MedNexus
2025年 · 第138卷第04期
出版日期 2025-02-20电子版 ￥0.00元
MedNexus
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Review Article
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线粒体氧化磷酸化障碍在男性不育中的作用机制Kai Meng, Qian Liu, Yiding Qin, Wenjie Qin, Ziming Zhu, Longlong Sun, Mingchao Jiang, Joseph Adu-Amankwaah, Fei Gao, Rubin Tan 等
中华医学杂志英文版2025年 138卷 04期
DOI: 10.1097/CM9.0000000000003126
摘要
Male infertility has become a global concern, accounting for 20-70% of infertility. Dysfunctional spermatogenesis is the most common cause of male infertility; thus, treating abnormal spermatogenesis may improve male infertility and has attracted the attention of the medical community. Mitochondria are essential organelles that maintain cell homeostasis and normal physiological functions in various ways, such as mitochondrial oxidative phosphorylation (OXPHOS). Mitochondrial OXPHOS transmits electrons through the respiratory chain, synthesizes adenosine triphosphate (ATP), and produces reactive oxygen species (ROS). These mechanisms are vital for spermatogenesis, especially to maintain the normal function of testicular Sertoli cells and germ cells. The disruption of mitochondrial OXPHOS caused by external factors can result in inadequate cellular energy supply, oxidative stress, apoptosis, or ferroptosis, all inhibiting spermatogenesis and damaging the male reproductive system, leading to male infertility. This article summarizes the latest pathological mechanism of mitochondrial OXPHOS disorder in testicular Sertoli cells and germ cells, which disrupts spermatogenesis and results in male infertility. In addition, we also briefly outline the current treatment of spermatogenic malfunction caused by mitochondrial OXPHOS disorders. However, relevant treatments have not been fully elucidated. Therefore, targeting mitochondrial OXPHOS disorders in Sertoli cells and germ cells is a research direction worthy of attention. We believe this review will provide new and more accurate ideas for treating male infertility.
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异位骨化：当前的发展和新兴的潜在疗法Mingjian Bei, Qiyong Cao, Chunpeng Zhao, Yaping Xiao, Yimin Chen, Honghu Xiao, Xu Sun, Faming Tian, Minghui Yang, Xinbao Wu
中华医学杂志英文版2025年 138卷 04期
DOI: 10.1097/CM9.0000000000003244
摘要
This review aimed to provide a comprehensive analysis of the etiology, epidemiology, pathology, and conventional treatment of heterotopic ossification (HO), especially emerging potential therapies. HO is the process of ectopic bone formation at non-skeletal sites. HO can be subdivided into two major forms, acquired and hereditary, with acquired HO predominating. Hereditary HO is a rare and life-threatening genetic disorder, but both acquired and hereditary form can cause severe complications, such as peripheral nerve entrapment, pressure ulcers, and disability if joint ankylosis develops, which heavily contributes to a reduced quality of life. Modalities have been proposed to treat HO, but none have emerged as the gold standard. Surgical excision remains the only effective modality; however, the optimal timing is controversial and may cause HO recurrence. Recently, potential therapeutic strategies have emerged that focus on the signaling pathways involved in HO, and small molecule inhibitors have been shown to be promising. Moreover, additional specific targets, such as small interfering RNAs (siRNAs) and non-coding RNAs, could be used to effectively block HO or develop combinatorial therapies for HO.
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低血压伴神经血管改变和认知功能障碍：流行病学、病理生物学和治疗综述Yingzhe Cheng, Lin Lin, Peilin Huang, Jiejun Zhang, Yanping Wang, Xiaodong Pan
中华医学杂志英文版2025年 138卷 04期
DOI: 10.1097/CM9.0000000000003103
摘要
Hypotension is a leading cause of age-related cognitive impairment. The available literature evidences that vascular factors are associated with dementia and that hypotension alters cerebral perfusion flow and can aggravate the neurodegeneration of Alzheimer’s disease (AD). Despite the discovery of biomarkers and the recent progress made in neurovascular biology, epidemiology, and brain imaging, some key issues remain largely unresolved: the potential mechanisms underlying the neural deterioration observed in AD, the effect of cerebrovascular alterations on cognitive deficits, and the positive effects of hypotension treatment on cognition. Therefore, further well-designed studies are needed to unravel the potential association between hypotension and cognitive dysfunction and reveal the potential benefits of hypotension treatment for AD patients. Here, we review the current epidemiological, pathobiological, and treatment-related literature on neurovascular changes and hypotension-related cognitive dysfunction and highlight the unsettled but imminent issues that warrant future research endeavors.
Original Article
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C/EBP β低甲基化触发的C/EBP β-LIN28A正反馈环增强再狭窄血管平滑肌细胞增殖和迁移Xiaojun Zhou, Shan Jiang, Siyi Guo, Shuai Yao, Qiqi Sheng, Qian Zhang, Jianjun Dong, Lin Liao
中华医学杂志英文版2025年 138卷 04期
DOI: 10.1097/CM9.0000000000003110
摘要
Background:
The main cause of restenosis after percutaneous transluminal angioplasty (PTA) is the excessive proliferation and migration of vascular smooth muscle cells (VSMCs). Lin28a has been reported to play critical regulatory roles in this process. However, whether CCAAT/enhancer-binding proteins β (C/EBPβ) binds to the Lin28a promoter and drives the progression of restenosis has not been clarified. Therefore, in the present study, we aim to clarify the role of C/EBPβ-Lin28a axis in restenosis.
Methods:
Restenosis and atherosclerosis rat models of type 2 diabetes (n = 20, for each group) were established by subjecting to PTA. Subsequently, the difference in DNA methylation status and expression of C/EBPβ between the two groups were assessed. EdU, Transwell, and rescue assays were performed to assess the effect of C/EBPβ on the proliferation and migration of VSMCs. DNA methylation status was further assessed using Methyltarget sequencing. The interaction between Lin28a and ten-eleven translocation 1 (TET1) was analysed using co-immunoprecipitation (Co-IP) assay. Student’s t-test and one-way analysis of variance were used for statistical analysis.
Results:
C/EBPβ expression was upregulated and accompanied by hypomethylation of its promoter in restenosis when compared with atherosclerosis. In vitro C/EBPβ overexpression facilitated the proliferation and migration of VSMCs and was associated with increased Lin28a expression. Conversely, C/EBPβ knockdown resulted in the opposite effects. Chromatin immunoprecipitation assays further demonstrated that C/EBPβ could directly bind to Lin28a promoter. Increased C/EBPβ expression and enhanced proliferation and migration of VSMCs were observed after decitabine treatment. Further, mechanical stretch promoted C/EBPβ and Lin28a expression accompanied by C/EBPβ hypomethylation. Additionally, Lin28a overexpression reduced C/EBPβ methylation via recruiting TET1 and enhanced C/EBPβ-mediated proliferation and migration of VSMCs. The opposite was noted in Lin28a knockdown cells.
Conclusion:
Our findings suggest that the C/EBPβ-Lin28a axis is a driver of restenosis progression, and presents a promising therapeutic target for restenosis.
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中国耐药性癫痫反应性神经刺激的早期评估：一项多中心、自身对照研究Yanfeng Yang, Penghu Wei, Jianwei Shi, Ying Mao, Jianmin Zhang, Ding Lei, Zhiquan Yang, Shiwei Song, Ruobing Qian, Wenling Li 等
中华医学杂志英文版2025年 138卷 04期
DOI: 10.1097/CM9.0000000000003292
摘要
Background:
To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (EpilcureTM, GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study.
Methods:
This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well.
Results:
The follow-up period for the 19 participants was 10.7 ± 3.4 months. Seizure counts decreased significantly 6 months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 (P <0.05). The average response rate after 13 months of treatment was 42%, with 21% (n = 4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 (β <0, P <0.05). No statistically significant differences were observed in patients’ scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed.
Conclusions:
The preliminary findings suggest that EpilcureTM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required.
Registration:
Chinese Clinical Trial Registry (No. ChiCTR2200055247)
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帕罗西汀通过GRK2介导的PI3K-AKT信号减轻类风湿关节炎树突状细胞和T淋巴细胞活化Tingting Liu, Chao Jin, Jing Sun, Lina Zhu, Chun Wang, Feng Xiao, Xiaochang Liu, Liying Lv, Xiaoke Yang, Wenjing Zhou 等
中华医学杂志英文版2025年 138卷 04期
DOI: 10.1097/CM9.0000000000003165
摘要
Background:
G protein-coupled receptor kinase 2 (GRK2) could participate in the regulation of diverse cells via interacting with non-G-protein-coupled receptors. In the present work, we explored how paroxetine, a GRK2 inhibitor, modulates the differentiation and activation of immune cells in rheumatoid arthritis (RA).
Methods:
The blood samples of healthy individuals and RA patients were collected between July 2021 and March 2022 from the First Affiliated Hospital of Anhui Medical University. C57BL/6 mice were used to induce the collagen-induced arthritis (CIA) model. Flow cytometry analysis was used to characterize the differentiation and function of dendritic cells (DCs)/T cells. Co-immunoprecipitation was used to explore the specific molecular mechanism.
Results:
In patients with RA, high expression of GRK2 in peripheral blood lymphocytes, accompanied by the increases of phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR). In animal model, a decrease in regulatory T cells (Tregs), an increase in the cluster of differentiation 8 positive (CD8+) T cells, and maturation of DCs were observed. Paroxetine, when used in vitro and in CIA mice, restrained the maturation of DCs and the differentiation of CD8+ T cells, and induced the proportion of Tregs. Paroxetine inhibited the secretion of pro-inflammatory cytokines, the expression of C-C motif chemokine receptor 7 in DCs and T cells. Simultaneously, paroxetine upregulated the expression of programmed death ligand 1, and anti-inflammatory cytokines. Additionally, paroxetine inhibited the PI3K-AKT-mTOR metabolic pathway in both DCs and T cells. This was associated with a reduction in mitochondrial membrane potential and changes in the utilization of glucose and lipids, particularly in DCs. Paroxetine reversed PI3K-AKT pathway activation induced by 740 Y-P (a PI3K agonist) through inhibiting the interaction between GRK2 and PI3K in DCs and T cells.
Conclusion:
Paroxetine exerts an immunosuppressive effect by targeting GRK2, which subsequently inhibits the metabolism-related PI3K-AKT-mTOR pathway of DCs and T cells in RA.
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特立氟胺在中国成人复发性多发性硬化患者中的安全性：一项为期24周的IV期多中心研究Chao Quan, Hongyu Zhou, Huan Yang, Zheng Jiao, Meini Zhang, Baorong Zhang, Guojun Tan, Bitao Bu, Tao Jin, Chunyang Li 等
中华医学杂志英文版2025年 138卷 04期
DOI: 10.1097/CM9.0000000000002990
摘要
Background:
Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS.
Methods:
This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide.
Results:
Eighty-two patients were assigned to variant (n = 42) and wild type groups (n = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] µg/mL; wild type, 49.1 [32.0] µg/mL) and area under plasma concentration-time curve over a dosing interval (AUCtau) (variant, 1731.3 [769.0] µg·h/mL; wild type, 1564.5 [1053.0] µg·h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study.
Conclusion:
ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients.
Registration:
NCT04410965, https://clinicaltrials.gov.
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免疫检查点抑制剂联合化疗的新辅助治疗vsHER2（-）局部晚期胃癌单独化疗：一项倾向评分匹配队列研究Gehan Xu, Tianjiao Liu, Jingyi Shen, Quanlin Guan
中华医学杂志英文版2025年 138卷 04期
DOI: 10.1097/CM9.0000000000003028
摘要
Background:
This study aims to compare the efficacy between neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy vs. chemotherapy, and neoadjuvant triplet vs. doublet chemotherapeutic regimens in locally advanced gastric/esophagogastric junction cancer (LAGC).
Methods:
We included LAGC patients from 47 hospitals in China’s National Cancer Information Database (NCID) from January 2019 to December 2022. Using propensity score matching (PSM), we retrospectively analyzed the efficacy between neoadjuvant ICIs plus chemotherapy vs. chemotherapy alone, and neoadjuvant triplet vs. doublet chemotherapeutic regimens. The primary study result was the pathologic complete response (pCR) rate. The secondary study results were disease-free survival (DFS) and overall survival (OS).
Results:
A total of 1205 LAGC patients were included. After PSM, the ICIs plus chemotherapy and the chemotherapy cohorts had 184 patients each, while the doublet and triplet chemotherapy cohorts had 246 patients each. The pCR rate (14.13% vs. 7.61%, χ2 = 4.039, P = 0.044), and the 2-year (77.60% vs. 61.02%, HR = 0.67, 95% confidence interval [CI] 0.43-0.98, P = 0.048) and 3-year (70.55% vs. 61.02%, HR = 0.58, 95% CI 0.32-0.93, P = 0.048) DFS rates in the ICIs plus chemotherapy cohort were improved compared to those in the chemotherapy cohort. No significant increase was observed in the OS rates at both 1 year and 2 years. The pCR rates, DFS rates at 1-3 years, and OS rates at 1-2 years did not differ significantly between the doublet and triplet cohorts, respectively. No differences were observed in postoperative complications between any of the group comparisons.
Conclusions:
Neoadjuvant ICIs plus chemotherapy improved the pCR rate and 2-3 years DFS rates of LAGC compared to chemotherapy alone, but whether short-term benefit could translate into long-term efficacy is unclear. The triplet regimen was not superior to the doublet regimen in terms of efficacy. The safety after surgery was similar between either ICIs plus chemotherapy and chemotherapy or the triplet and the doublet regimen.
Correspondence
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blinatumomab和嵌合抗原受体T细胞单倍体相合造血干细胞移植治疗儿童费城染色体阴性B细胞急性淋巴细胞白血病的比较Guanhua Hu, Pan Suo, Lu Bai, Xiaohui Zhang, Yifei Cheng, Xiaojun Huang
中华医学杂志英文版2025年 138卷 04期
DOI: 10.1097/CM9.0000000000003396
摘要
致编辑：复发或难治性（R/R）急性淋巴细胞白血病（ALL）患者预后较差，5年总生存期（OS）为25%~50%，缓解诱导治疗具有挑战性。[
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共病特征的聚类分析揭示慢性阻塞性肺疾病住院患者的异质性Haijie Chen, Dian Chen, Jing Zhang, Yahong Chen
中华医学杂志英文版2025年 138卷 04期
DOI: 10.1097/CM9.0000000000003370
摘要
致编辑慢性阻塞性肺疾病（COPD）是一个全球性的健康挑战，因为它的高患病率和相关的死亡率。[
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基于白蛋白—胆红素和体重指数的logistic模型预测免疫检查点抑制剂治疗的非小细胞肺癌肝转移生存结局的潜在效用Lianxi Song, Qinqin Xu, Ting Zhong, Wenhuan Guo, Shaoding Lin, Wenjuan Jiang, Zhan Wang, Li Deng, Zhe Huang, Haoyue Qin 等
中华医学杂志英文版2025年 138卷 04期
DOI: 10.1097/CM9.0000000000003385
摘要
致编辑：肺癌的特点是发病率和死亡率高，在全球范围内造成重大疾病负担。[
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基于深度学习的白光内镜下多类型胃病变诊断系统Qi Luo, Xianglei Yuan, Wei Liu, Ou Chen, Jiong Wu, Bing Hu
中华医学杂志英文版2025年 138卷 04期
DOI: 10.1097/CM9.0000000000003421
摘要
致编辑：胃镜检查被认为是诊断胃部病变的主要方法。[
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免疫细胞在血脂与颅内动脉瘤因果关系中的介导作用Haodong Jiang, Baowen Zhang, Junjun Li, Xiaobing Jiang
中华医学杂志英文版2025年 138卷 04期
DOI: 10.1097/CM9.0000000000003497
摘要
致编辑：目前，大多数关于脂质、免疫细胞和颅内动脉瘤（IAs）之间关系的研究，包括未破裂颅内动脉瘤（uIAs）和动脉瘤性蛛网膜下腔出血（aSAH），都源于观察性研究。[
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抗抑郁药物靶点与各种卒中亚型之间遗传关联的评估：孟德尔随机化方法Luyang Zhang, Yunhui Chu, Man Chen, Yue Tang, Xiaowei Pang, Luoqi Zhou, Sheng Yang, Minghao Dong, Jun Xiao, Ke Shang 等
中华医学杂志英文版2025年 138卷 04期
DOI: 10.1097/CM9.0000000000003429
摘要
致编辑：抑郁症是一种常见的精神疾病，影响着全球超过2.6亿所有年龄段的人。[
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匹配无关供体和半相合相关供体的异基因造血干细胞移植治疗重型地中海贫血Feiyan Wang, Yuhua Qu, Hua Jiang
中华医学杂志英文版2025年 138卷 04期
DOI: 10.1097/CM9.0000000000003465
摘要
致编辑重型地中海贫血（TM）是中国南方普遍存在的公共卫生问题，需要异基因造血干细胞移植（allo-HSCT）作为治愈性治疗。只有一小部分TM患者具有同胞相同供体（SID），因此移植中心越来越多地采用替代供体，包括人类白细胞抗原（HLA）匹配的无关供体（MUD）和单倍体相同供体（HID）。尽管早期并发症如移植物抗宿主病(GVHD)在MUD移植中更常见，但近年来有几个中心表明MUD移植在总生存期(OS)或无事件生存期(EFS)方面与SID移植没有区别。[
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中国2型糖尿病患者代谢手术的五年结局Yuqian Bao, Hui Liang, Pin Zhang, Cunchuan Wang, Tao Jiang, Nengwei Zhang, Jiangfan Zhu, Haoyong Yu, Junfeng Han, Yinfang Tu 等
中华医学杂志英文版2025年 138卷 04期
DOI: 10.1097/CM9.0000000000003454
摘要
致编辑：肥胖和2型糖尿病（T2D）在中国是重大的健康问题。尽管中国人的体重指数（身体质量指数）阈值通常低于西方人群，但中国人的中心性肥胖率通常较高，即使在较低的身体质量指数水平下，也会导致代谢风险增加。中国成人T2D患病率估计为11.2%。传统治疗，包括生活方式干预和药物治疗，通常无法在肥胖和T2D患者中实现持续的体重减轻和长期有效的血糖控制。
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替培非格司亭治疗乳腺癌化疗诱导的中性粒细胞减少症：一项多中心、随机、3期研究Yuankai Shi, Qingyuan Zhang, Junsheng Wang, Zhong Ouyang, Tienan Yi, Jiazhuan Mei, Xinshuai Wang, Zhidong Pei, Tao Sun, Junheng Bai 等
中华医学杂志英文版2025年 138卷 04期
DOI: 10.1097/CM9.0000000000003445
摘要
致编辑：化疗是乳腺癌(BC)患者的主要治疗方法之一，[
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38611例无胎儿结构异常孕妇无创产前筛查检测拷贝数变异的一致性和致病性Yunyun Liu, Jing Wang, Ling Wang, Lin Chen, Dan Xie, Li Wang, Sha Liu, Jianlong Liu, Ting Bai, Xiaosha Jing 等
中华医学杂志英文版2025年 138卷 04期
DOI: 10.1097/CM9.0000000000003449
摘要
致编辑：致病拷贝数变异（CNVs）与先天性异常和神经发育障碍有关。[
Comment
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血液透析患者肠道微生物群及其代谢产物Junxia Du, Xiaolin Zhao, Xiaonan Ding, Qinqin Ren, Haoran Wang, Qiuxia Han, Chenwen Song, Xiaochen Wang, Dong Zhang, Hanyu Zhu
中华医学杂志英文版2025年 138卷 04期
DOI: 10.1097/CM9.0000000000003423
摘要
慢性肾脏病（CKD）是影响人类健康的重要疾病，尤其是在CKD患病率和死亡率都很高的发展中国家。[
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