2023年 · 第136卷第15期

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.

To the Editor: It is well-known that bronchiectasis with non-tuberculous mycobacterial (NTM) infection, commonly reported in female never-smokers, is termed as Lady Windermere syndrome (LWS). The concept of LWS was first proposed in 1992.^[1]Polite and graceful women without previous lung disease might have the habit of voluntary cough suppression, which is responsible for lung infections, especially bronchial dilation in the middle lobe and lingular segment combined withMycobacterium aviumcomplex (MAC) infection. In clinical practice, we found that bronchiectasis with pulmonary nocardiosis also more frequently occurs in middle-aged and elderly women without history of smoking, and its microbial characteristics, clinical presentations, and radiographic findings are highly analogous to those of LWS. In this research, we retrospectively analyzed data of patients with bronchiectasis with NTM and bronchiectasis complicated withNocardiainfection who were admitted to our hospital in recent years, and studied their similarities and differences in clinical characteristics.

To the Editor: Ankle sprains are some of the most common emergency injuries from trauma. Due to the particularity of its anatomy, most sprains of the ankle are due to injuries of the lateral collateral ligaments, of which 80% are tears or ruptures of the anterior talofibular ligament (ATFL).^[1]If the treatment is not appropriate, the injury will affect the patient’s work and life in the long term, and the patient can even develop chronic ankle instability (CAI), increasing the treatment duration and resulting in higher economic burdens on the patients and the medical insurance system. Regarding the clinical epidemiology of ATFL injuries, at present, most research is focused on the exploration of the incidence, pathogenic causes, and treatment methods, but not enough attention has been given to individualized factors and the associated injuries. In addition, the guidance effect of the findings of these studies on clinical practice is limited. To the best of our knowledge, there have been no clinical epidemiological studies on ATFL injuries in ward patients in China. Therefore, this study retrospectively analyzed the clinical data of all patients with ATFL injuries in the Sports Medicine Center of the Southwest Hospital of Army Military Medical University from July 2007 to December 2020. The goal was to understand the characteristics and pattern distributions of ATFL injuries to provide a basis for their prevention, early diagnosis, and treatment. This study was approved by the Ethics Committee of The First Affiliated Hospital of Army Medical University (KY 2021026).

To the Editor:In recent years, total joint replacement has become the most effective method to preserve the joint function. However, with the increase in the numbers of surgeries, attention to post-operative complications has increased dramatically. The main complication is loosening of the prosthesis. Loosening can be caused by periprosthetic joint infection (PJI).^[1]The histopathology of periprosthetic tissue is one of the commonly used methods for diagnosing PJI. Since neutrophils can reflect the body’s response to infection, the diagnosis of PJI can be determined by the neutrophil counts in the tissues. However, the compliance and standard repeatability of the histological diagnosis and the clinical diagnosis remain to be further analyzed. The loosening of prosthetics can also be an aseptic process. Aseptic loosening is mainly caused by two factors: (1) polyethylene granules, bone cement, ceramics, metal particles, etc., which cause periprosthetic osteolysis; (2) lack of bone and implant stability which results in aseptic loosening. Whether it is infectious or aseptic loosening, connective tissue can wrap around with varying thickness and width, and this is known as the periprosthetic membrane, which can be formed between the prosthesis and the bone. The periprosthetic membrane can be removed by joint revision surgery. Pathological analysis of these membranes can provide an auxiliary diagnostic basis for infection on the one hand and an in-depth study of aseptic loosening on the other hand. In this study, we performed pathological analyses of periprosthetic tissues obtained during revision total hip and knee arthroplasty in our hospital and discussed the diagnostic value of pathologic analysis in PJI in patients with clinical infections. The aseptic lymphocytic vasculitis-associated lesion (ALVAL) score of the aseptic periprosthetic tissue and the observation of the wear particles of the implant provide relevant evidence for the evaluation of the tissue after clinical total joint replacement.

To the Editor: Upfront autologous stem cell transplantation (ASCT) has been an integral part of the management of young and eligible older patients with newly diagnosed multiple myeloma (NDMM) for over three decades. Tandem stem cell transplantation was defined as two planned sequential ASCTs within 3 to 6 months. More than two decades after its introduction, trials exploring the utility of tandem transplants have yielded mixed results. The role of tandem ASCT in multiple myeloma (MM) remains unclear and controversial. In the EMN02/HOVON95 study, as compared with single ASCT, both prolonged progression-free survival (PFS) and overall survival (OS) were seen in the tandem ASCT arm.^[1]However, long-term follow-up of the STaMINA (BMT CTN 0702) trial showed no PFS or OS difference between single and tandem transplants.^[2]Despite these discordant results, an upfront tandem ASCT should be considered in patients with high-risk cytogenetics in MM.^[3]To our knowledge, there are limited data concerning tandem ASCT for patients with MM in China. To review the real-world efficacy and safety of tandem ASCT in patients with NDMM treated in our center, we conducted a single-center retrospective analysis.

To the Editor: Ruptured abdominal aortic aneurysm (rAAA) is a fatal disease. Emergency surgery is the only way to provide an opportunity for survival. In 1994, endovascular aortic repair (EVAR) was reported as an emergency treatment for rAAA. Compared with traditional open surgery (OS), patients could benefit from its lower perioperative mortality and minimal invasiveness. Although recent guidelines have recommended an EVAR-first approach if suitable as judged by the clinician, the standard of whether to give a priority to EVAR varies among clinicians in practical applications, because hostile aortic morphology and hemodynamic conditions were thought to weaken the benefit of EVAR. Hence, controversies still exist regarding whether EVAR as a priority is applicable to most rAAAs. In addition, a search of the literature found few population-based studies with long-term outcomes. Given this, a population-based study was conducted by Zhongshan Hospital, Fudan University.

To the Editor: Turner syndrome is the most common sex-chromosome abnormality in females with an incidence of 1 per 2500 female live births, and it is associated with either complete or partial loss of one X chromosome.^[1]Predicting the risk of Turner syndrome in the first trimester of pregnancy is of critical importance, in order to provide parturient with reproductive choices for affected fetuses at the earliest opportunity.

To the Editor:The relationship between hypertension duration and the risk of cardiovascular diseases (CVDs) has received considerable attention in recent years.^[1,2,3]A cohort study based on 246,459 Korean adults found a linear dose-response relationship between hypertension duration and stroke.^[1]Another cohort study involving 15,472 White and 10,298 Black adults found that the hypertension duration-heart failure relationship was stronger for people with longer hypertension duration, and there was no evidence of race on the relationship.^[2]Notably, prospective data from 39,774 coal workers in Chinese Han suggested that the risk of CVDs and stroke increased with increasing hypertension duration, but no associations of CVDs and stroke with myocardial infarction were found.^[3]Importantly, to our knowledge, it remains unclear whether ethnicity differentially affects the associations between hypertension duration and CVDs in Chinese individuals.

To the Editor:Rosacea is a common chronic inflammatory skin disease with typical manifestations such as flushing, erythema, papules, pustules, and phymatous changes.^[1]It has been indicated that the resulting abnormal skin barrier structure and function was associated with the etiology and pathological process of rosacea.^[2]Transepidermal water loss (TEWL) and stratum corneum hydration (SCH) are commonly used to evaluate skin barrier function and must be measured using specific instruments, such as the Cutometer MPA 580 (Courage & Khazaka Electronic GmbH, Cologne, Germany) and GPSkin Barrier (GPO-WER Inc., Seoul, South Korea), which inter-correlate well.^[3]However, these instruments are not available to most dermatologists. Dermoscopy has been incorporated into the clinical practice of most dermatologists. Practically, dermoscopy is more accessible to clinical dermatologists than skin barrier measure instruments.

To the Editor: Cognitive impairment in older adults is becoming a more prominent issue as the population ages, affecting their social functioning and quality of life. The prevalence of mild cognitive impairment (MCI), as determined in population-based epidemiological studies, ranges from 3% to 19% in adults >65 years.^[1]Many risk factors for cognitive decline have been identified, with research identified hearing loss (HL) as an independent risk factor. Age-related hearing loss (ARHL), the third leading cause of chronic disability in older adults, predisposes individuals to cognitive impairment and dementia.