Resveratrol (RES), a natural polyphenolic phytochemical, has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer's disease (AD) by the activation of sirtuin 1 (Sirt1/Sir2). In this study, we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in a Drosophila model by overexpression of amyloid precursor protein (APP), whose duplications and mutations cause familial AD. We found a mild but significant transcriptional increase of Drosophila Sir2 (dSir2) by RES supplementation for up to 17 days in APP flies, but not for 7 days. RES and dSir2 almost completely reversed the sleep and memory deficits in APP flies. We further demonstrated that dSir2 acts as a sleep promotor in Drosophila neurons. Interestingly, RES increased sleep in the absence of dSir2 in dSir2-null mutants, and RES further enhanced sleep when dSir2 was either overexpressed or knocked down in APP flies. Finally, we showed that Aβ aggregates in APP flies were reduced by RES and dSir2, probably via inhibiting Drosophila β-secretase (dBACE). Our data suggest that RES rescues the APP-induced behavioral deficits and Aβ burden largely, but not exclusively, via dSir2.
Animals ; Alzheimer Disease/metabolism* ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor/metabolism* ; Drosophila/physiology* ; Drosophila Proteins/metabolism* ; Resveratrol/pharmacology* ; Sirtuin 1 ; Sleep

【Objective】 To investigate the mechanism of pristane inducing autophagy in macrophages. 【Methods】 Pristane was used to stimulate NR8383， a rat macrophage cell line. The changes in signaling pathways of AMPK， mTOR， and endoplasmic reticulum （ER） stress pathways including eIF2α and IRE1α in the cell model， as well as the expression of transcriptional factor TFEB and its translocation to the nucleus， were detected by using Western blotting. ER stress pathways were intervened by using an inducer DTT or an inhibitor 4-PBA to determin its effect on mTOR expression and autophay. 【Results】 In pristane-stimulated NR8383 cell model， ER stress pathway eIF2α was activated at 0.5 h after stimulation， and then mTOR expression was decreased at 1 and 3 h after stimulation. There was no change for AMPK and IRE1α pathways. With 4-PBA treatment， pristane-reduced mTOR expression and increased LC3-II were reversed， while with DTT treatment， mTOR expression decreased and LC3-II expression increased even more. Pristane induced the expression and activation of TFEB in NR8383 cells. 【Conclusion】 Pristane induces ER stress and leads to autophagy enhancement in rat macrophages.

Objective:To analyze the clinical characteristics of adult Chinese patients with syncope.Methods:This is a cross-sectional survey study. Patients with preliminary diagnosis of syncope in the Emergency Department, Geriatrics and Cardiology Outpatient Department, or Syncope Unit of 37 hospitals in 19 provinces, autonomous regions and the Hong Kong Special Administrative Region from June 2018 to March 2021 were included in this study. The clinical features of these patients with syncope were analyzed.Results:A total of 4 950 consecutive patients with syncope were included in this study. The age was (56.3±16.8)years, and 2 604 cases (52.6%) were male. The most common type of syncope was neurally mediated syncope (2 345 (47.4%)), followed by cardiac syncope (1 085 (21.9%)), orthostatic hypotensive syncope (311 (6.3%)), and unexplained syncope accounted for nearly one third (1 155 (23.3%)). Predisposing syncope was more common in patients under 65 years of age(2 066(72.4%) vs. 786(27.6%),χ 2=136.5, P<0.001). Presyncope was more common in patients with neurally mediated syncope (1 972(79.0%) vs.1 908(73.9%), χ 2=17.756, P<0.001). Premonitory symptoms were more common in women(1 837(80.0%) vs. 1 863(73.0%),χ 2=33.432, P<0.001). Presyncope syndrome was more common in patients under 65 years of age (2 482(77.8%) vs. 1 218(73.4%),χ 2=17.523, P=0.001). Cyanosis was more common in ≥65 years old patients (271(18.2%) vs. 369(12.7%), χ 2=23.235, P<0.001). Urinary incontinence was more common in old patients aged ≥65 years(252(15.2%) vs. 345(10.8%), χ 2=19.313, P<0.001). Family history was more common in patients with cardiogenic syncope compared with other types of syncope (264(24.3%) vs. 754(19.5%), χ 2=11.899, P=0.001). Hypertention(1 480(30.5%)), coronary heart disease(1 057(21.4%)), atrial flutter and atrial fibrillation(359(7.2%)), second degree atrioventricular block(236(4.8%)) were common complications of syncope. The proportion of patients with coronary heart disease was significantly higher in cardiac syncope than that of other types of syncope(417(38.4%) vs. 640(16.6%), χ 2=241.376, P<0.001). Other common complications included cerebrovascular diseases (551 (11.1%)) and diabetes mellitus (632(12.8%)). Conclusions:Neurally mediated syncope is the most common syncope in adult Chinese population. Patients with predisposing conditions and premonitory conditions are younger. Presyncope is more common in women. The proportion of family history and coronary heart disease is higher in patients with cardiogenic syncope.

OBJECTIVE：To study ongoing change characteristics of the contents of syringin and total flavonoids in different medicinal parts （root bark ，tree bark ，leaf）of Toricellia angulata from Guizhou ，and to provide reference for the development and application of T. angulata . METHODS ：The root bark ，tree bark and leaf parts of T. angulata during different harvesting periods （Jan.-Dec.） were taken as the research samples. The content of syringin was determined by HPLC. The determination was performed on Agela Promosil C 18 column with mobile phase consisted of 0.5％ phosphoric acid solution-acetonitrile （gradient elution）at the flow rate of 1.0 mL/min. The detection wavelength was set as 210 nm，and column temperature was 35 ℃. The sample size was 5 μL. The content of total flavonoids was determined by UV-visible spectrophotometry under detection wavelength of 510 nm. RESULTS ：The linear range of syringin and total flavonoids were 0.095 9-1.150 8 mg/mL（r＝0.999 6）and 0.072 2- 1.083 0 mg/mL（r＝0.999 9），respectively. RSDs of precision ，stability and repeatability tests were all less than 3％（n＝6）. The average recoveries were 101.74％（RSD＝2.36％ ，n＝6）and 99.63％（RSD＝2.19％ ，n＝6），respectively. During different harvesting periods ，the contents of syringin in root bark ，tree bark ，leaf of T. angulata collected on Aug. ，May and Sept. were the highest，and the contents of total flavonoids in samples collected on Feb. ，Dec. and Sept. were the highest. The contents of syringin in different medicinal parts of T. angulata were in descending order as follows as tree bark ＞root bark ＞leaf，and the content of syringin was commonly relatively high in tree bark part ；the content of total flavonoids in different medicinal parts of T. angulata were in descending order as follows as root bark ＞tree bark ＞leaf，and the contents of total flavonoids in three medicinal parts was generally low. The content of total flavonoids in root bark was the highest in Feb. of that year ，and the content of syringin in root bark at same month was second only to Aug. of that year ；the content of syringin in tree bark was the highest in May ，and the content of total flavonoids in tree bark at same month was second only to Oct. and Dec. of that year ；the contents of total flavonoids and syringin in leaf were the highest in Sept. of that year. CONCLUSIONS ：It is suggested that Feb. is the best time for harvesting root bark ，May for tree bark and Sept. for leaf of T. angulata .

Objective: To preliminarily investigate the effect of intraoperative goal-directed fluid management (GDFM) on pulmonary function and oxygen dynamics in patients with severe burns. Methods: From February 2017 to May 2018, 30 patients admitted to Burn Department of our hospital with severe burns who met the criteria for inclusion and needed escharectomy and skin grafting were enrolled in this prospective randomized controlled trial. The patients were divided into group GDFM of 15 cases [14 males and 1 female, (45±14) years old] and conventional liquid management group of 15 cases [12 males and 3 females, (42±10) years old] according to the random number table. During escharectomy and skin grafting, volume of patients in group GDFM was managed according to the GDFM scheme, based on cardiac output index, stroke volume variation, stroke volume index, hemoglobin, central venous oxygen saturation (ScvO₂), and other parameters; volume of patients in conventional liquid management group was managed according to clinical experience and conventional liquid management scheme, based on mean arterial pressure, central venous pressure, urine output, hemoglobin, and other parameters. At post operation hour (POH) 1, 6, 12, and 24, arterial and venous blood was collected from patients of the two groups to determine the levels of extravascular lung water index (ELWI), global end-diastolic volume index (GEDI), oxygenation index, ScvO₂, central venous-to-arterial blood carbon dioxide partial pressure difference (Pcv-aCO₂), lactic acid, pH value, bicarbonate ion, and base excess routinely. Data were processed with Fisher′s exact probability test, t test, analysis of variance for repeated measurement, and least significant difference test. Results: (1) The ELWI of patients in group GDFM was (4.3±1.1) mL/kg at POH 1, which was significantly lower than (6.5±3.6) mL/kg in conventional liquid management group (t=2.26, P<0.05). The ELWI levels of patients in group GDFM at POH 6, 12, and 24 were (6.8±2.2), (6.6±2.0), and (6.9±1.6) mL/kg, respectively, significantly higher than the level at POH 1 within the same group (P<0.01), and similar to (8.5±3.1), (7.8±2.3), and (8.0±3.5) mL/kg in conventional liquid management group (t=1.73, 1.53, 1.10, P>0.05). The GEDI levels between patients of the two groups were similar, and there was no significantly statistical difference between the two groups as a whole (treatment factor main effect F=2.35, time factor main effect F=0.44, interaction F=0.07, P>0.05). (2) The oxygenation index of patients in group GDFM was (350±78) mL/kg at POH 1, which was significantly higher than (259±109) mL/kg in conventional liquid management group (t=2.63, P<0.05). In conventional liquid management group, the oxygenation index of patients at POH 6 was significantly higher than that at POH 1, 12, or 24 (P<0.01). The ScvO₂ levels of patients in group GDFM at POH 1, 6, and 12 were 0.516±0.105, 0.679±0.121, and 0.713±0.104, respectively, which were significantly higher than 0.382±0.194, 0.545±0.194, and 0.595±0.191 in conventional liquid management group (t=2.35, 2.27, 2.10, P<0.05). The ScvO₂ levels of patients in the two groups at POH 6, 12, and 24 were significantly higher than those levels at POH 1 within the same group (P<0.01), and the ScvO₂ of patients in conventional liquid management group at POH 24 was significantly higher than that at POH 6 or 12 within the same group (P<0.05 or P<0.01). The Pcv-aCO₂ levels of patients in group GDFM were significantly lower than those in conventional liquid management group at POH 1 and 6 (t=2.55, 2.71, P<0.05). The Pcv-aCO₂ of patients in group GDFM at POH 12 was significantly lower than that at POH 6 or 24 within the same group (P<0.05). (3) The blood lactic acid levels and pH values between patients of the two groups were similar at POH 1, 6, 12, and 24 (t=0.89, 0.19, 0.26, 0.23; 1.55, 0.71, 0.77, 0.77, P>0.05). In conventional liquid management group, the blood lactic acid levels of patients at POH 6, 12, and 24 were significantly lower than the level at POH 1 within the same group (P<0.05), and the pH values of patients at POH 6, 12, and 24 were significantly higher than the value at POH 1 within the same group (P<0.05). The levels of bicarbonate ion and base excess between patients of the two groups were similar, and there were no significantly statistical differences between the two groups as a whole (treatment factor main effect F=0.06, 0.11, time factor main effect F=2.07, 1.59, interaction F=1.45, 0.91, P>0.05). Conclusions GDFM is helpful to improve the pulmonary function and oxygen dynamics in patients with severe burns in the short term after escharectomy and skin grafting. It has certain significance in preventing and reducing pulmonary edema and pulmonary complications in patients with severe burn after operation.

Objective To assess and compare the incidence,clinical characteristics,treatment,and prognosis of acute heart failure patients from different grades hospitals in Beijing.Methods In this prospective internet prognosis registered study (Beijing AHF Registry),a total of 3 335 consecutive patients admitted to 14 emergency departments in Beijing from January 1st 2011 to September 23rd 2012 were enrolled.According to hospital grade,these patients were divided into two groups,349 patients were from secondary hospitals,and 2 956 patients were from tertiary hospitals.Results Among the 3 335 patients,the medium age was 71 (58,79) years,and male accounted for 53.16％.The most common underlying disease were coronary disease (43.27％),hypertension (17.73％),cardiomyopathy (16.07％) etc.The average treatment time in Emergency Department was 66.82 h.The emergency department mortality rate was 3.81％ (127 cases).The 30-day and 1-year cumulative all-cause mortality were 15.3％ and 32.27％,respectively.The 30-day and 1-year cumulative all-cause readmission were 15.64％ and 46.89％,respectively.Compared with patients in tertiary hospitals,patients in secondary hospitals had more onset acute heart failure patients (63.64％ vs.49.93％),shorter emergency department treatment time (12 h vs.41 h),lower discharge rate (3.43％ vs.37.45％) and emergency department mortality(1.58％ vs.4.09％).Compared with those in tertiary hospitals,1-year cumulative all-cause mortality (25.6％ vs.33.2％),cardiovascular disease mortality (20.2％ vs.26.0％),aggravated heart failure mortality (22.4％ vs.28.8％) were lower in secondary hospitals.Following propensity score matching,compared to tertiary hospitals,patients in secondary hospitals showed lower utilization rate of beta-blockers and ACEFARB (4.51％ vs.28.17％,1.41％ vs.9.58％),except the pironolactone.Conclusion Acute heart failure in emergency department is associated with a high mortality rate and readmission rate.There is still a big gap between guidelines recommend medication current treatments for acute heart failure.

Objective To detect the changes of G protein-coupled inwardly rectifying potassium channels (GIRK)expression in allergic asthma model and identify the regulatory factors.Methods The E3 rat asthma models were induced by challenge with ovalbumin 14 days after immunization with ovalbumin and aluminium adjuvant.The asthma models were evaluated based on changes in lung pathomorphology and total IgE levels.The levels of GIRK1-4 mRNA and protein were detected using real time-PCR and Western blot.The anatomic sites where GIRK was expressed dominantly in the lung were identified using immunohistological staining.To identify the effects of IL-4 on the expressions of GIRK channels,GIRK 1 -4 mRNA and protein in IL-4 stimulated bronchial epithelial cell line A549 were detected by RT-PCR and Western blot.Results The levels of GIRK1-4 mRNA and protein decreased significantly in the lung in asthmatic E3 rats.The results of immunohistological staining showed that GIRK channels were dominantly expressed in airway epithelia in the lung.The levels of GIRK 1-4 mRNA and protein were down-regulated in time-and dose-dependent manners in IL-4 treated A549.Conclusion IL-4 down-regulates the expression levels of GIRK subunits in bronchial epithelia during allergic asthma.

Objective Gastrointestinal stromal tumor( GIST) is a rare mesenchymal tumor from gastroin-testinal tract,and surgery remains the only curative treatment.In order to improve the outcome of surgical treat-ment,reduce the risk of surgery,and increase the quality of life,preoperative imatinib( IM) treatment for GIST is investigated.Methods We retrospectively studied the multidisciplinary team model treatments for 8 GIST cases receiving preoperative IM treatment.The cases were prescribed IM of 400 mg daily for 12 to 40 weeks and exten-sively followed until surgery was considered feasibleg.The clinical significance and safety profile were analyzed. Results Partial responsive rate was 62.5% in this study.There was no intolerable sever adverse effects by IM preoperative treatment.All the cases received R0 dissection,with no intraoperative tumor rupture.The postopera-tive recovery was satisfied.Conclusion IM preoperative treatment brings significant clinical benefit to large stomach GISTs and cardiac region GISTs.The preoperative treatment should be monitored carefully under a multi-disciplinary team.Preoperative IM treatment is an evocative treatment strategy for high risk GIST.

Objective to investigate the application of the whole course case tracking method in continuous improvement of nursing quality of out-patient operation unit. Methods Administration frames were established for this project,such as monitoring group and executive group. the medi-cal treatment procedure and patients′experience were followed by referees. the results were quantified for statistical analysis. the problems were rec-ognized by priorities and rectification was correspondingly performed. Afterward,another group of patients were traced to evaluate the results of the rectification. We focus on those items of lower scores and undertook rectifications accordingly. Particularly,we optimized signs in outpatient unit, made pamphlets to clarify the procedures,and were cautious to provide more easy-to-understand informs. Results By the second round evaluate, these scores were effectively improved. Especially,the item of“clear informed consent”was statistically significant(P = 0.003). Meanwhile,the team of outpatient operation unit became more cohesion,with enhanced service consciousness,and was initiative to improve the work. Conclusion the whole course case tracking method is feasible for short-range medical service evaluation such as outpatient surgery. the evaluation results clarify the direction for quality improvement,thus set the starting point of quality management aiming at continuously improvement of the patients′ experi-ence and quality of nursing service.

Objective To evaluate the prognestic effect of thrombus aspiration combined tirofiban in patients of acute myocardial infarction. Methods 372 patients with acute ST segment elevation myocardial infarction were randomly divided into the observation group (n=183) and the control group (n=189). Patients in the observation group received thrombus aspiration combined tirofiban additional to conventional treatment, and cases in the control group received routine treatment. The curative effect, postoperative complications and adverse reactions were compared between the 2 groups. Results The postoperative TIMI classⅢperfusion was achieved in 152 cases (83.1%) in the observation group and 140 cases (74.1%) in the control group (P < 0.05). The left heart ejection fraction of the observation group on 7 and 30 days after surgery was (60.4±6.1)%and (64.3±5.6)%respectively which was higher than the control group with (52.4±5.9)% and (55.4±5.7)% on 7 and 30 days respectively (P < 0.05). Bleeding events were recorded in 36 cases(19.7%) in the observation group rensus 26 versus (13.8%) in the control group (P>0.05). MACE reorded within 30 d post operation was 10 cases(5.5%) in the observation group and 22 cases (11.6%) in the control group (P < 0.05). No thrombocytopenia recorded in both groups. Conclusions Thrombus aspiration combined tirofiban for patients with acute myocardial infarction during PCI can improve the postoperative coronary artery perfusion, left ventricular ejection function and reduce the incidence of MACE within 30 days.