Volume 139 · Issue 18 · 2026

Glioma, the most aggressive primary brain malignancy, arises from glial cells within the central nervous system. Despite aggressive treatment, the prognosis remains poor, with all patients expected to experience recurrence. An important component of glioma growth is the interaction with the other cells in the brain environs. This complex ecosystem, termed the tumor microenvironment (TME), includes recruited immune cells and the resident cells in the central nervous system. Glioma cells recruit myeloid cells and reprogram their phenotype to fuel tumor growth. Tumor cells and reprogrammed myeloid cells further suppress adaptive immune responses. Additionally, glioma co-opts normal brain cells—including endothelial cells, neurons, and astrocytes—to create a microenvironment favoring tumor progression. Following this phenotypic shift, normal cells synergize with tumor cells to drive proliferation, invasion, immunosuppression, and angiogenesis. This review integrates recent advances in understanding the multidimensional interactions within the glioma TME, including insights gained from single-cell and spatial transcriptomics approaches that reveal its heterogeneous architecture and functional niches. By elucidating the underlying cellular and molecular mechanisms, we highlight how targeting the TME offers potential therapeutic opportunities to overcome treatment resistance and improve patient outcomes.

The rapid development of high-throughput sequencing technologies and bioinformatics has enabled the identification of diverse microbial communities within tumor tissues, giving rise to the concept of intratumoral microbiota. Comprising bacteria, viruses, fungi, and archaea, the intratumoral microbiota has been shown to play critical roles in tumor initiation, progression, and therapeutic responses. This review systematically summarizes the composition, ecological characteristics, and functional roles of intratumoral microbiota, with particular emphasis on its dual regulatory mechanisms in tumorigenesis, progression, metastasis, and recurrence. We further delineate four principal mechanistic pathways through which intratumoral microbiota influence tumor biology, including receptor-mediated signaling, metabolic reprogramming, effector molecule secretion, and intracellular invasion. Additionally, we evaluate the translational potential of these findings in clinical oncology, offering innovative perspectives for tumor diagnosis, therapeutic intervention, and preventive strategies.

Cerebral ischemia (CI) is an acute central nervous system disorder resulting from the abrupt interruption of blood flow to brain tissue. The restoration of blood flow during treatment is frequently accompanied by cerebral ischemia/reperfusion (CI/R) injury, a secondary injury mechanism that substantially limits the overall efficacy of reperfusion therapy. The phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, a central regulator of cell survival, proliferation, and stress response, has attracted growing interest for its role in CI and CI/R injury. During the early ischemic phase, PI3K-Akt activation in neurons and brain microvascular endothelial cells serves as a crucial endogenous protective mechanism, inhibiting apoptosis and maintaining energy metabolic homeostasis, thereby mitigating initial brain damage. As ischemia progresses, downregulation of this pathway in microglia and infiltrating macrophages can promote excessive release of proinflammatory factors, such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), exacerbating local inflammation and tissue injury. In the reperfusion phase, reactivation of the PI3K-Akt pathway exerts multi-level neuroprotection: It counteracts neuronal apoptosis and oxidative stress, promotes angiogenesis and blood-brain barrier (BBB) repair in endothelial cells, and modulates neuroinflammation in glial cells. Importantly, the PI3K-Akt pathway does not function in isolation but engages in complex crosstalk with multiple signaling cascades, such as Wnt/β-catenin, nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), and mammalian target of rapamycin (mTOR). Moreover, it shapes the immune microenvironment by fine-tuning the functions of immune cells, including regulatory T cells (Tregs). This intricate network dynamically governs the survival of the neurovascular unit by regulating mitochondrial function, oxidative stress, inflammation, and autophagy. This review systematically explores the dynamic changes, cell-specific functions, and interactive mechanisms of the PI3K-Akt pathway during CI and CI/R injury, and discusses its potential for precision treatment strategies and clinical translation.

Background: Maternal morbidity and mortality are one of the key indicators of social development and are among the most challenging public health problems. This study aimed to analyze the trends and burden of maternal disorders in China from 1990 to 2023. Methods: The crude and age-standardized prevalence, mortality, and disability-adjusted life years (DALYs) for maternal disorders from 1990 to 2023 were analyzed using data on maternal disorders in China from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023. The changing trends of prevalence, mortality, and DALYs were evaluated by the average annual percentage change (AAPC) calculated using a log-transformed linear regression model. The ranks of the leading causes for maternal disorders in terms of prevalence, mortality, and DALYs in 1990, 2015, and 2023 were estimated to determine the impact of changes in the fertility strategy on maternal disorder patterns as China implemented the two-child policy in 2015. Results: In 2023, the age-standardized prevalence, mortality, and DALYs of maternal disorders among reproductive women aged 15-49 years in China were 193.04 (95% confidence interval [CI]: 192.56-193.54), 0.30 (95% CI: 0.28-0.32), and 27.78 (95% CI: 27.59-27.97) per 100,000 population, respectively. The prevalence showed a declining trend with fluctuations, and the mortality and DALYs both showed consistent decrease from 1990 to 2023, with AAPCs of -1.41% (95% CI: -1.92% to -0.90%), -10.64% (95% CI: -11.18% to -10.11%), and -9.37% (95% CI: -9.87% to -8.88%), respectively. In terms of the leading cause of death among the 10 available maternal disorders in GBD, maternal hemorrhage ranked first in 1990 (3.53 per 100,000) but decreased to third in 2015 (0.10 per 100,000) and 2023 (0.05 per 100,000). Among the 10 available maternal disorders in GBD 2023, the prevalence of maternal hypertensive disorders changed from first in 1990 to second both in 2015 and 2023. The other direct maternal disorders became the leading causes of prevalence and DALY during 2015 to 2023. Indirect maternal deaths ranked as the leading cause of mortality during 2015 to 2023. Conclusions: There has been a substantial decline in prevalence, mortality, and burden of maternal disorders in China during the past three decades. However, additional efforts are needed for decreasing the burden of maternal disorders, especially for maternal hypertensive disorders.

Background: Cryptogenic organizing pneumonia (COP) is classified as a subtype of idiopathic interstitial pneumonia (IIP), which has a good prognosis. Relapse remains one of the most challenging and intriguing aspects of COP. This study aimed to characterize the clinical features, prognosis, and relapse patterns of COP. Methods: In this prospective cohort study, patients diagnosed with COP between March 1, 2004 and June 30, 2022 at China-Japan Friendship Hospital and Beijing Chao-Yang Hospital were enrolled after a comprehensive multidisciplinary review. Patients were followed up through regular clinical visits every 3-6 months until October 30, 2023. Data collected included demographic characteristics, clinical presentation, laboratory findings, radiologic features, and prognostic outcomes. The primary outcome measure was relapse. Cox regression analyses were performed to explore factors related to the presence of relapse. Results: This study included 268 patients with a final diagnosis of COP based on multidisciplinary discussion. After diagnosis, the one-year survival rate was 99.6%, decreasing to 97.7% at 3 years, 94.5% at 5 years, and 81.7% at 10 years. Relapses occurred in 20.9% (56/268) of patients, with a median time to relapse of 12 months. Of these relapses, 28.6% (16/56) occurred when prednisone was tapered to below 10 mg/day, and 62.5% (35/56) occurred after discontinuation of prednisone therapy; fewer than 10% of relapses occurred at prednisone doses above 15 mg/day. Ground-glass opacities (GGOs) (225/268, 84.0%) and consolidations (212/268, 79.1%), predominantly with bilateral lung distribution, were the most common computed tomography (CT) features at diagnosis. No patient developed residual lung fibrosis on high-resolution CT, regardless of relapse status. Furthermore, no deaths were attributable to COP progression or relapse, and all-cause mortality was unrelated to COP itself. Conclusion: This study indicated that patients with COP had a good prognosis with favorable survival outcomes. However, relapse was relatively common, occurring in more than 20% of patients. Therefore, close follow-up is essential for early detection of relapses, particularly during corticosteroid tapering or after treatment discontinuation.

Background: Sequential bilateral sudden sensorineural hearing loss (Se-BSSHL) may occur after an initial unilateral episode, but the risk factors for contralateral ear involvement remain unclear. This research aims to identify risk factors associated with the occurrence of contralateral ear in patients suffering from sudden sensorineural hearing loss (SSHL). By leveraging machine learning algorithms, the study uses patients’ demographic and clinical data to develop a predictive model. Methods: We conducted an analysis on clinical data from 939 patients admitted to the Ear Department of the Chinese PLA General Hospital from 2008 to 2022, categorizing them into unilateral sudden sensorineural hearing loss (USSHL) and sequential bilateral sudden sensorineural hearing loss (Se-BSSHL) groups. Stratified sampling was executed to maintain a proportional representation of unilateral versus bilateral cases, leading to the creation of seven internal and three external datasets. Variable selection was performed using a decision tree-based recursive feature elimination method. We applied five-fold cross-validation on the internal datasets and conducted model testing on the external datasets. Four machine learning algorithms—random forest, extreme gradient boosting, logistic regression, and support vector machine—were used to build the predictive model and conduct external validation. Model efficacy was primarily appraised using the area under the receiver operating characteristic curve (AUC-ROC), calibration curves, decision curve analysis (DCA), and additional performance metrics including accuracy, precision, recall, and F1-score on the test set. The influence of the variables was illustrated through Shapley value plots. Statistical methods such as the t-test, analysis of variance, and chi-squared test were used. Results: We observed a 12.57% (118/939) incidence rate of contralateral ear complications in USSHL patients with otherwise normal hearing. The predictive model incorporated 19 variables, among them, age, hearing loss degree, and sex are the three most significant features influencing the occurrence in the healthy ear of the USSHL group. An increase in age and a more severe degree of hearing loss are risk factors for the occurrence of the disease, and females have a higher risk of disease occurrence. Other high-risk test indicators for disease occurrence can be summarized and categorized into two types of risk factors: lipoprotein dysfunction (total cholesterol, high-density lipoprotein cholesterol, apolipoprotein A1) and inflammation (eosinophils, lymphocyte count, neutrophil count). The AUC of the model on the external test reached 0.77, with an accuracy of 88%, a precision of 84%, a recall of 88%, and an F1 value of 0.85 using the default classification threshold of 0.5, demonstrating robust predictive capabilities. Conclusion: This investigation elucidates the risk factors for contralateral ear disease in USSHL patients and establishes a robust predictive model for such occurrence, which offers substantial reference value for managing and preventing complications in USSHL patients.

Background: Dexmedetomidine may suppress the surgery-induced inflammatory response, which is considered the underlying mechanism of postoperative complications. This study was designed to investigate whether perioperative dexmedetomidine could decrease the risk of postoperative complications among high-risk patients. Methods: This multicenter randomized controlled trial is a superiority trial. Central randomization was used. Elderly patients (age ≥60 years) with revised cardiac risk index (RCRI) ≥3 and scheduled for major non-cardiac surgery were enrolled. Patients in dexmedetomidine group received intraoperative dexmedetomidine (a loading dose of 0.5 µg/kg followed by 0.3 µg·kg-1·h-1) as adjuvant to general anesthesia and postoperative dexmedetomidine (2 µg/h for 72 h) as supplementation to patient-controlled analgesia with sufentanil. Patients in the control group received an equivalent dose of normal saline as placebo during anesthesia and sufentanil only for postoperative analgesia. The primary outcome was the incidence of major postoperative complications including neurologic, cardiovascular, renal, pulmonary coagulation, infectious, and gastrointestinal systems within postoperative 30 days. Secondary outcomes included pain intensity, sleep quality, postoperative length of in-hospital stay, and medical expenses during hospitalization. Neutrophil-to-lymphocyte ratio (NLR) was used to monitor inflammatory response. Results: This study included 272 patients, with similar median age (70 years vs. 69 years) and median RCRI (both 3) between dexmedetomidine and control groups. The incidence of major postoperative complications in the dexmedetomidine group was significantly lower than that in the control group (38.2% [52/136] vs. 52.9% [72/136], relative risk [RR] = 0.722, 95% confidence interval (CI) 0.554-0.942, P = 0.015). Postoperative in-hospital stay was shorter in the dexmedetomidine group than that in the control group (mean difference [MD] = -1 day, 95% CI: -2 to 0 days, P = 0.013). Other secondary outcomes were comparable between the two groups. The highest NLR within postoperative first 3 days in the dexmedetomidine group was lower than that in the control group (MD = -2.1, 95% CI: -4.1 to -0.3, P = 0.037). The proportion of all drug-related adverse events were comparable between the two groups. Conclusion: Dexmedetomidine, infused from the beginning of anesthesia to postoperative 72 h, decreased the risk of postoperative complications in high-risk elderly patients undergoing non-cardiac surgery.

Background: The alveolar sac, which serves as the primary site for gas exchange, comprises alveolar type 1 (AT1) and alveolar type 2 (AT2) cells. These epithelial cells initiate immune responses upon encountering external stimuli. However, the influenza virus infection patterns and antiviral responses exhibited by different types of alveolar epithelial cells remain understudied. This study aimed to investigate the differential susceptibility and antiviral responses of AT1 and AT2 cells during influenza virus infection. Methods: Immunofluorescence staining was performed to determine the spatial distribution of influenza A virus (IAV; H1N1). Primary murine epithelial in vitro culture models, including an AT2 sphere culture and an AT1 differentiation model, were established to elucidate the mechanisms underlying cellular susceptibility to IAV. Bulk RNA sequencing and quantitative polymerase chain reaction were performed to characterize the cellular responses to viral infection. Results: Mouse AT2 cells exhibited greater susceptibility to H1N1 than did AT1 cells. The in vitro primary epithelial cell culture models mimicked the in vivo cellular phenotype. They further reproduced the in vitro finding of relatively high viral replication in AT2 cells. Mechanistically, no significant difference was observed between AT1 and AT2 cells in the expression of α-2,3 or α-2,6 sialic acid (viral receptors). However, RNA sequencing revealed that gene ontology terms such as the response to viral infection, negative regulation of the viral life cycle, and regulation of type I interferon (IFN) production were enriched in AT1 cells. This finding was validated using quantitative polymerase chain reaction. From 12 to 48 h after infection, the expression levels of types I and III IFNs, chemokines, and IFN-stimulated genes remained lower in AT2 cells than in AT1 cells. Conclusion: Our findings indicate the localization of IAV in alveoli and highlight the vulnerability of AT2 cells, which exhibit delayed immune responses, resulting in increased viral replication.

Background: Myocardial ischemia/reperfusion (I/R) injury contributes significantly to cardiac dysfunction following myocardial infarction, mainly due to excessive oxidative stress and mitochondrial injury. Despite advances in reperfusion therapies, secondary injuries remain a challenge, necessitating deeper insight into the molecular mechanisms underlying I/R injury. In the present study, we aim to investigate the roles of circular ribonucleic acid (circRNA) RERE (circRERE) in myocardial I/R injury. Methods: Hypoxia/reperfusion (H/R) cells and an I/R mouse model were used. Cell apoptosis was assessed using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. The cell reactive oxygen species (ROS) and secreted lactate dehydrogenase (LDH) levels were measured. Quantitative reverse transcription polymerase chain reaction, western blot, immunofluorescence staining, and immunohistochemistry were used to assess mRNA and protein expression. MitoTracker and electron microscopy were used to examine mitochondrial morphology. The interactions between circRERE, Pumilio 2 (PUM2), ubiquitin-like with plant homeodomain and ring finger domain 1 (UHRF1), and dynamin-related protein 1 (Drp1) were validated by RNA immunoprecipitation, RNA pull-down, and/or chromatin immunoprecipitation assays. I/R-induced pathological changes in cardiac tissues were evaluated by hematoxylin and eosin (H&E) and 2,3,5-triphenyltetrazolium chloride (TTC) staining. Statistical analyses were performed using one-way analysis of variance and Student’s t-test, with P <0.05 considered a statistically significant difference. Results: CircRERE expression was significantly elevated during I/R injury (about a 3.1-fold increase, P <0.001). CircRERE knockdown reduced ROS levels by 39.5% (P <0.01), improved mitochondrial membrane potential (P <0.01), and decreased apoptotic rates (P <0.001). Mechanistically, circRERE promoted UHRF1 mRNA decay by interacting with PUM2, leading to reduced Drp1 promoter methylation, increased Drp1 expression, and subsequent mitochondrial fission and dysfunction. In vivo, circRERE knockdown significantly reduced infarct size by 24.27% (P <0.001), improved cardiac tissue morphology, and restored mitochondrial homeostasis. Conclusions: CircRERE exacerbated myocardial I/R injury by promoting UHRF1 mRNA degradation and mitochondrial dysfunction. Targeting the circRERE/UHRF1/Drp1 axis may represent a novel therapeutic strategy against myocardial I/R injury.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma and is characterized by high aggressiveness and rapid growth. Erianin, a natural compound derived from the Chinese herb Dendrobium, has been shown to exhibit anticancer effects in certain types of cancer; however, its role and mechanism of action in DLBCL have not yet been reported. Therefore, this study aimed to investigate the potential of erianin as a therapeutic drug for DLBCL. Methods: The cell counting kit-8 assay, lactate dehydrogenase release assay, flow cytometry, and 5-ethynyl-2’-deoxyuridine (EdU) assay were used to assess the inhibitory effect of erianin on DLBCL cells. RNA sequencing, western blotting, immunofluorescence, and flow cytometry were used to investigate the molecular mechanisms of the effect of erianin on DLBCL cells. Erianin was labeled with biotin or rhodamine, and its target proteins were identified using pull-down assays combined with proteomics, cellular thermal shift assays, and molecular docking. CompuSyn software was used to analyze the combination index of erianin and doxorubicin (DOX) for evaluating their synergistic anti-DLBCL effects. Results from the in vitro experiments were subsequently validated using in vivo experiments. Results: Erianin inhibited the proliferation of DLBCL cells, promoted G2/M phase arrest, and induced cell death. Mechanistically, erianin induced inhibition of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in DLBCL cells, which led to increased reactive oxygen species (ROS) formation, inflammasome activation, and caspase-1/Gasdermin D (GSDMD)-dependent pyroptosis. Erianin was found to bind to the S100A9 protein, suggesting a potential mechanism through which erianin activates downstream signaling pathways. Moreover, erianin synergistically enhanced the effects of DOX on DLBCL. Conclusions: Our study demonstrates that erianin binds to S100A9 and suppresses the PI3K/AKT signaling pathway in DLBCL cells, thereby elevating ROS levels, activating the inflammasome, and triggering caspase-1/GSDMD-dependent pyroptosis. Moreover, erianin increased the sensitivity of DLBCL cells to DOX both in vitro and in vivo. The effects of erianin on DLBCL imply its potential in the development of promising new drugs against this disease.