Volume 134 · Issue 09 · 2021

通过包括手术、放疗、全身治疗在内的综合治疗，乳腺癌患者的生存率大大提高，其中仍以手术治疗为主。乳腺外科医生不仅要掌握手术技巧，还要培养综合治疗疾病的能力。为提高我国乳腺外科医生早期诊断乳腺癌、进行合理手术治疗、提供综合治疗指导的能力，中国乳腺外科学会（CSBrS）通过意见征集和专家讨论，对浸润性乳腺癌诊治中的关键问题进行了报告。本集团使用分级建议评估、发展和评价系统评估相关证据，并制定了《浸润性乳腺癌患者诊断和治疗临床实践指南：CSBrS实践指南2021》，旨在为中国乳腺外科医生的临床实践提供指导。

乳腺纤维腺瘤是女性乳腺最常见的良性肿瘤，可发生于各个年龄段。然而，这些肿瘤更常见于15至35岁的女性。^[1]大多数纤维腺瘤通常经历自限性生长，通常在几年后稳定。临床诊断以临床触诊和超声检查为主，金标准诊断为病理检查。为规范乳腺纤维腺瘤的临床诊治，中国乳腺外科学会（CSBrS）对专家意见进行了文献综述，确定了乳腺纤维腺瘤临床实践指南的临床关键问题。本集团采用分级建议评估、开发和评价系统对相关证据进行评估，并制定了乳腺纤维腺瘤临床实践指南：CSBrS practice guideline 2021，旨在为中国乳腺外科医生提供临床实践指导。

Hypotension is a common complication caused by spinal anesthesia (SA), which may have adverse impacts on the condition of the parturient and fetus. Liquid infusion was found to be relatively effective for reducing the incidence of hypotension. However, the question of whether colloid preload can optimize hemodynamic variables in the cesarean section remains controversial. This study aims to determine the effects of colloid preload on the incidence of hypotension induced by SA in elective cesarean section.

Related keywords were searched on PubMed, EMBASE, and Cochrane Library from inception dates to May 2020. Studies included were evaluated for eligibility and quality. The primary outcome was the intra-operative incidence of hypotension and severe hypotension. The secondary outcomes included the lowest intra-operative systolic blood pressure, the maximal intra-operative heart rate, the intra-operative needs of ephedrine and phenylephrine, the incidence of maternal nausea and/or vomiting, and neonatal outcomes (umbilical artery pH and Apgar scores). Apart from the above, RevMan 5.3 was used for the data analysis.

Altogether nine randomized controlled trials were included in the meta-analysis. There were no significant differences in the incidence of intra-operative hypotension, severe hypotension, or neonatal outcomes between the colloid preload group and control group, except for the umbilical artery pH.

This meta-analysis suggests that colloid preload does not significantly reduce the incidence of hypotension associated with SA in elective cesarean section.

醛酮还原酶超家族（AKRs）由190多个成员组成，可分为16个不同的家族（访问www.med.upenn.edu/akr）。AKR1C3（醛固酮还原酶家族1的C3亚型）是指第一个AKR在家族1、亚家族C中，由AKR1C3基因。AKR1C3首先从人前列腺cDNA文库中克隆和表达。该蛋白是可溶性单体NADP(H)(烟酰胺腺嘌呤二核苷酸磷酸或烟酰胺腺嘌呤二核苷酸磷酸的还原形式)依赖性氧化还原酶。TheAKR蛋白质在氨基酸水平上表现出至少40%的序列同一性，并且在其结构内具有(α/β)8桶结构。尤其是，AKR1C3与具有86%序列同一性AKR1C1,AKR1C2，和AKR1C4[补充图1，http://links.lww.com/CM9/A460]。AKR1C3已知参与雌激素、雄激素、孕酮和前列腺素等的代谢和生物合成。^[1]

肿瘤微环境主要包括成纤维细胞、巨噬细胞、内皮细胞、免疫细胞。肿瘤免疫微环境（时间）的异质性影响不同患者对免疫治疗的反应。使用免疫检查点抑制剂（ICIs）的癌症免疫疗法可以通过单独或组合阻断程序性细胞死亡1（PD-1）/程序性死亡配体-1（PD-L1）或细胞毒性T淋巴细胞相关蛋白4（CTLA-4）途径的抗体来实现，促进了肿瘤学的新范式转变。然而，癌症患者对ICIs的应答率相对较低，并且报道的用于预测治疗功效的生物标志物的结果是相互矛盾的。因此，迫切需要新颖可靠的生物标志物来监测肿瘤特异性免疫应答，避免免疫相关不良事件，提高临床疗效。

溃疡性结肠炎(UC)和克罗恩病(CD)是炎症性肠病(IBD)的两种主要类型。近几十年来，包括抗肿瘤坏死因子(TNF)、抗整联蛋白、抗白细胞介素(IL)-12/IL-23和Janus激酶(JAK)抑制剂在内的生物制剂的使用促进了临床缓解和粘膜愈合并减少了手术，因此显著改善了IBD患者的生活质量。然而，据报道，在临床试验中，大约20%至30%的UC患者对抗TNF治疗没有反应（主要无反应者），另外15%至30%的患者随着时间的推移失去了反应。^[1]此外，据报道，在临床试验中，43%的UC患者出现了对抗整联蛋白治疗的原发性无应答。^[2]在一项真实世界多中心研究中，32.1%接受vedolizumab治疗的UC患者在第14周未达到临床缓解。^[3]对于长期疗效，只有33%的UC患者在400个治疗周时维持临床反应。^[4]

心脏病是全世界人类死亡的主要原因。开关/蔗糖非发酵（SWI/SNF）复合物在心脏发育和心脏病中起着至关重要的作用。梵天相关基因1（Brg1），SWI/SNF复合物的关键三磷酸腺苷酶（ATP）催化亚基，通过利用ATP水解产生的能量来调节基因转录、DNA修复和DNA复制，参与几个生理和病理过程。和Brg1涉及全身性疾病，包括神经、心血管和免疫系统疾病。最近，作用Brg1在心脏病中得到了深入的研究。越来越多的证据表明Brg1氧化应激机制、凋亡、增殖和心脏病期间的心脏重塑。^[1,2]这些发现表明Brg1通过多种生理功能参与疾病发展[图1].

Thyroid dysfunction is associated with cardiovascular diseases. However, the role of thyroid function in lipid metabolism remains partly unknown. The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization (MR).

The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial. A two-sample MR was performed to assess the causal association, using summary statistics from the Atrial Fibrillation Genetics Consortium (n = 537,409) and the Global Lipids Genetics Consortium (n = 188,577). The clinical measures of thyroid function include thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels, FT3:FT4 ratio and concentration of thyroid peroxidase antibodies (TPOAb). The serum lipid metabolism traits include total cholesterol (TC) and triglycerides, high-density lipoprotein, and low-density lipoprotein (LDL) levels. The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism.

The results demonstrated that increased TSH levels were significantly associated with higher TC (β = 0.052, P = 0.002) and LDL (β = 0.041, P = 0.018) levels. In addition, the FT3:FT4 ratio was significantly associated with TC (β = 0.240, P = 0.033) and LDL (β = 0.025, P = 0.027) levels. However, no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids.

Taken together, the results of the present study suggest an association between thyroid function and serum lipid metabolism, highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.

Fetal weight is an important parameter to ensure maternal and child safety. The purpose of this study was to use three-dimensional (3D) limb volume ultrasound combined with fetal abdominal circumference (AC) measurement to establish a model to predict fetal weight and evaluate its efficiency.

A total of 211 participants with single pregnancy (28-42 weeks) were selected between September 2017 and December 2018 in the Beijing Obstetrics and Gynecology Hospital of Capital Medical University. The upper arm (AVol)/thigh volume (TVol) of fetuses was measured by the 3D limb volume technique. Fetal AC was measured by two-dimensional ultrasound. Nine cases were excluded due to incomplete information or the interval between examination and delivery >7 days. The enrolled 202 participants were divided into a model group (134 cases, 70%) and a verification group (68 cases, 30%) by mechanical sampling method. The linear relationship between limb volume and fetal weight was evaluated using Pearson Chi-squared test. The prediction model formula was established by multivariate regression with data from the model group. Accuracy of the model formula was evaluated with verification group data and compared with traditional formulas (Hadlock, Lee2009, and INTERGROWTH-21^st) by paired t-test and residual analysis. Receiver operating characteristic curves were generated to predict macrosomia.

AC, AVol, and TVol were linearly related to fetal weight. Pearson correlation coefficient was 0.866, 0.862, and 0.910, respectively. The prediction model based on AVol/TVol and AC was established as follows: Y=-481.965+ 12.194TVol + 15.358AVol + 67.998AC, R²_adj = 0.868. The scatter plot showed that when birth weight fluctuated by 5% (i.e., 95% to 105%), the difference between the predicted fetal weight by the model and the actual weight was small. A paired t-test showed that there was no significant difference between the predicted fetal weight and the actual birth weight (t= -1.015, P = 0.314). Moreover, the residual analysis showed that the model formula’s prediction efficiency was better than the traditional formulas with a mean residual of 35,360.170. The combined model of AVol/TVol and AC was superior to the Lee2009 and INTERGROWTH-21^st formulas in the diagnosis of macrosomia. Its predictive sensitivity and specificity were 87.5% and 91.7%, respectively.

Fetal weight prediction model established by semi-automatic 3D limb volume combined with AC is of high accuracy, sensitivity, and specificity. The prediction model formula shows higher predictive efficiency, especially for the diagnosis of macrosomia.

ClinicalTrials.gov, NCT03002246; https://clinicaltrials.gov/ct2/show/NCT03002246?recrs=e&cond=fetal& draw=8&rank=67.

The association of lipids and cancer has varied greatly among different cancer types, lipid components and study populations. This study is aimed to investigate the association of serum lipids and the risk of malignant lesions in esophageal squamous epithelium.

In the "Endoscopic Screening for Esophageal Cancer in China" (ESECC) trial, serum samples were collected and tested for total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol at the time of subject enrollment. Cases were defined as malignant esophageal lesions identified by baseline endoscopic examination or by follow-up to May 31, 2018. Controls were randomly selected using incidence density sampling in the same cohort. Conditional logistic models were applied to identify the association of serum lipids and the risk of malignant esophageal lesions. Effect modification was evaluated by testing interaction terms of the factor under assessment and these serum lipid indicators.

No consistent association between serum lipid levels and esophageal malignant lesions were found in a pooled analysis of 211 cases and 2101 controls. For individuals with a family history of esophageal cancer (EC), high TC, and LDL-C were associated with a significantly increased risk of having malignant lesions (odds ratio [OR]_{Highvs.Low TC} = 2.22, 95% confidence interval [CI]: 1.14-4.35; OR_{Highvs.Low LDL-C} = 1.93, 95% CI: 1.01-3.65). However, a negative association was observed in participants without an EC family history (OR_{Highvs.Low TC} = 0.69, 95% CI: 0.48-0.98, P_interaction = 0.002; OR_{Highvs.Low LDL-C} = 0.50, 95% CI: 0.34-0.76, P_interaction < 0.001).

In this study, we found that the association of serum lipids and malignant esophageal lesions might be modified by EC family history. The stratified analysis would be crucial for population-based studies investigating the association of serum lipids and cancer. The mechanism by which a family history of EC modifies this association warrants further investigation.

Normal tension glaucoma (NTG) is a less pressure-dependent type of glaucoma with characteristic optic neuropathy. Recently, the biomechanical mechanism has been thought to account for glaucomatous optic neuropathy to some degree. We intended to compare dynamic corneal response parameters (DCRs) among patients with primary open-angle glaucoma with normal tension or hypertension and controls. The correlations between DCRs and known risk factors for glaucoma were also analyzed.

In this cross-sectional study, 49 NTG subjects, 45 hypertension glaucoma (HTG) subjects, and 50 control subjects were enrolled. We compared the differences in DCRs using corneal visualization Scheimpflug technology among the NTG, HTG, and control groups. We also analyzed the correlations between DCRs and known risk factors for glaucoma (eg, central corneal thickness [CCT], intraocular pressure [IOP], etc).

The maximum inverse concave radius (NTG: 0.18 [0.17, 0.20] mm^-1; control: 0.17 [0.16, 0.18] mm^-1; P= 0.033), deformation amplitude ratio of 2 mm (DAR 2 mm, NTG: 4.87 [4.33, 5.39]; control: 4.37 [4.07, 4.88]; P < 0.001), and DAR 1 mm (NTG: 1.62 [1.58, 1.65]; control: 1.58 [1.54, 1.61]; P < 0.001) were significantly higher in NTG than in the controls. The integrated radius (IR, NTG: 8.40 ± 1.07 mm^-1; HTG: 7.64 ± 1.31 mm^-1; P = 0.026) and DAR 2 mm (NTG: 4.87 [4.33, 5.39]; HTG: 4.44 [4.12, 5.02]; P < 0.007) were significantly higher, whereas the stiffness parameter at the first applanation (SP-A1, NTG: 91.23 [77.45, 107.45]; HTG: 102.36 [85.77, 125.12]; P = 0.007) was lower in NTG than in HTG. There were no significant differences in the DCRs between HTG and control groups (P > 0.05). In the univariate and multivariate analyses, some of the DCRs, such as IR, were negatively correlated with CCT and IOP, whereas SP-A1 was positively correlated with CCT and IOP.

The cornea was more deformable in NTG than in HTG or controls. There were no significant differences in corneal deformability between HTG and controls. The cornea was more deformable with the thinner cornea and lower IOP.

Although osteopontin (OPN) is expressed in the liver and pigment gallstones of patients with hepatolithiasis, its role in pigment gallstone formation remains unclear. This study aimed to explore the function of OPN in pigment gallstone formation.

Rats were fed a chow diet (CD) or lithogenic diet (LD) for 10 consecutive weeks; blocking tests were then performed using an OPN antibody (OPN-Ab). Incidence of gallstones and levels of several bile components, OPN, tumor necrosis factor alpha (TNF-α), and cholesterol 7 alpha-hydroxylase (CYP7A1) were analyzed. To determine TNF-α expression in hepatic macrophages and both CYP7A1 and bile acid (BA) expression in liver cells, recombinant rat OPN and recombinant rat TNF-α were used to treat rat hepatic macrophages and rat liver cells, respectively. Chi-square or Fisher exact tests were used to analyze qualitative data, Student t-test or one-way analysis of variance were used to analyze qualitative data.

Incidence of gallstones was higher in LD-fed rats than in CD-fed rats (80% vs. 10%, P < 0.05). BA content significantly decreased in bile (t= -36.08, P < 0.01) and liver tissue (t= -16.16, P < 0.01) of LD-fed rats. Both hepatic OPN protein expression (t= 9.78, P < 0.01) and TNF-α level (t= 8.83, P < 0.01) distinctly increased in the LD group; what’s more, CYP7A1 mRNA and protein levels (t= -12.35, P < 0.01) were markedly down-regulated in the LD group. Following OPN-Ab pretreatment, gallstone formation decreased (85% vs. 25%, χ² = 14.55, P < 0.01), liver TNF-α expression (F = 20.36, P < 0.01) was down-regulated in the LD group, and CYP7A1 expression (F = 17.51, P < 0.01) was up-regulated. Through CD44 and integrin receptors, OPN promoted TNF-α production in macrophage (F= 1041, P < 0.01), which suppressed CYP7A1 expression (F = 48.08, P < 0.01) and reduced liver BA synthesis (F= 119.4, P < 0.01).

We provide novel evidence of OPN involvement in pigmented gallstone pathogenesis in rats.

1986年，伯克霍夫和佐川^[1]在起搏实验中观察到左心室压力随着QRS持续时间（QRSd）的增加而线性降低。随后，人们认识到左束支传导阻滞（LBBB）或右心室起搏都可能导致QRSd延长，对心功能有潜在的有害影响，并增加心房颤动（AF）、心力衰竭和死亡率的风险。^[2]尽管先前的临床试验表明LBBB和心力衰竭患者可受益于双心室起搏（即，双心室心脏再同步治疗[BiV-CRT])，30%至40%的此类患者对BiV-CRT没有反应，并且大约另外10%的患者由于不合适的冠状窦静脉而仍未接受治疗。随着适当植入工具的发展，希氏束起搏（HBP）作为心力衰竭治疗中的辅助疗法对于增强起搏变得越来越重要。各种研究表明，使用HBP的CRT（His-CRT）可能对无反应或未能放置BiV-CRT的患者有价值。然而，HBP具有较高起搏阈值和较低R波振幅的缺点，不能纠正远端传导系统疾病患者的LBBB。

中风是全球第二大死亡原因，估计全球每年有550万人死亡。^[1]颈动脉血运重建术是降低脑卒中发生率的关键手术之一。颈动脉的慢性完全闭塞（TO）和接近完全闭塞（NO）是罕见的。TO和NO的治疗存在争议，存在潜在并发症，包括围手术期卒中、颅内出血和颈动脉海绵窦瘘（CCF）。^[2]已经尝试实施颈动脉内膜切除术（CEA）和血管内治疗，但成功率远不令人满意。对于TO患者，CEA和血管内技术的血运重建成功率分别约为40%和60%。^[3]对于NO患者，发病率和死亡率分别为3%和9%。

由于诊断成像方式的改进，先天性子宫异常（CUA）的发病率似乎高于以前认为的。^[1]最近的一项系统综述估计，在未选择的人群中，患病率为5.5%，在不孕妇女中为8.0%，在有流产史的妇女中为13.3%。所有人群中最常见的异常似乎是隔膜变异（即导管缺陷），其次是双角变异（即融合缺陷）。^[2]另一项荟萃分析显示，几种不良生殖结局与CUA相关，如流产率增加、早产率增加和围产期死亡率增加。^[3]

病理上，腹膜后脂肪肉瘤（RPLS）是一组恶性肿瘤，起源于腹膜后间隙的脂肪组织，几乎占所有腹膜后肿瘤的70%。RPLS没有最佳治疗方法。手术切除（R₀/R₁)是最有效的疗法；然而，复发率非常高。严重不完全手术切除（R₂）是RPLS早期复发的重要危险因素。^[1]

致编辑：类风湿性关节炎（RA）是一种以侵袭性关节炎为特征的自身免疫性疾病，影响约1%的全球人口。中青年女性易患RA，在病程中可经历一次或多次妊娠。健康和疾病的发展起源描述了年轻时发生的健康危害如何影响一个人晚年的健康。^[1]因此，怀孕期间暴露于类风湿性关节炎会影响后代的健康。本文讨论了RA妇女的妊娠状况以及RA对子代健康的可能影响。

致编辑：慢性子宫内膜炎（CE）是一种微妙类型的炎症，其特征是子宫内膜基质中持续存在浆细胞，通常无症状，仅有轻微症状，如异常子宫出血、骨盆疼痛、性交困难或白带。

致编辑：间质性肺病（ILD）是包括类风湿性关节炎（RA）在内的结缔组织疾病（CTD）患者中常见的关节外表现，其显著增加了疾病负担和超额死亡率。^[1]众所周知，RA相关ILD（RA-ILD）患者的死亡风险是没有ILD的RA患者的三倍。^[2]然而，在大约30%的ILD患者中，无法根据临床发现和高分辨率计算机断层扫描特征做出具体诊断，导致诊断和管理的不确定性。^[3]因此，具有诊断和预后效用的非侵入性血液生物标志物可以为识别脆弱患者提供替代信息，^[4]尤其是在医疗资源有限的临床环境中。在供体和特发性肺纤维化（IPF）患者的肺组织标本中发现Dickkof-1（DKK1）蛋白水平增加。^[5]在这种情况下，DKK1能够以剂量依赖性方式改变Wnt诱导的上皮细胞增殖，^[5]暗示DKK1在ILD和RA中的临床相关性。

致编辑：关于皮肤科门诊就诊与气象因素之间的关联的证据有限。以往的一项研究集中在气象因素对某一种疾病的影响上，似乎缺乏针对一类疾病的系统分析。^[1]在这里，我们调查了气象因素对皮肤病日门诊量的短期影响。

致编辑：感染性心内膜炎（IE）是肥厚性心肌病（HCM）的一种罕见并发症，如果感染得不到有效控制，可能导致致命的结局。我们报告了3例肥厚梗阻性心肌病（HOCM）并发IE的病例，其中2例因对抗生素缺乏临床反应、心力衰竭恶化和严重二尖瓣反流而成功接受二尖瓣置换术（MVR）和间隔肌切除术（SM）治疗。

致编辑：暴发性1型糖尿病(FT1DM)的特征是β细胞功能快速丧失、胰岛细胞抗体阴性、酮症酸中毒和胰酶升高。^[1]在日本的一项全国性调查中，分别在98%和70%的酮症酸中毒发作FT1DM患者中发现胰酶升高和腹痛。然而，腹部计算机断层扫描（CT）显示没有异常。胰酶升高与糖尿病酮症酸中毒有关。日本多位学者报道急性胰腺炎（AP）后出现FT1DM。到目前为止，国内还没有此类病例的报道。在这里，我们报告了两例AP后FT1DM的病例，回顾了以前的病例，并推测AP和FT1DM之间的关系。获得了两名患者的知情同意书。

致编辑：靶向肌肉再神经支配（TMR）是一种多神经转移的外科技术，通过表面肌电图（sEMG）在高位上肢截肢者中提供了改善直观假体控制的潜力。^[1]然而，存在一些神经再支配可能不成功的风险，尤其是对于尺神经。^[2]神经残端和受体的质量控制是手术的重要因素。在手术过程中评估神经残端并找到更多的肌肉作为受体可能会解决这个问题。肱二头肌、肱三头肌和肱肌大多被选为经肱骨截肢者神经再支配的受体。胸大肌和胸小肌大多被选为肩关节脱位患者神经再支配的受体。^[3]三角肌由前部、中部和后部组成，分别由腋神经的不同分支供应，可能是增加受体肌肉量的附加选择。^[4]在手术过程中，评估质量良好的残余神经残端的位置或为受体再神经支配而解剖的特定分支是具有挑战性的。^[5]我们对两名经肱骨水平截肢者进行了研究，他们使用三角肌后部作为受体之一接受了TMR，并通过术中电生理检查进行了神经评估。

致编辑：溃疡性结肠炎(UC)传统上已知局限于大肠。上胃肠（GI）受累的存在长期以来被认为是克罗恩病（CD）而不是UC的标志。然而，先前在UC中有上消化道和小肠受累的报道。^[1,2]重要的是，症状和内镜特征都容易导致急性糜烂性或感染性胃十二指肠炎的误诊。本病例强调需要考虑UC的上消化道受累作为鉴别诊断。这种情况可能会促使医生认识到成人发病的UC亚型累及上消化道的可能性；考虑上消化道受累是否应像CD一样被归类为特殊和罕见的UC类型，提示它可能是活动性疾病或预后不良的高危因素；并确定患有这种疾病的患者是否需要更积极的治疗。