N,N-dimethyltryptamine,a natural psychedelic,rap-idly improves spatial memory and hippocampal long-term potentiation:a potential rapid-acting therapy for dementia-associated wandering / 中国药理学与毒理学杂志

There is no fast-acting treatment strate-gies against Alzheimer's disease(AD),in particular dementia-related wandering.N,N-dimethyltryptamine(DMT)is a natural psychedelic that may have rapid-onset nootropic effects.In this study,5×FAD transgenic mice which recapitulated amyloid neuropathological features of AD received one single injection of 6 or 12 mg·kg-1 DMT and tested at 0.5,1,and 2 h thereafter in Y-maze for spatial memory.5×FAD transgenic mice exhibited pro-nounced decreases in time spent,number entered,and distance travelled in the novel arm of Y-maze.DMT at 12 mg·kg-1 partially or completely reversed the three behavioral indices at multiple time points,up to 2 h post injection.The rapid-onset behavioral improvement was consistent with pharmacokinetic analysis of DMT,showing approximately 30 min to reach the maximum concentra-tion in the brain tissue.The transgenic mice also displayed dramatically impaired hippocampal long-term potentiation(LTP),an electrophysiological feature of memory forma-tion and consolidation.DMT potently enhanced LTP and restored intracellular calcium activity,expression and phosphorylation of calcium/calmodulin-dependent protein kinase Ⅱ(CaMK Ⅱ)and AMPA-type glutamate receptor 1(GluR1),the two key calcium-activated mediators involved in LTP induction.Adenosine triphosphate(ATP)is purinergic signalling molecules that are involved in LTP induction and maintenance.DMT rapidly increased mito-chondrial ATP dynamics in in vivo and in vitro models.These results suggest that DMT rapidly improve spatial memory and hippocampal LTP by restoring the CaMK Ⅱ-GluR1 signaling pathway and mitochondrial ATP produc-tion.It may be served as a fast-acting nootropic agent for the treatment of AD in particular wandering.

Analysis of genomic information and biological characteristics of a bacteriophage against methicillin-resistant Staphylococcus aureus in patients with median sternal incision infection / 中华烧伤杂志

Objective: To isolate and purify a bacteriophage against methicillin-resistant Staphylococcus aureus (MRSA), and to analyze its genomic information and biological characteristics. Methods: The experimental research methods were adopted. MRSA (hereinafter referred to as host bacteria) solution was collected from the wound of a 63-year-old female patient with the median sternum incision infection admitted to the Second Affiliated Hospital of Army Medical University (the Third Military Medical University). The bacteriophage, named bacteriophage SAP23 was isolated and purified from the sewage of the Hospital by sewage co-culture method and double-layer agar plate method, and the plaque morphology was observed. The morphology of bacteriophage SAP23 was observed by transmission electron microscope after phosphotungstic acid negative staining. The whole genome of bacteriophage SAP23 was sequenced with NovaSeq PE15 platform after its DNA was prepared by sodium dodecyl sulfonate/protease cleavage scheme, and genomic analysis including sequence assembly, annotation, and phylogenetic tree were completed. The bacteriophage SAP23 solution was co-incubated with the host bacterial solution for 4 h at the multiplicity of infection (MOI) of 10.000 0, 1.000 0, 0.100 0, 0.010 0, 0.001 0, and 0.000 1, respectively, and then the bacteriophage titer was measured by the drip plate method to select the optimal MOI, with here and the following sample numbers of 3. The bacteriophage SAP23 solution was co-incubated with the host bacterial solution at the optimal MOI for 5, 10, and 15 min, respectively, and the bacteriophage titer was measured by the same method as mentioned above to select the optimal adsorption time. After the bacteriophage SAP23 solution was co-incubated with the host bacterial solution at the optimal MOI for the optimal adsorption time, the bacteriophage titers were measured by the same method as mentioned above at 0 (immediately), 5, 10, 15, 20, 30, 40, 50, 60, 80, 100, and 120 min after culture, respectively, and a one-step growth curve was drawn. The bacteriophage SAP23 solution was incubated at 4, 37, 50, 60, 70, and 80 ℃ and pH 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 for 1 h, respectively, to determine its stability. A total of 41 MRSA strains stored in the Department of Microbiology of Army Medical University (the Third Military Medical University) were used to determine the host spectrum of bacteriophage SAP23. Results: The bacteriophage SAP23 could form a transparent plaque on the host bacteria double-layer agar plate. The bacteriophage SAP23 has a polyhedral head with (88±4) nm in diameter and a tail with (279±21) nm in length and (22.6±2.6) nm in width. The bacteriophage SAP23 has a linear, double-stranded DNA with a full length of 151 618 bp and 11 681 bp long terminal repeats sequence in the sequence ends. There were 220 open reading frames predicted and the bacteriophage could encode 4 transfer RNAs, while no resistance genes or virulence factors were found. The annotation function of bacteriophage SAP23 genes could be divided into 5 groups. The GenBank accession number was MZ427930. According to the genomic collinearity analysis, there were 5 local collinear blocks in the whole genome between the bacteriophage SAP23 and the chosen 6 Staphylococcus bacteriophages, while within or outside the local collinear region, there were still some differences. The bacteriophage SAP23 belonged to the Herelleviridae family, Twortvirinae subfamily, and Kayvirus genus. The optimal MOI of bacteriophage SAP23 was 0.010 0, and the optimal adsorption time was 10 min. The bacteriophage SAP23 had a latent period of 20 min, and a growth phase of 80 min. The bacteriophage SAP23 was able to remain stable at the temperature between 4 and 37 ℃ and at the pH values between 4 and 9. The bacteriophage SAP23 could lyse 3 of the 41 tested MRSA strains. Conclusions: The bacteriophage SAP23 is a member of the Herelleviridae family, Twortvirinae subfamily, and Kayvirus genus. The bacteriophage SAP23 has a good tolerance for temperature and acid-base and a short latent period, and can lyse MRSA effectively. The bacteriophage SAP23 is a new type of potent narrow-spectrum bacteriophage without virulence factors and resistance genes.

Pharmacokinetics mechanism of ABC efflux proteins-mediated seven features of compatibility / 中国中药杂志

ABC efflux proteins are a kind of transporters mediating diversified endogenous and exogenous efflux protein substrates across the plasma membrane by depending on the chemical energy released by ATP hydrolysis. As a vitally important functional membrane, it is widely found in various tissues and organs. The drug changes the expressions and/or functions of the transport proteins, which will affect the disposal process of substrate drugs corresponding to transporters , and finally lead to the pharmacokinetic interactions. The efflux proteins take part in the absorption, distribution, metabolism and excretion of drugs, and mainly consist of P-glycoprotein(P-gp), multidrug resistance associated protein(MRP) and breast cancer resistance protein(BCRP). The induction effect or inhibition effect of drugs on efflux protein plays a greatly significant role in the drug interaction produced by the compatibility of traditional Chinese medicine, which may be one of the important mechanisms of the theory of seven features of compatibility. In this article, the effects of seven features of compatibility on the ABC efflux transporters were reviewed, in order to reveal the roles of efflux protein in the herb-pairs compatibility, and provide new ideas for the mechanism and rationality of herb compatibility.

Endothelial nitric oxide synthase gene polymorphisms associated with susceptibility to high altitude pulmonary edema in Chinese railway construction workers at Qinghai-Tibet over 4 500 meters above sea level / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To examine whether the polymorphisms of endothelial nitric oxide synthase (eNOS) gene are associated with the susceptibility to high altitude pulmonary edema (HAPE) in Chinese railway construction workers at Qinghai-Tibet where the altitude is over 4 500 m above sea level.</p><p><b>METHODS</b>A case-control study was conducted including 149 HAPE patients in the construction workers and 160 healthy controls randomly recruited from their co-workers, matching the patients in ethnicity, age, sex, lifestyle, and working conditions. Three polymorphisms of eNOS gene, T-786C in promoter, 894G/T in exon 7, and 27bp variable number tandem repeat (VNTR) in intron 4, were genotyped using polymerase chain reaction (PCR) and confirmed with DNA sequencing.</p><p><b>RESULTS</b>The frequencies of 894T allele and heterozygous G/T of the 894G/T variant were significantly higher in HAPE patients group than in the control group (P=0.0028 and P=0.0047, respectively). However, the frequencies of the T-786C in promoter and the 27bp VNTR in intron 4 were not significantly different between the two groups. Haplotypic analysis revealed that the frequencies of two haplotypes (H3,T-T-b, b indicates 5 repeats of 27 bp VNTR; H6, C-G-a, a indicates 4 repeats of 27 bp VNTR) were significantly higher in HAPE patients (both Pü0.0001). On the contrary, the frequencies of H1 (T-G-b) and H2 (T-G-a) were lower in HAPE patients than in healthy controls (both Pü0.001).</p><p><b>CONCLUSIONS</b>Two haplotypes (T-T-b and C-G-a) may be strongly associated with susceptibility to HAPE. Compared with the individual alleles of eNOS gene, the interaction of multiple genetic markers within a haplotype may be a major determinant for the susceptibility to HAPE.</p>

Effect of siRNA targeted against survivin on the malignant behaviors of human hepatoma cells / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study survivin expression in human hepatoma cells and the effects of survivin siRNA on the malignant phenotypes of human hepatocellular cell line HCCLM6.</p><p><b>METHODS</b>Four hepatocellular carcinoma (HCC) cell lines were used. Semi-quantitative RT-PCR and Western blot were used to measure and compare their survivin expressions. The siRNA expression vector pshRNA-survivin targeting the mRNA of survivin and vector pGPU6/GFP/Neo-NC (as a control) were constructed, and then transfected into HCCLM6 cells. FQ-PCR was used to quantify the mRNA levels of survivin. The malignant phenotypes of transfected HCCLM6 cells, including invasive activities and adhesive capabilities, were analyzed.</p><p><b>RESULTS</b>Survivin expression gradually increased with the increase of the invasion and metastasis behaviors of the four HCC cell lines (P<0.05). The expression of survivin was highest in cell line HCCLM6. Survivin mRNA level was decreased by 93.500%+/-3.117% after the pshRNA-survivin transfection. The cell adhesion rates significantly decreased in the cells transfected with pshRNA-survivin (cell adhesion rates were 11.403%+/-1.256% vs 32.545%+/-1.367%, t=20.732, P<0.01). The migrating number of HCCLM6 cells (13.5+/-0.9) transfected with pshRNA-survivin was also significantly decreased (t=14.5, P<0.01) as compared with the control group (32.6+/-1.4).</p><p><b>CONCLUSION</b>The expression of survivin in HCC might have a close relationship to their invasion and metastasis properties. Sequence-specific shRNA can significantly reduce the survivin expression in the HCCLM6 cell line. Suppression of survivin expression in HCCLM6 cells transfected with pshRNA-survivin can reduce their invasive and adhesive capabilities.</p>

Relationship between epithelial-mesenchymal transition and lung metastasis in hepatocellular carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the relationship between epithelial mesenchymal transition (EMT) and lung metastasis in hepatocellular carcinoma.</p><p><b>METHODS</b>There were 100 patients who underwent surgical resection of hepatocellular carcinoma between January 2000 and March 2004. They were classified with non-distance metastasis and lung metastasis depend on the close following up till March 2007. Their hepatocellular carcinoma specimens were retrospectively examined for EMT markers (E-cadherin, Vimentin, Fibronectin) with immunochemistry staining in tissue microarray. Univariate and multivariate analysis were used for study the relationship between EMT and lung metastasis.</p><p><b>RESULTS</b>Univariate analysis showed that down regulation of E-cadherin, overexpression of fibronectin, cytosolic expression of vimentin, AFP >or= 400 ng/ml, tumor size more than 10 cm, portal vein involvement, poorly differentiated of tumor had close correlation with lung metastasis. Multivariate analysis indicated that overexpression of fibronectin was independent factor for lung metastasis apart from tumor size more than 10 cm, portal vein involvement and poorly differentiated of tumor.</p><p><b>CONCLUSION</b>The results proposed that EMT has close relation with lung metastasis in hepatocellular carcinoma.</p>

Evaluation of Left Ventricular Rotation and Twist Using Speckle Tracking Imaging in Patients with Atrial Septal Defect / 华中科技大学学报（医学）（英德文版）

Speckle tracking imaging (STI) was employed to investigate the effect of right ventricular (RV) volume and pressure overload on left ventricular (LV) rotation and twist in 35 patients with atrial septal defect (ASD), 18 of which with pulmonary hypertension, and 21 healthy subjects serving as controls. The peak rotations of 6 segments at the basal and apical short-axises and the average peak rotation and interval time of the 6 segments in the opposite direction during early systolic phase were measured respectively. LV twist versus time profile was drawn and the peak twist and time to peak twist were calculated. LV ejection fraction (EF) was measured by Biplane Simpson. Compared to ASD patients without pulmonary hypertension and healthy subjects, the peak rotations of posterior, inferior and postsept walls at the basal level were lower (P<0.05), and the average counterclockwise peak rotation of 6 segments at the basal level during early systolic phase was higher (P<0.05), and the average interval time was delayed (P<0.05). LV peak twist was also lower (P<0.05), and had a significant negative correlation with pulmonary arterial systolic pressure (r=-0.57, P=0.001). No significant differences were found in LVEF among the three groups. It was suggested that although RV volume overload due to ASD has no significant effects on LV rotation and twist, LV peak twist is lower in ASD patients with pulmonary hypertension. Thus LV twist may serve as a new indicator of the presence of pulmonary hypertension in ASD patients.

Assessment of Right Ventricular Free Wall Longitudinal Myocardial Deformation Using Speckle Tracking Imaging in Normal Subjects / 华中科技大学学报（医学）（英德文版）

To assess right ventricular free wall longitudinal myocardium deformation and examine the changes with normal age by speckle tracking imaging (STI), myocardial systolic peak strain (ε), systolic peak strain rate (SRs), early diastolic peak strain rate (Sre), late diastolic peak strain rate (Sra), the ratio of Sre/Sra were measured in the basal, middle and apical segments of right ventricular free wall in 75 healthy volunteers (age range: 21-71 y) by STI from the apical 4-chamber view. RV longitudinal strain and strain rate were highest in the basal segment of the free wall. Older subjects had lower early diastolic strain rate (Sre) than younger subjects, but they had higher late diastolic strain rate (Sra). A negative correlation between age and the ratio of Sre/Sra was found in all RV free wall segments (r=-0.466 - -0.614, P<0.01). It is concluded that RV diastolic strain rate changes with age and STI can be used for the study of RV myocardial deformation.

Different expressions of chemokine receptors in human hepatocellular carcinoma cell lines with different metastatic potentials / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To compare different expression profiles of all known chemokine receptors in human hepatocellular carcinoma (HCC) cell lines with different metastasis potentials.</p><p><b>METHODS</b>Eighteen pairs of chemokine receptor primers were designed using Premier software. Expression profiles of the 18 chemokine receptors on four HCC cell lines of lower to higher potentials of metastasis (SMMC-7721, MHCC97-L, MHCC97-H and HCCLM6) were analyzed by RT-PCR. Expression of CXCR4 was detected by RT-PCR.</p><p><b>RESULTS</b>Expression profiles of chemokine receptors on four HCC cell lines with different metastatic potentials had significant differences (P < 0.01), in which CCR10, CXCR4 and CXCR6 expressions decreased gradually as the metastatic potential of the cell lines increased. The expressions of CCR3, CCR4, CCR10, CCR12 and XCR1 on HCCLM6 were significantly reduced compared with SMMC-7721 (P < 0.01), whereas the expressions of CXCR1 (P = 0.006) and CXCR5 (P = 0.003) exceeded that of SMMC-7721. Except for CXCR2, CXCR6 and XCR1, most of chemokine receptors on MHCC97-H were expressed differently compared with MHCC97-L (P < 0.05), in which expressions of CCR1 (P = 0.002), CCR2 (P = 0.004) and CCR5 (P = 0.046) exceeded MHCC97-L. CXCR4 was detected only on the positive controls and SMMC-7721 when the template of total RNA was reduced one-half in RT-PCR.</p><p><b>CONCLUSION</b>Chemokine receptors are expressed very differently at mRNA level on HCC cell lines with different metastatic potentials. The different profiles of chemokine receptors in tumor microenvironment and the function of CXCR4 in HCC should be further studied. Our findings have important implications in understanding the relationship between chemokine receptors and the metastatic potential of HCC.</p>

Osteopontin promotes the malignant phenotypes of human hepatocellular carcinoma cell line SMMC-7721 / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the effects of osteopontin (OPN) on the phenotypes of human hepatocellular carcinoma cell line SMMC-7721.</p><p><b>METHODS</b>Human hepatocellular carcinoma SMMC-7721 cells were transfected with plasmid pcDNA 3.1(-)/OPN and cells transfected with a mock plasmid served as controls. OPN expression was verified by RT-PCR and Western blot, and concentrations of OPN, MMP-2, MMP-9 and uPA were measured by ELISA. A series of functional assays in vitro were used to monitor the changes of SMMC-7721 malignant phenotypes.</p><p><b>RESULTS</b>OPN expression of SMMC-7721 cells was elevated after transfection. Concentrations of OPN, MMP-2 and uPA in the medium of SMMC-7721 cells after transfection were higher than those of the controls [(3.02+/-0.12) ng/ml vs (1.43+/-0.07) ng/ml, (43.04+/-3.06) ng/ml vs (22.15+/-4.34) ng/ml, and (4.78+/-0.70) ng/ml vs (1.61+/-0.34) ng/ml respectively, P less than 0.01], but MMP-9 concentration did not increase [(7.82+/-2.25) ng/ml vs (7.70+/-1.92) ng/ml]. Functional assays in vitro indicated that SMMC-7721 cells after transfection showed higher adhesive, migrant and invasive capabilities than those of the controls (cell adhesion rates were 75.33%+/-10.59% vs 57.34%+/-2.52%; number of outer surface cells in migrant assay was 14.33+/-2.51 vs 6.34+/-1.53; cell number in the invasive assay was 8.23+/-1.53 vs 4.12+/-1.29 respectively, P less than 0.05).</p><p><b>CONCLUSION</b>OPN might enhance the expression of MMP-2 and uPA to promote malignant phenotypes of SMMC-7721 cells.</p>

A preliminary investigation of nuclear factor kappa B in peripheral blood lymphocytes of patients with hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the activity of nuclear factor kappa B (NF-kappaB) in peripheral blood lymphocytes (PBL) of patients with hepatitis B.</p><p><b>METHODS</b>The PBL of patients with different types of hepatitis B and healthy individuals were isolated and then the nuclear extract was prepared. Assessment of NF-kappaB DNA binding activity was performed by electrophoretic mobility shift assay (EMSA) using digoxin labeled double-stranded oligonucleotide containing kappa B consensus sequence.</p><p><b>RESULTS</b>Densitometric scanning of the EMSA bands showed that the mean optical densities (A) from the groups of normal control, acute hepatitis B, chronic hepatitis B and chronic severe hepatitis B were 20.18+/-2.16, 27.75+/-4.11, 13.90+/-3.20 and 8.02+/-2.65 respectively. Analysis of variance showed the F value was 26.112 and the difference among the groups was significant. The difference between two groups with Dunnett T3 analysis showed there are statistically difference between the groups of the normal group and the chronic severe hepatitis B group, the acute hepatitis B group and the chronic hepatitis B group, and the acute hepatitis B group and the chronic severe hepatitis B.</p><p><b>CONCLUSION</b>The activity of NF-kappaB in PBL of patients with hepatitis B is related with the different outcomes of hepatitis B virus (HBV) infection. Decreased activity of NF-kappaB may be an important cause for the dysfunction of PBL in chronic HBV-infected patients.</p>

A study of high altitude environment affecting on worker's health during the constructing Qinghai-Xizang railway / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study high altitude environment affecting on worker's health</p><p><b>METHODS</b>Using the cohort study, the altitude reaction was investigated and the WBC, RBC, Hb and oxygenation indexes were measured on workers in several periods, namely, acclimatization period, initially arrived high altitude and resident 90 days.</p><p><b>RESULTS</b>The 83.3% of men had altitude reactions with different kinds at initially arrived high altitude. The headache was the most. The rate of abnormal blood pressure increased with altitude and resident time (P < 0.01). The rate of 90 day's group was 41.7%. The rise of diastole pressure was obvious (P < 0.01). As the beginning of arrived highland, the increase of WBC, RBC were significant (P < 0.01). The increase of Hb appeared only in 90 day's group. The level of malondialdehyde (MDA) obviously increased during acclimatization period and increased with altitude and resident time (P < 0.01). The activity of catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) increased significantly in 90 day's group [(222.36 +/- 36.52) x 10(3) U/L, (158.49 +/- 14.42) U/L, (45.74 +/- 8.31) NU/ml respectively] (P < 0.01).</p><p><b>CONCLUSION</b>The high altitude environment may result in the abnormal blood pressure, the rise of diastolic pressure was important. It lead to the increase of WBC, RBC, Hb. It initiated activity of oxygenation reaction. The symptoms of headache, dizziness, loss of appetite and insomnia appeared as working in high altitude environment.</p>

Peyronie's disease with venogenic impotence: A report of 3 cases / 대한비뇨기과학회지

We report our experience with unusual cases of Peyronie`s disease concurrent with venogenic impotence. Three patients have suffered from distressful sexual life including painful erection. penile curvature and poor penile tumescence. Following multidisciplinary work-ups for impotence in those patients. it proved be that they had venogenic impotence as well as Peyronie`s disease. Since intrapenile triamcinolone injection therapy did not improve their symptoms. a single-staged, surgical procedure was performed to resolve problems with Peyronie`s disease and venogenic impotence at a time in each patient It was proceeded with ligation of penile vein. excision of the fibrous plaque and replacement with dermal graft respectively. In a patient. additional Nesbit`s procedure was required to correct sustained penile curvature. Postoperative follow-up for 2 years shows that all the patients have remained Free from serious problem in their sexual life. We believe that above single-staged operation is worth application to the case of Peyronie`s disease concurrent with venogenic impotence.