Objective:By observing the hippocampus 5-HT1A receptor expression, MDA content and SOD activity and the effect of lentinan mouse model of chronic stress behavior,serum TNF-αand IL-6 content.To investigate the mechanism of antidepressant LNT.Methods:Healthy adult mice were 50,male,body weight (20 ±2) g,SPF grade,based on 1% sucrose water partial addicted degrees and were randomly divided into four groups,namely,normal control group (Normal controls,NG),model in the control group ( Model control,MG) ,LNT dose group ( L-LNT,2.5 mg/kg;H-LNT,5.0 mg/kg).Before the experiment began modeling 1 h daily oral administration,continuous administration 28 d, each experimental group administered according 1.0 ml/100 g weight.Application chronic unpredictable mild stress model of depression produced,and make improvements.Normal control group,not to stimulate,food and water properly.Model group and the experimental intervention group with the lone support,fasting,water deprivation (24 h),and accept the unpredictable stressors,the 28 d of the experiment,the animals were randomized to receive daily each only one stimulus, within five days after making the choreography the stimulus program was not repeated and unpredictable.Animals were observed daily behavior change,with a strange environment to start feeding feeding experimentally observed incubation period,forced swim stress test record swim immobility time,enzyme-linked immunosorbent assay of serum TNF-α,IL-6 content ,NBT assay of total SOD activity,thio-barbituric acid (thiobarbituric acid,TBA) MDA content assay,immune proteins mark (Western blot) to detect 5-HT1A receptor expression levels.Results:MG mice in an unfamiliar environment, feeding latency was significantly prolonged after giving LNT intervention can shorten lead to chronic stress in mice feeding latency in an unfamiliar environment,prolonged chronic stress leads to significantly reduce the stress in mice swimming in water immobility time extension,and 5-HT1A receptor expression enhancing,LNT intervention group increased SOD,MDA content decreased serum TNF-αand IL-6 was significantly reduced,compared with the model group MG indicators above improvements were statistically significant ( P<0.05 or P<0.01 ).Conclusion:LNT can significantly antagonize depressive symptoms in mouse models of chronic stress,increased locomotor activity in mice time;LNT increase SOD,MDA content may antagonize the antidepressant effects and mechanisms related to LNT.

BACKGROUNDSince an effective method for generating induced pluripotent stem cells (iPSCs) from human neural stem cells (hNSCs) can offer us a promising tool for studying brain diseases, here we reported direct reprogramming of adult hNSCs into iPSCs by retroviral transduction of four defined factors.

METHODSNSCs were successfully isolated and cultured from the hippocampus tissue of epilepsy patients. When combined with four factors (OCT3/4, SOX2, KLF4, and c-MYC), iPSCs colonies were successfully obtained.

RESULTSMorphological characterization and specific genetic expression confirmed that these hNSCs-derived iPSCs showed embryonic stem cells-like properties, which include the ability to differentiate into all three germ layers both in vitro and in vivo.

CONCLUSIONOur method would be useful for generating human iPSCs from NSCs and provide an important tool for studying neurological diseases.

Cell Differentiation ; genetics ; physiology ; Cells, Cultured ; Cellular Reprogramming ; genetics ; physiology ; Humans ; Immunohistochemistry ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; Kruppel-Like Transcription Factors ; metabolism ; Neural Stem Cells ; cytology ; metabolism ; Octamer Transcription Factor-3 ; metabolism ; Proto-Oncogene Proteins c-myc ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; SOXB1 Transcription Factors ; metabolism

Objective:To explore the predictive value of peripheral perfusion index (PI) combined with central venous-arterial carbon dioxide tension to arterial-venous oxygen content ratio(Pv-aCO 2/Ca-vO 2)for prognosis after initial resuscitation of septic shock. Methods:A total of 76 cases of patients with septic shock from January 2019 to January 2021 in emergency intensive care unit (EICU) of Harrson international peace hospital affiliated to Hebei Medical University were enrolled. All recovered according to 2016 Severe Sepsis and Septic Shock Treatment International Guidelines 2016 (SSC 2016) , and PI was monitored, central vein and arterial blood gas analysis was performed, and the ratio of Pv-aCO 2/Ca-vO 2 was calculated.The PI and Pv-aCO 2/Ca-vO 2 at 3 h,hemodynamic variables,oxygen metabolism indexes,APACHEⅡ and SOFA score were recorded.Patients were divided into survival group and death group according to 28 d survival condition, the dfferences in demographics and clinical data were compared between two groups.The Kaplan-Meier urviving curve was created and the survival of the patients was analyzed by the Log-rank test. Risk factors associated with the prognosis were analyzed using the Cox regression analysis. The role of PI and Pv-aCO 2/Ca-vO 2 in prediting death was evaluated by receiver operating characteristic curves(ROC). Results:There were 37 cases in survival group and 39 cases in death group.Compared with death group, PI in survival group [(1.77±0.63) vs. (0.89±0.69)]was significantly higher,and Pv-aCO 2/Ca-vO 2[(1.52±0.52) vs. (2.57±0.86)] was significantly lower ( P<0.05). Kaplan-Meier survival curve showed that the median survival time in the high PI group [20.09 d (95% CI:16.95-23.24) vs.11.00d (95% CI:7.14-14.86)] was longer than that in the low PI group(χ 2=12.424, P=0.000),and that in low Pv-aCO 2/Ca-vO 2 group [23.74 d (95% CI:20.35-27.13) vs.12.85d (95% CI:9.75-15.95)] was longer than that in the high Pv-aCO 2/Ca-vO 2 group (χ 2=12.200, P=0.000) .Cox regression analysis showed that both PI ( RR=0.397, 95% CI: 0.230-0.687, P =0.001) and Pv-aCO 2/Ca-vO 2 ( RR=1.878, 95% CI: 1.169-3.019, P =0.009) were predictors of 28 d mortality.The area under the ROC curve of PI and Pv-aCO 2/Ca-vO 2 for predicting 28 d death in patients with septic shock were 0.828 (95% CI: 0.732-0.923) and 0.785 (95% CI: 0.6777-0.893)respectively. The optimal cutoff values were 0.52 (sensitivity 58.3% and specificity 94.4%) and 0.35 (sensitivity 88.9% and specificity 63.9%)respectively, and the AUC of the combined prediction of the two indicators was 0.903 (95% CI: 0.835-0.971). Conclusions:Combination of PI and Pv-aCO 2/Ca-vO 2 is better to predict the risk of adverse outcomes of septie shock patients,and may provide useful information for the resuscitation at early stage.

Lysyl oxidase like 4 (LOXL4) is one member of the LOX protein family and is a secreted copper-dependent amine oxidase involved in the assembly and maintenance of extracellular matrix (ECM). LOXL4 is up-regulated in human liver cancer, gastric cancer, breast cancer, cervical cancer, head and neck squamous cell carcinoma, esophageal carcinoma and colorectal cancer, but down-regulated in human bladder and lung cancer. It also inhibits tumor growth in bladder and lung cancer, suggesting that L0XL4 has a dual role of promoting or inhibiting tumors in different types of human malignant tumors. L0XL4 in tumor cell exosomes promotes cell matrix adhesion and cell migration by activating the FAK/Src pathway, which is dependent on its amine oxidase activity through a hydrogen peroxide-mediated mechanism. Exosome-mediated L0XL4 can also promote tumor cell proliferation and immune escape by activating the PI3K/Akt signaling pathway. L0XL4 can be transported to macrophages via exosomes in tumor cells, where it further activates the immunosuppression function of cells and the expression of programmed death ligand 1 (PD-L1) via STAT1- and STAT3-mediated signaling pathways. It then will trigger the immunosuppressive function of macrophages and promote the immune escape of tumor cells. In addition, LOXL4 can also exert the tumor suppressive function by activating p53 and inhibiting the Ras/ERK pathway. This paper mainly reviews the structure and the function of LOXL4, and the relationship between LOXL4 and the pathogenesis and development of human malignant tumors. We then further explore the application of LOXL4 in the study of malignant tumors, laying a theoretical foundation for its future utilization in the clinical diagnosis and treatment, and screening of prognostic markers of human malignant tumors.

OBJECTIVETo express the recombinant D protein in prokaryotic expression system solubly and make preparation for producing D-carrier conjugate vaccine next step.

METHODSThe hpd gene fragment removed of signal peptide from genomic DNA of Hib CMCC was inserted into pET43. 1a. The recombinant plasmid was transformed to competent E. coli BL21 (DE3) for expression under induction of IPTG. The expressed recombination protein was precipitated with ammonium sulfate, purified by DEAE anion exchange column chromatography and identified for reactogenicity by Western Blot.

RESULTSThe expressed recombination protein, in a soluble form, constained about 50% of total somatic protein and showed specific reaction with the HIB antisera after preliminary purification.

CONCLUSIONThe D protein recombined expression plasmid was constructed successfully and expressed D protein in prokaryotic cells in a solube form.

Bacterial Proteins ; genetics ; Blotting, Western ; Carrier Proteins ; genetics ; Escherichia coli ; genetics ; Haemophilus influenzae type b ; genetics ; Immunoglobulin D ; genetics ; Lipoproteins ; genetics ; Plasmids ; Recombinant Proteins ; biosynthesis ; Solubility

Objective : To establish a laboratory model of heroin addiction in C57BL /6 mice based on associative learning mechanisms． Methods: The black box and white box were selected as the memory training environment， and three behavioral training paradigms were studied : ① Pavlovian conditional position preference ( CPP) training paradigm，mice were placed in the white box for memory reinforcement training for 30 min after intraperitoneal injection of 0. 1 ml of corresponding concentrations (5. 0，10. 0，20. 0 mg / kg) of heroin at 9 :00 a．m．，and 24 h later 0. 1 ml of 0. 9% NaCl solution was injected intraperitoneally into the black box for training，and after the training，the mice were tested for their memory preference for the black and white boxes (movement time of different boxes) . ② A naloxone conditional position aversion ( CPA) training paradigm was conductedbased on the results of the CPP training paradigm. ③ Behavioral sensitization training paradigm，heroin addiction rating scale was established based on the statistical results of 3 behavioral experiments and the lethality of experimental animal disease mice after drug administration．Three different doses of heroin (5. 0，10. 0，20. 0 mg / kg) were selected to induce heroin addiction，and the most appropriate heroin concentration was selected by the results on the rating scale. Results: In the CPP training paradigm，CPP was observed in all heroin groups (P＜0. 05，P＜0. 001，P＜0. 05) ．In the CPA training paradigm，the CPA induction rate was highest in the 10. 0 mg / kg heroin group compared to the control group (P ＜0. 01 ) ．In the behavioral sensitization training paradigm ，all heroin groups caused behavioral sensitization changes (P＜0. 001) ; but the 5. 0 and 10. 0 mg / kg heroin groups did not cause animal mortality．Overall，the 10. 0 mg / kg heroin group had the highest dose score on the rating scale．It could be used as a concentration to establish a stable experimental animal model of heroin addiction． Conclusion The study was effective in establishing a heroin addiction model in mice，and it was suitable for modeling drug concentration screening，with high animal survival rate and simple and practical．The combined learning mechanism can effectively shorten the model establishment period.

Based on 248 core biomedical journals indexed in the General Contents of Chinese Core Journals (2011 edition) released by Peking University,we established a Chinese Medicine Sciences Citation Index (CMSCI) database; in addition, based on the Chinese Library Classification (4(th) edition), we identified 13 259 articles concerning Chinese medicine interdisciplinary research. The knowledge mapping was performed for keywords co-occurence, total cites of articles, and total cites of authors using the CiteSpace3 software, with an attempt to reveal the research priorities,knowledge sources, and highly influential authors
Asian Continental Ancestry Group ; Databases, Factual ; Humans ; Medicine, Chinese Traditional ; Software

OBJECTIVETo explore the relationship between gene polymorphism of GABAA receptors and childhood autism by detecting rs140682, rs2081648 and rs140679 site of single nucleotide polymorphism (SNP) in GABAA receptors gene.

METHODSA total of 94 children with autism and 124 normal children were enrolled in a hospital from November 2010 to May 2011. Childhood autism rating scale (CARS) and autism behavior checklist (ABC) were used to evaluate or investigate the case group. After collecting venous blood and extracting the genome DNA, the allele and genotype of SNP rs140682, rs2081648 and rs140679 site in GABAA receptors gene were detected by PCR-RFLP. The allele and genotype of case group and control group were analyzed by χ(2) test, while the score of scales was analyzed by Spearman rank correlation analysis.

RESULTSThe age of the case group was 5.12 ± 0.32, and it was 5.25 ± 0.27 in the control group (P < 0.05). In case group, the frequency of genotype CC, CT and TT of rs140682 site was 44, 41 and 9, while it was 48, 65, and 11 in control group (P > 0.05), respectively. The frequency of genotype AA, AG and GG of rs2081648 site was 8, 58 and 28 in case group, while it was 12, 49 and 63 in control group (P < 0.05), respectively. In case group, the frequency of genotype CC, CT and TT of rs140679 site was 15, 36 and 43, while it was 18, 59 and 47 in control group (P > 0.05), respectively. It was revealed by Spearman rank correlation analysis that of rs2081648 site, there was a positive correlation between genotype AG and sensation factor (S), social intercourse factor (R), and language factor (L) of autism behavior checklist (ABC) (r values were 0.149, 0.165 and 0.155, all P values < 0.05). A negative correlation between genotype GG and S, R, L and self-help factor (V) was proved (r values were -0.140, -0.173, -0.158 and -0.135, all P values < 0.05). There was a positive correlation between allele A and R and L factors (r values were 0.153 and 0.137, all P values < 0.05), while a negative correlation between allele G and R and L factors (r values were -0.153 and -0.137, all P values < 0.05). In case group, 42 children were diagnosed with mild-to-moderate autism, while 52 children were severe autism. There was no statistically significant correlation between allele or genotype of SNP rs140682 and rs140679 site and the degree of autism (P > 0.05). There was a positive correlation between allele A and genotype AG and the degree of autism (r values were 0.147 and 0.616, all P values < 0.05), while a negative correlation between allele G and genotype GG and the degree of autism (r values were -0.159 and -0.616, all P values < 0.05).

CONCLUSIONThe SNP rs2081648 site which located in GABAA receptors gene may be related to autism. No evidence for significant association between rs140682 and rs140679 site and autism was found.

Alleles ; Autistic Disorder ; genetics ; Child ; Child, Preschool ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Polymorphism, Single Nucleotide ; Receptors, GABA-A ; genetics

Objective: To establish a rat model of preeclampsia (PE) in early pregnancy and to observe the changes in phenotype，pregnancy outcome and cognitive ability of offspring． Methods : The pregnant rats were randomly divided into model group and control group．Ultra-low dose lipopolysaccharide (LPS) (0. 5 μg / kg) and an equal volume of normal saline were injected into the tail vein of pregnant rats on the fifth day of pregnancy．The levels of blood pressure ，12-hour urinary protein ，peripheral blood coagulation factors and placental cytokines in the two groups were measured．Furthermore，placental pathology，pregnancy outcomes，and cognitive abilities of offspring were observed. Results: Blood pressure and urinary protein levels of model group were significantly higher than those of control group levels．Compared with the control group，the levels of platelet and antithrombin Ⅲ (AT Ⅲ) in the peripheral blood of pregnant rats in the model group were lower than those in the control group，while D-dimer was higher than that in the control group，the weight of the fetus and placenta in the model group decreased (P ＜0. 001) ，the expression levels of interleukin ( IL) -6，tumor necrosis factor α ( TNF-α) and interferon gamma (INF-γ) in peripheral blood increased，while the expression level of transforming growth factor β1 (TGF-β1) decreased(P＜0. 001) ．The water maze test showed that the latency of the offspring of the model group to the plat- form was longer than that of the control group (P＜0. 05) ，while the frequency of crossing the platform quadrant and the time of staying in the platform quadrant of the model group were lower than those of the control group (P < 0. 05 ) ．HE and PAS staining showed that there were infiltration of inflammatory cells in the basal layer of placenta， obvious decrease of blood vessels in labyrinthine area，slight edema of renal interstitium and degeneration of local renal tubular epithelial cells in the model group，while there were no above pathological changes in placenta and kidney in the control group． Conclusion A single injection of LPS in early pregnancy can successfully induce PE- related symptoms and adverse pregnancy outcomes such as fetal growth restriction and lead to the decline of cogni- tive ability of offspring.

We prepared moxifloxacin (MXF) loaded nanoparticles by nano-precipitation/self-assembly method, then compared the antibacterial activity of MXF and MXF loaded nanoparticles, and investigated the antibacterial mechanism of MXF loaded nanoparticles against Pseudomonas aeruginosa in vitro. The physicochemical properties such as particle size and zeta potential were investigated by laser particle size analyzer. The in vitro release characteristics were investigated by high performance liquid chromatography (HPLC). The effect of nanoparticles on HBE cells viability was investigated by CCK-8 assay. In addition, the in vitro antibacterial activity was investigated by minimum inhibitory concentration (MIC) assay, biofilm formation assays and transmission electron microscope (TEM) observation, then the antibacterial mechanism was initially explored. The particle size measurement showed that the nanoparticles had a size of 332.5 ± 2.7 nm, a polymer dispersion index (PDI) of 0.125 ± 0.053, a zeta potential of -24.3 ± 1.7 mV, and a uniform particle size distribution, drug loading content was (6.02 ± 1.27) %, encapsulation efficiency was (16.69 ± 1.17) %. The TEM results show that the nanoparticles have a spheroidal structure, and the particle size and distribution are consistent with the particle size measurement results. The nanoparticles can be effectively and rapidly released in phosphate buffer saline (PBS), releasing about 70% in 24 h, and releasing 87% in 72 h, and almost completely releasing the MXF at 120 h. At the same time, compared with moxifloxacin free drug, its MIC value is 8 μg·mL^-1, which is 1/2 of MXF solution, and can significantly inhibit the formation of bacterial biofilms. It has well antibacterial activity in vitro and can be targeted to the surface of bacteria to exert its efficacy and improve the antibacterial effect. The moxifloxacin nanoparticles prepared in this study has a uniform particle size distribution, well drug release performance and antibacterial effect, and provides new ideas and strategies for the treatment of bacterial lung infection and the development of new antibacterial nanoformulations.