半乳糖凝集素1与动脉粥样硬化风险之间的因果关联:一项两样本孟德尔随机化研究

目的]探讨遗传预测的半乳糖凝集素1(Gal-1)水平与动脉粥样硬化(As)之间的因果关联。 [方法]采用两样本孟德尔随机化(MR)研究方法,选择与Gal-1相关联的单核苷酸多态性(SNP)位点作为工具变量(IV),评估遗传预测的循环Gal-1水平与不同部位As风险的因果关联。 [结果]逆方差加权法(IVW)分析结果显示,经过Bonferroni校正后遗传预测的循环Gal-1水平与外周动脉粥样硬化及其他部位动脉粥样硬化(除外脑动脉、冠状动脉及外周动脉)的风险呈正相关(OR=1.6,5%CI:1.05～1.27,P＝0.002;OR=1.16,95%CI:1.12～1.20,P＝4.11E－17),而与冠状动脉粥样硬化和脑动脉粥样硬化发生风险均未发现存在因果关联的证据(OR=1.02,95%CI:0.91～1.14,P＝0.765;OR=1.10,95%CI:0.94～1.29,P＝0.220);在应用荟萃分析合并上述不同部位As的效应值后,遗传预测的循环Gal-1水平与As风险呈正相关(OR=1.12,95%CI:1.06～1.19)。 [结论]遗传预测的循环Gal-1水平与As的发病风险存在因果关联,Gal-1是预防As发生的潜在靶点。     

心房颤动与肠道恶性肿瘤因果关系的孟德尔随机化研究

目的:探讨心房颤动(AF)与肠道恶性肿瘤的因果关系。方法:运用单变量孟德尔随机化和全基因组关联研究(GWAS)结合超过100万名受试者的6项相关GWAS研究针对AF鉴定单核苷酸多态性(SNPs)。主要采用逆方差加权(IVW)方法进行孟德尔随机化分析。结果:单变量孟德尔随机化证实AF遗传易感性与结肠恶性肿瘤[OR=1.12,95%CI(1.00,1.25),P=0.043]以及小肠恶性肿瘤[OR=1.34,95%CI(1.04,1.74),P=0.025]风险增加存在明显的因果联系。结论:AF遗传易感性与肠道恶性肿瘤有潜在因果关系,为心血管疾病与消化道肿瘤的治疗和预防提供参考。     

不饱和脂肪酸与炎症性肠病因果关系的孟德尔随机化分析

背景：炎症性肠病（IBD）是一种慢性复发性胃肠道炎症性疾病，包括溃疡性结肠炎（UC）和克罗恩病（CD）。目前尚不清楚不饱和脂肪酸与IBD之间是否存在因果关系。目的：采用两样本孟德尔随机化分析探究不饱和脂肪酸与IBD之间的因果关系。方法：不饱和脂肪酸和IBD的全基因组关联研究（GWAS）数据均来源于网络公开数据库。采用逆方差加权分析法进行两样本孟德尔随机化分析，使用加权中位数法和MR-Egger回归分析验证因果效应，以OR及其95%CI评价不饱和脂肪酸与IBD风险的因果关系。结果：ω-6脂肪酸与CD无直接因果关系，与UC有直接因果关系，逆方差加权分析结果显示ω-6脂肪酸基因水平每增加一个标准差，UC风险增加16%(OR=1.16,95%CI:1.00～1.36,P=0.04)。而ω-3脂肪酸、单不饱和脂肪酸与IBD之间均未发现因果关系。结论：ω-6脂肪酸可能仅与UC存在因果关系，ω-3脂肪酸、单不饱和脂肪酸与IBD之间均未发现因果关系。     

血脂与心力衰竭风险的因果关系及冠状动脉疾病的中介作用：一项孟德尔随机化研究

目的 利用孟德尔随机化分析方法,探究血脂与心力衰竭风险之间的因果关系及冠状动脉疾病的潜在中介效应。方法 主要采用逆方差加权方法,对欧洲人群中的血脂水平(包括甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、载脂蛋白A1和载脂蛋白B)与心力衰竭的因果关系进行单变量孟德尔随机化分析。此外,采用中介分析方法探究冠状动脉疾病的潜在中介效应。结果 单变量孟德尔随机化分析结果显示,血脂与心力衰竭风险之间存在显著关联。其中甘油三酯(OR=1.15,95%CI 1.09～1.21)、低密度脂蛋白胆固醇(OR=1.15,95%CI 1.05～1.25)和载脂蛋白B(OR=1.16,95%CI 1.07～1.26)水平的升高与心力衰竭风险呈正相关。此外,高密度脂蛋白胆固醇(OR=0.88,95%CI 0.84～0.93)和载脂蛋白A1(OR=0.92,95%CI 0.87～0.97)水平的升高与心力衰竭风险呈负相关。敏感性分析验证了以上结果的稳健性。中介分析结果显示冠状动脉疾病在甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、载脂蛋白A1、载脂蛋白B与心力衰竭风险的因果关系中起到部分中介作用(分别为10...     

血残粒胆固醇水平与冠心病和心肌梗死风险的两样本孟德尔随机化研究

[目的]探索血液中残粒胆固醇(RC)水平与冠心病(CHD)和心肌梗死(MI)的因果关系。[方法]采用两样本孟德尔随机化(MR)分析方法研究RC与CHD和MI的潜在因果关系。使用随机效应逆方差加权(IVW)法作为两样本MR分析的主要分析方法,并采用敏感性分析(包括异质性检验、多效性分析和逐个剔除检验)评估MR分析结果的稳健性。[结果] IVW法分析结果显示,RC与CHD和MI发生风险之间的关联具有统计学意义(CHD:OR=1.57,95%CI:1.40～1.76,P=2.01E-14;MI:OR=1.59,95%CI:1.40～1.79,P=1.26E-13)。MR-Egger回归结果提示筛选出的单核苷酸多态性(SNP)与CHD和MI不存在基因多效性(分别为P=0.924 1、P=0.740 5)。[结论]血液中RC水平升高与CHD和MI风险增加存在因果关系。     

老年人群癌症与心血管疾病因果关联的孟德尔随机化研究

目的 采用孟德尔随机化方法(MR)分析欧洲60岁以上人群癌症(乳腺癌、肺癌、胃癌、皮肤癌、前列腺癌)与10种常见心血管病的因果联系。方法 通过公共全基因组关联分析(GWAS)数据库获得工具变量，样本均来自欧洲人群，以逆方差加权法为主要方法进行两样本MR分析，并对结果行敏感性分析。后选择糖尿病、吸烟、体质量指数(BMI)3个混杂因素对癌症进行校正，并行多样本MR研究。结果 通过两样本的MR分析共得到5种检验效能小于0.05的因果关联，分别是乳腺癌与心肌梗死、乳腺癌与脑梗死、肺癌与脑梗死、肺癌与房颤、肺癌与外周动脉疾病。在多样本MR分析中，调整混杂因素后，乳腺癌对心肌梗死，肺癌对外周动脉疾病的效应值仍然较强。结论 在欧洲老年人群中乳腺癌与心肌梗死的发生可能存在负相关风险，肺癌与外周动脉疾病发生率可能存在正相关风险。     

系统免疫炎症指数与颅内外动脉粥样硬化性狭窄的相关性分析

目的]分析系统免疫炎症指数(SII)与颅内外动脉粥样硬化性狭窄之间的关系。 [方法]回顾性分析徐州医科大学附属医院神经内科收治的489例脑梗死患者,所有患者均完成头颈部计算机体层血管成像(CTA)检查,基于这些患者的狭窄程度,相应归入无狭窄组、轻度狭窄组(狭窄程度＜50%)、中度狭窄组(狭窄程度≥50%且＜70%)、重度狭窄组(狭窄程度≥70%),并对患者的基线资料、血脂、血常规等进行记录、统计分析。经由多因素二元Logistic回归分析与狭窄发生相关的独立风险因子。用多因素Logistic回归分析与狭窄程度相关的独立风险因子,用ROC曲线分析SII预测颅内外动脉粥样硬化性狭窄的价值。 [结果]多因素二元Logistic回归分析发现,年龄(OR＝1.185,P＜0.05)、SII(OR＝1.482,P＜0.05)、性别(OR＝2.721,P＝0.003)、高血压(OR＝3.119,P＜0.001)为颅内外动脉粥样硬化性狭窄的独立风险因子。多因素Logistic回归分析发现,hs-CRP(OR＝1.197,P＝0.011)、SII(OR＝1.379,P＜0.001)、Hcy(OR＝1.517,P＝0.013)显著影响血管狭窄程度。ROC曲线分析显示,SII的曲线下面积(AUC)为0.747,最佳截断值为447.89。Spearman相关性分析结果显示,SII水平与颅内外动脉粥样硬化性狭窄、颅内外动脉粥样硬化性狭窄严重程度均呈显著正相关(r＝0.524、0.482,P＜0.05)。 [结论]SII水平与脑梗死患者颅内外动脉粥样硬化性狭窄程度独立正相关,对颅内外动脉粥样硬化性狭窄具一定预测价值。     

高血压与前列腺癌因果关系的孟德尔随机化研究

目的 众多研究阐述了高血压与前列腺癌风险的关系，但由于观察性研究中二者的因果关系并不明确。本研究通过双向两样本孟德尔随机化(MR)探讨高血压与前列腺癌的因果关系。方法 利用全基因组关联研究汇总数据，其中高血压来自于UKB数据库，前列腺癌数据来自于一项大型的全基因组关联研究。利用逆方差加权法、加权中位数法、MR-Egger等方法进行MR分析，然后进行敏感性分析包括水平多效性分析，Cochran Q检验及“留一法”评估结果可靠性。结果 68个与高血压密切相关的单核苷酸多态性位点被筛选出来作为工具变量。基于逆方差加权法，发现高血压与前列腺癌之间存在密切的因果关系(OR=0.53, 95%CI 0.286～0.966,P=0.038),这提示高血压与前列腺癌之间为负向因果关系。反向MR分析显示前列腺癌不是高血压发病风险的危险因素(P=0.208)。MR-Egger截距和Cochran Q检验表明，本研究中不存在水平多效性和异质性的易感性(P>0.05)。结论 MR分析提示高血压与前列腺癌风险反向相关，而前列腺癌并不增加高血压风险。     

基于孟德尔随机化探究高血压与抑郁症的因果关系

目的 采用两样本孟德尔随机化方法探究高血压与抑郁症的相关性,以便指导临床早期干预。方法 从布里斯托尔大学的IEU GWAS数据库中选择高血压与抑郁症的GWAS数据,以高血压作为暴露因素,并从高血压数据集中获取与其显著相关的单核苷酸多态性（SNPs）作为工具变量。抑郁症的数据集作为结局变量。采用逆方差加权法、加权中位数法以及MR-Egger回归等方法进行高血压与抑郁症的两样本孟德尔随机化分析,以OR值来评价高血压与抑郁症之间的因果关系,并借助Cochran’s Q统计量和MR Egger法评估异质性和水平多效性。结果 高血压与抑郁症存在正相关关系,逆方差加权法（OR=1.481,95%CI 1.209-1.815,P<0.001）、加权中位数法（OR=1.626,95%CI 1.188-2.226,P=0.002）以及MR-Egger回归（OR=2.002,95%CI 1.142-3.509,P=0.016）,不存在多效性及异质性。结论 高血压与抑郁症之间存在正向的因果关联,这表明高血压是抑郁症的危险因素,提示临床医师在高血压患者诊疗过程中应积极进行心理疏导。     

FT4/FT3比值对急性心肌梗死患者院内全因死亡风险的临床预测价值

目的]探讨游离甲状腺激素(FT4)/游离三碘甲状腺原氨酸(FT3)比值对急性心肌梗死(AMI)患者院内全因死亡风险的临床预测价值。 [方法]回顾性收集2016年1月─2022年12月于大连医科大学附属第二医院心血管内科进行冠状动脉造影或经皮冠状动脉介入治疗(PCI)的AMI患者的临床资料,其中病史资料完整且发生住院期间死亡的患者共63例,选取同期住院未发生住院期间死亡的AMI患者180例作为对照。 [结果]院内死亡组年龄、ST段抬高型心肌梗死(STEMI)比例、肾功能不全比例、心房颤动比例、心率、KillipⅢ/Ⅳ级比例、多支病变比例、心肌肌钙蛋白I、脑钠肽(BNP)均要高于生存组,射血分数(EF)低于生存组,差异具有统计学意义(P＜0.05);院内死亡组FT4、FT4/FT3比值高于生存组,FT3低于生存组,差异具有统计学意义(P＜0.05)。多因素Logistic回归分析结果显示,FT4/FT3比值与AMI患者院内全因死亡风险正相关(OR＝1.844,95%CI:1.193～2.850,P＜0.05),除此之外,年龄、心率、KillipⅢ/Ⅳ级、STEMI、肾功能不全、低EF也与AMI患者院内全因死亡风险正相关(OR＝1.084、1.031、2.847、2.508、4.085、4.407,P＜0.05)。ROC曲线分析结果显示,FT4/FT3比值预测住院期间全因死亡风险的能力(AUC＝0.774,95%CI:0.708～0.839,P＜0.001)优于FT4(AUC＝0.640,95%CI:0.561～0.719,P＝0.001)或FT3(AUC＝0.719,95%CI:0.647～0.790,P＜0.001)单独预测,ROC曲线下面积差异有统计学意义(P＝0.001和P＝0.042)。 [结论]FT4/FT3比值与AMI患者院内全因死亡风险相关,可预测AMI患者院内全因死亡风险;与单独的FT3或FT4相比,FT4/FT3比值对AMI患者院内全因死亡具有更好的临床预测价值。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.