2023年 · 第136卷第23期

人类卵母细胞和胚胎的冷冻保存是辅助生殖技术（ART）中的一个关键因素。基于最新的指导方针和共识^{[1,2,3,4,5,6,7,8]}并结合临床实践，中国生殖医学会呼吁专家总结了人卵母细胞和胚胎玻璃化冷冻的相关技术流程和细节。目的是为玻璃化提供一套全面和系统的指南，并提高生殖中心提供的服务质量。

Epidermal growth factor receptor (EGFR) mutations are common oncogenic driver mutations in patients with non-small cell lung cancer (NSCLC). The application of EGFR-tyrosine kinase inhibitors (TKIs) is beneficial for patients with advanced and early-stage NSCLC. With the development of next-generation sequencing technology, numerous patients have been found to have more than one genetic mutation in addition to a single EGFR mutation; however, the efficacy of conventional EGFR-TKIs and the optimal treatments for such patients remain largely unknown. Thus, we review the incidence, prognosis, and current treatment regimens of EGFR compound mutations and EGFR concomitant mutations to provide treatment recommendations and guidance for patients with these mutations.

As one of the most malignant tumors worldwide, lung cancer, fueled by metastasis, has shown rising mortality rates. However, effective clinical strategies aimed at preventing metastasis are lacking owing to its dynamic multi-step, complicated, and progressive nature. Immunotherapy has shown promise in treating cancer metastasis by reversing the immunosuppressive network of the tumor microenvironment. However, drug resistance inevitably develops due to inadequate delivery of immunostimulants and an uncontrolled immune response. Consequently, adverse effects occur, such as autoimmunity, from the non-specific immune activation and non-specific inflammation in off-target organs. Nanocarriers that improve drug solubility, permeability, stability, bioavailability, as well as sustained, controlled, and targeted delivery can effectively overcome drug resistance and enhance the therapeutic effect while reducing adverse effects. In particular, nanomedicine-based immunotherapy can be utilized to target tumor metastasis, presenting a promising therapeutic strategy for lung cancer. Nanotechnology strategies that boost the immunotherapy effect are classified based on the metastatic cascade related to the tumor immune microenvironment; the breaking away of primary tumors, circulating tumor cell dissemination, and premetastatic niche formation cause distant secondary site colonization. In this review, we focus on the opportunities and challenges of integrating immunotherapy with nanoparticle formulation to establish nanotechnology-based immunotherapy by modulating the tumor microenvironment for preclinical and clinical applications in the management of patients with metastatic lung cancer. We also discuss prospects for the emerging field and the clinical translation potential of these techniques.

Cancer is a major threat to human health and causes death worldwide. Research on the role of radiotherapy (RT) in the treatment of cancer is progressing; however, RT not only causes fatal DNA damage to tumor cells, but also affects the interactions between tumor cells and different components of the tumor microenvironment (TME), including immune cells, fibroblasts, macrophages, extracellular matrix, and some soluble products. Some cancer cells can survive radiation and have shown strong resistance to radiation through interaction with the TME. Currently, the complex relationships between the tumor cells and cellular components that play major roles in various TMEs are poorly understood. This review explores the relationship between RT and cell-cell communication in the TME from the perspective of immunity and hypoxia and aims to identify new RT biomarkers and treatment methods in lung cancer to improve the current status of unstable RT effect and provide a theoretical basis for further lung cancer RT sensitization research in the future.

Inflammation is a major underlying mechanism in the progression of numerous cardiovascular diseases (CVDs). Regulatory T cells (Tregs) are typical immune regulatory cells with recognized immunosuppressive properties. Despite the immunosuppressive properties, researchers have acknowledged the significance of Tregs in maintaining tissue homeostasis and facilitating repair/regeneration. Previous studies unveiled the heterogeneity of Tregs in the heart and aorta, which expanded in CVDs with unique transcriptional phenotypes and reparative/regenerative function. This review briefly summarizes the functional principles of Tregs, also including the synergistic effect of Tregs and other immune cells in CVDs. We discriminate the roles and therapeutic potential of Tregs in CVDs such as atherosclerosis, hypertension, abdominal arterial aneurysm, pulmonary arterial hypertension, Kawasaki disease, myocarditis, myocardial infarction, and heart failure. Tregs not only exert anti-inflammatory effects but also actively promote myocardial regeneration and vascular repair, maintaining the stability of the local microenvironment. Given that the specific mechanism of Tregs functioning in CVDs remains unclear, we reviewed previous clinical and basic studies and the latest findings on the function and mechanism of Tregs in CVDs.

Patients with schizophrenia (SCZ) and major depressive disorder (MDD) share significant clinical overlap, although it remains unknown to what extent this overlap reflects shared neural profiles. To identify the shared and specific abnormalities in SCZ and MDD, we performed a whole-brain voxel-based meta-analysis using magnetization transfer imaging, a technique that characterizes the macromolecular structural integrity of brain tissue in terms of the magnetization transfer ratio (MTR).

A systematic search based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in PubMed, EMBASE, International Scientific Index (ISI) Web of Science, and MEDLINE for relevant studies up to March 2022. Two researchers independently screened the articles. Rigorous scrutiny and data extraction were performed for the studies that met the inclusion criteria. Voxel-wise meta-analyses were conducted using anisotropic effect size-signed differential mapping with a unified template. Meta-regression was used to explore the potential effects of demographic and clinical characteristics.

A total of 15 studies with 17 datasets describing 365 SCZ patients, 224 MDD patients, and 550 healthy controls (HCs) were identified. The conjunction analysis showed that both disorders shared higher MTR than HC in the left cerebellum (P=0.0006) and left fusiform gyrus (P=0.0004). Additionally, SCZ patients showed disorder-specific lower MTR in the anterior cingulate/paracingulate gyrus, right superior temporal gyrus, and right superior frontal gyrus, and higher MTR in the left thalamus, precuneus/cuneus, posterior cingulate gyrus, and paracentral lobule; and MDD patients showed higher MTR in the left middle occipital region. Meta-regression showed no statistical significance in either group.

The results revealed a structural neural basis shared between SCZ and MDD patients, emphasizing the importance of shared neural substrates across psychopathology. Meanwhile, distinct disease-specific characteristics could have implications for future differential diagnosis and targeted treatment.

There is limited data to comprehensively evaluate the epidemiological characteristics of multiple myeloma (MM) in China; therefore, this study determined the characteristics of the disease burden of MM at national and provincial levels in China.

The burden of MM, including incidence, mortality, prevalence, and disability-adjusted life years (DALYs), with a 95% uncertainty interval (UI), was determined in China following the general analytical strategy used in the Global Burden of Disease, Injuries, and Risk Factors Study 2019. The trends in the burden of MM from 1990 to 2019 were also evaluated.

There were an estimated 347.45 thousand DALYs with an age-standardized DALY rate of 17.05 (95% UI, 12.31-20.77) per 100,000 in 2019. The estimated number of incident case and deaths of MM were 18,793 and 13,421, with age-standardized incidence and mortality rates of 0.93 (95% UI, 0.67-1.15) and 0.67 (95% UI, 0.50-0.82) per 100,000, respectively. The age-specific DALY rates per 100,000 increased to more than 10.00 in the 40 to 44 years age group reaching a peak (93.82) in the 70 to 74 years age group. Males had a higher burden than females, with approximately 1.5- to 2.0-fold sex difference in age-specific DALY rates in all age groups. From 1990 to 2019, the DALYs of MM increased 134%, from 148,479 in 1990 to 347,453 in 2019.

The burden of MM has doubled over the last three decades, which highlights the need to establish effective disease prevention and control strategies at both the national and provincial levels.

The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis.

In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis.

A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP.

Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.

Type 2 diabetes mellitus (T2DM) is an independent risk factor for colorectal cancer (CRC), and the patients with CRC and T2DM have worse survival. The human gut microbiota (GM) is linked to the development of CRC and T2DM, respectively. However, the GM characteristics in patients with CRC and T2DM remain unclear.

We performed fecal metagenomic and targeted metabolomics studies on 36 samples from CRC patients with T2DM (DCRC group, n = 12), CRC patients without diabetes (CRC group, n = 12), and healthy controls (Health group, n = 12). We analyzed the fecal microbiomes, characterized the composition and function based on the metagenomics of DCRC patients, and detected the short-chain fatty acids (SCFAs) and bile acids (BAs) levels in all fecal samples. Finally, we performed a correlation analysis of the differential bacteria and metabolites between different groups.

Compared with the CRC group, LefSe analysis showed that there is a specific GM community in DCRC group, including an increased abundance of Eggerthella, Hungatella, Peptostreptococcus, and Parvimonas, and decreased Butyricicoccus, Lactobacillus, and Paraprevotella. The metabolomics analysis results revealed that the butyric acid level was lower but the deoxycholic acid and 12-keto-lithocholic acid levels were higher in the DCRC group than other groups (P < 0.05). The correlation analysis showed that the dominant bacterial abundance in the DCRC group (Parvimonas, Desulfurispora, Sebaldella, and Veillonellales, among others) was negatively correlated with butyric acid, hyodeoxycholic acid, ursodeoxycholic acid, glycochenodeoxycholic acid, chenodeoxycholic acid, cholic acid and glycocholate. However, the abundance of mostly inferior bacteria was positively correlated with these metabolic acid levels, including Faecalibacterium, Thermococci, and Cellulophaga.

Unique fecal microbiome signatures exist in CRC patients with T2DM compared to those with non-diabetic CRC. Alterations in GM composition and SCFAs and secondary BAs levels may promote CRC development.

Red-cell transfusion is critical for surgery during the peri-operative period; however, the transfusion threshold remains controversial mainly owing to the diversity among patients. The patient’s medical status should be evaluated before making a transfusion decision. Herein, we developed an individualized transfusion strategy using the West-China-Liu’s Score based on the physiology of oxygen delivery/consumption balance and designed an open-label, multicenter, randomized clinical trial to verify whether it reduced red cell requirement as compared with that associated with restrictive and liberal strategies safely and effectively, providing valid evidence for peri-operative transfusion.

Patients aged >14 years undergoing elective non-cardiac surgery with estimated blood loss > 1000 mL or 20% blood volume and hemoglobin concentration <10 g/dL were randomly assigned to an individualized strategy, a restrictive strategy following China’s guideline or a liberal strategy with a transfusion threshold of hemoglobin concentration <9.5 g/dL. We evaluated two primary outcomes: the proportion of patients who received red blood cells (superiority test) and a composite of in-hospital complications and all-cause mortality by day 30 (non-inferiority test).

We enrolled 1182 patients: 379, 419, and 384 received individualized, restrictive, and liberal strategies, respectively. Approximately 30.6% (116/379) of patients in the individualized strategy received a red-cell transfusion, less than 62.5% (262/419) in the restrictive strategy (absolute risk difference, 31.92%; 97.5% confidence interval [CI]: 24.42-39.42%; odds ratio, 3.78%; 97.5% CI: 2.70-5.30%; P<0.001), and 89.8% (345/384) in the liberal strategy (absolute risk difference, 59.24%; 97.5% CI: 52.91-65.57%; odds ratio, 20.06; 97.5% CI: 12.74-31.57; P<0.001). No statistically significant differences were found in the composite of in-hospital complications and mortality by day 30 among the three strategies.

The individualized red-cell transfusion strategy using the West-China-Liu’s Score reduced red-cell transfusion without increasing in-hospital complications and mortality by day 30 when compared with restrictive and liberal strategies in elective non-cardiac surgeries.

ClinicalTrials.gov, NCT01597232.

Human neutrophil lipocalin (HNL) has been used extensively to differentiate acute bacterial infection from febrile diseases as a biomarker to reflect the activation of the neutrophil. The serum HNL levels in the adult-onset Still’s disease (AOSD) patients with and without infection, as well as the healthy controls (HCs), were analyzed statistically in this study to evaluate the value of HNL for the diagnosis of AOSD.

A total of 129 AOSD patients were enrolled, from whom blood samples were drawn and the AOSD diagnosis was confirmed through the review of the medical records, where the systemic score, demographic characteristics, clinical manifestations, and laboratory parameters were also collected for the patients; in addition, a total of 40 HCs were recruited among the blood donors from the healthcare center with the relevant information collected. The HNL test was done for the blood samples with the enzyme-linked immunosorbent assay and the analyses were done for the correlations of HNL with clinical manifestations and diagnostic effectiveness.

The serum HNL increased significantly in the patients with only AOSD as compared with that in the HCs (139.76 ± 8.99 ng/mL vs. 55.92 ± 6.12 ng/mL; P < 0.001). The serum HNL level was correlated with the white blood cell (WBC) count (r = 0.335, P < 0.001), neutrophil count (r = 0.334, P < 0.001), erythrocyte sedimentation rate (r = 0.241, P = 0.022), C-reactive protein (r = 0.442, P < 0.0001), and systemic score (r = 0.343, P < 0.0001) in the AOSD patients significantly. Patients with fever, leukocytosis ≥15,000/mm³, and myalgia in the HNL-positive group were observed relatively more than those in the HNL-negative group (P = 0.009, P = 0.023, and P = 0.007, respectively). HNL was a more sensitive indicator than ferritin and C-reactive protein (CRP) to differentiate the AOSD patients with bacterial infection from AOSD-only patients, and the Youden index was 0.6 for HNL and 0.29 for CRP.

Serum HNL can be used as a biomarker for the diagnosis of the AOSD, and HNL is also observed to be associated with the disease activity.

致编辑：银屑病是一种常见的慢性免疫介导的全身性炎症性疾病^[1]其特征是刺激性皮肤红斑、生活质量下降以及相关的全身性疾病，包括心血管疾病、糖尿病和代谢综合征。2017年，中国有0.5%的人口被诊断患有银屑病。^[2]为提高中国银屑病的整体诊疗水平，国家皮肤与免疫疾病临床医学研究中心启动了名为银屑病规范化诊疗中心（又称银屑病中心）的国家级协作项目，^[3]其中，到2022年，全国300多家医疗中心建立了首个国家级真实世界大数据收集平台银屑病中心注册中心。本研究旨在通过描述入组时的登记数据，更新当前中国银屑病患者的一般特征和治疗分布。

致编辑：常规合成疾病缓解抗风湿药物（csDMARDs）的引入在减轻类风湿性关节炎（RA）的体征和症状以及延迟或预防结构性关节损伤方面非常有效。此外，生物DMARDs(bDMARDs)和靶向合成DMARDs(tsDMARDs)的开发和临床使用极大地改变了RA患者的预后，特别是当它们与靶向治疗方案(T2T)组合时。^[1]因此，在过去的二十年里，全髋关节置换术（THA）和全膝关节置换术（TKA）的发生率在这些特殊患者群体中保持稳定甚至下降。然而，与骨关节炎患者相比，RA患者在关节成形术后具有更差的功能结局和更高的并发症发生率的风险。这可能归因于风湿性疾病过程的复杂性，包括高疾病活动性、合并症和免疫抑制药物。^[2]做出围手术期药物管理决策的关键是平衡假体周围感染的风险和疾病发作的风险。^[3]

致编辑：开颅术后一周内新发头痛通常被认为是急性开颅后头痛（PCH）。这种头痛主要发生在术后的最初几天内，并且与年龄较小、女性和乙状结肠后入路显著相关。^[1]PCH的机制主要涉及头皮肌肉、颅骨骨膜、硬脑膜和三叉神经的机械和化学刺激以及无菌性炎症。^[2]PCH的频繁发作导致日常活动受损、生活质量下降、术后恢复时间延长和社会功能恶化。急性PCH的鉴别诊断也可能导致患者接受许多不必要的检查，包括侵入性检查，如腰椎穿刺。

致编辑：系统性红斑狼疮(SLE)是一种以产生各种自身抗体为特征的自身免疫性疾病。成人患病率为每10万人20至70人，儿童患病率为每10万人1.89至25.7人。^[1,2]SLE的发病机制与免疫紊乱有关，特别是涉及B和T细胞的活化，其可导致来自去除受损细胞的免疫复合物(IC)的凋亡细胞的核和胞质抗原的异常抗体，以及补体系统的过度活化，从而导致靶器官如肾和肺的损伤。^[3,4]

致编辑：系统性红斑狼疮(SLE)是一种自身免疫性疾病，倾向于影响育龄女性。中国目前有近400万人患有SLE，其早期可引起多器官损害，严重影响患者的生活质量。^[1,2,3]月经紊乱在SLE患者中很常见，从大量月经出血到闭经不等。月经不调的病因包括疾病活动本身、糖皮质激素（GCs）治疗和一些免疫抑制剂的使用。^[4]这项多中心、横断面、基于网络的观察性研究调查了中国SLE患者的月经不调、妊娠结局和分娩结局。该研究获得了中国北京大学人民医院伦理委员会的批准（编号：2019PHB253-01）。患者被告知，完成问卷意味着同意，该过程是匿名和自愿的。

致编辑：急性肾损伤（AKI）是心脏和大型非心脏手术的常见并发症。体外循环（CPB）辅助心脏手术与其他无CPB的手术相比，AKI发生率更高，表明CPB可能是心脏手术相关AKI（CSA-AKI）的危险因素。^[1]然而，先前的研究证明了关于CPB和CSA-AKI之间关系的相互矛盾的结果，因为AKI的诊断是根据不同的标准做出的。^[2,3,4,5]AKI工作组对AKI的最新定义，肾脏疾病：改善总体结果（KDIGO），允许基于肾小球滤过率（GFR）的下降以及随后的血清肌酐的增加或一段时间的少尿来确定AKI。^[6]我们在接受体外循环或非体外循环冠状动脉旁路移植术（CABG）的患者中使用KDIGO定义进行了一项回顾性队列研究，以评估CPB与术后AKI的关系。

致编辑：最新的令人担忧的变种奥密克戎在2021年11月首次报告后立即成为占主导地位的全球变种。^[1]它在刺突蛋白中包含>30个突变，在受体结合结构域中有17个突变，使其具有增加的传播性和免疫逃避能力。^[1,2]此外，自冠状病毒疾病2019（新冠肺炎）疫苗接种以来，随着时间的推移，已经观察到保护作用的减弱。^[3]因此，强烈推荐使用助推器。英国一项评估BNT162b2或mRNA-1273加强疫苗接种有效性的大规模研究表明，加强注射大大增加了对确诊奥密克戎变异感染患者症状性感染的保护。^[3]然而，尽管实验室研究表明，与灭活COVID-19疫苗的同源加强剂也可以产生针对奥密克戎变异体的有效中和活性，^[4]关于该疫苗接种计划有效性的临床证据有限。

致编辑：被认为是数字孪生方法主要应用的经典案例是1970年的阿波罗13号任务。2003年，密歇根大学的迈克尔·格里夫斯教授提出了数字孪生的概念。然而，数字孪生概念的广泛传播要归功于美国国家航空航天局在2011年将数字孪生应用于航空航天器健康维护和保证。^[1]新一代信息技术的提升使得数字孪生技术的应用范围更加广泛，包括医疗保健。

致编辑：白癜风是一种以皮肤色素脱失斑块为特征的自身免疫性疾病，在有限的治疗选择下难以控制。干扰素(IFN)-γ-趋化因子轴似乎是白癜风的关键驱动因素。当面对黑素细胞抗原时，黑素细胞特异性CD8+T细胞产生IFN-γ，然后激活局部角质形成细胞中的Janus激酶(JAK)/信号转导子和转录激活子(STAT)途径，随后角质形成细胞产生下游趋化因子C-X-C基序趋化因子配体9和10，导致额外募集T细胞以攻击黑素细胞。