人胰岛素血糖控制不佳患者改用双时相门冬胰岛素30的治疗结果——A1chieve国际多中心观察性研究中国亚组结果

目的 观察人胰岛素改用双时相门冬胰岛素30治疗后的疗效和安全性.方法 A1chieve 是一项国际多中心、前瞻性、观察性、开放标签、非干预性、为期24周的胰岛素类似物研究.本文总结由人胰岛素转为双时相门冬胰岛素30治疗的患者数据.入选患者为经医师判断需要改用门冬胰岛素30的2型糖尿病患者,医师根据临床经验决定治疗方案并进行剂量调整,随访24周.结果 1 588例因人胰岛素血糖控制不佳而转为接受双时相门冬胰岛素30治疗的中国2型糖尿病患者,进入研究前接受预混人胰岛素治疗的患者比例最高(75.0％).研究期间未报告严重药物不良反应.经过24周治疗,所有低血糖事件、夜间低血糖事件、重度低血糖事件的发生率(次·人-1·年-1)分别从基线时6.54、1.84、0.43下降至2.36、0.45、0(均P＜0.01);HbA1C从基线时的(8.9±2.3)％,下降至24周时(7.0±1.1)％(P＜0.05);HbA1C达标率(＜7.0％)由基线时17.8％上升至24周时的54.8％.空腹和餐后2h血糖的下降值分别为(-2.3±3.3) mmol/L和(-3.8±4.4)mmol/L(均P＜0.05).结论 接受人胰岛素治疗血糖控制欠佳的中国2型糖尿病患者,改用双时相门冬胰岛素30治疗24周后耐受性和安全性良好,血糖控制得到显著改善.     

中国2型糖尿病患者接受双时相门冬胰岛素30治疗后血糖控制达标的预测因素分析:A1chieve研究亚组数据

目的预测T2DM患者由预混人胰岛素(BHI30)转为双时相门冬胰岛素30(BIAsp30)后治疗达标的基线特征。方法纳入A1chieve研究中BHI30血糖控制效果不佳而转用BIAsp30治疗的中国患者,以治疗24周后HbA_1c是否达标(7.0%)为因变量,患者基线特征为自变量,行单因素及多因素回归分析。结果基线HbA_1c、FPG及体重是患者接受BIAsp30治疗后HbA_1c达标的预测因素。基线HbA_1c水平每增加1%,治疗后HbA_1c达标的可能性降低25%;基线FPG水平每增加1mmol/L,治疗后HbA_1c达标的可能性降低7%;基线体重每增加1kg,治疗后HbA_1c达标的可能降低2%。结论本研究提示,由BHI30转为BIAsp30治疗,患者基线HbA_1c、FPG及体重越低,血糖控制的达标率越高。     

门冬胰岛素30强化治疗初诊2型糖尿病患者的临床观察

目的观察预混双相门冬胰岛素30强化治疗伴有明显高血糖的初诊2型糖尿病患学的血糖控制及对8细胞功能的影响。方法采用自身前后对照,42例初诊的2型糖尿病患者就诊时空腹血糖（FPG）≥11．1mmol／L和（或）餐后2小时血糖（2hPG）≥14mmol／L,糖化血红蛋白（HbA1c）〉18．0％,予门冬胰岛素30餐前皮下注射控制血糖12周,治疗前后分别检测FPG、空腹胰岛素（Fins）、空腹C-肽（FPC）、HbA1c和2hPG、餐后2小时胰岛素（2hIns）、餐后2小时C-肽（2hPC）、体重指数（BMI）,计算并比较治疗前后胰岛β细胞功能（HOMA-β）、胰岛素抵抗指数（HOMA-IR）。结果42例患者血糖达标时间平均为（12．3±4．5）天,治疗后FPG、2hPG、HbA1c较治疗前显著下降（P〈0．01）;FIns、2hIns、FPC、2hPC、HOMA—β较治疗前明显升高（P〈0．05）。结论门冬胰岛素30强化治疗伴有明显高血糖的初诊2型糖尿病患者,能够快速降低血糖并达标,有助于保护胰岛β细胞功能、延缓其衰竭。     

地特胰岛素与门冬胰岛素30起始治疗老年2型糖尿病伴轻度认知障碍患者的疗效比较

目的比较地特胰岛素与门冬胰岛素30起始治疗老年2型糖尿病伴轻度认知障碍(mild cognitive impairment,MCI)患者的有效性、安全性及对认知功能的影响。方法采用随机数字表法将100例老年2型糖尿病伴MCI患者分为地特胰岛素组和门冬胰岛素30组,每组50例。地特胰岛素组继续口服降糖药治疗,予地特胰岛素睡前注射;门冬胰岛素30组停用口服降糖药,予门冬胰岛素30早餐前和晚餐前皮下注射。治疗24周,观察空腹血糖(FPG)、餐后2 h血糖(2hPG)、糖化血红蛋白(HbA1c)、胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、血压、体重、体重指数(BMI)及蒙特利尔认知评估(MoCA)量表评分的变化,并记录血糖达标、低血糖及痴呆发生情况。结果两组治疗后FPG、2hPG、HbA1c、LDL-C均显著降低(P<0.05),且地特胰岛素组2hPG、HbA1c降低程度大于门冬胰岛素30组(P<0.05)。两组治疗前后TC、TG、血压、体重、BMI比较差异均无统计学意义(P>0.05)。地特胰岛素组血糖达标率高于门冬胰岛素30组(P<0.05)。两组患者治疗后低血糖发生少而轻微,不良反应发生率比较,差异无统计学意义(P>0.05),两组治疗前后MoCA量表评分比较,差异无统计学意义(P>0.05)。结论地特胰岛素与门冬胰岛素30起始治疗老年2型糖尿病伴MCI患者均安全、有效,可作为胰岛素起始治疗的首选用药。     

天麦消渴片与二甲双胍缓释片联合门冬胰岛素30治疗新诊断老年2型糖尿病患者疗效观察

目的观察天麦消渴片与二甲双胍缓释片联合门冬胰岛素30治疗新诊断老年T2DM患者的疗效。方法将新诊断老年T2DM患者83例分为对照组41例和治疗组42例,对照组予口服二甲双胍缓释片联合门冬胰岛素30治疗,治疗组在对照组基础上加用天麦消渴片,疗程12周,观察两组治疗前后各项指标。结果治疗组治疗后SBP、FPG、2hPG、HbA1c、TG、TC、胰岛素用量和血糖达标时间较对照组低[(138.0±11.0)vs(143.0±9.0)mmHg;(6.4±0.9)vs(8.0±1.2)mmol/L;(6.6±1.0)vs(8.3±1.2)mmol/L;(6.4±0.5)%vs(7.5±0.6)%;(3.04±1.03)vs(3.10±1.10)mmol/L;(6.04±1.13)vs(6.15±1.32)mmol/L;(22.0±2.0)vs(26.0±4.0)U;(8.5±2.0)vs(10.0±1.8)d,P<0.05]。两组均无严重低血糖事件发生。结论天麦消渴片与二甲双胍缓释片联合门冬胰岛素30治疗可有效降低新诊断老年T2DM患者SBP、FPG、2hPG、HbA1c、TG和TC水平,且胰岛素用量少,血糖达标时间短,无严重低血糖事件发生。     

门冬胰岛素50注射液与地特胰岛素联合口服药治疗初发2型糖尿病患者的疗效比较

目的比较门冬胰岛素50注射液与地特胰岛素联合口服药治疗初发2型糖尿病患者的临床疗效。方法连续收集2015年8月至2016年3月于河北省人民医院就诊的初发2型糖尿病患者60例,随机分为门冬胰岛素50注射液组(预混组)与地特胰岛素联合口服药治疗组(地特组),各30例,共干预12周。观察两组患者干预前后空腹血糖(FPG)、餐后2h血糖(2hPG)和糖化血红蛋白(HbA1c)的变化及低血糖的发生情况。结果预混组与地特组的基线临床特征无差异。干预12周后,预混组2hPG较地特组下降明显(8.54±1.37 vs.7.52±1.58),差异有统计学意义(P=0.009)。在干预12周时,预混组2hPG和HbA1c的水平均低于地特组(P0.05)。两组在低血糖发生率上无差异(P0.05)。结论在初发2型糖尿病患者中,门冬胰岛素50注射液与地特胰岛素联合口服药均可有效降低糖化血红蛋白,门冬胰岛素50注射液控制餐后血糖优于地特胰岛素联合口服药。     

门冬胰岛素联合地特胰岛素治疗2型糖尿病患者的临床效果回顾性分析

目的回顾性分析门冬胰岛素联合地特胰岛素治疗2型糖尿病患者的临床效果。方法将2016年8月—2017年8月期间该院收治的130例2型糖尿病患者的临床资料进行回顾性分析,随机将其分为两组,单纯使用门冬胰岛素治疗的65例患者归为单纯组,将门冬胰岛素联合地特胰岛素治疗的65例患者归为联合组。就上述两组患者治疗前后[空腹血糖(FPG)、餐后2 h血糖(2hPG)、糖化血红蛋白(HbA1c)、空腹血清C肽(FC-P)、餐后2 h血清C肽(2 h C-P)、体质量(BMI)]各指标水平变化情况进行对比,并将两组患者的不良反应发生情况进行对比。结果治疗前,两组患者的FPG、2hPG、HbA1c水平对比差异无统计学意义(P0.05);治疗后,联合组患者的FPG为(5.54±0.52)mmol/L、2hPG为(7.26±1.13)mmol/L、HbA1c为(6.45±0.44)%,均较治疗前降低,且降低幅度大于单纯组,差异有统计学意义(P0.05);两组患者治疗前的FC-P、2 h C-P、BMI水平对比差异无统计学意义(P0.05);治疗后,两组患者的各指标均较治疗前改善(P0.05);联合组FC-P为(1.64±0.28)mmol/L、2 h C-P为(3.89±1.65)mmol/L,均较治疗前升高,且高于单纯组,差异有统计学意义(P0.05);两组患者的BMI水平并差异无统计学意义(P0.05);两组患者的不良反应发生率对比,差异无统计学意义(P0.05)。结论对于2型糖尿病患者,采用门冬胰岛素联合地特胰岛素治疗的效果显著,可控制血糖水平,值得在今后临床中推荐应用。     

既往接受基础胰岛素治疗的中国2型糖尿病患者转为接受门冬胰岛素30治疗24周后的安全性和疗效:A_1chieve研究亚组分析

目的研究使用基础胰岛素血糖控制不佳的中国T2DM患者,转为接受门冬胰岛素30治疗的安全性及有效性。方法 A1chieve是1项为期24周的国际多中心、前瞻性、开放标签及非干预性的有关胰岛素类似物的研究。安全性指标为低血糖事件和药物不良反应的发生情况。主要疗效指标包括HbA1c、平均FPG和2hPG。本亚组分析选取进入研究前接受基础胰岛素治疗,在亚组分析中接受门冬胰岛素30治疗的中国T2DM患者进行分析。结果本亚组分析包括T2DM患者238例。研究对象所有重度、夜间低血糖事件发生率(次/患者年)基线时分别为3.61、0.27及0.60;24周时分别为2.02、0.00及0.52。治疗24周后平均HbA1c由9.0%降至7.1%(下降值为-1.9%,P0.05);平均FPG由9.2mmol/L降至6.9mmol/L(下降值为-2.3 mmol/L,P0.05);总体HbA1c达标率(7.0%)由15.3%升至46.0%;平均体重增加0.4kg(P0.05)。结论对于使用基础胰岛素治疗血糖控制不佳的中国T2DM患者,使用门冬胰岛素30后安全性及耐受性良好,血糖控制显著改善。     

双时相门冬胰岛素30联合二甲双胍治疗基础胰岛素控制不佳的2型糖尿病患者:疗效及安全性评价

目的 评价既往基础胰岛素联合口服降糖药物(OAD)治疗血糖控制不佳的2型糖尿病患者转用双时相门冬胰岛素30(BIAsp30)联合二甲双胍治疗的疗效及安全性.方法 本试验为多中心、非随机、开放、单组治疗达标研究,包括2周筛选期、4周导入期和16周治疗期.既往使用基础胰岛素联合OAD治疗血糖控制不佳的2型糖尿病患者转用每日两次BIAsp30注射联合口服二甲双胍治疗.收集疗效及安全性数据进行统计学分析.结果 共293例患者(男154,女139)入选,平均年龄(54.0±9.6)岁,平均糖尿病病程(8.54±5.49)年,平均体重指数(24.89±3.28)kg/m2,HbA1c 8.16%±0.89%,122例既往使用基础胰岛素类似物,169例使用人中效胰岛素.经16周的治疗,平均HbA1C降幅达1.30%±0.96%(P＜0.01);HbA1C达到＜7.0%和≤6.5%的患者比例分别为60.4%和38.9%.患者8点血糖谱各点血糖值均有显著降低(P＜0.01),8点血糖均值由基线时的(10.53±2.58)mmol/L降至(7.79±1.58)mmol/L(P＜0.01),降幅为2.76 mmol/L.早餐和晚餐后血糖增幅显著下降,分别下降了1.73 mmol/L(P＜0.01)和1.28 mmol/L(P＜0.01),而午餐后的血糖增幅未发现显著性降低(-0.09 mmol/L,P=0.734 5).研究治疗中无严重不良事件和重度低血糖事件报告,总体低血糖发生率为2.68例/患者年;患者体重平均增加(0.76±0.14)kg(P＜0.01).结论 BIAsp30联合二甲双胍可显著改善基础胰岛素联合OAD血糖控制不佳的2型糖尿病患者的血糖控制,并具有良好的安全性.     

90例2型糖尿病应用甘精胰岛素的疗效和依从性观察

目的观察90例2型糖尿病患者应用甘精胰岛素的疗效和依从性。方法选取90例空腹血糖（FPG）≥8mmol／L,糖化血红蛋白（HbA1c）≥7％的2型糖尿病患者,均以甘精胰岛素为基础治疗,配合餐前用药,经半个月的调整用药,使FPG≤7mmol／L,餐后2小时血糖（2hPG）≤9mmol／L,记录治疗3个月结束时胰岛素剂量、血糖改善、胰岛素依从性及低血糖情况。结果血糖达标时甘精胰岛素剂量0．19～0．23IU／kg,与基线FPG及2hPG、病程有一定的相关关系,治疗结束患者血糖明显改善,低血糖发生率低,单种口服药与甘精胰岛素配伍依从性高。结论甘精胰岛素的使用需兼顾疗效和依从性,提倡血糖失控的2型糖尿病患者在病程早期即开始采用甘精胰岛素治疗。     

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.     

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.     

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.     

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.