Volume 138  ·   Issue 05  ·  2025

Human mpox (formerly known as monkeypox) historically received little attention until its emergence beyond African countries in 2022. As of September 30, 2024, a total of 109,699 laboratory-confirmed mpox cases have been reported to the World Health Organization (WHO).^[1]It has been more than one year since the WHO announced on May 11, 2023 that the mpox epidemic did not constitute a public health emergency of international concern (PHEIC). However, on August 14, 2024, the WHO declared that the upsurge of mpox in the Democratic Republic of the Congo (DRC) and an increasing number of countries in Africa constituted a PHEIC once again. Although the WHO has proposed the "Strategic Framework for Enhancing Prevention and Control of Mpox 2024-2027", controlling and eliminating the mpox from 2024 to 2025, as planned, appears to be a significant challenge.^[2]Additionally, various vulnerable populations (such as children, pregnant women, and immunosuppressed individuals), adverse outcomes (such as myocarditis), and hospital management strategies for mpox complicate prevention and control efforts.^[3,4,5]To effectively prevent and control mpox in the public, it is critical to understand the epidemic trends, the threat posed by Clade Ib, and the necessary control measures.

The remarkable efficacy of chimeric antigen receptor (CAR) T cell therapy in hematological malignancies has provided a solid basis for the therapeutic concept, wherein specific pathogenic cell populations can be eradicated by means of targeted recognition. During the past few years, CAR-based cell therapies have been extensively investigated in preclinical and clinical research across various non-tumor diseases, with particular emphasis in the treatment of autoimmune diseases (ADs), yielding significant advancements. The recent deployment of CD19-directed CAR T cells has induced long-lasting, drug-free remission in patients with systemic lupus erythematosus (SLE) and other systemic ADs, alongside a more profound immune reconstruction of B cell repertoire compared with conventional immunosuppressive agents and B cell-targeting biologics. Despite the initial success achieved by CAR T cell therapy, it is critical to acknowledge the divergences in its application between cancer and ADs. Through examining recent clinical studies and ongoing research, we highlight the transformative potential of this therapeutic approach in the treatment of SLE, while also addressing the challenges and future directions necessary to enhance the long-term efficacy and safety of CAR-based cell therapies in clinical practice.

Ferroptosis, an iron-dependent programmed cell death process driven by reactive oxygen species-mediated lipid peroxidation, is regulated by several metabolic processes, including iron metabolism, lipid metabolism, and redox system. Macrophages are a group of innate immune cells that are widely distributed throughout the body, and play pivotal roles in maintaining metabolic balance by its phagocytic and efferocytotic effects. There is a profound association between the biological functions of macrophage and ferroptosis. Therefore, this review aims to elucidate three key aspects of the unique relationship between macrophages and ferroptosis, including macrophage metabolism and their regulation of cellular ferroptosis; ferroptotic stress that modulates functions of macrophage and promotion of inflammation; and the effects of macrophage ferroptosis and its role in diseases. Finally, we also summarize the possible mechanisms of macrophages in regulating the ferroptosis process at the global and local levels, as well as the role of ferroptosis in the macrophage-mediated inflammatory process, to provide new therapeutic insights for a variety of diseases.

The combination of immune checkpoint inhibitors and chemotherapy (ICI + Chemo) shows promise in treatment of recurrent or metastatic nasopharyngeal carcinoma (RM-NPC), but some patients received limited benefit and the prognostic factors of the treatments remain unclear. Furthermore, ICIs efficacy in subsequent treatments needs further evaluation.

A systematic search on PubMed, Embase, the Cochrane Library, and major conference proceedings was conducted to identify relevant studies for meta-analysis. The study was designed to compare ICI + Chemo with chemotherapy in first-line treatment and identify efficacy predictors, and to evaluate ICIs alone in subsequent-line treatment for RM-NPC, with a focus on progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (AEs).

Fifteen trials involving 1928 patients were included. Three trials compared ICI + Chemo with chemotherapy as a first-line treatment, while 12 trials evaluated ICIs alone in subsequent-line treatment of RM-NPC patients. First-line ICI + Chemo showed superior PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.43-0.63; P <0.001) and ORR (risk ratio [RR] = 1.14, 95% CI, 1.05-1.24; P <0.001) compared to chemotherapy, without increased AEs (RR = 1.01, 95% CI, 0.99-1.03; P = 0.481). Neither programmed death-ligand 1 (PD-L1) nor other factors predicted the efficacy of ICI + Chemo vs. chemotherapy. Subsequent-line ICIs alone had a median PFS of 4.12 months (95% CI, 2.93-5.31 months), an ORR of 24% (95% CI, 20-28%), with grade 1-5/grade 3-5 AEs at 79%/14%. However, ICIs alone were associated with significantly shorter PFS (HR = 1.31, 95% CI, 1.01-1.68; P = 0.040) than chemotherapy alone.

ICI + Chemo confers superior survival benefits compared to chemotherapy in first-line RM-NPC treatment, independent of PD-L1 expression or other factors. However, ICIs alone demonstrate a manageable safety profile but do not surpass chemotherapy in efficacy for subsequent-line treatment.

Heart transplantation encounters significant hurdles, prominently among them post-transplant immune rejection.^[1]Present anti-rejection medications, encompassing calcineurin inhibitors (such as tacrolimus and cyclosporine), antimetabolites (such as mycophenolate mofetil), and corticosteroids,^[2]efficiently dampen immune responses but come with inherent limitations. Prolonged usage of these medications elevates the risk of infections, metabolic complications, and potential organ damage. Despite their efficacy, these medications fall short of ensuring absolute prevention of rejection, thereby exposing recipients to potential acute or chronic rejection episodes. Furthermore, their adverse effects contribute to cardiovascular issues, renal dysfunction, and an elevated vulnerability to malignancies.^[3]Ongoing innovations in immunosuppression strive to surmount these challenges by exploring novel drugs with diminished side effects or alternative approaches. The ultimate goal is to strike a delicate balance between preventing rejection and minimizing the risks inherent in prolonged immunosuppressive therapy for individuals undergoing heart transplantation.

Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke.

This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days.

There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively (median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups (P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03).

ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis.

Clinicaltrials.gov, No. NCT04475328.

Approximately 40% of individuals with diabetes worldwide are at risk of developing diabetic kidney disease (DKD), which is not only the leading cause of kidney failure, but also significantly increases the risk of cardiovascular disease, causing significant societal health and financial burdens. This study aimed to describe the burden of DKD and explore its cross-country epidemiological status, predict development trends, and assess its risk factors and sociodemographic transitions.

Based on the Global Burden of Diseases (GBD) Study 2021, data on DKD due to type 1 diabetes (DKD-T1DM) and type 2 diabetes (DKD-T2DM) were analyzed by sex, age, year, and location. Numbers and age-standardized rates were used to compare the disease burden between DKD-T1DM and DKD-T2DM among locations. Decomposition analysis was used to assess the potential drivers. Locally weighted scatter plot smoothing and Frontier analysis were used to estimate sociodemographic transitions of DKD disability-adjusted life years (DALYs).

The DALYs due to DKD increased markedly from 1990 to 2021, with a 74.0% (from 2,227,518 to 3,875,628) and 173.6% (from 4,122,919 to 11,278,935) increase for DKD-T1DM and DKD-T2DM, respectively. In 2030, the estimated DALYs for DKD-T1DM surpassed 4.4 million, with that of DKD-T2DM exceeding 14.6 million. Notably, middle-sociodemographic index (SDI) quintile was responsible for the most significant DALYs. Decomposition analysis revealed that population growth and aging were major drivers for the increased DKD DALYs in most regions. Interestingly, the most pronounced effect of positive DALYs change from 1990 to 2021 was presented in high-SDI quintile, while in low-SDI quintile, DALYs for DKD-T1DM and DKD-T2DM presented a decreasing trend over the past years. Frontiers analysis revealed that there was a negative association between SDI quintiles and age-standardized DALY rates (ASDRs) in DKD-T1DM and DKD-T2DM. Countries with middle-SDI shouldered disproportionately high DKD burden. Kidney dysfunction (nearly 100.0% for DKD-T1DM and DKD-T2DM), high fasting plasma glucose (70.8% for DKD-T1DM and 87.4% for DKD-T2DM), and non-optimal temperatures (low and high, 5.0% for DKD-T1DM and 5.1% for DKD-T2DM) were common risk factors for age-standardized DALYs in T1DM-DKD and T2DM-DKD. There were other specific risk factors for DKD-T2DM such as high body mass index (38.2%), high systolic blood pressure (10.2%), dietary risks (17.8%), low physical activity (6.2%), lead exposure (1.2%), and other environmental risks.

DKD markedly increased and varied significantly across regions, contributing to a substantial disease burden, especially in middle-SDI countries. The rise in DKD is primarily driven by population growth, aging, and key risk factors such as high fasting plasma glucose and kidney dysfunction, with projections suggesting continued escalation of the burden by 2030.

Hepatitis B poses a heavy burden for children in China, however, the national studies on the distributional characteristics and health care costs of children with severe hepatitis B is still lacking. This study aimed to analyze the disease characteristics, health economic effects, and medical cost for children with severe hepatitis B in China.

Based on patient information in the Hospital Quality Monitoring System, cases with severe hepatitis B were divided into four groups according to age, and the etiology and symptoms of each group were quantified. The cost of hospitalization was calculated for cases with different disease processes, and severity of disease. The spatial aggregation of cases and the relationship with health economic factors were analyzed by Moran’s I analysis.

The total number of children discharged with hepatitis B from January 2016 to April 2022 was 1603, with an average age of 10.5 years. Liver failure cases accounted for 43.48% (697/1603) of total cases and cirrhosis cases accounted for 11.23% (180/1603). According to the grouping of disease progression, there were 1292 cases without associated complications, and the median hospitalization cost was $818.12. According to the spatial analysis, the aggregation of cases was statistically significant at the prefectural and provincial levels in 2019, 2020, and 2021 (all P <0.05). The number of severe cases was negatively correlated with gross domestic product (Moran’s I <0) and percentage of urban population (Moran’s I <0), and positively correlated with the number of pediatric beds per million population (Moran’s I >0).

The number of severe hepatitis B cases is low in areas with high gross domestic product levels and high urban population ratios, and health care costs have been declining over the years.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder impacting populations worldwide, although its clinical characteristics and patient demographics remain uncharacterized in China. The aim of this study was to investigate the demographics, comorbidities, aggravating factors, and treatments in AD patients across different age groups in China.

This cross-sectional study included Chinese AD patients from 205 hospitals spanning 30 provinces. Patients completed dermatologist-led surveys of general medical history, comorbidities, AD-related aggravating factors, and medications. Two-level mixed-ordered logistic regression was used to evaluate aggravating factors.

Overall, 16,838 respondents were included in the final analysis (aged 30.9 ± 24.1 years). The proportion of severe AD was the highest in patients with AD onset at ≥60 years (26.73%). Allergic rhinitis and hypertension were the most common atopic and metabolism-related non-atopic comorbidities, respectively. AD severity was significantly associated with chronic urticaria, food allergies, and diabetes. Aggravating factors including foods, seasonal changes, and psychological factors were also linked to AD severity. The cross-sectional survey implied that severe AD may be related to the undertreatment of effective systemic or topical interventions.

To enhance the management of AD, it is crucial to consider both aggravating factors and the increased utilization of systemic immunotherapy.

ClinicalTrials.gov, NCT05316805

Several randomized controlled studies have suggested that the prophylactic use of proton pump inhibitors (PPIs) in intensive care unit (ICU) patients could not reduce the incidence of gastrointestinal bleeding (GIB) and may increase adverse events such as intestinal infection and pneumonia. Gut microbiota may play a critical role in the process. PPIs have been widely prescribed for GIB prophylaxis in patients with acute coronary syndrome (ACS). This study aimed to determine the short-term effects of PPI and histamine-2 receptor antagonist (H2RA) treatment on gut microbiota of ACS patients.

The study was designed as a single-blind, multicenter, three-parallel-arm, randomized controlled trial conducted at three centers in Beijing, China. We enrolled ACS patients at low-to-medium risk of GIB and randomized (2:2:1) them to either PPI (n = 40), H2RA (n = 31), or control group (n = 21). The primary outcomes were the alterations in gut microbiota after 7 days of acid suppressant therapy. Stool samples were collected at baseline and 7 days and analyzed by 16S ribosomal RNA (rRNA) gene sequencing.

There were no significant changes in the diversity of gut microbiota after the short-term use of acid suppressants, but the abundance of Fusobacterium significantly increased and that of Bifidobacterium significantly decreased, especially in PPI users. In addition, the abundance of some pathogenic bacteria, including Enterococcus and Desulfovibrio, was significantly elevated in the PPI users. The fecal microbiota of the PPI users included more arachidonic acid metabolism than that of control group.

PPIs may increase the risk of infection by adversely altering gut microbiota and elevating arachidonic acid metabolism, which may produce multiple proinflammatory mediators. For ACS patients at low-to-medium risk of GIB, sufficient caution should be paid when acid-suppressant drugs are prescribed, especially PPIs.

www.chictr.org.cn (ChiCTR2000029552).

To the Editor: Regrettably, the oncological discourse has historically sidelined fertility considerations. Patient-practitioner dialogs rarely traverse the domain of fertility conservation, a situation worsened by a general lack of specialized knowledge among healthcare providers. Research endeavors in the field of radiation and oncofertility are nascent, with a lack of detailed explanation on the radiation doses for different tissues and insufficient elaboration on reproductive physio-endocrinology, leaving vast territories uncharted.

To the Editor: Mechanotransduction is crucial for cellular and tissue adaptation to mechanical stimuli.Piezo1channels, key mechanosensitive ion channels, confer sensitivity to these cues. Bone remodels in response to mechanical stimuli, maintaining homeostasis. Accumulated scientific evidence underscores the mechanosensitivity of both skeletal lineage cells and osteoclasts, marked by their robust expression ofPiezo1channels. Furthermore, insights garnered from bone-related studies have illuminated the indispensable function ofPiezo1in orchestrating bone development, repair processes, and other mechanobiology-driven activities.

To the Editor:Hepatocellular carcinoma (HCC) is a prominent contributor to cancer-related mortality on a global scale. While therapeutic approaches, such as surgical resection, liver transplantation, and radiofrequency ablation, have demonstrated effectiveness for specific patient populations, the 5-year overall survival (OS) rate in HCC is discouragingly low, estimated at only 18%. This unfavorable outcome can primarily be attributed to the high recurrence and metastasis rates.^[1]Therefore, there is an urgent need for novel therapeutic strategies or targets to surmount the challenges in treating HCC.

To the Editor: Bullous pemphigoid (BP) is a rare autoimmune skin disorder characterized by significant mortality, with BP prevalence ranging from 1.46 to 47.99 cases per 100,000 people.^[1]The pathogenic mechanism of BP is attributed to pathogenic autoantibodies targeting BP180 and BP230 antigens, resulting in the formation of subepidermal blisters.^[1]Reports indicate that some BP patients also have circulating anti-desmoglein (Dsg) autoantibodies, which are pathogenic antibodies in pemphigus.^[2]However, it remains uninvestigated whether the concomitant anti-Dsg antibodies in BP are pathogenic and thereby represent a coincidental occurrence or signify the coexistence of the two diseases. This knowledge gap introduces uncertainty in patient care management. Therefore, a comprehensive analysis was performed to explore the clinicohistopathological characteristics, human leukocyte antigen (HLA) genetic risk factors, and pathogenicity of anti-Dsg antibodies in BP patients with anti-Dsg antibodies compared to those without.

To the Editor: Autoimmune bullous diseases (AIBDs) are a diverse group of autoimmune disorders affecting the skin and mucous membranes, characterized by vesicles, blisters, and erosions due to autoantibodies targeting structural proteins. AIBDs are mainly categorized into pemphigus,^[1]with antibodies against epidermal cell surface proteins, and pemphigoid diseases,^[2]targeting proteins in the epidermal basement membrane.^[3]Pemphigus vulgaris (PV) is the most common intraepidermal AIBD and typically affects individuals aged 40-60 years, while bullous pemphigoid (BP) is the leading subepidermal AIBD, with incidence increasing among older populations. Given the variety of available topical and systemic treatments, it is vital to evaluate their effectiveness and safety. However, there is a lack of knowledge regarding the comparative effectiveness of these therapies. Our objective is to synthesize existing evidence on AIBD management through direct comparisons and generate treatment rankings using network meta-analysis (NMA) to inform clinical decision-making and optimize therapeutic strategies.

To the Editor:Thrombotic microangiopathy (TMA) is an uncommon hematological involvement in systemic lupus erythematosus (SLE) patients with an estimated incidence of 0.5-1.0%, including but not limited to thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), and other secondary conditions. SLE-TMA has a rapid onset and poor prognosis, manifesting as microvascular thrombosis, thrombocytopenia, and microangiopathic hemolytic anemia.^[1]Based on the Chinese SLE Treatment and Research Group (CSTAR) registry, we aimed to summarize clinical characteristics and explore prognostic risk factors in SLE-TMA patients through a retrospective multicenter study.

To the Editor: Common symptoms of osteoporosis include low bone mass and deteriorating bone microarchitecture, leading to bone fragility and fractures. Indeed, bone is a complex tissue composed of collagen fibers, vasculature, and numerous specialized cells. Both cellular metabolism and cellular behavior in bone are regulated by the extracellular matrix (ECM). As the main ECM in the skeletal system, collagen hydrolysates have great potential in alleviating osteoporosis by promoting osteogenesis and angiogenesis. However, the composition and structure of collagen hydrolysate are complex. The peptides in collagen hydrolysates have different sequences and spatial structures, resulting in diverse biological activities.^[1]Furthermore, recent studies have focused primarily on alterations in bone metabolism and the validation of specific gene pathways. Gene regulatory mechanism analysis is still scarce.^[2]This work investigated the key peptide sequences in the prepared collagen hydrolysate (CH) responsible for osteogenic and angiogenic activities and their molecular mechanisms. Additionally, the protective or restorative effects of CH in osteoporotic mice and the regulation of the CH on osteoporosis-related genes were systematically studied.

To the Editor: Co-reactivation of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) is common after haploidentical stem cell transplantation (haplo-SCT) and can lead to potentially life-threatening complications.^[1,2]Adoptive immunotherapy with virus-specific T lymphocytes (VSTs) is a critical treatment option that has shown promising results in controlling CMV and EBV infections in several clinical studies, providing protection for 70-90% of patients.^[3]Multi-virus-specific T cell lines offer an advanced method for simultaneously addressing multiple challenging viral infections. However, data regarding its long-term efficacy are limited. Additionally, clinical trials with multi-virus-specific T cells have predominantly focused on single virus reactivation, leaving gaps in our understanding of the effectiveness of VSTs during multi-virus co-reactivation. Antigenic competition may affect the expansion of virus-specific T cellsin vitroduring the generation of multi-virus-specific cell lines. Whetherin vivocompetition among infused cells compromises the efficacy of adoptively transferred VSTs remains unclear.

To the Editor: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an essential treatment for various malignant hematological diseases, non-malignant hematological diseases, immunodeficiency diseases, and metabolic diseases in children.^[1]During the period of post allo-HSCT immunodeficiency before complete immune reconstitution, transplant recipients having a compromised immune system are more susceptible to infectious diseases than the general population. Therefore, revaccination plays a crucial role in protecting pediatric allo-HSCT recipients from vaccine-preventable diseases. Inactivated vaccines are generally safer and can be administered starting from 6-12 months after transplantation. Live-attenuated vaccines should be administered at least 24 months after transplantation and at least one year after stopping immunosuppressive drugs due to the risk of severe vaccine-induced infection when administered with immunosuppressive agents.^[2,3]

To the Editor: More than half of the patients undergoing invasive coronary angiography for angina or signs of myocardial ischemia present with non-obstructive coronary arteries (NOCA, <50% diameter reduction or fractional flow reserve >0.80).^[1]Coronary microvascular dysfunction (CMD) is a significant pathophysiological factor in these patients and is linked to adverse outcomes.^[2]Although coronary reactivity testing (CRT) remains the gold standard for diagnosing CMD, it is both invasive and costly. Stress cardiac magnetic resonance (CMR) is a non-invasive and promising alternative, providing essential perfusion parameters such as myocardial perfusion reserve index (MPRI) and myocardial perfusion reserve (MPR) to diagnose CMD. Thus, based on current literature, there is robust evidence supporting the effectiveness of stress CMR in diagnosing CMD in patients with NOCA, as defined by CRT.