Erratum: CXCL12-mediated monocyte transmigration into brain perivascular space leads to neuroinflammation and memory deficit in neuropathic pain: Erratum.

[This corrects the article DOI: 10.7150/thno.44364.].

Associations between brain gene expression perturbations implicated by COVID-19 and psychiatric disorders.

BACKGROUND: Currently, there is increasing evidence from clinic, epidemiology, as well as neuroimaging, demonstrating neuropsychiatric abnormalities in COVID-19, however, whether there were associations between brain changes caused by COVID-19 and genetic susceptibility of psychiatric disorders was still unknown. METHODS: In this study, we performed a meta-analysis to investigate these associations by combing single-cell RNA sequencing datasets of brain tissues of COVID-19 and genome-wide association study summary statistics of psychiatric disorders. RESULTS: The analysis demonstrated that among ten psychiatric disorders, gene expression perturbations implicated by COVID-19 in excitatory neurons of choroid plexus were significantly associated with schizophrenia. CONCLUSIONS: Our analysis might provide insights for the underlying mechanism of the psychiatric consequence of COVID-19.

Interactome overlap between risk genes of epilepsy and targets of anti-epileptic drugs.

Aanti-epileptic drugs have been used for treating epilepsy for decades, meanwhile, more than one hundred genes have been identified to be associated with risk of epilepsy; however, the interaction mechanism between anti-epileptic drugs and risk genes of epilepsy was still not clearly understood. In this study, we systematically explored the interaction of epilepsy risk genes and anti-epileptic drug targets through a network-based approach. Our results revealed that anti-epileptic drug targets were significantly over-represented in risk genes of epilepsy with 17 overlapping genes and P-value = 2.2 ×10 -16. We identified a significantly localized PPI network with 55 epileptic risk genes and 94 anti-epileptic drug target genes, and network overlap analysis showed significant interactome overlap between risk genes and drug targets with P-value = 0.04. Besides, genes from PPI network were significantly enriched in the co-expression network of epilepsy with 22 enriched genes and P-value = 1.3 ×10 -15; meanwhile, cell type enrichment analysis indicated genes in this network were significantly enriched in 4 brain cell types (Interneuron, Medium Spiny Neuron, CA1 pyramidal Neuron, and Somatosensory pyramidal Neuron). These results provide evidence for significant interactions between epilepsy risk genes and anti-epileptic drug targets from the perspective of network biology.

CXCL12-mediated monocyte transmigration into brain perivascular space leads to neuroinflammation and memory deficit in neuropathic pain.

Emerging clinical and experimental evidence demonstrates that neuroinflammation plays an important role in cognitive impairment associated with neuropathic pain. However, how peripheral nerve challenge induces remote inflammation in the brain remains largely unknown. Methods: The circulating leukocytes and plasma C-X-C motif chemokine 12 (CXCL12) and brain perivascular macrophages (PVMs) were analyzed by flow cytometry, Western blotting, ELISA, and immunostaining in spared nerve injury (SNI) mice. The memory function was evaluated with a novel object recognition test (NORT) in mice and with Montreal Cognitive Assessment (MoCA) in chronic pain patients. Results: The classical monocytes and CXCL12 in the blood, PVMs in the perivascular space, and gliosis in the brain, particularly in the hippocampus, were persistently increased following SNI in mice. Using the transgenic CCR2RFP/+ and CX3CR1GFP/+ mice, we discovered that at least some of the PVMs were recruited from circulating monocytes. The SNI-induced increase in hippocampal PVMs, gliosis, and memory decline were substantially prevented by either depleting circulating monocytes via intravenous injection of clodronate liposomes or blockade of CXCL12-CXCR4 signaling. On the contrary, intravenous injection of CXCL12 at a pathological concentration in naïve mice mimicked SNI effects. Significantly, we found that circulating monocytes and plasma CXCL12 were elevated in chronic pain patients, and both of them were closely correlated with memory decline. Conclusion: CXCL12-mediated monocyte recruitment into the perivascular space is critical for neuroinflammation and the resultant cognitive impairment in neuropathic pain.

The effect of magnetic stimulation on differentiation of human induced pluripotent stem cells into neuron.

The effect of stem cell transplantation in the treatment of neural lesions is so far not satisfactory. Magnetic stimulation is a feasible exogenous interference to improve transplantation outcome. However, the effect of magnetic stimulation on the differentiation of induced pluripotent stem cells (iPSCs) into neuron has not been studied. In this experiment, an in vitro neuron differentiation system from human iPSCs were established and confirmed. Three magnetic stimuli (high frequency [HF], low frequency [LF], intermittent theta-burst stimulation [iTBS]) were applied twice a day during the differentiation process. Immunofluorescence and quantitative polymerase chain reaction (Q-PCR) were performed to analyze the effect of magnetic stimulation. Neural stem cells were obtained on day 12, manifested as floating neurospheres expressing neural precursor markers. All groups can differentiate into neurons while glial cell markers were not detected. Both Immunofluorescence and PCR results showed LF and iTBS increased the transcription and expression of neuronal nuclei (NeuN). HF significantly increased vesicular glutamate transporters2 transcription while iTBS promoted transcription of both synaptophysin and postsynaptic density protein 95. These results indicate that LF and iTBS can promote the generation of mature neurons from human iPSCs; HF may promote differentiate into glutamatergic neurons while iTBS may promote synapse formation during the differentiation.

Impact of Dwell Time of Retrievable IVC Filters on IVC Lumen Diameter: A Series of 36 Cases.

BACKGROUND: Inferior vena cava (IVC) filters are effective in preventing pulmonary embolism in patients at risk. This study aimed to investigate whether the dwell time of retrievable IVC filters have impact on IVC lumen diameter. METHODS: The clinical data of 36 patients treated with retrievable IVC filters from January 2016 to November 2018 were retrospectively collected. A total of 33 filters were successfully removed. At times of filter placement and removal, the IVC lumen diameter (at upper, middle, and lower levels of the filter), distance between the filter upper end and the right renal vein opening, and degree of filter tilt were measured. RESULTS: IVC filters were placed because of deep vein thrombosis in the lower limbs after fractures in 26 patients. The median dwell time of the IVC filters was 18 days. From the time of filter placement to that of removal, the IVC diameter decreased significantly at the middle (28.07 ± 5.92 vs. 25.73 ± 7.33 mm, P = 0.002) and lower levels (27.48 ± 4.73 vs. 26.36 ± 4.72 mm, P = 0.003) of the filters. No significant difference was noticed in the IVC diameter at the upper levels of the filters (27.78 ± 6.43 vs. 27.11 ± 6.63 mm, P = 0.082). Positive correlation was noticed between filter dwell time and IVC diameter changes at the upper (r = 0.381, P = 0.029) and middle (r = 0.555, P = 0.001) levels of the filters. No significant change was noticed in the distance from the filter upper end to the right renal vein opening and the degree of filter tilt. CONCLUSIONS: Retrievable IVC filters are associated with IVC stenosis. The severity of IVC stenosis is positively correlated with the dwell time of filters.

hTERT-Immortalized Bone Mesenchymal Stromal Cells Expressing Rat Galanin via a Single Tetracycline-Inducible Lentivirus System.

The use of human telomerase reverse transcriptase-immortalized bone marrow mesenchymal stromal cells (hTERT-BMSCs) as vehicles to deliver antinociceptive galanin (GAL) molecules into pain-processing centers represents a novel cell therapy strategy for pain management. Here, an hTERT-BMSCs/Tet-on/GAL cell line was constructed using a single Tet-on-inducible lentivirus system, and subsequent experiments demonstrated that the secretion of rat GAL from hTERT-BMSCs/Tet-on/GAL was switched on and off under the control of an inducer in a dose-dependent manner. The construction of this cell line is the first promising step in the regulation of GAL secretion from hTERT-immortalized BMSCs, and the potential application of this system may provide a stem cell-based research platform for pain.

MicroRNA-200a inhibits cell growth and metastasis by targeting Foxa2 in hepatocellular carcinoma.

Background: MicroRNAs (miRNAs) are a class of endogenous, small non-coding RNAs which function as essential posttranscriptional modulators of gene expression tightly involved in a wide range of diseases, including the hepatocellular carcinoma (HCC). Here, the present study was designed to investigate the expression levels and cellular roles of miR-200a in HCC. Methods: Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-200a in serums and cell lines. Bioinformation analysis, the luciferase reporter assay, qRT-PCR and western blotting were employed to validate Foxa2 as a direct target gene of miR-200a. Cell proliferation, migration and invasion were assessed to identify whether miR-200a could regulate the biological behaviors of HCC cells by targeting Foxa2. Results: In this study, a low level of miR-200a was observed in patients' serums and HCC cell lines. Overexpression of miR-200a in HCC cell lines reduced cell proliferation, migration and invasion. In addition, transcription factor forkhead box A2 (Foxa2) was identified as a novel target of miR-200a and downregulated at mRNA and protein levels in miR-200a overexpressed cells. Meanwhile, restoration of Foxa2 significantly reversed the tumor suppressive effects of miR-200a. Conclusions: These findings indicate that miR-200a regulates the proliferation, migration and invasion of HCC cells by targeting Foxa2, suggesting that miR-200a may function as a potential therapeutic molecular for the diagnosis and treatment of the liver cancer.

Anesthesia for tracheobronchial foreign bodies removal via self-retaining laryngoscopy and Hopkins telescopy in children.

This study attempted to explore suitable anesthetic methods used for removal of tracheobronchial foreign body (FB) via self-retaining laryngoscopy and Hopkins telescopy in children. 92 cases had undergone FB removal via self-retaining laryngoscopy and Hopkins telescopy or rigid bronchoscopy in our hospital since 2006, of which 56 cases were under intravenous anesthesia and endotracheal intubation with muscle relaxation (IAEI with MR), and the other 36 cases were under intravenous anesthesia with spontaneous breathing (IASB). Operative parameters and intraoperative vital signs were analyzed. Tracheobronchial foreign body was successfully removed in 87 cases, and not found in the other 5 cases. SpO(2) was below 90% transiently in 41 cases, 29 cases of which were under IAEI with MR and 12 cases were under IASB. Laryngospasm and choke were found in 12 cases under IASB. Vital signs including P(ET)CO(2) and heart rate were stable in all the cases. The mean surgical time, anaesthetic induction and recovery time of IAEI with MR via self-retaining laryngoscopy group were (5.69 ± 3.43) min, (9.68 ± 1.66) min and (26.13 ± 6.94) min, IASB via self-retaining laryngoscopy group were (21.35 ± 17.25) min, (13.71 ± 3.79) min and (24.64 ± 5.44) min, IAEI with MR via rigid bronchoscopy group were (10.20 ± 5.01) min, (10.31 ± 3.56) min and (25.13 ± 6.21) min, and IASB via rigid bronchoscopy group were (25.35 ± 13.25) min, (14.71 ± 3.61) min and (26.22 ± 5.65) min. It's a new and wonderful surgical procedure that combining self-retaining laryngoscopy and Hopkins telescopy for removal of tracheobronchial foreign body. IAEI with MR is suitable for bronchial FBA cases via them, while IASB is better for tracheal FBA or complicated cases.

Protective effect of Astragalus membranaceus on intestinal mucosa reperfusion injury after hemorrhagic shock in rats.

AIM: To study the protective effect of Astragalus membranaceus on intestinal mucosa reperfusion injury and its mechanism after hemorrhagic shock in rats. METHODS: A total of 32 SD rats were randomly divided into four groups (n = 8, each group): normal group, model group, low dosage group (treated with 10 g/kg Astragalus membranaceus) and high dosage group (treated with 20 g/kg Astragalus membranaceus). The model of hemorrhagic shock for 60 min and reperfusion for 90 min was established. Therapeutic solution (3 mL) was administrated before reperfusion. At the end of the study, the observed intestinal pathology was analyzed. The blood concentrations of lactic acid (LD), nitric oxide (NO), endothelin-1 (ET-1), malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) in intestinal mucosa were determined. RESULTS: The intestinal mucosa pathology showed severe damage in model group and low dosage group, slight damage in high dosage group and no obvious damage in normal group. The Chiu's score in low dose group and high dose group was significantly lower than that in model group. The content of MDA in model group was higher than that in low and high dose groups, while that in high dose group was almost the same as in normal group. The activity of SOD and GSH-PX was the lowest in model group and significantly higher in high dose group than in normal and low dose groups. The concentrations of LD and ET-1 in model group were the highest. The concentrations of NO in model group and low dose group were significantly lower than those in high dose group and normal group. CONCLUSION: High dose Astragalus membranaeus has much better protective effect on hemorrhagic shock-reperfusion injury of intestinal mucosa than low dose Astragalus membranaceus. The mechanism may be that Astragalus membranaceus can improve antioxidative effect and regulate NO/ET level during hemorrhagic reperfusion.