Aging attenuates the ovarian circadian rhythm

ObjectiveTo study the effect of aging on ovarian circadian rhythm.DesignHuman and animal study.SettingUniversity hospital and research laboratory.Patients/animalsHuman granulosa cells were obtained by follicular aspiration from women undergoing in vitro fertilization (IVF), and ovarian and liver tissues were obtained from female C57BL/6 mice.Intervention(s)None.Main outcome measure(s)Expression of circadian genes in young and older human granulosa cells and circadian rhythm in ovaries and livers of young and older mice.Result(s)All examined circadian clock genes in human granulosa cells showed a downward trend in expression with aging, and their mRNA expression levels were negatively correlated with age (P < 0.05). Older patients (≥ 40 years of age) had significantly reduced serum anti-Müllerian hormone (AMH) levels. Except for Rev-erbα, all other examined circadian clock genes were positively correlated with the level of AMH (P < 0.05). The circadian rhythm in the ovaries of older mice (8 months) was changed significantly relative to that in ovaries of young mice (12 weeks), although the circadian rhythm in the livers of older mice was basically consistent with that of young mice.Conclusion(s)Lower ovarian reserve in older women is partially due to ovarian circadian dysrhythmia as a result of aging.Electronic supplementary materialThe online version of this article (10.1007/s10815-020-01943-y) contains supplementary material, which is available to authorized users.     

中医药治疗耳鼻咽喉头颈外科领域临床优势病种的探讨

在耳鼻咽喉头颈外科常见病的诊疗中，中西医各有优势与局限。临床诊疗中，中西医结合治疗的疗效肯定，但在优势病种选择及诊疗方案选择方面尚无统一意见。中华中医药学会组织中西医耳鼻咽喉头颈科专家一起进行探讨，从病因、机制、临床诊疗方法等方面出发，基于多项临床研究结果，综合专家意见，推荐将急性咽炎、慢性咽喉炎、咽异感症、癔症性失音、过敏性鼻炎、主观性耳鸣、耳源性眩晕遴选为优势病种，制定出中西医融合的诊疗方案及建议并形成专家指导意见，供临床参考。以期通过中西医结合治疗，使更多的患者受益。     

缺牙间隙对美学区水平骨增量延期种植的临床效果影响研究

目的:评价不同缺牙间隙大小对上前牙区连续缺牙伴水平骨量不足、行水平骨增量延期种植的临床效果影响.方法:回顾性分析2013年1月～2019年6月期间,于烟台市口腔医院种植科就诊,上颌前牙连续缺失,行水平骨增量延期种植的患者,根据缺牙间隙分为两组,A组为2颗牙连续缺失,B组为3～6颗牙连续缺失.通过Mimics软件重建骨增量区3D模型,测量骨增量的体积及宽度;通过Image J软件测量平行投照根尖片种植体周围边缘骨丧失高度.使用SPSS 26.0软件,对测得的结果进行统计分析,P<0.05为差异具有统计学意义.结果:纳入44例患者,年龄18～60(平均38.52±12.56)岁.共计122个位点,植入94枚种植体,其中A组44枚,B组50枚.A、B组每牙位骨增量体积差异无统计学意义(P>0.05);A组每牙位骨增量宽度小于B组每牙位骨增量宽度(P<0.05);种植体周围骨质丧失高度随时间变化而增加(P<0.05);组别对种植体近中及远中骨边缘丧失高度的影响差异无统计学意义(P>0.05).结论:美学区水平骨增量延期种植可获得满意的临床效果,缺牙间隙对对骨增量体积及种植体周围边缘骨质稳定性无影响.     

A Phase I Dose Escalation Study of the Safety,Tolerability, and Pharmacokinetics of Ipilimumab in Chinese Patients with Select Advanced Solid Tumors

Lessons Learned

• The overall safety profiles of ipilimumab 3 mg/kg and 10 mg/kg administered every 3 weeks, were consistent between Chinese patients with solid tumors in the current study and patients from previous U.S. ipilimumab monotherapy studies. No new safety signals were identified.
• The mean systemic exposures to ipilimumab (assessed by first dose area under the curve during the dosing interval and maximum serum concentration) were numerically lower in the Chinese patient population than in U.S. patients for both 3 mg/kg and 10 mg/kg doses; however, the range of serum concentrations in the Chinese and U.S. populations overlapped (3 mg/kg and 10 mg/kg), suggesting that ipilimumab pharmacokinetics was ethnically insensitive in this study.

BackgroundThis phase I, open‐label study assessed ipilimumab safety, tolerability, pharmacokinetics (PK), immunogenicity, and antitumor activity in Chinese patients with unresectable, metastatic, recurrent malignant melanoma (MM) or nasopharyngeal carcinoma (NPC).MethodsOf 39 patients enrolled, 25 received ipilimumab (11 patients received 3 mg/kg, and 14 patients received 10 mg/kg). Reasons for not receiving treatment were withdrawal of consent (3 patients), no longer meeting the criteria (10 patients), and one recorded as “other.” During the induction phase, patients received ipilimumab (3 mg/kg, i.v.), on day 1 of a 3‐week cycle, to a maximum of four doses or progressive disease (PD). During the maintenance phase at week 24, patients received ipilimumab (3 mg/kg, i.v.) on day 1 of a 12‐week cycle, to a maximum of 3 years or PD. Considering the co‐primary safety and PK endpoints, the successive dosing required nine patients with two or fewer dose‐limiting toxicities during the 42‐day observation period to proceed with a new cohort of nine patients at 10 mg/kg.ResultsIpilimumab safety and PK profiles were similar in Chinese and predominantly White populations. Ipilimumab was well tolerated. Most adverse events (AEs) were grades 1–2 and experienced by 11 patients treated with 3 mg/kg and 14 patients treated with 10 mg/kg. There were no new safety concerns. Incidence of anti‐ipilimumab antibodies was low (1 of 10 in the 3 mg/kg patients and 2 of 13 in the 10 mg/kg patients) and without safety implications. In the 3 mg/kg group, 8 of 11 patients had PD. In the 10 mg/kg group (all NPC, 0 MM patients), 11 of 14 patients had PD. Three patients had stable disease (one at 3 mg/kg and two at 10 mg/kg).ConclusionIpilimumab was well tolerated in Chinese patients, showing similar safety and PK to previous studies in predominantly White populations.     

新冠肺炎临床评价核心指标集比较分析＊

目的 对已公开发表的新冠肺炎核心指标集及其研究方法进行比较分析，为临床试验和证据转化研究提供参考信息。方法 计算机检索COMET数据库，并补充检索CNKI、WanFang、PubMed、Web of Science、The Cochrane Library等数据库，收集发表的新型冠状病毒肺炎（Coronavirus Disease 2019，COVID-19）核心指标集（Core Outcome Set，COS）研究，检索时间截至为2021年3月31日。按照纳入排除标准筛选文献，并提取研究基本信息、研究方法及指标数据，对其进行描述性分析。结果 共纳入5项COVID-19核心指标集相关研究（4项为COVID-19-COS研究，1项为COVID-19核心指标测量工具研究）。相同的结局指标包括死亡率、病毒核酸检测、临床进展、恢复期、临床症状评分及临床分型等。指标来源主要来自临床试验注册平台和问卷调查；达成共识的方法主要采用共识会议；利益相关群体中临床专家、方法学专家和医疗管理人员涉及较多。结论 不同的新冠肺炎核心指标集研究有一定的共性，但由于应用场景不同，也存在一定差异。随着对疾病认识的深化，相关COVID-19核心指标需要加强测量方法和疗程推荐。