Effect of acid sphingomyelinase on nonalcoholic fatty liver disease via PPARα- PGC-1α pathway / 中国药理学通报

Aim To investigate the effects of acid sphingomyelinase(ASMase)on high-fat induced nonalcoholic fatty liver disease in mice and its regulation of PPARα- PGC-1α pathway. Methods ASMase knockout mice based on C57BL/6 background were constructed. Closed group heterozygotes were obtained through hybridized with wild-type mice(ASMase+/-),together with the littermate WT mice were prepared for NAFLD model in this study. The experiment was divided into four groups:WT+Chow:the WT mice were fed with normal diet for 12 weeks; WT+HFD:the WT mice were fed with high-fat diet for 12 weeks; ASMase+/-+Chow:the ASMase+/- mice were fed with normal diet for 12 weeks; ASMase+/- +HFD:the ASMase+/- mice were fed with high fat diet for 12 weeks. Biochemical method was used to detect serum TC,TG and liver TC,TG contents and liver function such as ALT and AST. Oil red staining,HE staining,Masson staining and Sirius red staining were performed to detect liver lipid accumulation,hepatocyte morphology and liver fibrosis. AmplexTM red sphingomyelinase kit was applied to detect ASMase activity. Western blot was performed to detect protein expressions of ASMase,PPARα,PGC-1α and CPT1. Results WT+HFD group displayed hypercholesterolemia and liver dysfunction. Levels of liver triglyceride(TG)were significantly higher than those in WT+Chow group(P<0.05 or P<0.01). Meanwhile,the hepatocytes showed marked steatosis,balloon-like changes,and fibrosis. Protein expression and activity of ASMase in liver increased significantly(P<0.01 or P<0.001),whereas CPT1,PPARα and PGC-1α expressions were not statistically significant compared with matched control group. Heterozygously ASMase-deficient mice reduced the elevated liver TG induced by HFD,as well as improving balloon-like changes and liver fibrosis. Furthermore,the expressions of PPARα,PGC-1α and CPT1 were up-regulated in ASMase+/- +HFD mice compared with WT+Chow group.Conclusions ASMase promotes hepatic steatosis and fibrosis,which may be related to its inhibition of PPARα-PGC-1α pathway.

Inhibitory effect of astragalus membranaceus injection on apoptosis and autophagy induced by enterovirus 71 / 中国生物制品学杂志

@#Objective To investigate the effect of astragalus membranaceus（AM）injection on apoptosis and autophagy of human gastric epithelial cell line（GES⁃1）induced by enterovirus 71（EV71）. Methods GES⁃1 cells were cultured in vitro and divided into infected group（EV71 infected at a MOI of 3 and control group（no virus infected）. The morpho⁃logical changes of EV71 infected cells were observed by inverted microscope. The level of VP1 in GES⁃1 cells infected with EV71 was detected by Western blot；CCK⁃8 assay was used to detect the viability of GES⁃1 cells infected with EV71；Nuclear staining with DAPI was used to observe the morphological changes of nuclear apoptosis infected with EV71. GES⁃1 cells were divided into control group（without virus infection），infection group and AM intervention group with final concentration of 1，2. 5，5 and 10 μg／mL，respectively. Western blot was used to detect the effect of AM intervention on the expression of apoptosis⁃related proteins Caspase⁃3，PARP and autophagy⁃related proteins LC3 and P62 in GES⁃1 cells infected withEV71. CCK⁃8 method was used to detect the effect of AM intervention on the viability of GES⁃1 cells infected with EV71. Results GES⁃1 cells were round，shrunken with nuclear pyknosis and uneven size；VP1 level increased（t = 41. 56，P < 0. 01），cell viability decreased（t = 19. 07，P < 0. 01），Caspase⁃3 and PARP proteins were cut off（t = 35. 29 and 3. 648， P < 0. 01 and 0. 021 8，respectively），LC3Ⅱ／LC3Ⅰ ratio increased（t = 10. 16，P = 0. 000 5）and P62 protein was degraded（t = 68. 68，P < 0. 01）；AM inhibited the degradation of Caspase⁃3，PARP and P62 proteins induced by EV71 （t = 52. 66，59. 60 and 40. 22，respectively，each P < 0. 01）and increased the ratio of LC3Ⅱ／LC3Ⅰ（t = 5. 521，P = 0. 005 3），andreducedtheinhibitoryeffectofEV71ontheviabilityofGES⁃1cells（t =4. 420，P =0. 0115）. Conclusion EV71 infection induced apoptosis of GES⁃ 1 cells and AM intervention inhibited EV71 induced apoptosis by inhibiting EV71 induced autophagy.

The Effect of hnRNPK/Beclin1 Signaling on the Drug Resistance of Imatinib in Ph+ Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of hnRNPK/Beclin1 signaling on the drug resistance of imatinib in Ph+ leukemia.@*METHODS@#Expression level of hnRNPK was verified in the imatinib resistant and sensitive Ph+ leukemia cell lines by using Western blot. hnRNPK expression was down-regulated by using RNAi. Expression level of LC3I/II and Beclin1 were detected by Western blot and the sensitivity of imatinib was analyzed by CCK-8 assay before and after modulation of hnRNPK expression.@*RESULTS@#hnRNPK showed overexpressed in imatinib resistant leukemia cell line. After the expression level of hnRNPK was down-regulated by RNAi, the sensitivity of drug resistance lines to imatinib restored, while the expression level of LC3I/II and Beclin1 were consistant with the modulation of hnRNPK expression.@*CONCLUSION@#hnRNP K/Beclin1 signaling may be involved in the development of imatinib resistance in Ph+ leukemia through the regulation of autophagy.

Experimental investigation of early assessment of corpora cavernosa fibrosis with two-dimensional shear wave elastography / 亚洲男科学杂志(英文版)

This study explored the usefulness of two-dimensional shear wave elastography (2D-SWE) in the early assessment of corpora cavernosa fibrosis (CCF). New Zealand male rabbits were randomly assigned to an experimental group or a control group. Recombinant human transforming growth factor beta 1 (TGF-β1) was injected into the dorsal penis tissue of rabbits in the experimental group. Conventional ultrasound and 2D-SWE examinations were performed before and 20 days after injection. Penile histological analysis was performed by hematoxylin-eosin staining, sirius red staining, and immunohistochemistry. Measurement of 2D-SWE examination results was performed using shear wave elastography quantitative measurement (SWQ). Histological analysis outcomes were the proportion of smooth muscle cells (SMCs), collagen fibers (CFs), collagen type I (Col I), and collagen type III (Col III), as well as the SMCs/CFs ratio, measured by sirius red staining. Other histological analysis outcomes were the positive area proportion (PAP) of TGF-β1 (PAPT), fibronectin (PAPF), and Col III (PAPC), measured by immunohistochemistry. After recombinant human TGF-β1 injection, SWQ was higher in the experimental group than that in the control group (P < 0.001); however, there were no differences in conventional ultrasound results. There were significant differences in histological outcomes between the two groups (all P < 0.05). These results indicated that 2D-SWE was superior for identifying early histological changes in CCF.

Subchronic Oral Toxicity Evaluation of Sodium Dehydroacetate: A 90-day Repeated Dose Study in Rats / 生物医学与环境科学（英文）

Objective@#The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate (DHA-Na) and to determine the point of departure (POD), which is a critical factor in the establishment of an acceptable dietary intake.@*Methods@#DHA-Na was administered once daily by gavage to Sprague-Dawley rats at dose levels of 0.0, 31.0, 62.0, and 124.0 mg/kg BW per day for 90 days, followed by a recovery period of 4 weeks in the control and 124.0 mg/kg BW per day groups. The outcome parameters were mortality, clinical observations, body weights, food consumption, hematology and clinical biochemistry, endocrine hormone levels, and ophthalmic, urinary, and histopathologic indicators. The benchmark dose (BMD) approach was applied to estimate the POD.@*Results@#Significant decreases were found in the 62.0 and 124.0 mg/kg BW groups in terms of the body weight and food utilization rate, whereas a significant increase was found in the thyroid stimulating hormone levels of the 124.0 mg/kg BW group. Importantly, the 95% lower confidence limit on the BMD of 51.7 mg/kg BW was modeled for a reduction in body weight.@*Conclusion@#The repeated-dose study indicated the slight systemic toxicity of DHA-Na at certain levels (62.0 and 124.0 mg/kg BW) after a 90-day oral exposure.

Relationship between Small-world Network and Cognitive Impairment for Patients with White Matter Lesions Based On Diffusion Tensor Imaging / 中国康复理论与实践

Objective:To explore the relationship between small-worldness of brain network and cognitive impairment in patients with white matter lesions (WMLs) based on diffusion tensor imaging (DTI). Methods:From January, 2016 to December, 2017, 46 WMLs patients and 36 controls matched genders, ages and education levels from Beijing Tiantan Hospital were screened with DTI. The patients were divided into vascular cognitive impairment non-dementia (VCIND) and vascular dementia (VaD) groups according to the results of cognitive assessments. The brain structure network was created based on DTI data, and the topological properties of the whole-brain small-world network were calculated, and the correlation between the small-worldness and the severity of cognitive impairment was analyzed. Results:The global efficiency, local efficiency, shortest path length and clustering coefficient were different between the patients and the controls (F > 3.252, P < 0.05), as well as the properties of the small-world network, λ, γ and σ (F > 7.378, P < 0.01). The λ, γ and σ were correlated with the total score of Montreal Cognitive Assessment (|r| > 0.402, P < 0.05). Conclusion:The brain structure network is small-world network for patients with WMLs, and the decrease of small-world properties may relate to the cognitive impairment.

Trans-base and trans-vault low-velocity penetrating brain injury: A retrospective comparative study of characteristics, treatment, and outcomes / 中华创伤杂志(英文版)

PURPOSE@#Low-velocity penetrating brain injury (LVPBI) caused by foreign bodies can pose life-threatening emergencies. Their complexity and lack of validated classification data have prevented standardization of clinical management. We aimed to compare the trans-base and trans-vault phenotypes of LVPBI to help provide guidance for clinical decision-making of such injury type.@*METHODS@#A retrospective study on LVPBI patients managed at our institution from November 2013 to March 2020 was conducted. We included LVPBI patients admitted for the first time for surgery, and excluded those with multiple injuries, gunshot wounds, pregnancy, severe blunt head trauma, etc. Patients were categorized into trans-base and trans-vault LVPBI groups based on the penetration pathway. Discharged patients were followed up by outpatient visit or telephone. The data were entered into the Electronic Medical Record system by clinicians, and subsequently derived by researchers. The demography and injury characteristics, treatment protocols, complications, and outcomes were analyzed and compared between the two groups. A t-test was used for analysis of normally distributed data, and a Mann-Whitney U test for non-parametric data. A generalized linear model was further established to determine whether the factors length of stay and performance scale score were influenced by each factor.@*RESULTS@#A total of 27 LVPBI patients were included in this analysis, comprised of 13 (48.1%) trans-base cases and 14 (51.9%) trans-vault cases. Statistical analyses suggested that trans-base LVPBI was correlated with deeper wounds; while the trans-vault phenotype was correlated with injury by metal foreign bodies. There was no difference in Glasgow Coma Scale score and the risk of intracranial hemorrhage between the two groups. Surgical approaches in the trans-base LVPBI group included subfrontal (n = 5, 38.5%), subtemporal (n = 5, 38.5%), lateral fissure (n = 2, 15.4%), and distal lateral (n = 1, 7.7%). All patients in the trans-vault group underwent a brain convex approach using the foreign body as reference (n = 14, 100%). Moreover, the two groups differed in application prerequisites for intracranial pressure monitoring and vessel-related treatment. Trans-base LVPBI was associated with higher rates of cranial nerve and major vessel injuries; in contrast, trans-vault LVPBI was associated with lower functional outcome scores.@*CONCLUSION@#Our findings suggest that trans-base and trans-vault LVPBIs differ in terms of characteristics, treatment, and outcomes. Further understanding of these differences may help guide clinical decisions and contribute to a better management of LVPBIs.

Effect of surgical treatment on prognosis in preterm infants with obstructive hydrocephalus / 中国当代儿科杂志

OBJECTIVES@#To study the effect of surgical treatment on prognosis in preterm infants with obstructive hydrocephalus.@*METHODS@#A retrospective analysis was performed on the medical data of 49 preterm infants with obstructive hydrocephalus. According to the treatment regimen, they were divided into two groups: surgical treatment (@*RESULTS@#Among the 49 preterm infants with obstructive hydrocephalus, severe intracranial hemorrhage (37 cases; 76%) and central nervous system infection (10 cases, 20%) were the main causes of hydrocephalus. There was no significant difference in the composition of etiology between the two groups (@*CONCLUSIONS@#Surgical treatment can improve the survival rate of preterm infants with obstructive hydrocephalus and the prognosis of preterm infants with severe intracranial hemorrhage.

Nivolumab-associated pulmonary toxicities： a retrospective study based on FARES database from 2016 to 2019 / 上海预防医学

Objective:Nivolumab is one of the most common programmed death 1 （PD-1） inhibitors used as an immune checkpoint inhibitor （ICI）. It brings significant therapeutic effects but often accompanied by serious drug toxicity. The pulmonary toxicities of nivolumab are not clear. This study aims to systematically explore the nivolumab-associated pulmonary toxicities and provide reference for clinical treatment. Methods:Data were extracted from US Food and Drug Administration （FDA） Adverse Event Reporting System （FAERS） database from January 1， 2016 to September 30， 2019. Two types of disproportionality analysis， information component （IC） and reporting odds ratio （ROR）， were applied in nivolumab-associated pulmonary adverse events （AEs） signal detection. Results:A total of 28 489 309 records were extracted from FAERS database and 8 181 records were associated with nivolumab. Analysis was conducted in 179 AEs and 86 signals were detected. Notably， potent signals were detected in radiation pneumonitis （IC025： 3.99， ROR025： 17.25）， pneumonitis （IC025： 3.34， ROR025： 10.64） and bronchial fistula （IC025： 2.94， ROR025： 8.78）. Nivolumab-associated pulmonary toxicities were more frequently reported in dyspnoea （IC025： 0.50， ROR025： 1.44）， pneumonia （IC025： 0.08， ROR025： 1.07） and pneumonitis （IC025： 3.34， ROR025： 10.64）. Results of IC and ROR methods were similar to each other. Most pulmonary toxicities were observed in patients with non-small cell lung cancer （N=3 711， 32.13%）， malignant melanoma （N=1 658， 14.36%） and renal cell carcinoma （N=731， 6.33%）. Conclusion:Significant pulmonary toxicities were detected in patients treated with nivolumab. Thus， it is highly important for clinicians to be vigilant about nivolumab-associated pulmonary AEs and be prepared to take immediate action for patient safety.

Study on potential molecular mechanism of Mongolian medicine Bawei Sanxiang San in treatment of chronic heart failure based on network pharmacology and molecular docking / 中国中药杂志

To explore the potential molecular mechanism of Mongolian medicine Bawei Sanxiang San in the treatment of chronic heart failure(CHF) through network pharmacology and molecular docking technology. The active ingredients and potential targets of Bawei Sanxiang San were collected by applying TCMSP, BATMAN databases and literature mining. CHF-related genes were collected through TTD, GeneCards and CTD databases. After the potential common targets between Bawei Sanxiang San and CHF were disco-vered, the interaction network diagram of "compound-target-pathway" was constructed using Cytoscape. The intersecting targets were imported into the DAVID database for GO function and KEGG pathway enrichment analysis. Finally, the Autodock_vina software was used to molecularly dock the selected proteins with the active ingredients of Bawei Sanxiang San. The results showed that there were 60 active ingredients in Bawei Sanxiang San that might be used to treat CHF, involving 311 target genes and 7 signaling pathways that directly related to CHF, such as HIF-1 signaling pathway, TNF signaling pathway, adrenergic signaling in cardiomyocytes, aldosterone-regulated sodium reabsorption, calcium signaling pathway, cGMP-PKG signaling pathway, renin secretion. Additionally, molecular docking showed that the bioactive compounds had good binding activity with the protein receptors of key target genes. Bawei Sanxiang San might exert therapeutic effects on CHF by regulating cardiomyocytes, angiogenic and inflammation related targets and pathways in a multi-component, multi-target and multi-pathway manner.

Relationship between depression-like behavior and expression of aquaporin 4 in brain of urea transporter B null mice / 解剖学报

[Abstract] Objective To investigate the ultrastructural changes of hippocampus in urea transporter B (UT-B) null mice and the alterations of distribution and expression level of aquaporin 4 (AQP4) in brain, and to discuss the relationship between AQP4 expression changes and depression-like behaviors in UT-B null mice. Methods Behavior differences of wild-type and UT-B null mice(10 in each group) were detected with sucrose preference and forced swimming test. The ultrastructural changes of hippocampus were observed by transmission electron microscopy (TEM). Immunohistochemistry and Western blotting were performed to detect the distribution and expression level of AQP4 in both genotypes. Results The sucrose preference index of wild-type mice and UT-B null mice were (84. 67 ± 1. 62)% and (65. 67±2. 66)%, respectively (P<0. 001). The immobility time of forced swimming was (209. 1±7. 00) seconds and (128. 6±3. 75) seconds respectively (P<0. 001). The two behavioral test results showed that UT-B null mice exhibited depression-like behavior. TEM results displayed the abnormal neurons with swelling of myelinated and unmyelinated fibers and degenerative changes, and perivascular astrocyte end-feet swelling. Immunohistochemistry results showed AQP4-immunoreactive (IR) cells were significantly reduced in cortex, hippocampus and thalamus. AQP4-IR cells were distributed in the pia matter, ependymal and cerebrovascular, but the perivascular immunostaining decreased. Western blotting analysis showed that the expression level of AQP4 in hippocampus was down-regulated by 27. 1% (P< 0. 05). Conclusion Reduced expression of AQP4 in the cerebral cortex and hippocampus of UT-B null mice might induce depressive behaviors by inference neurogenesis and cerebral metabolism.

Flipped classroom teaching:Practice and evaluation / 上海预防医学

Objective To evaluate the feasibility and effectiveness of flipped classroom teaching in medical research design class with more than 50 undergraduate. Methods Using randomized parallel-control study, two classes were chosen for this study:flipped classroom teaching group (i.e.FC group) and traditional teaching group (i.e.control group).Except for different teaching modes, all the other conditions of these two groups remained the same, including learning materials, network reference materials and teaching equipment. Results The FC group had 52 students and the control group had 69 students.After teaching, the final test score on study design in FC group was 11.53 higher (95%CI:4.75-18.32, t=3.37, P=0.001).However, there was no statistically significant difference between the test scores of other medical statistic teaching units (t=0.223, P=0.824). Conclusion FC teaching can be used in large class (more than 50 students) in medical undergraduate education.For flipped classroom teaching with large number of students, teachers should strengthen the arrangement of students′ self-study before class, organize effective team discussion, and make full use of new technologies to support teaching.

Synthesis and evaluation of a dendritic poly(L-glutamic acid)-graft-polyethylenimine copolymer as an efficient gene delivery vector / 药学学报

The study was designed to synthesize a novel dendritic copolymer composed of polyamidoamine dendrimer G0 as the inner core and poly(L-glutamic acid) grafted low molecular weight polyethylenimine (PGLP) as surrounding arms for gene delivery vector. The molecular structure of PGLP was confirmed by 1H NMR (proton nuclear magnetic resonance spectroscopy). The DNA combination capability of PGLP was examined by gel retardation electrophoresis. The particle sizes and zeta potentials of PGLP/pDNA complexes were determined by dynamic light scattering (DLS). The cytotoxicity of PGLP was evaluated by Cell Counting Kit-8 (CCK-8) and hemolysis assays, which was approved by Research Ethics Committee of the First Affiliated Hospital of Nanchang University. The in vitro transfection efficiency of PGLP was measured by a flow cytometry. The results of physicochemical properties suggested that PGLP could self-assemble with DNA to form complexes with average particle sizes of about 105-200 nm and zeta potentials of about +10 - +28 mV, which could protect DNA from serum degradation. The results of biological properties suggested that PGLP showed more higher transfection efficiencies but lower cytotoxicity than PEI 25K or Lipofectamine 2000 in various cell lines (HEK 293T, HeLa, BEL 7402, RASMC). Importantly, it was found that PGLP/pDNA complexes at w/w = 8 showed more strong serum-resistant capacity than PEI 25K/pDNA complexes. Therefore, PGLP is a promising candidate vector for gene delivery.

Study on intention to quit smoking and influencing factors among current smokers aged 15 to 69 years in Gansu Province / 中华疾病控制杂志

Objective To understand the intention to quit smoking and its influencing factors among current smokers in Gansu Province, so as to provide scientific basis for tobacco control. Methods A multi-stage sampling method was used to extract current smokers aged 15-69 years, and a face-to-face survey was conducted using the questionnaire on smoking among residents in China. Intention to quit smoking between current smokers with different characteristics was analyzed. Logistic regression was used to explore influencing factors of intention to quit smoking. Results The intention of current smokers to quit smoking in Gansu Province was 16.4% (95% CI:15.5%-17.3%). Multivariate logistic regression analysis showed that current smokers who were in rural areas (OR=1.199, 95% CI:1.022-1.408, P=0.026); family smoking prohibited (OR=1.767, 95% CI: 1.273-2.454, P=0.001), medical staff discouraged smoking within 12 months (OR=1.599, 95% CI:1.359-1.842, P<0.001), visited smoking clinics (OR=3.089, 95% CI:2.031-4.698, P＜001), higher educational level of junior high school, senior high school and college or above (OR=1.383, 95% CI:1.101-1.736; OR=1.627, 95% CI:1.252-2.116; OR=1.374, 95% CI:1.009-1.873, all P<0.05), tobacco hazards knowledge with higher scores of 1-, 3- and 5-6 (OR=1.248, 95% CI:1.030-1.514; OR=1.574, 95% CI:1.289-1.922; OR=2.288, 95% CI:1.879-2.786, all P<0.05) were more likely to quit smoking; furthermore, smokers aged 20-, 30- years or smoking 20-, 30- years had a lower chance of quit smoking (all P<0.05). Conclusions The intention of current smokers to quit smoking in Gansu province is generally not high. In the future, knowledge of tobacco hazards should be further promoted, medical staff should provide more smoking cessation services during the treatment process, and more smoking cessation clinics should be established.

Dynamics of Proliferation and Differentiation after Transplantation of Hematopoietic Cells in Mouse / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of Listeria monocytogenes infection on hematopoietic stem and progenitor cell (HSPC) composition, cell cycle and cell colony-forming ability in mouse bone marrow.@*METHODS@#The C57BL/6J mice were divided into infected group and control group. The mice in injected group were infected intraperitoneally with 6.7×10 CFU Listeria monocytogenes,while the mice in control group were injecfed with PBS of same volume.The serum levels of IFNγ were detected at different time points. After 24 hours, the HS/PC composition, cell cycle and cell colony-forming ability in bone marrow of mice were measured, and the difference between the control group and the infected group was statistically analyzed.@*RESULTS@#Serum IFNγ levels peaked at 24 hours after infection with Listeria monocytogenes. After 24 h, the proportion of LSK, LSK in S phase, and short-term hematopoietic stem cells (ST-HSC) in the infected group were significantly higher than those in the control group (P＜0.001), long-term hematopoietic stem cells (LT-HSC) and the proportion of LT-HSC in S phase were significantly increased (P＜0.01), and the cell colony-forming ability of bone marrow significantly decreased (P＜0.01). [WTHZ]Conclusion: [WTB1]After infection with Listeria monocytogenes, bone marrow hematopoietic stem cells enter the proliferative state from rest, the cell colony-forming ability decreases, suggesting that Listeria monocytogenes infection can cause hematopoietic stem cell depletion.

Novel noninvasive quantification of penile corpus cavernosum lesions in hyperlipidemia-induced erectile dysfunction in rabbits by two-dimensional shear-wave elastography / 亚洲男科学杂志(英文版)

Structural alterations in fibroelastic components of the penile corpus cavernousum (CC) may impair its compliance, resulting in venous leakage and erectile dysfunction (ED). Our study evaluated the effectiveness of noninvasive two-dimensional shear-wave elastography (2-D SWE) in quantifying penile CC lesions in rabbits with hyperlipidemia-induced ED. A total of 12 New Zealand white rabbits were randomly divided into two groups. Six were fed a high-cholesterol diet containing 2% cholesterol and 8.5% lard for 10 weeks and the other six were fed normal diet as controls. We measured the shear-wave elastic quantitative (SWQ) value of penile CC by 2-D SWE. Erectile function was investigated by intracavernous injection of papaverine, and immunohistochemical (IHC) staining and the western blot analysis to determine the penile CC lesions. After 10 weeks, the SWQ values obtained from penile CC were remarkably higher in the high-cholesterol-fed compared with the control group, and the ΔICP (ICP plateau minus ICP baseline)/MAP (ICP: intracavernous pressure, MAP: mean arterial pressure) was markedly decreased. The IHC staining and western blot revealed extracellular matrix (ECM) accumulation in penile cavernous tissues, and the smooth muscle cell (SMC) phenotypic transition was affected, as indicated by reduced alpha-smooth muscle actin and calponin-1 expression and increased phospho-myosin light chain20 (p-MLC20)/MLC20 and osteopontin expression. Hyperlipidemia resulted in ECM accumulation accompanied with SMC phenotypic transition in penile CC and impaired the erectile function eventually. These might, in turn, lead to variations in the SWQ values. It suggests that 2-D SWE may be a novel, noninvasive and effective approach that distinguishes penile CC lesions secondary to hyperlipidemia from normal.

Role of human liver and intestine esterases in drug design and development / 药学学报

Human carboxylesterase (CES) and arylacetamide deacetylase (AADAC) are important numbers of the serine esterase superfamily. They are involved in hydrolytic procedure of human endogenous cholesteryl esters, as well as drug metabolism, activation and detoxication. They are closely related to the personalized medication of drugs, especially for prodrugs. This review summarizes their structure and distribution, metabolic characteristics and research progress in recent years, which will provide a reference for new drug development and rational drug design.

Advance in Default Mode Network,Salience Network and Central Executive Network about Cognitive Function in Old Persons(review) / 中国康复理论与实践

@#A lot of researches indicate the relationship between cognitive impairment and functional connectivity of default mode network,salience network and central executive network.The changes of networks are various in different cognitive dys-function.It is important to apply resting state functional magnetic resonance in the old adults with cognitive dysfunction.

Subchronic Oral Toxicity of Silica Nanoparticles and Silica Microparticles in Rats / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the subchronic oral toxicity of silica nanoparticles (NPs) and silica microparticles (MPs) in rats and to compare the difference in toxicity between two particle sizes.</p><p><b>METHODS</b>Sprague-Dawley rats were randomly divided into seven groups: the control group; the silica NPs low-, middle-, and high-dose groups; and the silica MPs low-, middle-, and high-dose groups [166.7, 500, and 1,500 mg/(kg•bw•day)]. All rats were gavaged daily for 90 days, and deionized water was administered to the control group. Clinical observations were made daily, and body weights and food consumption were determined weekly. Blood samples were collected on day 91 for measurement of hematology and clinical biochemistry. Animals were euthanized for necropsy, and selected organs were weighed and fixed for histological examination. The tissue distribution of silicon in the blood, liver, kidneys, and testis were determined.</p><p><b>RESULTS</b>There were no toxicologically significant changes in mortality, clinical signs, body weight, food consumption, necropsy findings, and organ weights. Differences between the silica groups and the control group in some hematological and clinical biochemical values and histopathological findings were not considered treatment related. The tissue distribution of silicon was comparable across all groups.</p><p><b>CONCLUSION</b>Our study demonstrated that neither silica NPs nor silica MPs induced toxicological effects after subchronic oral exposure in rats.</p>

Subchronic Oral Toxicity Evaluation of Lanthanum: A 90-day, Repeated Dose Study in Rats / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>The present study was undertaken to evaluate the subchronic toxicity of lanthanum and to determine the no observed adverse effect level (NOAEL), which is a critical factor in the establishment of an acceptable dietary intake (ADI).</p><p><b>METHODS</b>In accordance with the Organization for Economic Co-operation and Development (OECD) testing guidelines, lanthanum nitrate was administered once daily by gavage to Sprague-Dawley (SD) rats at dose levels of 0, 1.5, 6.0, 24.0, and 144.0 mg/kg body weight (BW) per day for 90 days, followed by a recovery period of 4 weeks in the 144.0 mg/kg BW per day and normal control groups. Outcome parameters were mortality, clinical symptoms, body and organ weights, serum chemistry, and food consumption, as well as ophthalmic, urinary, hematologic, and histopathologic indicators. The benchmark dose (BMD) approach was applied to estimate a point of departure for the hazard risk assessment of lanthanum.</p><p><b>RESULTS</b>Significant decreases were found in the 144.0 mg/kg BW group in the growth index, including body weight, organ weights, and food consumption. This study suggests that the NOAEL of lanthanum nitrate is 24.0 mg/kg BW per day. Importantly, the 95% lower confidence value of the benchmark dose (BMDL) was estimated as 9.4 mg/kg BW per day in females and 19.3 mg/kg BW per day in males.</p><p><b>CONCLUSION</b>The present subchronic oral exposure toxicity study may provide scientific data for the risk assessment of lanthanum and other rare earth elements (REEs).</p>