[Association between neonatal discharge preparedness and adverse health events]. / æ–°ç”Ÿå„¿å‡ºé™¢å‡†å¤‡åº¦ä¸Žä¸è‰¯å¥åº·äº‹ä»¶çš„å ³ç³».

OBJECTIVES: To study the association between neonatal discharge preparedness and adverse health events. METHODS: The neonates who were born in hospitals from different regions of Gansu Province in China and their parents were enrolled as subjects, and an investigation was performed for the discharge preparedness. According to the level of discharge preparedness, the subjects were divided into low-, middle-, and high-level groups. The neonates were followed up to observe the incidence rate of adverse health events within one month after discharge. The association between neonatal discharge preparedness and adverse health events was analyzed. RESULTS: The neonates with adverse health events had a significantly lower level of discharge preparedness than those without adverse events (P<0.05). The multivariate logistic regression analysis showed that the incidence rate of adverse health events was reduced by 34.8% in the middle-level group and 78.7% in the high-level group compared with the low-level group (P<0.05). The readmission rate of neonates was 8.1% (35/430), and the neonates readmitted had a significantly lower level of discharge preparedness than those not readmitted (P<0.05). The multivariate logistic regression analysis showed that the readmission rate of neonates was reduced by 67.4% in the middle-level group and 84.2% in the high-level group compared with the low-level group (P<0.05). CONCLUSIONS: Discharge preparedness may affect the incidence of adverse health events and the rate of readmission within one month after discharge. Medical staff should adopt effective intervention measures to improve discharge preparedness, so as to reduce the incidence of adverse health events and the rate of readmission.

Chromene and chromone derivatives as liver X receptors modulators from a marine-derived Pestalotiopsis neglecta fungus.

Four new chromene derivatives, pestalotiochromenoic acids A - D (1, 2, 4, and 5), and two new chromone derivatives, pestalotiochromones A and B (6 and 7), were obtained from the marine alga-derived fungus Pestalotiopsis neglecta SCSIO41403, as well as a reported derivate named piperochromenoic acid (3) with its configuration determined for the first time. Their structures were determined by detailed nuclear magnetic resonance (NMR) and mass spectroscopic analyses, while the absolute configurations were established by theoretical NMR and electronic circular dichroism (ECD) calculation, including Mo2(OAc)4-induced ECD experiments. Those chromene and chromone derivatives displayed weak cytotoxicity, but showed obvious liver X receptors (LXRs) modulatory activities, by in vitro tests on the expression of LXRα, LXRß and theirtarget gene ABCA1, as well as in silico docking analysis. Moreover, the high binding affinities between pestalotiochromone A (6) and LXRα, revealed by surface plasmon resonance (SPR) with the dissociation equilibrium constant (KD) value of 6.2 µM, demonstrated 6 could act as a new potential LXR agonist.

Overexpression of circular RNA circ-CDC45 facilitates glioma cell progression by sponging miR-516b and miR-527 and predicts an adverse prognosis.

Glioma (GM) is a highly lethal human cancer. Circular RNAs (circRNAs) act as an imperative factor in oncogenesis. We aimed to investigate the biological functions and mechanisms of circ-CDC45 in GM. circ-CDC45 expression in GM specimens and cell lines was measured by real-time quantitative reverse transcription polymerase chain reaction. Fisher's exact test and Kaplan-Meier curves further analyzed its clinical implications. A gain/loss-of-function study was conducted to investigate the role of circ-CDC45 in GM. Additionally, luciferase reporter and rescue assays were performed to unravel the mechanisms of circ-CDC45. High circ-CDC45 expression was found in GM specimens and cells, which was tightly related to a larger tumor size, higher world health organization (WHO) stages, and worse survival for patients with GM. Functionally, manipulation of circ-CDC45 expression strongly affected cell growth, apoptosis, migration and invasion, which suggests the oncogenic function of circ-CDC45 in GM oncogenesis. Stepwise mechanism studies indicated that circ-CDC45 sponged and regulated the expression of miR-516b and miR-527 to promote cell growth and invasion. Briefly, the regulatory network of circ-CDC45/miR-516b/miR-527 plays a pivotal role in GM tumorigenesis and may act as a potential target for GM treatment.

Ene-yne Hydroquinones from a Marine-derived Strain of the Fungus Pestalotiopsis neglecta with Effects on Liver X Receptor Alpha.

Seven unusual new ene-yne hydroquinones (1-3, 5-8), including three rare glycosylated derivatives named pestalotioquinosides A-C (6-8), were obtained from the marine-derived strain SCSIO41403 of the fungus Pestalotiopsis neglecta. Their structures including absolute configurations were elucidated by spectroscopic analysis and induced electronic circular dichroism experiments. In silico molecular docking and in vitro surface plasmon resonance studies showed that pestalotioquinoside C (8) could act as a liver X receptor alpha (LXRα) modulator. Further study showed that LXR target gene ABCA1 was significantly upregulated by 8, which revealed 8 as a potential LXRα agonist.

Sorbicillfurans A and B, two novel sorbicillinoid adducts from the fungus Penicillium citrinum SCSIO41402.

Two novel sorbicillinoid adducts containing bicyclo[2.2.2]octane and tetrahydrofuran moieties, named sorbicillfurans A and B (1 and 2), were isolated from the static culture of the marine-derived fungus Penicillium citrinum SCSIO41402. Their structures including absolute configurations were determined by spectroscopic and calculated ECD analyses. Sorbicillfurans A and B (1 and 2) are the first examples of sorbicillinoids possessing a tetrahydrofuran unit. In the proposed biosynthetic pathway, sorbicillfuran B (2), harboring a rare and complex polycyclic framework, is probably formed by two Diels-Alder reactions. Both isolates were evaluated for the cytotoxicity against six human cancer cell lines, only sorbicillfuran B (2) showed weak cytotoxicity against HL-60 cells with an IC50 value of 9.6 µM.

Spirostaphylotrichin X from a Marine-Derived Fungus as an Anti-influenza Agent Targeting RNA Polymerase PB2.

A new spirocyclic γ-lactam, named spirostaphylotrichin X (1), and three related known spirostaphylotrichins (2-4) were isolated from the marine-derived fungus Cochliobolus lunatus SCSIO41401. Their structures were determined by spectroscopic analyses. Spirostaphylotrichin X (1) displayed obvious inhibitory activities against multiple influenza virus strains, with IC50 values from 1.2 to 5.5 µM. Investigation of the mechanism showed that 1 inhibited viral polymerase activity and interfered with the production of progeny viral RNA. Homogeneous time-resolved fluorescence, surface plasmon resonance assays, and a molecular docking study revealed that 1 could inhibit polymerase PB2 protein activity by binding to the highly conserved region of the cap-binding domain of PB2. These results suggest that 1 inhibits the replication of influenza A virus by interfering with the activity of PB2 protein and that 1 represents a new type of potential lead compound for the development of anti-influenza therapeutics.

Cytotoxic and Antibacterial Eremophilane Sesquiterpenes from the Marine-Derived Fungus Cochliobolus lunatus SCSIO41401.

Three new eremophilane sesquiterpenes, dendryphiellins H-J (1-3), and three new phthalide natural products (4-6) were isolated from the marine-derived fungus Cochliobolus lunatus SCSIO41401. Their structures including absolute configurations were determined by spectroscopic and calculated ECD analyses. Dendryphiellin I (2) showed cytotoxic and antibacterial activities against five cancer cell lines (IC50 1.4 to 4.3 µM) and three bacterial species (MIC 1.5 to 13 µg/mL), respectively. Dendryphiellin J (3), a rare naturally occurring aldoxime analogue, displayed cytotoxicities against ACHN and HepG-2 cells with IC50 values of 3.1 and 5.9 µM, respectively. Further studies indicated that 3 induced apoptosis in ACHN cells in a dose- and time-dependent manner.

Genipin Inhibits LPS-Induced Inflammatory Response in BV2 Microglial Cells.

Genipin, an aglycon of geniposide, has been reported to have anti-inflammatory effect. However, the anti-inflammatory activity of genipin on LPS-stimulated BV2 microglial cells has not been reported. In this study, we investigated the molecular mechanisms responsible for the anti-inflammatory activity of genipin both in vivo and in vitro. The levels of TNF-α, IL-1ß, NO and PGE2 were detected by ELISA. The expression of Nrf2, HO-1, and NF-κB were detected by western blot analysis. In vivo, genipin significantly attenuated LPS-induced memory deficit in the Morris water maze and passive avoidance tasks. Genipin also inhibited LPS-induced TNF-α and IL-1ß expression in brain tissues. In vitro, our results showed that genipin inhibited LPS-induced TNF-α, IL-1ß, NO and PGE2 production in a concentration-dependent manner. Genipin also suppressed LPS-induced NF-κB activation. In addition, the expression of Nrf2 and HO-1 were up-regulated by treatment of genipin. Furthermore, the inhibition of genipin on inflammatory mediator production was attenuated by transfection with Nrf2 siRNA. In conclusion, genipin inhibited LPS-induced inflammatory response by activating Nrf2 signaling pathway in BV2 microglia.

Asperpyrone-Type Bis-Naphtho-γ-Pyrones with COX-2-Inhibitory Activities from Marine-Derived Fungus Aspergillus niger.

Bis-naphtho-γ-pyrones (BNPs) are an important group of aromatic polyketides derived from fungi, and asperpyrone-type BNPs are produced primarily by Aspergillus species. The fungal strain Aspergillus niger SCSIO Jcsw6F30, isolated from a marine alga, Sargassum sp., and identified according to its morphological traits and the internal transcribed spacer (ITS) region sequence, was studied for BNPs secondary metabolisms. After HPLC/MS analysis of crude extract of the fermentation broth, 11 asperpyrone-type BNPs were obtained directly and quickly by chromatographic separation in the extract, and those isolated asperpyrone-type BNPs were structurally identified by NMR and MS analyses. All of the BNPs showed weak cytotoxicities against 10 human tumor cells (IC50 > 30 µM). However, three of them, aurasperone F (3), aurasperone C (6) and asperpyrone A (8), exhibited obvious COX-2-inhibitory activities, with the IC50 values being 11.1, 4.2, and 6.4 µM, respectively. This is the first time the COX-2-inhibitory activities of BNPs have been reported.

miR-590-3p suppresses cancer cell migration, invasion and epithelial-mesenchymal transition in glioblastoma multiforme by targeting ZEB1 and ZEB2.

Invasion and migration of glioblastoma multiforme (GBM) is a multistep process and an important phenotype that causes this disease to invade surrounding tissues in the brain. The purpose of this study was to determine the role of miR-590-3p in regulation of epithelial mesenchymal transition (EMT) and metastasis of GBM cells. Expression levels of miR-590-3p in 15 GBM specimens with adjacent tissues and five GBM cell lines were assessed by quantitative RT-PCR. We found that miR-590-3p was down-regulated in detected GBM tissue samples and all of the GBM cell lines. In addition, Ectopic expression of miR-590-3p suppressed and miR-590-3p-in promoted EMT, migration, and invasion in U87MG and A172 cells. Bioinformatics coupled with luciferase and Western blot assays also revealed that miR-590-3p inhibited expression of ZEB1 and ZEB2, which are master regulators of tumor metastasis. Our study first indicates that miR-590-3p functions as a suppressor of GBM EMT and metastasis by targeting ZEB1 and ZEB2, and it may be a therapeutic target for metastatic GBM.

Association between glutathione S-transferase T1 null genotype and glioma susceptibility: a meta-analysis.

The relationship between genetic polymorphisms of glutathione S-transferase (GST) and the development of glioma has been investigated in several epidemiologic studies. However, these studies report inconsistent results. In order to get this precise result, a meta-analysis was conducted by calculating the pooled odds ratios (OR) and the 95% confidence intervals (95 % CI). Eleven case-control research studies with a total of 2,416 glioma cases and 4,850 controls were included into this meta-analysis. The combined results based on all studies showed that there was no significant association between the GSTT1 null allele and glioma risk (OR = 1.188, 95% CI = 0.929­1.520, P(heterogeneity) = 0.003, P = 0.170). In the subgroup analysis, the same results were found in our work. There was no risk of publication bias in this meta-analysis. Our results suggest that GSTT1 null genotype was not associated with the increased risk of glioma.

Effects of tetrandrine on glioma cell malignant phenotype via inhibition of ADAM17.

Tetrandrine (TET), a bisbenzylisoquinoline alkaloid isolated from the root of Hang-Fang-Chi (Stephania tetrandra S. Moore), exhibits broad pharmacological effects, including antitumor activity in various malignant neoplasms. Recently, the beneficial effects of TET on cytotoxicity towards tumor cells, radiosensitization, circumventing multidrug resistance, normal tissue radioprotection, and antiangiogenesis have been examined extensively. However, the potential molecular mechanisms of the effect on glioma of TET are yet unknown. This study is explored to evaluate whether TET can inhibit cell proliferation, invasion, and the possible underlying mechanisms in glioma U87 cell. In the present study, cell proliferation was determined by using the Cell Counting Kit-8 (CCK-8) viability assay. The invasion and migration were evaluated by means of wound-scratch assay and Matrigel-Transwell methods. The mRNA expression and protein expression of ADAM metallopeptidase domain 17 (ADAM17) in glioma cell lines and glioma samples were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. Moreover, the expression of epidermal growth factor receptor (EGFR)/p-EGFR and AKT/p-AKT was studied to clarify the molecular mechanism. Our results suggested that TET inhibited cell proliferation in a dose- and time-dependent manner, and cell migration and invasion in vitro. In addition, our results indicated that ADAM17 expression significantly increased in glioma compared to nontumored human brain tissue and according to the histopathological grade of glioma. Western blot analysis showed that protein expressions of ADAM17, p-EGFR, and p-AKT were inhibited by TET in U87 cells. These data also suggest that suppression of ADAM17 and downregulation of EGFR-phosphoinositide-3-kinase (PI3K)-AKT signaling pathways may contribute to TET-induced decrease of proliferation, migration, and invasiveness.

Spatial and temporal clustering analysis of pulmonary tuberculosis and its associated risk factors in southwest China.

Pulmonary tuberculosis (PTB) remains a serious public health problem, especially in areas of developing countries. This study aimed to explore the spatial-temporal clusters and associated risk factors of PTB in south-western China. Space-time scan statistics were used to explore the spatial and temporal distribution characteristics of PTB. We collected data on PTB, population, geographic information and possible influencing factors (average temperature, average rainfall, average altitude, planting area of crops and population density) from 11 towns in Mengzi, a prefecture-level city in China, between 1 January 2015 and 31 December 2019. A total of 901 reported PTB cases were collected in the study area and a spatial lag model was conducted to analyse the association between these variables and the PTB incidence. Kulldorff's scan results identified two significant space-time clusters, with the most likely cluster (RR = 2.24, p < 0.001) mainly located in northeastern Mengzi involving five towns in the time frame June 2017 - November 2019. A secondary cluster (RR = 2.09, p < 0.05) was located in southern Mengzi, covering two towns and persisting from July 2017 to December 2019. The results of the spatial lag model showed that average rainfall was associated with PTB incidence. Precautions and protective measures should be strengthened in high-risk areas to avoid spread of the disease.

A pH-mediated field amplification sample stacking technique based on portable microchip electrophoresis heavy metal ion detection system.

We built a portable microchip electrophoresis heavy metal ion detection system and proposed a pH-mediated field amplified sample stacking (pH-mediated FASS) online preconcentration method. The pH-mediated FASS focuses and stacks heavy metal cations by controlling electrophoretic mobilities with a pH change between the analyte and the background electrolyte (BGE) in solution to improve the detection sensitivity of the system. We optimized and adjusted sample matrix solution (SMS) ratios and pH to create concentration and pH gradients for SMS and BGE. Furthermore, we optimize the microchannel width to improve the preconcentration effect further. The system and method analyzed soil leachates polluted with heavy metals and separated Pb2+ and Cd2+ within 90 s, obtaining their levels at 58.01 mg/L and 4.91 mg/L with sensitivity enhancement factors (SEF) of 26.40 and 43.73. Compared with inductively coupled plasma atomic emission spectrometry (ICP-AES), the detection error of the system was less than 8.80%.

Sox11 modulates neocortical development by regulating the proliferation and neuronal differentiation of cortical intermediate precursors.

Neural precursor cells play important roles in the neocortical development, but the mechanisms of neural progenitor proliferation, neuronal differentiation, and migration, as well as patterning are still unclear. Sox11, one of SoxC family members, has been reported to be essential for embryonic and adult neurogenesis. But there is no report about the roles of Sox11 in corticogenesis. In order to investigate Sox11 function during cortical development, loss of function experiment was performed in this study. Knockdown of Sox11 by Sox11 siRNA constructs resulted in a diminished neuronal differentiation, but enhanced proliferation of intermediate progenitors. Accompanied with the high expression of Sox11 in the postmitotic neurons, but low expression of Sox11 in the dividing neural progenitors, all the observations indicate that Sox11 induces neuronal differentiation during the neocortical development.

A Novel Planar Grounded Capacitively Coupled Contactless Conductivity Detector for Microchip Electrophoresis.

In the microchip electrophoresis with capacitively coupled contactless conductivity detection, the stray capacitance of the detector causes high background noise, which seriously affects the sensitivity and stability of the detection system. To reduce the effect, a novel design of planar grounded capacitively coupled contactless conductivity detector (PG-C4D) based on printed circuit board (PCB) is proposed. The entire circuit plane except the sensing electrodes is covered by the ground electrode, greatly reducing the stray capacitance. The efficacy of the design has been verified by the electrical field simulation and the electrophoresis detection experiments of inorganic ions. The baseline intensity of the PG-C4D was less than 1/6 of that of the traditional C4D. The PG-C4D with the new design also demonstrated a good repeatability of migration time, peak area, and peak height (n = 5, relative standard deviation, RSD ≤ 0.3%, 3%, and 4%, respectively), and good linear coefficients within the range of 0.05-0.75 mM (R2 ≥ 0.986). The detection sensitivity of K+, Na+, and Li+ reached 0.05, 0.1, and 0.1 mM respectively. Those results prove that the new design is an effective and economical approach which can improve sensitivity and repeatability of a PCB based PG-C4D, which indicate a great application potential in agricultural and environmental monitoring.

[Comparison of MGMT and ERCC2 expression in temozolomide for the treatment of malignant glioma drug resistance and their genetic relationship].

OBJECTIVE: To study the impact of two human glioma tissue resistance genes MGMT and ERCC(2) on the temozolomide-based treatment of malignant gliomas and detect the relationship of their expressions. METHODS: A total of 58 malignant glioma patients aged 19 - 68 years old receiving a chemotherapy of temozolomide were followed up and classified as non-sensitive group (n = 30) and sensitive group (n = 28). Immunohistochemistry was employed to detect the expression rates of MGMT and ERCC(2). And the correlation between the expressions of two genes was analyzed by immunohistochemistry and RT-PCR (reverse transcription-polymerase chain reaction). RESULTS: The expression rates of MGMT and ERCC(2) were 10.71% and 3.57% in the sensitive group and 63.33% and 56.67% in the non-sensitive group. It had an obvious correlation with the expressions of MEGT and ERCC(2) through an analysis of immunohistochemistry and RT-PCR (both P < 0.01). CONCLUSION: The expressions of MGMT and ERCC(2) in the sensitive group are markedly lower than those in the non-sensitive group. The expression of two genes may be related to tumor prognosis. Maybe these two genes have an intrinsic link between their expressions. Both participate in the repair of cellular DNA damage and the formation of tumor drug resistance. And the prognosis has obvious relevance.

New pestallic acids and diphenylketone derivatives from the marine alga-derived endophytic fungus Pestalotiopsis neglecta SCSIO41403.

Three new carboxylic acid derivatives, pestallic acids F and G (1 and 2), pestalotiopyrone N (3), and a new diphenylketone derivative named neopestalone (5) were obtained from the liquid cultures of marine alga-derived endophytic fungus Pestalotiopsis neglecta SCSIO41403, along with six known compounds (4, 6-10). The structures of those new compounds were elucidated mainly by analysis of their NMR and MS data. The isolated compounds were evaluated for their anti-Dengue virus and COX-2 inhibitory activities, and two diphenylketone derivatives (5 and 6) exhibited obvious COX-2 inhibitory activities, with the IC50 values being 5.8 and 3.4 µM, respectively.

Long Non-coding RNA EPIC1 Promotes Cell Proliferation and Motility and Drug Resistance in Glioma.

Evidence has revealed that long non-coding RNAs (lncRNAs) are involved in carcinogenesis and tumor progression. lncRNAs play an important role in regulation of numerous cellular processes including cell proliferation, apoptosis, cell cycle, differentiation, and motility. Several studies have demonstrated that lncRNA EPIC1 governs cell growth, cell cycle, migration, invasion, and drug resistance in human malignancies. However, the role of EPIC1 and its underlying molecular mechanisms in glioma have not been investigated. In this study, we determined the function of EPIC1 in glioma cells via upregulation or downregulation of EPIC1. We further dissected the mechanism of EPIC1-mediated tumor progression in glioma. Our results showed that inhibition of EPIC1 suppressed cell viability, induced apoptosis, inhibited cell invasion, and increased cell sensitivity to temozolomide in glioma cells. Consistently, overexpression of EPIC1 exhibited the opposite effects in glioma cells. Moreover, our data suggest that EPIC1 exerts its biological functions via targeting Cdc20 in glioma cells. In line with this, overexpression of Cdc20 reversed the EPIC1-mediated tumor progression in glioma cells. Therefore, targeting EPIC1 might be a useful approach for glioma treatment.

miR­342 inhibits glioma cell proliferation by targeting GPRC5A.

Accumulating evidence suggests that microRNAs (miRNAs) play a key role in the biological behaviors and progression of glioma. However, the function and bio­molecular mechanisms of miR­342 in glioma remain largely unclear. In the present study, reverse transcription quantitative­polymerase chain reaction and western blotting were performed to determine the mRNA and protein expression levels of the factors investigated. MTT assay was performed to examine the proliferation rates. Luciferase reporter assay was performed to test the binding between miRNA­342 and its putative target. Data indicated that miR­342 expression was markedly decreased in human glioma tissues and cell line U87, and reduced miR­342 expression significantly promoted cell proliferation. In order to explore the mechanisms, G­protein coupled receptor family C group 5 member A (GPRC5A) was identified as a target of miR­342 and depletion of GPRC5A suppressed cell proliferation. Our findings demonstrated that miR­342 regulates the cell proliferation of glioma by targeting GPRC5A, which indicates that miR­342 is a target of interest regarding the treatment of refractory glioma, and it may provide a promising prognostic and therapeutic strategy for glioma treatment.