1.Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy.
Yue ZHANG ; Jingwen GAO ; Na LI ; Peng XU ; Shimeng QU ; Jinqian CHENG ; Mingrui WANG ; Xueru LI ; Yaheng SONG ; Fan XIAO ; Xinyu YANG ; Jihong LIU ; Hao HONG ; Ronghao MU ; Xiaotian LI ; Youmei WANG ; Hui XU ; Yuan XIE ; Tianming GAO ; Guangji WANG ; Jiye AA
Acta Pharmaceutica Sinica B 2024;14(2):667-681
Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.
2.Effects of gingipain extract on the biological characteristics of oral squamous cell carcinoma cell HN6
Huxiao LI ; Xiaotian LI ; Xuri ZHAO ; Huanyu ZHANG ; Wei ZHOU ; Zhongchen SONG
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(2):161-168
Objective·To observe the effects of gingipain extract on the biological characteristics of oral squamous cell carcinoma cell HN6.Methods·The HN6 cell line was selected,cultivated,and divided into different groups based on the protein concentration of gingipain extract from Porphyromonas gingivalis:control group,3.125 μg/mL group,6.25 μg/mL group,12.5 μg/mL group,25 μg/mL group,50 μg/mL group,and 100 μg/mL group.After 24 and 48 h of cultivation,CCK-8 assay was used to detect the effects of gingipain extract on HN6 cell proliferation activity.Subsequent experiments were divided into control group,25 μg/mL group and 50 μg/mL group.Flow cytometry was used to examine the effects of gingipain extract on cell cycle.Scratch assay and Transwell assay were performed to evaluate cell migration and invasion ability.Real-time PCR(RT-PCR)and Western blotting were used to measure the expression of E-cadherin and N-cadherin proteins and genes in cells.Results·Stimulated with gingipain extract for 24 h,the HN6 cells showed significantly increased proliferation activity in the 25 μg/mL(P=0.025),50 μg/mL(P=0.000),and 100 μg/mL(P=0.049)groups compared to the control group.After 48 h,proliferation activity was significantly higher in the 6.25 μg/mL(P=0.024),12.5 μg/mL(P=0.006),25 μg/mL(P=0.000),50 μg/mL(P=0.000),and 100 μg/mL(P=0.000)groups compared to the control group.Cell cycle analysis revealed that,after 24 h of gingipain stimulation,the proportion of HN6 cells in the G1 phase decreased,while the proportion in the S+G2 phase significantly increased compared to the control group(25 μg/mL group:P=0.024;50 μg/mL group:P=0.001).Compared to the control group,the scratch assay demonstrated a significant increase in the percentage of scratch closure as the concentration of gingipain extract increased(P=0.001).Compared to the control group,the Transwell invasion assay showed a significant increase in the number of cells passing through the bottom of the chamber as the concentration of gingipain extract increased.RT-PCR and Western blotting results indicated that as the concentration of gingipain extract increased,the expression levels of N-cadherin mRNA and protein in HN6 cells significantly increased,while the expression levels of E-cadherin mRNA and protein significantly decreased compared to the control group.Conclusion·Gingipain extract could promote proliferation,migration,and invasion of oral squamous cell carcinoma HN6 cells.
3.Effect of minimalist shoes on foot muscle morphology:systematic evaluation and Meta-analysis
Xiaotian BAI ; Zhaoying CHEN ; Yiling SONG ; Ye WANG ; Jingmin LIU
Chinese Journal of Tissue Engineering Research 2024;28(4):646-650
OBJECTIVE:With the popularity of simulated barefoot running,minimalist shoes have become a new way of foot exercise.As an important muscle group of the foot,the maintenance of foot muscle morphology is important for the execution of foot functions.In this paper,by combing the literature about the effect of minimalist shoes on foot muscle morphology in recent years,we systematically evaluate the effect of minimalist shoes on foot muscle morphology compared with traditional running shoes. METHODS:The relevant articles published from 2012 to 2022 were searched in Chinese and English databases(PubMed,Web of Science,ProQuest,CNKI and WanFang databases)with"minimal shoes,minimal footwear,minimalist shoes,minimalist footwear,foot muscle,feet muscle"as Chinese and English keywords,respectively.Meta-analysis,sensitivity tests were performed on the included literature using Review Manager 5.4.1 and Stata 14 software,the Egger method was used to test for publication bias in the literature,and Meta-regression was used to identify the subgroups with heterogeneity. RESULTS:Compared with traditional running shoes,minimalist shoes increased muscle circumference of the abductor hallucis[standardized mean difference=2.034,95%confidence interval(1.192,2.877),Z=4.73,P<0.001].And the results were not reversed after clipping and patching,with a more robust combined effect size(P<0.05).For the toe short flexors,the total combined effect size did not show a difference between traditional running shoes and minimalist shoes[standardized mean difference=0.470,95%confidence interval(-0.45,1.39),Z=1.00,P=0.318]. CONCLUSION:Compared with traditional running shoes,minimalist shoes intervention can effectively improve muscle circumference of the abductor hallucis,but the promoting effect on the flexor digitorum brevis muscle is not obvious.Running in minimalist shoes has positive implications for the maintenance of the medial longitudinal arch,but it is necessary to enrich the research content of minimalist shoes on different foot muscles and different populations in order to further explore the mechanisms by which minimalist shoe interventions promote foot function.
4.Clinical observation of posterior staphyloma marginal retinal photocoagulation in vitrectomy for macular hole retinal detachment in high myopia
Guanghui HE ; Ge TIAN ; Song CHEN ; Bin WU ; Meng DONG ; Xiaotian ZHANG ; Meng WANG ; Guannan WU
Chinese Journal of Ocular Fundus Diseases 2021;37(4):271-276
Objective:To observe the outcome of posterior staphyloma (PS) marginal retinal photocoagulation in pars plana vitrectomy (PPV) for high myopia macular hole retinal detachment eyes accompanied with PS.Methods:From January 2017 to June 2019, 49 patients (49 eyes) with high myopia macular hole retinal detachment accompanied with PS who were undergone PPV operation from Tianjin Eye Hospital were included in this study. There were 13 males (13 eyes) and 36 females (36 eyes). All patients underwent best corrected visual acuities (BCVA) and optical coherence tomography examinations. The standard logarithmic visual acuity chart was used for BCVA examination, and the visual acuity was converted to minimum resolution angle in logarithmic (logMAR) when recorded. The patients were randomly divided into two groups according to surgical options: conventional PPV with internal limiting membrane (ILM) peeling (group A, 24 eyes), PS marginal retinal photocoagulation in PPV with ILM peeling (group A, 25 eyes). The mean preoperative logMAR BCVA of group A and B were 1.87±0.28 and 1.80±0.37, the difference was not statistically significant ( t=0.604, P=0.551). The patients in the group A received 23G PPV, triamcinolone acetonide staining during the operation, the epiretinal membrane was peeled off, indocyanine green assisted staining, the posterior macular ILM was peeled off, and the peripheral retina was examined in detail during the operation. Areas with retinal degeneration were reinforced by laser photocoagulation, and the subretinal fluid was drained through the macular hole and filled with silicone oil. The eyes of the group B were subjected to retinal photocoagulation for 2 to 3 rows at the edge of the PS in addition to the usual surgical procedures. The average follow-up time was 8.34±3.21 months. Surgical outcome were estimated by the average number of operation, retinal reattachment rate, macular hole closure rate and BCVA. The χ2 test or Fisher exact probability was used to compare the count data. Independent sample t test was used to compare the measurement data. Results:Retinal reattachment was obtained in 17 eyes (70.8%, 17/24) and 24 eyes (96.0%, 24/25) in group A and B after first surgery respectively, the difference was statistically significant ( χ2=3.984, P=0.046). Final retinal reattachment was obtained in all 49 eyes. Final macular hole closure was in 15 eyes (62.5%, 15/24) and 19 eyes (76.0%, 19/25) in group A and B, respectively, the difference was not statistically significant ( χ2=1.051, P=0.305). The mean postoperative logMAR BCVA of group A (1.20±0.47) and B (1.08±0.39) were all improved than preoperative BCVA, the differences were all statistically significant ( t=2.899, 5.327; P=0.001, 0.000), the differences of mean postoperative logMAR BCVA between two groups was not statistically significant ( t=0.675, P=0.506). The mean number of operation of group A (2.63±0.88) was more than group B (2.08±0.28), the difference was statistically significant ( t=3.003, P=0.006). Conclusion:In comparison with conventional PPV, combined PS marginal retinal photocoagulation can improve retinal reattachment rate after first surgery, and reduce the number of reoperations.
5.Changes of retinal microvasculature and visual acuity prognostic of aflibercept treatment in macular edema secondary to retinal vein occlusion
Guannan WU ; Xiaotian ZHANG ; Guanghui HE ; Meng DONG ; Xiang GAO ; Meng WANG ; Song CHEN
Chinese Journal of Ocular Fundus Diseases 2021;37(4):290-297
Objective:To observe the changes of macular microvessels in patients with retinal vein occlusion (RVO) and macular edema (ME) after intravitreal injection of aflibercept (IVA), and analyze its correlation with best corrected visual acuity (BCVA).Methods:A retrospective case study. Thirty patients (30 eyes) with monocular RVO with ME (RVO-ME) who were diagnosed in the clinical examination of Tianjin Eye Hospital from April 2019 to February 2020 were included in the study. Among them, there were 12 males (12 eyes) and 18 females(18 eyes); the average age was 54.30±13.17 years. The average course of disease was3.43±1.97 months. Both eyes were examined by BCVA and optical coherence tomography (OCTA). The on-demand injection was adopted after the first injection in IVA treatment regimen. The macular area 6 mm×6 mm in both eyes was scanned with an OCTA instrument, and the area of the foveal avascular area (FAZ), FAZ circumference (PERIM), and out-of-roundness were measured at baseline and 1, 3, and 6 months after treatment. Index (AI), blood flow density within 300 μm width of FAZ (FD-300), foveal retinal thickness (CMT), superficial retinal capillary plexus (SCP), deep retinal capillary plexus (DCP) blood flow density. The paired t test was used to compare the quantitative parameters of the affected eye and the contralateral healthy eye at baseline; the changes of the quantitative parameters at baseline and 1, 3, and 6 months after treatment were analyzed by repeated measures analysis of variance. Pearson correlation analysis was used to analyze the correlation between BCVA, retinal perfusion, and macular blood supply parameters at 6 months after IVA treatment. Results:At baseline, compared with the contralateral healthy eye, the FAZ area ( t=-4.091), PERIM ( t=-5.098) and AI ( t=-9.093) of the RVO-ME eye were enlarged, and FD-300 ( t=7.237) and overall SCP and DCP blood flow density ( t=8.735, 9.897) decreased, the difference was statistically significant ( P<0.001). Six months after treatment, the BCVA of RVO-ME eyes was significantly increased, CMT decreased, FAZ area expanded, and AI decreased ( t=8.566, 16.739, -6.469, 9.719; P<0.001), the difference was statistically significant. There was no significant change in the blood flow density of FD-300 and overall SCP and DCP, and the difference was not statistically significant ( t=1.017, 1.197, 0.987; P>0.05). Compared with baseline, the FAZ area of RVO-ME eyes gradually expanded at 3 and 6 months after treatment, and the difference was statistically significant ( F=21.979, P<0.001). Correlation analysis results showed that BCVA at 6 months after treatment was positively correlated with the overall SCP and DCP blood flow density at baseline and 6 months after treatment ( r=-0.538, -0.484, -0.879, -0.854; P<0.05). There was a negative correlation with the area of FAZ 6 months after treatment ( r=0.544, P=0.001). The number of ME recurrences was negatively correlated with BCVA and overall SCP and DCP blood flow density 6 months after treatment ( r=0.604, -0.462, -0.528; P<0.05), it was positively correlated with FAZ area ( r=0.379, P=0.043). Conclusion:Within 6 months of IVA treatment in RVO-ME eyes, ME is significantly reduced and visual acuity is improved; SCP blood flow density decreases, and FAZ area expands.
6.Epidural versus intravenous analgesia following radical gastrectomy for gastric cancer: A systematic review and Meta-analysis
Jie CHEN ; Bo LIAN ; Dan SONG ; Shuai XU ; Xiaotian SONG ; Qingchuan ZHAO
International Journal of Surgery 2020;47(4):255-261,290
Objective:To compare the application of epidural analgesia (EA) with intravenous analgesia (IA) in radical gastrectomy for gastric cancer.Methods:A systematic review and meta-analysis of randomized controlled trials of EA and IA in radical gastrectomy was conducted. Primary outcome was pain scores at 24 h after surgery, while the secondary outcomes included incidence of postoperative complications, first flatus time and (LOS).Results:A total of 6 randomized controlled studies was identified and 393 patients were enrolled in this review, 4 published in English and 2 in Chinese. Meta-analysis revealed that, the EA group had lower pain score at 24h either pain at rest ( WMD=-0.74, 95% CI: -1.35~-0.13, P=0.02) or pain on movement or coughing( WMD=-1.5, 95% CI: -1.95~-1.05, P<0.001) than that of the IA group. In terms of complications, postoperative nausea and vomiting ( RR=0.32, 95% CI: 0.18~0.58, P<0.001) and respiratory complications ( RR=0.50, 95% CI: 0.29~0.85, P=0.01) in EA group were obviously lower than those of the IA group. No difference was observed in postoperative urinary complications between the two groups ( RR=0.87, 95% CI: 0.38~1.96, P=0.73). However, the incidence of hypotension was obviously higher than that of IA group ( RR=3.27, 95% CI: 1.28~8.32, P=0.01). Time of first exhaust time after operation ( WMD=-14.01, 95% CI: -22.85~-5.17, P=0.002), postoperative length of hospital stay ( WMD=-0.69, 95% CI: -0.90~-0.49, P<0.001) were shorter than IA group. Conclusions:For patients who undergoing radical gastrectomy for gastric cancer, epidural analgesia could provide better pain control either pain at rest or on movement, although a rising incidence of hypotension was leaded, reduced pulmonary complications, nausea and vomiting were found, and promote the bowel function and shorten the duration of hospital stay.
7. Mortality and influencing factors on injecting drug users with HIV/AIDS in Guizhou province, 1996-2015
Yang CHEN ; Xiaotian SONG ; Yongming YAO ; Lu HUANG ; Zhu AN ; Jun YUAN ; Bing XIONG ; Yuehui LIU ; Yuqiong ZHANG
Chinese Journal of Epidemiology 2019;40(7):765-769
Objective:
To understand the mortality and influencing factors on injecting drug users (IDUs) with HIV/AIDS, in Guizhou province, 1996-2015.
Methods:
A retrospective cohort study was conducted on IDUs with HIV/AIDS that were reported through national comprehensive HIV/AIDS information system, in Guizhou province during 1996-2015. Cox proportional hazard regression model was used to analyze the influencing factors on the mortality of HIV/AIDS.
Results:
A total of 3 958 cases of IDUs with HIV/AIDS were recruited in this study, with all-cause mortality rate of 44.01
8.Construction and analysis of muscle functional network for exoskeleton robot.
Lingling CHEN ; Cun ZHANG ; Xiaowei SONG ; Tengyu ZHANG ; Xiaotian LIU ; Zekun YANG
Journal of Biomedical Engineering 2019;36(4):565-572
Exoskeleton nursing robot is a typical human-machine co-drive system. To full play the subjective control and action orientation of human, it is necessary to comprehensively analyze exoskeleton wearer's surface electromyography (EMG) in the process of moving patients, especially identifying the spatial distribution and internal relationship of the EMG information. Aiming at the location of electrodes and internal relation between EMG channels, the complex muscle system at the upper limb was abstracted as a muscle functional network. Firstly, the correlation characteristics were analyzed among EMG channels of the upper limb using the mutual information method, so that the muscle function network was established. Secondly, by calculating the characteristic index of network node, the features of muscle function network were analyzed for different movements. Finally, the node contraction method was applied to determine the key muscle group that reflected the intention of wearer's movement, and the characteristics of muscle function network were analyzed in each stage of moving patients. Experimental results showed that the location of the myoelectric collection could be determined quickly and efficiently, and also various stages of the moving process could effectively be distinguished using the muscle functional network with the key muscle groups. This study provides new ideas and methods to decode the relationship between neural controls of upper limb and physical motion.
Electromyography
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Exoskeleton Device
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Humans
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Muscle, Skeletal
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physiology
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Robotics
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Upper Extremity
9.Distribution and therapy strategy of culture microorganisms of kidney perfusion fluid
Liang TAN ; Xubiao XIE ; Longkai PENG ; Fenghua PENG ; Gongbin LAN ; Shaojie YU ; Yu WANG ; Xiaotian TANG ; Chunhua FANG ; Manhua NIE ; Feng LIU ; Mingjie XU ; Lei SONG
Chinese Journal of Organ Transplantation 2018;39(3):135-139
Objective To analyze the distribution of microorganisms in kidney perfusion fluid and perirenal drainage of the renal allografts,and provide evidence to guide clinical practice.Methods The clinical data from the kidney donors and the recipients,the microbiologic culture results of kidney perfusion fluid and perirenal drainage were retrospectively analyzed.Results Ninety-one kidney perfusion fluid samples and 91 perirenal drainage samples were collected from 61 individual renal allografts,and 48 renal allografts were paired.Fourteen (15.4%,14/91) cultured kidney perfusion fluid samples were positive,17 strains were confirmed including 13 strains of bacteria and 4 strains of fungal,and 9 (69.2%,9/13) of bacterial strains were multidrug-resistance with 7 strains resistant to carbapenems,but there was no significant heterogeneity in the outcome of recipients with positive or negative culture results of kidney perfusion fluid samples.Eight (8.8%,8/91) perirenal drainage samples from different recipients were positive,5 of 8 bacterial strains were multidrug-resistance and 3 of them were resistant to carbapenems including meropenem or imipenern.There was no significant correlation between the length of donors' hospital stay and the culture results (P>0.05),and there was also no significant correlation between the length of recipients' hospital stay after transplantation and the culture results (P>0.05).Conclusion The kidney with positive perfusion fluid microbiologic culture can be transplanted safely using the prophylaxis or preemptive anti-infection therapy.
10.Overexpression of miR-191 Predicts Poor Prognosis and Promotes Proliferation and Invasion in Esophageal Squamous Cell Carcinoma.
Xiaotian GAO ; Zhanqiang XIE ; Zhigang WANG ; Keluo CHENG ; Ke LIANG ; Zeqing SONG
Yonsei Medical Journal 2017;58(6):1101-1110
PURPOSE: Accumulating evidence has shown that dysregulation of microRNA-191 (miR-191) is closely associated with tumorigenesis and progression in a wide range of cancers. This study aimed to explore the potential role of miR-191 in esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: miR-191 expression was assessed in 93 ESCC tissue specimens by real-time polymerase chain reaction, and survival analysis was performed via Kaplan-Meier and Cox regression analyses. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, plate colony-forming, BrdU, and Transwell assays were conducted to observe the effect of miR-191 on ESCC proliferation and invasion. Luciferase reporter and western blot assays were taken to identify target genes of miR-191. RESULTS: miR-191 was overexpressed in 93 cases of ESCC, compared with adjacent normal tissues, and miR-191 expression was significantly related to differentiation, depth of invasion, TNM stage, lymph node metastasis, and distant metastasis of tumor. Kaplan-Meier and Cox regression analyses demonstrated that overexpression of miR-191 was an independent and significant predictor of ESCC prognosis. Both gain-of-function and loss-of-function experiments showed that miR-191 promoted ESCC cell proliferation and invasion activities in vitro. Early growth response 1 (EGR1), a tumor suppressor, was predicted as a direct target of miR-191. Luciferase reporter and western blot assays proved that miR-191 reduced EGR1 expression by directly binding its 3' untranslated region. Moreover, EGR1 knockdown by siRNA enhanced ESCC cell growth and invasion. CONCLUSION: Our findings provide specific biological roles of miR-191 in ESCC survival and progression. Targeting the novel miR-191/EGR1 axis represents a potential new therapeutic way to block ESCC development.
3' Untranslated Regions
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Blotting, Western
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Bromodeoxyuridine
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Carcinogenesis
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Carcinoma, Squamous Cell*
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Cell Proliferation
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Epithelial Cells*
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In Vitro Techniques
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Luciferases
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Lymph Nodes
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Neoplasm Metastasis
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Prognosis*
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Real-Time Polymerase Chain Reaction
;
RNA, Small Interfering

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