ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia（FD） and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats（7 days old） were randomly divided into the normal group（n=12） and the modeling group（n=48）， and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared， the rats in the modeling group were randomly divided into the model group， the low-dose and high-dose groups of Xingpi capsules（0.135， 0.54 g·kg^-1） and the domperidone group（3 mg·kg^-1）， with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water， and rats in the rest of the groups were gavaged with the corresponding medicinal solution， once a day for 7 d. The general survival condition of the rats was observed， and the water intake and food intake of the rats were measured， the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment， the pathological damage of the rat duodenum was examined by hematoxylin-eosin（HE） staining， and the expressions of colonic tight junction protein（Occludin） and zonula occludens protein-1（ZO-1） were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group， and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration， and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were carried out. The transcriptomic results were validated by Western blot， immunofluorescence， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group， the general survival condition of rats in the model group was poorer， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly reduced（P<0.05）， inflammatory infiltration was seen in duodenal pathology， and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced（P<0.01）. Compared with the model group， the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly increased（P<0.05）， the duodenal pathology showed a decrease in inflammatory infiltration， and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased（P<0.01）. Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） through the key genes such as Slc5a1， Abhd6. The validation results showed that compared with the normal group， the phosphorylation levels of PI3K and Akt proteins， the protein expression level of interleukin（IL）-1β， and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3， Slc5a9 and other key genes were significantly increased（P<0.01）. Compared with the model group， the phosphorylation levels of PI3K and Akt， the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3 and Slc5a9 were significantly reduced（P<0.05）. Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein， and linarionoside A， valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats， its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum， and E-nerolidol， Z-nerolidol， linarionoside A， valerosidatum and senkirkine may be its key active ingredients.

ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia（FD） and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats（7 days old） were randomly divided into the normal group（n=12） and the modeling group（n=48）， and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared， the rats in the modeling group were randomly divided into the model group， the low-dose and high-dose groups of Xingpi capsules（0.135， 0.54 g·kg^-1） and the domperidone group（3 mg·kg^-1）， with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water， and rats in the rest of the groups were gavaged with the corresponding medicinal solution， once a day for 7 d. The general survival condition of the rats was observed， and the water intake and food intake of the rats were measured， the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment， the pathological damage of the rat duodenum was examined by hematoxylin-eosin（HE） staining， and the expressions of colonic tight junction protein（Occludin） and zonula occludens protein-1（ZO-1） were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group， and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration， and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were carried out. The transcriptomic results were validated by Western blot， immunofluorescence， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group， the general survival condition of rats in the model group was poorer， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly reduced（P<0.05）， inflammatory infiltration was seen in duodenal pathology， and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced（P<0.01）. Compared with the model group， the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly increased（P<0.05）， the duodenal pathology showed a decrease in inflammatory infiltration， and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased（P<0.01）. Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） through the key genes such as Slc5a1， Abhd6. The validation results showed that compared with the normal group， the phosphorylation levels of PI3K and Akt proteins， the protein expression level of interleukin（IL）-1β， and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3， Slc5a9 and other key genes were significantly increased（P<0.01）. Compared with the model group， the phosphorylation levels of PI3K and Akt， the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3 and Slc5a9 were significantly reduced（P<0.05）. Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein， and linarionoside A， valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats， its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum， and E-nerolidol， Z-nerolidol， linarionoside A， valerosidatum and senkirkine may be its key active ingredients.

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

OBJECTIVE: To investigate a family with congenital dysfibrinogenemia, and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of the proband and her family members were detected by automatic coagulometer, fibrinogen (Fg) activity and antigen were detected by Clauss method and PT algorithm respectively. Meanwhile, thromboelastometry was analyzed for proband and her family members. Then, peripheral blood samples of the proband and her family members were collected, and all exons of FGA, FGB and FGG and their flanks were amplified by PCR and sequenced to search for gene mutations. RESULTS: The proband had normal APTT and PT, slightly prolonged TT, reduced level of Fg activity (Clauss method). The Fg of the proband's aunt, son and daughter all decreased to varying degrees. The results of thromboelastogram indicated that Fg function of the proband and her family members (except her son) was basically normal. Gene analysis showed that there were 6233 G/A (p.AαArg35His) heterozygous mutations in exon 2 of FGA gene in the proband, her children and aunt. In addition, 2 polymorphic loci were found in the family, they were FGA gene g.9308A/G (p.AαThr331Ala) and FGB gene g.12628G/A (p.BβArg478Iys) polymorphism, respectively. The proband was injected with 10 units of cryoprecipitate 2 hours before delivery to prevent bleeding, and no obvious bleeding occurred during and after delivery. CONCLUSION Heterozygous mutation of 6233G/A (p.AαArg35His) of FGA gene is the biogenetic basis of the disease in this family with congenital dysfibrinogenemia.
Humans ; Child ; Female ; Fibrinogen/genetics* ; Pedigree ; Afibrinogenemia/genetics* ; Mutation ; Blood Transfusion

Non-alcoholic fatty liver disease (NAFLD) is considered to be a manifestation of metabolic syndrome and has become one of the chronic diseases that endanger health around the world. There is still a lack of effective therapeutic drugs in clinical practice. Farnesoid X receptor (FXR) has been a popular target for NAFLD research in recent years. Fexaramine (Fex) is a potent and selective agonist of FXR, and its mechanism of action to improve NAFLD is unclear. Therefore, in this study, a mouse model of NAFLD was constructed using a high-fat, high-cholesterol diet and treated with Fex orally for 6 weeks. We evaluated the ameliorative effect of Fex on disorders of glucolipid metabolism in NAFLD mice, and preliminarily explored its potential mechanism of action. The animal experiments were approved by the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval number: PZSHUTCM210913011). In this study, it was found that 100 mg·kg^-1 Fex significantly inhibited body weight gain, alleviated insulin resistance, improved liver injury and lipid accumulation in NAFLD mice. The effect of Fex on the expression of hepatic intestinal FXR and its target genes in NAFLD mice was further examined. Analysis of serum and hepatic bile acid profiles and expression related to hepatic lipid metabolism. It was found that Fex could stimulate intestinal FXR, promote fibroblast growth factor 15 (FGF15) secretion, inhibit the expression of cytochrome P450 family 7 subfamily A member 1 (CYP7A1), the rate-limiting enzyme of bile acid synthesis in liver, regulate bile acid synthesis by negative feedback, and improve the disorder of bile acid metabolism. At the same time, Fex reduces liver lipid synthesis and absorption, increases fatty acid oxidation, thus improving liver lipid metabolism. This study shows that Fex can improve NAFLD by activating intestinal FXR-FGF15 signal pathway and regulating liver lipid metabolism.

In recent years, due to the emergence of ultrafast ultrasound imaging technology, the sensitivity of detecting slow and micro blood flow with ultrasound has been dramatically improved, and functional ultrasound imaging (fUSI) has been developed. fUSI is a novel technology for neurological imaging that utilizes neurovascular coupling to detect the functional activity of the central nervous system (CNS) with high spatiotemporal resolution and high sensitivity, which is dynamic, non-invasive or minimally invasive. fUSI fills the gap between functional magnetic resonance imaging (fMRI) and optical imaging with its high accessibility and portability. Moreover, it is compatible with electrophysiological recording and optogenetics. In this paper, we review the developments of fUSI and its applications in neuroimaging. To date, fUSI has been used in various animals ranging from mice to non-human primates, as well as in clinical surgeries and bedside functional brain imaging of neonates. In conclusion, fUSI has great potential in neuroscience research and is expected to become an important tool for neuroscientists, pathologists and pharmacologists.
Animals ; Mice ; Ultrasonography/methods* ; Brain/physiology* ; Magnetic Resonance Imaging ; Optogenetics ; Hemodynamics

Female ; Humans ; Lactobacillus ; drug effects ; Ozone ; pharmacology ; Vagina ; microbiology ; Water ; chemistry ; pharmacology

OBJECTIVE: To explore the changes of normal vaginal micro-ecological environment after vaginal lavage with ozonated water and its effect on lactobacillus.METHODS: From April to October 2016,30 volunteers with normal vaginal microecological examination results were recruited from female workers in Beijing Tsinghua Changgung Hospital and selected to receive vaginal lavage with ozonated water,during non-menstrual periods 5 minutes per day,for 3 consecutive days.The vaginal secretions were taken before the first vaginal ozone lavage,the first week,the second week and the third week after the last lavage,and the microecological examination and the difference in the diversity and abundance of the vaginal microbial community were analyzed after 16 S rRNA high-through put sequencing.RESULTS: Before and after healthy women received ozone water for vaginal lavage,there were no significant differences in the microflora evaluation of vaginal secretions,vaginal microbial community diversity or lactobacillus(|cor. p| <0.2).CONCLUSION: Ozonated water for vaginal lavage does not destroy the normal vaginal microecology and has no significant effect on lactobacilli.

OBJECTIVE: To study the effects of Kushen gel on the growth of six common vaginal lactobacilli in vitro.METHODS: This study was conducted at Beijing Tsinghua Changgung Hospital from June 2018 to March 2019.Six different vaginal lactobacilli isolated from the healthy women of reproductive age in China were purified and cultured in vitro. The effect of different concentrations of Sophora flavescens alkaloid,which was the main active ingredient of Kushen gel,on the growth of various clinical lactobacillus isolates was observed by the agar dilution method.RESULTS: The minimum inhibitory concentration(MIC)of Sophora flavescens alkaloid to Lactobacillus rhamnosus was 40 mg/mL. The MICs for Lactobacillus crispatus,Lactobacillus jensenii,Lactobacillus gasseri and Lactobacillus reuteri were all 20 mg/mL. The MIC for Lactobacillus vaginalis was 10 mg/mL.When the concentration of Sophora flavescens alkaloid was lower than the MIC value,it had a certain effect on promoting proliferation of both Lactobacillus gasseri and Lactobacillus reuteri,but had no effect on Lactobacillus crispatus or Lactobacillus vaginalis.CONCLUSION: Under the clinical dosage,Kushen gel does not inhibit the growth of common vaginal lactobacilli,which is conducive to the recovery of the vaginal microecosystem.

The aim of the present study was to examine the relationship between the protein expression of vascular endothelial growth factor (VEGF) and lymph node metastasis (LNM) in papillary thyroid cancer (PTC).VEGF-related articles that had been published until August 2016 were searched from the PubMed,EMBASE,and MEDLINE to identify the risk factors of LNM in PTC.RevMan 5.3 software was used for the meta-analysis.Finally,9 articles met the inclusion criteria and were included in our meta-analysis.LNM was found to be present in 176 of 318 patients (57.8％) with high VEGF expression and in 71 of 159 patients (47.0％) with low VEGF expression.The overall OR was 2.81 (95％ confidence interval,1.49-5.29).LNM occurred more frequently in patients with high VEGF expression than in those with low VEGF expression (P=0.001).Heterogeneity was markedly decreased in the subgroup analyses of LNM in terms of the patients' country of origin and the detection methods.Our meta-analysis concluded that the VEGF protein expression is associated with LNM in PTC.