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Background: Polygoni Cuspidati Rhizoma et Radix (PCRR; the root and rhizome of Polygonum cuspidatum Sieb. et Zucc) has long been used to treat atherosclerosis, gastrointestinal disorders, and liver disease. However, the underlying mechanism of PCRR against liver steatosis remains unclear. Purpose: The aim of this study was to determine the potential therapeutic targets and molecular mechanisms of PCRR in improving liver steatosis. Methods: A high-fat diet (HFD)-induced simple steatosis model in rats was used to evaluate the therapeutic effect of polyphenol-rich water extract from PCRR. Its underlying mechanisms were revealed using untargeted mass spectrometry-based serum metabolomics, hepatic lipidomic profiling approaches, qPCR, and Western blotting assays. Results: Our study showed that PCRR-treated rats displayed significant reduction of serum TC and LDL-C, hepatic TG, TC levels, and total liver lipid content under a HFD feeding condition. Untargeted metabolomics showed that PCRR significantly restored the overall levels of nine lipid classes in liver tissues and elevated the bile acid levels in the serum samples. We demonstrated that PCRR prevented HFD-induced hepatic steatosis by regulating the expressions of TG metabolism proteins, including p-AMPK, p-ACC, PPARα, and FAS, as well as the expressions of TC metabolism proteins, including p-AMPK, LDLR, and CYP7A1. Moreover, resveratrol and/or polydatin­-derived metabolites were solely detected in the serum samples of the PCRR-treated group, indicating these microbial transformed metabolites might partly contribute to the beneficial effects of PCRR. Conclusion: PCRR can be employed as a therapeutic agent to improve non-alcoholic fatty liver disease via regulating lipid metabolism.

Abstract Background Circular RNAs (circRNAs) are pivotal regulators of various human cancers and circ-ERBB2 is abnormally expressed in breast cancer cells. However, the role and mechanism of circ-ERBB2 in HER2-positive breast cancer are still unknown. Methods The circ-ERBB2 expressions in the tumor tissues of HER2-positive breast cancer patients were tested using quantitative real-time PCR. The circ-ERBB2 function was investigated by cell counting kit 8 assay, Transwell, flow cytometry and Western blot. Mechanistically, fluorescence in situ hybridization, RNA immunoprecipitation, RNA pull-down and dual-luciferase reporter gene assays were conducted to confirm the interaction between circ-ERBB2 and miR-136-5p or miR-198 in HER2-positive breast cancer cells. Results Circ-ERBB2 was elevated in the tumor tissues of HER2-positive breast cancer patients. Functionally, the interference with circ-ERBB2 repressed HER2-positive breast cancer cell proliferation, migration, invasion and accelerated cell apoptosis. Furthermore, the mechanistic analysis corroborated that circ-ERBB2 acted as a competing endogenous RNA for miR-136-5p or miR-198 to relieve the repressive influence of miR-136-5p or miR-198 on its target transcription factor activator protein 2C (TFAP2C). Meanwhile, in vivo assays further corroborated the oncogenic function of circ-ERBB2 in HER2-positive breast cancer. Conclusions Circ-ERBB2 accelerated HER2-positive breast cancer progression through the circ-ERBB2/miR-136-5p/TFAP2C axis or the circ-ERBB2/miR-198/TFAP2C axis.

Abstract There is still no consensus on how to determine the dose of spinal anaesthesia with adequate sensory block for a planned surgery. This retrospective study aimed to explore the associations of miscellaneous factors with peak sensory block level after spinal anaesthesia with hyperbaric bupivacaine, and to construct a predictive model for single-shot spinal anaesthesia. We collected the records of 401 non-pregnant adults who underwent spinal anaesthesia with 0.5% hyperbaric bupivacaine at the L3–4 or L4–5 intervertebral space for lower body surgeries. Multiple linear regression analysis was used to investigate predictors of the block level and build up the predictive model. Five variables were identified as independent predictors of the peak sensory block level, including bupivacaine dose, height, weight, gender and age. The predictive model for peak block level after spinal anaesthesia could be expressed as a formula with these five variables and the estimated predictive power was 0.72. Based on this model, it is possible to determine a reasonable dose of hyperbaric bupivacaine for spinal anaesthesia, which gives adequate sensory block required for diverse surgical procedures in various patients and could be considered as a dose reference for sensory block height in spinal anaesthesia.

AIM: To investigate the relationship between retinal arteriosclerosisand cardiovascular and cerebrovascular diseases in type 2 diabetes mellitus. METHODS:Totally 85 patients with type 2 diabetes mellitus in our hospital from January 2016 to January 2017 were selected as the research subjects. Fundus examination was carried out to determine the classification of ophthalmic arteriosclerosis. The blood glucose level of the patients was detected and the glycosylated hemoglobin,fasting blood glucose and postprandial blood glucose levels were measured. All patients were followed up for at least 1 and a half years, and the cardiovascular and cerebrovascular diseases rate was statistically analyzed during the follow up period. The blood glucose level and cardiovascular and cerebrovascular diseases rate in patients with different ocular fundus arteriosclerosis grades were compared, meanwhile the relationship between ocular fundus arteriosclerosis grades with the blood glucose levels and cardiovascular and cerebrovascular diseases rate were analyzed. RESULTS: Among the 85 patients, 15%(13/85), 52%(44/85)and 33%(28/85)of the patients were classified asocular fundus arteriosclerosis grades Ⅰ, Ⅱ and Ⅲ respectively. The cardiovascular and cerebrovascular diseases rate during the follow up period was 27%(23/85). The glycosylated hemoglobin,fasting blood glucose, postprandial blood glucose and cardiovascular and cerebrovascular diseases rates were all increased with the elevation of ophthalmic arteriosclerosis(Prs=0.875, 0.792, 0.835, 0.878; PCONCLUSION:Type 2 diabetes mellitus patients has severe fundus arteriosclerosis, which is closely related to blood glucose level and cardiovascular and cerebrovascular diseases.

In recent years, the issues of energy use reduction and sustainable development have garnered considerable interest. This study has conducted a patent search using United States Patent and Trademarks Office (USPTO) data to investigate technological trends in sustainable development, using shading devices for buildings as an example, because they have the potential to save energy by effectively preventing heat from coming indoors, and lowering the indoor heat load. The purpose of this study was to explore the status of shading devices and analyze patent activity, major assignees, assignee countries, core technology fields, patent citations, potential competitors of patent assignees, and developmental path based on patent analysis using a database that spanned the years from 1974 to 2011. The results provide a clear picture of, and evidence for, the pattern of shading device technology; they suggest that automatic sensing shading de­vices are the focus of current technological developments, thus saving time and costs in future research development. First published online: 24 Aug 2015

AIM:To study the effect of posterior sub-Tenon's capsule injection of triamcinolone acetonide(TA)in treatment of patients with diffuse diabetic macular edema(DME)before panretinal photocoagulation(PRP).METHODS:Retrospective analysis of the clinical data of 96 cases(96 eyes)with DME treated in our hospital from October 2008 to May 2012, and the patients were divided into the study group and control group, each group with 48 cases(48 eyes), the control group were only treated with PRP, and for the study group, TA was injected one week before PRP. At 6mo after treatment, best-corrected visual acuity(BCVA)and retinal thickness changes of two groups were compared, the changes of intraocular pressure in two groups was analyzed. RESULTS:After treatment, two groups were followed up for 6mo, compared with before treatment, the expression of BCVA in control group was reduced, and rise in the study group, with significant difference between the two groups(PP>0.05), the study group had foveal thickness reduction of 9.6μm, the control group was increased by 31.9μm, with significant difference(PP>0.05). CONCLUSION:TA injection in patients with diffuse DME before PRP is safe and effective, and it is superior to simple PRP therapy, and it can be applied in primary hospital.

Desipramine (DP) is a tricyclic antidepressant used for treating depression and numerous other psychiatric disorders. Recent studies have shown that DP can promote neurogenesis and improve the survival rate of hippocampal neurons. However, whether DP induces neuroprotection or promotes the differentiation of neural stem cells (NSCs) needs to be elucidated. In this study, we cultured NSCs derived from the hippocampal tissues of adult rats as an in vitro model to evaluate the modulation effect of DP on NSCs. First, we demonstrated that the expression of Bcl-2 mRNA and nestin in 2 μM DP-treated NSCs were up-regulated and detected by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The results of Western blotting and immunofluorescent study confirmed that Bcl-2 protein expression was significantly increased in Day 3 DP-treated NSCs. Using the Bcl-2 small interfering RNA (siRNA) method, our results further showed that DP protects the lipopolysaccharide (LPS)- induced apoptosis in NSCs, in part by activating the expression of Bcl-2. Furthermore, DP treatment significantly inhibited the induction of proinflammatory factor interleukin (IL)-1β, IL-6, and tumor necrosis factor-á in the culture medium of LPS-treated NSCs mediated by Bcl-2 modulation. The results of high performance liquid chromatography coupled to electrochemical detection further confirmed that DP significantly increased the functional production of serotonin (26 ± 3.5 ìM, DP-treated 96 h) and noradrenaline (50 ± 8.9 μM, DP-treated 96 h) in NSCs through activation of the MAPK/ERK pathway and partially mediated by Bcl-2. In conclusion, the present results indicate that DP can increase neuroprotection ability by inhibiting the LPS-induced inflammatory process in NSCs via the modulation of Bcl-2 expression, as confirmed by the siRNA method. Keywords:: desipramine, neural stem cell, real-time RT-PCR, small interfering RNA (siRNA)

NG2 cells, a fourth type of glial cell in the mammalian CNS, undergo reactive changes in response to a wide variety of brain insults. Recent studies have demonstrated that neuronally expressed acid-sensing ion channels (ASICs) are implicated in various neurological disorders including brain ischemia and seizures. Acidosis is a common feature of acute neurological conditions. It is postulated that a drop in pH may be the link between the pathological process and activation of NG2 cells. Such postulate immediately prompts the following questions: Do NG2 cells express ASICs? If so, what are their functional properties and subunit composition? Here, using a combination of electrophysiology, Ca2+ imaging and immunocytochemistry, we present evidence to demonstrate that NG2 cells of the rat hippocampus express high density of Ca2+-permeable ASIC1a channels compared with several types of hippocampal neurons. First, nucleated patch recordings from NG2 cells revealed high density of proton-activated currents. The magnitude of proton-activated current was pH dependent, with a pH for half-maximal activation of 6.3. Second, the current-voltage relationship showed a reversal close to the equilibrium potential for Na+. Third, psalmotoxin 1, a blocker specific for the ASIC1a channel, largely inhibited proton-activated currents. Fourth, Ca2+ imaging showed that activation of proton-activated channels led to an increase of [Ca2+]i. Finally, immunocytochemistry showed co-localization of ASIC1a and NG2 proteins in the hippocampus. Thus the acid chemosensor, the ASIC1a channel, may serve for inducing membrane depolarization and Ca2+ influx, thereby playing a crucial role in the NG2 cell response to injury following ischemia.

Lamotrigine (LTG) is generally considered as a voltage-gated sodium (Nav) channel blocker. However, recent studies suggest that LTG can also serve as a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel enhancer and can increase the excitability of GABAergic interneurons (INs). Perisomatic inhibitory INs, predominantly fast-spiking basket cells (BCs), powerfully inhibit granule cells (GCs) in the hippocampal dentate gyrus. Notably, BCs express abundant Nav channels and HCN channels, both of which are able to support sustained action potential generation. Using whole-cell recording in rat hippocampal slices, we investigated the net LTG effect on BC output. We showed that bath application of LTG significantly decreased the amplitude of evoked compound inhibitory postsynaptic currents (IPSCs) in GCs. In contrast, simultaneous paired recordings from BCs to GCs showed that LTG had no effect on both the amplitude and the paired-pulse ratio of the unitary IPSCs, suggesting that LTG did not affect GABA release, though it suppressed cell excitability. In line with this, LTG decreased spontaneous IPSC (sIPSC) frequency, but not miniature IPSC frequency. When re-examining the LTG effect on GABAergic transmission in the cornus ammonis region 1 (CA1) area, we found that LTG markedly inhibits both the excitability of dendrite-targeting INs in the stratum oriens and the concurrent sIPSCs recorded on their targeting pyramidal cells (PCs) without significant hyperpolarization-activated current (Ih) enhancement. In summary, LTG has no effect on augmenting Ih in GABAergic INs and does not promote GABAergic inhibitory output. The antiepileptic effect of LTG is likely through Nav channel inhibition and the suppression of global neuronal network activity. [ABSTRACT FROM AUTHOR]

Acid-sensing ion channel-la (ASICla) is localized in brain regions with high synaptic density and is thought to contribute to synaptic plasticity, learning, and memory. A prominent hypothesis is that activation of postsynaptic ASICs promotes depolarization, thereby augmenting JV-methyl-D-aspartate receptor function and contributing to the induction of long-term potentiation (LTP). However, evi-dence for activation of postsynaptic ASICs during neurotransmission has not been established. Here, we re-examined the role of ASICla in LTP in the hippocampus using pharmacological and genetic approaches. Our results showed that a tarantula peptide psalmotoxin, which profoundly blocked ASIC currents in the hippocampal neurons, had no effect on LTP. Similarly, normal LTP was robustly gener-ated in ASICla-null mice. A further behavioral analysis showed that mice lacking ASICla had normal performance in hippocampus-dependent spatial memory. In summary, our results indicate that ASICla is not required for hippocampal LTP and spatial memory. We therefore propose that the role of ASICla in LTP and spatial learning should be reassessed. [ABSTRACT FROM AUTHOR]

GABAergic signaling in hippocampal pyramidal neurons undergoes a switch from depolarizing to hyperpolarizing during early neuronal development. Whether such a transformation of GABAergic action occurs in dentate granule cells (DGCs), located at the first stage of the hippocampal trisynaptic circuit, is unclear. Here, we use noninvasive extracellular recording to monitor the effect of synaptically released GABA on the DGC population. We find that GABAergic responses in adolescent and adult rat DGCs are still depolarizing from rest. Using a morphologically realistic DGC model, we show that GABAergic action, depending on its precise timing and location, can have either an excitatory or inhibitory role in signal processing in the dentate gyrus. [ABSTRACT FROM AUTHOR]

NG2 cells, a fourth type of glial cell in the mammalian CNS, undergo reactive changes in response to a wide variety of brain insults. Recent studies have demonstrated that neuronally expressed acid-sensing ion channels (ASICs) are implicated in various neurological disorders including brain ischemia and seizures. Acidosis is a common feature of acute neurological conditions. It is postulated that a drop in pH may be the link between the pathological process and activation of NG2 cells. Such postulate immediately prompts the following questions: Do NG2 cells express ASICs? If so, what are their functional properties and subunit composition? Here, using a combination of electrophysiology, Ca2+ imaging and immunocytochemistry, we present evidence to demonstrate that NG2 cells of the rat hippocampus express high density of Ca2+- permeable ASIC1a channels compared with several types of hippocampal neurons. First, nucleated patch recordings from NG2 cells revealed high density of proton-activated currents. The magnitude of proton-activated current was pH dependent, with a pH for half-maximal activation of 6.3. Second, the current-voltage relationship showed a reversal close to the equilibrium potential for Na+. Third, psalmotoxin 1, a blocker specific for the ASIC1a channel, largely inhibited proton-activated currents. Fourth, Ca2+ imaging showed that activation of proton-activated channels led to an increase of [Ca2+]i. Finally, immunocytochemistry showed co-localization of ASIC1a and NG2 proteins in the hippocampus. Thus the acid chemosensor, the ASIC1a channel, may serve for inducing membrane depolarization and Ca2+ influx, thereby playing a crucial role in the NG2 cell response to injury following ischemia. [ABSTRACT FROM AUTHOR]