Mechanism of Honghua Oral Liquid in Alleviating Neuropathic Pain / 中国实验方剂学杂志

ObjectiveTo investigate the pharmacodynamic characteristics and explore the molecular mechanism of Honghua oral liquid （HOL） in relieving neuropathic pain （NP）. MethodHealthy male SD rats were randomly assigned into sham group， model group， low-， medium-， high-dose （0.5， 1.0， 2.0 mL·kg-1·d-1， respectively） HOL groups， and a positive drug （pregabalin， 25 mg·kg-1·d-1） group， with 6 rats in each group. Spinal nerve ligation （SNL） of L5 was conducted in other groups except the sham group. Drug administration was performed 3 days after the SNL surgery for 2 consecutive weeks， and samples were collected after the end of the administration. During the treatment period， the mechanical pain threshold and cold pain threshold were determined to measure the pain-relieving effect of HOL. Transcriptome sequencing was performed on hippocampal tissue samples from the sham， model， and high-dose HOL groups， and differentially expressed genes between the sham group and the model group as well as the model group and HOL high-dose group were obtained. After pathway enrichment analysis， we selected the targets which were closely related to neuroinflammation for validation， and predicted the specific binding sites of the major active components in HOL with the targets through molecular docking. In addition， the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-10 （IL-10） were determined by enzyme-linked immunosorbent assay （ELISA） to evaluate the effect of HOL on neuroinflammation in NP rats. ResultCompared with the sham group， SNL decreased the mechanical pain threshold and cold pain threshold （P<0.05）. Compared with the model group， HOL recovered the mechanical pain threshold and cold pain threshold （P<0.05）. The transcriptome data showed that 376 differentially expressed genes （DEGs） were identified between the model group and the sham group， including 124 upregulated genes and 252 downregulated genes， and 194 DEGs between the model group and the high-dose HOL group， including 33 upregulated genes and 161 downregulated genes. Among them， insulin-like growth factor 1（IGF1）， matrix metallopeptidase-2 （MMP-2）， matrix metallopeptidase-14 （MMP-14）， erb-B2 receptor tyrosine kinase 2 （ERBB2）， and integrin subunit alpha 5 （ITGA5） associated with NP were selected for further validation. The Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） results showed that compared with the sham group， the modeling up-gurelated the mRNA levels of the above five molecules in the hippocampus （P<0.01）. Compared with model group， HOL down-regulated the mRNA levels of these molecules （P<0.01）. The molecular docking results showed that the main active components of safflower， hydroxysafflor yellow A， kaempferol， and quercetin， formed stable hydrogen bonds with the amino acid residues of IGF1， MMP-2， MMP-14， ERBB2， and ITGA5. The enzyme-linked immunosorbent assay（ELISA） results showed that compared with those in the sham group， the serum levels of TNF-α and IL-10 were out of balance in the model rats （P<0.01）. Compared with the model group， HOL lowered the level of the pro-inflammatory cytokine TNF-α （P<0.01） and elevated that of the anti-inflammatory cytokine IL-10 （P<0.05）. ConclusionHOL exerts analgesic effect on SNL rats by inhibiting neuroinflammation.

Mechanism of Glycyrrhizae Radix et Rhizoma Alleviating Tripterygium wilfordii Polyglycoside Tablets-induced Liver Injury / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect of cytochrome P4502D6 （CYP2D6） and cytochrome P4503A4 （CYP3A4）， key enzymes of drug metabolism in liver， on acute liver injury in water extract of Glycyrrhizae Radix et Rhizoma （WEOGRR）. MethodHealthy male Kunming mice were divided into normal group， model group， WEOGRR low-， medium- and high-dose groups （5， 10， 15 g·kg-1·d-1） and positive drug group （diammonium glycyrrhizinate， 75 mg·kg-1·d-1）， with 10 in each group. One week after preventive administration， acute liver injury model was induced by single intragastric administration of 270 mg·kg-1 Tripterygium Glycosides tablets， and samples were collected after 18 h. The pathological changes of liver were observed by hematoxylin-eosin （HE） staining. Serum liver function indexes including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyl transpeptadase （γ-GT）， alkaline phosphatase （ALP）， and total bilirubin （TBIL） as well as the levels of oxidative stress indexes including malondialdehyde （MDA） and superoxide dismutase （SOD） in hepatocytes were determined by biochemical method. Real-time polymerase chain reaction （Real-time PCR） and Western blot were performed to detect the mRNA and protein expression levels of CYP2D6 and CYP3A4， respectively. ResultCompared with normal group， model group had significant hepatocyte swelling and inflammatory cell infiltration （P<0.01）， increased AST， ALT， γ-GT， ALP and TBIL （P<0.05）， elevated MDA and decreased SOD （P<0.01） as well as down-regulated mRNA and protein expression levels of CYP2D6 and CYP3A4 （P<0.05）. Compared with the model group， the normal group had intact liver structure without obvious abnormality， and the WEOGRR groups and positive drug group presented alleviated hepatocyte swelling and inflammatory cell infiltration （P<0.01）， reduced AST， ALT， γ-GT， ALP and TBIL （P<0.01）， lowered MDA and increased SOD （P<0.01） as well as up-regulated expression levels of CYP2D6 and CYP3A4 （P<0.01）. ConclusionThe protective effect of WEOGRR on acute liver injury induced by Tripterygium glycosides tablets may be related to reducing the contents of AST， ALT， γ-GT， ALP and TBIL in serum， inhibiting MDA and increasing the activity of SOD in liver cells， and enhancing the activities of CYP2D6 and CYP3A4， thus accelerating the metabolism of toxic substances.

Analysis of gene mutation in a pedigree with autosomal dominant Charcot-Marie-Tooth disease / 南方医科大学学报

OBJECTIVE@#To investigate the molecular genetic mechanism of Charcot- Marie-Tooth (CMT) disease in a pedigree.@*METHODS@#Genomic DNA was extracted from the peripheral blood of the family members of a pedigree with autosomal dominant CMT disease, and 65 candidate genes of the proband were screened using target exon capture and the next generation sequencing, and the suspicious genes were verified using Sanger sequencing. PolyPhen-2, PROVEAN and SIFT software were used to predict the function of the mutant genes, and PyMOL-1 software was used to simulate the mutant protein structure.@*RESULTS@#A heterozygous missense mutation [c.371A>G (p.Y124C)] was detected in exon 3 of gene of the proband. This heterozygous mutation was also detected in both the proband's mother and her brother, but not in her father. Multiple sequence alignment analysis showed that tyrosine at codon 124 of GDAP1 protein was highly conserved. All the 3 prediction software predicted that the mutation was harmful. Molecular structure simulation showed a weakened interaction force between the amino acid residues at codon 124 and the surrounding amino acid residues to affect the overall stability of the protein.@*CONCLUSIONS@#The mutation of gene may be related to the pathogenesis of autosomal dominant AD-CMT in this pedigree. The newly discovered c.371A>G mutation (p.Y124C) expands the mutation spectrum of gene, but further study is needed to clarify the underlying pathogenesis.

Diffusion-weighted imaging in transient ischemic attack / 国际脑血管病杂志

Transient ischemic attack (TIA) traditionally refers to temporary brain dysfunction lasting no longer than 24 hours due to a shortage of blood and oxygen, without any residual neurological deficit. In recent years, the development of imaging technology enables us to have a new awareness about TIA. This article reviews the effects of MRI, especially diffusion-weighted imaging, in the diagnosis and prognostic prediction of TIA.

The incidence of depression after minimally invasive hematoma stereotactic aspiration in patients with intracerebral hemorrhage A clinical observation / 国际脑血管病杂志

Objective To prospectively study the minimally invasive hematoma stereotactic aspiration and the recovery of neurological deficits after conservative medical treatment alone, as well as the incidence of post-stroke depression (PSD) in patients with intracerebral hemorrhage, so as to investigate the effect of minimally invasive hernatorna stereotactic aspiration on the recovery of neurological deficits and the incidence of PSD. Methods Fifty-five patients with intracerebral hemorrhage received minimally invasive hematoma stereotactic aspiration (n =25) and conservative medical treatment (n = 30), respectively. The neurological deficits of the patients were assessed by the National Institutes of Health Stroke Scale (NIHSS) at admission, day 14 and 90. The decreased values (all compared to baseline score) of the NIHSS scores were calculated at day 14 and 90, respectively; the modified Rankin Scale (mRS) was used to assess the disabled degree at day 90; the 17-item Hamilton Depression Rating Scale (HAMD) was used to assess the PDS status at day 14 and 90. The correlation between PSD and the degrees of neurological deficit and disability in patients was analyzed. Results The decreased value of the NIHSS score in the stereotactic group at day 14 and 90 was significantly higher than that in the conservative treatment group (all P ＜0. 05), and the value of the mRS score was significantly lover than that in the conservative treatment group at day90 (P＜0. 05). The incidence and the total incidence of PSD in the stereotactic group at day 90 were significantly lover than those in the conservative treatment group (all P ＜0.05). There were significant positive correlation between HAMD and NIHSS scores and HAMD and mRS scores. Conclusions The recovery of neurological deficits was faster after the minimally invasive hematoma stereotactic aspiration. The degree of disability in patients was lower, and the incidence of PSD was also lower than that in the conservative treatment group. PSD was closely correlated with the degrees of neurological deficits and disability.

Stereotactic Minimally Invasive Aspiration for Small Thalamic Hemorrhage A Clinical Study / 国际脑血管病杂志

Objective:To explore the feasibilitv of stereotactic minimally invasive aspiration of small thalamic bemorrhage.Methods:Twenty-two patients with small thalamic hemowhage(5 to 10 mL)were divided into two groups:a stereotactic group(n=10)and a control group(n= 12).The patients in the stereotactic group received stereomctic minimally invasive puncture and drainage of hematomas.According to the condition,repeated infusion of urokinase(10-20 kU) into the hematoma cavities were administered 12 hours after the procedure,and the hematomas were irrigated and drained so as to removal of them completely after retaining for 2-4 hours, The appropriate symptomatic treatment was administered in the patients in both groups.National Institutes of Health Stroke Scale(NIHSS)scores were determined 14 and 30 days before and after the treatment in all the patients.The reductiom of the NIJSS scores (as compared with those before treatment)were calculated at day 14 and 30 respectively after the treatment. Results:The reductiom of the NIHSS scores in the stereotactic group at day 14 and 30 were significantly higher than those in the control group.It was suggested that the neurological functional recovery of the patients was faster after stereotmtic minimally invasive puncture and drainage of intracranial hematorna in the stereotactic group.Concision:The stereotactic minimally invasive puncture and drainage of intracranial hematoma may significantly improve the outcome in patients with small thalamic hemorrhage.