2024年 · 第137卷第16期

30多年来，放射治疗一直是局部晚期（II-III期）直肠癌标准术前治疗的一部分。虽然术前放疗已被证实可减少局部复发，但严重影响生活质量，不能提高长期生存率。随着全直肠系膜切除术（TME）的引入，局部复发急剧减少，旧酒是否仍然适合新瓶值得商榷。在本文中，我们在文献和我们中心超过10年的临床研究的背景下讨论了这一观点。

Fatty acid synthase (FASN) is an essential molecule in lipid metabolic pathways, which are crucial for cancer-related studies. Recent studies have focused on a comprehensive understanding of the novel and important regulatory effects of FASN on malignant biological behavior and immune-cell infiltration, which are closely related to tumor occurrence and development, immune escape, and immune response. FASN-targeting antitumor treatment strategies are being developed. Therefore, in this review, we focused on the effects of FASN on tumor and immune-cell infiltration and reviewed the progress of related antitumor therapy development.

The usage of electronic cigarettes (e-cigarettes) sparked an outbreak of unidentified vaping-related lung disease in the US during late 2019. With e-cigarettes becoming more and more popular, smokers have more options other than conventional cigarettes. Under these circumstances, a comprehensive evaluation of the general safety of new tobacco and tobacco-related products, represented by e-cigarettes, to human health is necessary. In this review, we summarize the current research on potential negative impacts of e-cigarette exposure on human health. In particular, studies detailing the relationship between e-cigarettes and the digestive system are summarized, with mechanisms mainly including hepatic metabolic dysfunction, impaired gut barrier, and worsened outcomes of inflammatory bowel disease (IBD). Although believed to be safer than traditional cigarettes, e-cigarettes exert adverse effects on systemic health and induce the development of multiple diseases including asthma, cardiovascular disease, and IBD. Moreover, nicotine-containing e-cigarettes have a negative impact on the childhood development and increase the risk of arterial stiffness compared to the non-nicotine e-cigarettes. However, non-nicotine e-cigarette components have detrimental effects including promoting liver damage and metabolic disorders.

Biomolecular aggregation within cellular environments via liquid–liquid phase separation (LLPS) spontaneously forms droplet-like structures, which play pivotal roles in diverse biological processes. These structures are closely associated with a range of diseases, including neurodegenerative disorders, cancer and infectious diseases, highlighting the significance of understanding LLPS mechanisms for elucidating disease pathogenesis, and exploring potential therapeutic interventions. In this review, we delineate recent advancements in LLPS research, emphasizing its pathological relevance, therapeutic considerations, and the pivotal role of bioinformatic tools and databases in facilitating LLPS investigations. Additionally, we undertook a comprehensive analysis of bioinformatic resources dedicated to LLPS research in order to elucidate their functionality and applicability. By providing comprehensive insights into current LLPS-related bioinformatics resources, this review highlights its implications for human health and disease.

In East Asia, Helicobacter pylori (H. pylori) infection and related diseases are common, primarily during childhood and adolescence. The rates of primary antibiotic resistance in H. pylori among East Asian children and adolescents have not been extensively explored; few relevant systematic reviews or meta-analyses have been conducted. We evaluated the rates of antibiotic resistance in H. pylori among East Asian children and adolescents, with the goal of facilitating individualized treatment recommendations.

We searched PubMed, Embase, and the Cochrane Library for studies in any language published up to February 2023 that explored antibiotic resistance in H. pylori among East Asian children and adolescents. We used MeSH and non-MeSH terms related to the topic, including terms related to children, adolescents, antibiotic resistance, H. pylori, and nations or regions. Additionally, we reviewed the reference lists of relevant articles. Studies that matched our strict predefined eligibility criteria were included in the screening process. Using established assessment methods, we evaluated the quality of the included studies.

We identified 15 observational studies involving 4831 H. pylori isolates, all published between 2001 and 2022. There was substantial primary antibiotic resistance in H. pylori isolates from East Asian children and adolescents. The rates of primary resistance were 51% (95% confidence interval [CI]: 40–62%) for metronidazole; 37% (95% CI: 20–53%) for clarithromycin; 19% (95% CI: 11–28%) for levofloxacin; and less than 3% each for amoxicillin, tetracycline, and furazolidone. Subgroup analysis revealed a prominent increase in metronidazole resistance over time. Clarithromycin and levofloxacin resistance rates fluctuated between 2005 and 2015, then remained stable; other antibiotic resistance rates were generally stable. Metronidazole, clarithromycin, and levofloxacin resistance rates were significantly higher in the Chinese mainland than in other East Asian regions. The rates of dual and multiple antibiotic resistance were 28% (95% CI: 21–36%) and 10% (95% CI: 7–14%), highlighting the potential for diverse resistance patterns.

H. pylori isolates from East Asian children and adolescents exhibit high levels of metronidazole and clarithromycin resistance, particularly in the Chinese mainland. The non-negligible rates of dual and multiple resistance highlight the complexity of this problem.

PROSPERO, No. CRD42023402510.

In vitro fertilization (IVF) has emerged as a transformative solution for infertility. However, achieving favorable live-birth outcomes remains challenging. Current clinical IVF practices in IVF involve the collection of heterogeneous embryo data through diverse methods, including static images and temporal videos. However, traditional embryo selection methods, primarily reliant on visual inspection of morphology, exhibit variability and are contingent on the experience of practitioners. Therefore, an automated system that can evaluate heterogeneous embryo data to predict the final outcomes of live births is highly desirable.

We employed artificial intelligence (AI) for embryo morphological grading, blastocyst embryo selection, aneuploidy prediction, and final live-birth outcome prediction. We developed and validated the AI models using multitask learning for embryo morphological assessment, including pronucleus type on day 1 and the number of blastomeres, asymmetry, and fragmentation of blastomeres on day 3, using 19,201 embryo photographs from 8271 patients. A neural network was trained on embryo and clinical metadata to identify good-quality embryos for implantation on day 3 or day 5, and predict live-birth outcomes. Additionally, a 3D convolutional neural network was trained on 418 time-lapse videos of preimplantation genetic testing (PGT)-based ploidy outcomes for the prediction of aneuploidy and consequent live-birth outcomes.

These two approaches enabled us to automatically assess the implantation potential. By combining embryo and maternal metrics in an ensemble AI model, we evaluated live-birth outcomes in a prospective cohort that achieved higher accuracy than experienced embryologists (46.1% vs. 30.7% on day 3, 55.0% vs. 40.7% on day 5). Our results demonstrate the potential for AI-based selection of embryos based on characteristics beyond the observational abilities of human clinicians (area under the curve: 0.769, 95% confidence interval: 0.709–0.820). These findings could potentially provide a noninvasive, high-throughput, and low-cost screening tool to facilitate embryo selection and achieve better outcomes.

Our study underscores the AI model’s ability to provide interpretable evidence for clinicians in assisted reproduction, highlighting its potential as a noninvasive, efficient, and cost-effective tool for improved embryo selection and enhanced IVF outcomes. The convergence of cutting-edge technology and reproductive medicine has opened new avenues for addressing infertility challenges and optimizing IVF success rates.

Interpreting genes of interest is essential for identifying molecular mechanisms, but acquiring such information typically involves tedious manual retrieval. To streamline this process, the fanyi package offers tools to retrieve gene information from sources like National Center for Biotechnology Information (NCBI), significantly enhancing accessibility. Additionally, understanding the latest research advancements and sharing achievements are crucial for junior researchers. However, language barriers often restrict knowledge absorption and career development. To address these challenges, we developed the fanyi package, which leverages artificial intelligence (AI)-driven online translation services to accurately translate among multiple languages. This dual functionality allows researchers to quickly capture and comprehend information, promotes a multilingual environment, and fosters innovation in academic community. Meanwhile, the translation functions are versatile and applicable beyond biomedicine research to other domains as well. The fanyi package is freely available at https://github.com/YuLab-SMU/fanyi.

Digestive system cancers constitute a significant number of cancer cases, but their burden is not uniform. As Global Cancer Observatory (GLOBOCAN) 2022 has recently updated its estimates of cancer burden, we aimed to investigate the burden of six major digestive system cancers both worldwide and in China, along with geographical and temporal variations in cancer-specific incidence and mortality.

We extracted data on primary cancers of the esophagus, stomach, colorectum, liver, pancreas, and gallbladder from the GLOBOCAN database for 2022. Age-standardized incidence and mortality rates were calculated and stratified by sex, country, region, and human development index (HDI). We used the 2022 revision of the World Population Prospects (United Nations) to obtain demographic data for various age groups in China from 1988 to 2012 and used the joinpoint model and the average annual percentage change (AAPC) to analyze cancer incidence trends in China.

In 2022, the estimated global incidence of digestive system cancers reached 4,905,882, with an estimated 3,324,774 cancer-related deaths. Colorectal cancer was most prevalent in terms of incidence and mortality. There was a significant correlation between the burden of gastrointestinal cancers and country HDI. From 1988 to 2012, the incidence of esophageal, gastric, and liver cancers declined in China, whereas colorectal and pancreatic cancer incidences continued to increase. By 2050, colorectal and liver cancers are projected to remain the leading cancer types in China in terms of incidence and mortality, respectively.

Digestive system cancers remain a significant public health challenge globally and in China. Although progress has been made in the prevention and control of some cancers, the burden of digestive system cancers persists. The implementation of tertiary prevention strategies must be intensified to reduce the incidence and mortality of digestive system cancers, mitigating their impact on public health.

The potential impact of pre-existing coronary artery stenosis (CAS) on acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I (hs-cTnI) levels in patients with PE.

In this multicenter, prospective case-control study, 88 cases and 163 controls matched for age, sex, and study center were enrolled. Cases were patients with PE with elevated hs-cTnI. Controls were patients with PE with normal hs-cTnI. Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation.

The percentage of CAS was higher in the case group compared to the control group (44.3% [39/88] vs. 30.1% [49/163]; P = 0.024). In multivariable conditional logistic regression model 1, CAS (adjusted odds ratio [OR], 2.680; 95% confidence interval [CI], 1.243–5.779), heart rate >75 beats/min (OR, 2.306; 95% CI, 1.056–5.036) and N-terminal pro-B type natriuretic peptide (NT-proBNP) >420 pg/mL (OR, 12.169; 95% CI, 4.792–30.900) were independently associated with elevated hs-cTnI. In model 2, right CAS (OR, 3.615; 95% CI, 1.467–8.909) and NT-proBNP >420 pg/mL (OR, 13.890; 95% CI, 5.288–36.484) were independently associated with elevated hs-cTnI.

CAS was independently associated with myocardial injury in patients with PE. Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.

作为肝细胞癌（HCC）的根治性治疗，肝移植（LT）已成为某些HCC患者的理想治疗选择。对于超过米兰标准的患者，高HCC复发风险是影响预后的重要因素。西罗莫司是雷帕霉素（mTOR）抑制剂的第一代哺乳动物靶点，与基于钙调神经磷酸酶抑制剂（CNI）的无mTOR抑制剂免疫抑制相比，可降低复发率并延长总生存期（OS）。^[1]然而，在临床实践中，一些在LT后定期服用西罗莫司的患者仍然会出现HCC复发。由此可见，从分子病理学角度预测西罗莫司疗效有望突破这一瓶颈。

脊髓性肌萎缩症（SMA），一种由存活运动神经元1突变引起的神经退行性疾病（SMN1)导致存活运动神经元(SMN)蛋白表达降低，以常染色体隐性方式遗传。SMA 1型是SMA最常见的亚型，其特征是在出生6个月前发病，不能实现独立坐位，以及快速进行性呼吸和延髓恶化，导致2岁前死亡率>90%。^[1]目前，已经有两种终身剪接修饰疗法（nusinersen和risdiplam），以及一种通过静脉注射onasemnogene abeparvovec用于SMA 1型患者的单剂量基因替代疗法，获得了美国食品和药物管理局（FDA）的批准。^[2]

致编辑：子宫内膜癌(EC)是女性中诊断的第六种最常见的癌症，据报道其患病率在世界范围内正在增加。子宫内膜透明细胞癌（ECCC）占所有EC的2-5%，是一种罕见但不祥的高危EC亚型，预后较差，表现出更大的化疗耐药性。由于ECCC的罕见性，很少有临床试验专门纳入患有该疾病的患者，与其他更常见的EC亚型相比，关于其发病机制和临床进展的数据有限。

致编辑：谵妄是老年患者常见的术后并发症，与多种不良临床结局相关。^[1]根据发病时间，术后阶段谵妄可分为涌现性谵妄（ED）和术后谵妄（POD）。ED发生在全身麻醉苏醒期间或之后立即，而POD通常在术后1-7天发现。评估患者的ED提供了可能的术后神经认知障碍的第一个线索。^[2]右美托咪定（DEX）是一种高选择性α-2受体激动剂，越来越多地用于围手术期诱导镇静、镇痛、抗焦虑和交感神经张力抑制。既往研究提示，DEX可能是一种有效的术中辅助药物，可减轻老年患者骨科手术后的激越，改善恢复。^[3,4]然而，很少有研究关注DEX和ED之间的关系。本随机对照试验（RCT）旨在探讨老年下肢骨科手术患者术中给予DEX与ED发病率的关系，并检查DEX对老年患者出现期脑电图（EEG）轨迹的影响及其与ED发生的相关性。

致编辑：乳腺癌（BC）是女性中最常见的癌症，每年影响226万人，68万人死亡。约70%的病例涉及雌激素激活的雌激素受体（ER），其通过基因调控和细胞信号传导促进肿瘤生长。没有配体的ER再激活有助于治疗耐药性。雌激素受体阳性（ER+）乳腺肿瘤中的内分泌抵抗可由ER突变、与辅激活因子/辅阻遏因子相互作用改变或与生长因子受体和致癌途径的串扰引起。^[1]此外，长非编码RNA（lncRNA）是在不同癌症类型中具有不同表达模式的不同分子，在肿瘤发生中起关键作用。^[2]值得注意的是，肌动蛋白γ 1假基因（AGPG）正在成为一种值得注意的lncRNA，有望成为有效管理内分泌抗性BC的新治疗靶点。

致编辑核心减压（CD）是治疗股骨头塌陷前骨坏死（ONFH）的主要保髋手术，以其改善的短期结果和相对较低的术后并发症发生率而闻名；然而，文献中报道的中长期生存率各不相同，并且是一个有争议的主题。因此，我们进行了一项大型前瞻性队列研究，以评估从CD转换为全髋关节置换术（THA）的频率和时间及其相关因素。

致编辑：特应性皮炎（AD）是一种慢性炎症性皮肤病，病程复发缓解，需要灵活给药。^[1,2]在中国，abrocitinib是一种口服、每日一次的Janus激酶1选择性抑制剂，起始剂量为100 mg，用于对其他全身治疗（即皮质类固醇或生物制剂）反应不充分或不建议接受这些治疗的难治性中重度AD成人患者。如果abrocitinib 100 mg达到的缓解不足，可考虑200 mg给药，可作为短期治疗（≤12周）给药。^[3]3期JADE方案试验（Clinicaltrials.gov，NCT03627767）评估了对abrocitinib诱导治疗有反应的中度至重度AD患者使用持续剂量abrocitinib（200 mg）、减少剂量abrocitinib（100 mg）或停药（安慰剂）维持反应的情况。^[4]在此，我们旨在描述JADE方案中abrocitinib在中国大陆亚组中的疗效和安全性。

致编辑：尽管小儿肝移植（LT）的预后有了显著改善，但术后并发症仍然是移植物和患者死亡的主要原因。由于病因的差异、发育不全导致的肝血管狭窄、更细致的手术技术和其他因素，儿童接受者比成人接受者具有更高的血栓并发症风险。^[1]血栓并发症包括肝动脉血栓形成(HAT)、门静脉血栓形成(PVT)和静脉流出道阻塞(VOTO)，包括下腔静脉阻塞和肝静脉流出道阻塞。目前，仍有3-10%的PVT发生率和5-15%的HAT发生率，VOTO在1%-13%之间变化。^[2]临床医生倾向于过度强调抗血栓治疗以降低小儿LT后血栓形成的风险，这导致更高的出血风险，需要更好的抗血栓管理。关于平衡血栓事件和出血事件的难题，临床医生迫切需要感知术后血栓形成的风险，以协助优化抗血栓方案，并且在临床实践中没有可用的定量风险评估工具来方便直观地识别高危儿童。

致编辑：银屑病是一种常见的慢性炎症性皮肤病，在世界范围内发生，在任何年龄都有表现。^[1]生物制剂是银屑病治疗中最重要的治疗进展。^[2]随着16S rRNA测序技术的发展，银屑病与肠道菌群的关联逐渐被揭示。一些细菌分泌具有抗炎特性的短链脂肪酸（SCFAs），作为调节肠道和其他组织中免疫细胞功能的活性微生物代谢物。^[3]然而，生物治疗对银屑病患者肠道微生物群和相关功能变化的影响仍不清楚。我们的研究旨在探索生物治疗对银屑病患者肠道微生物群的影响。

致编辑：青光眼是全世界不可逆失明的主要原因。^[1]丝裂霉素C（MMC）小梁切除术已成为降低眼内压（IOP）和减缓青光眼进展的标准手术干预。^[2]然而，小梁切除术后可发生一些具有毁灭性后果的严重并发症，如水泡相关感染、脉络膜上腔出血、玻璃体出血和恶性青光眼。在过去的十年中，许多新型眼科手术装置已用于青光眼。XEN45微型支架（Allergan，Dublin，CA，USA）是一种亲水性交联猪明胶支架。它被植入内部，将房水引流到结膜下空间，而不需要形成结膜瓣、巩膜瓣或虹膜切除术。穿透性导管成形术（PCP），由梁首次提出等人^[3]，是一种相对较新的基于Schlemm管的手术。该手术将小梁切除术整合到椎管成形术中，在前房和Schlemm管口之间建立直接连通，以恢复房水的内部引流。PCP以不依赖于泡的方式恢复房水流出，并且不需要MMC。本研究的目的是比较XEN45植入、MMC小梁切除术和PCP在中国开角型青光眼患者12个月内的手术成功率和术后并发症。

致编辑：失眠影响着全球30%-50%的成年人，导致生活质量下降，并增加了发展身体和精神需求障碍的风险。^[1]先前的研究主要在西方人群中进行，报告了失眠和饮食质量差之间的联系，饮食质量差的特点是能量摄入较高，蔬菜消费较低，以及对高脂肪食物的偏好，这些都是导致主要慢性疾病的风险因素。^[2]然而，在饮食模式显著不同的亚洲人群中，这种关联仍未得到充分探索。此外，研究表明，睡眠质量差通常与深夜进食和不吃早餐等夜间行为有关。^[3,4]吃早餐通常与更好的饮食质量有关，而晚上吃东西往往与较差的饮食质量有关。此外，失眠对这种饮食行为的具体影响，以及它们在潜在介导失眠和饮食质量之间关系中的作用，还没有被彻底探索，特别是在基于社区的人群中。因此，我们在中国进行了一项大规模的基于社区的研究，以评估患有失眠症的参与者是否更有可能具有较低的饮食质量和不健康的行为（即经常从事夜间进食和不吃早餐）。我们进一步研究了这些饮食行为是否介导了失眠和饮食质量之间的潜在联系。

致编辑：多囊卵巢综合征（PCOS）的特征是少无排卵、高雄激素血症和多囊卵巢，是最常见的内分泌疾病，影响5-15%的育龄妇女。^[1,2]它可导致多种内分泌和代谢紊乱，包括无排卵性不孕、胰岛素抵抗、糖耐量受损、糖尿病、肥胖症、血脂异常和心血管疾病，这些疾病可以以不同的组合和不同的强度发生。^[2]甲状腺功能障碍是另一种常见的内分泌疾病，与卵巢功能障碍、月经不调、生育力低下和育龄妇女不孕有关。甲状腺功能障碍最常见的原因是自身免疫性甲状腺疾病（AITD），这在不孕妇女中非常常见，并与不良的辅助生殖技术（ART）结果有关。^[3]考虑到AITD和PCOS在育龄妇女中的高患病率，已阐明了其常见的病因和发病机制，包括易感基因多态性、胸腺疾病、维生素D缺乏和性激素失调。^[4]几项研究阐明了甲状腺功能与自身免疫指标之间的负相关体外受精/卵胞浆内单精子注射（IVF/ICSI）结果和妊娠结果。^[3]然而，仍然缺乏关于PCOS妇女甲状腺功能和自身免疫指标与IVF/ICSI结果之间关系的证据。我们旨在研究甲状腺功能和自身免疫指标对甲状腺功能正常的PCOS妇女IVF/ICSI早期发育和妊娠结局的潜在影响。