2024年 · 第137卷第13期

Chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide, led to approximately 3.23 million deaths in 2019 and imposed significant economic and health burdens. However, cardiovascular mortality accounts for approximately one-third of deaths in patients with COPD,^[1]particularly in those with mild or moderate disease severity.^[2]Studies have also identified a substantial increase in the risk of cardiovascular events in patients with COPD.^[3,4]Given the notable risk of cardiopulmonary (pulmonary and cardiovascular) events in COPD, the management of COPD should incorporate strategies aiming at reducing the risk of cardiopulmonary events. Optimized treatment of patients with COPD may reduce their risk of cardiopulmonary events and potentially enhance survival benefit. Fully understanding the risk of cardiovascular events in patients with COPD is crucial for comprehensive management of disease. Thus, this article aims to offer an update on the risk of cardiovascular events in COPD and emphasize the importance of cooperation between pulmonologists and cardiologists.

Hyperpolarized (HP)¹³C magnetic resonance imaging (MRI) is a powerful molecular imaging technique. With dissolution dynamic nuclear polarization (d-DNP), it can achieve dramatic signal increase and allows for dynamic and quantitative investigation of real-time metabolismin vivo.^[1]The typical HP¹³C MRI workflow begins with formulating the¹³C probe, and then placing it in the hyperpolarization equipment to achieve the desired signal amplification level, which typically amounts to an increase in the MRI signal by more than 10,000 folds. The subsequent data acquisition is supported by a specialized¹³C coil and¹³C acquisition sequence, and finally quantitative and visualized metabolic information is obtained through a post-processing algorithm. To date, research of HP¹³C MRI has focused on diabetes, cardiovascular diseases, and cancers,^[2]showing great promises in tumor detection and the evaluation of therapeutic efficacy.

Balanoposthitis (BP), a common male genitalia inflammation, is managed by clinicians from different specialties, including urology, pediatrics, dermatology, and venereology. Due to this diverse array of clinicians involved, there exists a lack of consistent, evidence-based recommendations for BP. The development of the consensus engaged 19 representative hospitals and it adhered to rigorous protocols, encompassing international registration (IPGRP-2021CN003) and the application of evidence grading criteria and recommendation standards [Appendix S1, Supplementary File, http://links.lww.com/CM9/C42]. Over the period from December 2020 to October 2022, consensus on 12 clinical issues was reached through comprehensive evidence searches and two iterations of Delphi surveys [Supplementary File, 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.

To the Editor:The amide proton transfer (APT) magnetic resonance imaging (MRI) is an emerging molecular imaging method for detecting mobile proteins/peptides and the potential of hydrogen (pH) with enhanced detection sensitivity compared to direct measurement without external magnetic resonance contrast agents [Figure 1]. Such changes may be potential markers for tumor aggressiveness, treatment efficacy, and overall prognosis. Consequently, the utilization of APT can assist medical professionals in devising treatment regimens tailored to the individual needs of cancer patients, resulting in improved therapeutic outcomes.

To the Editor: Cancer, as one of the foremost health challenges in the world today, has garnered significant attention from the medical and scientific communities. As an emerging technology, 3D microfluidic chips have shown great potentials in the treatment of various diseases. Therefore, we aimed to conduct a bibliometric analysis of the relevant literature on 3D microfluidic chips in cancer showcasing their current status, hotspots, and development trends.

To the Editor: Diffuse large B-cell lymphoma (DLBCL) exhibits clinical significance and biological diversity. Over the last two decades, rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has substantially improved outcomes for DLBCL patients. However, approximately one-third of DLBCL cases continue to experience disease progression, resulting in long-term survival ranging from 50% to 60%.^[1]Efforts to improve DLBCL patient outcomes by modifying R-CHOP dosing schedules have yielded limited success, and the addition of new drugs has benefited only specific patient subgroups. Nevertheless, intensive immunochemotherapy (IIC) has demonstrated promise and cost-effectiveness in recent years. The regimen of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) has led to improved outcomes, particularly in patients with unfavorable clinical characteristics, and has generally been well-tolerated.^[2]Furthermore, advances in DLBCL biology have identified specific high-risk factors, such as double-/triple-hit (DH/TH) andTP53aberrations. Consequently, we initiated a planned observational study in 2012, employing a risk-adapted paradigm that integrated Age-adjusted International Prognostic Index (aaIPI) and biological high-risk (bio-HR) features to optimize outcomes for young patients with DLBCL.

To the Editor:Male breast cancer is relatively rare, accounting for just 1% of all breast cancer cases.^[1]The management strategies for male breast cancer are mainly based on a limited number of retrospective studies and speculation based on female breast cancer. This study presents a comprehensive account of a decade-long observation of male metastatic breast cancer (mMBC) in our institution. The Affiliated Cancer Hospital of Zhengzhou University database had records of 2853 advanced breast cancer cases that were treated from January 1, 2010 to December 31, 2019. Out of the total number, 18 cases were identified as mMBC. The analysis encompassed data about the treatment administered, the treatment’s effectiveness, and the patient’s survival outcomes. The present investigation entails a retrospective examination of our institution’s 10-year experience with patients diagnosed with mMBC and a comprehensive evaluation of relevant literature.

To the Editor:Hematopoietic cell transplantation (HCT) is a vital modality to cure severe hematological disorders.^[1]Global or regional summarized data of HCT are annually reported by the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG), European Society for Blood and Marrow Transplantation (EBMT) and Center for International Blood and Marrow Transplant Research (CIBMTR). It is shown that the number of transplants is continuously increasing, particularly in China in recent years.^[2]Since the donor accessibility is significantly addressed by the well-established protocol of haplo-identical HCT (haplo-HCT), the requirements of HCTs in China are expected to be sustained for decades.^[3]However, the capacity of Chinese HCT centers is hardly investigated. A comprehensive description of the current status is beneficial for capacity construction adapted to the rapid development of HCT in the future.

To the Editor:Stroke is a major cause of death and long-term serious disability in adults worldwide. Hypertension is the most important modifiable risk factor for primary and secondary prevention of stroke.^[1]Even a modest reduction in clinical blood pressure (BP) of approximately 10/5 mmHg is associated with a significant 30% risk reduction of adverse clinical events. While clinical evidence strongly advocated the effectiveness of managing BP to reduce adverse outcomes after ischemic stroke,^[2]the management and control of BP in ischemic stroke patients after discharge remain poor.

To the Editor:Parkinson’s disease (PD) is one of the most common neurodegenerative movement disorders.^[1]The severity of PD-related motor symptoms is usually semi-quantitatively ( "normal", "slight", "mild", "moderate", and "severe" ) evaluated by expert physicians according to the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS III).^[2]However, the MDS-UPDRS III is semiquantitative and subjective, which might mask mild treatment effects or even provide false-positive results.