The antifertility effectiveness of copper/low-density polyethylene nanocomposite and its influence on the endometrial environment in rats

PURPOSE: The study was conducted to investigate the antifertility effectiveness of copper/low-density polyethylene nanocomposite (nano-Cu/LDPE) and its influence on the endometrial environment in rats. METHODS: One hundred and seventy sexually mature female Sprague-Dawley (SD) rats were randomly divided into five groups: sham-operated control group (SO group, n=10), bulk copper group (Cu group, n=40), LDPE group (n=40), and nano-Cu/LDPE groups I (n=40) and II (n=40). Twenty rats in each group except for the SO group were mated with male rats of proven fertility, from 30 days after insertion, and the antifertility rates (ATs) were observed at Day 11 of pregnancy. The concentrations of prostaglandin E(2) (PGE(2)) and tissue plasminogen activator (tPA) in the endometrium of the remaining rats in each group were measured by using ELISA at the 30th and 60th day after insertion, respectively. RESULTS: ATs in the Cu group and nano-Cu/LDPE groups I and II (100%) were significantly higher than those in the LDPE group (p<.05). Compared with those in the SO group, the concentrations of PGE(2) and tPA in all experimental groups except for PGE(2) levels in the LDPE group were significantly increased at Day 30 after insertion, and these parameters in the nano-Cu/LDPE groups were significantly lower than in the Cu group (p<.05). At Day 60 after insertion, tPA levels were still higher in the Cu and nano-Cu/LDPE groups, but there was no difference in PGE(2) levels in all groups except for the Cu group. CONCLUSION: Nano-Cu/LDPE exhibits satisfactory contraceptive efficacy with less influence on the endometrium PGE(2) and tPA levels.     

爱母牌MYCu宫内节育器与TCu220C宫内节育器的临床应用对比

目的探讨爱母牌MYCu宫内节育器(intrauterin econtraceptive device,IUD)与TCu220C宫内节育器(TCu220CIUD)的临床应用效果。方法选择来嘉定中心医院要求放置IUD避孕的育龄妇女,随机放置MYCuIUD与TCu220CIUD各150例,放置后1、3、6、12个月定期随访观察。结果放置满12个月时,MYCuIUD组与TCu220CIUD组累计带器妊娠率均为0.67/每百妇女年,累计脱落率分别为0.67/每百妇女年、2.00/每百妇女年;因不良反应取出率为2.01/每百妇女年、4.14/每百妇女年,差异均无统计学意义(P>0.05);续用率分别为96.00/每百妇女年、92.30/每百妇女年;4次随访主诉发生率MYCuIUD组低于TCu220CIUD组,差异有统计学意义(P<0.05),主诉中最常见的不良反应为出血和疼痛。结论 MYCuIUD抗生育效果好,脱落率低,置器后不良反应小,是效果理想的IUD,值得进一步推广应用。     

GyneFixIN与TCu220C宫内节育器临床使用效果比较观察

目的:比较吉妮固定式宫内节育器(IUD)和TCu220C IUD的临床使用效果。方法:选择自愿放置IUD的已婚育龄妇女600例,随机分成两组(各300例),分别放置吉妮IUD和TCu220C IUD,并进行24个月随访观察。结果:吉妮IUD的脱落率显著低于TCu220C IUD(P<0.05),妊娠率、因症取出率及终止率,吉妮IUD与TCu220C IUD比较,有显著性差异(P<0.05)。结论:吉妮IUD是避孕效果优于TCu220C IUD,可在临床上推广使用。     

TCu220C宫内节育器副反应及其影响因素的meta分析

目的:通过mtea分析评价使用TCu220CIUD副反应发生情况及其相关影响因素,为安全使用提供科学依据。方法:利用计算机检索PubMed、EMBASE、CENTRAL等9种数据库和WHO/FDA/IUD生产企业/临床试验注册相关网站,采用Openmeta analyst软件对数据进行分析。结果:共检索到7726篇文献,根据纳入及排除标准,最终纳入涉及TCu220C副反应的文献15篇,均为RCT或准RCT,共计22253例观察对象,其中TCu220C组7558例。mtea分析表明出血、疼痛和感染副反应及总体发生率均随置器时间延长呈现下降趋势。随访12个月时,国外组TCu220C疼痛、感染和总副反应发生率高于国内组。产褥期末放置对象6个月和12个月随访时的出血发生率高于正常月经间期放置对象。结论:建议医务人员在TCu220CIUD放置初期应关注出血的处理,若为产褥期末放置IUD对象还应加强后期随访,以减少TCu220CIUD副反应的发生。     

去尾丝HCu280型花式IUD临床效果观察

目的:探讨放置去尾丝HCu280型花式宫内节育器(IUD)的临床效果,为推广使用提供科学依据。方法:21~45岁已婚已育且无放置IUD禁忌证妇女中,选择自愿放置去尾丝HCu280型花式IUD妇女200例为观察对象(HCu280IUD组),以选择放置TCu380AIUD妇女198例为对照(TCu380AIUD组),分别于放置后1、3、6和12个月进行随访,比较两组避孕效果、副作用主诉情况。结果:置器12个月HCu280IUD组和TCu380AIUD组带器妊娠率分别为每百妇女年0和0.5(P0.05);脱落率分别为每百妇年0.5和4.2(P0.05);与IUD使用相关终止率分别为每百妇女年3.5和9.6(P0.05);总终止率分别为每百妇女年4.0和10.1(P0.05);续用率分别为每百妇女年96.0和89.9。置器后1、3、6、12个月副作用主诉率,HCu280IUD组低于TCu380AIUD组。结论:HCu280型花式IUD避孕效果好,副作用主诉少,续用率高。     

MCu110和TCu220C、TCu380A宫内节育器比较的系统评估

目的：评价MCu110功能性宫内节育器的有效性、副反应和可接受性。方法：通过电子和手工检索查阅2000年1月～2008年12月国内外发表的相关文献,并依照循证医学的方法对纳入评估的文献进行筛选、评价和分析。结果：共获得合格文献10篇,均为随机对照临床试验且正式发表。评估结果显示,置器后12月和24月,MCu110的临床综合效果优于TCu220C;脱落率略低于TCu380A,可接受性略优于TCu380A,副反应各项指标二者互有优劣,而带器妊娠率差别未发现有统计学意义。结论：与TCu380A相比,能够证实MCu110有效性、副反应和可接受性的多中心随机对照试验并不多,尤其是长期随访研究;建议由非MCu110研制单位组织开展多中心随机对照试验,观察年限不少于5年。     

TCu220C宫内节育器脱落率影响因素的系统评价

目的:采用meta分析方法评价不同地区、不同放置时期对TCu220CIUD脱落率的影响,为IUD安全使用提供科学依据。方法:采用计算机检索PubMed、EMBASE、CENTRAL等9个数据库和WHO/FDA/IUD生产企业/临床试验注册相关网站,采用Openmeta analyst和RevMan5.3.3进行数据的分析与合并。结果:共检索到7726篇文献,根据纳入及排除标准,最终纳入31篇文献,均为RCT(随机对照试验)或准RCT。比较TCu220C和其它10种IUD分析结果显示:①不同放置时期的TCu220C脱落率中,人工流产术时放置TCu220C脱落率是月经间期放置的3.8倍(P0.05)。②在1年随访时TCu220C的脱落率高于爱母型IUD和MCuⅡIUD(P0.05)。在随访时,TCu220C的脱落率低于金属单环(P0.05);与活性165、MLCu250、活性γ型、V铜、宫铜300、MLCu375、TCu380A等7种IUD比较均无统计学意义。结论:本研究首次报告了基于RCT的TCu220C的脱落率影响因素定量分析的系统评价结果,国外的研究数据表明人工流产术时放置增加TCu220CIUD脱落的风险;在TCu220C的临床应用中应关注高风险人群,提高TCu220C的避孕效果。     

A randomized trial on the clinical performance of Nova T380 and Gyne T380 Slimline copper IUDs

PURPOSE: The objective of this open randomized study was to compare the clinical performance of Nova T380 and Gyne T380 Slimline copper intrauterine devices (IUDs). MATERIALS AND METHODS: Eligible for analyses were 957 Norwegian parous women aged 18-45 years. Clinical performance was measured upon the removal of IUD due to contraceptive failure, expulsion, bleeding, pain, pelvic inflammatory disease and other medical reasons during a 5-year study period. RESULTS: The discontinuation rate due to contraceptive failure was significantly higher in the first year for Nova T380 users than for Gyne T380 Slimline users, whereas no differences were observed thereafter (the 5-year cumulative failure rates were 4.4% and 2.2%, respectively, per 100 women). However, the partial expulsion rate was significantly higher in the first year for Gyne T380 Slimline users than for Nova T380 users (the 5-year cumulative rates were 3.4% and 1.1,% respectively, per 100 women). No other major differences in reasons for discontinuation were found between the study groups. There was a slight nonsignificant increase in hemoglobin levels for both study groups over the course of the study. CONCLUSION: Clinical performance was considered satisfactorily high for both devices.     

Long-term reversible contraception: Twelve years of experience with the TCu380A and TCu220C

Few data on the long-term efficacy of intrauterine devies (IUD) are available, and this article reports on the final 12-year experience with the TCu220C and TCu380A devices from two randomized, multicenter trials conducted in 24 centers. A total of 3,277 and 1,396 women, respectively, were recruited for use of each device between 1981 and 1986 and followed at 3, 6, and 12 months after insertion and yearly thereafter. At the end of 12 years, a total of 17,098 women-years of experience had been accumulated for the TCu220C and 7,159 women-years for the TCu380A. The cumulative 12-year intrauterine pregnancy rates were 7.0 (standard error [SE] 0.6) per 100 women for the TCu220C and 1.9 (SE 0.5) for the TCu380A (p < 0.001). Pregnancy rates were highest in the first years after insertion; the TCu220C had a consistently higher annual pregnancy rate than did the TCu380A at all intervals since insertion. No pregnancies were reported with the TCu380A after 8 years of use. Total medical removals were approximately 6% in the first year and dropped to approximately 4% per year for each device for up to 12 years of use (cumulative 12 year rates were 37.3 [SE 1.3] and 40.2 [SE 2.1] per 100 women for the TCu220C and TCu380A devices, respectively). The overall continuation rate at all intervals since insertion was higher with the TCu220C device, mainly due to higher removal rates for nonmedical reasons with the TCu380A. The cumulative ectopic pregnancy rates were 0.7 and 0.4 for the TCu220C and TCu380A, respectively. Pregnancy rates were higher in the Chinese compared with the non-Chinese centers for both devices, though the greater efficacy of the TCu380A was apparent in both groups of centers. The total medical and nonmedical removal rates were lower in the Chinese compared with the non-Chinese centers, and did not show any substantial differences between the devices. We conclude that both devices are safe and effective for at least 12 years of use and the low pregnancy rate with the TCu380A is comparable with that reported in the United States among women who had undergone tubal sterilization. The very high efficacy of the TCu380A makes it the IUD of choice, and it can be considered as a potentially reversible, nonsurgical alternative to sterilization for women requiring very long-term pregnancy protection.     

Comparative study and evaluation of side effects of low-dose contraceptive pills administered by the oral and vaginal route

This was a comparative study of side effects and acceptability of low-dose pills administered by the oral and vaginal rout. In an experimental clinical trial study, undesirable side effects of nausea, dysmenorrhea, breast tenderness, gastrointestinal disorders, vertigo, headache, and breakthrough bleeding (BTB) were studied. The participants of the case and the control groups were the same women. The side effects were compared in 143 women using contraceptive pill containing 150 microg levonorgestrel and 30 microg ethinyl estradiol by vaginal and oral route. The efficacy and acceptability were evaluated. The side effects among the patients who used the contraceptive pills orally were significantly higher than among those who used the vaginal route (p < 0.0001). BTB occurred more often with the oral route, but there was no significant difference between their incidences (p = 0.267). Most participants in this study expressed a high level of acceptability with the vaginal route. There was only one unwanted pregnancy, which occurred when the participant used the contraceptive pill vaginally, but used it incorrectly. Using the contraceptive pill administered by vaginal route is a safe method with fewer side effects and more acceptability when compared with the oral route.     

A comparison of the clinical performance, contraceptive efficacy, reversibility and acceptability of Norplant implants and Ortho Gynae T380 intrauterine copper contraceptive device

In this comparative study, the five-year continuity rate of 53.7% in the Norplant implants group was comparable to that of 52.7% in the copper IUD group. The difference was not statistically significant. Only one accidental pregnancy occurred during the five years of copper IUD use.Desire for future pregnancy was the main reason for removal in the Norplant implants group (35.9%) while expulsion of the IUD (13.2%) was the main reason for removal of the copper IUD. Menstrual disturbance was not a major side-effect in either group.The post-removal conception rates of 78.6% in the Norplant implants group and 75.0% in the copper IUD were good and comparable.Both the Norplant implants and copper IUD are acceptable and effective contraceptive methods in Singapore.     

格卡瑞韦/哌仑他韦治疗HCV/HIV合并感染患者的临床研究

目的 分析格卡瑞韦/哌仑他韦治疗丙型肝炎病毒(HCV)/人类免疫缺陷病毒(HIV)合并感染患者的临床效果和安全性, 以期为临床治疗提供科学依据。 方法 选择2021年1月—2022年1月凉山州布拖县某医院收治的89例HCV/HIV合并感染无肝硬化的初治患者, 均予以8周的格卡瑞韦/哌仑他韦治疗, 随访12周。观察并记录治疗结束时的病毒学应答率、治疗结束12周后的持续病毒性应答率(SVR12)及不良反应发生情况。 结果 89例HCV/HIV合并感染无肝硬化的初治患者多为中青年已婚男性(79例, 88.8%), HIV感染主要经性接触传播(62例, 69.7%) 和静脉注射毒品传播(27例, 30.3%)。HCV基因型最常见的是基因1b型(33例, 37.1%) 和基因3b型(25例, 28.1%)。全部患者均顺利完成8周治疗, 且治疗结束时HCV RNA载量均低于检测值下限(＜25 IU/mL)。其中, 8例患者未能完成随访, 余81例(100%)患者均获得持续病毒学应答。患者观察期间均未出现严重不良反应, 但有11例患者发生轻度不良反应。 结论 格卡瑞韦/哌仑他韦8周方案治疗基因1、3、6型HCV/HIV合并感染无肝硬化的初治患者SVR12达100%, 且安全性和耐受性均较好, 可以作为此类患者临床治疗的优先选择。     

某新上市国产冻干A+C群脑膜炎球菌多糖结合疫苗免疫原性及安全性观察

目的评价某新上市国产冻干A+C群脑膜炎球菌多糖结合疫苗接种婴幼儿的安全性和免疫原性。方法采用随机、盲法、对照的方法,选择900名6~23月龄健康儿童,其中6~11月龄300人,12~23月龄600人,每个年龄组按1∶1比例随机分到试验组和对照组。实验组接种某新上市疫苗,对照组接种罗益(无锡)生物制药有限公司生产的同类疫苗。每人接种2剂疫苗,间隔1个月,评价试验组和对照组疫苗免疫后不良反应发生率、抗体阳转率及抗体几何平均滴度(GMT)。结果免疫后两个年龄段A、C群抗体阳转(4倍增长)率均95%,试验组与对照组的阳转率差异无统计学意义。12~23月龄接种1剂、2剂疫苗后抗体阳转率差异无统计学意义;6~11月龄段,试验组A群抗体水平高于对照组;两个年龄段试验组的C群抗体水平均低于对照组,但均处于较高水平(1∶128)。实验组与对照组全身及局部不良反应率差异无统计学意义,未观察到与试验疫苗相关的严重不良事件。结论某新上市国产冻干A+C群脑膜炎球菌多糖结合疫苗在6~23月龄的儿童中具有良好安全性和免疫原性。     

Comparative study of the effects of two once-a-month injectable contraceptives (Cyclofem and Mesigyna) and one oral contraceptive (Ortho-Novum 1/35) on coagulation and fibrinolysis

A randomized controlled multicenter study was undertaken to monitor the effects on hemostasis of two once-a-month injectable contraceptive preparations, Mesigyna® (50 mg norethisterone enanthate and 5 mg estradiol valerate) and Cyclofem® (25 mg medroxyprogesterone acetate and 5 mg estradiol cypionate) in comparison with a well-known oral contraceptive (OC) Ortho-Novum 1/35® (norethisterone 1 mg and ethinyl estradiol 35 μg). A total of 378 volunteers from four centers (Bangkok, Hangzhou, Santiago and Singapore) were monitored. Blood sampling took place in one pretreatment cycle, the third and ninth injection intervals and one posttreatment cycle. In each of the three treatment groups, a rise in hemoglobin, and increases in platelet count and in prothrombin time were observed. With treatment there was a significant increase in activated partial thromboplastin time among Mesigyna users, no change among Cyclofem users and a significant decrease among OC users. OC use led to increases in plasma levels of fibrinogen, factor VII, factor X, plasminogen, protein C and decreases in plasma levels of t-PAI and antithrombin. Use of combined injectables induced no change (Cyclofem) or decreases (Mesigyna) in plasma levels of fibrinogen, factor VII, factor X and antithrombin. Use of both combined injectables led to decreases in protein C, slight decreases in plasminogen and increases in plasminogen and fibrinogen. Overall, the injectable preparations may be more beneficial than the oral preparation in not enhancing a hypercoagulable state because of the reduced synthesis of fibrinogen, factors VII and X; however, decreases in antithrombin and protein C, which are potent coagulation inhibitors, may raise some concern. Whether these changes can lead to modifications in the risk of arterial or venous disease can only be ascertained by conducting epidemiological studies.     

益生菌VSL#3对大鼠慢性实验性结肠炎疗效及Th1/Th2细胞因子影响的研究

目的 研究益生菌VSL#3对葡聚糖硫酸钠诱导的大鼠慢性实验性结肠炎预防作用及机制.方法 反复自由饮用5％葡聚糖硫酸钠溶液诱导大鼠慢性结肠炎模型,30只SD大鼠分为3组,正常对照组（n=10）,益生菌VSL#3组（n=10）,模型组（n=10）,实验第69天处死大鼠,评价大肠病理学损伤,应用Real-time PCR方法与ELISA方法分别检测大肠组织以及血清中IFN-γ及IL-4的表达水平.结果 益生菌VSL#3组Hamamoto评分（4.23±1.08）明显低于模型组（6.25±1.36）（P＜0.05）;与模型组相比,益生菌VSL#3组IFN-γ表达水平降低[血清（26.13±5.11） pg/ml vs（40.13±9.15）pg/ml,大肠组织：8.93±1.81 vs 13.27±1.65,P＜0.05];益生菌VSL#3组IL-4表达水平升高[血清（37.25±6.86） pg/ml vs（24.47±7.93） pg/ml,大肠组织：9.55±2.31 vs7.16±1.19,P ＜0.05].结论 益生菌VSL#3能够通过提高IL-4活性,降低IFN-γ的活性防治DSS诱导的大鼠慢性实验性结肠炎的肠道炎症.     

An open-label, comparative study of the effects of a dose-reduced oral contraceptive containing 0.02 mg ethinylestradiol/2 mg chlormadinone acetate on hemostatic parameters and lipid and carbohydrate metabolism variables

Objective

The study was conducted to compare the effects of 0.02 mg ethinylestradiol (EE)/2 mg chlormadinone acetate (CMA), given for 24 days each cycle, with those of 0.02 mg EE/0.15 mg desogestrel (DSG) and 0.03 mg EE/0.15 mg levonorgestrel (LNG), given for 21 days each cycle, on hemostatic, lipid, and carbohydrate metabolism parameters in healthy subjects, over six medication cycles.

Study design

A randomized, multicentre, open-label, Phase II trial measured markers of hemostasis, and of lipid and carbohydrate metabolism in 165 subjects randomly assigned to treatment with one of three combined oral contraceptives (COCs).

Results

EE/CMA and EE/DSG had a similar effect on hemostatic parameters, the EE/LNG group showed comparatively smaller increases in the activity of factor VII [8.1% vs. 36.6% (EE/CMA) and 28.2% (EE/DSG)], protein C [5.9% vs. 32.9% (EE/CMA) and 21% (EE/DSG)] and endogenous thrombin potential-based activated protein C resistance [44.1% vs. 93.5% (EE/CMA) and 108.1% (EE/DSG)], and in contrast, free protein S levels decreased in the EE/CMA and EE/DSG groups (−12.7% and −4.3%, respectively) but rose in the EE/LNG group (20.4%). In all treatments, total cholesterol, total triglyceride and apolipoproteins increased. Levels of very low-density lipoprotein cholesterol particularly rose across all groups. Slight increases in high-density lipoprotein (HDL) cholesterol were observed for EE/CMA (14.6%) and EE/DSG (8.5%), with a rise above the upper limit of normal in 30% of the subjects taking EE/CMA. Conversely, for EE/LNG slight decreases in HDL cholesterol were observed (−12.4%) lipoprotein (a) levels decreased in the EE/CMA (−6.6%) and EE/LNG (−16.9%) groups and were unchanged in the EE/DSG group.

Conclusions

The changes observed were typical of those seen across low-dose COCs that differ according to commonly-used progestogens.