Volume 135 · Issue 21 · 2022

妊娠期糖尿病（GDM），定义为在妊娠期间发病或首次识别的任何程度的葡萄糖不耐受，是一种常见的妊娠结局。^[1]GDM对母亲、胎儿、新生儿和后代的童年都有风险。患有GDM的女性可能会增加妊娠期高血压和先兆子痫、初次剖宫产以及未来肥胖、高血压、血脂异常、代谢综合征和心血管疾病的风险。^[2,3,4,5,6]约20-50%既往患有GDM的女性会在妊娠3-5年内发展为2型糖尿病，如果随访≥10年，70%会发展为2型糖尿病。^[7,8,9]更令人担忧的是，接触GDM的儿童子宫内出生时有一系列不良妊娠结局，包括早产、出生体重过高和低血糖，也有更高的肥胖风险，^[10]糖耐量受损和2型糖尿病、^[10]高血压、^[11]以及晚年血脂异常。^[12]因此，GDM可能导致肥胖和2型糖尿病的恶性代际循环。^[13]

鲜红斑痣（PWS）是一种毁容性疾病，其分子发病机制仍不明确。目前PWS的金标准治疗是脉冲染料激光（PDL）；^[1]同时，血卟啉单甲醚光动力疗法（HMME-PDT）已应用于临床5年。^[2]由于血管的异质性，很难用肉眼预测和评价其疗效。因此，将需要一种一致、可重复、无创的技术来提供准确的图像和定量的评估指标。在本研究中，我们回顾了皮肤镜、反射共焦显微镜（RCM）、高频超声（HFUS）、光学相干断层扫描（OCT）和激光散斑成像（LSI）等。在预测疗效、术中监测和客观评价PWS治疗的有效性[图1].

高血压作为心血管疾病的主要可改变危险因素，是死亡的首要原因，老年人是最脆弱的人群。^[1]在中国，≥65岁的公民中有>55%患有高血压。^[2]中国在不久的将来将面临更严重的血压负担，因为到2050年老年人预计将占总人口的30%。^[3]对于≥60岁的患者，单纯收缩期高血压是最常见的高血压亚型，定义为收缩压(SBP)≥140 mmHg，舒张压<90毫米汞柱。^[4]心血管系统的老化导致大动脉僵硬度和对心脏的动脉波反射的增加，转化为SBP的升高。^[5]然而，老年高血压患者的治疗仍然具有挑战性，这不仅是因为该人群中药物代谢的差异、多种伴随药物的使用和血压变异性的增强通常难以达到治疗目标，还因为血压目标不明确。目前基于指南的老年人SBP目标建议仍然不一致，引入了高血压治疗最佳目标的不确定性。目标是<150 mmHg在美国内科医师学会-美国家庭医师学会指南，^[6]欧洲指南中的130至139 mmHg，^[7]和<美国心脏病学会-美国心脏协会指南中的130 mmHg。^[8]因此，迫切需要确定老年高血压患者的最佳SBP目标。

The potential impact of β cell function and insulin sensitivity on adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM) remains uncertain. We aimed to investigate the association between β cell dysfunction, insulin resistance, and the composite adverse pregnancy outcomes.

This observational study included 482 women diagnosed with GDM during pregnancy. Quantitative metrics on β cell function and insulin sensitivity during pregnancy were calculated using traditional equations. The association of β cell dysfunction and insulin resistance with the risk of the composite adverse pregnancy outcomes was investigated using multivariable-adjusted logistic regression models.

Multivariable-adjusted odds ratios (ORs) of adverse pregnancy outcomes across quartiles of homeostatic model assessment for insulin resistance (HOMA-IR) were 1.00, 0.95, 1.34, and 2.25, respectively (P for trend = 0.011). When HOMA-IR was considered as a continuous variable, the multivariable-adjusted OR of adverse pregnancy outcomes was 1.34 (95% confidence interval 1.16-1.56) for each 1-unit increase in HOMA-IR. Multivariable-adjusted ORs of adverse pregnancy outcomes across quartiles of homeostatic model assessment for β cell function (HOMA-β) were 1.00, 0.51, 0.60, and 0.53, respectively (P for trend = 0.068). When HOMA-β was considered as a continuous variable, the multivariable-adjusted OR of adverse pregnancy outcomes was 0.57 (95% CI 0.24-0.90) for each 1-unit increase in HOMA-β. However, other quantitative metrics were not associated with the composite adverse pregnancy outcomes.

We demonstrated a significant association of β cell function and insulin sensitivity with the risk of adverse pregnancy outcomes. We have provided additional evidence on the early identification of adverse pregnancy outcomes besides the glycemic values.

Data on the glycemic profile of pregnant women with gestational diabetes mellitus (GDM) during the perinatal period are sparse. This study described the intrapartum and early postpartum glucose profiles among pregnant women with GDM, and analyzed factors potentially affecting glycemic parameters during the period.

This was a prospective observational study conducted from March 2020 to November 2021. Pregnant women with GDM receiving lifestyle interventions alone during pregnancy and matched women with non-diabetic pregnancies (NDPs) were enrolled from among patients admitted to the obstetrics department for childbirth. Glucose monitoring was performed via a flash glucose monitoring (FGM) system on admission, and glucose readings during labor and early postpartum were analyzed. The clinical characteristics and FGM-based parameters of participants in the two groups were compared.

A total of 124 participants (mean age: 29.5 ± 3.5 years, 92 [74.2%] primipara) were included in the final analysis. A total of 17,571 glucose readings were retrieved. There were no significant differences in clinical characteristics between the GDM (n = 60) and NDP (n = 64) groups. The average glucose level was 92.2 mg/dL, and the level was higher in the GDM group (95.5 ± 12.1 mg/dL vs. 89.1 ± 13.4 mg/dL, P = 0.008) during the intrapartum and early postpartum periods. The data were split into the intrapartum period (from the start of labor to delivery of the placenta) and the early postpartum period (within 24 h after placental delivery) for analysis. During intrapartum, women with GDM exhibited glycemic profiles and fluctuations similar to those in the NDP group. However, women with GDM had higher postpartum glucose levels (97.7 ± 13.4 mg/dL vs. 90.8 ± 15.3 mg/dL, P = 0.009), a longer time spent >140 mg/dL (8.7 ± 9.3% vs. 5.9 ± 10.3%, P = 0.011), and greater glycemic fluctuations than those with NDP. Postpartum hyperglycemia in GDM might be associated with high parity and postprandial glucose abnormalities in GDM screening tests.

Compared to those with normoglycemia, pregnant women with GDM receiving lifestyle interventions alone had similar intrapartum glucose profiles but higher early postpartum glucose levels and greater glucose variability, providing evidence for modification of the current perinatal glucose monitoring strategy for GDM.

ChiCTR.org.cn, ChiCTR2000030972

Abnormal lipids are strong predictors of cardiovascular disease in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). However, the potential associations of insulin resistance (IR) and beta-cell function (BCF) with abnormal lipids in newly diagnosed T1DM or T2DM patients are not fully understood.

A cross-sectional survey of 15,928 participants was conducted. Homeostasis model assessment and postprandial C-peptide levels were used to estimate IR and BCF. A restricted cubic spline (RCS) nested in binary logistic regression was used to examine the associations of IR and BCF with abnormal lipids.

High triglyceride (TG), low high-density lipoprotein cholesterol, and high low-density lipoprotein cholesterol (LDL-C) accounted for 49.7%, 47.8%, and 59.2% of the participants, respectively. In multivariable analysis, high IR was associated with an increased risk of high TGs (P for trend <0.001) in T1DM and is associated with an elevated risk of high TG and low HDL-C (all P for trend <0.01) in T2DM. Low BCF was not associated with risks of dyslipidemia in patients with T1DM or T2DM after adjustment for potential confounders.

High IR had different associations with the risk of dyslipidemia in newly diagnosed T1DM and T2DM patients, suggesting that early treatment that improves IR may benefit abnormal lipid metabolism.

Dermatophagoides pteronyssinus is a common allergen causing allergic diseases in China. The aim of this study was to evaluate the efficacy and safety of D. pteronyssinus extracts produced by Peking Union Medical College Hospital (PUMCH) for the skin prick test (SPT) in the diagnosis of D. pteronyssinus allergy.

A total of 910 subjects with allergic diseases were prescribed D. pteronyssinus SPT and specific sIgE (sIgE) test among the Outpatients of Department of Allergy, PUMCH from August 10, 2015 to August 30, 2017. Receiver operating characteristic curve (ROC) analysis was performed according to the results of D. pteronyssinus-sIgE detection. The accuracy of D. pteronyssinus extracts used for SPT in the diagnosis of D. pteronyssinus allergy was evaluated under different cutoff values. Adverse events after SPT were recorded to evaluate safety.

There were 796 and 618 subjects in the full analysis set (FAS) and the per protocol set (PPS), respectively. The areas under the curve of FAS and PPS were 0.871 and 0.873, respectively. According to the ROC of PPS, the optimal and 95% specificity diagnostic cutoff values of D. pteronyssinus SPT mean wheal diameter were 3.25 and 3.75 mm, respectively. No adverse events occurred.

The extracts of D. pteronyssinus for SPT were simple, highly accurate, and safe and should be considered for recommendation in the clinical diagnosis of D. pteronyssinus allergy.

Although various therapies have been developed to treat malalignment in osteoarthritic knees, the pattern of malalignment progression is still unclear. This study aimed to identify homogeneous subgroups with distinct trajectories of malalignment progression in subjects with symptomatic knee osteoarthritis (KOA) and to determine corresponding risk factors.

Eight-year follow-up (from 2004 to 2012) data on 1252 participants with symptomatic KOA from the Osteoarthritis Initiative were included. Varus/valgus angle progression was characterized by group-based trajectory models. Time-varying covariates were introduced into the model to investigate how they affected trajectories. Multinomial logistic regression for trajectory group membership was applied to ascertain risk factors.

Five subgroups were identified. Participants in the varus worsening trajectory (n = 166) or valgus worsening trajectory (n = 118) proceeded to worsen malalignment over time. The neutral trajectory (n = 378), varus stable trajectory (n = 328), and valgus stable trajectory (n = 262) maintained close to the initial varus/valgus angle over 8 years. Higher baseline Kellgren and Lawrence grade (odds ratio [OR] = 4.35, P < 0.001 for varus; OR= 3.85, P < 0.001 for valgus) and "severe" baseline malalignment (OR = 13.57, P < 0.001 for varus; OR = 23.04, P < 0.001 for valgus) were risk factors for worsening trajectories. The cutoff point of the baseline varus/valgus angle to discriminate between stable or worsening trajectory was -4.5° for varus and 3.6° for valgus.

This study identified the malalignment progression pattern — minor malalignment (-4.5° to +3.6°) tends to remain stable, while major baseline malalignment is likely to progress. This provides a reference for therapy to prevent malalignment from deteriorating and emphasizes the necessity of determining the trigger factors for malalignment onset.

For patients with severe neck angulation (SNA), hemodynamic and clinical outcomes following endovascular aneurysm repair (EVAR) are still unclear. This study aimed to explore the influence of SNA on hemodynamic and clinical outcomes following EVAR.

This study included a hemodynamic analysis and a retrospective cohort study from West China Hospital of Sichuan University between January 2011 and December 2020. The Cox regression model, inverse probability of treatment weighting (IPTW) analysis, sensitivity analysis, and subgroup analysis were applied. Primary outcome was type IA endoleak (T1AEL).

In this hemodynamic analysis, nine non-severe neck angulation (nSNA) and 16 SNA idealized models were constructed. We found a significant difference in drag force between SNA and nSNA models (7.016 ± 2.579 N vs. 4.283 ± 1.460 N, P = 0.008), and proximal neck angles were significantly associated with the magnitude of drag force (F = 0.082 × α-0.006 × β + 2.818, α: 95% confidence interval [CI] 0.070-0.094; P = 0.001; β: 95% CI -0.019 to 0.007; P = 0.319). In our cohort study, 514 nSNA patients (71.5 ± 8.5 years; 459 males) and 208 SNA patients (72.5 ± 7.8 years; 135 males) were included, with a median follow-up duration of 34 months (16-63 months). All baseline characteristics were well balanced after IPTW matching. We found that SNA was associated with a significant risk of adverse limb event (hazard ratio [HR] 2.18, 95% CI 1.09-3.12), yet was not associated with T1AEL, overall survival, or reintervention. In patients without proximal or distal additional procedures (DAP), subgroup analyses suggested a significant risk of T1AEL (Proximal: HR 5.25, 95% CI 1.51-18.23; Distal: HR 5.07, 95% CI 1.60-16.07) and adverse limb event (Proximal: HR 2.27, 95% CI 1.01-5.07; Distal: HR 2.91, 95% CI 1.30-6.54) in SNA patients. However, no noticeable difference was observed in patients with proximal or DAP.

SNA has a critical influence on hemodynamic and clinical outcomes following EVAR. Appropriate additional procedures may be of great benefit to SNA patients.

Gut-resident macrophages (gMacs) supplemented by monocytes-to-gMacs differentiation play a critical role in maintaining intestinal homeostasis. Activating transcription factor 4 (ATF4) is involved in immune cell differentiation. We therefore set out to investigate the role of ATF4-regulated monocytes-to-gMacs differentiation in sepsis-induced intestinal injury.

Sepsis was induced in C57BL/6 wild type (WT) mice and Atf4-knockdown (Atf4^+/-) mice by cecal ligation and puncture or administration of lipopolysaccharide (LPS). Colon, peripheral blood mononuclear cells, sera, lung, liver, and mesenteric lymph nodes were collected for flow cytometry, hematoxylin and eosin staining, immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively.

CD64, CD11b, Ly6C, major histocompatibility complex-II (MHC-II), CX3CR1, Ly6G, and SSC were identified as optimal primary markers for detecting the process of monocytes-to-gMacs differentiation in the colon of WT mice. Monocytes-to-gMacs differentiation was impaired in the colon during sepsis and was associated with decreased expression of ATF4 in P1 (Ly6C^hi monocytes), the precursor cells of gMacs. Atf4 knockdown exacerbated the impairment of monocytes-to-gMacs differentiation in response to LPS, resulting in a significant reduction of gMacs in the colon. Furthermore, compared with WT mice, Atf4^+/- mice exhibited higher pathology scores, increased expression of inflammatory factor genes (TNF-α, IL-1β), suppressed expression of CD31 and vascular endothelial-cadherin in the colon, and increased translocation of intestinal bacteria to lymph nodes and lungs following exposure to LPS. However, the aggravation of sepsis-induced intestinal injury resulting from Atf4 knockdown was not caused by the enhanced inflammatory effect of Ly6C^hi monocytes and gMacs.

ATF4, as a novel regulator of monocytes-to-gMacs differentiation, plays a critical role in protecting mice against sepsis-induced intestinal injury, suggesting that ATF4 might be a potential therapeutic target for sepsis treatment.

肝细胞癌（HCC）的发病率呈逐年上升趋势。国际癌症研究机构（IARC）报告称，2020年有超过63万人被诊断患有HCC，超过一半的HCC新病例发生在中国。越来越多的病人使医疗系统不堪重负，手术前的等待时间越来越长。这对传统手术管理模式的适用性提出了新的挑战。周末进行的择期手术可以为这个问题提供有效的解决方案。然而，周末手术的安全性存在争议，因为与工作日相比，手术患者在周末的严重并发症发生率和术后死亡率更高（ie、周末效应）。一瞥和艾尔^[1]报道称，与工作日的类似手术相比，在周末接受中高风险手术的美国患者死亡和重大并发症的风险在临床上显著增加。

随着腹腔镜肝切除术的技术进步和新的导航设备，如柔性腹腔镜超声探头、吲哚菁绿（ICG）荧光成像和三维成像，腹腔镜肝段切除术（LS）在确保足够的手术切缘的同时，最大限度地保留了功能性肝储备和未来重复肝切除术的可能性，已成为治疗肝细胞癌（HCC）的可行替代方案。^[1,2]然而，对于侵犯左叶中两个或更多（亚）节段的单个HCC，由于左叶的体积相对较小，大多数外科医生自动选择左半肝切除术（LH）而不考虑肿瘤的解剖分布。事实上，中国80%~90%的HCC患者存在基础肝硬化。^[3]研究证明，肝硬化患者术后肝功能障碍甚至衰竭约有三分之一归因于LH。^[4,5]因此，在当前微创手术时代，需要更精确的算法来指导左叶HCC的手术策略。在此，我们提出了一种新的以分类为导向的腹腔镜解剖肝切除术策略，用于侵犯左叶两个或多个（亚）节段的单个HCC，称为Wu分类。

嗜酸性粒细胞增多综合征（HES）是一种罕见的全身性疾病，于1968年首次被描述。作为HES的一种亚型，特发性嗜酸性粒细胞增多综合征（IHES）被定义为不明原因的嗜酸性粒细胞增多，不包括肿瘤、感染、过敏和免疫系统疾病。在大多数情况下，IHE患者中超过1个器官受到影响。^[1]治疗IHES的一线药物为糖皮质激素，对嗜酸性粒细胞增多和临床表现均有效。^[2]然而，当激素治疗的结果不令人满意时，也可以给予免疫抑制剂或抗肿瘤剂。^[3]由于IHES发病率较低，目前缺乏对该病的大规模回顾性研究。我们的目的是确定预测预后的因素，并确定药物治疗后的终点嗜酸性粒细胞（EOS）计数以及激素治疗失败后应考虑改变治疗的时间。

致编辑：糖尿病的全球患病率正在急剧增加。^[1]为了预防和治疗糖尿病及其心血管并发症，临床实践指南建议评估糖尿病患者中普遍存在的不可改变的危险因素。中国动脉粥样硬化性心血管疾病（ASCVD）风险预测（China-PAR）模型是专门为预测中国ASCVD的10年风险而开发的。^[2]该模型中使用的风险方程基于两个大型当代中国参与者队列的数据，包括年龄、收缩压、总胆固醇、高密度脂蛋白胆固醇（HDL-C）、当前吸烟和糖尿病。该模型在中国人群中的10年ASCVD风险预测中表现良好。

致编辑：1型糖尿病(T1D)是由自身免疫介导的胰岛β细胞破坏引起的，其中胰岛自身免疫是T1D发病机制中的基本成分。^[1]然而，由于采样困难，对人类胰岛的研究受到限制。因此，应重视外周血单核细胞（PBMCs）的免疫学变化。一方面，胰岛浸润免疫细胞可能与循环池处于平衡状态，PBMC的变化可能部分反映胰岛炎症。另一方面，PBMC代表了检测疾病生物标志物的有用工具。^[2]传统上，对T1D中PBMC的研究的特征在于使用有限数量的细胞表面标志物和分泌的细胞因子，使用流式检测和其他基于抗体的测定法测量。最近，基因表达微阵列等高通量测序技术允许在群体水平鉴定PBMC转录组特征。这些研究大多集中在PBMC中的差异表达基因（DEGs），但很少有人验证DEGs并研究其细胞类型。

致编辑：原发性全身性糖皮质激素超敏反应是一种罕见的疾病，其特征是对糖皮质激素的全身性、部分靶组织超敏反应。因此，低浓度的糖皮质激素足以有效维持患者的细胞生理效应，抑制下丘脑-垂体-肾上腺轴。我们的研究旨在为何时应考虑糖皮质激素超敏反应以及如何诊断提供一些见解。我们还根据我们的经验和以前的文献综述，首次提出了糖皮质激素超敏反应的诊断流程图。该研究由复旦大学华山医院机构审查委员会审查并批准（编号：KY2020-049）。

致编辑：寻常痤疮是一种慢性、炎性和毁容性皮肤病，伴有病变、炎症后色素沉着过度和疤痕。化学脱皮是一种简单且耐受性良好的治疗轻度至中度痤疮的方法。乙醇酸（GA）是水溶性的，在所有α-羟基酸中分子量最小。高浓度GA（20%-70%），在医院或美容诊所以2至4周的间隔应用，已被证明对痤疮有效。^[1]低浓度GA（≤10%）安全方便，可在家中使用。^[2]到目前为止，还没有报道低浓度和高浓度GA对寻常痤疮的疗效差异。本研究比较了5%GA复合物和20%GA对痤疮患者的疗效和安全性，以指导不同浓度GA的选择。

致编辑：海洋分枝杆菌是一种非结核分枝杆菌，可引起人类机会性感染，范围从单一皮肤病变到播散性疾病。^[1]它于1926年首次从鱼中分离出来，并于1951年被确定为人类感染的原因。^[1]在不同国家，估计年发病率为每10万人0.04至0.27人。的爆发海洋分枝杆菌与处理鱼有关的感染并不常见，但也有报道。

致编辑：乳腺外佩吉特病（EMPD）是一种罕见的皮肤表皮内腺癌，起源有争议，常发生在男性的阴茎阴囊区。原发性EMPD起源于表皮或顶汗腺，通常是一种原地局限于表皮的疾病预后良好，而继发性EMPD被认为与潜在的内部恶性肿瘤有关。EMPD原地有可能成为转移率较高、预后较差的侵袭性EMPD。^[1]因此，识别与侵袭的生物学行为相关的转录组谱对于改善未来侵袭性EMPD的治疗是重要的。

致编辑：中轴性脊柱关节炎（axSpA）是一种慢性炎症性疾病。^[1]强直性脊柱炎（AS）表型的标志是骶髂关节和脊柱损伤，其特征是新骨形成和关节融合，这导致不可逆的功能残疾和生活质量下降。

致编辑：中轴性脊柱关节炎(axSpA)的特征在于骶髂关节炎症、脊柱炎症、骨破坏和成骨。脊柱和/或髋关节强直可能发生在后期，显著影响患者的生活质量。骶髂关节炎作为axSpA最早和最常见的影像学表现，可分为早期活动性病变和晚期结构性病变。磁共振成像（MRI）不仅检测计算机断层扫描（CT）或X射线中无法发现的活动性炎症变化，而且在检测结构性病变方面具有与CT相似的敏感性。^[1]然而，常规MRI仅提供骶髂关节病变的定性诊断，而不提供定量信息。客观、准确和可重复的定量评估，特别是对于与疾病预后相关的骨髓水肿（BME）和脂肪化生，为评估疾病状态和治疗效果提供了潜在的成像方法。合成MRI作为一种新的成像技术，在同一次扫描的基础上提供定性和定量信息。在本研究中，我们旨在验证与常规MRI相比，合成MRI是否对axSpA患者的骶髂关节病变提供了相似的定性诊断价值，并评估合成MRI生成的定量图在检测骶髂关节BME和脂肪化生方面的定量诊断性能。据我们所知，这项研究首次调查了合成MRI评估axSpA参与者骶髂关节病变的潜在实用性。

致编辑：中轴性脊柱关节炎（axSpA）是一种影响脊柱和骶髂（SI）关节的慢性和进行性疾病，引起炎性背痛、僵硬并诱导新骨形成（严重形式的联合韧带增生和最终强直）。axSpA由两个亚组患者组成：非放射学axSpA（nr-axSpA）患者和强直性脊柱炎（AS）患者，也称为放射学axSpA。AxSpA与患者和医疗保健系统的大量临床和经济负担相关。axSpA患者的身体限制会对就业、工作效率、休闲活动、情绪和人际关系产生不利影响。

致编辑：听力损失是人类最常见的感觉障碍。每1000名新生儿中就有一例先天性耳聋，在50%的病例中，耳聋是遗传性的。耳聋表现出高度的遗传异质性。迄今为止，已经鉴定了超过110个非综合征性耳聋基因(https://hereditaryhearingloss.org/)。这些基因中的许多可导致常染色体显性听力损失(ADNSHL)和常染色体隐性非综合征性听力损失(ARNSHL)TMC1（编码跨膜通道样1）就是其中之一。TMC1（OMIM：606706）是位于9q21.13的TMC家族成员。该蛋白包含760个氨基酸，具有6个跨膜区。TMC1在耳蜗的内毛细胞和外毛细胞中表达。一个TMC1突变在2002年首次被证明会导致耳聋。^[1]的流行TMC1变异范围从巴基斯坦ARNSHL家族的3.4%（19/557）到土耳其家族的8.1%（7/86）。迄今为止，约有20个听力损失家庭与TMC1中国已经报告了变种。