Protective effect of Liujing Toutong Tablets on rats with permanent cerebral ischemia via NF-κB signaling pathway / 中国中药杂志

This study investigated the neuroprotective effects and underlying mechanism of Liujing Toutong Tablets(LJTT) on a rat model of permanent middle cerebral artery occlusion(pMCAO). The pMCAO model was established using the suture method. Eighty-four male SPF-grade SD rats were randomly divided into a sham operation group, a model group, a nimodipine group(0.020 g·kg~(-1)), and high-, medium-, and low-dose LJTT groups(2.8, 1.4, and 0.7 g·kg~(-1)). The Longa score, adhesive removal test and laser speckle contrast imaging technique were used to evaluate the degree of neurological functional impairment and changes in local cerebral blood flow. The survival and mortality of rats in each group were recorded daily. After seven days of continuous administration following the model induction, the rats in each group were euthanized, and brain tissue and blood samples were collected for corresponding parameter measurements. Nissl staining was used to examine pathological changes in brain tissue neurons. The levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-1β, vascular endothelial growth factor(VEGF), calcitonin gene-related peptide(CGRP), beta-endorphin(β-EP), and endogenous nitric oxide(NO) in rat serum were measured using specific assay kits. The entropy weight method was used to analyze the weights of various indicators. The protein expression levels of nuclear factor kappa-B(NF-κB), inhibitor kappaB alpha(IκBα), phosphorylated IκBα(p-IκBα), and phosphorylated inhibitor of NF-κB kinase alpha(p-IKKα) in brain tissue were determined using Western blot. Immunohistochemistry was used to detect the protein expression of chemokine-like factor 1(CKLF1) and C-C chemokine receptor 5(CCR5) in rat brain tissue. Compared with the sham operation group, the model group showed significantly higher neurological functional impairment scores, prolonged adhesive removal time, decreased cerebral blood flow, increased neuronal damage, reduced survival rate, significantly increased levels of TNF-α, IL-1β, IL-6, CGRP, and NO in serum, significantly decreased levels of VEGF and β-EP, significantly increased expression levels of NF-κB p65, p-IκBα/IκBα, and p-IKKα in rat brain tissue, and significantly upregulated protein expression of CKLF1 and CCR5. Compared with the model group, the high-dose LJTT group significantly improved the neurological functional score of pMCAO rats after oral administration for 7 days. LJTT at all doses significantly reduced adhesive removal time and restored cerebral blood flow. The high-and medium-dose LJTT groups significantly improved neuronal damage. The LJTT groups at all doses showed reduced levels of TNF-α, IL-1β, IL-6, CGRP, and NO in rat serum, increased VEGF and β-EP levels, and significantly decreased expression levels of NF-κB p65, p-IκBα/IκBα, p-IKKα, and CCR5 protein in rat brain tissue. The entropy weight analysis revealed that CGRP and β-EP were significantly affected during the model induction, and LJTT exhibited a strong effect in reducing the release of inflammatory factors such as TNF-α and IL-1β. LJTT may exert a neuroprotective effect on rats with permanent cerebral ischemia by reducing neuroinflammatory damage, and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the regulation of the CKLF1/CCR5 axis. Additionally, LJTT may exert certain analgesic effects by reducing CGRP and NO levels and increasing β-EP levels.

Analysis of A Pedigree with Hereditary Coagulation Factor Ⅻ Deficiency Caused by Compound Heterozygous Mutations / 中国实验血液学杂志

OBJECTIVE@#To analysis clinical phenotype and potential genetic cause of a family affected with hereditary coagulation factor Ⅻ deficiency.@*METHODS@#The prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-Dimer (D-D), coagulation factor Ⅻ activity (FⅫ:C) and coagulation factor Ⅻ antigen (FⅫ:Ag) were determined for phenotype diagnosis of the proband and his family members(3 generations and 5 people). Targeted capture and whole exome sequencing were performed in peripheral blood sample of the proband. Possible disease-causing mutations of F12 gene were obtained and further confirmed by Sanger sequencing. The corresponding mutation sites of the family members were analyzed afterwards. The online bioinformatics software AutoPVS1 and Mutation Taster was used to predict the effects of mutation sites on protein function.@*RESULTS@#The APTT of the proband was significantly prolonged, reaching 180.9s. FⅫ:C and FⅫ:Ag of the proband was significantly reduced to 0.8% and 4.17%, respectively. The results of whole exome sequencing displayed that there were compound heterozygous mutations in F12 gene of the proband, including the c.1261G＞T heterozygous nonsense mutation in exon 11 (causing p.Glu421*) and the c.251dupG heterozygous frameshift mutation in exon 4 (causing p.Trp85Metfs*53). Both mutations are loss of function mutations with very strong pathogenicity, leading to premature termination of the protein. AutoPVS1 and Mutation Taster software predicted both mutations as pathogenic mutations. The results of Sanger sequencing revealed that c.1261G＞T heterozygous mutation of the proband was inherited from his mother, for which his brother and his daughter were c.1261G＞T heterozygous carriers. Genotype-phenotype cosegregation was observed in this family.@*CONCLUSION@#The c.1261G＞T heterozygous nonsense mutation in exon 11 and the c.251dupG heterozygous frameshift mutation in exon 4 of the F12 gene probably account for coagulation factor Ⅻ deficiency in this family. This study reports two novel pathogenic F12 mutations for the first time worldwide.

Nutritional recovery after discharge in hospitalized children with malnutrition / 中国当代儿科杂志

OBJECTIVE@#To investigate the nutritional recovery status of children with moderate or severe malnutrition during hospitalization after discharge.@*METHODS@#The children with moderate or severe malnutrition were given nutrition support during hospitalization. They received a regular follow-up and nutrition guidance after discharge. The weight-for-age and height-for-age Z-scores reaching above -2 SD were considered the nutrition criterion for ending follow-up.@*RESULTS@#Among the 298 children with moderate or severe malnutrition, 174 (58.4%) reached the criterion for ending follow-up, 100 (33.6%) were lost to follow-up, 18 (6.0%) died, and 6 (2.0%) did not reach the criterion for ending follow-up after 18 months of follow-up. The children with malnutrition in the department of surgery had a significantly higher proportion of children reaching the criterion for ending follow-up than those in the department of internal medicine (P<0.05). The children with severe malnutrition had a significantly higher loss to follow-up rate than those with moderate nutrition (P<0.05). The majority of children with emaciation reached the criterion for ending follow-up at month 3 after discharge, while those with growth retardation reached such the criterion at months 3-6 after discharge. Up to 1 year after discharge, more than 80% of the children with different types of malnutrition reached the nutrition criterion for ending follow-up.@*CONCLUSIONS@#Most of the children with malnutrition who adhere to follow-up can reach the expected nutrition criterion within 1 year after discharge. The children with growth retardation have slower nutritional recovery than those with emaciation.

Data mining of the prescription containing Codonopsis and study on the molecular mechanism of prevention and treatment of gastrointestinal disease / 药学学报

The medication rules of high frequency herb-pairs containing Codonopsis pilosula (Dangshen) were analyzed with data mining tools, and the molecular mechanisms of these herb-pairs on the gastrointestinal diseases were predicted with the network pharmacology. The R language association rules were used to mine the high frequency herb-pairs from TCM formulae containing Dangshen, and these herb-pairs would be screened out, which satisfied the following requirements with support ≥ 0.3 and confidence ≥ 0.9 at the same time. Using the Integrated Pharmacology Platform of Traditional Chinese Medicine (TCMIP) to predict the key core targets of the high frequency herb-pairs, the network of Chinese medicine-compound-target-pathway related to Dangshen were built to explore the preventing and treating molecular mechanism on gastrointestinal diseases. At last, the relation of the main active components from Dangshen and its herbal pairs with target proteins were validated by Systems Dock Web Site. The 185 formulae were selected from 543 formulae containing Dangshen, and 6 herbal pairs with Dangshen, which includes Angelica (Danggui), Licorice (Gancao), Atractylodes macrocephala (Baizhu), Poria cocos (Fuling), dried tangerine peel (Chenpi) and Astragalus membranaceus (Huangqi), were discovered with Apriori algorithm. The combination of 6 herbal pairs is similar to Bu Zhong Yi Qi Decoction; 6 herbal pairs with Dangshen were related to the target of POMC, OPRM1, CCR9 and HTR2C in TCMIP. The known targets (HTR2C, POMC, OPRM1, CCR9, OPRD1) and potential drug-targets (GNB1, GCK, SDHD, SLC25A2, DHRS4) for gastrointestinal diseases were predicted about the high frequency pairs with Dangshen. The results of GO enrichment analysis showed that the biological function was mainly located in the mitochondria and myelin sheath, and involved in the biological processes of three carboxylic acid cycle, platelet activation, and aspartic acid metabolism. KEGG pathway enrichment analysis showed that the main metabolic pathways related with Dangshen pairs involved amino acid metabolism, energy metabolism and endocrine metabolism. The prediction results showed many targets of the frequency herbal pairs with Dangshen preventing and treating gastrointestinal diseases were related with nerve cells. These herbal pairs could prevent and treat the gastrointestinal diseases through the neuroendocrine system and the brain gut axis.

Study of the association between SNP rs7903146(C/T) in TCF7L2 and metabolic syndrome in Chinese Korean and Han populations from Yanbian / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association between a rs7903146(C/T) polymorphism of TCF7L2 gene and metabolic syndrome (MS), plasma lipoprotein, and plasma adiponectin (PA) in Chinese Korean and Han populations from Yanbian region.</p><p><b>METHODS</b>Polymerase chain reaction and DNA sequencing were used to determine the genotype of rs7903146 in 310 Chinese Korean (190 in case group and 120 in control group) and 344 Chinese Han (255 in case group and 89 in control group). ELIAS was used to test serum insulin (INS) and PA.</p><p><b>RESULTS</b>The frequency of T allele was higher in ethnic Han compared with ethnic Koreans (0.022 vs. 0.008), lower than that of Europeans (0.279) and Africans (0.257), but similar to those of Beijing Chinese and Japanese. For ethnic Korean Chinese, the frequencies of TT and CT genotypes as well as the T allele in patients with EH were significantly higher than those of the control group (P< 0.01), which also showed an increasing trend for both MS and T2DM groups (P=0.09 and P=0.07, respectively). By contrast, for Chinese Han, the frequencies of genotypes and particular allele in patients with MS, T2DM and EH showed no significant difference from those of the control group. For T2DM, EH, and control groups, PA level of individuals with CT or TT genotypes was significantly higher compared with that of the CC genotype (P< 0.05). The TC and LDL-C levels were significantly higher in T2DM, MS and EH groups compared with those of the control group. The PA level was lower in MS group compared with the control group.</p><p><b>CONCLUSION</b>The T allele of SNP rs7903146 of TCF7L2 gene may be a risk factor for EH in Chinese Korean population from Yanbian region. The T allele also affects the PA level; lower PA is a risk factor for MS. The rs7903146 polymorphism showed a racial and ethnic difference.</p>

Pathologic features of ulegyria in refractory epilepsy by modified anatomic hemispherectomy: a clinicopathologic study of 39 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic features of the brain tissue diagnosed as ulegyria from modified anatomic hemispherectomy for refractory epilepsy.</p><p><b>METHODS</b>The clinical and pathologic findings were reviewed in 39 patients who underwent modified anatomic hemispherectomy and diagnosed as ulegyria in the Epilepsy Center of Tsinghua University Yuquan Hospital from 2007 to 2011.</p><p><b>RESULTS</b>All patients including 30 males and 9 females had medically intractable seizures, and the mean age of seizure onset and disease duration were 4.0 years and 7.3 years respectively. Significant history included febrile seizure in 14 patients (35.9%), cerebral hemorrhage in 8 patients (20.5%), fetal distress and surgical trauma each in 6 patients (15.4%), vascular malformation and cerebral hemorrhage in 1 patient (2.6%), and unclear history in 4 patients (10.2%). Histologically, all cases were characterized by cortical destruction, with neuronal loss and gliosis. All cases were accompanied by varying degree of cortical dysplasia, which were diagnosed as focal cortical dysplasia IIId. Hippocampus sclerosis was identified in 2 cases. Seizure outcome after surgery revealed 37 patients (94.9%) had an Engel grade I, two patients (5.1%) had an Engel grade II.</p><p><b>CONCLUSIONS</b>Febrile seizure, cerebral hemorrhage, fetal distress and surgical trauma in childhood can lead to refractory epilepsy. Histopathological change in the brain is ulegyria accompanied by focal cortical dysplasia IIId. Modified anatomic hemispherectomy is an effective therapy to treat those patients with extensive changes of one hemisphere.</p>

The killing effect of two different formulations paclitaxel in KB cell in vitro / 中国药学杂志

OBJECTIVE: To investigate the killing effect of albumin-bound paclitaxel and paclitaxel solution on human oral epithelial carcinoma KB cells in vitro. METHODS: The KB cell line was cultured with different concentrations of albumin-bound paclitaxel or paclitaxel solution. MTT assay, inverted microscopic observation and flow cytometry assay were then used to monitor the growth and proliferation of the cell line. RESULTS: When treated with different concentrations of albumin-bound paclitaxel or paclitaxel solution for 36 and 72 h, KB cells survival rate decreased significantly, however, the difference between their IC50 was no significant; degeneration and necrosis of KB cells were found under microscope; the rate of cell apoptosis was increased gradually; the rate of S phase was reduced, and the percentage of G2/M cells treated with 0.1, 1 and 10 μmol · L-1 albumin-bound paclitaxel or paclitaxel was increased, which significantly higher than that of G2/M cells treated with 100 μmol · L-1 albumin-bound paclitaxel or paclitaxel. However, the two groups with the same concentration showed no significant differences in apoptosis rate and cell cycle (P > 0.05). CONCLUSION: Compared with paclitaxel, albumin-bound paclitaxel have the similar ability to inhibit proliferate and promote apoptosis in KB cells. Copyright 2012 by the Chinese Pharmaceutical Association.