Chronic trichlorfon stress induces differential transcriptome expression and interferes with multifunctional pathways in the brain of Rana chensinensis.

Trichlorfon is widely used to control pest insects and various parasitic infestations in agriculture, aquaculture and human medicine. However, the long-term widespread use and overuse of trichlorfon poses risks to public and environmental health. Thus, the aim of this study was to evaluate the interference of trichlorfon on gene transcription patterns in the brain of Rana chensinensis with 4 weeks treatment under control conditions and 0.1 mg/L exposure. In total, 102,013 unigenes were obtained from the brain tissue of R. chensinensis, and 874 differentially expressed genes (DEGs) were identified. Functional annotation indicated that out of 118,643 unigenes, 45,600 (44.7%) were annotated in the Nr, Nt, the Swiss-Prot, KEGG, COG, and GO databases. The differential expression patterns of 4 genes associated with neural activity were selected and validated by quantitative polymerase chain reaction (qPCR). The results revealed that except for the canonical cholinesterase-based mechanism, trichlorfon could act on other receptors and alter certain types of neuronal ion channels as the major target sites. All of these effects ultimately cause disorders of multifunctional pathways and other neurotransmitter pathways in the host. The results further our understanding of the mechanisms underlying nontarget effects of organophosphate insecticides (OPs) through multitargets studies.

[Invasive ductal carcinomas of breast showing partial reversed cell polarity are associated with lymphatic tumor spread].

OBJECTIVE: To investigate the relationship between partial reversed cell polarity (PRCP) and lymphatic tumor spread in invasive ductal carcinoma (IDC), not othervise specified (NOS). METHODS: Immunohistochemistry (EnVision method) was used to examine the expression of epithelial membrane antigen (EMA) and the reversed cell polarity in 199 cases of IDC. RESULTS: Of the 199 cases, including five cases with micropapillary differentiation,30 cases with PRCP and 164 cases of IDC-NOS (without micropapillary differentiation and/or PRCP), lymphovascular invasion was seen in four (4/5), 13(43.3%) and 30 cases (18.3%) respectively; nodal metastasis was seen in four (4/5), 19 (63.3%) and 56 cases (34.1%) respectively. The rates of lymphovascular invasion and nodal metastasis were significantly higher in IDC with PRCP or IMPC than IDC-NOS (P = 0.00); there was however no significant difference between IDC with PRCP and IMPC for lymphovascular invasion and nodal metastasis (P = 0.18, P = 0.64). CONCLUSIONS: IDC with PRCP, similar to IMPC, is more likely to show lymphovascular invasion and nodal metastasis. Complete or partial reversal of cell polarity may play a significant role in lymphatic tumor spread.

[Relationship between placental pathology and small-for-gestational age neonates].

OBJECTIVE: To investigate the relationship between pathological abnormalities of placenta and small-for-gestational-age neonates. METHODS: One hundred placentas of small-for-gestational-age (SGA group) and 200 appropriate-for-gestational-age (AGA group) with single living birth in third trimester were investigated by gross and microscopic examination. The AGA placentas were collected from 2 cases following every SGA placenta. All cases were collected from Shanghai Changning District Maternity and Infant Health Hospital from January 2010 to December 2011. RESULTS: The gestational week, neonatal birth weight, full-term neonatal birth weight, the preterm birth rate and vaginal spontaneous delivery rate were significantly lower in SGA group than that in AGA group (P < 0.002). Full-term placental volume, placental weight and fetal placental weight ratio were lower in SGA group than that in AGA group (P < 0.05). Unusual insertion and torsion of umbilical cord were more common in SGA group (P < 0.05). Syncytial knots increase, avascular villi and villous infarcts were significantly higher in SGA group (P < 0.005), but there were no significant difference between SGA group and AGA group in intervillous thrombi, chronic villitis and chorangiosis (P > 0.05). Gestational hypertension disease and abnormality of fetal monitoring were more common in SGA group (P < 0.05). CONCLUSIONS: Gestational hypertension disease is the main clinical cause of SGA. Some placental abnormality can affect the growth and development of intrauterine fetus.

[The effects of activated protein C on the von Willebrand factor and von Willebrand factor cleaving protease of rat aortic endothelial cell induced by lipopolysaccharide].

OBJECTIVE: To investigate the activated protein C (APC) on the von Willebrand factor antigen (vWFAg) and von Willebrand factor cleaving protease (ADAMTS-13) protein expression in rat aortic endothelial cells (RAECs) induced by lipopolysaccharide (LPS). METHODS: RAECs from Wistar rats were cultured with the tissue explants adherence method. RAECs were cultured for one week, After one week culture, RAECs in 4-5 generations were divided into control group, LPS stimulation groups (1 mg/L) and APC intervention groups (0.1, 1 and 10 mg/L APC was added after LPS stimulation). The supernatants were obtained at 12, 24, 48, and 72 hours after LPS stimulated to determine the vWFAg and protein of ADAMTS-13 expression by enzyme-linked immunoadsorbent assay (ELISA). RESULTS: In the control group, RAECs expressed little vWFAg and protein of ADAMTS-13. With stimulation of LPS, the vWFAg was significantly increased at 12 hours, and reached the peak at 48 hours [(285.45±30.13)%], and the level of ADAMTS-13 (µg/L) was gradually decreased, and reached the nadir at 72 hours (13.32±2.37), there was significant difference compared with control group [vWFAg: (94.53±7.83)%, ADAMTS-13: 115.76±2.36, both P<0.01). The effects on vWFAg promoting and ADAMTS-13 inhibition after LPS stimulation could be dose-dependently reversed by APC. 10 mg/L of APC could decrease the peak of vWFAg at 48 hours of LPS stimulation [(198.43±17.92)% vs. (285.45±30.13)%], and increase the minimize of ADAMTS-13 (µg/L) at 72 hours of LPS stimulation (125.25±2.70 vs. 13.32±2.37), with significant difference (both P<0.01). CONCLUSIONS: After stimulation with LPS, the level of vWFAg was time-dependent increased, as the protein of ADAMTS-13 was decreased. APC could attenuate the effect of LPS on vWFAg and protein of ADAMTS-13 with dose-dependent and time-dependent patterns.

N'-(2-Meth-oxy-benzyl-idene)-4-nitro-benzohydrazide.

The mol-ecule of the title compound, C(15)H(13)N(3)O(4), adopts an E configuration with respect to the C=N bond. The dihedral angle between the two benzene rings is 6.0 (3)°. In the crystal, mol-ecules are linked through inter-molecular N-H⋯O hydrogen bonds to form chains along the c axis.

[Induction of expression of von Willebrand factor cleaving protease of rat aortic endothelial cell by lipopolysaccharide challenge].

OBJECTIVE: To investigate the dose response effect and time response effect of lipopolysaccharide(LPS) on von Willebrand factor cleaving protease (ADAMTS-13, Vwf-cp) mRNA expression and protein in rat aortic endothelial cells (RAECs). METHODS: RAECs were grown by culturing of aortic tissue. When ARECs were cultured for one week, it was co-cultured by 1:3 to reach 4-5 generations. ARECs were randomly divided into five groups: control group and four LPS stimulation groups (0.01, 0.1, 1 and 5 µg/ml) . The RAECs and supernatants were obtained at 12, 24, 48, and 72 hours after being stimulated by LPS. ADAMTS-13 mRNA expression of RAECs was assessed by quantitation reverse transcription-polymerase chain reaction (RT-PCR), and protein of ADAMTS-13 in supernatants was determined by enzyme linked immunoadsorbent assay (ELISA). RESULTS: In the control group RAECs were shown to express ADAMTS-13 at both protein and mRNA levels. With the increase of concentration of LPS, or increase in stimulus duration, expression of ADAMTS-13 mRNA and protein were gradually lowered. Compared with the control group (25.22 ±1.41), the level of ADAMTS-13 mRNA in 0.01 µg/ml LPS stimulation group was markedly decreased at 48 hours (18.78±0.86, P<0.01). At 24 hours, the levels of ADAMTS-13 mRNA (23.43±0.63, 22.41±0.76) were markedly decreased in 0.1 µg/ml and 1 µg/ml LPS stimulation groups (P<0.05 and P<0.01). The level of ADAMTS-13 mRNA (20.01±2.47) in 5 µg/ml LPS stimulation group was markedly decreased at 12 hours (P<0.01). Compared with the control group [(115.76±2.36) ng/ml], protein level of ADAMTS-13 [(113.43±1.07) ng/ml] was markedly decreased at 12 hours in 0.01 µg/ml LPS stimulation group (P<0.05). The protein level of ADAMTS-13 [(7.63±2.64) ng/ml] was lowest in 5 µg/ml LPS stimulation group at 72 hours (P<0.01). CONCLUSION: Normal RAECs can express ADAMTS-13 at both mRNA and protein to certain extent. The expression of ADAMTS-13 mRNA and protein are decreased after LPS challenge in different concentrations for different duration in dose dependent and time dependent manner.

6-Bromo-2'-(2-chlorobenzylidene)nicotinohydrazide and 6-Bromo-2'-(3-bromo-5-chloro-2-hydroxybenzylidene) nicotinohydrazide Methanol Solvate: Synthesis, Characterization, Crystal Structures and Antimicrobial Activities.

Two newly synthesized nicotinohydrazones, 6-bromo-2'-(2-chlorobenzylidene)nicotinohydrazide (1) and 6-bromo-2'-(3-bromo-5-chloro-2-hydroxybenzylidene)nicotinohydrazide methanol solvate (2), have been obtained and structurally characterized by spectroscopic method and single crystal X-ray determination. The molecules in both compounds are in E configuration regarding to the azomethine groups. The molecules of compound 1 are linked via hydrogen bonds of N?H∙∙∙O, generating one dimensional chains running along the c-axis direction. The hydrazone molecules of compound 2 are linked by methanol molecules via hydrogen bonds of N?H∙∙∙O and O?H∙∙∙N, generating dimers. The in vitro antimicrobial activities of these compounds indicate that they are interesting antibacterial agents.

Global, Regional, and National Incidence and Year Lived with Disability for Benign Prostatic Hyperplasia from 1990 to 2019.

The objective of this study is to provide comprehensive and up-to-date estimates on the disease burden of BPH in 204 countries and territories between 1990 and 2019. Data about incidence, year lived with disability (YLD), and their age-standardized rates (ASRs) for 21 regions, 5 Socio-demographic Index (SDI) quintiles, 204 countries and territories, and 12 age categories from 1990 to 2019 were obtained from the Global Burden of Disease 2019 study. Estimated annual percentage changes (EAPCs) of the ASRs and the associations between SDI and the ASRs were estimated. The effects of population growth, population aging, and age-specific rate on the changes in the absolute numbers of incidence and YLD were quantified. Globally, there were 11.26 million (95% uncertainty interval [UI]: 8.79, 14.46) new cases and 1.86 million (95%UI: 1.13, 2.78) YLD due to BPH in 2019. The global ASRs of incidence (EAPC: -0.031, 95% CI: -0.050, -0.012) and YLD (EAPC: -0.058, 95% CI: -0.084, -0.031) decreased slightly from 1990 to 2019, whereas the absolute numbers increased dramatically from 1990 (incidence by 105.7% and YLD by 110.6%), mainly driven by the population growth (53.5% for incidence and 54.4% for YLD) and population aging (55.7% for incidence and 63.2% for YLD). The burden of BPH varied markedly among different regions, socioeconomic status, and countries. As the population is growing and aging, great efforts are required to develop effective prevention, treatment and management strategies to meet the high and increasing burden of BPH worldwide.

N'-(3,5-Dichloro-2-hy-droxy-benzyl-idene)-4-nitro-benzohydrazide methanol solvate.

In the title compound, C(14)H(9)Cl(2)N(3)O(4)·CH(4)O, the dihedral angle between the two benzene rings in the hydrazone mol-ecule is 6.3 (3)°. An intra-molecular N-H⋯O hydrogen bond stabilizes the mol-ecular conformation. In the crystal, centrosymmetrically related mol-ecules are linked through inter-molecular O-H⋯O and N-H⋯O hydrogen bonds.

Extracellular regulated kinase 5 mediates osteoporosis through modulating viability and apoptosis of osteoblasts in ovariectomized rats.

Postmenopausal osteoporosis is a common condition characterized by the increase and activation of osteoclasts. The present study aimed to investigate the effects of extracellular signal-regulated kinase (ERK) 5 (ERK-5) on postmenopausal osteoporosis by regulating the biological behaviors of osteoblasts. Sprague-Dawley (SD) rats were ovariectomized to develop an osteoporosis model. A lentivirus packaging system was employed to generate lentiviruses capable of up- or down-regulating the expression of ERK-5 in ovariectomized rats. The femoral biomechanical properties, bone mineral density (BMD), contents of calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) and bone turnover markers in rats, as well as viability, cycle and apoptosis of osteoblasts and ALP activity in osteoblasts were measured in the ovariectomized rats so as to explore the functional significance of ERK-5 in postmenopausal osteoporosis. The femoral mechanical strength of ovariectomized rats was enhanced by overexpression of ERK-5. Meanwhile femoral BMD, and bone metabolism were increased, and bone turnover normalized in the ovariectomized rats when ERK-5 was overexpressed. Lentivirus-mediated ERK-5 overexpression in osteoblasts was observed to inhibit osteoblast apoptosis, and promote viability, accompanied with increased ALP activity. Taken together, ERK-5 could decelerate osteoblast apoptosis and improve postmenopausal osteoporosis by increasing osteoblast viability. Thus, our study provides further understanding on a promising therapeutic target for postmenopausal osteoporosis.

A 3-Dimensional Finite Element Analysis of Adjacent Segment Disk Degeneration Induced by Transforaminal Lumbar Interbody Fusion After Pedicle Screw Fixation.

BACKGROUND: Transforaminal lumbar interbody fusion (TLIF) is an effective treatment of upper lumbar intervertebral disk herniation. However, its clinical efficacy for adjacent segment disk degeneration (ASDD) remains undefined. Therefore, the biomechanical evaluation of ASDD caused by TLIF after pedicle screw fixation (PSF) was explored via a 3-dimensional (3D) finite element analysis. METHODS: Computed tomography images of a healthy male adult volunteer were used in this study. A L3-4 3D finite element model (model) was successfully constructed using Pro/E software, which was also used to establish the L4-5 of the TLIF, PSF, and PSF + TLIF models. Under the same loading conditions, the protrusion and retraction of the adjacent intervertebral disk and the stress distribution of the annulus fibrosis, facet joint, and articular process in the TLIF, PSF, and PSF + TLIF models were all compared. RESULTS: Protrusion and retraction of the adjacent intervertebral disk were more notable in the PSF + TLIF model than in the PSF model under the same loading conditions. The stress of the annulus fibrosis of the PSF + TLIF model was stronger relative to that of the PSF model under flexion, extension, or lateral bending. The stress of the articular process of the PSF + TLIF model was also stronger than that of the PSF model under extension or lateral bending. CONCLUSIONS: This study provides evidence that TLIF may aggravate ASDD after PSF. Furthermore, the findings provided in this report represent the theoretic basis for the clinical analysis of ASDD caused by TLIF after PSF.

Predictive value of microRNA-132 and its target gene NAG-1 in evaluating therapeutic efficacy of non-steroidal anti-inflammatory drugs treatment in patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a common chronic rheumatic disorder, accompanied by the differential expression of various microRNAs (miRNAs) in patients suffering from the condition, some of which have the potential to serve as novel complementary AS biomarkers. During this study, AS patients were recruited in connection with our investigation into the correlation of microRNA-132 (miR-132) in peripheral blood and its target gene NAG-1 expressions in relation with the clinical efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) treatment in patients with AS. A total of 218 AS patients who had been previously treated with oral diclofenac sodium and were placed into either the response (n = 175) or non-response groups (n = 43) following a 16-week period of therapeutic evaluation. An additional 113 healthy patients were also recruited for the purposes of the study. AS patient peripheral blood samples were obtained at the 0th, 8th, and 16th week, with the corresponding samples of the healthy patients collected at week 0. The expressions of miR-132 and NAG-1 were detected by RT-qPCR and analyzed using a ROC curve for the elucidation of the diagnostic value of peripheral blood miR-132 expressions as well as their predictive value among AS patients undergoing NSAIDs treatment. The targeting relations of miR-132 and NAG-1 were validated by microRNA.org and luciferase assay. Greater levels of peripheral blood miR-132 expression were observed among AS patients prior to treatment, in comparison to the healthy patients in the study. Prior to treatment, the area under the miR-132 ROC curve (AUC) of AS patients was 0.965, with a critical point of 2.605. The sensitivity and specificity of miR-132 were 91.7 and 97.3%, respectively, in regard to the AS diagnostic clinical efficacy. In comparison with the non-response group, the miR-132 expression of patients in the response group exhibited descended levels while the mRNA expression of NAG-1 increased. The ROC results indicated that the AUC of miR-132 was 0.876 with its sensitivity and specificity observed to be 95.3 and 80.0%, respectively. The AUC of NAG-1 was 0.912 with its sensitivity and specificity observed to be 76.6 and 79.1%, respectively. In comparison with the high miR-132 expression group and the low NAG-1 mRNA expression group, significantly improved blood biochemistry indexes, sign indexes, blood indexes, and adverse reaction rate were observed among the low miR-132 expression group and the high NAG-1 mRNA expression group. The microRNA.org and luciferase assay revealed NAG-1 to be a target of miR-132. Based on the results of this study, it was concluded that the expressions of MiR-132 and NAG-1 could serve as biological markers in the prediction of the therapeutic efficiency of NSAID treatment in AS patients.

An initial study of three-dimensional perfused blood volume computed tomography imaging of patients with anterior circulation hyperacute cerebral infarction.

AIM: To evaluate the value of three-dimensional (3D) whole brain perfused volume computed tomography (3D PBV CT) based on CT angiography (CTA) data in patients with hyperacute cerebral infarction. METHODS: Thirty-five patients who had suffered stroke with anterior circulation within 3 hours underwent nonenhanced CT (NECT) scanning and CTA. Neuro PBV, a 3D software, was utilized to process the raw CTA data and a PBV image of the brain was obtained. Magnetic resonance imaging (MRI) was performed 6 hours after CT imaging. The volume and quantity of the ischemic lesion on 3D PBV and NECT were compared with MR-diffuse-weighted imaging (DWI). RESULTS: The numbers of cerebral infarcts detected by MRI, PBV, and NECT were 40, 38 and 16, respectively. The results of kappa analysis between NECT and PBV with MR were -.0128 and .7622, and a paired t-test analysis for the measurement of infarct volume between PBV and MRI was t = 7.249, P > .05. The lesions that were not detected by PBV volumes less than 4.5 cm(3). CONCLUSION: 3D PBV CT has the potential to assess the full extent of an ischemic stroke at an early stage, whereas PBV is limited to the detection of small infarcts. The 3D PBV CT technique based on CTA data requires no additional radiation exposure or contrast medium injection, and can be performed in a short period of time.