Objective To investigate the effect of microplastic(MPs)exposure on learning and memory in mice,and its mechanism by observing the protein expression of brain-derived neurotrophic factor(BDNF)/tyrosine receptor kinase B(TrkB)/N-methyl-D-aspartate receptor subtype 2B(NR2B)signaling pathway and neurogenesis.Methods Forty male C57BL/6 mice were randomly divided into control group(Ctrl)and microplastics exposure group(MPs).Mice in MPs group were treated with 0.3 mg/(kg·d)microplastics,administered by gavage at a volume of 200 μl for 30 consecutive days.Morris water maze test was used to evaluate the spatial learning and memory ability of mice.Western blotting was used to detect the protein levels of BDNF,TrkB and NR2B in hippocampus of mice.Immunofluorescent staining was used to observe the number of doublecortin(DCX)and neuronal nuclei antigen(NeuN)positive cells in the hippocampus of mice to evaluate hippocampal neurogenesis.Results Compared with the control group,the ability of learning and memory decreased significantly in MPs group mice(P＜0.01).The expression levels of BDNF,TrkB and NR2B in the hippocampus of MPs group mice were significantly lower than those of control group(P＜0.05).The number of DCX and NeuN positive cells in the hippocampus of MPs group was significantly lower than that of control group(P＜0.01).Conclusion MPs exposure induces learning and memory impairment which may be related to inhibiting BDNF/TrkB/NR2B signaling pathway and reducing hippocampal neurogenesis.

AIM To study the chemical constituents from n-butanol fraction of Corydalis impatiens(Pall.)Fisch.and their antioxidant activities.METHODS The n-butanol fraction was isolated and purified by silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antioxidant activities were determined by DPPH method and tyrosinase method.RESULTS Fourteen compounds were isolated and identified as nicotinamide(1),methyl L-pyroglutamate(2),bungeanoline F(3),monomethyl fumarate(4),5-hydroxymethylfurfural(5),4-hydroxybenzoic acid(6),hydroxybenzoate(7),methyl 3,4-dihydroxybenzoate(8),methyl ferulate(9),dimethylcaffeic acid(10),dimethyl feruloyl malate(11),(-)-4-O-feruloylquinic acid(12),syringaresinol(13)and(-)-loliolide(14).Compounds 1,8,11 and 13 showed strong antioxidant activites on DPPH free radicals,with IC50 values ranging from 54.47 to 97.4 μmol/L.Compound 13 had potential inhibitory effect on tyrosinase.CONCLUSION Compounds 4-14 are first isolated from Corydalis genus,and 3 is isolated from this plant for the first time.Compounds 1,8,11 and 13 have strong antioxidant activities.

Objective To investigate the value of intraoperative transesophageal echocardiography (TEE) in the diagnosis and treatment of renal cell carcinoma with inferior vena cava tumor thrombus. Methods Ten patients of renal cell carcinoma with inferior vena cava tumor thrombus treated in the Second Hospital of Hebei Medical University from January 2017 to January 2021 were selected.TEE was employed to locate the position of the tumor thrombus,determine the occlusion point of the inferior vena cava,count the intraoperative tumor thrombus shedding rate,examine the tumor thrombus resection integrity,and measure blood loss and other indicators,on the basis of which the application value of TEE in the operation of renal cell carcinoma with inferior vena cava tumor thrombus was evaluated. Results All the 10 patients had completed the operations successfully,including 8 patients of open operation and 2 patients of laparoscopic operation.TEE showed tumor thrombi clearly,and all the tumor thrombi were completely removed.There was no tumor thrombus shedding during the operation.The blood loss varied within the range of 300-800 ml,with the mean of (520.0±193.2) ml.The grade III tumor thrombi in 2 patients and the grade I tumor thrombus in 1 patient diagnosed before operation were reduced to grade Ⅱ and upgraded to grade Ⅱ,respectively,by TEE.One patient had no floating tumor thrombus at the end of tumor thrombus before operation,and the blocking position was adjusted in time with the assistance of TEE to avoid the shedding of the floating tumor thrombus. Conclusion TEE can accurately determine and dynamically monitor the location and shape of inferior vena cava tumor thrombus,which provides an important reference and has a significant clinical value in the operation of renal cell carcinoma with inferior vena cava tumor thrombus.
Humans ; Carcinoma, Renal Cell/surgery* ; Echocardiography, Transesophageal ; Vena Cava, Inferior ; Echocardiography ; Kidney Neoplasms/surgery*

Objective To investigate long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) interactions and identify the critical gene regulatory network during Schistosoma japonicum infections and praziquantel treatment using whole transcriptome sequencing. Methods A total of 110 male C57BL/6 mice were randomly divided into the control group, the infection group and the treatment group. Mice in the infection treatment and the control group were infected with S. japonicum cercariae via the abdomen, and liver specimens were sampled from 10 mice 3, 6, 8 weeks post-infection. Praziquantel treatment was given to mice in the treatment group 8 weeks post-infection, and liver specimens were sampled from 10 mice 2, 4, 6, 8, 10 weeks post-treatment. Total RNA was isolated from mouse liver specimens, and the transcriptome library was constructed for highthroughput whole transcriptome sequencing. The significant differentially expressed genes were subjected to functional annotations, Gene Ontology (GO) terms enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Correlation analysis of liver specimens was performed using R Corrplot and Himsc functions, and the lncRNAmiRNA-mRNA interaction network analysis was performed using R MixOmics and Himsc functions. Results There were 1 176 differentially expressed miRNAs, 5 270 differentially expressed mRNAs, and 2 682 differentially expressed lncRNAs between the infection group and the control group, 1 289 differentially expressed miRNAs, 7 differentially expressed mRNAs, and 69 differentially expressed lncRNAs between the treatment group and the infection group, and 1 210 differentially expressed miRNAs, 4 456 differentially expressed mRNAs, and 2 016 differentially expressed lncRNAs between the treatment group and the control group. Correlation analysis showed a higher correlation of gene expression between the treatment group and the control group. Principal component analysis showed obvious separate clustering between the infection group and the treatment group. The differentially expressed genes with significant relevance were significantly enriched in 24 GO terms, including arachidonic acid metabolic process, xenobiotic catabolic process, unsaturated fatty acid metabolic process, xenobiotic metabolic process, long-chain fatty acid metabolic process, and 8 KEGG metabolic pathways, including cholesterol metabolism, tyrosine metabolism, linoleic acid metabolism, retinol metabolism, and steroid hormone biometabolism. Conclusions There were 23 mRNAs including Cyp2b9 and 14 lncRNAs including Rmrpr in the core position of the gene regulatory network, which may play a critical role in S. japonicum infections and praziquantel treatment, and 9 miRNAs including miR-8105 may serve as potential molecular markers for diagnosis of S. japonicum infections.

Aim To study the effects of naringenin on MCD diet-induced liver fibrosis and its related mechanisms.Methods LX2 cells were incubated with TGF-β1 for 24 h to establish the in vitro fibrosis model.LX2 cells were treated with NGN at the same time.Male C57BL/6 mice were fed with MCD diet for six weeks to induce liver fibrosis.100 mg·kg-1·d-1 NGN was administered by gavage simultaneously.The protein expressions of α-SMA, col1, TGF-β1, p-smad2 and p-smad3 were evaluated by Western blot.The mRNA expressions of α-SMA, col1 and col3 were detected by qRT-PCR.The degree of liver fibrosis was evaluated by Sirius red staining.Results Both in in vivo and in vitro experiments, compared with model group, the mRNA levels of α-SMA, col1 and col3 and protein levels of α-SMA, TGF-β1, p-smad2 and p-smad3 significantly decreased in NGN treatment group.The results of HE staining and Sirius red staining also indicated that NGN significantly decreased liver fibrosis induced by MCD diet.Conclusions Naringin can significantly inhibit liver fibrosis induced by MCD diet, which may be related to TGF-β1/Smad pathway.

BACKGROUND: Gastric cancer (GC) is one of the most globally prevalent cancers in the world. The pathogenesis of GC has not been fully elucidated, and there still lacks effective targeted therapeutics. The influence of altered kinesin superfamily protein 22 (KIF22) expression in GC progression is still unclearly. The aim of this study was to investigate the KIF22 effects on GC and related mechanisms. METHODS: Gastric carcinoma tissues and matching non-cancerous tissues were collected from patients with GC who have accepted a radical gastrectomy in Lanzhou University Second Hospital from May 2013 to December 2014. The expression of KIF22 was examined in GC of 67 patients and 20 para-carcinoma tissues by immunochemical staining. The relationship between the expression of KIF22 and clinicopathologic characteristics was next investigated in the remaining 52 patients except for 15 patients who did not complete follow-up for 5 years. Cell viability was performed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test and colony formation assay in the MGC-803 and BGC-823 GC cells. Cell scratch and trans-well invasion assay was performed to assess migration ability in the MGC-803 and BGC-823 GC cells. Gene set enrichment analysis (GSEA) pathway enrichment analysis was performed to explore the potential functions. Cell cycle was detected by flow cytometry. In addition, the two GC cell lines were used to elucidate the underlying mechanism of KIF22 in GC in vitro via assessing the effects on mitogen-activated protein kinase and extracellular regulated protein kinases (MAPK/ERK) signal transduction pathway-related expressions by Western blotting assays. The differences were compared by t tests, one-way analysis of variance, and Chi-squared tests. RESULTS: The study showed that KIF22 was up-regulated in GC, and KIF22 high expression was significantly related to differentiation degree (χ = 12.842, P = 0.002) and poorly overall survivals. GSEA pathway enrichment analysis showed that KIF22 was correlated with the cell cycle. Silence of KIF22 decreased the ability of the proliferation and migration in gastric cells, induced G1/S phase cell cycle arrest via regulating the MAPK-ERK pathways. CONCLUSIONS KIF22 protein level was negatively correlated with prognosis. KIF22 knockdown might inhibit proliferation and metastasis of GC cells via the MAPK-ERK signaling pathway.

Objective:To construct oxaliplatin (L-OHP) drug-resistant cell line HCT-116/L-OHP in human colon cancer, in order to observe the reversal effect of curcumin (cur) on its drug resistance, and preliminarily explore the possible drug resistance mechanism. Method:The concentration gradient increasing method was used to gradually increase the L-OHP concentration of HCT-116 in parental colon cancer cells, and the cell line HCT-116/L-OHP resistant to L-OHP was established. The cytotoxicity of L-OHP and curcumin to HCT-116 and HCT-116/L-OHP cells was detected by cell counting kit-8(CCK-8) method to observe whether curative resistance could be reversed. Western blot was used to detect the expressions of drug-resistance-related proteins. Real-time PCR was used to detect changes in related genes. Result:Human colon cancer cell line resistant to L-OHP were successfully established and named as HCT-116/L-OHP, with a drug resistance index of 12.6.Compared with HCT-116 cell lines, the expression levels of resected and repaired cross complementation gene 1 (ERCC1) protein and gene in HCT-116/L-OHP cell lines were significantly increased (P<0.01). The expressions of B-cell lymphoma-2 (Bcl-2), glutathione-s-transferase-consciousness (GST-consciousness), multidrug resistance-associated protein (MRP), P-glycoprotein (P-gp) and apoptotic inhibitory gene (Survivin) also increased significantly (P<0.01). After the treatment with different concentrations of curcumin (5,10,20,30,40 μmol·L^-1), the expression of ERCC1 decreased (P<0.01), and the expressions of Bcl-2,GST-π,MRP,P-gp,Survivin also decreased to different degrees (P<0.05). Conclusion:HCT-116/L-OHP cell lines have a stable drug resistance, and its drug resistance mechanism may be up-regulated with the expression of ERCC1, which leads to the up-regulation of Bcl-2,GST-π,MRP,P-gp,Survivin and other related proteins, and enables tumor cells to acquire drug resistance. Curcumin can reverse the drug resistance of HCT-116/L-OHP, and its mechanism may be to reduce the expression of ERCC1, thereby down-regulating the expressions of Bcl-2,GST-π,MRP,P-gp,Survivin and other drug-resistant related genes and proteins, and increase the sensitivity of tumor to L-OHP, so as to reverse the drug resistance of tumor cells.

Objective: To explore the anti-lung cancer mechanism of Maimendong Tang and Qianjin Weijingtang (Jin Fang) by detecting the expression profiles of long noncoding RNA (lncRNA) and mRNA in mice tumor tissues of orthotopic Lewis lung cancer model. Method: C57BL/6 mice were randomly divided into normal group, model group and Jin Fang group (20 g·kg^-1·d^-1). After successful establishment of Lewis lung cancer model in situ in mice, Jin Fang was given orally the next day after treatment. Using gene chip technology, differential lncRNA and mRNA closely related with Jin Fang' s anti-lung cancer effect were detected, and cluster analysis was performed. The key lncRNA and mRNA were screened out by t-test and fold change of differential expression. Bioinformatic methods were used to predict target genes regulated by differential lncRNA, and functional and pathway analysis was performed. The histopathological technique was used to detect the differences in the tumor tissue of each group under light microscope. Result: lncRNA and mRNA chip hybridization results showed that Jin Fang regulated differential expressions of 887 lncRNA, in which 442 were up-regulated and 445 were down-regulated (P<0.05). There were 610 differential mRNA expressions, in which 376 were up-regulated and 234 were down-regulated(P<0.05). GO analysis showed that down-regulated or up-regulated target genes were mainly involved in biological processes (BP), such as cell metabolism regulation and signal pathway regulation. Molecular function (MF) analysis showed such functions DNA binding, protein binding, receptor binding and transcription factor activity in down-regulated or up-regulated target genes. Target genes were involved in multiple biological processes, cellular components and molecular functions. Signal pathway predictions indicated that Jin Fang can regulate the Janus kinase/signal transducer and activator of tran-ions(JAK/STAT) and other signaling pathways closely related to the development of lung cancer. The results of histopathological examination confirmed that Jin Fang could significantly improve the pathological changes of lung tissues in the mice compared with the model group. Conclusion: Jin Fang may exert its anti-lung cancer effect by regulating the expressions of multiple lncRNAs and mRNAs, and down-regulating related signaling pathways.

In 2013,China pharmaceutical regulatory department issued guiduance on postmarketing drug safety monitoring for industry. It aimed to encourage industry to carry out postmarketing drug safety monitoring including hospital-based intensive monitoring of postmarketing Chinese patent medicine. Subsequently,more and more such kind of studies have been performed all over China. However,in view of the current situation in this field,the development of hospital-based intensive monitoring of postmarketing Chinese patent medicine lacks standardization,such as unreasonable design,omission of reports about adverse drug reactions,inadequate process of quality control,non-standardized interpretation of adverse reactions,etc. Therefore,it is necessary to formulate relevant technical specifications to guide this area. The developing of this technical specification refered to the international post-marketing safety monitoring model and advanced design concepts and methods. We developed it under the guidance of relevant laws,regulations and technical documents in China. Meanwhile the characteristics of Chinese patent medicines and the real situation in this area were considered. The aim of this technical specification is to obtain the incidence,type,degree and clinical manifestation of adverse drug reactions of Chinese patent medicines,to find new risk signals of adverse reactions,to identify risk factors,and to provide a basis for the formulation of risk management and control plans. This specification has been approved by China association of Chinese medicine which is numbered T/CACM011-2016.
Adverse Drug Reaction Reporting Systems ; China ; Hospitals ; Medicine, Chinese Traditional ; Nonprescription Drugs ; Product Surveillance, Postmarketing

OBJECTIVE: To investigate the use of antibiotics in children with community-acquired pneumonia (CAP) in multiple regions of China, and to provide a reference for CAP standard treatment and rational antibiotic use in children. METHODS: The medical data of 1 383 children with CAP who were hospitalized in the department of pediatrics in 10 grade A tertiary hospitals from 9 cities between April 14, 2014 and January 1, 2016 were reviewed, to analyze the status of antibiotic use in hospitalized children in North China, Northeast China, East China, and South China. RESULTS: The overall rate of antibiotic use in children with CAP was 89.08%, with 88.7% in North China, 95.5% in Northeast China, 83.3% in East China, and 86.6% in South China. The main types of antibiotics used were cephalosporins, macrolides, compound preparations of β-lactam antibiotics, polyphosphoric broad-spectrum antibiotics and other β-lactam antibiotics. The selection of antibiotics was generally rational, but antibiotics were still used in some patients with viral infection alone or a combined use of ≥2 kinds of antibiotics were noted in some patients with infection caused by one kind of pathogen. Irrational antibiotic use was observed in 131 children (10.63%). CONCLUSIONS There are high rates of antibiotic use and irrational use of antibiotics among children with CAP. Standard management of antibiotic use in children with CAP should be strengthened.
Anti-Bacterial Agents ; therapeutic use ; Child ; Child, Hospitalized ; China ; Community-Acquired Infections ; drug therapy ; Humans