ABSTRACT
OBJECTIVE To explore the potential targets and mechanisms of the modified Baihe dihuang decoction （MBD/ BDD） applied in post-stroke depression （PSD）. METHODS Network pharmacology was used to mine the potential targets and key pathways of MBD/BDD in the treatment of PSD. PSD model rats were induced by focal cerebral ischemia surgery combined with chronic unforeseen mild stress， and then were randomly divided into PSD model group， MBD/BDD group （12.6 g/kg， by raw drug）， and fluoxetine hydrochloride （FLX） group （positive control， 2.3 mg/kg）； a blank control group was also set up， with 8 rats in each group. Each administration group was given a corresponding medication solution by gavage once a day for 21 consecutive days. The intervention effect of MBD/BDD on depression-like symptoms in model rats was evaluated by open field and forced swimming tests. The brain tissues of rats in each group were dissected and total RNA was extracted for transcriptome sequencing and bioinformatics analysis. The mRNA and protein expressions of genes with significant changes and common neurotrophic factors were verified based on the above results. RESULTS A total of 131 MBD/BDD antidepressant-related target genes were obtained （such as IL1B and AKT1， etc.）， which were closely related to neural active ligand-receptor interactions and cyclic adenosine monophosphate signaling pathway. MBD/BDD could significantly prolong or increase the total time spent and distance traveled in the central grid of qiangzhe@cqtcm.edu.cn PSD model rats， and significantly shorten the cumulative immobility time （P＜0.05）. After treatment with MBD/BDD， the number of genes that changed in rat brain tissue was much higher than that in the FLX group， and there were significant differences in gene profiles among the PSD model group， MBD/BDD group， and FLX group. There were 1 351 differentially expressed genes （DEGs） between the MBD/BDD group and the PSD model group， of which 178 were significantly down-regulated and 1 173 were significantly up-regulated （P＜0.05）. Above 1 351 DEGs were involved in neuronal differentiation， chemical synaptic transmission regulation. They were significantly enriched in axonal guidance， cholinergic synapses and neuroactive ligand-receptor interactions. The top 30 genes in terms of up-regulation in the brain tissue of rats of MBD/BDD group were all associated with neuronal proliferation， development， differentiation， and migration. After MBD/BDD intervention， the expressions of Fezf2， Arx， Ostn， Nrgn genes， brain-derived neurotrophic factor and tyrosine kinase receptor B protein in brain tissue of rats were significantly increased （P＜0.05）. CONCLUSIONS The anti-PSD effect of MBD/BDD may be related to the up-regulation of the expression of genes related to neuronal proliferation， development， differentiation and migration， as well as the promotion of neural structural and functional repair.
ABSTRACT
OBJECTIVE To investigate the treatment plan for az treonam-resistant metallo- β-lactamase（MBL）-producing Enterobacteriaceae infection in pediatric solid organ transplant recipients. METHODS The clinical data of aztreonam-resistant MBL-producing Klebsiella pneumoniae caused intra-abdominal infection of an infant after liver transplantation were retrospectively analyzed. Abdominal infection occurred after operation. The pathogenic bacterium was MBL-producing K. pneumoniae . The drug sensitivity results showed that the infant was resistant to aztreonam. Based on the results of sensitivity test ，polymyxin B combined with tigecycline were selected as initial regimen. The treatment effect was poor ，with recurrent disease and shock spots. The clinical pharmacist assisted the clinician to formulate treatment regimen of ceftazidime avibactam 0.5 g，q8 h combined with aztreonam 0.18 g，q6 h. Relevant domestic and foreign literature were reviewed ，and the treatment plan of MBL-producing Enterobacteriaceae infection after solid organ transplantation was summarized. RESULTS & CONCLUSIONS The infant was finally cured and discharged with ceftazidime avibatan combined and aztreonam. Several foreign literature reported that ceftazidime avibactam combined with aztreonam could effectively treat the infection caused by aztreonam-resistant MBL-producing Enterobacteriaceae infection in patients with organ transplantation. It is expected to be an effective treatment for aztreonam-resistant MBL-producing Enterobacteriaceae infection in pediatric solid organ transplant recipients.
ABSTRACT
Objective:To evaluate the clinical prognostic significance of molecular markers with high predictive value for lymph node metastasis (LNM) before operation in gastric cancer (GC).Methods:From January 2013 to December 2015, at Peking University Third Hospital, 85 patients with GC confirmed by preoperative biopsy under gastroendoscopy and receiving radical gastrectomy were selected. Among 85 patients with GC, 34 patients had LNM and the other 51 patients were without LNM. The expression levels of macrophage capping protein G (CapG), tyrosine kinase receptor B (TrkB), prosperohomeobox protein l (Prox-1), matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor-C (VEGF-C) and vascular endothelial growth factor receptor 3 (VEGFR3) were detected by immunohistochemistry (IHC) in preoperative gastric biopsy tissues. Chi-square test was performed to analyze the correlation between the expression of different markers and various clinicopathological characteristics. Receiver operating characteristic (ROC) curve was drawn to compare the predictive value of different markers on LNM of GC. Kaplan-Meier curve was applied to evaluate the impact of different markers on the prognosis of GC patients.Results:The positive expression rates of CapG, TrkB, Prox-1, MMP-2, VEGF-C and VEGFR3 of the LNM-positive group were higher than those of the LNM-negative group (85.3%, 29/34 vs. 35.3%, 18/51; 76.5%, 26/34 vs. 29.4%, 15/51; 67.6%, 23/34 vs. 11.8%, 6/51; 64.7%, 22/34 vs. 33.3%, 17/51; 61.8%, 21/34 vs. 29.4%, 15/51; 52.9%, 18/34 vs. 23.5%, 12/51, respectively), and the differences were statistically significant ( χ2=20.631, 18.093, 28.342, 8.086, 8.746 and 7.727, all P<0.01). The area under the ROC curve (AUC) values and 95% confidence interval ( CI) of CapG, TrkB, Prox-1, MMP-2, VEGF-C and VEGFR3 in predicting LNM of GC before operation were 0.787 (0.687 to 0.880), 0.772 (0.656 to 0.860), 0.761 (0.661 to 0.883), 0.724 (0.618 to 0.830), 0.687 (0.571 to 0.803) and 0.583 (0.452 to 0.715), respectively. Among them, the AUC values of CapG, Prox-1 and TrkB were relatively high. The expression levels of CapG and Prox-1 were correlated with invasion depth and TNM stage of GC ( χ2=4.792, 13.664, 4.204 and 19.948, all P<0.05). And TrkB expression was correlated with TNM stage of GC ( χ2=12.036, P<0.05). Kaplan-Meier curves revealed that the overall survival rates of CapG, TrkB or Prox-1 positive groups were significantly lower than those of CapG, TrkB or Prox-1 negative groups (70.2%, 33/47 vs. 94.7%, 36/38; 70.7%, 29/41 vs. 90.9%, 40/44; 69.0%, 20/29 vs. 87.5%, 49/56, respectively), and the differences were statistically significant ( χ2=9.820, 4.909 and 4.683, all P<0.05). Conclusions:CapG, TrkB and Prox-1 are markers with relatively high predictive value for LNM of GC, and all of them are correlated with the progression and poor prognosis of GC.
ABSTRACT
Objective To explore the mechanism underlying the inhibitory effects of Hydrotalcite on Helicobacter pylori (H.pylori).Methods H.pylori international standard strain 26695 was resuscitated and incubated in Columbia solid culture medium and brucella broth.It was divided int6 blank control group,H.pylori injured group and H.pylori with Hydrotalcite group.H.pylori were treated by Hydrotalcite,and the viability changes of H.pylori were observed.The morphological changes of H.pylori were detected by Gram's stain.The changes of mycoproteins expression of H.pylori were examined by Coomassie blue stain.The effects of H.pylori on cell apoptosis of gastric epithelial cell line GES-1 was compared between groups with and without Hydrotalcite.Subcellular structure and attachment ability of H.pylori on GES-1 cells were observed with transmission electron microscopy and scanning electron microscopy.T test was performed for statistical analysis.Results Hydrotalcite could inhibit the growth of H.pylori.However there were no significant morphological changes of H.pylori.Many mycoproteins were regulated by Hydrotalcite.Without Hydrotalcite,a large amount of H.pylori attached on the cell surface of GES-1 promoted the apoptosis of GES-1 cell.Compared with blank control group,the apoptosis rate of GES-1 cells increased after treated by H.pylori ((5.52 ± 1.31)％ vs (28.96 ±3.14)％),and the difference was statistically significant (t=-11.94,P＜0.05).Hydrotalcite could prevent the attachment of H.pylori on cells,which reduced the apoptosis caused by H.pylori ((28.96 ±3.14) ％ vs (19.38 ± 1.91) ％),and the difference was stattstically significant (t =4.52,P ＜ 0.05).Conclusion Hydrotalcite has inhibitory effects on H.pylori in vitro and play a role in regulation of many mycoproteins.Hydrotalcite can reduce the attachment of H.pylori on gastric epithelial cells,and protect cells from H.pylori injury.
ABSTRACT
Background: CKLF-like MARVEL transmembrane domain containing (CMTM) superfamily is involved in the occurrence and development of inflammation, cancer and a variety of diseases.Human CMTM3 has been proposed as a putative tumor suppressor gene.Aims: To investigate the expression of CMTM3 in Helicobacter pylori (Hp) infection-related chronic gastritis and its significance.Methods: Sixty cases of outpatients with chronic gastritis (30 Hp-positive and 30 Hp-negative) were enrolled for detection of CMTM3 and interleukin-6 (IL-6) expressions in gastric mucosa by immunohistochemistry.The correlation of expressions of CMTM3 and IL-6 was analyzed.Results: The positivity rates of CMTM3 and IL-6 in gastric mucosa were significantly higher in Hp-positive chronic gastritis than in Hp-negative ones (CMTM3: 63.3% vs.30.0%, P<0.05;IL-6: 73.3% vs.13.3%, P<0.01).In patients with Hp-positive chronic gastritis, CMTM3 and IL-6 were co-expressed in 53.3% (16/30) of the patients and localized in the same position.Expression of CMTM3 was positively correlated with IL-6 expression in Hp-positive chronic gastritis patients (r=0.58, P<0.05).Conclusions: CMTM3 is highly expressed in chronic gastritis patients with Hp infection.It may participate in the occurrence and development of Hp infection-related chronic gastritis with inflammatory cytokines such as IL-6.Hp infection might be one of the mechanisms involved in CMTM3 up-regulation.
ABSTRACT
[Summary] Gastric cancer is seriously dangerous to human health with constantly high incidence .Human gastric mucosa can express gastrokines that can inhibit cancer cell growth .Gastrokines is expressed abundantly in normal tissues while downregulated or absent in gastric cancer and precancerous lesion .It plays an important role in the suppression of gastric cancer proliferation combining with the other factors such as helicobacter pylori infection or trefoil factors .In this paper we made a review about the suppression of gastrokines on gastric cancer cell proliferation .