Volume 135 · Issue 09 · 2022

表观遗传调控是控制基因转录和细胞命运的关键机制。在过去的几十年中，已经观察到组蛋白、DNA和RNA修饰参与决定神经干细胞(NSC)的命运。这些修饰包括组蛋白乙酰化和甲基化，以及DNA和RNA甲基化。值得注意的是，非编码RNA也参与神经分化。^[1]除了乙酰化之外，已经鉴定了组蛋白赖氨酸的许多其他类型的酰化，包括巴豆酰化、丙酰化、琥珀酰化和丙二酰化。^[2]这些组蛋白酰化在神经科学中的作用仍然难以捉摸。

心力衰竭（HF）是目前世界范围内的主要疾病负担之一。充血性心力衰竭相关的医疗保险支出仍然很高，构成了全球性挑战。尽管采用了现代治疗策略，心力衰竭患者在表现后仍面临显著增加的复发住院、发病率和死亡率风险。^[1]

我们有如此多的患者患有射血分数保留的心力衰竭（HFpEF），治疗仍然存在问题。大约一半的心力衰竭患者保留了左心室（LV）收缩功能，并且通常具有某种程度的舒张功能障碍。收缩功能降低或保留的患者可能具有相似的症状，并且在临床上可能难以根据体征和症状区分两者。在发达国家，导致心肌梗塞和功能心肌丧失（缺血性心肌病）的冠状动脉疾病（CAD）是收缩性心力衰竭的最常见原因。全身性高血压仍然是心力衰竭的重要原因，在美国甚至更常见，是由于其他原因（如CAD）导致心功能不全的患者的加重因素。几种过程可能表现为扩张型或充血性心肌病，其特征是LV或双心室扩张和全身性收缩功能障碍。扩张型心肌病的罕见原因包括浸润性疾病（血色病、结节病和淀粉样变性）、其他感染因子、代谢紊乱、心脏毒素和药物毒性。心脏瓣膜疾病——特别是退行性主动脉瓣狭窄和慢性主动脉瓣或二尖瓣反流——是心力衰竭的常见原因。持续性心动过速常与房性心律失常有关，可引起收缩功能障碍，通过控制心率可能是可逆的。舒张性心脏功能障碍与衰老和相关的心肌硬化以及通常由高血压引起的左心室肥大(LVH)有关。肥厚性或限制性心肌病、糖尿病和心包疾病等病症可产生相同的临床表现。伴有或不伴有快速心室反应的房颤可能导致左心室充盈受损。

Ciprofol (HSK3486; Haisco Pharmaceutical Group Co., Ltd., Chengdu, China), developed as a novel 2,6-disubstituted phenol derivative showed similar tolerability and efficacy characteristics as propofol when applicated as continuous intravenous infusion for 12 h maintenance sedation in a previous phase 1 trial. The phase 2 trial was designed to investigate the safety, efficacy, and pharmacokinetic characteristics of ciprofol for sedation of patients undergoing mechanical ventilation.

In this multicenter, open label, randomized, propofol positive-controlled, phase 2 trial, 39 Chinese intensive care unit patients receiving mechanical ventilation were enrolled and randomly assigned to a ciprofol or propofol group in a 2:1 ratio. The ciprofol infusion was started with a loading infusion of 0.1-0.2 mg/kg for 0.5-5.0 min, followed by an initial maintenance infusion rate of 0.30 mg·kg^-1·h^-1, which could be adjusted to an infusion rate of 0.06 to 0.80 mg·kg^-1·h^-1, whereas for propofol the loading infusion dose was 0.5-1.0 mg/kg for 0.5-5.0 min, followed by an initial maintenance infusion rate of 1.50 mg·kg^-1·h^-1, which could be adjusted to 0.30-4.00 mg·kg^-1·h^-1 to achieve -2 to +1 Richmond Agitation-Sedation Scale sedation within 6-24 h of drug administration.

Of the 39 enrolled patients, 36 completed the trial. The median (min, max) of the average time to sedation compliance values for ciprofol and propofol were 60.0 (52.6, 60.0) min and 60.0 (55.2, 60.0) min, with median difference of 0.00 (95% confidence interval: 0.00, 0.00). In total, 29 (74.4%) patients comprising 18 (69.2%) in the ciprofol and 11 (84.6%) in the propofol group experienced 86 treatment emergent adverse events (TEAEs), the majority being of severity grade 1 or 2. Drug- and sedation-related TEAEs were hypotension (7.7% vs. 23.1%, P = 0.310) and sinus bradycardia (3.8% vs. 7.7%, P = 1.000) in the ciprofol and propofol groups, respectively. The plasma concentration-time curves for ciprofol and propofol were similar.

ciprofol is comparable to propofol with good tolerance and efficacy for sedation of Chinese intensive care unit patients undergoing mechanical ventilation in the present study setting.

ClinicalTrials.gov, NCT04147416.

Time in range (TIR) refers to the time an individual spends within their target glucose range, which now has been popularized as an important metric to classify glycemic management and also recognized as an important outcome of current diabetes therapies. This study aimed to investigate the association between TIR and the severity of the urinary albumin excretion rate (UAER) in patients with type 2 diabetes mellitus (T2DM).

We retrospectively analyzed the data of 1014 inpatients with T2DM at the Department of Endocrinology and Metabolism of Peking University International Hospital, China. TIR was defined as the percentage of blood glucose within the target range of 3.90-10.00 mmol/L. Urine samples for assessment of UAER were collected for 3 consecutive days from the start of hospitalization.

The TIR values for patients with normal urine levels of albumin, microalbuminuria, and macroalbuminuria were 70% ± 20%, 50% ± 20%, and 30% ± 20%, respectively (all P < 0.001). The patients were stratified according to quartiles of TIR as follows: quartile (Q) 1, <55%; Q2, 55%-72%; Q3, 73%-83%; and Q4, >83%. The incidences of microalbuminuria in Q1, Q2, Q3, and Q4 were 41.1%, 21.6%, 7.1%, and 5.5% (all P < 0.001), respectively. The respective incidences of macroalbuminuria were 24.2%, 1.1%, 1.4%, and 0% (all P < 0.001). In multinomial logistic regression analyses, TIR was significantly correlated with microalbuminuria (odds ratio [OR] 0.58, 95% confidence interval [CI]: 0.52-0.65, P < 0.001) and macroalbuminuria (OR 0.26, 95% CI: 0.18-0.38, P < 0.001) after adjusting for age, sex, body mass index, diabetes duration, systolic blood pressure, and levels of triglycerides, glycosylated hemoglobin A1c, and creatinine.

The proportion of blood glucose in TIR is closely related to the severity of UAER in patients with T2DM.

Gestational weight gain (GWG) is associated with the risk of gestational diabetes mellitus (GDM). However, the effect of weight gain in different trimesters on the risk of GDM is unclear. This study aimed to evaluate the effect of GWG on GDM during different trimesters.

A birth cohort study was conducted from 2017 to 2020 in Shenzhen, China. In total, 51,205 participants were included comprising two models (early pregnancy model and middle pregnancy model). Gestational weight (kg) was measured at each prenatal clinical visit using a standardized weight scale. Logistic regression analysis was used to assess the risk of GDM. Interaction analysis and mediation effect analysis were performed in the middle pregnancy model.

In the early pregnancy model, the risk of GDM was 0.858 times lower (95% confidence interval [CI]: 0.786, 0.937) with insufficient GWG (iGWG) and 1.201 times higher (95% CI: 1.097, 1.316) with excessive GWG after adjustment. In the middle pregnancy model, the risk of GDM associated with iGWG increased 1.595 times (95% CI: 1.418, 1.794) after adjustment; for excessive GWG, no significant difference was found (P = 0.223). Interaction analysis showed no interaction between GWG in early pregnancy (GWG-E) and GWG in middle pregnancy (GWG-M) (F = 1.268; P = 0.280). The mediation effect analysis indicated that GWG-M plays a partial mediating role, with an effect proportion of 14.9%.

eGWG-E and iGWG-M are associated with an increased risk of GDM. Strict control of weight gain in early pregnancy is needed, and sufficient nutrition should be provided in middle pregnancy.

It is crucial to improve the quality of care provided to ICU patient, therefore a national survey of the medical quality of intensive care units (ICUs) was conducted to analyze adherence to quality metrics and outcomes among critically ill patients in China from 2015 to 2019.

This was an ICU-level study based on a 15-indicator online survey conducted in China. Considering that ICU care quality may vary between secondary and tertiary hospitals, direct standardization was adopted to compare the rates of ICU quality indicators among provinces/regions. Multivariate analysis was performed to identify potential factors for in-hospital mortality and factors related to ventilator-associated pneumonia (VAP), catheter-related bloodstream infections (CRBSIs), and catheter-associated urinary tract infections (CAUTIs).

From the survey, the proportions of structural indicators were 1.83% for the number of ICU inpatients relative to the total number of inpatients, 1.44% for ICU bed occupancy relative to the total inpatient bed occupancy, and 51.08% for inpatients with Acute Physiology and Chronic Health Evaluation II scores ≥15. The proportions of procedural indicators were 74.37% and 76.60% for 3-hour and 6-hour surviving sepsis campaign bundle compliance, respectively, 62.93% for microbiology detection, 58.24% for deep vein thrombosis prophylaxis, 1.49% for unplanned endotracheal extubations, 1.99% for extubated inpatients reintubated within 48 hours, 6.38% for unplanned transfer to the ICU, and 1.20% for 48-hour ICU readmission. The proportions of outcome indicators were 1.28‰ for VAP, 3.06‰ for CRBSI, 3.65‰ for CAUTI, and 10.19% for in-hospital mortality. Although the indicators varied greatly across provinces and regions, the treatment level of ICUs in China has been stable and improved based on various quality control indicators in the past 5 years. The overall mortality rate has dropped from 10.19% to approximately 8%.

The quality indicators of medical care in China’s ICUs are heterogeneous, which is reflected in geographic disparities and grades of hospitals. This study is of great significance for improving the homogeneity of ICUs in China.

Fibrosis in the peripheral airways contributes to airflow limitation in patients with chronic obstructive pulmonary disease (COPD). However, the key proteins involved in its development are still poorly understood. Thus, we aimed to identify the differentially expressed proteins (DEPs) between smoker patients with and without COPD and elucidate the molecular mechanisms involved by investigating the effects of the identified biomarker candidate on lung fibroblasts.

The potential DEPs were identified by isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis. The messenger RNA and protein levels of clusterin (CLU) in COPD patients and 12% cigarette smoke extract (CSE)-treated human bronchial epithelial cells were determined at the indicated time points. Furthermore, an in vitro COPD model was established via the administration of 8% CSE to normal human lung fibroblasts (NHLFs) at indicated time points. The effects of CSE treatment and CLU silencing on proliferation and activation of lung fibroblasts were analyzed.

A total of 144 DEPs were identified between COPD patients and normal smokers. The iTRAQ-based proteomics and bioinformatics analyses identified CLU as a serum biomarker candidate. We also discovered that CLU levels were significantly increased (P < 0.0001) in Global Initiative for Obstructive Lung Disease II, III, and IV patients and correlated (P < 0.0001) with forced expiratory volume in 1 s (R=-0.7705), residual volume (RV) (R = 0.6281), RV/total lung capacity (R = 0.5454), and computerized tomography emphysema (R = 0.7878). Similarly, CLU levels were significantly increased in CSE-treated cells at indicated time points (P < 0.0001). The CSE treatment significantly inhibited the proliferation, promoted the inflammatory response, differentiation of NHLFs, and collagen matrix deposition, and induced the apoptosis of NHLFs; however, these effects were partially reversed by CLU silencing.

Our findings suggest that CLU may play significant roles during airway fibrosis in COPD by regulating lung fibroblast activation.

The combination of high-frequency oscillations (HFOs) with single-mode imaging methods has been proved useful in identifying epileptogenic zones, whereas few studies have examined HFOs combined with multimodal imaging methods. The aim of this study was to evaluate the prognostic value of ripples, an HFO subtype with a frequency of 80 to 200 Hz is combined with multimodal imaging methods in predicting epilepsy surgery outcome.

HFOs were analyzed in 21 consecutive medically refractory epilepsy patients who underwent epilepsy surgery. All patients underwent positron emission tomography (PET) and deep electrode implantation for stereo-electroencephalography (SEEG); 11 patients underwent magnetoencephalography (MEG). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in predicting surgical outcome were calculated for ripples combined with PET, MEG, both PET and MEG, and PET combined with MEG. Kaplan-Meier survival analyses were conducted in each group to estimate prognostic value.

The study included 13 men and 8 women. Accuracy for ripples, PET, and MEG alone in predicting surgical outcome was 42.9%, 42.9%, and 81.8%, respectively. Accuracy for ripples combined with PET and MEG was the highest. Resection of regions identified by ripples, MEG dipoles, and combined PET findings was significantly associated with better surgical outcome (P < 0.05).

Intracranial electrodes are essential to detect regions which generate ripples and to remove these areas which indicate good surgical outcome for medically intractable epilepsy. With the assistance of presurgical noninvasive imaging examinations, PET and MEG, for example, the SEEG electrodes would identify epileptogenic regions more effectively.

脑出血（ICH）是一种严重的神经系统疾病，发病率和死亡率都很高。^[1,2]据报道，ICH患者的感染率为26%至58%。^[3]感染不仅会增加住院时间和医疗费用，还会增加死亡率、恶化功能结局和增加再入院率。本研究旨在确定ICH患者感染的患病率和相关风险因素，并调查其对患者出院后结局的影响。

致编辑：心力衰竭(HF)是目前公认的影响全球约1%-2%成年人的疾病。^[1]心力衰竭最常见的原因是瓣膜性心脏病、慢性或急性心脏缺血以及由酒精、多柔比星(Dox)、高血压、糖尿病和代谢综合征引起的普遍心肌病。^[2]近年来开发的各种治疗方法通常仅在临床前受试者中成功，并且仍然需要对HF进行有效的治疗。^[3]因此，迫切需要一种更实用的治疗策略和治疗候选物。黄芪甲苷IV（AS-IV）是黄芪(Astragalus membranaceus Bunge)、是一种广泛应用于心力衰竭患者的中药。^[4]越来越多的证据证实了AS-IV治疗心力衰竭的有效性和安全性体内和体外。然而，迄今为止，该领域的研究仅限于AS-IV的广泛作用。

致编辑：越来越多的证据表明，肠道微生物群-宿主相互作用在人类健康和疾病中起着至关重要的作用。然而，微生物与其宿主之间的动态平衡限制了单一菌株或微生物特征作为疾病风险预测和结果评估的标志物的效用。^[1]使用多组学方法分析肠道微环境的变化现已成为常规。^[2]在炎症性肠病中，尤其是在急性期，肠道微环境在2周内发生显著变化。因此，需要每2至3天获取一次粪便样本的有效策略。然而，标本储存、运输和处理方面的挑战限制了长期采样能力。在室温下储存>24小时的粪便样品的微生物组成显著改变。排空后立即在-80°C下储存粪便标本是标准程序，但在现实生活中不切实际。另一种方法是在-20°C下储存长达1个月，然后进行样品运输和实验室分析。本研究的目的是评估每2至3天收集一次并在家中-20°C下储存长达1个月的粪便标本中的肠道微环境是否可以保存。

致编辑：半咀嚼痉挛（HMS）是一种相对罕见的单侧三叉神经（TN）运动分支功能障碍，其发病机制目前尚不清楚。HMS的临床表现为相关单侧三叉神经运动支支配的肌肉不自主阵发性抽搐。近来学术界对HMS提出了两种病因：TN压迫和中枢病变学说。^[1]临床上，HMS必须与口下颌肌张力障碍、面部肌肉痉挛、多发性硬化疼痛痉挛、局灶性癫痫等相鉴别。通常，肌电图（EMG）可以确诊。目前多药和肉毒杆菌毒素注射治疗的结果仍然不令人满意。只有脑神经血管冲突的患者对微血管减压（MVD）手术反应良好。

致编辑：复发性妊娠丢失（RPL）被定义为两次或两次以上临床公认的妊娠失败。^[1]父母和胚胎/胎儿因素都与RPL相关。父母因素包括平衡染色体重排、母体抗磷脂综合征、子宫异常和激素或代谢紊乱。^[2]在检查的受孕产物（POC）中，大约60%的早期妊娠损失是由胚胎中散发的染色体异常引起的，特别是染色体数目错误。然而，高达50%的RPL病例仍然无法用已知原因解释。在这里，我们报告了一对在妊娠10周内连续四次临床妊娠丢失的夫妇，并描述了一种新的（延伸因子Tu GTP结合结构域，含有2[EFTUD2通过全外显子组测序（WES）分析，在最近三次流产的胚胎组织中发现了无义突变（c.1012G>T，p.E 338*）。此外，我们产生了一个突变与人类同源的斑马鱼系EFTUD2破坏，以调查这种突变和RPL之间的关系。我们假设该突变与胚胎致死性相关，这可能会在患者中诱导RPL。该研究由中国四川大学华西第二大学医院医学伦理委员会批准（2016[029]）。在基因检测之前，获得了这对夫妇的书面知情同意。

致编辑：左心耳（LAA）是儿童房性心律失常的主要来源之一。^[1]但起源于心外膜LAA的房性心动过速（AT）并不常见，通常起源于基底。^[2]导管消融（CA）可能是房性心律失常患者的重要策略，^[3]尤其是由于LAA发射触发器。^[4]由于大量的小梁和真正的心外膜位置，LAA的心内膜CA可能会失败，甚至导致致命的填塞。^[2,5]心外膜CA可能是一种替代方法。^[6]由于LAA具有非常薄的壁并且可能易于穿孔，因此在进行LAA消融时应谨慎，^[4]即使在心外膜消融期间。AT可能复发，可能需要手术左心耳切除术（SAE）。

致编辑：肺部超声（LUS）可能是评估冠状病毒疾病2019（新冠肺炎）肺损伤的一种有前途的技术。然而，LUS的特征及其评估价值还没有得到很好的描述。我们旨在探讨不同疾病严重程度的新冠肺炎患者的LUS特征及其评估价值。

致编辑：香港是一个医疗和产科护理水平很高的地方。保健标准的主要指标之一是孕产妇死亡率。过去数十年，香港的孕产妇死亡率一直在逐步下降。^[1]2017年，中国香港的MMR为1.7，低于或类似于许多其他高收入国家：韩国的MMR为11、新加坡8、日本5、英国7、澳大利亚6、意大利和挪威2。^[2]

致编辑：刻板行为是指一系列频率较高、没有明显目的和意义的行为。也包括兴趣狭隘，难以接受事物的变化。除自闭症谱系障碍（ASD）外，刻板行为还存在于各种神经发育障碍中，如抽动秽语综合征、脆性X综合征、Prader-Willi综合征、强迫症，以及许多其他疾病，被认为与纹状体功能障碍有关。

致编辑：院外心脏骤停（OHCA）是一个重大的公共卫生挑战。据报道，早期启动、高质量的心肺复苏（CPR）和使用自动体外除颤器（AED）可显著改善OHCA幸存者的生存率和长期结局。^[1]

致编辑：骨肉瘤（OS）是最常见的恶性原发性骨肿瘤，主要影响儿童、青少年和年轻人。统计研究表明，高达20%的OS患者在就诊时具有临床上可检测到的转移性肿瘤，并且>85%的转移发生在肺部。因此，确定反映OS生物学特征和生存率的风险因素可以为患者带来更好的干预。

在最初的文章发表之后，^[1]作者告诉我们以下错误。在高分辨率图形的最终合成过程中，无意中为图3f中NHK的蛋白质印迹β-肌动蛋白和间质蛋白酶图像放置了错误的图片。因此，图3f的公布版本是不正确的。该图的校正版本如下所示。唯一的变化是在图3f中，其余的所有图都与公布的版本相同。错误不影响文章的结果和结论。该图的校正版本如下所示。作者真诚地为这一疏忽和造成的任何混乱道歉。