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OBJECTIVE Epilepsy is considered a cir-cuit-level dysfunction associated with imbalanced excita-tion-inhibition,it is therapeutically necessary to identify key brain regions and related circuits in epilepsy.The subic-ulum is an essential participant in epileptic seizures,but the circuit mechanism underlying its role remains largely elusive.METHODS Here we deconstruct the diversity of subicular circuits in mouse models of epilepsy.Fiber pho-tometry was used to detect intrinsic activities of subicular PV,SST-positive interneurons and CaMK Ⅱ α-positive pyramidal neurons.Optogenetics and chemogenetics were used to selectively active or inactive subicular neu-rons or their projecting terminals.We also used in vivo and in vitro electrophysiology to record membrane charac-teristics of single neuron in distinct sub-regions of the subiculum.Finally,single pulse test was used to detect synaptic transmission strength between the subiculum and its downstream target.RESULTS First,we found that two majority of subicular interneurons,which inner-vate local pyramidal neurons to constrain their excitability,PV and SST-positive neurons showcase distinct calcium dynamics during hippocampal seizures.This could be attributed to distinct neural inputs from para-hippocampal regions of these two neuronal types.During epileptogen-esis,PV and SST neurons undergo different circuit reor-ganization patterns,that is,remarkable increase of exter-nal input to subicular PV neurons are seen after seizures,while SST cells receive decimated neural input.As their downstream targets,excitatory subicular pyramidal neu-rons are also intrinsically activated during hippocampal seizures.Moreover,we found that the subiculum hetero-geneously controls the generalization of hippocampal sei-zures by projecting to different downstream regions.No-tably,anterior thalamus projecting subicular neurons bidi-rectionally mediate seizures,while entorhinal cortex-pro-jecting subicular neurons act oppositely in seizure modu-lation.These two subpopulations are structurally and functionally dissociable.An intrinsically enhanced hyper-polarization-activated current and robust bursting intensity in anterior thalamus-projecting neurons facilitate synaptic transmission,thus contributing to the generalization of hippocampal seizures.CONCLUSION These results demonstrate that subicular neurons and circuits have diverse roles in epilepsy,suggesting the necessity to pre-cisely target specific subicular circuits for effective treat-ment of epilepsy.
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OBJECTIVE Cognitive deficit is a com-mon comorbidity in temporal lobe epilepsy(TLE)and that is not well controlled by current therapeutics.Currently,how epileptic seizure affects cognitive performance remains largely unclear.The subiculum is the major out-put of the hippocampus,which projects to entorhinal cor-tex and other more distinct brain regions.Physiologically,the subiculum codes spatial working memory and naviga-tion information including place,speed,and trajectory.Importantly,prior studies have noted the importance of the subiculum in the beginning,spreading,and generaliz-ing process of hippocampal seizure.How seizure-activated neurons in subiculum participate in cognitive impairment remains largely elusive.METHODS In this study,we sought to label the subicular seizure-activated c-fos+ neu-rons with a special promoter with enhanced synaptic activity-responsive element E-SARE in the subiculum,combined with chemogenetics and designer receptors exclusively activated by designer drugs(DREADDs),Ca2+ fiber photometry approaches,and behavioral tasks,to reveal the role of these neurons in cognitive impairment in epilepsy.RESULTS We found that chemogenetic inhibi-tion of subicular seizure-tagged c-fos+ neurons(mainly CaMK Ⅱ α+ glutamatergic neurons)alleviates seizure generalization and improves cognitive performance in the hippocampal CA3 kindling TLE model.While inhibition of seizure-labeled c-fos+ GABAergic interneuron shows no effect on seizure and cognition.As a comparison,che-mogenetic inhibition of the whole subicular CaMK Ⅱ α+ neuron impairs cognitive function in na?ve mice in basal condition.Notably,inhibition of subicular seizure-tagged c-fos+ neurons enhances the recruitment of cognition-responsive c-fos+ neurons via increasing neural excitability during cognition tasks.CONCLUSION Our results dem-onstrate that subicular seizure-activated c-fos+ neurons contribute to cognitive impairment in TLE,suggesting sei-zure-tagged c-fos+ neurons as the potential therapeutic target to alleviate cognitive impairment in TLE.
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Coronavirus disease 2019 (COVID-19) has been confirmed to transmit by contact and respiratory droplets, and possibly by aerosols. Medical staff of oral and maxillofacial surgery departments need close contact with head and face of patients during the diagnosis and treatment, and aerosols may be generated during the operation. The risk of infection exposure is high, and the ward management is facing severe challenges. During the COVID-19 epidemic, the diagnosis and treatment in oral and maxillofacial surgery wards should be carried out reasonably after comprehensive assessment of patient condition. We put forward relevant prevention and control measures during the epidemic from the aspects of patient treatment, ward infection prevention and control, supply management, emergency plan, and training of medical staff, so as to provide references for prevention and control of the epidemic in oral and maxillofacial surgery wards.
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Objective Toinvestigatetheinterventionaltreatmentmethodsofbenignesophagealstenosisinchildren,includingballoondilation, stentimplantationandcontinuousballoondilation.Methods 42casesofesophagealstenosisdiagnosedbybariumexaminationinour hospitalfromJanuary2010toJune2017.Accordingtothetreatmentmethods,theyweredividedintoballoondilationgroup(13cases),stent implantationgroup (11cases),continuousballoondilationgroup (18cases),andthecomplicationsandrecurrenceratesofthree methodswerecompared.Results Balloonorstentsweresuccessfullyplacedorremovedinallcases,andtheclinicalsymptomswere significantlyimproved.Therewerenoseriouscomplicationssuchasruptureofesophagus,perforationandmassivehemorrhageI.nballoondilation group,restenosisoccurredin10cases3to10monthsafteroperation,withcomplicationsrateof76.9% andrecurrencerateof76.9%. Instentimplantationgroup,sentfallingoffordisplacedoccurredin4casesandrestenosisin4cases,withthecomplicationsrateof 72.7% andrecurrencerateof36.3%.Incontinuousballoondilationgroup,therewere2casesofballoondescendingand4casesof restenosis,withcomplicationsrateof33.3% andrecurrencerateof22.2%.Comparingthecomplication,theballoondilationgroup>thestentimplantationgroup(χ2=0.056,P>0.05),thestentimplantationgroup>thecontinuousballoondilationgroup(χ2=4.243, P<0 .05 ),the balloon dilation group>the continuous balloon dilation group (χ2=5 .743 ,P<0 .05 ).Co m paring the recurrence rate ,the balloondilationgroup>thestentimplantationgroup(χ2=4.033,P<0.05),thestentimplanationgroup>thecontinuousballoondilationgroup (χ2=0.684,P>0.05),theballoondilationgroup>thecontinuousballoondilationgroup(χ2=9.120,P<0.05).Conclusion There aredifferentincidenceofcomplicationsandrecurrenceinthreemethods,andthecontinuousballoondilationissimplerandlesscomplicationsand recurrencethantheothertwomethods.Itcanbethefirstchoiceforinterventionaltreatmentofesophagealstenosis.
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Pituitary tumors are usually benign but can occasionally exhibit hormonal and proliferative behaviors. Dysregulation of the G1/S restriction point largely contributes to the over-proliferation of pituitary tumor cells. F-box protein S-phase kinase-interacting protein-2 (SKP2) reportedly targets and inhibits the expression of p27(Kip1), a well-known negative regulator of G1 cell cycle progression. In this study, SKP2 expression was found to be upregulated while p27(Kip1) expression was determined to be downregulated in rat and human pituitary tumor cells. Furthermore, SKP2 knockdown induced upregulation of p27(Kip1) and cell growth inhibition in rat and human pituitary tumor cells, while SKP2overexpression elicited opposite effects on p27(Kip1) expression and cell growth. The expression of microRNA-186 (miR-186) was reported to be reduced in pituitary tumors. Online tools predicted SKP2 to be a direct downstream target of miR-186, which was further confirmed by luciferase reporter gene assays. Moreover, miR-186 could modulate the cell proliferation and p27(Kip1)-mediated cell cycle alternation of rat and human pituitary tumor cells through SKP2. As further confirmation of these findings, miR-186 and p27(Kip1) expression were downregulated, while SKP2 expression was upregulated in human pituitary tumor tissue samples; thus, SKP2 expression negatively correlated with miR-186 and p27(Kip1) expression. In contrast, miR-186 expression positively associated with p27(Kip1) expression. Taken together, we discovered a novel mechanism by which miR-186/SKP2 axis modulates pituitary tumor cell proliferation through p27(Kip1)-mediated cell cycle alternation.
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Animals , Humans , Rats , Cell Cycle , Cell Proliferation , Cyclin-Dependent Kinase Inhibitor p27 , Genes, Reporter , Luciferases , Pituitary Neoplasms , Up-RegulationABSTRACT
Objective: To investigate the morbidity of skin diseases in Southern Theater Command, and explore the possible influencing factors. Methods: Fifteen basic units were selected in Southern Theater Command by random sampling. The total sample included 1111 soldiers who aged between 17 to 45 (23.5 ± 4.4) years old, from five services: army, navy, air force, rocket force and logistic service force. A cross-sectional survey was conducted. Questionnaires were sent out one by one, retrieved on the spot, then transferred into EpiData database by double entry. Data were exported from EpiData uniformly and analyzed by SPSS 20.0. Results: 1073 valid questionnaires were retrieved and the effective questionnaire rate was 96.58%. The results showed that the total prevalence of skin diseases in Southern Theater Command was 54.89%. Foot and hand tinea (27.84%, 164/589), prickly heat (23.94%, 141/589), eczema (18.34%, 108/589), paronychia (18.17%, 107/589) and insect bite dermatitis (15.28%, 90/589) were the top five of the constituent ratios in all skin diseases. The prevalence rates in army 65.02% (210/323) and rocket force 61.79% (152/246) were relatively high. According to the multivariate logistic regression analysis, age, services, whether drinking, whether allergic constitution, whether vitamin-deficient, whether washing hands before eating and after toilet, and whether interchanging beds with others might be the possible influencing factors (P<0.05). Conclusions The prevalence rate of skin diseases in Southern Theater Command is still high, with particularly serious situations in the army and the rocket force. To reduce the occurrence of skin diseases effectively, further reinforcement needed in prevention and treatment of skin diseases in military officers and soldiers.
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Objective@#Study the response of GMDTC to cadmium ions and metal ions in vivo to determine whether GMDTC are specifically complexed with cadmium ions to provide a reference for the safety and dfficacy of GMDTC.@*Methods@#Complexometric titration, HPLC and HPLC-MS were applied to research the complexation reaction of GMDTC and various metal ions. The molecular ion peak of GMDTC, GMDTC-Cd complex and GMDTC-Pb complex also detected by LC-MS. Additionally, the initial structure was determined by DFT simulation method.@*Results@#Results of complexometric titration and HPLC detection showed that GMDTC characteristic absorption peak area was proportional to the concentration of itself and there was no color change and peak time change when the GMDTC mixed with Ca2+, Fe2+, Mg2+, Zn2+. However, the color changed to black transition when the GMDTC mixed with Cu2+ and the color changed from yellow precipitate to light yellow transparent transition when GMDTC mix with Hg2+. Moreover, the peak area as well as the retention time has changed a lot which indicated that a chemical reaction has already happened. When the GMDTC mixed with Cd2+ and Pb2+, the color has changed from pale yellow to colorless transparent and the peak area of GMDTC has increased a lot. Finally, the GMDTC-Cd complex ratio both of which are 2:1 were calculated based on the results of LC-MS instrument and atomic calculations.@*Conclusion@#The specific cadmium chelating agent GMDTC can not react with the Ca2+, Fe2+, Mg2+, Zn2+, but it can react chemically with Cu2+ and Hg2+, even specific complex with Pb2+ and Cd2+.
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Rabdosia japonica(Burm.f.) Hara var.glaucocalyx(Maxim.) Hara is a traditional Chinese medicine, and is known to have anti-tumor effects. This study aims to investigate the effect of glaucocalyxin A (GLA), a diterpenoids extracted from Glaucocalyx Hara, on apoptosis of glioma cells and its mechanism. This study investigated the molecular signaling mechanism of GLA-induced glioma cell apoptosis by analyzing survival rate of C6 rat glioma cells, cell morphology, colony formation ability, interference ribonucleic acid, polymerase chain reaction, and Western blot. The result showed that in the presentce of GLA, the survival rate of C6 rat glioma cells decreased significantly, while the expression of guanine nucleotide-exchange factor-H1 was up-regulated, causing phosphorylation of extracellular regulated protein kinases proteins and apoptosis. Hence, the mechanism of GLA-induced glioma cell apoptosis was the GEF-H1/ERK pathway.
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OBJECTIVE: To study the effects of dimethyltin chloride( DMT) on the activity of renal H~+K~+-ATPase( HKA)and Na~+K~+-ATPase( NKA) in SD rats. METHODS: i) In vitro experiment. Five specific pathogen free( SPF) healthy female SD rats were used. The kidney homogenates made with 0. 90% sodium chloride solution was added with DMT( mass concentration,1. 0 g/L) to make final concentrations of 0,1,25,125 and 625 mg/L respectively,then the HKA and NKA activities were detected by the enzyme-linked immunosorbent assay( ELISA). ii) In vivo experiment. Forty SPF healthy SD rats were divided into control group and exposure group,with 20 rats( 10 males and 10 females) in each group. The exposure group was given one-time intraperitoneal injection with DMT( 16. 000 mg / kg body weight),while the control group was given one-time intraperitoneal injection with same volume of 0. 90% sodium chloride solution. The rats were executed 1 and 24 hours after exposure. The kidney tissue was extracted to make kidney homogenates for determination of HKA and NKA activity by microplate reader. The blood from abdominal aorta was collected to measure the levels of serum K~+,Na~+and Cl-. RESULTS: i) In vitro experiment. The HKA activity was inhibited by DMT,and the effect of inhibition increased with the increase of DMT exposure dose( P < 0. 01),showing a dose-effect relationship. The DMT had no effect on NKA activity( P > 0. 05). ii) In vivo experiment. The body weight of rats at 24 hours time point in exposed group was lower than that in control group( P < 0. 01). The HKA activity of the kidney tissue in rats in exposed group was lower than that of control group( P < 0. 01). The NKA activity in kidney tissue of rats and the level serum K~+,Na~+and Cl-did not show statistical difference in main and interactive effects concerning treatment and exposure time( P > 0. 05). CONCLUSION: DMT could inhibit the HKA activity in kidney homogenates,but had no obvious effect on NKA activity.
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Platinum-based anticancer drugs have been becoming one of the most effective drugs for clinical treatment of malignant tumors for its unique mechanism of action and broad range of anticancer spectrum. But, there are still several problems such as side effects, drug resistance/cross resistance and no-specific targeting, becoming obstacles to restrict its expanding of clinical application. In recent years, supramolecular chemistry drug delivery systems have been gradually concerned for their favorable safety and low toxicity. Supramolecular macrocycles-platinum complexes increased the water solubility, stability and safety of traditional platinum drugs, and have become hot focus of developing novel platinum-based anticancer drugs because of its potential targeting of tumor tissues/organs. This article concentrates in the research progress of the new drug delivery system between platinum-based anticancer drugs with three generations of macrocycles: crown ether, cyclodextrin, cucurbituril and calixarene.
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Platinum-based anticancer drugs have been becoming one of the most effective drugs for clinical treatment of malignant tumors for its unique mechanism of action and broad range of anticancer spectrum. But, there are still several problems such as side effects, drug resistance/cross resistance and no-specific targeting, becoming obstacles to restrict its expanding of clinical application. In recent years, supramolecular chemistry drug delivery systems have been gradually concerned for their favorable safety and low toxicity. Supramolecular macrocycles-platinum complexes increased the water solubility, stability and safety of traditional platinum drugs, and have become hot focus of developing novel platinum-based anticancer drugs because of its potential targeting of tumor tissues/organs. This article concentrates in the research progress of the new drug delivery system between platinum-based anticancer drugs with three generations of macrocycles: crown ether, cyclodextrin, cucurbituril and calixarene.
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Humans , Antineoplastic Agents , Pharmacology , Calixarenes , Crown Compounds , Cyclodextrins , Drug Delivery Systems , Macrocyclic Compounds , Pharmacology , Neoplasms , Drug Therapy , Platinum Compounds , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To study the epidemical characteristics of influenza/novel influenza A (H1N1) in Shanxi province from 2009 to 2010, and to provide scientific foundations for predicting and controlling the pandemic outbreak of influenza/novel influenza A (H1N1) effectively.</p><p><b>METHODS</b>All samples were collected from cases that resemble influenza cases in sentinel hospital and influenza outbreak. The influenza were detected by PCR and isolated by MDCK cell culture method. Finally, Shanxi province surveillance data from May, 2009 to April, 2010 of influenza like illness (ILI) cases and pathogen detections were analyzed.</p><p><b>RESULTS</b>In Shanxi province, influenza viruses kept activation in whole year. The predominant pandemic strain in 2009 was novel influenza A (H1N1) virus. The strong peak was around November, 2009 [positive rate: 58.1%, novel influenza A ( H1N1) of the total: 88.1%]. As well, the people infected influenza caused by novel influenza A (H1N1) were mainly under 59-year-old, and the higher positive rates were concentrated in the people from 5-year-old to 24-year-old. In 2010, influenza B (Victoria) viruses were mainly detected from clinical specimens and became the dominant strain.</p><p><b>CONCLUSION</b>Surveillance of Influenza liue illnes, (ILI) and etiology, which can promptly reflect the influenza epidemic situation, play a significant role for understanding epidemic rule of influenza/novel influenza A (H1N1).</p>
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Adolescent , Adult , Aged , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Middle Aged , Age Factors , Influenza A Virus, H1N1 Subtype , Influenza, Human , Virology , Time FactorsABSTRACT
Background and purpose:Proteasome inhibitors such as bortezomib,represent an interesting new class of potential anticancer drugs.In the present study,we explored the sensitivity of ovarian cancer cell line SKOV3 to paclitaxel,proteasome inhibitors and their combination,and also studied the involvement of GSK-3?/Mcl-1 signaling pathway in the regulation of apoptosis induced by those agent.Methods:Methyl thiazolyl tetrazolium (MTT)assay was applied to examine the cell viability,Annexin-V/PI apoptosis detection kit was used to determine the apoptosis rate of different groups,and western blot assay was introduced to evaluate the expression levels of phosphorylated GSK-3?and Mcl-1.Results:In the MTT assay,the cell viability ratios of combination group at serial time points from 12 to 72 hr were(65.2?5.8)%,(58.3?14.4)%,(35.3?5.0)%,(19.2?1.5)% and(11.4?2.5)%,and there were significant differences as compared to the treatment of paclitaxel alone(P