Volume 137 · Issue 18 · 2024

原发性肝癌（PLC）是中国第四大常见恶性肿瘤和第二大肿瘤相关死亡原因。肝细胞癌（HCC）占PLC的75-85%。^[1]目前，根治性手术仍是HCC最有效的治疗方案，包括肝切除和肝移植（LT）。由于供体肝脏短缺以及术后肿瘤复发和转移的风险，LT治疗HCC的适应症相对严格。肿瘤负荷超过LT标准的患者可以接受降级治疗以满足标准。近年来，针对HCC的新药不断研发。其中，以分子靶向药物和免疫检查点抑制剂（ICIs）为代表的全身治疗药物开创了HCC治疗的新纪元。^[2]LT后，受体面临的主要问题是肿瘤复发和转移。既往研究显示，LT后5年肿瘤复发率为20.0-57.8%，HCC复发后受者中位生存期仅为12.9个月。^[3,4]LT后肿瘤复发转移可采用消融、介入、放射治疗等多种区域性治疗。全身治疗，如靶向药物和化疗，也用于临床。然而，关于ICIs预防或治疗肿瘤复发和转移的应用仍存在一些争议。目前，国内外医学界对ICIs在HCC LT中的应用尚无标准化指南或广泛共识。为实现LT前后HCC患者ICIs的有效安全应用，2023年8月，中华医学会器官移植分会召集全国专家共同制定了《免疫检查点抑制剂在肝细胞癌肝移植中应用的中国专家共识》（共识全文见补充文件，http://links.lww.com/CM9/C97）。

The incidence of early-onset gastric cancer (EOGC) is consistently increasing, and its etiology is notably complex. This increase may be attributed to distinctive factors that differ from those associated with late-onset gastric cancer (LOGC), including genetic predispositions, dietary factors, gastric microbiota dysbiosis, and screening of high-risk cases. These factors collectively contribute to the onset of cancer. EOGC significantly differs from LOGC in terms of clinicopathological and molecular characteristics. Moreover, multiple differences in prognosis and clinical management also exist. This study aimed to systematically review the latest research advancements in the epidemiological characteristics, etiological factors, clinicopathological and molecular features, prognosis, and treatment modalities of EOGC.

Breast cancer, a malignant tumor with a high incidence in women, lacks in vitro research models that can represent the biological functions of breast tumors in vivo. As a new biological tool, the organoid model has unique advantages over traditional methods, such as cell culture and patient-derived xenografts. Combining organoids with other emerging technologies, such as gene engineering and microfluidic chip technology, provides an effective method to compensate for the deficiencies in organoid models of breast cancer in vivo. The emergence of breast cancer organoids has provided new tools and research directions in precision medicine, and drug research. In this review, we summarized the merits and demerits of organoids compared to traditional biological models, explored the latest developments in the combination of new technologies and organoid models, and discussed the construction methods and application prospects of different breast cancer organoid models.

Bacterial outer membrane vesicles (OMVs) are diminutive vesicles naturally released by Gram-negative bacteria. These vesicles possess distinctive characteristics that attract attention for their potential use in drug administration and immunotherapy in cancer treatment. Therapeutic medicines may be delivered via OMVs directly to the tumor sites, thereby minimizing exposure to healthy cells and lowering the risk of systemic toxicity. Furthermore, the activation of the immune system by OMVs has been demonstrated to facilitate the recognition and elimination of cancer cells, which makes them a desirable tool for immunotherapy. They can also be genetically modified to carry specific antigens, immunomodulatory compounds, and small interfering RNAs, enhancing the immune response to cancerous cells and silencing genes associated with disease progression. Combining OMVs with other cancer treatments like chemotherapy and radiation has shown promising synergistic effects. This review highlights the crucial role of bacterial OMVs in cancer, emphasizing their potential as vectors for novel cancer targeted therapies. As researchers delve deeper into the complexities of these vesicles and their interactions with tumors, there is a growing sense of optimism that this avenue of study will bring positive outcomes and renewed hope to cancer patients in the foreseeable future.

Evaluating the impact of digestive system diseases is vital for devising effective prevention strategies. However, comprehensive reports on the burden of digestive system diseases in China are lacking. Our study aimed to provide an overview of the burden and trends of digestive system diseases from 1990 to 2019 in China and its provinces.

This cross-sectional study utilized the Global Disease Burden Study 2019 to estimate the incidence, mortality rate, disability-adjusted life years (DALYs), years of life disability, years of life lost, and changes in the burden of digestive diseases across Chinese provinces from 1990 to 2019. The analysis of disease burden primarily examines the characteristics of sub-disease distribution, time trends, age distribution, and sex distribution. Additionally, we compared provincial age-standardized DALYs for digestive diseases with the expected rates based on the socio-demographic index (SDI).

In 2019, there were 499.2 million cases of digestive system diseases in China, resulting in 1,557,310 deaths. Stomach cancer, colon and rectal cancer, and esophageal cancer are the top three diseases associated with mortality and DALY related to digestive system diseases. Meanwhile, cirrhosis and other chronic liver diseases, gastroesophageal reflux disease, and gallbladder and biliary diseases are the top three kinds of diseases with the highest prevalence among digestive system diseases. The risk of gastric cancer sharply increases among men after the age of 40 years, leading to a significant disparity in burden between men and women. As the SDI increased, the DALYs associated with digestive system diseases in China and its provinces showed a downward trend.

Our study highlights the inverse correlation between DALYs associated with digestive system diseases and the SDI.

Female breast and five gynecological cancers remain substantial burden in China and worldwide. GLOBOCAN 2022 has recently updated the estimates of cancer burden. This study aims to depict the profiles of disease burden and to compare the age-specific rates of female breast and five gynecological cancers in China with those in other countries.

The latest estimates of incidence and mortality of female breast and five gynecological cancers from various regions and countries were extracted from the GLOBOCAN 2022 database. We compared the proportion of total cases or deaths for cancers affecting female breast and five gynecological cancers and other tumor types in China and globally. Correlation analysis was conducted to evaluate the relationship between age-standardized incidence rate (ASIR) or age-standardized mortality rate (ASMR) and the Human Development Index (HDI). Additionally, age-specific rate curves were plotted for ten exemplary countries with different income levels.

Female breast and five gynecological cancers in China accounted for 30.2% of all newly diagnosed cancer cases. Breast cancer and cervical cancer are the most commonly diagnosed, with nearly 507,000 new cases, representing 23.48% of the new cases. The incidence rates of breast, uterine corpus, ovarian, and vulvar cancers were positively associated with HDI tiers. Chinese women aged 50-54 years are experiencing high incidence rates of breast, cervix uteri, corpus uteri, and ovarian cancers.

Female breast and five gynecological cancers continue to be a significant health concern for women in China and worldwide. It is crucial to implement comprehensive prevention strategies tailored to address the increasing trend among younger individuals and reduce regional disparities.

Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD). This study aimed to develop and validate a novel genetic-clinical-radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism.

This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demographics, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram.

Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276-13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086-0.405, P <0.001), increased caregiver burden inventory score (OR = 8.993, 95% CI: 3.830-21.119, P <0.001), and decreased brain stem volume (OR = 0.006, 95% CI: 0.001-0.191, P = 0.004). These variables were incorporated into the nomogram. The area under the ROC curve was 0.925 (95% CI: 0.884-0.967, P <0.001) in the internal validation and 0.791 (95% CI: 0.686-0.895, P <0.001) in the external validation. The calibration plots showed favorable consistency between the prediction of nomogram and actual observations, and the DCA showed that the model was clinically useful in both validations.

A novel nomogram was established and validated based on lipid metabolism-related genes, nutritional status, and brain stem volumes, which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD.

Chictr.org.cn, ChiCTR2100049131.

Programmed death 1 (PD-1) blockade plus chemotherapy has become the new first-line standard of care for patients with advanced non-small-cell lung cancer (NSCLC). Yet not all NSCLC patients benefit from this regimen. This study aimed to investigate the predictors of PD-1 blockade plus chemotherapy in untreated advanced NSCLC.

We integrated clinical, genomic, and survival data from 287 patients with untreated advanced NSCLC who were enrolled in one of five registered phase 3 trials and received PD-1 blockade plus chemotherapy or chemotherapy alone. We randomly assigned these patients into a discovery cohort (n = 125), a validation cohort (n = 82), and a control cohort (n = 80). The candidate genes that could predict the response to PD-1 blockade plus chemotherapy were identified using data from the discovery cohort and their predictive values were then evaluated in the three cohorts. Immune deconvolution was conducted using transcriptome data of 1014 NSCLC patients from The Cancer Genome Atlas dataset.

A genomic variation signature, in which one or more of the 15 candidate genes were altered, was correlated with significantly inferior response rates and survival outcomes in patients treated with first-line PD-1 blockade plus chemotherapy in both discovery and validation cohorts. Its predictive value held in multivariate analyses when adjusted for baseline parameters, programmed cell death ligand 1 (PD-L1) expression level, and tumor mutation burden. Moreover, applying both the 15-gene panel and PD-L1 expression level produced better performance than either alone in predicting benefit from this treatment combination. Immune landscape analyses revealed that tumors with one or more variation in the 15-gene panel were associated with few immune infiltrates, indicating an immune-desert tumor microenvironment.

These findings indicate that a 15-gene panel can serve as a negative prediction biomarker for first-line PD-1 blockade plus chemotherapy in patients with advanced NSCLC.

Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) can profoundly affect the mental health of the people living with HIV (PLWH), with higher rates of anxiety, depression, and sleep disturbances. The disparities in neuropsychological problems evaluated by physicians and self-assessed by patients are still unknown.

A total of 5000 PLWH and 500 physicians from 167 hospitals were enrolled in this cross-sectional study from September 2022 to February 2023. 4-Item Patient Health Questionnaire (PHQ-4) was used for the evaluation of depressive issues and anxiety issues by PLWH. Each physician assessed 10 PLWH under their care for the presence of depressive or anxiety issues. The primary outcomes of this study are the concordance rates on the depressive issues and anxiety issues evaluation between physicians and PLWH. The Cohen’s kappa test was used to assess the agreement between physicians and PLWH.

The concordance rate for the evaluation of depressive issues is 73.84% (95% confidence interval [CI]: 72.60-75.04%), and it is significantly different from the expected rate of 80% (P <0.001). Similarly, the concordance rate for the evaluation of anxiety issues is 71.74% (95% CI: 70.47-72.97%), which is significantly different from the expected rate of 80% as per the null hypothesis (P <0.001). The overestimation rate by physicians on depressive issues is 12.20% (95% CI: 11.32-13.14%), and for anxiety issues is 12.76% (95% CI: 11.86-13.71%). The mismatch rate for depressive issues is 26.16% (95% CI: 24.96-27.40%), and for anxiety issues is 28.26% (95% CI: 27.02-29.53%). The underestimation rate by physicians on depressive issues is 13.96% (95% CI: 13.03-14.95%), and for anxiety issues is 15.50% (95% CI: 14.52-16.53%). For the treatment regiments, PLWH sustained on innovative treatment regimen (IR) related to a lower prevalence of depressive issues (odds ratio [OR] = 0.71, 95% CI: 0.59-0.87, P = 0.003) and a lower prevalence of anxiety issues (OR = 0.63, 95% CI: 0.52-0.76, P <0.001). PLWH switch from conventional treatment regimen (CR) to IR also related to a lower prevalence of depressive issues (OR = 0.79, 95% CI: 0.64-0.98) and a lower prevalence of anxiety issues (OR = 0.81, 95% CI: 0.67-0.99).

Nearly one in three PLWH had their condition misjudged by their physicians. The findings underscore the need for improved communication and standardized assessment protocols in the care of PLWH, especially during the acute phase of HIV infection.

认知健康是人类生存和生活质量的主要决定因素。随着越来越多的全球人口进入老年（定义为60岁及以上），痴呆症已成为公共卫生和社会护理的优先事项。^[1]中国约有1507万痴呆患者，占全球痴呆总人口的25%。^[2]由于进入老年的个人比例相对较高，预计中国在未来几十年将成为所有国家中痴呆症病例增长最快的国家，造成越来越大的社会和经济影响。

致编辑：胰十二指肠切除术(PD)、远端胰腺切除术(DP)和中央胰腺切除术(CP)通常导致功能性胰腺实质的不良损失、消化道连续性的破坏和并发症的高发生率。近年来，传统的胰腺剜除术（TPE）越来越多地用于距离主管道（MD）>2 mm的小型良性和低度恶性胰腺病变，因为它可以最大限度地保留功能性胰腺实质并保持消化道的连续性。距离太短（≤2 mm）的病例不是很好的候选病例，因为在进行TPE时，距离太短可能会损坏MD。^[1]本文介绍了一种新的胰腺摘除术，主管道优先入路胰腺摘除术（MDFAPE），用于距离MD≤2 mm的小型良性和低度恶性病变。

致编辑：2019冠状病毒病（COVID-19）大流行造成了重大的全球健康危机，导致了惊人的死亡率，并带来了巨大的经济负担。^[1]肺炎是新冠肺炎患者死亡的主要原因。在疫情高峰期，患者激增给医疗保健系统带来了严重压力，凸显了对快速且经济高效的筛查方法的需求。尽管胸部X射线（CXR）经济实惠且方便，但其低灵敏度限制了其检测肺部异常的有效性。计算机断层扫描（CT）被认为是诊断肺炎（包括新冠肺炎）的金标准，但它使患者暴露在高剂量辐射（3-7毫希沃特）下，远远超过世界卫生组织建议的每年1毫希沃特阈值。即使是低剂量CT也能提供1.6 mSv的平均有效剂量，增加了患者的辐射负担。^[2]

致编辑：流感病毒不断进化，具有感染广泛宿主的能力，导致反复感染和持续发病。^[1]在中国，呼吸道传染病监测已专门针对流感和其他呼吸道传染病进行。然而，目前的监测系统严重依赖对临床确诊流感病例的分析，已经落后于时代。^[2]建立更准确的流感预测模型非常重要，尤其是在人口稠密的特大城市。我们的研究旨在探索和开发更准确和敏感的模型来预测流感爆发。

致编辑：特应性皮炎（AD）是世界范围内最常见的慢性过敏性皮肤病。屋尘螨（HDM）是最普遍的空气过敏原和致病原因，可引发皮肤屏障破坏和多敏化。过敏原免疫疗法（AIT）可能是通过应用一定剂量的特定过敏原刺激体内适应性免疫来改善AD自然病史的唯一病因治疗。^[1,2]然而，HDM AIT的效果最近显示出有争议的结果。本研究旨在探讨AIT治疗HDM的有效性和安全性。

致编辑：恶性胆道狭窄通常与高度侵袭性和诊断上具有挑战性的疾病相关，包括胆管癌、胰腺癌、胆囊癌、肝癌和转移性癌症。^[1]内镜逆行胰胆管造影（ERCP）术中胆道活检是诊断胆道狭窄的主要方法。通过镊子取样进行活检是一种技术上复杂的程序，涉及操纵活检镊子通过十二指肠乳头以进入胆道区域。此外，取样不足会导致活检阳性率降低。^[2]

致编辑：非酒精性脂肪性肝病（NAFLD）是一种进行性肝病，与肝脏中的脂肪蓄积密切相关。NAFLD的发病机制从肝脏脂肪变性到更严重的脂肪性肝炎，然后发展为纤维化和终末期肝硬化。该病已成为全球范围内肝脏相关和全因死亡率的独立危险因素。随着生活水平的提高，NAFLD是中国主要的慢性肝病。中国NAFLD负担的增加已成为公共健康的重要威胁，特别是与之相关的肝硬化和其他慢性肝病。先前的一项研究通过系统综述和荟萃分析评估了中国NAFLD的流行病学、危险因素、并发症和管理。^[1]关于NAFLD和相关肝脏并发症的长期和局部全国性流行病学研究很少见。我国目前对NAFLD的防控程度及未来发展趋势尚不明确。因此，有必要对中国NAFLD相关肝硬化及其他慢性病的疾病负担进行分析和预测。

致编辑静脉血栓栓塞（VTE）是原位肝移植（OLT）后常见的并发症，发生率为2.8-8.6%，^[1,2,3]影响移植后患者的生活质量。目前的VTE风险评估工具，如Caprini评分，在应用于该人群时存在局限性，这强调了开发为OLT接受者量身定制的早期VTE风险评估模型的必要性。

致编辑：儿童肥胖是一个严重的公共卫生问题，会对身体和心理健康产生长期影响。生活方式干预已被广泛用于治疗儿童肥胖。值得注意的是，个体对同一干预的反应因遗传背景而异。先前的研究人员已经探索了几种糖代谢相关基因对儿童肥胖干预的调节作用，包括TCF7L2^[1]和RPTOR.^[2]然而，这些研究在研究设计（没有对照组）和持续时间（不超过一年）方面受到限制，并且没有研究探索INSR（另一种葡萄糖代谢相关基因）变体。此外，先前的研究仅集中于基于单核苷酸多态性（SNP）的分析，而不是基于基因的分析。因此，我们研究了INSR中国8-10岁儿童对基于生活方式的肥胖干预反应的基因变异在基因和SNP水平上。

致编辑：肥胖目前已成为一个重要的公共卫生问题，已被认为是多种慢性疾病患者的积极预后因素，包括肺动脉高压，这种现象被称为“肥胖悖论”。^[1]然而，这种现象是否存在于慢性肺病继发的肺动脉高压（PH）（CLD-PH）中仍然未知。本研究旨在阐明CLD-PH患者体重指数（身体质量指数）与死亡率之间的关系。

致编辑：2006年Takahashi和Yamanaka发现的诱导多能干细胞（iPSCs）被誉为干细胞研究的重大突破。并且大量实验研究证明，转化生长因子-β（TGF-β）信号通路是iPSC重编程中的关键信号通路。TGF-β信号通路在不同条件下可促进或抑制iPSC重编程[图1].本文描述了TGF-β信号通路在iPSC重编程中的作用。