Volume 138 · Issue 07 · 2025

哮喘是一种常见的气道慢性炎症性疾病，在临床症状、严重程度和治疗结果方面表现出显著的异质性，从而对公众健康构成严重威胁。^[1]中国肺健康（CPH）研究结果表明，中国≥20岁人群中哮喘患病率为4.2%。^[2]全球哮喘倡议（GINA）强调，哮喘的治疗目标是实现“哮喘的总体控制”，即既要实现当前症状控制，又要降低未来发作的风险。^[3]然而，目前世界范围内的哮喘控制方法并不令人满意，严重哮喘占所有哮喘病例的5-10%，给医疗保健系统带来了巨大的经济负担。^[4]

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a chronic inflammation of the gastrointestinal tract with unknown etiology. The cause of IBD is widely considered multifactorial, with prevailing hypotheses suggesting that the microbiome and various environmental factors contribute to inappropriate activation of the mucosal immune system in genetically susceptible individuals. Although the incidence of IBD has stabilized in Western countries, it is rapidly increasing in newly industrialized countries, particularly China, making IBD a global disease. Significant changes in multiple biomarkers before IBD diagnosis during the preclinical phase provide opportunities for earlier diagnosis and intervention. Advances in technology have driven the development of telemonitoring tools, such as home-testing kits for fecal calprotectin, serum cytokines, and therapeutic drug concentrations, as well as wearable devices for testing sweat cytokines and heart rate variability. These tools enable real-time disease activity assessment and timely treatment strategy adjustments. A wide range of novel drugs for IBD, including interleukin-23 inhibitors (mirikizumab, risankizumab, and guselkumab) and small-molecule drugs (etrasimod and upadacitinib), have been introduced in the past few years. Despite these advancements, approximately one-third of patients remain primary non-responders to the initial treatment, and half eventually lose response over time. Precision medicine integrating multi-omics data, advanced combination therapy, and complementary approaches, including stem cell transplantation, psychological therapies, neuromodulation, and gut microbiome modulation therapy, may offer solutions to break through the therapeutic ceiling.

Oncolytic virotherapy is a promising therapeutic approach treating tumors, where oncolytic viruses (OVs) can selectively infect and lyse tumor cells through replication, while also triggering long-lasting anti-tumor immune responses. Vaccinia virus (VV) has emerged as a leading candidate for use as an OV due to its broad cytophilicity and robust capacity to express exogenous genes. Consequently, oncolytic vaccinia virus (OVV) has entered clinical trials. This review provides an overview of the key strategies used in the development of OVV, summarizes the findings from clinical trials, and addresses the challenges that must be overcome in the advancement of OVV-based therapies. Furthermore, it explores potential future strategies for enhancing the development and clinical application of OVV, intending to improve tumor treatment outcomes. The review aims to facilitate the further development and clinical adoption of OVV, thereby advancing tumor therapies.

The high failure rates in clinical drug development based on animal models highlight the urgent need for more representative human models in biomedical research. In response to this demand, organoids and organ chips were integrated for greater physiological relevance and dynamic, controlled experimental conditions. This innovative platform—the organoids-on-a-chip technology—shows great promise in disease modeling, drug discovery, and personalized medicine, attracting interest from researchers, clinicians, regulatory authorities, and industry stakeholders. This review traces the evolution from organoids to organoids-on-a-chip, driven by the necessity for advanced biological models. We summarize the applications of organoids-on-a-chip in simulating physiological and pathological phenotypes and therapeutic evaluation of this technology. This section highlights how integrating technologies from organ chips, such as microfluidic systems, mechanical stimulation, and sensor integration, optimizes organoid cell types, spatial structure, and physiological functions, thereby expanding their biomedical applications. We conclude by addressing the current challenges in the development of organoids-on-a-chip and offering insights into the prospects. The advancement of organoids-on-a-chip is poised to enhance fidelity, standardization, and scalability. Furthermore, the integration of cutting-edge technologies and interdisciplinary collaborations will be crucial for the progression of organoids-on-a-chip technology.

In recent years, the roles of mitochondrial RNA and its associated human diseases have been reported to increase significantly. Treatments based on mtRNA metabolic processes and nuclear gene mutations are thus discussed. The mitochondrial oxidative phosphorylation process is affected by mtRNA metabolism, including mtRNA production, maturation, stabilization, and degradation, which leads to a variety of inherited human mitochondrial diseases. Moreover, mitochondrial diseases are caused by mitochondrial messenger RNA, mitochondrial transfer RNA, and mitochondrial ribosomal RNA gene mutations. This review presents the molecular mechanisms of human mtRNA metabolism and pathological mutations in mtRNA metabolism-related nuclear-encoded/nonencoded genes and mitochondrial DNA mutations to highlight the importance of mitochondrial RNA-related diseases and treatments.

Physical activity, sedentary behavior (SB), and sleep duration are associated with brain health. Effects of those on developing Parkinson’s disease (PD) are poorly investigated. This study aimed to examine the independent and joint associations of physical activity, SB, sleep with PD risk.

We analyzed data on 401,697 participants from the UK Biobank cohort, which was enrolled in 2006–2010. Physical activities were measured based on a questionnaire. Sleep and SB time were defined through self-reported total number of hours. Models fitted with restricted cubic spline were conducted to test for linear and non-linear shapes of each association. Cox proportional hazards regression models were used to estimate the association of three modifiable behaviors.

Our analytic sample included 401,697 participants with 3030 identified cases of PD (mean age, 63 years; 62.9% male). PD risk was 18% lower in the high total physical activity group (95% CI, 0.75–0.90), 22% lower in the high leisure-time physical activity (LTPA) group (95% CI, 0.71–0.86) compared with the low level and 14% higher in the high sleep duration group (95% CI, 1.05–1.24) compared to moderate group. Total SB time was irrelevant with PD risk, while high TV viewing showed a 12% increase of PD risk compared to the low group (95% CI, 1.02–1.22). Low computer use (0 h/day) was associated with a 14% higher risk compared to 1 h/day use (95% CI, 1.04–1.26). Those associations were independent. A combination of 7 h/day sleep, moderate-to-high computer use, and moderate-to-vigorous intensity of LTPA showed lowest PD risk (HR, 0.70; 95% CI, 0.57–0.85).

Physical activity, SB, and sleep were associated with PD risks separately. Our findings emphasize the possibility for changing these three daily activities concurrently to lower the risk of PD. These findings may promote an active lifestyle for PD prevention.

Metabolic-associated fatty liver disease (MAFLD) is the predominant form of chronic liver disease worldwide. This study was designed to investigate the proportion and characteristics of MAFLD within the general Chinese population and to identify the contributory risk factors for liver fibrosis among MAFLD individuals.

The participants were recruited from a cohort undergoing routine health evaluations at the Third Hospital of Hebei Medical University between May 2019 and March 2023. The diagnosis of MAFLD was based on the established clinical practice guidelines. The fibrosis-4 index score (FIB-4) was employed to evaluate hepatic fibrosis, with a FIB-4 score of ≥1.3 indicating significant fibrosis. Binary logistic regression analyses were used to determine risk factors associated with significant hepatic fibrosis in MAFLD.

A total of 22,970 participants who underwent comprehensive medical examinations were included in the analysis. The overall proportion of MAFLD was 28.77% (6608/22,970), with 16.87% (1115/6608) of these patients showing significant fibrosis as assessed using FIB-4. Independent risk factors for significant liver fibrosis in MAFLD patients were male (odds ratio [OR] = 0.676, 95% confidence interval [CI]: 0.558–0.821), hepatitis B surface antigen (HBsAg) positivity (OR = 2.611, 95% CI: 1.557–4.379), body mass index ≥23.00 kg/m² (OR = 0.632, 95% CI: 0.470–0.851), blood pressure ≥130/85 mmHg (OR = 1.885, 95% CI: 1.564–2.272), and plasma glucose ≥5.6 mmol/L (OR = 1.815, 95% CI: 1.507–2.186) (all P <0.001).

The proportion of MAFLD in an urban Chinese population is 28.77%. About 16.87% of MAFLD patients presented with significant liver fibrosis. Independent risk factors for significant liver fibrosis in MAFLD patients should be noticed.

The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown.

Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3′-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice.

POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo. Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p, and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p, miR-29a-3p, PIK3R1, and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1, PIK3R1, and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples.

The POU2F1-miR-29b-3p/miR-29a-3p-PIK3R1/PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.

Molecular subtyping is an essential complementarity after pathological analyses for targeted therapy. This study aimed to investigate the consistency of next-generation sequencing (NGS) results between circulating tumor DNA (ctDNA)-based and tissue-based in non-small cell lung cancer (NSCLC) and identify the patient characteristics that favor ctDNA testing.

Patients who diagnosed with NSCLC and received both ctDNA- and cancer tissue-based NGS before surgery or systemic treatment in Lung Cancer Center, Sichuan University West China Hospital between December 2017 and August 2022 were enrolled. A 425-cancer panel with a HiSeq 4000 NGS platform was used for NGS. The unweighted Cohen’s kappa coefficient was employed to discriminate the high-concordance group from the low-concordance group with a cutoff value of 0.6. Six machine learning models were used to identify patient characteristics that relate to high concordance between ctDNA-based and tissue-based NGS.

A total of 85 patients were enrolled, of which 22.4% (19/85) had stage III disease and 56.5% (48/85) had stage IV disease. Forty-four patients (51.8%) showed consistent gene mutation types between ctDNA-based and tissue-based NGS, while one patient (1.2%) tested negative in both approaches. Patients with advanced diseases and metastases to other organs would be suitable for the ctDNA-based NGS, and the generalized linear model showed that T stage, M stage, and tumor mutation burden were the critical discriminators to predict the consistency of results between ctDNA-based and tissue-based NGS.

ctDNA-based NGS showed comparable detection performance in the targeted gene mutations compared with tissue-based NGS, and it could be considered in advanced or metastatic NSCLC.

Fibrosis of the connective tissue in the vaginal wall predominates in pelvic organ prolapse (POP), which is characterized by excessive fibroblast-to-myofibroblast differentiation and abnormal deposition of the extracellular matrix (ECM). Our study aimed to investigate the effect of ECM stiffness on vaginal fibroblasts and to explore the role of methyltransferase 3 (METTL3) in the development of POP.

Polyacrylamide hydrogels were applied to create an ECM microenvironment with variable stiffness to evaluate the effects of ECM stiffness on the proliferation, differentiation, and expression of ECM components in vaginal fibroblasts. METTL3 small interfering RNA and an overexpression vector were transfected into vaginal fibroblasts to evaluate the effects of METTL3 silencing and overexpression on matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal modulation of the ECM. Both procedures were detected by 5-ethynyl-2′-deoxyuridine (EdU) staining, Western blotting (WB), quantitative real-time polymerase chain reaction (RT–qPCR), and immunofluorescence (IF).

Vaginal fibroblasts from POP patients exhibited increased proliferation ability, increased expression of α-smooth muscle actin (α-SMA), decreased expression of collagen I/III, and significantly decreased expression of tissue inhibitors of matrix metalloproteinases (TIMPs) in the stiff matrix (P <0.05). Compared with those from non-POP patients, vaginal wall tissues from POP patients demonstrated a significant increase in METTL3 content (P <0.05). However, silencing METTL3 expression in vaginal fibroblasts with high ECM stiffness resulted in decreased proliferation ability, decreased α-SMA expression, an increased ratio of collagen I/III, and increased TIMP1 and TIMP2 expression. Conversely, METTL3 overexpression significantly promoted the process of increased proliferation ability, increased α-SMA expression, decreased ratio of collagen I/III and decreased TIMP1 and TIMP2 expression in the soft matrix (P <0.05).

Elevated ECM stiffness can promote excessive proliferation, differentiation, and abnormal ECM modulation, and the expression of METTL3 plays an important role in alleviating or aggravating matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal ECM modulation.

作为终末期膝关节骨关节炎的有效治疗方法，全膝关节置换术（TKA）在过去几年中已在全球范围内广泛开展。尽管其有效性，但接受TKA的患者有一系列并发症的风险，从感染到血栓栓塞，^[1]以及大量失血，这仍然是整形外科医生关注的问题，导致输血的可能性增加、住院时间延长和费用增加。^[2,3]

致编辑：在中国，多发性骨髓瘤（MM）的粗患病率为每10万人口中有7人，发病率为每10万人口中有1.6人。^[1]术语“2021年第一季度异常”是指遗传改变，包括1号染色体的2021年第一季度区中的缺失、重复和扩增。2021年第一季度病的获得或扩增(2021年第一季度+)是指1号染色体长臂21位处遗传物质的额外拷贝或多个拷贝，是一种与MM患者的不良临床结局相关的充分记录的异常，并且已被证明与新诊断的MM(NDMM)和复发/难治性MM(RRMM)的不良预后、耐药性和疾病进展相关。^[2]然而，由于缺乏临床数据，指南中很少推荐专门针对2021年第一季度+患者的治疗方案，除了2018年梅奥骨髓瘤分层和风险适应治疗（mSMART）3.0，它对符合移植条件的NDMM患者提出了建议。本研究旨在评估2021年第一季度+治疗RRMM方案的有效性，并回顾相关研究。

致编辑：肺炎支原体(肺炎支原体），一种缺乏细胞壁的非典型病原体，是儿童社区获得性肺炎的主要原因；它主要影响学龄儿童。^[1]社区获得性呼吸窘迫综合征(CARDS)毒素，一种二磷酸腺苷核糖基化和空泡化外毒素肺炎支原体，诱导细胞肿胀和空泡化。^[2]迄今为止，CARDS毒素的精确功能特征尚未完全阐明。

致编辑：先前的研究报道了人类白细胞抗原（HLA）等位基因在血液疾病患者中的频率增加，包括急性髓性白血病（AML）、急性淋巴细胞白血病（ALL）、骨髓增生异常综合征（MDS）和再生障碍性贫血（AA）。^[1]然而，目前缺乏分析与血液疾病相关的HLA区组和单倍型的大样本研究。HLA以单倍型的形式遗传，染色体上相邻的HLA基因座之间存在很强的连锁不平衡。HLA-A位于α嵌段内；HLA-B和C位于β嵌段内；HLA-DRB1、DQB1、DRB3/4/5和DQA1位于δ区；HLA-DPA1和DPB1位于ε区。当HLA等位基因的频率增加时，在相同区块或单倍型内连接的其他基因座处的等位基因也可能表现出增加的频率。本研究旨在分析频率增加的等位基因是否位于同一区块或单倍型内，并调查HLA区块分析或单倍型分析对于血液疾病的关联研究是否更有意义。

致编辑：重症监护病房获得性虚弱（ICU-AW）是危重患者的一种严重并发症，与机械通气（MV）延长、ICU住院时间延长、住院费用增加和死亡率较高有关。目前的研究表明，蛋白质可能是维持危重患者肌肉质量和身体功能以及改善临床结果的最关键底物。^[1]