Objective:To investigate the expression of miR-383(Micro RNA-383)in osteosarcoma cells and to verify whether upregulation of miR-383 can enhance the therapeutic efficacy of bortezomib against osteosarcoma.Methods:Fluorescence in situ hybridization (FISH) was used to detect the expression of miR-383 in osteosarcoma and normal bone tissues. Real-time quantitative polymerase chain reaction (qRT-PCR) was employed to measure the expression of miR-383 in different osteosarcoma cell lines (SaoS-2, HOS, U-2OS, and MG63)and the osteoblast cell line hFOB 1.19.The proliferative capacity of osteosarcoma cells treated with 5 nmol/L and 10 nmol/L bortezomib was assessed using the cell counting kit-8 (CCK-8) with dimethyl sulfoxide (DMSO) as a control. The activity of caspase-3 was also measured. HOS and MG63 cells were treated with DMSO, bortezomib, miR-383 mimics, or negative controls, and the proliferative capacity and apoptosis levels were re-evaluated using CCK-8 and flow cytometry, respectively.Results:FISH results showed that the level of miR-383-5p in osteosarcoma tissues was significantly lower than that in normal bone tissues ( P<0.05). qRT-PCR results indicated that miR-383 levels in osteosarcoma cells (MG63, HOS, Saos-2, U-2OS) were lower than those in osteoblasts (hFOB1.19), with significant differences among different osteosarcoma cell lines(all P<0.05).The lowest levels of miR-383 were observed in HOS and MG63 cells. CCK-8 and caspase-3 activity assays revealed that among the cells treated with DMSO and two doses of bortezomib, HOS and MG63 cells had higher baseline proliferative capacity. Compared with DMSO-treated control cells, cells treated with 5 nmol/L and 10 nmol/L bortezomib exhibited inhibited proliferation (all P<0.05) and increased caspase-3 activity (all P<0.05). The effect of 10 nmol/L bortezomib was stronger than that of 5 nmol/L (all P<0.05). Compared with negative control-transfected cells, osteosarcoma cells (MG63 and HOS) with overexpressed miR-383 showed inhibited proliferation and increased apoptosis levels (all P<0.05). After bortezomib treatment, osteosarcoma cells (MG63 and HOS)with overexpressed miR-383 exhibited reduced proliferative capacity and enhanced apoptosis levels (all P<0.05). Conclusions:miR-383 exerts anticancer effects in osteosarcoma by inhibiting cell proliferation. Its overexpression significantly enhances the therapeutic efficacy of bortezomib, offering a new direction for the treatment strategies of osteosarcoma.

Objective:To investigate the expression of miR-383(Micro RNA-383)in osteosarcoma cells and to verify whether upregulation of miR-383 can enhance the therapeutic efficacy of bortezomib against osteosarcoma.Methods:Fluorescence in situ hybridization (FISH) was used to detect the expression of miR-383 in osteosarcoma and normal bone tissues. Real-time quantitative polymerase chain reaction (qRT-PCR) was employed to measure the expression of miR-383 in different osteosarcoma cell lines (SaoS-2, HOS, U-2OS, and MG63)and the osteoblast cell line hFOB 1.19.The proliferative capacity of osteosarcoma cells treated with 5 nmol/L and 10 nmol/L bortezomib was assessed using the cell counting kit-8 (CCK-8) with dimethyl sulfoxide (DMSO) as a control. The activity of caspase-3 was also measured. HOS and MG63 cells were treated with DMSO, bortezomib, miR-383 mimics, or negative controls, and the proliferative capacity and apoptosis levels were re-evaluated using CCK-8 and flow cytometry, respectively.Results:FISH results showed that the level of miR-383-5p in osteosarcoma tissues was significantly lower than that in normal bone tissues ( P<0.05). qRT-PCR results indicated that miR-383 levels in osteosarcoma cells (MG63, HOS, Saos-2, U-2OS) were lower than those in osteoblasts (hFOB1.19), with significant differences among different osteosarcoma cell lines(all P<0.05).The lowest levels of miR-383 were observed in HOS and MG63 cells. CCK-8 and caspase-3 activity assays revealed that among the cells treated with DMSO and two doses of bortezomib, HOS and MG63 cells had higher baseline proliferative capacity. Compared with DMSO-treated control cells, cells treated with 5 nmol/L and 10 nmol/L bortezomib exhibited inhibited proliferation (all P<0.05) and increased caspase-3 activity (all P<0.05). The effect of 10 nmol/L bortezomib was stronger than that of 5 nmol/L (all P<0.05). Compared with negative control-transfected cells, osteosarcoma cells (MG63 and HOS) with overexpressed miR-383 showed inhibited proliferation and increased apoptosis levels (all P<0.05). After bortezomib treatment, osteosarcoma cells (MG63 and HOS)with overexpressed miR-383 exhibited reduced proliferative capacity and enhanced apoptosis levels (all P<0.05). Conclusions:miR-383 exerts anticancer effects in osteosarcoma by inhibiting cell proliferation. Its overexpression significantly enhances the therapeutic efficacy of bortezomib, offering a new direction for the treatment strategies of osteosarcoma.

MRI technology has been widely used in brain connectivity analysis to explore the neurobiological mechanism of ASD. Analysis of brain structural connectivity found atypical growth and development in patients with ASD, excessive growth in infancy, and excessive decline in functions from adolescence to middle age. Functional connectivity analysis suggests that default mode network (DMN) may be related to theory of mind (ToM) and self-referential processing, abnormal salience network (SN) connections can lead to social communication disorders, and abnormal reward network (RN) may be related to repetitive and restricted behaviors. Effective connectivity analysis found that information transmission between brain regions was abnormal in ASD patients, which was associated with social dysfunction. This article introduces the latest development of MRI research, and discusses the differences between ASD patients and normal human brain connections, so as to provide theoretical reference for further investigations of the neural activity mechanism of ASD patients.

MRI technology has been widely used in brain connectivity analysis to explore the neurobiological mechanism of ASD. Analysis of brain structural connectivity found atypical growth and development in patients with ASD, excessive growth in infancy, and excessive decline in functions from adolescence to middle age. Functional connectivity analysis suggests that default mode network (DMN) may be related to theory of mind (ToM) and self-referential processing, abnormal salience network (SN) connections can lead to social communication disorders, and abnormal reward network (RN) may be related to repetitive and restricted behaviors. Effective connectivity analysis found that information transmission between brain regions was abnormal in ASD patients, which was associated with social dysfunction. This article introduces the latest development of MRI research, and discusses the differences between ASD patients and normal human brain connections, so as to provide theoretical reference for further investigations of the neural activity mechanism of ASD patients.

Objective To explore abnormalities in functional connectivity of the affective network (AN) in relapse of major depressive disorder (MDD) after antidepressant treatment combined with resting state functional connectivity analysis.Methods Eleven recurrent MDD subjects after treatment,seventeen non recurrent MDD subjects after treatment and seventy-two healthy controls underwent fMRI scan.The amygdala,the pallidum,the insular cortex and the anterior cingulate cortex of the AN were selected as the template.Group independent component analysis (ICA) was performed to decompose the fMRI images into spatially independent components and the independent component which fit this template best was selected as AN.Two-sample t-tests were performed to investigate the changes in functional connectivity of the AN.Finally,the right amygdala and the medial prefrontal cortex were defined as seed regions.Results Compared with healthy control subjects and non-recurrent MDD group,recurrent MDD group showed significantly increased functional connectivity in the right amygdala in AN(P＜0.001).Meanwhile,the functional connectivity between the right amygdala and the medial prefrontal cortex was significantly decreased in recurrent MDD group(P ＜0.05).Conclusion Abnormal resting-state functional connectivity of the right amygdala after antidepressant treatment in MDD was found,suggesting that altered amygdala functional connectivity may serve as a predicator of relapse of the MDD.

Objective To explore the effects of abnormal effective connectivity within the default mode network (DMN)in relapsed patients with major depressive disorder.Methods Resting-state functional magnetic resonance imaging (rs-fMRI)data were collected from 21 patients of first-episode depression and 16 patients with relapsed depression,and 37 matched healthy controls.The effective connectivity within the DMN was investigated with spectral dynamic causal modeling (spDCM)method.Results spDCM analysis showed that the effective connections from left parietal cortex(LPC)to right parietal cortex(RPC)and medial frontal cortex(mPFC)were significantly decreased,while the connection from posterior cingulate cortex(PCC)to mPFC was increased in patients of first episode depression compared to healthy controls.Furthermore,the connectivity between mPFC and LPC were enhanced in patients with recurrent depression compared withhealthy control subjects,as well as PCC.Meanwhile,the connectivity between mPFC and PCC was enhanced in patients with relapse depression compared with patients of first episode depression.Conclusion Both first-episode and relapsed patients demonstrated abnormal effective connectivity of LPC,implicating that abnormal LPC connectivity may be associated with the neural substrates of depression.In contrast,the patients with relapsed depression showed aberrant connectivity with the mPFC,suggesting that abnormal effective connectivity of the mPFC may play an important role in the relapse of depression.