针对新修订的医疗器械和体外诊断试剂法规与指导原则在临床试验实施阶段的主要变化,总结研究者、医疗器械临床试验机构和申办者需要关注的重要问题,通过对盲法、医疗器械/体外诊断试剂和生物样本管理的典型案例分析,加强对临床试验实施环节中风险及质控要点的理解,通过多方合作不断提高医疗器械和体外诊断试剂临床试验的质量.

多囊卵巢综合征(PCOS)是育龄期女性最常见的妇科内分泌疾病之一.生酮饮食(KD)是一种以低碳水化合物、高脂肪、适量蛋白质为特点的饮食结构.2019年专家组组织了妇科专家和营养专家共同制定并发布了《生酮饮食干预多囊卵巢综合征中国专家共识(2018年版)》.鉴于近5年KD治疗在安全性和应用范围方面出现了大量新的临床数据,专家组决定对《生酮饮食干预多囊卵巢综合征中国专家共识(2018年版)》进行修订和数据更新.主要更新内容有:①更新中国PCOS患病率研究数据;②增加PCOS中的代谢综合征与饮食干预临床证据;③增加KD改善PCOS的循证证据及中国临床研究证据;④增加KD对与PCOS相关代谢综合征影响的循证医学证据;⑤提供短期和长期KD有效性和安全性证据;⑥增加低能量生酮饮食(LCKD)在PCOS中的应用及安全性证据;⑦增加PCOS治疗常用药物联合KD干预效果的证据;⑧完善KD干预PCOS的适应证、禁忌证、不良反应及对策;⑨完善KD中食物种类的选择及操作方法建议.

Objective:To investigate the diagnostic value of neutrophil CD64 index (nCD64) in disseminated nontuberculous mycobacteria (NTM) infection.Methods:Thirty-six patients with NTM infection from January 2020 to June 2021 in Huashan Hospital, Fudan University were included. Patients were classified into groups of disseminated infection and focal infection according to their medical history and discharge diagnosis. The expressions of nCD64 in patients with focal infection and disseminated infection before treatment were collected and analyzed. Statistical analysis was performed using the Mann-Whitney U test, and the diagnostic value of nCD64 for disseminated NTM infection was analyzed using the receiver operator characteristic curve (ROC curve). Results:Among the 36 patients with NTM infection, 18 cases were focal infection (due to the low white blood cell count of the patient with myelodysplastic syndrome, the detection results were biased, which were excluded from the subsequent analysis) and 18 cases were disseminated infection. The expression of nCD64 in focal infection was 0.72(0.50, 1.55), and that in disseminated infection was 13.63(6.77, 32.31). The difference was statistically significant ( U=15.50, P<0.001). Using focal infection as a control, the area under the ROC curve for the operational characteristics of the subjects was 0.949 3 for disseminated NTM infection. The diagnostic cut-off value of nCD64 was 3.06, with the sensitivity and specificity of the disseminated NTM infection were 88.89% and 100.00%, respectively. Conclusions:In patients with NTM infection before effective treatment, the diagnostic cut-off value of nCD64 of 3.06 has high sensitivity and specificity, which is useful for the aided diagnosis of disseminated NTM infection.

目的 建立和验证临床试验质量管理量化测评体系.方法 参考国内外指南,结合本院实践对质量问题进行分类、分级与评分,建立测评体系.用相关性与配对符号秩检验分析重测信度与测试员间可信度.结果 用本院临床试验项目验证该体系,同一测试员间隔2周重复判定质量问题,分类的相关系数为0.643～1.000,质量评分、重要和一般级别为0.895以上.不同测试员对分类判定的相关系数为0.616～1.000,质量评分、重要和一般级别为0.828以上.所有判定结果间无显著差异(P＞0.05).严重级别的信度虽不高,但不影响整体判定.结论 本研究建立了可信度高的量化测评体系,可为临床试验质量管理提供标准化方法.

Objective:To analyze the statuses of CD8 + T cell exhaustion in patients with human immunodeficiency virus (HIV) infection, Mycobacterium tuberculosis (MTB) infection and co-infection. Methods:A total of 87 patients infected with HIV and/or MTB in Wuxi Fifth People′s Hospital and Taicang First People′s Hospital from August 2019 to January 2020 were enrolled, including 18 cases of HIV infection, 34 cases of active tuberculosis (ATB), 19 cases of latent tuberculosis infection (LTB), seven cases of HIV coinfected with ATB, and nine cases of HIV coinfected with LTB. Another 11 healthy controls were also included. The peripheral blood of all subjects was collected for cell surface staining and intracellular cytokine staining, and flow cytometry was used to detect the expressions of activation molecules including CD62 ligand, CD44 and CD127, the transcription factor like eomesodermin (EOMES), T cell factor 1 (TCF-1), T-box expressed in T cells (T-bet), B lymphocyte-induced maturation protein 1 (Blimp-1), inhibitory receptors including programmed death-1 (PD-1) and T-cell immunoglobulin and mucin domain 3 (Tim-3) on CD8 + T cells. Mann-Whitney U test was used for statistical analysis. Results:The mean fluorescence intensities (MFIs) of the activation molecules CD62 ligand and CD44 in the HIV group were lower than those in the healthy control group, while the inhibitory receptor Tim-3 was higher than that in the healthy control group. The differences were all statistically significant ( U=31.00, 1.00 and 0.00, respectively, all P<0.010). The MFIs of CD62 ligand and CD44 in HIV coinfected with LTB group were lower than those in LTB group, while PD-1 and Tim-3 were higher than those in LTB group. The differences were all statistically significant ( U=4.00, 26.00, 6.00 and 3.00, respectively, all P<0.010). The MFIs of CD62 ligand, CD44 and CD127 in HIV coinfected with ATB group were lower than those in ATB group, while PD-1 and Tim-3 were higher than those in ATB group. The differences were all statistically significant ( U=9.00, 40.00, 45.50, 28.00 and 7.00, respectively, all P<0.010). The proportion of terminal effector CD8 + T cells in the HIV group was higher than that in the healthy control group, while the proportion of central memory CD8 + T cells was lower than that in the healthy control group. The differences were both statistically significant ( U=15.00 and 33.00, respectively, both P<0.010). The proportion of terminal effector CD8 + T cells in the HIV coinfected with LTB group was higher than the LTB group, while the proportion of central memory CD8 + T cells was lower than that in the LTB group. The differences were both statistically significant ( U=7.00 and 20.00, respectively, both P<0.010). The proportion of terminal effector CD8 + T cells in the HIV coinfected with ATB group was higher than that in ATB group, while the proportion of central memory CD8 + T cells was lower than that in ATB group. The differences were statistically significant (both U=7.00, P<0.001). The expression level of PD-1 + Tim-3 + T cells in HIV group was higher than that in healthy control group, that in HIV coinfected with LTB group was higher than that in LTB group, and that in HIV coinfected with ATB group was higher than that in ATB group. The differences were all statistically significant ( U=21.00, 6.00 and 5.50, respectively, all P<0.001). The MFI of transcription factors EOMES and TCF-1 in HIV coinfected with LTB group were lower than those in HIV group, while the MFI of T-bet was higher than that in HIV group. The differences were all statistically significant ( U=3.00, 4.00 and 9.00, respectively, all P<0.001). The MFI of EOMES and TCF-1 in HIV coinfected with ATB group were lower than those in HIV group, while the MFI of T-bet and Blimp-1 were higher than those in the HIV group. The differences were all statistically significant ( U=11.00, 14.00, 7.00 and 22.00, respectively, all P<0.050). Conclusions:MTB co-infected with HIV patients present lower immune function and a higher degree of CD8 + T cell exhaustion. In addition, HIV patients co-infected with LTB and ATB have a higher degree of CD8 + T cell exhaustion than HIV infected patients.

目的 通过评估经鼻高流量湿化氧疗在肺部感染患者中的临床疗效,为肺部感染尤其是重症肺炎的患者呼吸道管理策略提供一定的参考依据.方法 2015年9月至2017年9月,采用方便抽样法选取收治于复旦大学附属华山医院感染科的375例肺部感染患者作为研究对象.依据入组时间将其分为对照组和观察组,对照组接受常规治疗,观察组在对照组的基础上根据病情接受经鼻高流量湿化氧疗.比较两组患者的气管插管例数及预后转归,并比较有无接受经鼻高流量湿化氧疗重症肺炎患者的预后情况.结果 两组患者住院期间插管率、出院后28 d内死亡率比较,差异均无统计学意义(P>0.05);观察组入院时重症肺炎率大于对照组(P<0.05);观察组入院时重症肺炎患者出院后28 d内死亡率小于对照组(P<0.05);观察组接受HHFNC的重症肺炎患者治疗后的呼吸频率、心率、氧饱和度、氧分压均较治疗前有所改善(P<0.05).结论 肺部感染患者例数增多且病情加重,经鼻高流量湿化氧疗能有效改善重症肺炎患者临床症状,值得临床推广使用.

The establishment of pregnancy depends on the normal function of endometrium. CD55 is up-regulated in the secretory endometrium and reaches the peak during the window of implantation, while abnormal expression of CD55 is associated with recurrent abortion, repeated implantation failure, endometriosis, endometrial cancer and other endometria-related diseases. Besides inhibiting the complement-dependent cytotoxicity as a complement regulatory protein, CD55 in endometrium also plays a role in regulating cell cycle, promoting cell proliferation, inhibiting apoptosis, and promoting cell invasion, migration and adhesion. CD55 can also bind its ligand CD97 as inhibitory signals of T cells and natural killer (NK) cells and participate in promoting cell invasion and migration in non-immune cells. This review summarizes the role of CD55 in endometrium and its potential regulatory mechanism, providing more evidence for exploring the function of CD55 in endometrial receptivity establishment and embryo implantation.

Objective:To explore the influence of anxiety on the quality of life and its associated factors in patients with polycystic ovary syndrome (PCOS).Methods:PCOS patients were enrolled in this cross sectional study in Reproductive Endocrinology, Obstetrics and Gynecology Hospital of Fudan University from May 2019 to January 2022. Anxiety and quality of life were scored for patients diagnosed with PCOS. All patients were divided into PCOS with or without anxiety group. The associated factors of PCOS complicated with anxiety were screened from clinical features, endocrine, ovarian reserve function and metabolic status by logistic analysis and receiver operating characteristic (ROC).Results:Totally 125 PCOS patients were enrolled, of whom 44 were complicated with anxiety. The scores for the quality of life in patients with PCOS and anxiety related to obesity (12.7±1.4 vs. 18.8±0.9, P<0.001), abnormal menstruation (17.9±0.9 vs. 23.2±0.6, P<0.001) and PCOS itself (28.3±1.6 vs. 35.0±0.9, P<0.001) were all lower than those in PCOS patients without anxiety. The body mass index (BMI) [(25.74±0.97) kg/m 2vs. (23.46±0.45) kg/m 2, P=0.038] and area of insulin under the curve (IAUC) [(2 844.28±303.61) pmol/L vs. (1 834.28±147.89) pmol/L, P=0.001] of PCOS patients with anxiety were all higher, while sex hormone binding globulin (SHBG) levels [(33.29±6.21) nmol/L vs. (41.94±4.11) nmol/L, P=0.045] were lower than those without anxiety, and the differences were all statistically significant. Logistic regression analysis screened out the most relevant factor with anxiety in PCOS as IAUC ( OR=1.001, 95% Cl=1.000-1.001, P=0.021) and BMI ( OR=1.113, 95% CI=1.016-1.219, P=0.003). ROC analysis showed that IAUC was an associated factor for PCOS complicated with anxiety, and the area under the ROC curve were 0.701 ( P=0.020). Conclusion:The prevalence of anxiety in PCOS patients is higher than that in the general population. The quality of life is lower in PCOS patients with anxiety than those without. Anxiety may be closely related to weight gain and hyperinsulinemia/insulin resistance in PCOS patients.

减重这件事,不是在路上,就是准备上路.这不,体重达65千克的小菁为了穿上最爱的那款婚纱,也加入了减肥大军,晨跑、夜跑、拳击、私教课,一个不落.在饮食上也是绝对控制,连着2个月几乎没吃米饭.到了第4个月的时候,小菁的体重直降至44千克.高兴之余,小菁才发现她已经连着3个月没来月经了.去医院检查排除怀孕后,医生告诉小菁是因为"减肥过猛".这是怎么回事?

目的 探讨体质指数(Body Mass Index,BMI)对妊娠中期羊水炎症标志物和基质金属蛋白酶(Matrix Metalloproteinases,MMPs)的影响,了解肥胖产妇胎儿的炎症环境暴露情况.方法 自2017年4月-2019年5月,在上海交通大学附属国际和平妇幼保健院选取妊娠16～24周单胎孕妇进行选择性羊膜腔穿刺术行核型分析的羊水样本中采集102例样本,用于白细胞介素-1β(IL-13)、白细胞介素-6(IL-6),基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-6(MMP-6)和基质金属蛋白酶-13(MMP-13)的检测.根据世界卫生组织(WHO)的BMI标准确定每组的分类:第1组:正常体质量(BMI 18.5～24.9),24例;第2组:超重(BMI 25.0～29.9),28例;第3组:Ⅰ级肥胖(BMI 30～35),26例;第4组:Ⅱ～Ⅲ级肥胖(BMI 35～40和＞40),24例.记录每例产妇羊膜穿刺术的年龄、胎次、BMI、孕龄、围产期并发症以及新生儿结局.采用SPSS 23.0软件比较各组羊水细胞因子、MMPs、孕妇一般情况、妇婴围产期结局的差异.结果 Ⅱ～Ⅲ级肥胖患者的IL-Ip水平显著高于Ⅰ级肥胖、超重和正常体质量患者(P＜0.05).正常体质量组的IL-1β水平显著低于其他各组(P＜0.05).IL-6水平在正常体质量组中最低,在Ⅱ～Ⅲ级肥胖患者中最高,Ⅰ级肥胖和Ⅱ～Ⅲ级肥胖组患者的IL-6水平显著高于正常组和超重组(P＜0.05).Ⅱ～Ⅲ级肥胖患者羊水MMP-1,MMP-6和MMP-13显著高于其他各组(P＜0.05).正常体质量组中MMP-6和MMP-13水平显著低于所有其各组(P＜0.05).Ⅱ～Ⅲ级肥胖患者产前先兆子痫和妊娠期糖尿病(Gestational Diabetes Mellitus,GDM)发生率明显高于其他组(P＜0.05).Ⅰ级和Ⅱ～Ⅲ级肥胖患者的新生儿出生体质量明显高于其他组.Ⅱ～Ⅲ类肥胖患者新生儿第5分钟阿普加评分(Apgar Score)评分低于7分的例数最多,且新生儿重症监护病房(Neonatal Intensive Care Unit, NICU)入住率最高.结论 肥胖孕妇的胎儿在子宫内接触的促炎细胞因子和MMPs水平高于正常体质量孕妇,这种高水平的暴露可能与妊娠期肥胖相关的不良围产期结局有关.

饮食如何影响多囊 有70％ ～80％的多囊患者会发生胰岛素抵抗,这意味着什么呢? 胰岛素是由胰岛产生的一种激素,帮助身体利用葡萄糖,将葡萄糖转换为能量供身体应用.而胰岛素抵抗意味着你的身体不能很好地利用胰岛素,所以会努力产生更多的胰岛素以维持血糖正常.在饮食结构中,碳水化合物(如淀粉、含糖的食物),以及致炎性食物(油炸、红肉及加工肉类)的长期摄入过多,就会导致胰岛素抵抗.而胰岛素抵抗正是引起多囊卵巢综合征的诱因之一.与此同时,多囊卵巢综合征的雄激素增高的特征,反过来又会促进胰岛素抵抗.因此,两者之间是恶性循环的关系.

小陈今年26岁,近半年来月经失调,已有三个月不来月经了.她非常担心,到医院就诊后查了激素六项,检查结果显示她得了高催乳素血症.医生建议她进一步行磁共振检查.经检查,确诊为垂体催乳素瘤.一听自己患上了垂体催乳素瘤,小陈心里纳闷:本来是来看月经失调的,怎么会是“瘤”呢?

Objective To investigate the effects of Rapamycin, a mammalian target of rapamycin (mTOR) specific inhibitor, on the activation and growth of primordial follicles in mice from the signal transduction of follicular development. Methods A total of 40 C57BL/6 female mice were randomly divided into control group (n=20, same volume of saline) and Rapamycin treatment group (n=20, 5 mg/kg Rapamycin). Seven mice in each group were treated after 30 d, and ovarian histomorphological changes were observed by HE staining, the expressions of DDx4/MVH and Ki-67 were detected by immunohistochemistry, the level of mTOR and its downstream molecules were detected by Western blotting. Eight weeks after administration, 6 mice in control group and Rapamycin treatment group were selected for follicle count, and the expressions of anti-Mullerian hormone (AMH) and Ki-67 were detected by immunohistochemistry. Another 7 mice of both groups were treated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) for ovulation induction. The ovaries were obtained for histomorphological observation by HE staining. Results The number of primordial follicle in Rapamycin treatment group was significantly increased compared with control group (P=0.040), and a large number of primordial follicles were clustered, while the number of growing follicles was significantly decreased(P=0.002). The number of primordial follicle, expressing DDx4/MVH molecule, was increased, while the expression of Ki-67 was decreased compared with control group. Eight weeks after Rapamycin treatment, the number of primordial follicles was still more than that in control group, and the expressions of Ki-67 and AMH in growing follicles were normal. After ovulation induction treatment, large numbers of mature follicles or corpus luteum could be observed in both two groups. Western blotting showed that the phosphorylation levels of mTOR and its downstream molecules p70S6K, rpS6 and eIF4B in Rapamycin treated group were significantly lower than those in control group, while the total molecular level did not change significantly (P>0.05). Conclusion Rapamycin could inhibit the activation of primordial follicles by inhibiting the phosphorylation of mTOR signaling pathway, and slow down the transformation rate of primordial follicles to the growth follicles, and also inhibit the development of growing follicles, thus protect the ovarian reserve function.

Objective:To evaluate the changes of mTOR signaling molecules in granulosa cells from polycystic ovary syndrome (PCOS) patients, and whether the change of mTOR siganaling is related to serum hormones.Methods:The phosphorylation levels of mTOR signaling molecules in primary granulosa cells were compared between PCOS group and control group. The correlation between phosphorylation levels of mTOR signaling and serum hormones was also analyzed. Then effects of exogenous testosterone and insulin on mTOR signaling were investigated in vitro. Results:Granulosa cells from PCOS patients (0.66±0.29) had higher phosphorylation levels of mTOR compared with control group (0.34±0.32, P=0.02). The level of p-s6k1 in PCOS group (0.95±0.42) was higher than that in control group (0.62±0.29), but the difference was not statistically significant ( P>0.05). The serum testosterone was associated with p-mTOR and p-S6k1 ( P=0.01, P=0.01). Serum follicle-stimulating hormone (FSH) ( P=0.67, P=0.75) and luteinizing hormone (LH) ( P=0.75, P=0.37) levels were irrelevant with p-mTOR and p-S6k1. Conclusion:Granulosa cells from PCOS patients had higher activated mTOR signaling. Testosterone and insulin could elevate the phosphorylation levels of mTOR signaling of granulosa cells in vitro, which maybe contributed to the dysfunction of granulosa cells and follicular development stagnation of PCOS.

多囊卵巢综合征是育龄妇女最常见的生殖内分泌紊乱及代谢失调综合征.该病的发病率高达5％ ～10％,主要临床表现为月经失调、高雄激素血症、肥胖和不孕等,并可导致子宫内膜癌、糖尿病、代谢综合征和心血管疾病等远期并发症,影响患者余生的健康.对多囊卵巢综合征的治疗多采取对症治疗,其中生活方式干预是首选治疗方法,治疗药物则主要有复方口服避孕药、二甲双胍等,目的是控制疾病症状、改善患者的生活质量和预防远期并发症.

在药物临床试验中,受试者常会因检验检查、候诊等时间较长造成脱落或失访,影响临床试验的进度和质量,而检验检查报告的可溯源性又直接影响着数据的真实性和可靠性.本文介绍了本院药物临床试验受试者就诊“绿色通道”及信息化建设的背景、设计思路和功能特点,其不仅可覆盖受试者访视的全周期,还可实现检验检查优先叫号的“绿色通道”功能,提高临床试验数据的信息化和可溯源性以及受试者就诊流程的规范化和便捷性.

多囊卵巢综合征(polycystic ovarian syndrome,PCOS)是中国育龄妇女的常见疾病,具有发病率高、高雄激素血症患者比例高、继发代谢综合征比率高和重视程度低的“三高一低”特征.生活方式干预是PCOS患者首选的基础治疗,但是传统的膳食干预和运动强化方式减肥效果并不理想.生酮饮食作为一种较为高效的体质量管理方式,在PCOS的临床应用中具有较为广阔的前景.

The clinical trial data inspection has achieved the phased objectives since China Food and Drug Administration issued the announcements about clinical trial data self-inspection and verification.This paper analyzed findings of clinical trial data inspections conducted from July 2015 to June 2017 and put forward corresponding control measures to common problems,which existed in the records and traceability of clinical data and medical examination,protocol compliance,investigational drug management,recording and reporting of safety information,screening and inclusion of subjects,obtaining of informed consent,and so on.

自然流产的发生率高达10％左右.而反反复复发生的流产,医学上叫复发性流产,定义是发生超过两次以上的自然流产.流产的反复发生会给家庭造成打击,给夫妻造成精神创伤和心理压力.为什么会反复发生自然流产?如何才能预防流产再发生?这都是患者急需了解的知识.

我们都怕老,尤其是女性,除了担心衰老带来的健康问题,更担心美丽容颜的逝去. 说起女人的容颜,不能忘了卵巢这个功臣,成熟女性卵巢每月排卵,主司生殖,还有一个功能是分泌雌激素和孕激素.雌激素和孕激素主管生殖器官生长及女人的月经来潮,此外,还管着女性美丽的曲线、丰满的乳房、细腻光滑的肌肤.