氧化型低密度脂蛋白对骨髓内皮前体细胞增殖、凋亡及NO分泌功能的影响

目的:探讨氧化低密度脂蛋白(ox-LDL)对骨髓内皮前体细胞(EPCs)增殖、凋亡及一氧化氮(NO)分泌功能的影响. 方法: 密度梯度离心法获得猪的骨髓EPCs,不同浓度ox-LDL(B组5 mg/L,C组10 mg/L,D组20 mg/L)作用于EPCs,MTT法检测ox-LDL对EPCs增殖能力的影响,流式细胞仪检测ox-LDL对细胞的凋亡率的影响,硝酸还原酶法检测细胞培养液中NO含量的变化,观察ox-LDL对细胞及其功能的影响. 结果: 与对照组相比,ox-LDL抑制EPCs增殖(B组0.189±0.007,C组0.112±0.008,D组0.070±0.008)(n=8),促进EPCs的凋亡(B组18.35±0.08,C组24.22±0.07,D组40.37±0.13) (n=6),损伤细胞的分泌功能,作用随ox-LDL浓度增大而增强(P《0.001). 结论: Ox-LDL抑制EPCs的增殖,损伤细胞分泌功能,促进细胞凋亡,与临床上观察到的冠心患者EPCs数量减少可能有一定的关系.     

补阳还五汤对缺血性脑卒后遗症大鼠神经增殖作用的影响

目的 观察补阳还五汤对缺血性脑卒后遗症大鼠神经增殖作用的影响。方法 采用机械开颅电凝法阻断大脑中动脉24h后,用随机电脉冲刺激仪每天刺激2h,连续刺激20d,造成大鼠缺血性脑卒后遗症模型。治疗组在造模结束后灌服补阳还五汤水煎液,连续给药15d。给药结束后处死大鼠,并取出大脑,处死前均腹腔注射5-溴脱氧核苷尿嘧啶（BrdU）,用免疫组织化学方法检测大鼠脑组织中BrdU的表达。结果 与模型组相比,补阳还五汤治疗组BrdU阳性细胞数量显著增多。结论补阳还五汤对缺血性脑卒后遗症大鼠神经增殖具有促进作用。     

三苯氧胺联合塞来昔布预防大鼠乳腺癌发生的实验研究

背景与目的:三苯氧胺能有效预防乳腺癌的发生,但并非全部有效。多种肿瘤细胞表达环氧化酶-2(cyclooxygenase-2,COX-2),其表达与肿瘤的发生发展有关。本研究观察三苯氧胺联合COX-2选择性抑制剂塞来昔布对化学致癌剂7,12-二甲基苯蒽(7,12-dimethybenzanthracene,DMBA)诱发的大鼠乳腺癌形成的影响。方法:DMBA油剂灌胃制备大鼠乳腺癌模型,每组30只大鼠,分为单纯诱癌组、三苯氧胺组、塞来昔布组和联合药物组4组,观察各组肿瘤发生率、潜伏期、肿瘤数目及体积的差异。结果:(1)乳腺肿瘤发生率三苯氧胺组(48.15%,13/27)、塞来昔布组(50.00%,14/28)低于单纯诱癌组(85.71%,24/28),高于联合药物组(21.43%,6/28);(2)乳腺肿瘤发生时间三苯氧胺组[(97.54±1.85)天]、塞来昔布组[(96.79±2.89)天]晚于单纯诱癌组[(89.50±5.99)天],早于联合药物组[(103.67±3.39)天];(3)乳腺肿瘤数目三苯氧胺组[(1.77±0.73)个]、塞来昔布组[(1.71±0.61)个]小于单纯诱癌组[(3.50±1.62)个],大于联合药物组[(1.17±0.42)个];(4)乳腺肿瘤体积三苯氧胺组[(1.78±0.71)cm3]、塞来昔布组[(2.05±1.04)cm3]小于单纯诱癌组[(6.42±3.96)cm3],大于联合药物组[(0.71±0.96)cm3],且均有统计学意义(均为P<0.05)。结论:塞来昔布和三苯氧胺能抑制DMBA诱发的大鼠乳腺癌的发生、发展,两者联合使用效果更好。     

Bridging the Local Persistence and Long-Range Dispersal of Highly Pathogenic Avian Influenza Virus (HPAIv): A Case Study of HPAIv-Infected Sedentary and Migratory Wildfowls Inhabiting Infected Premises

The past two decades have seen the emergence of highly pathogenic avian influenza (HPAI) infections that are characterized as extremely contagious, with a high fatality rate in chickens, and humans; this has sparked considerable concerns for global health. Generally, the new variant of the HPAI virus crossed into various countries through wild bird migration, and persisted in the local environment through the interactions between wild and farmed birds. Nevertheless, no studies have found informative cases associated with connecting local persistence and long-range dispersal. During the 2016–2017 HPAI H5N6 epidemic in South Korea, we observed several waterfowls with avian influenza infection under telemetric monitoring. Based on the telemetry records and surveillance data, we conducted a case study to test hypotheses related to the transmission pathway between wild birds and poultry. One sedentary wildfowl naturally infected with HPAI H5N6, which overlapped with the home range of one migratory bird with H5-specific antibody-positive, showed itself to be phylogenetically close to the isolates from a chicken farm located within its habitat. Our study is the first observational study that provides scientific evidence supporting the hypothesis that the HPAI spillover into poultry farms is caused by local persistence in sedentary birds, in addition to its long-range dispersal by sympatric migratory birds.     

以肺部超声为应用的多学科诊疗体系在高原性肺水肿诊疗中的价值

目的　探索以肺部超声为应用的多学科诊疗体系在高原性肺水肿诊疗中的价值。方法　选取 2018—2022年在甘孜州稻城县人民医院急诊科收治的 200例疑似高原性肺水肿患者为研究对象,将其中确诊的 115例患 者按照平衡序贯法随机分为试验组（采用以肺部超声为应用的多学科诊疗体系,n=56）和对照组（采用常规诊疗方式, n=59）,比较两组的诊疗效果。结果　在早期诊断高原性肺水肿中,肺部超声的灵敏度、正确指数及阴性预测值均高于X 线检查结果（P<0.05）,而与CT检查结果比较差异无统计学意义（P>0.05）。试验组的诊疗时效性、抗生素使用率、心衰 发生率、无创呼吸机上机率、康复期恢复等方面优于对照组（P<0.05）。结论　以肺部超声为应用的多学科诊疗体系在 高原性肺水肿早期诊断中具有较高的灵敏度、正确指数及阴性预测值,可促进患者愈后及康复。     

Prognostic value of targeted temperature management on outcomes of hanging-induced out-of-hospital cardiac arrest: A nationwide observational study

This study aimed to evaluate the prognostic significance of targeted temperature management (TTM) on hanging-induced out-of-hospital cardiac arrest (OHCA) patients using nationwide data of South Korea.Adult hanging-induced OHCA patients from 2008 to 2018 were included in this nationwide observational study. Patients who assigned into 2 groups based on whether they did (TTM group) or did not (non-TTM group) receive TTM. Outcome measures included survival to hospital discharge and a good neurological outcome at hospital discharge.Among the 293,852 OHCA patients, 3545 patients (non-TTM, n = 2762; TTM, n = 783) were investigated. After propensity score matching for all patients, 783 matched pairs were available for analysis. We observed no significant inter-group differences in the survival to hospital discharge (non-TTM, n = 27 [3.4%] vs TTM, n = 23 [2.9%], P = .666) or good neurological outcomes (non-TTM, n = 23 [2.9%] vs TTM, n = 14 [1.8%], P = .183). In the multivariate analysis, prehospital return of spontaneous circulation (odds ratio [OR], 22.849; 95% confidence interval [CI], 11.479–45.481, P < .001) was associated with an increase in survival to hospital discharge, and age (OR, 0.971; 95% CI, 0.944–0.998, P = .035), heart disease (OR, 16.875; 95% CI, 3.028–94.036, P = .001), and prehospital return of spontaneous circulation (OR, 133.251; 95% CI, 30.512–581.930, P < .001) were significant prognostic factors of good neurological outcome. However, TTM showed no significant association with either outcome.There were no significant differences in the survival to hospital discharge and good neurological outcomes between non-TTM and TTM groups of hanging-induced OHCA patients.     

4例妊娠并存干燥综合征患者的护理

对4例妊娠并存干燥综合征(SS)患者进行心理护理、基础护理和专科护理.结果均顺利分娩,母婴安全,恢复良好,如期出院.提出对妊娠并存SS患者既要考虑到SS的损害,又要考虑到患者的生理变化,采用针对性的心理护理、基础护理和专科护理,使其顺利安全分娩.     

Discovery of a dual-action small molecule that improves neuropathological features of Alzheimer’s disease mice

Alzheimer’s disease (AD) is characterized by complex, multifactorial neuropathology, suggesting that small molecules targeting multiple neuropathological factors are likely required to successfully impact clinical progression. Acid sphingomyelinase (ASM) activation has been recognized as an important contributor to these neuropathological features in AD, leading to the concept of using ASM inhibitors for the treatment of this disorder. Here we report the identification of KARI 201, a direct ASM inhibitor evaluated for AD treatment. KARI 201 exhibits highly selective inhibition effects on ASM, with excellent pharmacokinetic properties, especially with regard to brain distribution. Unexpectedly, we found another role of KARI 201 as a ghrelin receptor agonist, which also has therapeutic potential for AD treatment. This dual role of KARI 201 in neurons efficiently rescued neuropathological features in AD mice, including amyloid beta deposition, autophagy dysfunction, neuroinflammation, synaptic loss, and decreased hippocampal neurogenesis and synaptic plasticity, leading to an improvement in memory function. Our data highlight the possibility of potential clinical application of KARI 201 as an innovative and multifaceted drug for AD treatment.

Alzheimer’s disease (AD) is a multifaceted neurodegenerative disease with underlying pathologies that extend well beyond the widely recognized accumulation of amyloid beta (Aβ). Many studies have demonstrated that memory impairment in AD is driven by the interaction of various pathologic processes, such as cell death (1), impaired synapse plasticity (2), neurogenesis loss (3), autophagy dysfunction (4), vascular abnormalities (5), blood–brain barrier (BBB) damage (6), and systemic inflammation (7). Thus, effective drug development for this disorder must focus on therapeutic strategies that target the complex and multiple neuropathological features in AD.We and others have previously reported that the activity of several sphingolipid-metabolizing enzymes, especially acid sphingomyelinase (ASM), which is encoded by the SMPD1 gene, is abnormally expressed in AD patients and mouse models (8–10). The primary role of ASM is to catalyze the conversion of sphingomyelin, a major component of membranes, into ceramide and phosphocholine (11). The increased ASM activity in the blood and brain of AD mice contributes to various pathological features, including cell apoptosis (12), defective autophagy (8), neurogenesis loss (13), BBB leakage (14), and inflammation (15, 16), suggesting that ASM inhibition could be an important therapeutic target that addresses the neuropathological features of AD (17). Although some studies have previously identified direct or indirect functional inhibitors (17–20) of ASM, these inhibitors have lacked specificity, leading to the potential for off-target effects and unclear potential mechanisms of action in AD. Therefore, there is an important need to develop new compounds that block ASM activity by direct interaction with the enzyme.Here, we identify KARI 201 as a direct, selective, and competitive ASM inhibitor with excellent brain distribution and druggability. Interestingly, we also found an unexpected role of KARI 201 as an agonist of growth hormone secretagogue receptor 1α (GHSR1α, also known as the ghrelin receptor) via GPCR (G protein–coupled receptor) screening based on RNA-sequencing (RNA-seq) analysis in KARI 201–treated AD mice. This activity is critical for hippocampal synaptic physiology and may impact neuropathological features in AD as well (21–23). The dual action in neurons of KARI 201 as a direct ASM inhibitor and GHSR1α agonist led to outstanding, synergetic therapeutic effects in AD mouse models on neuropathological features involving learning and memory impairment. Therefore, our data highlight the possibility of clinical application of KARI 201 as an innovative and multifaceted drug for AD treatment.