Volume 136 · Issue 15 · 2023

Immune escape mechanisms in non-small cell lung cancer (NSCLC) can disrupt every step of the anti-cancer immune response. In recent years, an increased understanding of the specific mechanisms fueling immune escape has allowed for the development of numerous immunotherapeutic treatments that have been introduced into the clinical practice. The advent of immunotherapy has dramatically changed the current treatment landscape of advanced or metastatic NSCLC because of its durable efficacy and manageable toxicity. In this review, we will first present a brief overview of recent evidence on immune escape mechanisms in NSCLC. We will then discuss the current promising immunotherapeutic strategies in advanced or metastatic NSCLC tumors.

Organoids are three-dimensional cellular structures with self-organizing and self-differentiation capacities. They faithfully recapitulate structures and functions of in vivo organs as represented by functionality and microstructural definitions. Heterogeneity in in vitro disease modeling is one of the main reasons for anti-cancer therapy failures. Establishing a powerful model to represent tumor heterogeneity is crucial for elucidating tumor biology and developing effective therapeutic strategies. Tumor organoids can retain the original tumor heterogeneity and are commonly used to mimic the cancer microenvironment when co-cultured with fibroblasts and immune cells; therefore, considerable effort has been made recently to promote the use of this new technology from basic research to clinical studies in tumors. In combination with gene editing technology and microfluidic chip systems, engineered tumor organoids show promising abilities to recapitulate tumorigenesis and metastasis. In many studies, the responses of tumor organoids to various drugs have shown a positive correlation with patient responses. Owing to these consistent responses and personalized characteristics with patient data, tumor organoids show excellent potential for preclinical research. Here, we summarize the properties of different tumor models and review their current state and progress in tumor organoids. We further discuss the substantial challenges and prospects in the rapidly developing tumor organoid field.

Sarcopenia is an age-related disease that mainly involves decreases in muscle mass, muscle strength and muscle function. At the same time, the body fat content increases with aging, especially the visceral fat content. Adipose tissue is an endocrine organ that secretes biologically active factors called adipokines, which act on local and distant tissues. Studies have revealed that some adipokines exert regulatory effects on muscle, such as higher serum leptin levels causing a decrease in muscle function and adiponectin inhibits the transcriptional activity of Forkhead box O3 (FoxO3) by activating peroxisome proliferators-activated receptor-γ coactivator-1α (PGC-1α) and sensitizing cells to insulin, thereby repressing atrophy-related genes (atrogin-1 and muscle RING finger 1 [MuRF1]) to prevent the loss of muscle mass. Here, we describe the effects on muscle of adipokines produced by adipose tissue, such as leptin, adiponectin, resistin, mucin and lipocalin-2, and discuss the importance of these adipokines for understanding the development of sarcopenia.

Psoriasis is a chronic inflammatory skin disease with significant physical and psychological burdens. The interplay between the innate and adaptive immune systems is thought to contribute to the pathogenesis; however, the details of the pathogenesis remain unclear. In addition, reliable biomarkers for diagnosis, assessment of disease activity, and monitoring of therapeutic response are limited. Metabolomics is an emerging science that can be used to identify and analyze low molecular weight molecules in biological systems. During the past decade, metabolomics has been widely used in psoriasis research, and substantial progress has been made. This review summarizes and discusses studies that applied metabolomics to psoriatic disease. These studies have identified dysregulation of amino acids, carnitines, fatty acids, lipids, and carbohydrates in psoriasis. The results from these studies have advanced our understanding of: (1) the molecular mechanisms of psoriasis pathogenesis; (2) diagnosis of psoriasis and assessment of disease activity; (3) the mechanism of treatment and how to monitor treatment response; and (4) the link between psoriasis and comorbid diseases. We discuss common research strategies and progress in the application of metabolomics to psoriasis, as well as emerging trends and future directions.

Despite the advent of innovative knee prosthesis design, a consistent first-option knee implant design in total knee arthroplasty (TKA) remained unsettled. This study aimed to compare the clinical effects among posterior-stabilized (PS), cruciate-retaining (CR), bi-cruciate substituting (BCS), and bi-cruciate retaining designs for primary TKA.

Electronic databases were systematically searched to identify eligible randomized controlled trials (RCTs) and cohort studies from inception up to July 30, 2021. The primary outcomes were the range of knee motion (ROM), and the secondary outcomes were the patient-reported outcome measures (PROMs) and complication and revision rates. Confidence in evidence was assessed using Confidence in Network Meta-Analysis. The Bayesian network meta-analysis was performed for synthesis.

A total of 15 RCTs and 18 cohort studies involving 3520 knees were included. The heterogeneity and inconsistency were acceptable. There was a significant difference in ROM at the early follow-up when PS was compared with CR (mean difference [MD] = 3.17, 95% confidence interval [CI] 0.07, 7.18) and BCS was compared with CR (MD = 9.69, 95% CI 2.18, 17.51). But at the long-term follow-up, there was no significant difference in ROM in any one knee implant compared with the others. No significant increase was found in the PROMs and complication and revision rates at the final follow-up time.

At early follow-up after TKA, PS and BCS knee implants significantly outperform the CR knee implant in ROM. But in the long run, the available evidence suggests different knee prostheses could make no difference in clinical outcomes after TKA with extended follow-up.

Measuring the health of the population is of great significance to the development of a region. We aimed to estimate the population, probability of death, and quality of life in western China.

We calculated the age-specific mortality rate and prevalence rate of diseases and injuries using the Full Population Database and the Home Page of Inpatient Medical Record. We used multiple interpolation methods to insert missing information from the death data and the model of Kannisto to adjust the mortality rate for elderly individuals. The age-specific prevalence rate of diseases and injuries was adjusted according to the standard ratio of age and methods of equal proportional allocation. Life expectancy was calculated by a life table, and the quality of life was estimated using the Sullivan method.

The total population continued to increase in 2015 to 2019 in the Shaanxi Province, China. The mortality rate of children under five has improved, and the mortality rate of people over 65 is decreasing year by year. Life expectancy increased from 74.66 years in 2015 to 77.19 years in 2019. Even with the total risk of disease and injury, the health-adjusted life expectancy increased by 1.90 years within 5 years, and the number of unhealthy years significantly improved. Health-adjusted life expectancy increased by 1.75 years when only considered the ten major disease systems (tumors; endocrinology, nutrition and metabolism; mental and behavioral disorders; nervous system; sensory diseases; circulatory system; respiratory system; digestive system; genitourinary system; musculoskeletal system and connective tissue), and the number of unhealthy years increased slightly.

In the past five years, Shaanxi Province has made progress in improving life expectancy and controlling the development of chronic diseases. It is necessary to take specific preventive measures and improve the quality of basic public health services.

Perturbations in bone marrow mesenchymal stem cell (BMSC) differentiation play an important role in steroid-induced osteonecrosis of the femoral head (SONFH). At present, studies on SONFH concentrate upon the balance within BMSC osteogenic and adipogenic differentiation. However, BMSC apoptosis as well as proliferation are important prerequisites in their differentiation. The hedgehog (HH) signaling pathway regulates bone cell apoptosis. Baicalin (BA), a well-known compound in traditional Chinese medicine, can affect the proliferation and apoptosis of numerous cell types via HH signaling. However, the potential role and mechanisms of BA on BMSCs are unclear. Thus, we aimed to explore the role of BA in dexamethasone (Dex)-induced BMSC apoptosis in this study.

Primary BMSCs were treated with 10^-6 mol/L Dex alone or with 5.0 μmol/L, 10.0 μmol/L, or 50.0 μmol/L BA for 24 hours followed by co-treatment with 5.0 μmol/L, 10.0 μmol/L, or 50.0 μmol/L BA and 10^-6 mol/L Dex. Cell viability was assayed through the Cell Counting Kit-8 (CCK-8). Cell apoptosis was evaluated using Annexin V-fluorescein isothiocyanate/propidium iodide (PI) staining followed by flow cytometry. The imaging and counting, respectively, of Hochest 33342/PI-stained cells were used to assess the morphological characteristics and proportion of apoptotic cells. To quantify the apoptosis-related proteins (e.g., apoptosis regulator BAX [Bax], B-cell lymphoma 2 [Bcl-2], caspase-3, and cleaved caspase-3) and HH signaling pathway proteins, western blotting was used. A HH-signaling pathway inhibitor was used to demonstrate that BA exerts its anti-apoptotic effects via the HH signaling pathway.

The results of CCK-8, Hoechst 33342/PI-staining, and flow cytometry showed that BA did not significantly promote cell proliferation (CCK-8: 0 μmol/L, 100%; 2.5 μmol/L, 98.58%; 5.0 μmol/L, 95.18%; 10.0 μmol/L, 98.11%; 50.0 μmol/L, 99.38%, F = 2.33, P > 0.05), but it did attenuate the effect of Dex on apoptosis (Hoechst 33342/PI-staining: Dex+ 50.0 μmol/L BA, 12.27% vs. Dex, 39.27%, t = 20.62; flow cytometry: Dex + 50.0 μmol/L BA, 12.68% vs. Dex, 37.43%, t= 11.56; Both P < 0.05). The results of western blotting analysis showed that BA reversed Dex-induced apoptosis by activating the HH signaling pathway, which down-regulated the expression of Bax, cleaved-caspase 3, and suppressor of fused (SUFU) while up-regulating Bcl-2, sonic hedgehog (SHH), and zinc finger protein GLI-1 (GLI-1) expression (Bax/Bcl-2: Dex+ 50.0 μmol/L BA, 1.09 vs. Dex, 2.76, t= 35.12; cleaved caspase-3/caspase-3: Dex + 50.0 μmol/L BA, 0.38 vs. Dex, 0.73, t= 10.62; SHH: Dex + 50.0 μmol/L BA, 0.50 vs. Dex, 0.12, t= 34.01; SUFU: Dex+ 50.0 μmol/L BA, 0.75 vs. Dex, 1.19, t= 10.78; GLI-1: Dex+ 50.0 μmol/L BA, 0.40 vs. Dex, 0.11, t= 30.68. All P < 0.05).

BA antagonizes Dex-induced apoptosis of human BMSCs by activating the HH signaling pathway. It is a potential candidate for preventing SONFH.

The HELIOS stent is a sirolimus-eluting stent with a biodegradable polymer and titanium oxide film as the tie-layer. The study aimed to evaluate the safety and efficacy of HELIOS stent in a real-world setting.

The HELIOS registry is a prospective, multicenter, cohort study conducted at 38 centers across China between November 2018 and December 2019. A total of 3060 consecutive patients were enrolled after application of minimal inclusion and exclusion criteria. The primary endpoint was target lesion failure (TLF), defined as a composite of cardiac death, non-fatal target vessel myocardial infarction (MI), and clinically indicated target lesion revascularization (TLR) at 1-year follow-up. Kaplan-Meier methods were used to estimate the cumulative incidence of clinical events and construct survival curves.

A total of 2998 (98.0%) patients completed the 1-year follow-up. The 1-year incidence of TLF was 3.10% (94/2998, 95% closed interval: 2.54-3.78%). The rates of cardiac death, non-fatal target vessel MI and clinically indicated TLR were 2.33% (70/2998), 0.20% (6/2998), and 0.70% (21/2998), respectively. The rate of stent thrombosis was 0.33% (10/2998). Age ≥60 years, diabetes mellitus, family history of coronary artery disease, acute myocardial infarction at admission, and device success were independent predictors of TLF at 1 year.

The 1-year incidence rates of TLF and stent thrombosis were 3.10% and 0.33%, respectively, in patients treated with HELIOS stents. Our results provide clinical evidence for interventional cardiologists and policymakers to evaluate HELIOS stent.

ClinicalTrials.gov, NCT03916432

Although the need for consolidation chemotherapy after successful induction therapy is well established in patients with acute myeloid leukemia (AML) in first complete remission (CR1), the value of consolidation chemotherapy before allogeneic hematopoietic stem cell transplantation remains controversial.

We retrospectively compared the effect of the number of pre-transplant consolidation chemotherapies on outcomes of human leukocyte antigen-matched sibling stem cell transplantation (MSDT) for patients with AML in CR1 in multicenters across China. In our study, we analyzed data of 373 AML patients in CR1 from three centers across China.

With a median follow-up of 969 days, patients with ≥ 3 courses of consolidation chemotherapy had higher probabilities of leukemia-free survival (LFS) (85.6% vs. 67.0%, P < 0.001) and overall survival (89.2% vs. 78.5%, P= 0.007), and better cumulative incidences of relapse (10.5% vs. 19.6%, P = 0.020) and non-relapse mortality (4.2% vs. 14.9%, P = 0.001) than those with ≤ 2 courses of consolidation chemotherapy. Pre-transplantation minimal residual disease-negative patients with AML in CR1 who received MSDT with ≥ 3 courses of consolidation chemotherapy had a higher probability of LFS (85.9% vs. 67.7%, P = 0.003) and a lower cumulative incidence of relapse (9.6% vs. 23.3%, P = 0.013) than those with ≤ 2 courses.

Our results indicate that patients with AML in CR1 who received MSDT might benefit from pre-transplant consolidation chemotherapy.

致编辑众所周知，支气管扩张伴非结核分枝杆菌(NTM)感染，常见于女性从不吸烟者，被称为Lady Windermere综合征(LWS)。LWS的概念于1992年首次提出。^[1]有礼貌、优雅、既往无肺部疾病的女性可能有自愿抑制咳嗽的习惯，这是肺部感染的原因，尤其是中叶和舌段支气管扩张合并鸟分枝杆菌复杂（MAC）感染。在临床实践中，我们发现支气管扩张伴肺诺卡菌病也多见于无吸烟史的中老年女性，其微生物特征、临床表现和影像学表现与LWS高度相似。在本研究中，我们回顾性分析了支气管扩张合并NTM和支气管扩张合并诺卡氏菌对我院近年收治的感染患者进行分析，研究其临床特点的异同。

致编辑脚踝扭伤是创伤中最常见的紧急损伤之一。由于其解剖的特殊性，踝关节的扭伤大多是由于外侧副韧带的损伤，其中80%是距腓前韧带（ATFL）的撕裂或断裂。^[1]如果治疗不当，损伤会长期影响患者的工作和生活，患者甚至会发展为慢性踝关节不稳定（CAI），增加治疗持续时间，给患者和医疗保险系统带来更高的经济负担。关于ATFL损伤的临床流行病学，目前大多数研究集中在对其发病率、致病原因和治疗方法的探索上，而对个体化因素和相关损伤没有给予足够的重视。此外，这些研究的发现对临床实践的指导作用有限。据我们所知，中国尚未有关于病房患者ATFL损伤的临床流行病学研究。因此，本研究回顾性分析了2007年7月至2020年12月陆军军医大学西南医院运动医学中心所有ATFL损伤患者的临床资料。目的是了解ATFL损伤的特点和模式分布，为其预防、早期诊断和治疗提供依据。本研究由陆军军医大学第一附属医院伦理委员会批准（KY 2021026）。

致编辑：近年来，全关节置换已成为保留关节功能最有效的方法。然而，随着手术数量的增加，对术后并发症的关注急剧增加。主要并发症是假体松动。松动可由假体周围关节感染（PJI）引起。^[1]假体周围组织的组织病理学是诊断PJI的常用方法之一。由于中性粒细胞可以反映机体对感染的反应，PJI的诊断可以通过组织中的中性粒细胞计数来确定。然而，组织学诊断与临床诊断的依从性和标准重复性仍有待进一步分析。假体的松动也可以是无菌过程。无菌性松动主要由两个因素引起：（1）聚乙烯颗粒、骨水泥、陶瓷、金属颗粒等引起假体周围骨溶解；（2）骨和植入物缺乏稳定性，导致无菌性松动。无论是感染性松动还是无菌性松动，结缔组织可以以不同的厚度和宽度包裹，这被称为假体周围膜，其可以在假体和骨之间形成。假体周围膜可以通过关节翻修手术去除。对这些膜进行病理分析，一方面可以为感染提供辅助诊断依据，另一方面可以为无菌性松动的深入研究提供依据。在本研究中，我们对我院翻修全髋关节和膝关节置换术中获得的假体周围组织进行了病理学分析，并讨论了病理学分析对PJI临床感染患者的诊断价值。无菌假体周围组织的无菌性淋巴细胞性血管炎相关病变（ALVAL）评分和种植体磨损颗粒的观察为临床全关节置换术后组织的评估提供了相关证据。

致编辑：三十多年来，前期自体干细胞移植（ASCT）一直是新诊断多发性骨髓瘤（NDMM）的年轻和符合条件的老年患者管理的一个组成部分。串联干细胞移植定义为3至6个月内两次计划的连续ASCT。在推出二十多年后，探索串联移植效用的试验产生了好坏参半的结果。串联ASCT在多发性骨髓瘤（MM）中的作用仍不清楚且有争议。在EMN02/HOVON95研究中，与单次ASCT相比，串联ASCT组的无进展生存期（PFS）和总生存期（OS）均延长。^[1]然而，STaMINA（BMT CTN 0702）试验的长期随访显示，单次移植和串联移植之间没有PFS或OS差异。^[2]尽管这些结果不一致，但在具有高危细胞遗传学的MM患者中，仍应考虑进行前期串联ASCT。^[3]据我们所知，关于中国MM患者串联ASCT的数据有限。为了回顾串联ASCT在我们中心治疗的NDMM患者中的真实疗效和安全性，我们进行了一项单中心回顾性分析。

致编辑：腹主动脉瘤破裂（rAAA）是一种致命的疾病。紧急手术是提供生存机会的唯一方法。1994年，血管内主动脉修复术（EVAR）被报道为rAAA的紧急治疗。与传统开放手术（OS）相比，患者可受益于其较低的围手术期死亡率和微创性。尽管最近的指南推荐了腹主动脉瘤腔内修复术优先的方法，但在实际应用中，是否优先进行腹主动脉瘤腔内修复术的标准因临床医生而异，因为不良的主动脉形态和血流动力学条件被认为会削弱腹主动脉瘤腔内修复术的益处。因此，关于EVAR作为优先事项是否适用于大多数rAAAs仍然存在争议。此外，对文献的搜索发现很少有具有长期结果的基于人群的研究。鉴于此，复旦大学中山医院进行了一项基于人群的研究。

致编辑：特纳综合征是女性中最常见的性染色体异常，发病率为1/2500女性活产，并且与一条X染色体的完全或部分丢失有关。^[1]预测妊娠前三个月特纳综合征的风险至关重要，以便尽早为产妇提供受影响胎儿的生殖选择。

致编辑：近年来，高血压病程与心血管疾病（CVDs）风险之间的关系受到了相当大的关注。^[1,2,3]一项基于246,459名韩国成年人的队列研究发现，高血压持续时间与卒中之间存在线性剂量反应关系。^[1]另一项涉及15,472名白人和10,298名黑人成年人的队列研究发现，对于高血压持续时间较长的人来说，高血压持续时间与心力衰竭的关系更强，并且没有种族证据表明这种关系。^[2]值得注意的是，来自中国汉族39,774名煤炭工人的前瞻性数据表明，心血管疾病和中风的风险随着高血压病程的增加而增加，但没有发现心血管疾病和中风与心肌梗死的相关性。^[3]重要的是，据我们所知，尚不清楚种族是否不同地影响中国个体高血压持续时间和心血管疾病之间的关系。

致编辑：酒渣鼻是一种常见的慢性炎症性皮肤病，具有潮红、红斑、丘疹、脓疱、phymatous改变等典型表现。^[1]已经表明，由此导致的皮肤屏障结构和功能的异常与酒渣鼻的病因和病理过程有关。^[2]经表皮失水（TEWL）和角质层水合（SCH）通常用于评估皮肤屏障功能，并且必须使用特定的仪器进行测量，例如Cutometer MPA 580（Courage&Khazaka Electronic GmbH，科隆，德国）和GPSkin Barrier（GPO-WER Inc.，首尔，韩国），它们相互关联良好。^[3]然而，这些仪器对于大多数皮肤科医生来说是不可用的。皮肤镜检查已经被纳入大多数皮肤科医生的临床实践中。实际上，皮肤镜检查比皮肤屏障测量仪器更容易被临床皮肤科医生使用。

致编辑：随着人口老龄化，老年人的认知障碍正成为一个更加突出的问题，影响他们的社会功能和生活质量。根据基于人群的流行病学研究，轻度认知障碍（MCI）的患病率在>65岁的成年人中为3%至19%。^[1]认知能力下降的许多风险因素已经被确定，研究确定听力损失（HL）是一个独立的风险因素。年龄相关性听力损失（ARHL）是老年人慢性残疾的第三大原因，使个人易患认知障碍和痴呆。