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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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Fluorescence-guided surgery (FGS) with tumor-targeted imaging agents, particularly those using the near-infrared wavelength, has emerged as a real-time technique to highlight the tumor location and margins during a surgical procedure. For accurate visualization of prostate cancer (PCa) boundary and lymphatic metastasis, we developed a new approach involving an efficient self-quenched near-infrared fluorescence probe, Cy-KUE-OA, with dual PCa-membrane affinity. Cy-KUE-OA specifically targeted the prostate-specific membrane antigen (PSMA), anchored into the phospholipids of the cell membrane of PCa cells and consequently showed a strong Cy7-de-quenching effect. This dual-membrane-targeting probe allowed us to detect PSMA-expressing PCa cells both in vitro and in vivo and enabled clear visualization of the tumor boundary during fluorescence-guided laparoscopic surgery in PCa mouse models. Furthermore, the high PCa preference of Cy-KUE-OA was confirmed on surgically resected patient specimens of healthy tissues, PCa, and lymph node metastases. Taken together, our results serve as a bridge between preclinical and clinical research in FGS of PCa and lay a solid foundation for further clinical research.
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【Objective:】 Evaluating the service quality and medical experience of elderly-friendly medical institutions from the perspective of elderly patients and their accompanying relatives and friends is a specific measure and work focus to promote the construction of elderly-friendly medical institutions, optimize the medical procedures for the elderly, solve the intelligent technology difficulties encountered in the medical process for the elderly, promote public hospitals to fully implement preferential policies for elderly medical services, and continuously improve the health and well-being of the elderly. 【Methods:】 Based on literature analysis and expert consultation, the satisfaction evaluation indicators for elderly-friendly medical institutions were formed. The Analytic Hierarchy Process was used to assign weights to the indicators. And then, the satisfaction evaluation index system for elderly-friendly medical institutions was formed. 【Results:】 After two rounds of Delphi method, and the scoring and demonstration of 15 experts, four primary indicators and 21 secondary indicators were finally formed, and then, assigned weight coefficients to them through analysis. 【Conclusion:】 After the expert demonstration, the satisfaction evaluation system for elderly-friendly medical institutions has good reliability and validity, providing the basis for the construction of elderly-friendly medical institutions and contributing to the formation of a sustainable, systematic, and diversified elderly-friendly service system.
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Objective:To investigate the clinical effect of the first dorsal metatarsal-dorsal phalangeal artery flap in repairing large area of soft tissue defect on the palmar side of finger.Methods:From February, 2016 to June, 2018, 11 fingers of 11 patients (7 males and 4 females, aged 19-46 years old with an average of 32.5 years old) with large area of soft tissue defect on the palmar side of the finger were repaired with the first dorsal metatarsal-dorsal phalangeal artery flap. These included 3 with the first dorsal metatarsal-first dorsal phalangeal artery blood supply, and 8 with the first dorsal metatarsal-second dorsal phalangeal artery blood supply. In which 3 with retained finger pulp was for repairing the defects and bridging arteries, including 1 flexor tendon defect repaired by the extensor digitorum brevis tendon of the second toe with the flap. The type of blood vessel was Gilbert I detected by CDU before surgery. The area of the flaps was from 1.5 cm×5.0 cm to 3.0 cm×8.0 cm. The donor area of the flaps was compressed with full thickness skin grafts of the shank. The follow-up data was collected by outpatient clinic visits and telephone interviews.Results:All the 11 flaps survived and were followed-up for an average of 14 months, ranged from 6 months to 24 months. The colour and texture of the flaps were good. Sensing of temperature, pain and touch restored, without swelling. Function of the fingers was well restored. The range of motion of distal and proximal interphalangeal joints was closed to normal. The TPD of the flaps was 5-11 mm, with an average of 8 mm. Ten had primary wound healing in the donor sites of foot. One case had necrosis of the proximal toe of the skin graft and healed after dressing change. Long-term follow-up of the skin grafting area was wear-resistant, and does not hinder walking without rupture.Conclusion:Application of the first dorsal metatarsal-dorsal toe artery flap to repair large area of soft tissue defect on the palmar side of finger has number of advantages such as it, covers the wound and carry the tendons, bridges the arteries at the same time, plus delivers satisfactory outcome.
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Objective@#To explore the application and effect of using the lateral second toe flap transfer for reconstruction of great toe defect.@*Methods@#The flap on tibial of second toe was designed according to the size of defect. The pedicle of the flap is the tibial proper plantar digital artery of the toe, and the rotation point is located between the toe web.13 cases of the great toe′s defects were repaired by this method, with the donor sites covered by full thickness skin from the leg.@*Results@#13 flaps survived postoperatively. All cases were subject to postoperative follow-up, follow-up time was 6-48 months, an average of 18 months. Skin color and texture was close to that of the surrounding tissues, appearance is not bloated.@*Conclusions@#The second toe lateral skin flap is easy to operate, is flexible for rotating. As local material, it is an ideal skin flap to repair the great toe defect.
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Objective To explore the application and clinical effect of blood bridge venous flap in finger wound with proper palmar digital artery defect. Methods From February,2007 to September,2016,11 cases of fin-ger wound with artery defect were repaired with forearm vein free flap by the way of bridging blood vessels. The time from injury to surgery was 1.5 to 6 hours(average 2.5 hours).Vascular defect length was 1.4 to 3.4 cm(average 2.3 cm). 8 cases were bridged the unilateral digital artery and 3 cases were bridged the both side. The area of skin flap was 1.5 cm × 2.0 cm to 2.2 cm × 3.5 cm and the donor site was sutured directly. Results One case appeared necrosis in marginal part and healed after dressing change. The other flaps and finger survived and the incisions healed well.All the 11 cases were followed up after operation. The follow-up time ranged from 6 to 20 months, aver-aged 10 months. The color and texture were well,the sensation of temperature, pain and tactile were recovered, and the flap had good contour. According to TAM system evaluation method: 6 cases got excellent results,4 cases were good,1 case was poor. The donor site only had a linear scar and the flexion and extension of wrist were not limited. Conclusion Flow bridging venous flap can reconstruct the finger blood and repair the wound simultaneously. To the finger with nerve or tendon defect,bridged with the cutaneous nerve or palmaris longus tendon can also get satisfactory result.
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A five-step synthetic method of ambrisentan starting from benzophenone was developed.The reaction methods of resolution and substitution were optimized.A stable,facilitating method of detection and efficient resolution reagent,L-phenylglycinamide,was used and helped to obtain highly optical pure intermediates.In the substitution reaction,NaOH was chosen as the base,which is safe and suitable for the industry.This method was mild,easily operated with a total yield up to 31.0％,and may have a good application prospect.
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To assess the value of echocardiography for detection of the flow-dependent epicardial coronary vasodilation, the changes in internal diameter of the left anterior descending coronary arteries (LAD) induced by reactive hyperemia were studied by echocardiography in 12 health anesthetized open-chest dogs. Reactive hyperemia was induced by brief occlusion of the left anterior descending coronary artery for 30 s followed by rapid release. The two- dimensional images of the left anterior descending coronary artery before and after reactive hyperemia with and without intracoronary infusion of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase(NOS) were investigated. The internal diameter of LAD was measured and its percent change induced by reactive hyperemia was calculated. Our results showed that the internal diameter of LAD was 2.23±0.19 mm before intracoronary infusion of L-NAME (baseline). The internal diameter of LAD significantly increased to 2.52±0.24 mm (P＜0.01) after reactive hyperemia at baseline, and the percent change in internal diameter of LAD was (13. 10±3.59) %. The internal diameter of LAD before and after reactive hyperemia under the condition of intracoronary infusion of L-NAME was not different from that before reactive hyperemia at baseline. The percent change in internal diameter of LAD was (1.07±2.97) %, and it was significantly lower than that at baseline (P＜0.001). We are led to conclude that the change in internal diameter of LAD responding to reactive hyperemia was detected sensitively by echocardiography, and this change was associated with endothelium-derived nitric oxide.
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Objective To determine whether endogenous endothelin(ET) plays a role in the echocardiographic evaluation of the flow-dependent epicardial coronary vasodilation induced by reactive hyperemia(RH) after blockade of nitric oxide(NO) formation. Methods In six anesthetized open-chest dogs, changes in internal diameter of the left anterior descending coronary artery(LAD) induced by RH were investigated via echocardiography before intracoronary infusion of GN-nitro-L-arginine methyl ester(L-NAME), after blockade of NO formation by L-NAME, and after L-NAME plus intracoronary infusion of BQ-123, an ETA receptor blocker.Results Before intracoronary infusion of L-NAME, the diameter of LAD increased significantly from((2.24)?(0.21))mm to ((2.51)?(0.23))mm (P