The association between gray matter volume in the hippocampal subfield and antidepressant efficacy mediated by abnormal dynamic functional connectivity.

An abnormality of structures and functions in the hippocampus may have a key role in the pathophysiology of major depressive disorder (MDD). However, it is unclear whether structure factors of the hippocampus effectively impact antidepressant responses by hippocampal functional activity in MDD patients. We collected longitudinal data from 36 MDD patients before and after a 3-month course of antidepressant pharmacotherapy. Additionally, we obtained baseline data from 43 healthy controls matched for sex and age. Using resting-state functional magnetic resonance imaging (rs-fMRI), we estimated the dynamic functional connectivity (dFC) of the hippocampal subregions using a sliding-window method. The gray matter volume was calculated using voxel-based morphometry (VBM). The results indicated that patients with MDD exhibited significantly lower dFC of the left rostral hippocampus (rHipp.L) with the right precentral gyrus, left superior temporal gyrus and left postcentral gyrus compared to healthy controls at baseline. In MDD patients, the dFC of the rHipp.L with right precentral gyrus at baseline was correlated with both the rHipp.L volume and HAMD remission rate, and also mediated the effects of the rHipp.L volume on antidepressant performance. Our findings suggested that the interaction between hippocampal structure and functional activity might affect antidepressant performance, which provided a novel insight into the hippocampus-related neurobiological mechanism of MDD.

Linking inter-subject variability of cerebellar functional connectome to clinical symptoms in major depressive disorder.

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder with remarkable inter-subject variability in clinical manifestations. Neuroimaging changes of the cerebellum have been recently proposed as a way to characterize MDD-related brain disruptions and might further explain various clinical symptoms. However, the cerebellar contributions to MDD clinical heterogeneity remain largely unknown. The analyzed data consisted of 251 MDD patients and 235 matching healthy controls (HC). The inter-subject variability of functional connectomes (IVFC) was estimated via Pearson's correlation analysis between each pair of the cerebellar and cerebral regions based on resting-state functional magnetic resonance imaging (rs-fMRI). A partial least squares (PLS) regression analysis was performed to determine the potential dimension linking the IVFC to clinical symptom measures. The results indicated that similar spatial distribution patterns of the cerebellar IVFC were observed between MDD and HC, but the MDD group exhibited abnormal IVFC alterations in the bilateral Cerebelum_4_5, bilateral Cerebelum_6, Vermis_1_2 and Vermis_8. The PLS model revealed that the IVFC pattern in the left Cerebelum_6 was significantly associated with three HAMD-17 items including the work and activities, psychomotor retardation, and depressed mood. These findings provided new evidence for the cerebellar changes in MDD. Specifically, we found that the altered inter-subject variability measurements correlated with clinical manifestations of this illness. Elucidating this variability could prove helpful for the evaluation of MDD heterogeneity as well as for understanding its pathophysiological mechanism.

Interpretation of guidance on non-clinical safety evaluation for nanomedicines / 药学学报

With the rapid development of nanotechnology, the research and development of nanomedicines have become one of the development directions of drug innovation. Nanomedicines have special physical and chemical properties, such as nanoscale effects and nanostructure effects, so they have special biological properties, which may change the pharmacokinetic profiles such as absorption and tissue distribution of drug molecules, and thus affect their safety and effectiveness. There are many special concerns on the non-clinical safety evaluation of nanomedicines at the basis of ordinary drug because of the particularity of nanomedicines. On August 25, 2021, China issued Guidance on Non-clinical Safety Evaluation for Nanomedicines(interim). This article interprets comprehensively the guidance, focuses on the key points of non-clinical safety evaluation for nanomedicines, and expounds combined with some cases, aiming to provide reference for drug researchers.

Experimental study of proteasome inhibitor MG132 up-regulates Wnt/β-catenin signaling pathway to improve osteoporosis / 中国骨伤

OBJECTIVE@#To explore the mechanism of proteasome inhibitor MG132 in improving osteoporosis.@*METHODS@#Total of 32 female SD rats, weighing 220 to 250 g and 8 weeks old, were selected. They were randomly divided into 4 groups(n=8). Rats of group A and group B were cut off ovaris on both sides to make model of osteoporosis, and then they were given proteasome inhibitors MG132 and dimethyl sufoxide (DMSO) respectively. Group C was a sham group and rats were given MG132. Group D was a normal group and rats were given MG132 too. The rats were killed in batches at 6 and 12 weeks after administration, and the femoral neck tissues were obtained. Relevant data were analyzed, such as pathomorphological observation, micro-CT analysis, detection of 20S proteasome activity in tissues, and expression of Wnt and β-catenin.@*RESULTS@#Morphological observation showed that the trabecular were slightly thinner, reticulated, and occasionally interrupted in group A, while the trabecular were obviously thinner and discontinuous in group B. And the trabecular were intact and arranged reticulated in group C and D. The analysis results of bone mineral density(BMD), bone surface(BS), bone volume/total volume(BV/TV) and trabecular thickness(Tb.Th) showed that group B was worse than other groups in all parameters at different time points(P<0.05), and group A was worse than group C and group D in BS(P<0.05), there was no significant difference in all parameters between group C and group D. RFU value of 20S proteasome in group B was significantly higher than that in other groups(P<0.05). According to the results of Western blot, the gray values of Wnt protein and β-catenin protein in group A were significantly higher than those in other groups (P<0.05).@*CONCLUSION@#MG-132, a ubiquitin proteasome inhibitor, can regulate Wnt/β-catenin signaling pathway by inhibiting the degradation of β-catenin protein, and delaying the occurrence and development of osteoporosis.

Treatment of patients with hyperthyroidism complicated with liver failure with methimazole cream:A report of 2 cases and literature review / 吉林大学学报(医学版)

Objective:To investigate the efficacy of local application of methimazole cream in the patients with hyperthyroidism complicated with liver failure, and to provide reference for its clinical treatment.Methods:Two patients were admitted to hospital with jaundice as the main performance.Liver function and coagulation function supported the diagnosis of liver failure.The thyroid function indicators suggested hyperthyroidism.Combined with other related examination results, liver failure, hyperthyroidism and hepatitis B virus were diagnosed, and the local treatment of methimazole cream and other related treatments were given.Results:After treatment, the liver function of two patients returned to normal and the thyroid function was improved.After follow-up, one patient changed the external use of methimazole cream to oral treatment, and another patient was still treated in a local manner.Conclusion:There is a conflict in the treatment of hyperthyroidism complicated with liver failure.The local application of methimazole cream in the topic of reducing the risk of liver damage caused by drugs has good results in the treatment of hyperthyroidism.This method also provides the new ideas for its clinical treatment.

Treatment of thoracolumbar burst fractures with intelligent inflated reduction combined with percutaneous pedicle screw fixation / 中国骨伤

<p><b>OBJECTIVE</b>To evaluate the clinical outcome of intelligent inflated reduction combined with percutaneous pedicle screw fixation in treating thoracolumbar burst fractures.</p><p><b>METHODS</b>The clinical data of 22 patients with thoracolumbar burst fractures of single segment treated from January 2013 to December 2015 were retrospectively analyzed. There were 12 males and 10 females, aged from 32 to 56 years old with an average of (42.4±8.6) years. Self-made intelligent pneumatic reset instrument was applied to 22 cases under anaesthesia reduction, and then percutaneous pedicle screw fixation was performed. Clinical features were observed and the clinical effects were evaluated by VAS, ODI, kyphotic angle (Cobb angle) and the injured vertebral anterior border height before and after operation.</p><p><b>RESULTS</b>All the patients were followed up from 1 to 2.5 years with an average of 18 months. All fractures obtained bone healing, no complications such as loosening, displacement, breakage of pedicle screw and kyphosis were found. Preoperative, 1 week postoperative, and final follow-up, VAS scores of lumbar pain were 7.82±0.85, 3.09±0.92, 1.05±0.72;ODI scores were 84.2±11.2, 46.3±9.0, 12.2±4.3;Cobb angle were (16.3±5.4)°, (3.7±2.2)°, ( 5.5±2.6)°; the injured vertebral anterior border heights were (59.5±7.8)%, (86.9±6.0)%, (83.5±5.5)%, respectively. There was significant differences in VAS, ODI scores between any two times(<0.05). At 1 week postoperative and final follow-up, Cobb angle, injuried vertebral anterior border height were obviously improved (<0.05), and there was no significant difference between postoperative 1 week and final follow-up (>0.05).</p><p><b>CONCLUSIONS</b>It is safe and feasible surgical technique that intelligent inflated reduction combined with percutaneous pedicle screw fixation for thoracolumbar burst fractures. It has advantage of little trauma, reliable fixation, and less complication, etc. Therefore, it is a better choice for single-segment thoracolumbar burst fractures.</p>

Effects of IL-12 combined with GM-CSF on apoptosis of H22 hepatoma cells / 中国综合临床

Objective To investigate the effects of granulocyte macrophage colony-stimulating factor (GM-CSF) combined with interleukin-12 (IL-12) genes on apoptosis of hepatoma cells.Methods The hepatoma cell lines were cultured in vitro and were divided into four groups: GM-CSF transfection group,IL-12 transfection group,GM-CSF and IL-12 co-transfection group,negative control group (empty load group),respectively.The PIB-CMV3-GM-CSF and PIB-CMV3-IL-12 eukayotic expression vector was built,and 36 h after transfection,fluorescence microscope was used to detect the transfection effect;the expression level of IL-12,GM-CSF,p53,p38 and C-JUN mRNA were detected by RT-PCR,and Western blot was used to examine the expression level of IL-12,GM-CSF,p53,p38 and C-JUN protein.In addition,the flow cytometry was applied to detect cell apoptosis.Results Through fluorescence microscope,green fluorescence was observed in cells of GM-CSF transfection group,IL-12 transfection group,GM-CSF and IL-12 co-transfection group,indicating that the plasmid has successfully transferred into cells.In addition,the expression of p53mRNA in empty load group,GM-CSF transfection group,IL-12 transfection group,GM-CSF and IL-12 co-transfection group were 1.2±0.10,4.3±0.98,4.2±0.34,9.2±0.87,and the protein expression were 1.0±0.10,3.6±0.34,3.8±0.30,5.0±0.60.Compared with the empty load group,the expression level of p53 mRNA and protein were significantly increased in the three plasmid transfection groups (P<0.01).The expression of p53 mRNA and protein were significantly increased in co-transfection group than GM-CSF group and IL-12 group (P<0.01),while in the comparison with GM-CSF transfection group and IL-12 transfection group,the expression level of p53mRNA and protein in the co-transfection group could be improved to a higher degree(P<0.01).Meanwhile,p38 C-JUN mRNA expression levels in empty load group,GM-CSF transfection group,IL-12 transfection group,GM-CSF and IL-12 co-transfection group were as follows: 7.5± 0.9,3.5±0.45,3.7±0.25,1.0±0.11,while p38protein expression levels were 10.1±1.03,6.1± 0.67,7.1 ± 0.61,1.0 ± 0.12,respectively,C-JUN mRNA expression levels were 11.2 ± 1.20,4.1 ± 0.19,3.3 ± 0.30,1.0 ± 0.01,separately,C-JUN protein expression levels were 2.25 ± 0.2,1.8 ± 0.13,1.4 ± 0.12,1.0 ± 0.09.P38, C-JUN mRNA and protein levels were significantly reduced in the three plasmid transfection groups compared with the empty load group (P<0.01).The expression of p38,C-JUN mRNA and protein were reduced to a lower degree in co-transfection group than in GM-CSF transfection group and IL-12 transfection group (P<0.01).Flow cytometer showed that the hepatoma cell apoptosis rate of the empty load group,GM-CSF transfection group,IL-12 transfection group,co-transfection group were (3.43±0.9)%,(5.87±1.02)%,(7.32±1.1)%,(17.47±2.11)%,the rates of the three plasmid transfection groups were significantly higher than that of the empty load group (P<0.01).And the apoptosis rate was significantly increased in the co-transfected group compared with other plasmid groups (P<0.01). Conclusion The combination of GM-CSF and IL-12 could significantly accelerate the apoptosis of hepatoma cells by up-regulating the expression of p53,and down-regulating the expression of p38 and C-JUN.

Treatment of low lumbar degenerative disease with unilateral pedicle screw combined with contralateral percutaneous transfacet screws fixation / 中国骨伤

<p><b>OBJECTIVE</b>To explore the operative skills and effect of unilateral pedicle screw combined with contralateral percutaneous transfacet screws fixation in treating degenerative low lumbar disease.</p><p><b>METHODS</b>From January 2009 to December 2011,22 patients with degenerative low lumbar disease were treated with transforaminal lumbar interbody fusion, during the operations, unilateral pedicle screw and contralateral percutaneous transfacet screw fixation were performed. There were 16 males and 6 females, aged from 32 to 71 years old with an average of (51.1 ± 10.6) years, including single segment in 20 cases and two segments in 2 cases. Clinical effects were evaluated according to visual analogue score (VAS) and Oswestry Disability Index (ODI).</p><p><b>RESULTS</b>All patients were followed up from 1 to 2.5 years with an average of 18 months. One case complicated with leakage of cerebrospinal fluid after operation and 1 case with lower limb pain of decompression-side on the 3rd day after operation. Twenty-two patients got bony fusion. There were no instability and evidence of instrument failure during follow-up. The VAS and ODI score decreased from preoperative 8.24 ± 0.72, 36.72 ± 6.84 respectively to 3.18 ± 0.66, 4.36 ± 1.12 at the final follow-up (P < 0.05).</p><p><b>CONCLUSION</b>Unilateral pedicle screw combined with contralateral percutaneous transfacet screw fixation is safe and feasible surgical technique in treating low lumbar degenerative disease. It has advantages of little trauma, rigid fixation, high fusion rate, and less complication. etc.</p>

Progress on pathogenesis and treatment of paraquat-induced pulmonary fibrosis / 浙江大学学报·医学版

Paraquat (PQ) is a highly effective herbicide with contact toxicity. PQ mainly accumulates in the lungs after absorption into the blood circulation. The respiratory function failure caused by PQ-induced lung injury, especially the irreversible pulmonary fibrosis in late phase, is the leading cause of death in patients with PQ poisoning. The mechanism of PQ poisoning is still unclear. Now it is speculated that oxidative stress and inflammation injury are the main pathogenic mechanisms, and abnormal gene expression, mitochondrial damage, loss of pulmonary surfactant, cytokine network and unbalanced matrix metalloproteinases/tissue inhibitors may be also involved in the pathogenesis. In addition to reducing poison absorption and increasing its removal, the current clinical treatment is mainly composed of antioxidant and anti-immune response, but has poor therapeutic effects. Although many novel methods of treatment have been proposed, most of them are still in the experimental stage. It is a hot spot to clarify the mechanism of PQ poisoning and to seek safe and effective treatment of pulmonary fibrosis. This article reviews the research progress on pathogenesis and treatment of PQ-induced pulmonary fibrosis.