Volume 137 · Issue 05 · 2024

先天性巨结肠（HSCR）是一种由肠道神经系统发育缺失引起的先天性肠道异常，导致不同长度的肠道功能障碍，需要手术干预。^[1]由于HSCR病因复杂、术式多、术后并发症多，其诊断和治疗策略一直是世界各国小儿外科医生关注的焦点。来自中国几乎所有国家和省级儿童医学中心的70名具有丰富临床经验的小儿外科专家组成了中国先天性巨结肠研究组（CRGHSCR）。所有成员根据以前文章的现有证据，结合最新的高质量证据，讨论并汇编了关于HSCR的诊断、治疗【补充文件，http：//links.lww.com/CM9/B890】和围手术期管理的分歧。目前的共识声明旨在规范诊断和手术策略，并强调术后康复训练，以系统地改善术后恢复并提高长期随访的生活质量。

The brain is a complex organ that requires precise mapping to understand its structure and function. Brain atlases provide a powerful tool for studying brain circuits, discovering biological markers for early diagnosis, and developing personalized treatments for neuropsychiatric disorders. Neuromodulation techniques, such as transcranial magnetic stimulation and deep brain stimulation, have revolutionized clinical therapies for neuropsychiatric disorders. However, the lack of fine-scale brain atlases limits the precision and effectiveness of these techniques. Advances in neuroimaging and machine learning techniques have led to the emergence of stereotactic-assisted neurosurgery and navigation systems. Still, the individual variability among patients and the diversity of brain diseases make it necessary to develop personalized solutions. The article provides an overview of recent advances in individualized brain mapping and navigated neuromodulation and discusses the methodological profiles, advantages, disadvantages, and future trends of these techniques. The article concludes by posing open questions about the future development of individualized brain mapping and navigated neuromodulation.

Biliary tract cancers (BTC), a heterogeneous disease with poor prognosis, including gallbladder cancer (GBC), intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (ECC). Although surgery is currently the primary regimen to treat BTC, most BTC patients are diagnosed at an advanced stage and miss the opportunity of surgical eradication. As a result, non-surgical therapy serves as the main intervention for advanced BTC. In recent years, immunotherapy has emerged as one of the most promising therapies in a number of solid cancers, and it includes immune checkpoint inhibitors (ICIs) monotherapy or combined therapy, tumor vaccines, oncolytic virus immunotherapy, adoptive cell therapy (ACT), and cytokine therapy. However, these therapies have been practiced in limited clinical settings in patients with BTC. In this review, we focus on the discussion of latest advances of immunotherapy in BTC and update the progress of multiple current clinical trials with different immunotherapies.

Lung cancer remains the most common cause of cancer death. Given the continued research into new drugs and combination therapies, outcomes in lung cancer have been improved, and clinical benefits have been expanded to a broader patient population. However, the overall cure and survival rates for lung cancer patients remain low, especially in metastatic cases. Among the available lung cancer treatment options, such as surgery, radiation therapy, chemotherapy, targeted therapies, and alternative therapies, immunotherapy has shown to be the most promising. The exponential progress in immuno-oncology research and recent advancements made in the field of immunotherapy will further increase the survival and quality of life for lung cancer patients. Substantial progress has been made in targeted therapies using tyrosine kinase inhibitors and monoclonal antibody immune checkpoint inhibitors with many US Food And Drug Administration (FDA)-approved drugs targeting the programmed cell death ligand-1 protein (e.g., durvalumab, atezolizumab), the programmed cell death-1 receptor (e.g., nivolumab, pembrolizumab), and cytotoxic T-lymphocyte-associated antigen 4 (e.g., tremelimumab, ipilimumab). Cytokines, cancer vaccines, adoptive T cell therapies, and Natural killer cell mono- and combinational therapies are rapidly being studied, yet to date, there are currently none that are FDA-approved for the treatment of lung cancer. In this review, we discuss the current lung cancer therapies with an emphasis on immunotherapy, including the challenges for future research and clinical applications.

Differentiated thyroid cancer (DTC) is commonly diagnosed in women of child-bearing age, but whether pregnancy influences the prognosis of DTC remains controversial. This study aimed to summarize existing evidence regarding the association of pregnancy with recurrence risk in patients previously treated for DTC.

We searched PubMed, Embase, Web of Science, Cochrane, and Scopus based on the prespecified protocol registered at PROSPERO (CRD42022367896). After study selection, two researchers independently extracted data from the included studies. For quantitative data synthesis, we used random-effects meta-analysis models to pool the proportion of recurrence (for pregnant women only) and odds ratio (OR; comparing the risk of recurrence between the pregnancy group and the nonpregnancy group), respectively. Then we conducted subgroup analyses to explore whether risk of recurrence differed by response to therapy status or duration of follow-up time. We also assessed quality of the included studies.

A total of ten studies were included. The sample size ranged from 8 to 235, with participants’ age at pregnancy or delivery ranging from 28 to 35 years. The follow-up time varied from 0.1 to 36.0 years. The pooled proportion of recurrence in all pregnant patients was 0.13 (95% confidence intervals [CI]: 0.06-0.25; I²: 0.58). Among six included studies reporting response to therapy status before pregnancy, we observed a trend for increasingly higher risk of recurrence from excellent, indeterminate, and biochemically incomplete to structurally incomplete response to therapy (P_trend <0.05). The pooled risk of recurrence in the pregnancy group showed no evidence of a significant difference from that in the nonpregnancy group (OR: 0.75; 95% CI: 0.45-1.23; I²: 0). The difference in follow-up time (below/above five years) was not associated with either the proportion of recurrence in all pregnant patients (P >0.05) or the OR of recurrence in studies with a comparison group (P >0.05). Two included studies that focused on patients with distant metastasis also did not show a significant difference in disease recurrence between pregnancy and nonpregnancy groups (OR: 0.51 [95% CI: 0.14-1.87; I²: 59%]).

In general, pregnancy appears to have a minimal association with the disease recurrence of DTC with initial treatment. Clinicians should pay more attention to progression of DTC among pregnant women with biochemical and/or structural persistence.

PROSPERO, https://www.crd.york.ac.uk/PROSPERO/; No. CRD42022367896.

随着小分子药物的出现，炎症性肠病（IBD）的治疗进入了一个新的阶段。与生物制剂相反，小分子药物可以制成半衰期较短的口服剂型，适合每天给药1-2次。小分子药物通过抑制溃疡性结肠炎(UC)和克罗恩病(CD)发病机制中关键细胞内信号通路的传递而发挥作用[图1].它们不会在患者体内诱导抗药物抗体或导致治疗后失去反应。

结核病（TB）是一种由结核分枝杆菌尽管肺结核（PTB）的诊断技术已经进步，但PTB的准确和鉴别诊断仍然具有挑战性。近年来，人工智能（AI）的快速发展及其在医疗领域的广泛应用，为诊断和治疗结核病和PTB提供了新的机遇。人工智能的机器学习模型不仅帮助医生提高了诊断准确性，还使他们能够为感染风险增加的个人做出早期预防性诊断。再者，AI可以指导医生针对不同病情的PTB患者制定针对性的治疗策略。

几十年来，坏死性小肠结肠炎(NEC)是一种毁灭性的胃肠道疾病，然而，它仍然是早产儿发病率和死亡率的主要原因。^[1]尽管据报道包括胃肠道细菌定植、不成熟和配方喂养在内的多种因素参与了NEC的发病机制，但确切的机制尚不清楚。由于宏基因组测序的进展，充分的证据表明NEC婴儿存在肠道菌群失调，其特征是变形菌丰度升高，厚壁菌门丰度降低，细菌多样性总体降低，为NEC进展提供了新的见解。^[1,2]此外，细菌复制率，特别是肠杆菌科的复制率，在NEC诊断前两天迅速增加。^[2]此外，肠道细菌组的异常变化与NEC严重程度相关。在NEC期间，肠积气的发生和胃肠道壁中空气的存在表明粘膜再生受损和细菌入侵。^[3]从这个角度来看，入侵细菌或其毒素可以诱导级联炎症介质的分泌，这被认为有助于NEC的发作。然而，必须提到的是，尽管特定的细菌特征先于NEC发作，但肠道菌群失调和NEC发作之间的因果关系需要研究，并且异常肠道细菌组在多大程度上可归因于NEC进展的进一步问题应该是进一步研究的领域。

Hyperglycemia frequently induces apoptosis in endothelial cells and ultimately contributes to microvascular dysfunction in patients with diabetes mellitus (DM). Previous research reported that the expression of integrins as well as their ligands was elevated in the diseased vessels of DM patients. However, the association between integrins and hyperglycemia-induced cell death is still unclear. This research was designed to investigate the role played by integrin subunit β5 (ITGB5) in hyperglycemia-induced endothelial cell apoptosis.

We used leptin receptor knockout (Lepr-KO) (db/db) mice as spontaneous diabetes animal model. Selective deletion of ITGB5 in endothelial cell was achieved by injecting vascular targeted adeno-associated virus via tail vein. Besides, we also applied small interfering RNA in vitro to study the mechanism of ITGB5 in regulating high glucose-induced cell apoptosis.

ITGB5 and its ligand, fibronectin, were both upregulated after exposure to high glucose in vivo and in vitro. ITGB5 knockdown alleviated hyperglycemia-induced vascular endothelial cell apoptosis and microvascular rarefaction in vivo. In vitro analysis revealed that knockdown of either ITGB5 or fibronectin ameliorated high glucose-induced apoptosis in human umbilical vascular endothelial cells (HUVECs). In addition, knockdown of ITGB5 inhibited fibronectin-induced HUVEC apoptosis, which indicated that the fibronectin-ITGB5 interaction participated in high glucose-induced endothelial cell apoptosis. By using RNA-sequencing technology and bioinformatic analysis, we identified Forkhead Box Protein O1 (FoxO1) as an important downstream target regulated by ITGB5. Moreover, we demonstrated that the excessive macroautophagy induced by high glucose can contribute to HUVEC apoptosis, which was regulated by the ITGB5-FoxO1 axis.

The study revealed that high glucose-induced endothelial cell apoptosis was positively regulated by ITGB5, which suggested that ITGB5 could potentially be used to predict and treat DM-related vascular complications.

While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.

We evaluated phenotypic associations using data from the United Kingdom Biobank (N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: N_case/N_control = 74,124/824,006; T2DM adjusted for BMI [T2DM_adjBMI]: N_case/N_control = 50,409/523,897) and for CAD (N_case/N_control = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM (N_case/N_control = 180,834/1,159,055).

Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed (r_g = 0.39, P = 1.43 × 10^-75), which was largely independent of BMI (T2DM_adjBMI–CAD: r_g = 0.31, P = 1.20 × 10^–36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively.

Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Cerebrovascular disease (CVD) ranks among the foremost factors responsible for mortality on a global scale. The mortality patterns of CVDs and temporal trends in China need to be well-illustrated and updated.

We collected mortality data on patients with CVD from Chinese Center for Disease Control and Prevention’s Disease Surveillance Points (CDC-DSP) system. The mortality of CVD in 2020 was described by age, sex, residence, and region. The temporal trend from 2013 to 2019 was evaluated using joinpoint regression, and estimated rates of decline were extrapolated until 2030 using time series models.

In 2019, the age-standardized mortality in China (ASMRC) per 100,000 individuals was 113.2. The ASMRC for males (137.7/10⁵) and rural areas (123.0/10⁵) were both higher when stratified by gender and urban/rural residence. The central region had the highest mortality (126.5/10⁵), the western region had a slightly lower mortality (123.5/10⁵), and the eastern region had the lowest mortality (97.3/10⁵). The age-specific mortality showed an accelerated upward trend from aged 55-59 years, with maximum mortality observed in individuals over 85 years of age. The age-standardized mortality of CVD decreased by 2.43% (95% confidence interval, 1.02-3.81%) annually from 2013 to 2019. Notably, the age-specific mortality of CVD increased from 2013 to 2019 for the age group of over 85 years. In 2020, both the absolute number of CVD cases and the crude mortality of CVD have increased compared to their values in 2019. The estimated total deaths due to CVD were estimated to reach 2.3 million in 2025 and 2.4 million in 2030.

The heightened focus on the burden of CVD among males, rural areas, the central and western of China, and individuals aged 75 years and above has emerged as a pivotal determinant in further decreasing mortalities, consequently presenting novel challenges to strategies for disease prevention and control.

Copper and zinc are involved in the development of multiple malignancies; yet, epidemiological evidence on hepatocellular carcinoma (HCC) is limited. This study aimed to investigate the association between dietary intake and serum levels of copper and zinc with the risk of HCC.

A total of 434 case-control pairs matched for sex and age (±1 year) were included in this study. Cases with newly diagnosed HCC were from the Guangdong Liver Cancer Cohort (GLCC) study, and healthy controls were from the Guangzhou Nutrition and Health Study (GNHS). A semi-quantitative 79-item food frequency questionnaire (FFQ) was used to assess habitual dietary intakes of copper and zinc. Serum levels of copper and zinc were measured by using inductively coupled plasma mass spectrometry. The copper (Cu)/ zinc (Zn) ratio was computed by dividing copper levels by zinc levels. Conditional logistic regression models were performed to calculate the odds ratio (OR) and 95% confidence intervals (CI) for per 1 standard deviation increase (per-SD increase) in copper and zinc levels.

Higher dietary intake (OR_{per-SD increase} = 0.65, 95% CI: 0.44, 0.96, P_trend = 0.029) and serum levels of zinc (OR_{per-SD increase} = 0.11, 95% CI: 0.04, 0.30, P_trend <0.001) were both associated with a lower risk of HCC. Subgroup analyses showed that the inverse association was only pronounced in men but not in women (P_interaction = 0.041 for dietary zinc intake and 0.010 for serum zinc levels). Serum copper levels (OR_{per-SD increase} = 2.05, 95% CI: 1.39, 3.03, P_trend = 0.020) and serum Cu/Zn ratio (OR_{per-SD increase} = 6.53, 95% CI: 2.52, 16.92, P_trend <0.001) were positively associated with HCC risk, while dietary copper intake and dietary Cu/Zn ratio were not associated with HCC risk.

Zinc may be a protective factor for HCC, especially among men, but the effects of copper on HCC risk are not clear.

Polycystic ovarian syndrome (PCOS) is a heterogeneous and complex reproductive endocrinological disease that could lead to infertility. There were many attempts to classify PCOS but it remains unclear whether there is a specific subgroup of PCOS that is associated with the best or worst reproductive outcomes of assisted reproductive techniques (ART).

Infertile PCOS patients who underwent their first cycle of in vitro fertilization (IVF) in West China Second University Hospital, Sichuan University from January 2019 to December 2021 were included. Basic clinical and laboratory information of each individual were extracted. Unsupervised cluster analysis was performed. Controlled ovarian stimulation parameters and reproductive outcomes were collected and compared between the different clusters of PCOS.

Our analysis clustered women with PCOS into "reproductive", "metabolic", and "balanced" clusters based on nine traits. Reproductive group was characterized by high levels of testosterone (T), sex hormone-binding globulin (SHBG), follicular stimulation hormone (FSH), luteinizing hormone (LH), and anti-Müllerian hormone (AMH). Metabolic group was characterized by high levels of body mass index (BMI), fasting insulin, and fasting glucose. Balanced group was characterized by low levels of the aforementioned reproductive and metabolic parameters, except for SHBG. Compared with PCOS patients in reproductive and balanced clusters, those in metabolic cluster had lower rates of good quality day 3 embryo and blastocyst formation. Moreover, PCOS patients in the reproductive cluster had greater fresh embryo transfer (ET) cancelation rate and clinical pregnancy rate after fresh ET than metabolic cluster (odds ratio [OR] = 3.37, 95% confidence interval [CI]: 1.77-6.44, and OR = 6.19, 95% CI: 1.58-24.24, respectively). And compared with PCOS of metabolic cluster, PCOS of balanced cluster also had higher chance for fresh ET cancelation (OR = 2.83, 95% CI: 1.26-6.35).

Our study suggested that PCOS patients in metabolic cluster may be associated with adverse reproductive outcomes and might need individualized treatment and careful monitoring before and during ART.

致编辑：与瓣膜疾病相关的三尖瓣反流（TR）是一个普遍的医学问题，患病率和社会经济负担都在增加。据报道，TR，尤其是中度或重度TR与心力衰竭和死亡率风险增加相关。^[1]研究表明，血钙水平和血磷水平对人体有很大影响，尤其是对心血管系统的影响。据报道，血清钙水平升高是心血管疾病的危险因素。^[2]一项荟萃分析报告称，适度的膳食钙摄入可预防心血管和全因死亡率，补充钙可降低女性死亡率。^[3]

致编辑：脂肪变性肝病的命名法自2020年以来一直是争论的话题。常规表达非酒精性脂肪性肝病(NAFLD)于1980年引入，用于描述在没有其他肝病的情况下脂肪变性的发生。然而，近年来，逐步淘汰和退休这一术语的运动越来越多。2020年，Eslam等人^[1]提出了一个新的定义——代谢（功能障碍）相关脂肪性肝病（MAFLD）——重新定义了该疾病，将肝脂肪变性以及其他因素，如糖尿病、肥胖、超重或符合代谢功能障碍的标准。从NAFLD到MAFLD的转变被认为是必要的，原因有几个，包括NAFLD不能清楚地解释疾病的病理生理学，由于术语“酒精”导致患者耻辱的可能性，患者和医生之间潜在的沟通不畅，以及倾向于通过阳性诊断标准而不是通过排除来定义疾病。^[1]尽管MAFLD和NAFLD不对应于相同的人群，但NAFLD和MAFLD之间有很高的一致性。^[2]在没有全面理解其含义的情况下改变术语也遇到了阻力，主要是因为它可能造成潜在的混乱。为了结束正在进行的辩论，一个由来自56个不同国家的236名专家组成的团队努力确定一个新的、更合适的名称来取代NAFLD一词。达成的共识是将该疾病重新命名为代谢功能障碍相关脂肪变性肝病（MASLD）。MASLD的定义包括脂肪变性与五个预定心脏代谢标准中的至少一个配对。心脏代谢因素与继发性病因的存在已与MASLD分开分类。^[3]

致编辑：重症急性胰腺炎（SAP）是消化内科常见的危重疾病，69.3%的患者合并急性肾损伤（AKI）。^[1]早期诊断和治疗对改善这些患者的预后非常重要。

致编辑：重度抑郁症（MDD）是一种情绪障碍，其特征是情绪、认知和行为症状的复杂模式以及日常功能的缺陷。生殖器症状，包括性欲下降和月经紊乱，几十年来一直被认为是MDD的经典症状。先前的证据已经达成了广泛的共识，即MDD患者的生殖器症状发生率高于普通人群。一项系统综述和荟萃分析发现MDD和生殖器症状之间存在双向关联，MDD患者出现生殖器症状的风险增加50-70%，而有生殖器症状的个体出现MDD的风险增加130-210%。^[1]如前所述，50-70%的MDD患者经历性功能障碍。^[2]迄今为止，很少有研究关注有和无生殖器症状的MDD患者的临床特征以及纵向预后的比较。

致编辑：肺结节定义为直径达30mm的局限性混浊，被肺实质包围或位于胸膜附近。^[1]肺结节的理想管理是根据一般指南，尽早诊断和治疗恶性结节，并尽量减少辐射暴露。临床实践指南（CPG）始终基于对高质量证据和报告的系统审查提供有效的建议，以优化患者护理。^[2]越来越多的证据表明，遵守指南可以改善患者的预后。^[3]然而，CPG的报告质量似乎很差。^[4]已经产生了几种仪器来评估CpG的质量。国际医疗保健实践指南报告项目（RIGHT）清单广泛用于评估CPG的报告质量，并提供了一个系统的报告框架，为CPG的创建、报告和评估提供信息。^[5]带有解释和阐述声明的正确清单可以帮助开发者报告指南，在考虑指南报告时支持期刊编辑和同行评审员，并帮助医疗保健从业者理解和实施指南。在这项研究中，我们使用正确的清单评估了2012年至2022年发布的肺结节CpG的报告质量，以支持未来更透明、清晰和明确的指南报告。

致编辑：高血压是心血管疾病的主要危险因素之一，影响约30%的成年人。^[1,2]环境重金属污染是一个重要的公共卫生问题。有毒金属可能会增加高血压或其他心血管疾病的风险，甚至超出常规行为危险因素的影响。^[3]同时，某些必需微量元素，如硒、锌和铁，参与与血压调节直接相关的各种酶反应，在特定范围内对人体有益。^[4]由于有毒金属和必需微量元素之间的非线性关系和相互作用，分析金属混合物特有的健康结果具有挑战性。^[5]分析混合物的创新统计方法的发展极大地促进了多种污染物暴露对健康影响的探索，如贝叶斯核机回归（BKMR）和分位数g计算（QG-C）。BKMR可用于估计暴露-响应函数，包括非线性暴露-响应曲线、具有主要效应及其相互作用的线性函数，以及包含它们之间协同相互作用的非线性函数。QG-C模型考虑了单个暴露效应和整体混合物的非线性和非可加性，通过计算每个方向上每个元素的权重，能够有效推断单个对金属混合物的贡献。