Volume 137 · Issue 13 · 2024

慢性阻塞性肺病（COPD）是全球第三大死亡原因，2019年导致约323万人死亡，并带来了巨大的经济和健康负担。然而，心血管死亡率约占COPD患者死亡的三分之一，^[1]特别是在轻度或中度疾病严重程度的患者中。^[2]研究还发现，COPD患者发生心血管事件的风险显著增加。^[3,4]鉴于COPD中心肺（肺和心血管）事件的显著风险，COPD的管理应纳入旨在降低心肺事件风险的策略。COPD患者的优化治疗可能会降低其心肺事件的风险，并可能提高生存获益。充分了解COPD患者发生心血管事件的风险对于疾病的综合管理至关重要。因此，本文旨在提供COPD心血管事件风险的最新信息，并强调肺病学家和心脏病学家之间合作的重要性。

超极化（HP）¹³C磁共振成像（MRI）是一种强大的分子成像技术。通过溶解动态核极化（d-DNP），它可以实现显著的信号增加，并允许实时代谢的动态和定量研究体内.^[1]典型的惠普¹³C MRI工作流程从制定¹³C探针，然后将其放置在超极化设备中以实现期望的信号放大水平，这通常相当于MRI信号增加超过10,000倍。随后的数据采集由专门的¹³C线圈和¹³C采集序列，最后通过后处理算法获得定量、可视化的代谢信息。迄今为止，惠普的研究¹³C MRI已专注于糖尿病、心血管疾病和癌症，^[2]在肿瘤检测和疗效评估方面显示出巨大的前景。

龟头包皮炎（BP）是一种常见的男性生殖器炎症，由来自不同专业的临床医生管理，包括泌尿外科、儿科、皮肤科和性病科。由于涉及的临床医生多种多样，缺乏一致的、基于证据的BP建议。共识的制定涉及19家代表性医院，并遵守严格的协议，包括国际注册（IPGRP-2021CN003）以及证据分级标准和推荐标准的应用【附录S1，补充文件，http：//links.lww.com/CM9/C42】。在2020年12月至2022年10月期间，通过全面的证据搜索和两次迭代德尔菲调查，就12个临床问题达成了共识【补充文件，http：//links.lww.com/CM9/C42】。

Sepsis poses a health challenge globally owing to markedly high rates of morbidity and mortality. Despite employing bundle therapy over two decades, approaches including transient organ supportive therapy and clinical trials focusing on signaling pathways have failed in effectively reversing multiple organ failure in patients with sepsis. Prompt and appropriate perioperative management for surgical patients with concurrent sepsis is urgent. Consequently, innovative therapies focusing on remedying organ injuries are necessitated. Cell therapy has emerged as a promising therapeutic avenue for repairing local damage to vital organs and restoring homeostasis during perioperative treatment for sepsis. Given the pivotal role of immune cell responses in the pathogenesis of sepsis, stem cell-based interventions that primarily modulate immune responses by interacting with multiple immune cells have progressed into clinical trials. The strides made in single-cell sequencing and gene-editing technologies have advanced the understanding of disease-specific immune responses in sepsis. Chimeric antigen receptor (CAR)-immune cell therapy offers an intriguing option for the treatment of sepsis. This review provides a concise overview of immune cell therapy, its current status, and the strides made in the context of sepsis research, discussing potential strategies for the management of patients with sepsis during perioperative stages.

This systematic review aimed to examine whether dual-task (DT) training was superior to single-task (ST) training in improving DT walking, balance and cognitive functions for individuals with Parkinson’s disease (PD).

Literature search was performed in the following electronic databases: PubMed, the Cochrane Library, Web of Science, and Metstr covering inception to May 10, 2023. And in order to facilitate comparison across trials, we calculated the effect size (Hedges’ g) of gait, balance, cognitive, and other parameters under both ST and DT conditions, using the mean change score and standard deviation (SD) of change score of the experimental and control groups. Randomized controlled trials that examined the effects of DT motor and cognitive training in individuals with Parkinson’s disease were included for this systematic review.

A total of 214 participants recruited from six articles (actually five trials) were involved in this review. In terms of walking ability, only double support time and stride time variability showed significant between-group difference (Hedges’ g = 0.34, 0.18, respectively). Compared to ST training group, DT training group had a more improvement effect in laboratory balance measurement (Hedges’ g = 0.18, 1.25), but no significant improvement in clinical balance measurement. No significant between-group differences were observed, thus its training effect on cognitive function was inconclusive.

The DT training failed to achieve promising results better than ST training in improving DT walking and balance functions for individuals with PD. Any firm conclusion cannot be drawn at present, due to the limited number of eligible publications. Larger sample size and high-quality studies are needed to investigate the effectiveness of DT training in individuals with PD.

Studies that comprehensively address the characteristics of centenarian deaths are rare. The present study aimed to depict the characteristics of centenarian deaths in China and their changing trends.

Data on centenarian deaths between 2013 and 2020 were obtained from the national mortality surveillance system of China, including date, place of death (PoD), and underlying cause of death (CoD). Descriptive analyses were performed to understand the epidemiological characteristics, and a joinpoint regression model was adopted to examine the changing trends in the proportions of different PoDs, CoDs among centenarians, and centenarian deaths accounting for all deaths and deaths among people aged 65 years and older.

There were 46,938 registered centenarian deaths between 2013 and 2020 that included 34,311 females (73.10%) and 12,627 males (26.90%). January (12.05%), February (9.99%), and December (9.74%) were the top three months with the highest number of deaths. The proportions of deaths that occurred in homes, hospitals, and nursing homes were 81.71%, 13.63%, and 2.68%, respectively. The proportion of deaths in nursing homes increased by 9.60% (95% confidence intervals [CIs], 6.4-12.9%) from 2014 to 2020. Heart disease (35.72%) was the leading cause of death, followed by respiratory diseases (17.63%), cerebrovascular disease (15.60%), and old age (11.22%). The proportion of respiratory diseases decreased by 4.8% (95% CI, -8.8 to -0.7%), and the proportion of deaths from old age decreased by 2.3 % (95% CI, -4.4 to -0.1%) per year. Shanghai had the highest proportions of deaths in hospitals (39.38%) and nursing homes (14.68%). Sichuan had the highest proportion of deaths attributed to respiratory diseases (32.30%), while Jiangsu (26.58%) and Zhejiang (23.61%) had the highest proportions of deaths from old age.

Unlike other countries, centenarian deaths in China are characterized by a higher proportion of home and heart disease deaths, and this death pattern differs across provinces.

Life’s Simple 7, the former construct of cardiovascular health (CVH) has been used to evaluate adverse non-communicable chronic diseases (NCDs). However, some flaws have been recognized in recent years and Life’s Essential 8 has been established. In this study, we aimed to analyze the association between CVH defined by Life’s Essential 8 and risk of 44 common NCDs and further estimate the population attributable fractions (PAFs) of low-moderate CVH scores in the 44 NCDs.

In the UK Biobank, 170,726 participants free of 44 common NCDs at baseline were included. The Life’s Essential 8 composite measure consists of four health behaviours (diet, physical activity, nicotine exposure, and sleep) and four health factors (body mass index, non-high density lipoprotein cholesterol, blood glucose, and blood pressure), and the maximum CVH score was 100 points. CVH score was categorized into low, moderate, and high groups. Participants were followed up for 44 NCDs diagnosis across 10 human system disorders according to the International Classification of Diseases 10th edition (ICD-10) code using linkage to national health records until 2022. Cox proportional hazard models were used in this study. The hazard ratios (HRs) and PAFs of 44 NCDs associated with CVH score were examined.

During the median follow-up of 10.85 years, 58, 889 incident NCD cases were documented. Significant linear dose-response associations were found between higher CVH score and lower risk of 25 (56.8%) of 44 NCDs. Low-moderate CVH (<80 points) score accounted for the largest proportion of incident cases in diabetes (PAF: 80.3%), followed by gout (59.6%), sleep disorder (55.6%), chronic liver disease (45.9%), chronic kidney disease (40.9%), ischemic heart disease (40.8%), chronic obstructive pulmonary disease (40.0%), endometrium cancer (35.8%), lung cancer (34.0%), and heart failure (34.0%) as the top 10. Among the eight modifiable factors, overweight/obesity explained the largest number of cases of incident NCDs in endocrine, nutritional, and metabolic diseases (35.4%), digestive system disorders (21.4%), mental and behavioral disorders (12.6%), and cancer (10.3%); however, the PAF of ideal sleep duration ranked first in nervous system (27.5%) and neuropsychiatric disorders (9.9%).

Improving CVH score based on Life’s Essential 8 may lower risk of 25 common NCDs. Among CVH metrics, avoiding overweight/obesity may be especially important to prevent new cases of metabolic diseases, NCDs in digestive system, mental and behavioral disorders, and cancer.

Alterations in the placental expression of glucose transporters (GLUTs), the crucial maternal-fetal nutrient transporters, have been found in women with hyperglycemia in pregnancy (HIP). However, there is still uncertainty about the underlying effect of the high-glucose environment on placental GLUTs expression in HIP.

We quantitatively evaluated the activity of mammalian target of rapamycin (mTOR) and expression of GLUTs (GLUT1, GLUT3, and GLUT4) in the placenta of women with normal pregnancies (CTRL, n = 12) and pregnant women complicated with poorly controlled type 2 diabetes mellitus (T2DM, n = 12) by immunohistochemistry. In addition, BeWo cells were treated with different glucose concentrations to verify the regulation of hyperglycemia. Then, changes in the expression of GLUTs following the activation or suppression of the mTOR pathway were also assessed using MHY1485/rapamycin (RAPA) treatment or small interfering RNA (siRNA)-mediated silencing approaches. Moreover, we further explored the alteration and potential upstream regulatory role of methyltransferase-like 3 (METTL3) when exposed to hyperglycemia.

mTOR, phosphorylated mTOR (p-mTOR), and GLUT1 protein levels were upregulated in the placenta of women with T2DM compared with those CTRL. In BeWo cells, mTOR activity increased with increasing glucose concentration, and the expression of GLUT1, GLUT3, and GLUT4 as well as GLUT1 cell membrane translocation were upregulated by hyperglycemia to varying degrees. Both the drug-mediated and genetic depletion of mTOR signaling in BeWo cells suppressed GLUTs expression, whereas MHY1485-induced mTOR activation upregulated GLUTs expression. Additionally, high glucose levels upregulated METTL3 expression and nuclear translocation, and decreasing METTL3 levels suppressed GLUTs expression and mTOR activity and vice versa. Furthermore, in METTL3 knockdown BeWo cells, the inhibitory effect on GLUTs expression was eliminated by activating the mTOR signaling pathway using MHY1485.

High-glucose environment-induced upregulation of METTL3 in trophoblasts regulates the expression of GLUTs through mTOR signaling, contributing to disordered nutrient transport in women with HIP.

Although the treatment of peripheral T-cell lymphoma (PTCL) has undergone advancements during the past several years, the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory—particularly for relapsed or refractory (R/R) patients. This phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone, cyclophosphamide, and thalidomide (CPCT) for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of reasons.

We conducted a multicenter phase II clinical trial in which we combined chidamide (30 mg twice weekly) with prednisone (20 mg daily after breakfast), cyclophosphamide (50 mg daily after lunch), and thalidomide (100 mg daily at bedtime) (the CPCT regimen) for a total of fewer than 12 cycles as an induction-combined treatment period, and then applied chidamide as single-drug maintenance. Forty-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine centers. Our primary objective was to assess the overall response rate (ORR) after the treatment with CPCT.

Of the 45 enrolled patients, the optimal ORR and complete response (CR)/CR unconfirmed (CRu) were 71.1% (32/45) and 28.9% (13/45), respectively, and after a median follow-up period of 56 months, the median progression-free survival (PFS) and overall survival (OS) were 8.5 months and 17.2 months, respectively. The five-year PFS and OS rates were 21.2% (95% confidence interval [CI], 7.9-34.5%) and 43.8% (95% CI, 28.3-59.3%), respectively. The most common adverse event was neutropenia (20/45, 44.4%), but we observed no treatment-related death.

The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various reasons.

ClinicalTrials.gov, NCT02879526.

Psychological stress has been reported to be a potential risk factor for hypertension among females, but it remains unclear whether spousal chronic stress levels alter the risk of hypertension among women. We examined the associations between stress within the family and hypertension among married women.

Reproductive-aged women who were planning for pregnancy and their husbands were recruited from the National Free Pre-pregnancy Checkup Projects (NFPCP) across 31 provinces in China in 2016 and 2017. Perceived stress of wives or husbands was measured with a 5-point Likert-type scale, and assessed from three domains: work/life-related stress, economic stress, and overall stress. Multivariable-adjusted logistic regression models were used to assess the associations between stress status and the prevalence of hypertension.

Of 10,027,644 couples, 261,098 (2.60%) women had hypertension. The results showed that higher stress levels among themselves or their husbands were associated with a higher prevalence of hypertension in women (P_{for trend} <0.001). Compared with non-stressed participants, female participants with the highest stress themselves were at a greater risk of hypertension, with adjusted odds ratio (OR) of 1.31 (95% confidence interval [CI]: 1.25-1.37); and compared with participants whose husbands had no stress, those whose husbands had the highest stress level were at a higher risk of hypertension with adjusted OR of 1.24 (95% CI: 1.20-1.29). Moreover, compared with non-stressed status for both couples, only-wife-stressed, only-husband-stressed, and both-stressed couples were found to be significantly associated with increased risks of wives’ hypertension, with adjusted ORs of 1.28 (95% CI: 1.25-1.31), 1.19 (95% CI: 1.17-1.21), and 1.28 (95% CI: 1.26-1.31), respectively.

Moderate to severe stress in both spouses might be associated with female hypertension prevalence, which highlights the importance of paying attention to the psychological stresses of couples within the family.

Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in many critically ill patients. Although inflammasome activation plays an important role in the induction of acute lung injury (ALI) and ARDS, the regulatory mechanism of this process is still unclear. When cells are stimulated by inflammation, the integrity and physiological function of mitochondria play a crucial part in pyroptosis. However, the underlying mechanisms and function of mitochondrial proteins in the process of pyroptosis are largely not yet known. Here, we identified the 18-kDa translocator protein (TSPO), a mitochondrial outer membrane protein, as an important mediator regulating nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in macrophages during ALI.

TSPO gene knockout (KO) and lipopolysaccharide (LPS)-induced ALI/ARDS mouse models were employed to investigate the biological role of TSPO in the pathogenesis of ARDS. Murine macrophages were used to further characterize the effect of TSPO on the NLRP3 inflammasome pathway. Activation of NLRP3 inflammasome was preformed through LPS + adenosine triphosphate (ATP) co-stimulation, followed by detection of mitochondrial membrane potential, reactive oxygen species (ROS) production, and cell death to evaluate the potential biological function of TSPO. Comparisons between two groups were performed with a two-sided unpaired t-test.

TSPO-KO mice exhibited more severe pulmonary inflammation in response to LPS-induced ALI. TSPO deficiency resulted in enhanced activation of the NLRP3 inflammasome pathway, promoting more proinflammatory cytokine production of macrophages in LPS-injured lung tissue, including interleukin (IL)-1β, IL-18, and macrophage inflammatory protein (MIP)-2. Mitochondria in TSPO-KO macrophages tended to depolarize in response to cellular stress. The increased production of mitochondrial damage-associated molecular pattern led to enhanced mitochondrial membrane depolarization and pyroptosis in TSPO-KO cells.

TSPO may be the key regulator of cellular pyroptosis, and it plays a vital protective role in ARDS occurrence and development.

Although significant advances have been made in the treatment of multiple myeloma (MM), leading to unprecedented response and survival rates among patients, the majority eventually relapse, and a cure remains elusive. This situation is closely related to an incomplete understanding of the immune microenvironment, especially monocytes/macrophages in patients with treatment-naïve MM. The aim of this study was to provide insight into the immune microenvironment, especially monocytes/macrophages, in patients with treatment-naïve MM.

This study used the single-cell RNA sequencing (scRNA-seq) data of both patients with MM and heathy donors to identify immune cells, including natural killer (NK) cells, T cells, dendritic cells (DCs), and monocytes/macrophages. Transcriptomic data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-naïve MM patients.

A significant difference was observed between the bone marrow (BM) immune cells of the healthy controls and treatment-naïve MM patients through scRNA-seq. It is noteworthy that, through an scRNA-seq data analysis, this study found that interferon (IFN)-induced NK/T cells, terminally differentiated effector memory (TEMRA) cells, T-helper cells characterized by expression of IFN-stimulated genes (ISG⁺Th cells), IFN-responding exhausted T cells, mannose receptor C-type 1 (MRC1)⁺ DCs, IFN-responding DCs, MHCII⁺ DCs, and immunosuppressive monocytes/macrophages were enriched in patients with treatment-naïve MM. Significantly, transcriptomic data of monocytes/macrophages demonstrated that "don’t eat me" -related genes and IFN-induced genes increase in treatment-naïve MM patients. Furthermore, scRNA-seq, transcriptomic data, and flow cytometry also showed an increased proportion of CD16⁺ monocytes/macrophages and expression level of CD16. Cell-cell communication analysis indicated that monocytes/macrophages, whose related important signaling pathways include migration inhibitory factor (MIF) and interleukin 16 (IL-16) signaling pathway, are key players in treatment-naïve MM patients.

Our findings provide a comprehensive and in-depth molecular characterization of BM immune cell census in MM patients, especially for monocytes/macrophages. Targeting macrophages may be a novel treatment strategy for patients with MM.

致编辑：酰胺质子转移（APT）磁共振成像（MRI）是一种新兴的分子成像方法，用于检测移动蛋白/肽和氢（pH）的电位，与没有外部磁共振造影剂的直接测量相比，具有增强的检测灵敏度[图1].这些变化可能是肿瘤侵袭性、治疗功效和总体预后的潜在标志物。因此，APT的利用可以帮助医疗专业人员设计适合癌症患者个体需求的治疗方案，从而改善治疗结果。

致编辑：癌症作为当今世界最重要的健康挑战之一，已经引起了医学界和科学界的极大关注。3D微流控芯片作为一种新兴技术，在多种疾病的治疗中显示出巨大的潜力。因此，我们旨在对3D微流控芯片在癌症中的相关文献进行文献计量分析，展示其现状、热点和发展趋势。

致编辑：弥漫性大B细胞淋巴瘤（DLBCL）表现出临床意义和生物学多样性。在过去的二十年中，利妥昔单抗联合环磷酰胺、多柔比星、长春新碱和泼尼松（R-CHOP）显著改善了DLBCL患者的预后。然而，大约三分之一的DLBCL病例继续经历疾病进展，导致50%至60%的长期生存率。^[1]通过修改R-CHOP给药方案来改善DLBCL患者结局的努力取得了有限的成功，新药的加入仅使特定的患者亚组受益。然而，强化免疫化疗（IIC）近年来已显示出前景和成本效益。剂量调整的依托泊苷、泼尼松、长春新碱、环磷酰胺、多柔比星和利妥昔单抗（DA-EPOCH-R）方案改善了结局，特别是在具有不利临床特征的患者中，并且通常耐受性良好。^[2]此外，DLBCL生物学的进展已经确定了特定的高危因素，如双重/三重打击（DH/TH）和TP53畸变。因此，我们在2012年启动了一项有计划的观察性研究，采用了一种风险适应范式，整合了年龄调整的国际预后指数（aaIPI）和生物学高风险（bio-HR）特征，以优化年轻DLBCL患者的结局。

致编辑：男性乳腺癌相对罕见，仅占所有乳腺癌病例的1%。^[1]男性乳腺癌的管理策略主要基于数量有限的回顾性研究和基于女性乳腺癌的推测。本研究全面介绍了我们机构对男性转移性乳腺癌（mMBC）长达十年的观察。郑州大学附属肿瘤医院数据库有2010年1月1日至2019年12月31日收治的2853例晚期乳腺癌病例记录。在总数中，18例病例被确定为mMBC。该分析包括关于所给予的治疗、治疗的有效性和患者的生存结果的数据。本研究需要对我们机构10年来诊断为mMBC的患者的经验进行回顾性检查，并对相关文献进行全面评估。

致编辑：造血细胞移植（HCT）是治疗严重血液疾病的重要手段。^[1]HCT的全球或区域汇总数据由中国血液和骨髓移植注册小组（CBMTRG）、欧洲血液和骨髓移植学会（EBMT）和国际血液和骨髓移植研究中心（CIBMTR）每年报告。研究表明，移植的数量正在持续增加，尤其是近年来在中国。^[2]由于单倍体相同HCT（haplo-HCT）的成熟方案显著解决了供体可及性，因此中国对HCT的需求预计将持续数十年。^[3]然而，中国HCT中心的能力几乎没有被调查。全面描述现状，有利于适应未来HCT快速发展的能力建设。

致编辑：中风是全球成年人死亡和长期严重残疾的主要原因。高血压是卒中一级和二级预防最重要的可改变危险因素。^[1]即使临床血压（BP）适度降低约10/5 mmHg，不良临床事件的风险也显著降低30%。虽然临床证据强烈支持控制血压以减少缺血性卒中后不良结局的有效性，^[2]缺血性卒中患者出院后血压的管理和控制仍然较差。

致编辑：帕金森病（PD）是最常见的神经退行性运动障碍之一。^[1]PD相关运动症状的严重程度通常由专家医师根据运动障碍协会发起的统一帕金森病评定量表第三部分(MDS-UPDRS III)的修订版半定量(“正常”、“轻微”、“轻度”、“中度”和“重度”)评估。^[2]然而，MDS-UPDRS III是半定量和主观的，这可能掩盖轻微的治疗效果，甚至提供假阳性结果。