基于网络药理学的济脉通片降压机制研究

目的 采用网络药理学阐明济脉通片多成分-多靶点-多途径的作用理念，为进一步研究济脉通片降压药效物质基础和机制提供一定理论参考。方法 通过TCMSP数据库，结合口服利用度（≥ 30%）和类药性分析（≥ 0.18）参数，筛选济脉通片的活性成分；通过Drugbank和TCMSP数据库进行靶点预测分析；通过GENCARD数据库筛选出高血压疾病相关基因；结合DAVID和KEGG数据库进行GO分析和通路分析；使用Cystoscope软件构建"化合物-靶点-作用通路"网络图。结果 经筛选后得到济脉通片的33个化合物，148个潜在靶基因并映射到了223条信号通路，其中31条信号通路与高血压的发生发展密切相关，其中AGE-RAGE signaling pathway in diabetic complications、PI3K-Akt signaling pathway、TNFsignaling pathway、Adrenergic signaling in cardiomyocytes和Focal adhesion为重要的通路枢纽。结论 济脉通片主要通过多成分、多靶点、多通路调节血管内皮功能、炎症反应、钙钠离子转运、糖脂代谢等参与血管舒张、改善炎症、调节机体代谢、调节离子转运等而产生降压作用。     

Predator stress-induced depression is associated with inhibition of hippocampal neurogenesis in adult male mice

Stress has been suggested to disturb the 5-hydroxytryptamine system and decrease neurogenesis, which contribute to the development of depression. Few studies have investigated the effect of predator stress, a type of psychological stress, on depression and hippocampal neurogenesis in adult mice; we therefore investigated this in the present study. A total of 35 adult male Kunming mice were allocated to a cat stress group, cat odor stress group, cat stress + fluoxetine group, cat odor stress + fluoxetine group, or a control group(no stress/treatment). After 12 days of cat stress or cat odor stress, behavioral correlates of depression were measured using the open field test, elevated plus maze test, and dark-avoidance test. The concentrations of hippocampal 5-hydroxytryptamine and 5-hydroxyindoleacetic acid were measured using high-performance liquid chromatography-electrochemical detection. Neurogenesis was also analyzed using a bromodeoxyuridine and doublecortin double-immunostaining method. Cat stress and cat odor stress induced depression-like behaviors; this effect was stronger in the cat stress model. Furthermore, compared with the control group, cat stress mice exhibited lower 5-hydroxytryptamine concentrations, higher 5-hydroxyindoleacetic acid concentrations, and significantly fewer bromodeoxyuridine+/doublecortin+-labeled cells in the dentate gyrus, which was indicative of less neurogenesis. The changes observed in the cat stress group were not seen in the cat stress + fluoxetine group, which suggests that the effects of predator stress on depression and neurogenesis were reversed by fluoxetine. Taken together, our results indicate that depression-like behaviors induced by predator stress are associated with the inhibition of hippocampal neurogenesis.     

延安地区泌尿系结石成分分析的研究

目的利用红外光谱法测定延安大学附属医院泌尿外科手术获得的泌尿系结石成分,探讨延安地区泌尿系结石成分与年龄、性别等关系,比较上、下尿路结石成分特点,分析延安地区泌尿系结石发生的流行病学情况,为临床制定有效的个体化治疗及预防措施提供参考依据。方法收集2013年1月至2017年1月在延安大学附属医院泌尿外科治疗1984例尿路结石患者的年龄、性别、结石部位等临床资料,对比分析延安地区泌尿系结石在不同年龄、不同性别、不同解剖部位的分布特点。结果在1984例泌尿系结石的患者中,按每10岁年龄大小分组排序,统计各年龄阶段泌尿系结石发病情况,男性患者有1346例,女性患者有638例,男性年龄(50.23±14.48)岁,女性年龄(47.87±14.51)岁,男、女患者比例约2.11∶1。在66~75岁年龄段,尿路结石发病率性别差异具有统计学意义(P<0.05)。结石成分以混合性结石为主,以混合性结石为主,共1582例,占79.76%。其中1665例(83.92%)为上尿路结石,上、下尿路结石的比例为5.22∶1,其余为肾结石合并膀胱结石。上尿路结石中男性1062例,女性603例,男女比例为1.76∶1;下尿路结石中男性284例,女性35例,男女比例为8.11∶1。青壮年(年龄≤45岁)泌尿系结石患者草酸钙为主结石、感染性结石多见;中老年(年龄>45岁)泌尿系结石者草酸钙为主结石、尿酸类结石多见。感染性结石患者性别差异具有统计学意义(P<0.05)。结论在延安地区男性较女性更容易患泌尿系结石。同时,不同年龄段结石构成成分具有差异。对于年龄≤45岁患者,主要以草酸钙为主结石、感染性结石多见,这与结石整体发病率基本一致;而对于年龄>45岁患者,主要以草酸钙为主结石、尿酸性结石多见。表明对于不同年龄段的结石患者,可以根据上述结果在结石的预防和治疗上综合考量,给予明确而更加合理的治疗。     

Molecular profiling of Chinese R-CHOP treated DLBCL patients: Identifying a high-risk subgroup

Diffuse large B-cell lymphoma (DLBCL) is a clinically aggressive and heterogenous disease. Although most patients can be cured by immunochemotherapy, 30% to 40% patient will ultimately develop relapsed or refractory disease. Here, we investigated the molecular landscapes of patients with diverse responses to R-CHOP. We performed capture-based targeted sequencing on baseline samples of 105 DLBCL patients using a panel consisting of 112 lymphoma-related genes. Subsequently, 81 treatment-naïve patients with measurable disease and followed for over 1 year were included for survival analysis. Collectively, the most commonly seen mutations included IGH fusion (69%), PIM1(33%), MYD88 (29%), BCL2 (29%), TP53 (29%), CD79B (25%) and KMT2D (24%). Patients with TP53 mutations were more likely to have primary refractory disease (87.0% vs 50.0%, P = .009). For those with TP53 disruptive mutations, 91.7% patients were in the primary refractory group. Interestingly, BCL-2 somatic hypermutation was only seen in patients without primary refractory disease (P = .014). In multivariate analysis, BCL-2 amplification (hazard ratio [HR] = 2.94, P = .022), B2M mutation (HR = 2.99, P = .017) and TP53 mutation (HR = 3.19, P < .001) were independently associated with shorter time to progression (TTP). Furthermore, TP53 mutations was correlated with worse overall survival (P = .049). Next, we investigated mutation landscape in patients with wild-type (WT) TP53 (n = 58) and found that patients harboring MYD88 L265P had significantly inferior TTP than those with WT or non-265P (P = .046). Our study reveals the mutation spectrum of treatment-naive Chinese DLBCL patients. It also confirms the clinical significance of TP53 mutations and indicates the prognostic value of MYD88 L265P in TP53 WT patients.     

Advantages of Anti-Inflammatory Acupuncture in Treating Sepsis of Coronavirus Disease 2019

Background: Sepsisis one of the mostserious complications and a leading cause of death in patients with coronavirus disease 2019 (COVID-19). In general, it isthe result of an unregulated inflammatory cascade such as a postinfection “cytokine storm.” The conventional treatment mainly relies on glucocorticoids, of which curative effects are not ideal, as they come with significant side effects. It is critical to seek or develop other effective therapeutics in dealing cytokine storm to fight COVID-19 with sepsis. Aims and Objectives: Raise awareness of the significance applying anti-inflammatory acupuncture in dealing COVID-19 patients with sepsis and provide an appropriate acupuncture protocol that can be easily integrated into existing medical guideline. Materials and Methods: Current evidences from animal experiments and clinical trials about acupuncture in treating infectious sepsis are reviewed, and a detailed discussion on advantages of anti?inflammatory acupuncture is followed, then the rationality on the point selection and stimulation parameters of acupuncture is analyzed to propose an appropriate acupuncture protocol. Results: Current experiments have shown that acupuncture can play a significant role to improve inflammation reaction and reduce mortality in infectious animal and patients with sepsis and its mechanisms are mainly achieved by stimulating the vagus?cholinergic anti?inflammatory pathways.Applying acupuncture in treating COVID-19 patients with sepsis hasfour aspects of advantages. Moreover, a simple and convenient clinical acupuncture protocol including point selection and appropriate stimulation parameters is proposed. Conclusion: Acupuncture, especially electroacupuncture, has shown potentials in effectively treating infectious sepsis of animal models and critically ill patients in small sample studies by stimulating the nervous system, but has been largely overlooked in the clinic so far. It is advised that acupuncture should be integrated into the existing medical guidelines in dealing with COVID-19 complicated with sepsis.     

改良单图像法手工测量髌骨不稳患者胫骨结节-股骨滑车沟间距的可行性分析

目的 探讨改良单图像法手工测量髌骨不稳患者胫骨结节-股骨滑车沟（tibial tuberosity-trochlear groove，TT-TG）间距的可行性。 方法 选取髌骨不稳患者30例。高年资手术医师A、B，使用改良单图像法手工测量髌骨不稳患者TT-TG间距，对比高资年影像学医师C，使用双图法测量髌骨不稳患者TT-TG间距。应用Cronbach′s alpha系数评价结果的可信度。应用组内相关系数（intraclass correlation coefficient，ICC）评价结果的可重复性。使用Bland-Altman分析图评价结果的一致性。 结果 高年资手术医师A、B使用改良单图像法手工测量髌骨不稳患者TT-TG间距分别和高年资影像学医师C使用双图法测量髌骨不稳患者TT-TG间距比较，Cronbach′s alpha系数分别为0.913和0.959，组内相关系数分别为0.913和0.958。Bland-Altman分析图显示，TT-TG间距差值（mm）的均值为-0.276（95%CI：-3.526~2.974）和0.143（95%CI：-3.110~3.397）。A、B医师之间使用改良单图像法手工测量髌骨不稳患者TT-TG间距比较，Cronbach′s alpha系数为0.891，组内相关系数为0.891。Bland-Altman分析图显示TT-TG间距差值（mm）的均值为-0.276（95%CI：-3.526~2.974）。 结论 改良单图像法手工测量髌骨不稳患者TT-TG间距操作简单，可以准确测量出髌骨不稳患者的TT-TG间距，该方法和双图法可以相互替换使用。     

Prospective observation: Clinical utility of plasma Epstein–Barr virus DNA load in EBV-associated gastric carcinoma patients

Epstein–Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) may account for 8–9% of all gastric cancer (GC) patients. All previous reports on EBVaGC were retrospective. Prospective study is warranted to evaluate the exact role of EBV status in predicting the prognosis of GC. It is of special interest to figure out whether dynamic detection of plasma EBV-DNA load could be a feasible biomarker for the monitor of EBVaGC. From October 2014 to September 2017, we consecutively collected GC patients (n = 2,760) from Sun Yat-sen University Cancer Center for EBER examination. We detected EBV-DNA load in plasma and tissue samples of EBVaGC patients at baseline. Subsequently, plasma EBV-DNA load was dynamically monitored in EBVaGC patients. The overall prevalence of EBVaGC is 5.1% (140/2,760). The incidence rate of EBVaGC decreased with advanced AJCC 7th TNM stage (p < 0.001), with the corresponding percentages of 9.3, 9.9, 6.7 and 1.4% for Stage I, II, III and IV patients. EBVaGC patients were predominately young males with better histologic differentiation and earlier TNM stage than EBV-negative GC (EBVnGC) patients. EBVaGC patients were confirmed to had a favorable 3-year survival rate (EBVaGC vs. EBVnGC: 76.8% vs. 58.2%, p = 0.0001). Though only 52.1% (73/140) EBVaGC patients gained detectable EBV-DNA and 43.6% (61/140) reached a positive cutoff of 100 copies/ml, we found the plasma EBV-DNA load in EBVaGC decreased when patients got response, while it increased when disease progressed. Our results suggested that plasma EBV-DNA is a good marker in predicting recurrence and chemotherapy response for EBVaGC patients.