利用条件错误发现率方法识别抑郁症和失眠症的多效性位点

背景 抑郁症和失眠症常共病存在,两者存在一些共同的发病机制,并可能受相同的多效性基因调控。既往全基因组关联研究（GWAS）一般采用单性状研究,在解释基因多效性方面存在一定的狭窄性。目的 识别与失眠症和抑郁症相关的遗传变异位点,检验抑郁症和失眠症是否存在共同的遗传因素。方法 抑郁症GWAS数据来自精神疾病遗传学联盟（PGC）,共包含246 363例抑郁症患者和561 190例正常对照。失眠症GWAS数据来自睡眠障碍知识门户,共包含1 331 010例受试者。采用条件错误发现率（cFDR）和联合的条件错误发现率（ccFDR）方法筛选与抑郁症和失眠症相关的遗传位点,采用通路富集分析检验这些位点的生物学功能。结果 抑郁症和失眠症存在显著的多效性富集现象。利用cFDR方法,以cFDR<0.01作为显著性阈值,鉴定出21个易感位点与抑郁症相关（其中17个是新识别的）,38个易感位点与失眠症相关（其中28个是新识别的）。以ccFDR<0.05为显著性阈值,识别出16个多效性位点与抑郁症和失眠症均相关,其中15个是本研究新识别的。通路富集分析结果显示,与抑郁症和失眠症均关联的易感位点富集于突触传递相关通路,如突触后密度（GO：0014069,P=4.91E-04,FDR=4.84E-03）、不对称突触（GO：0032279,P=5.09E-0,FDR=4.84E-03）、突触后膜神经递质受体水平的调节（GO：0099072,P=5.11E-04,FDR=1.69E-02）。结论 失眠症与抑郁症之间存在多效性富集现象,其共病机制与突触传递有关。     

Association Between Nap and Reported Cognitive Function and Role of Sleep Debt: A Population-Based Study

Background and PurposeThe relationship between napping and cognition remains controversial. This study aimed to investigate the association between napping and cognition according to sleep debt in the Korean adult population.MethodsA population-based nationwide cross-sectional survey was conducted in 2018. A two-stage stratified random sample of Koreans aged ≥19 years was selected and evaluated using questionnaires by trained interviewers. Cognitive function was assessed using the Mail-In Cognitive Function Screening Instrument (MCFSI). Sleep habits on weekdays and weekends, napping, and subjective sleep requirements were assessed using the questionnaires. Accumulated sleep debt was calculated by subtracting the weekly average sleep duration from subjective sleep requirements. Sleep quality, daytime sleepiness, insomnia, depression, demographics, and comorbidities were assessed. Participants were grouped into those with sleep debt ≤60 min and those with sleep debt >60 min. Multiple linear regression was used to estimate the independent association between the factors and cognition.ResultsIn total, 2,501 participants were included in the analysis. Naps were reported in 726 (29.0%) participants (nappers). The mean MCFSI score was higher in nappers (3.4±3.6) than in non-nappers (2.3±3.0) (p<0.001). Multiple linear regression controlling for age, alcohol, smoking, depression, insomnia, daytime sleepiness, sleep quality, and education revealed that 30 to 60 min of napping was associated with worse cognitive function in participants with sleep debts ≤60 min, while >60 min of napping was associated with better cognitive function in participants with sleep debts >60 min.ConclusionsIn general, naps are associated with worse cognitive function in the Korean adult population. However, for those with sleep debt of >60 min, naps for >60 min were associated with better cognitive function.     

医药电商平台持续使用意愿及影响因素研究

构建医药电商平台持续使用意愿理论模型,采用问卷调查分析用户对医药电商平台持续使用意愿及影响因素,结果表明感知有用性和用户主观规范正向影响用户对平台持续使用意愿,感知风险负向影响持续使用意愿.在此基础上提出平台运营建议,包括设计创新、口碑化宣传、建设生态链等.     

内生真菌SEF15927对截短侧耳素的微生物羟化研究

目的 研究植物内生真菌SEF15927对截短侧耳素的转化作用.方法 利用液体培养生长细胞对截短侧耳素进行生物转化.发酵液经乙酸乙酯萃取和硅胶柱层析分离获得一个羟化产物.运用质谱和核磁共振光谱鉴定结构.结果 转化产物为2-羟基截短侧耳素.结论 植物内生真菌SEF15927为一具有高转化率的截短侧耳素羟化菌株,     

Quantitative analysis by reversed-phase high-performance liquid chromatography and retinal neuroprotection after topical administration of moxonidine

AIM: To determine moxonidine in aqueous humor and iris-ciliary body by reversed-phase high performance liquid chromatography (RP-HPLC), and to evaluate the retinal neuroprotective effect after topical administration with moxonidine in a high intraocular pressure (IOP) model. METHODS: The eyes of albino rabbits were administered topically and ipsilaterally with 0.2% moxonidine. A RP-HPLC method was employed for the identification and quantification of moxonidine between 2 and 480min, which presented in the aqueous humor and iris-ciliary body. Flash electroretinography (F-ERG) amplitude and superoxide dismutase (SOD) level were measured between day 1 and day 15 after topical administration with moxonidine in a rabbit model of high IOP. Histological and ultrastructural observation underwent to analyze the changes of retinal morphology, the inner retinal layers (IRL) thickness, and retinal ganglion cell (RGC) counting. RESULTS: Moxonidine was detectable between 2 and 480min after administration, and the peak concentration developed both in the two tissues at 30min, 0.51 μg/mL in aqueous humor and 1.03 μg/g in iris-ciliary body. In comparison to control, F-ERG b-wave amplitude in moxonidine eyes were significantly differences between day 3 and day 15 (P<0.01) in the high IOP model; SOD levels were significantly higher at all time-points (P<0.01) with a maximum level of 20.29 U/mgprot at day 15; and RGCs were significantly higher (P<0.05). CONCLUSION: Moxonidine is a viable neuroprotective agent with application to high IOP model. All layers of retina, including RGC layer, retinal nerve fiber layer and INL, are more preserved after moxonidine administration. SOD plays a neuroprotective role in ocular hypertension-mediated RGC death.     

Intracellular pH regulation by a Na+/H+ exchanger in cultured bovine trabecular cells.

Intracellular pH (pHi) of cultured bovine trabecular cells was measured using video-imaging techniques with a pH-sensitive intracellular fluorescent dye, BCECF. In bicarbonate-rich Ringer at pH 7.4, pHi was 7.29 +/- 0.03 (+/- SEM, n = 12 monolayers, 120 cells sampled). Exposure to 20 mM NH4Cl immediately alkalinized pHi: replacement with a Na(+)-rich solution acidified pHi before recovery to resting levels. When NH4Cl was replaced by a low Na+ solution, acidification was sustained but pHi recovery occurred after Na(+)-rich solution. A pHi of 7.11 +/- 0.02 (n = 2 monolayers, 20 cells) occurred in pH 6.8 and pHi was 7.72 +/- 0.03 (n = 2 monolayers, 20 cells) in pH 8.0. Amiloride (1 mM) acidified pHi but DIDS (1 mM) treatment, HCO3(-)-free condition, 1 mM ouabain, 50 mM K+, and 2 mM BaCl2 failed to change pHi. Hydrogen peroxide (1 mM) acidified pHi but no change occurred with 50 microM. Trabecular cells possess an Na+/H+ exchanger similar to that in other cell types.     

Therapeutic effects of total alkaloids of Tripterygium wilfordii Hook f. on collagen-induced arthritis in rats

Ethnopharmacological relevance

Tripterygium wilfordii Hook f. is one of Traditional Chinese Medicines which is commonly used to treat rheumatoid arthritis (RA). The total alkaloids were the main constituent part of Tripterygium wilfordii Hook f. It has a great significance to study the effects of the total alkaloids of Tripterygium wilfordii Hook f. (ATW) on RA.

Aim of the study

This paper aims at investigating the therapeutic effect of ATW on RA and its possible mechanism, and providing a theoretical and experimental basis for the clinical use of ATW.

Materials and methods

The model of wistar rats of type II collagen-induced arthritis (CIA) was made, and the rats were perfused a stomach with ATW for 4 weeks continuously. Then the levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-<alpha>, in the serum of CIA rats were detected by enzyme linked immunosorbent assay (ELISA), and the joint pathological section of CIA rats was observed by hematoxylin and eosin (HE) staining method and the expression of IL-6, IL-8, nuclear factor kappa B (NF-κB), TNF-α were measure by immunohistochemistry staining method.

Results

Compared with model group, ATW could significantly reduce paw swelling and suppresse articular cartilage degenerated. The results also found that there was significant reduction levels of IL-6, IL-8 and TNF-α in serum of CIA rats treated with ATW and ATW inhibited the expression of IL-6, IL-8, NF-κB, TNF-α in synovial tissue.

Conclusion

ATW not only could inhibit the symptom of CIA rats significantly but also could inhibit the production of IL-6, IL-8, TNF-α in serum and the expression of IL-6, IL-8, NF-κB and TNF-α in synovial tissue targeting the inflammatory. ATW would be a drug as a novel botanical drug for the treatment of RA.     

喷雾冷冻干燥对家蝇幼虫活性成分抗菌及抗炎活性影响

以人工饲养繁殖的家蝇（Musca）3龄幼虫为材料,探讨喷雾冷冻干燥对家蝇幼虫活性提取物抗菌及抗炎活性的影响。结果表明,经喷雾冷冻干燥处理的家蝇幼虫活性提取物对金黄色葡萄球菌和大肠埃希菌具有有效抑制作用;对LPS诱导的巨噬细胞炎症因子TNF—α和IL-6表达具有明显的抑制作用。     

Ureteral injuries during classic intrafascial supracervical hysterectomy: an 11-year experience in 1163 patients

STUDY OBJECTIVE: To examine the incidence, characteristics, and treatment of ureteral injuries during classic intrafascial supracervical hysterectomy for benign gynecologic diseases. DESIGN: Retrospective study (Canadian Task Force classification II-3). SETTING: Department of obstetrics and gynecology, university teaching hospital. PATIENTS: A total of 1163 women with benign gynecologic diseases. INTERVENTIONS: Classic intrafascial supracervical hysterectomy. MEASUREMENTS AND MAIN RESULTS: A retrospective chart review was conducted to determine the rate of ureteral injury. Four cases of ureteral injuries occurred among the 1163 classic intrafascial supracervical hysterectomy procedures (0.34%). Ureteral injury occurred during peritoneal dissection in 1 case, which was treated immediately with laparoscopy. In 2 cases, ureteral injuries were recognized by watery vaginal discharge several days after the operation and were treated with laparotomy procedures. Ureteral injury was not detected postoperatively in another case, resulting in a laparoscopic nephrectomy caused by a nonfunctioning kidney 3 years after the initial operation. The predisposing factors for ureteral injury were adhesion as a result of endometriosis, and earlier surgery in which the normal pelvic anatomy was distorted. CONCLUSION: The incidence of ureteral injury during classic intrafascial supracervical hysterectomy as noted in this study is 0.34%. Postoperative cases were associated with high morbidity. Early detection of ureteral injury is crucial for appropriate management as intraoperative diagnosis and repair of the injury then has fewer consequences and less serious complications than postoperative cases.