Volume 138 · Issue 09 · 2025

阿尔茨海默病（AD）是痴呆的主要原因，其发病率持续增加，从而给护理人员以及整个社会带来沉重负担。AD的主要病理特征包括细胞外淀粉样蛋白-β(A β)斑块和细胞内神经原纤维缠结(NFT)，以及突触和神经元丢失、活化的小胶质细胞和反应性星形胶质细胞。^[1]这些病理变化通常从无症状阶段进展为临床上可检测的认知障碍，并且该过程通常持续数年。用降低淀粉样斑块负荷的单克隆抗体治疗最近被批准用于治疗早期AD患者，从而强调了准确反映AD病理的生物标志物在临床实践中的重要性。^[2]生物标志物可以指示AD的早期迹象，并能够在疾病过程中进行早期干预。补充图1，http://links.lww.com/CM9/C404说明了可以使用流体或成像生物标志物检测的AD脑的神经病理学特征。

世界正在见证临床实践中遇到的肝病病因学的巨大变化。这部分是由于有效的抗病毒治疗加上健全的公共卫生政策，两者的结合在控制乙型肝炎和减轻慢性丙型肝炎的负担方面非常成功。不幸的是，经济繁荣、生活水平的提高以及饮食模式和体力活动的变化预示着肝病的新时代，其定义为代谢综合征和随之而来的代谢功能障碍相关脂肪性肝病(MAFLD)的发病率上升。后者与肝脏相关并发症有关，但也与不良的肝外结局有关。根据最近的估计，至少三分之一的全球人口患有MAFLD，其中16%的患者患有代谢功能障碍相关脂肪性肝炎(MASH)的进行性亚型。^[1]酒精相关肝病在患者表型中继续显著重叠，需要采用整体和多学科的方法进行病例检测和循证治疗。越来越多的人认识到脂肪肝疾病是一个主要的公共卫生问题，这导致了欧洲和最近的中国指南的更新迭代，其明确的目标是积极影响疾病的自然史并预防其不良临床结果。^[2,3]

经颅交流电刺激（tACS）是一种非侵入性神经调节技术，通过头皮电极向目标脑区施加特定频率的正弦交流电来调节脑功能。^[1]本指导原则旨在评价和总结tACS在临床应用中的疗效和安全性。我们使用术语“tACS”或“经颅交流刺激”在主要数据库中进行了结构化文献检索，以确定截至2022年6月的所有相关文献。经过严格筛选，共有35篇文章被纳入本指南（详细的搜索和筛选过程见补充图1，http://links.lww.com/CM9/C402）。指南采用了世界卫生组织（WHO）为这35项临床试验建立的推荐、评估、开发、评价等级（GRADE）证据质量评价和推荐强度分级标准。^[2]按照德尔菲法，向多个专门小组分发了电子问卷。经过收集、汇总、反馈，最终确定了tACS在各病种中的应用意见和推荐等级（详细流程见补充材料1，http://links.lww.com/CM9/C402）。

Noncoding RNAs (ncRNAs) are a class of RNA molecules with little or no protein-coding potential. Emerging evidence indicates that ncRNAs are frequently dysregulated and play pivotal roles in the pathogenesis of pancreatic cancer. Their aberrant expression can arise from chromosomal abnormalities, dysregulated transcriptional control, and epigenetic modifications. ncRNAs function as protein scaffolds or molecular decoys to modulate interactions between proteins and other biomolecules, thereby regulating gene expression and contributing to pancreatic cancer progression. In this review, we summarize the mechanisms underlying ncRNA dysregulation in pancreatic cancer, emphasize the biological significance of ncRNA–protein interactions, and highlight their clinical relevance. A deeper understanding of ncRNA–protein interactions is essential to elucidate molecular mechanisms and advance translational research in pancreatic cancer.

Nanozymes are a distinct category of nanomaterials that exhibit catalytic properties resembling those of enzymes such as peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Nanozymes derived from Chinese herbal medicines exhibit the catalytic functions of their enzyme mimics, while retaining the specific medicinal properties of the herb (termed "herbzymes" ). These nanozymes can be categorized into three main groups based on their method of synthesis: herb carbon dot nanozymes, polyphenol–metal nanozymes, and herb extract nanozymes. The reported catalytic activities of herbzymes include POD, SOD, CAT, and GPx. This review presents an overview of the catalytic activities and potential applications of nanozymes, introduces the novel concept of herbzymes, provides a comprehensive review of their classification and synthesis, and discusses recent advances in their biomedical applications. Furthermore, we also discuss the significance of research into herbzymes, including the primary challenges faced and future development directions.

The production of high-quality oocytes requires precisely orchestrated intercellular communication. Extracellular vesicles (EVs) are cell-derived nanoparticles that play a vital role in the transfer of bioactive molecules, which has gained much attention in the field of diagnosis and treatment. Over the past ten years, the participation of EVs in the reproductive processes of oocytes has been broadly studied and has shown great potential for elucidating the intricacies of female reproductive health. This review provides an extensive discussion of the influence of EVs on oocytes, emphasizing their involvement in normal physiology and altered cargo under pathological conditions. In addition, the positive impact of therapeutic EVs on oocyte quality and their role in alleviating ovarian pathological conditions are summarized.

Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor that recognizes multiple pathogen-associated molecular patterns and damage-associated molecular patterns. It is a cytoplasmic immune factor that responds to cellular stress signals, and it is usually activated after infection or inflammation, forming an NLRP3 inflammasome to protect the body. Aberrant NLRP3 inflammasome activation is reportedly associated with some inflammatory diseases and metabolic diseases. Recently, there have been mounting indications that NLRP3 inflammasomes play an important role in liver injuries caused by a variety of diseases, specifically hepatic ischemia/reperfusion injury, hepatitis, and liver failure. Herein, we summarize new research pertaining to NLRP3 inflammasomes in hepatic injury, hepatitis, and liver failure. The review addresses the potential mechanisms of action of the NLRP3 inflammasome, and its regulation in these liver diseases.

Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation.

Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs. 38.0 days, Z = 2.095, P = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs. 84.5% vs. 80.6%, P <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs. 73.9%, P = 0.003).

Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).

The level of measurable residual disease (MRD) before and after transplantation is related to inferior transplant outcomes, and post-hematopoietic stem cell transplantation measurable residual disease (post-HSCT MRD) has higher prognostic value in determining risk than pre-hematopoietic stem cell transplantation measurable residual disease (pre-HSCT MRD). However, only a few work has been devoted to the risk factors for positive post-HSCT MRD in patients with acute lymphoblastic leukemia (ALL). This study evaluated the risk factors for post-HSCT MRD positivity in patients with ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT).

A total of 1683 ALL patients from Peking University People’s Hospital between January 2009 and December 2019 were enrolled to evaluate the cumulative incidence of post-HSCT MRD. Cox proportional hazard regression models were built for time-to-event outcomes. Multivariable analysis was performed to determine independent influencing factors from the univariable analysis.

Both in total patients and in T-cell ALL or B-cell ALL, pediatric or adult, human leukocyte antigen-matched sibling donor transplantation or haploidentical SCT subgroups, positive pre-HSCT MRD was a risk factor for post-HSCT MRD positivity (P <0.001 for all). Disease status (complete remission 1 [CR1] vs. ≥CR2) was also a risk factor for post-HSCT MRD positivity in all patients and in the B cell-ALL, pediatric, or haploidentical SCT subgroups (P = 0.027; P = 0.003; P = 0.035; P = 0.003, respectively). A risk score for post-HSCT MRD positivity was developed using the variables pre-HSCT MRD and disease status. The cumulative incidence of post-HSCT MRD positivity was 12.3%, 25.1%, and 38.8% for subjects with scores of 0, 1, and 2–3, respectively (P <0.001). Multivariable analysis confirmed the association of the risk score with the cumulative incidence of post-HSCT MRD positivity and relapse as well as leukemia-free survival and overall survival.

Our results indicated that positive pre-MRD and disease status were two independent risk factors for post-HSCT MRD positivity in patients with ALL who underwent allo-HSCT.

Gait impairment is closely related to quality of life in patients with Parkinson’s disease (PD). This study aimed to explore alterations in brain microstructure in PD patients and healthy controls (HCs) and to identify the correlation of gait impairment in the ON and OFF states of patients with PD, respectively.

We enrolled 24 PD patients and 29 HCs from the Movement Disorders Program at Beijing Friendship Hospital Capital Medical University between 2019 and 2020. We acquired magnetic resonance imaging (MRI) scans and processed the diffusion kurtosis imaging (DKI) images. Preprocessing of diffusion-weighted data was performed with Mrtrix3 software, using a directional distribution function to track participants’ main white matter fiber bundles. Demographic and clinical characteristics were recorded. Quantitative gait and clinical scales were used to assess the status of medication ON and OFF in PD patients.

The axial kurtosis (AK), mean kurtosis (MK), and radial kurtosis (RK) of five specific white matter fiber tracts, the bilateral corticospinal tract, left superior longitudinal fasciculus, left anterior thalamic radiation, forceps minor, and forceps major were significantly higher in PD patients compared to HCs. Additionally, the MK values were negatively correlated with Timed Up and Go Test (TUG) scores in both the ON and OFF in PD patients. Within the PD group, higher AK, MK, and RK values, whether the patients were ON or OFF, were associated with better gait performance (i.e., higher velocity and stride length).

PD exhibits characteristic regional patterns of white matter microstructural degradation. Correlations between objective gait parameters and DKI values suggest that dopamine-responsive gait function depends on preserved white matter microstructure. DKI-based Tract-Based Spatial Statistics (TBSS) analysis may serve as a tool for evaluating PD-related motor impairments (e.g., gait impairment) and could yield potential neuroimaging biomarkers.

Hepatic inflammatory cell accumulation and the subsequent systematic inflammation drive acute-on-chronic liver failure (ACLF) development. Previous studies showed that the vagus nerve exerts anti-inflammatory activity in many inflammatory diseases. Here, we aimed to identify the key molecule mediating the inflammatory process in ACLF and reveal the neuroimmune communication arising from the vagus nerve and immunological disorders of ACLF.

Proteomic analysis was performed and validated in ACLF model mice or patients, and intervention animal experiments were conducted using neutralizing antibodies. PNU-282987 (acetylcholine receptor agonist) and vagotomy were applied for perturbing vagus nerve activity. Single-cell RNA sequencing (scRNA-seq), flow cytometry, immunohistochemical and immunofluorescence staining, and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) technology were used for in vivo or in vitro mechanistic studies.

The unbiased proteomics identified C-X-C motif chemokine ligand 9 (CXCL9) as the greatest differential protein in the livers of mice with ACLF and its relation to the systematic inflammation and mortality were confirmed in patients with ACLF. Interventions on CXCL9 and its receptor C-X-C chemokine receptor 3 (CXCR3) improved liver injury and decreased mortality of ACLF mice, which were related to the suppressing of hepatic immune cells’ accumulation and activation. Vagus nerve stimulation attenuated while vagotomy aggravated the expression of CXCL9 and the severity of ACLF. Blocking CXCL9 and CXCR3 ameliorated liver inflammation and increased ACLF-associated mortality in ACLF mice with vagotomy. scRNA-seq revealed that hepatic macrophages served as the major source of CXCL9 in ACLF and were validated by immunofluorescence staining and flow cytometry analysis. Notably, the expression of CXCL9 in macrophages was modulated by vagus nerve-mediated cholinergic signaling.

Our novel findings highlighted that the neuroimmune communication of the vagus nerve–macrophage–CXCL9 axis contributed to ACLF development. These results provided evidence for neuromodulation as a promising approach for preventing and treating ACLF.

Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia. We compared the effects of acarbose and sitagliptin add on to metformin on time in range (TIR) and glycemic variability (GV) in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring (CGM).

This study was a randomized, open-label, active-controlled, parallel-group trial conducted at 15 centers in China from January 2020 to August 2022. We recruited patients with type 2 diabetes aged 18–65 years with body mass index (BMI) within 19–40 kg/m² and hemoglobin A1c (HbA1c) between 6.5% and 9.0%. Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days. After the first 14-day treatment period, patients wore CGM and entered another 14-day treatment period. The primary outcome was the level of TIR after treatment between groups. We also performed time series decomposition, dimensionality reduction, and clustering using the CGM data.

A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin. There was no statistically significant difference in TIR between the two groups. Time below range (TBR) and coefficient of variation (CV) levels in acarbose users were significantly lower than those in sitagliptin users. Median (25th percentile, 75th percentile) of TBR below target level <3.9 mmol/L (TBR_3.9): Acarbose: 0.45% (0, 2.13%) vs. Sitagliptin: 0.78% (0, 3.12%), P = 0.042; Median (25th percentile, 75th percentile) of TBR below target level <3.0 mmol/L (TBR_3.0): Acarbose: 0 (0, 0.22%) vs. Sitagliptin: 0 (0, 0.63%), P = 0.033; CV: Acarbose: 22.44 ± 5.08% vs. Sitagliptin: 23.96 ± 5.19%, P <0.001. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV (group with small wave, moderate wave and big wave). No significant difference was found in the complexity of glucose time series index (CGI) between acarbose users and sitagliptin users. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV.

Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia. Time series analysis of CGM data may predict GV and the risk of hypoglycemia.

Chinese Clinical Trial Registry: ChiCTR2000039424.

在冠状病毒疾病2019（新冠肺炎）疫情期间，新冠肺炎的疾病严重程度因受感染患者的潜在状况而有很大差异。^[1]间质性肺病(ILD)包括一组与显著发病率和死亡率相关的弥漫性实质性肺病。^[2]目前，在中国，评估已有ILD和新冠肺炎患者结局的多中心数据有限。我们的研究基于本集团自2017年起在中国进行的全国性多中心前瞻性ILD注册研究。我们对该队列中的严重急性呼吸综合征冠状病毒2型（新型冠状病毒）感染患者进行了随访，并描述了他们的特征、疾病严重程度和结局。我们还探讨了新冠肺炎严重程度和结果的风险因素。

致编辑：青年成熟型糖尿病(MODY)的特征是具有常染色体显性遗传模式的非自身免疫性糖尿病。由于MODY之间的临床表型重叠，如1型糖尿病（T1DM）和2型糖尿病（T2DM），超过80%的MODY患者最初被误诊。^[1]近几十年来，下一代测序技术的出现和发展促进了对MODY的更深入了解。高通量测序显著扩展了我们对不同人群中MODY致病模式的了解。^[2,3]鉴于MODY的患病率因种族、临床或研究环境、识别病例的选择标准和测序方法而异，不同研究人群中致病基因的检出率不同。^[4]由于大多数先前关于单基因糖尿病的研究主要集中在欧洲血统的人群，特别是在儿科群体中，缺乏对中国患者MODY的临床和遗传结构的全面了解限制了医疗保健系统内相关遗传服务的发展。因此，在这项多中心研究中，我们旨在从三个中心的三个队列中鉴定MODY基因的新致病变异，从而获得对中国MODY患者有效实施风险评估、遗传咨询和个性化治疗的必要信息。

致编辑：Charcot-Marie-Tooth病2A型（CMT2A），由线粒体融合蛋白-2突变引起（最惠国待遇），是轴突CMT最常见的形式，占CMT2的20-30%。^[1,2]CMT2A表现出临床和遗传异质性，大多数致病突变位于保守的鸟苷三磷酸酶（GTPase）结构域内。^[3]已经观察到家族内的家族内变异性。因此，CMT2A的全面基因型-表型研究，特别是在大型队列中，对于促进对CMT的理解至关重要。此外，定性肌肉磁共振成像（MRI）已被用于评估CMT的疾病严重程度。^[4]然而，关于CMT2A患者肌内脂肪分数（FF）（一种潜在的敏感标志物）的研究在文献中仍然很少。