depression.Methods:Prospectively, a total of 80 SLE subjects were recruited from the psychiatry and psychology clinic of the Jiangsu University Affiliated Yixing Hospital between January 2021 and December 2022, with 16 normal controls (NC) enrolled concurrently. The 17 items Hamilton depression scale (HAMD-17) and social readjustment rating scale (SRRS) were used to assess depressive symptoms and stress levels. RNA sequencing information of peripheral blood and imaging data at baseline were collected. Based on whether depression occurred during the 2-year follow-up period, SLE subjects were divided into the SLE-depression group ( n=15) and the SLE-non-depression group ( n=65). Differentially expressed genes (DEGs) were screened using differential analysis and protein-protein interaction (PPI) networks. Fractional anisotropy (FA) of white matter tracts and gray matter volume (GMV) were extracted using tract-based spatial statistics and voxel-based morphometry.Using analysis of variance compared inter-group differences in gene expression, GMV and white matter FA values. Partial correlation analysis was used to explore correlations between DEGs, altered GMV and white matter microstructure. Gene set enrichment analysis (GSEA) was performed on key genes to identify potential biological pathways. Propensity score matching constructed sensitivity subgroups to verify result robustness. Results:The SLE-depression group showed significantly higher SRRS and HAMD-17 scores at baseline and at the end of follow-up compared to the SLE-non-depression group and the NC group ( H=47.773, 35.427, 41.114, all P<0.05). Expression levels of IL-10 (2.12±0.28, 2.43±0.44), EZH2 (2.11±0.43, 2.45±0.51), NCAM1 (3.60±0.30, 3.03±0.39), CD3E (4.95±0.37, 4.57±0.48), CCK (3.29±0.28, 3.02±0.42), and CX3CR1 (5.55±0.40, 5.91±0.34) were significantly different between the SLE-depression group and SLE-non-depression group( F=5.549~28.371, all P<0.05). Compared with the SLE-non-depression group, the SLE-depression group exhibited significantly lower FA values in the genu of the corpus callosum (0.29±0.04, 0.31±0.04) and the left uncinate fasciculus (0.31±0.02, 0.33±0.02), as well as significantly smaller GMV in the right hippocampus (0.29±0.07, 0.33±0.06), bilateral middle frontal gyrus (left: 0.27±0.05, 0.31±0.05; right: 0.28±0.06, 0.32±0.06), right insula (0.36±0.03, 0.38±0.04), and left precentral gyrus (0.19±0.04, 0.24±0.05) ( F=4.593-12.064, all P<0.05, FDR correction). GMV in the right anterior cingulate and paracingulate gyri was significantly larger than that in the SLE-non-depression group (0.34±0.05, 0.29±0.06) ( F=6.704, P=0.034, FDR correction). Partial correlation analysis revealed significantly stronger correlations between hub DEGs and altered brain regions in the SLE-depression group ( r=0.017-0.801) compared to the SLE-non-depression group ( r=0.002-0.382), with a statistically significant difference ( U=629, P<0.001; Cliff's Delta=0.454). GSEA indicated that the aforementioned genes were primarily involved in pathways including the ribosome, spliceosome, ribosome biogenesis in eukaryotes, and neuroactive ligand-receptor interaction. Sensitivity analysis confirmed that the above results remained statistically significant after balancing sample sizes (all P<0.05). Conclusion:The SLE-depression group showed specific RNA expression and brain structure alterations compared to the SLE-non-depression group, and the correlation between RNA and brain structure was significantly enhanced in the SLE-depression group. This suggests that the correlation between genes and brain structure in the SLE population may be related to their susceptibility to depression.
3.Changes in expression of c-fos protein in spinal cord in a rat model of oxycodone dependence or withdrawal response
Xing YAN ; Ke LUO ; Jiali SHAO ; Xiaoyan ZHANG ; Yuefeng XIA ; Jiao WU ; Huiping SUN ; Jingshi LIU ; Jinfeng YANG
Chinese Journal of Anesthesiology 2018;38(12):1456-1459
Objective To evaluate the changes in the expression of c-fos protein in the spinal cord in a rat model of oxycodone dependence or withdrawal response.Methods Thirty SPF adult male Sprague-Dawley rats,aged 6-8 weeks,weighing 180-220 g,were divided into 3 groups (n=10 each) using a random number table method:normal saline group (group NS),oxycodone dependence group (group OD),and oxycodone withdrawal group (group OW).In OD and OW groups,oxycodone was injected subcutaneously in back,5 days in total,with the dose of 2,3,4,5 and 6 mg/kg in turn,3 times a day (8:00/15:00/22:00).The equal volume of normal saline was given instead in group NS.The mechanical paw withdrawal threshold was measured at 3 days before administration and 30 min after the last administration every day.The oxycodone withdrawal was induced by intraperitoneal injection of naloxone 4 mg/kg at 8 h after the last administration of oxycodone on 5th day in group OW.The withdrawal response scores and range of weight changes were recorded within 15 min after giving naloxone or normal saline in NS and OW groups.Spinal cord tissues were collected at 1 h after the last administration on 5th day in group OD and at 1 h after giving normal saline or naloxone on 5th day in NS and OW groups for determination of the expression of c-fos protein by Western blot.Results Compared with group NS,the mechanical paw withdrawal threshold was significantly increased on 1 and 2 days after administration,and the expression of c-fos protein in the spinal cord was up-regulated in OD and OW groups,and withdrawal response scores were significantly increased,and the range of weight change was increased in group OW (P<0.05).The expression of c-fos protein was significantly down-regulated in group OW as compared with group OD (P<0.05).Conclusion Oxycodone dependence or withdrawal response may be related to the expression of c-fos protein in the spinal cord of rats,and the expression is up-regulated during oxycodone dependence,while down-regulated during oxycodone withdrawal.
4.Research progress of AIDS treatment
Yansheng YAN ; Pingping YAN ; Liang CHEN ; Shouli WU ; Meirong XIE ; Tingting WU ; Pincang XIA ; Yuefeng QIU
Chinese Journal of Zoonoses 2017;33(5):383-388
AIDS antiviral therapy (ART) has achieved great success.Originaly,AIDS had been regarded as a fatal disease,but it has become a kind of infectious disease that could be cured and administrated.Global HIV / AIDS cases were still up to about 38 million,but more than half have been effectively treated.In addition to drug treatment,at present,some new technologies and new methods,such as genome editing,have also been involved in the treatment of AIDS,and in the humanized animal experiment has shown very good results.There is no doubt that AIDS will eventually be stopped its epidemic.However,with the continuous development of AIDS antiviral treatment,the most fundamental problem is that HIV latent library has become increasingly prominent one,whether molecular therapy and hybrid cure have being developed for AIDS treatment,there are still such problem existence.Great efforts shoud be made to continuously search for new markers of latent viral cells and to reduce the latent pool.In addition,despite the prevention and treatment of AIDS has made great achievements,but the world still produces nearly 6000 cases of HIV/AIDS every day.Therefore,the development of safe and effective vaccine,whether in the field of prevention,or in clinical treatment,has its positive significance.
5.Optimization of Ultrasonic Extraction Technology of Salidroside in Rhodiola rosea by Orthogonal Design-Multiple Regression Method
Yufang HUANG ; Yuefeng LI ; Juli YUAN ; Jing SHAO ; Pengfei XIA ; Xiaofeng SHI
China Pharmacy 2015;(22):3128-3130
OBJECTIVE:To optimize the ultrasonic extraction technology of salidroside in Rhodiola rosea. METHODS:With the content of salidroside as the index,L16(45)orthogonal test was designed to observe the effects of 4 factors including the mass fraction of ethanol,solid-liquid ratio,extraction time and ultrasonic power on the content of salidroside in R. rosea extraction solu-tion. By using Matlab 6.5 software,mathematical simulation of ultrasonic extraction process of salidroside was made with the data of orthogonal test. Multiple regression analysis method was adopted to optimize the ultrasonic extraction technology of salidroside, and then the extraction result of optimal technology and that of traditional heating reflux technology were compared. RESULTS:The optimal extraction technology of salidroside was as follows as ethanol mass fraction of 77%,solid-liquid ratio of 1∶34 (g∶ml),extraction time of 34 min,ultrasonic power of 237 W(ultrasonic frequency of 40 kHz). Under the above-mentioned condi-tions,the content of salidroside was up to 0.982 4%,close to the predicted value of 0.989 4%. Compared to heating reflux meth-od,the ultrasonic method has similar content of salidroside but extraction time was shortened by 62.2%. CONCLUSIONS:The ul-trasonic extraction method for extracting the salidroside in R. rosea is simple,requires shorter time,and giving rise to higher extrac-tion rate.
6.The effects of different tropisetron administration routes and dosages on cisplatin-induced kaolin intake in rats
Yanghui XUE ; Yuefeng XIA ; Jinfeng YANG ; Wenqian YANG ; Yongjun SUN ; Mingde WANG
Journal of Chinese Physician 2012;(12):1603-1605
Objective To compare the effects of different administration routes and dosages of tropisetron on cisplatin-induced kaolin intake in rats.Methods Ninety-six healthy adult male Wistar SPF rats were randomly divided into 8 groups(n =12 each):intrathecal (IT) control group (group TC) and 3 tropisetron groups receiving IT tropisetron 10,20 and 30 μg,the volume of each group was 30 μl (group T10,T20,T30),intravenous(Ⅳ) control group (group IC) and 3 tropisetron groups receiving Ⅳ tropisetron 0.3,0.5 and 0.7 mg/kg respectively (group I0.3,I0.5,I0.7).In group TC and IC,normal saline 30 μl and 0.5 ml were injected IT and Ⅳ,respectively.All rats received cisplatin 3mg/kg by intraperitoneal injection at the time point of thirty minutes after administration,each rat weight,the daily food and kaolin intakes were detected at the time point of 48 hours after cisplatin administration.Results Compared with group Tc,each rat weight loss,the kaolin intakes were significantly decreased (P < 0.05),and food intake dose was significantly increased in group T20 (P < 0.05).Compared with group IC,each rat weight loss,the kaolin intakes were significantly decreased (P < 0.05),and food intake dose was significantly increased in group I0.5 and I0.7 (P <0.05).There was no significant difference between group I0.5,I0.7 and group T20.Conclusions The kaolin intakes and the rat weight loss can be decreased by IT tropisetron,and the food take dose was increased meanwhile,and IT tropisetron 20 μg has equivalent efficacy to IV tropisetron 0.5 or 0.7 mg/kg.IT could be the new administration route of tropisetron.
7.Delayed effect of isoflurane on hippocampal proteome after anesthesia in adult and aged rats
Kaiming DUAN ; Wen OUYANG ; Manhong CHEN ; Yuefeng XIA ; Saiying WANG
Journal of Central South University(Medical Sciences) 2009;34(7):589-594
Objective To investigate the delayed alteration of hippocampus proteome after an-esthesia with isoflurane in aduh and aged rats. Methods Ten 8-month-old SD rats were randomly divided into group Caduh and group Iadult (5 in each group) , and another ten 22-month-old SD rats were randomly divided into group Caged and group Iaged (5 in each group). The rats in group Iadult and group Iaged received 2 h anesthesia with 1.2 % isoflurane. The rats in group Cadult and group Caged inhaled 40% oxygen for contrast. The hippocampal proteome of each rat was measured by 2-dimensional gel electrophoresis and mass spectrometry. Results The vital signs of the rats in group Iadult and group Iaged were stable. There were 878±34 protein spots in group Cadult, 864±49 protein spots in group Iadult, 834±47 in group Caged, and 819±24 in group Iaged. There were 12 (4/8)different protein spots between group Iadult and group Cadult. There were 11 (3/8) different protein spots between group Iaged and group Caged. All of the protein spots were identified by MALDI-TOF-MS. Most of the different proteins were related to metabolism, anti-oxidation, and signal conditioning of synapse. Conclusion Isoflurane may cause the alteration of hippocampal pro-teome in rats, which is age-related.

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