Guang Fu Hospital

Early non-invasive detection is crucial for improving the prognosis of gastric cancer (GC). Dysbiosis in the oral and gastric microbiome is closely associated with GC development, yet its complex nature poses challenges for traditional analytical methods. This study aims to integrate oral and gastric microbial characteristics and employ machine learning algorithms to construct a high-precision GC diagnostic model. We collected saliva, gastric fluid, and gastric mucosa samples from 106 GC patients and 111 healthy controls. Microbiome data were obtained via 16S rRNA sequencing, with analyses conducted on species abundance, diversity and community composition. Algorithms including random forest and support vector machines were employed to identify the most discriminative bacterial genera. Multiple diagnostic models were trained based on these findings and evaluated through ten-fold cross-validation and independent external datasets. Results revealed significant differences in microbial composition between GC patients and healthy individuals. Diagnostic models constructed based on key bacterial genera demonstrated excellent performance: AUC values in the training set reached 0.96, 0.87, and 0.96 for oral, gastric fluid and gastric mucosa classifiers respectively, maintaining robust performance in external validation. Functional prediction revealed dysregulation in the microbiota of GC patients, while correlation analysis further indicated symbiotic relationships among cancer-associated bacterial genera. This study successfully established a GC diagnostic model based on oral and gastric microbial signatures. Its outstanding performance validates the substantial potential of the ‘oral-stomach’ microbial axis in GC auxiliary diagnosis, offering a novel cost-effective strategy for early screening.

Globally, ~33% of patients with non-small cell lung cancer receiving anti-PD-1 antibody therapy may experience significant immune-related adverse events (irAEs). Among these, myocarditis is a rare but lethal irAE. The aim of the present study was to preliminarily explore the role of CD8+ T cells in anti-PD-1 antibody-induced myocarditis in C57BL/6 mice with Lewis lung carcinoma (LLC). Orthotopic transplantation models were established using wild-type or CD8 knockout (CD8-/-) C57BL/6 mice. Wild-type and CD8-/- C57BL/6 mice were separately divided into three groups: Control, LLC and LLC + anti-PD-1. LLC cell suspensions (1x105 cells) with 50 µl Matrigel Matrix were orthotopically injected into the left lung lobe of wild-type or CD8-/- C57BL/6 mice. Following needle removal, the incision was sutured. At 10 days post-surgery, mice in the anti-PD-1 groups received an intraperitoneal injection of anti-PD-1 antibody (200 µg). After 3 weeks, all mice were humanely euthanized via intraperitoneal injection of sodium pentobarbital (200 mg/kg). The histopathological examination of tumor, lung and heart tissue was performed by Masson's trichrome and hematoxylin and eosin staining. Reverse transcription-quantitative PCR was carried out to determine the mRNA expression of monocyte chemotactic protein-1, interleukin-6, interferon-γ and tumor necrosis factor-α in myocardial tissue. Flow cytometry was used to analyze the ratio of CD8+ and CD4+ T cells and macrophages in myocardial tissues. Anti-PD-1 therapy effectively inhibited tumor growth and mitigated lung tissue damage. In wild-type C57BL/6 mouse, treatment with anti-PD-1 was associated with myocardial injury, inflammatory responses and a notable increase in the ratios of CD8+ and CD4+ T cells and macrophages. However, in CD8-/- C57BL/6 mice, no significant differences were observed in myocardial histopathology, inflammatory cytokine levels and the ratios of CD4+ T cells and macrophages between the control, LLC and LLC + anti-PD-1 groups. Anti-PD-1 therapy did not cause significant damage to myocardial tissue. The presence of CD8+ T cells facilitated the development of anti-PD-1-induced myocarditis by activating CD4+ T cells, macrophages and inflammatory responses.

Cognitive impairment is a globally prevalent public health disorder following rapid population aging. Although depression can trigger cognitive decline, few studies have focused on how anxiety and its comorbidity with depression can affect cognitive decline development. Cognitive impairment was recognized based on the Mini-Mental State Examination (MMSE), while dementia was diagnosed with self-/proxy-reported evaluations. The 10-item Center for Epidemiologic Studies Depression Scale (CESD-10) and the 7-item Generalized Anxiety Disorder Scale (GAD-7) were employed for evaluating depressive and anxiety symptoms. The impact of comorbidity on cognitive outcomes was assessed with logistic and linear regression models. The study involved 13,792 adults (age ≥ 65 years; mean age: 84.2 ± 11.5 years) from the Chinese Longitudinal Healthy Longevity Survey. Among them, comorbid depressive and anxiety symptoms occurred in 7.7% of older adults. Prevalence was 9.2% for cognitive impairment and 1.4% for dementia. Compared to individuals with only depressive or anxiety symptoms, those with both symptoms exhibited a higher probability of developing cognitive impairment (adjusted OR: 2.07, 95% CI: 1.44, 2.97) and dementia (adjusted OR: 2.55, 95% CI: 1.39, 4.69), with adults aged ≥ 80 years exhibiting a stronger association. Additionally, women, particularly the oldest-old, were at a higher risk of comorbidity-associated dementia. We also observed an identical correlation for MMSE scores, where psychiatric comorbidity correlated significantly with lower scores. The interaction between individual characteristics and depression and anxiety showed no significant effects on cognitive impairment or dementia. Comorbidity of depression and anxiety shows an association with dementia and cognitive impairment in Chinese older adults, particularly in oldest-old individuals. Early screening and interventions targeting psychiatric comorbidity may delay dementia progression in this population. Not applicable.

Rationale:Bronchial artery aneurysm (BAA) is a rare condition, but it can be life-threatening if the aneurysm ruptures. While endovascular therapy is the primary treatment, the selection of embolic material is limited by the tortuous and short aneurysm neck.Patient concerns:We report a huge, suspected ruptured BAA was unexpectedly detected in a 69-year-old man during a routine medical examination.Diagnoses:Enhanced chest computed tomography angiography and selective bronchial arteriography both revealed that the BAA was located at the proximal portion of the left bronchial artery It was characterized by a large aneurysm sac and a short, irregularly dilated aneurysm neck.Interventions:We successfully occluded the huge BAA using a single amplatzer vascular plug.Outcomes:The 6-month computed tomography angiography follow-up scan showed no signs of aneurysm recurrence.Lessons:Transcatheter embolization utilizing a single amplatzer vascular plug has proven to be an effective and cost-efficient treatment for BAAs that are characterized by a large aneurysm sac and a short, tortuous, irregularly dilated aneurysm neck.

Rationale: Macrophage phagocytosis is essential for pathogen clearance during sepsis. We previously demonstrated that the glycolytic enzyme 6-phosphofructokinase, muscle type (PFKM), modulates macrophage functions and its deficiency alleviates sepsis in mice. However, the function of PFKM in regulating macrophage phagocytosis remains unclear.Methods: CD14+ monocytes were sorted by flow cytometry from healthy volunteers and septic patients, and the subcellular localization of PFKM was assessed by immunofluorescence. Nuclear translocation mechanisms and PFKM-p53 interaction were identified by Co-immunoprecipitation coupled with mass spectrometry (Co-IP/MS) and validated by Co-IP. Transcriptomic sequencing was used to identify the downstream target of the PFKM-p53 complex. Inflammatory cytokine levels were detected by ELISA and real-time RT-PCR, and the phagocytosis of macrophages was assessed by flow cytometry. Dual-luciferase reporter assays and ChIP were employed to investigate whether PFKM acts as a co-regulator of p53 in mediating Pdcd1 transcription. Nanobodies targeting PFKM-p53 were screened and subsequently synthesized according to the sequences. The effect of nuclear PFKM and the therapeutic effect of nanobodies were evaluated on the well-established sepsis mouse models induced by Escherichia coli or cecal ligation and puncture.Results: PFKM translocated to the macrophage nucleus during sepsis. Nuclear accumulation of PFKM impaired phagocytosis through a non-glycolytic “moonlighting” function and exacerbated sepsis. Mechanistically, PFKM interacts with p53, which facilitates its nuclear translocation. Subsequently, PFKM promotes p53 acetylation at K120, enhancing p53 binding to the Pdcd1 promoter and driving its transcription, thereby suppressing macrophage phagocytosis. Blocking the PFKM-p53 interaction with a nanobody, Nb07, restored phagocytosis of macrophages and alleviated sepsis in mice.Conclusion: Our data reveal the PFKM-p53-PD-1 axis that suppresses macrophage phagocytosis in sepsis and highlight the therapeutic potential of targeting this pathway with nanobody-based strategies.

BackgroundGestational diabetes mellitus (GDM), a prevalent complication during pregnancy, is closely associated with an elevated risk of adverse maternal and neonatal outcomes. Mobile health (mHealth) technologies have emerged as convenient tools for GDM management; however, their clinical efficacy in improving maternal and neonatal outcomes among GDM-affected pregnant individuals remains to be comprehensively evaluated.ObjectiveThe study aims to evaluate the effectiveness of mHealth interventions in improving maternal and neonatal outcomes among pregnant individuals with GDM.MethodsThis study systematically searched the PubMed, Web of Science, Scopus, Cochrane Library, and EMBASE databases from their inception to July 23, 2025. Two researchers independently screened the studies, extracted data, and assessed quality. All data analyses were performed using STATA 17.0 software.ResultsCompared with routine care, mHealth interventions significantly reduced the risk of cesarean section (OR 0.76, 95% CI 0.63–0.91) and emergency cesarean (OR 0.55, 95% CI 0.39–0.77) among women with GDM. Additionally, a significant reduction in the risk of composite neonatal complications was observed (OR 0.63, 95% CI 0.44–0.89). Furthermore, mHealth interventions significantly improved 2-hour postprandial blood glucose levels (SMD −0.36, 95% CI −0.53 to −0.19). A trend toward reduced gestational weight gain was also noted in the mHealth intervention group (SMD −0.37, 95% CI −0.83 to 0.08).ConclusionmHealth interventions can reduce the risk of cesarean section rate and emergency cesarean section, as well as the risk of composite neonatal complications. mHealth interventions may also improve two-hour postprandial blood glucose control in pregnant women with GDM and can effectively supplement conventional clinical care for GDM.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420251149505.

BackgroundColorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, with the tumor microenvironment (TME) playing a pivotal role in its progression and therapeutic resistance. The ubiquitin–proteasome system (UPS), a central regulator of intracellular protein degradation, is increasingly recognized for its involvement in cancer pathogenesis, though its specific role in modulating the CRC TME remains to be fully elucidated. This review aims to systematically summarize current evidence on how the UPS influences the immunosuppressive network within the CRC TME and to evaluate its potential as a therapeutic target.MethodsWe conducted a comprehensive literature search in PubMed, Web of Science, and Scopus databases for original research articles and reviews published between January 2010 and August 2025, using keywords including “ubiquitin–proteasome system,” “colorectal cancer,” “tumor microenvironment,”“immune escape,”and “targeted therapy.” Studies were selected based on their relevance to UPS-mediated regulatory mechanisms in CRC TME remodeling, immune cell function, and treatment response.ResultsOur analysis of preclinical and clinical evidence reveals that the UPS critically regulates immune evasion in CRC through multiple mechanisms: (1) USP14 stabilizes indoleamine 2,3-dioxygenase 1 (IDO1), enhancing tryptophan catabolism and kynurenine accumulation, which suppresses T-cell activity; (2) E3 ligases including SPOP, C-Cbl, KLHL22, and FBW7 modulate PD-L1/PD-1 protein stability via ubiquitination, thereby influencing immune checkpoint signaling; and (3) ZFP91 facilitates K63-linked ubiquitination of PP2Ac, impairing mTORC1-mediated glycolysis in T cells and reinforcing regulatory T-cell immunosuppression. Additionally, the UPS intersects with key oncogenic pathways such as Wnt/β-catenin, NF-κB, and p53, further shaping the immunosuppressive landscape of CRC.ConclusionsTargeting the UPS represents a promising strategy to reverse immunosuppression and overcome therapy resistance in CRC. The primary advantage of this approach lies in its ability to simultaneously disrupt multiple immunosuppressive pathways within the TME, offering a potential solution to the limitations of single-target therapies. Current approaches include proteasome inhibitors, E3 ligase modulators, and deubiquitinating enzyme inhibitors, with combination regimens—such as UPS inhibitors with immune checkpoint blockade—showing synergistic efficacy in preclinical models. Future efforts should focus on enhancing the selectivity of UPS-targeting agents, minimizing off-target effects, and integrating genomic profiling to guide personalized treatment. While current evidence strongly supports the therapeutic potential of UPS targeting, its establishment as a reliable alternative therapy in the clinic will depend on overcoming these challenges and validating efficacy in human trials. This review underscores the UPS as a central regulator of the CRC TME and provides a rational basis for novel therapeutic development.

Postoperative cognitive dysfunction (POCD) is a complication that occurs mostly after cardiac, skeletal, and other surgical procedures, commonly present in the elderly. Salidroside (SAL) is an active ingredient extracted from the herb rhodiola rosea that has been verified to protect nerve function and inhibit neuroinflammatory responses. SAL nanoliposomes (SAL-Nanos) were first prepared, and the apparent morphology was observed by electron microscopy and transmission electron microscopy, followed by evaluation using zeta potential and encapsulation efficiency. POCD mouse models were established using exploratory laparotomy and then subjected to Morris water maze (MWM). Mouse hippocampal tissues were subjected to hematoxylin-eosin (H&E) staining, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and enzyme-linked immunosorbent assay (ELISA). Subsequently, mouse hippocampal tissues from each group were taken for transcriptome sequencing, namely differential analysis, trend analysis, and enrichment analysis. Neuroinflammation models were constructed using LPS-induced microglia to observe the effects of SAL and SAL-Nanos on inflammatory factor levels and Fos expression. Changes in inflammatory factor levels and Fos expression were observed by knocking down Fos expression in microglia. Administering Fos inhibitor (T5224), pathological phenotypic changes in POCD mice and Fos expression levels in hippocampal tissues were observed by H&E staining, TUNEL staining, and ELISA. SAL-Nanos were successfully prepared and could well ameliorate hippocampal inflammation, reduce apoptosis, and protect memory in POCD mice. Transcriptome analysis identified the Toll-like receptor (TLR) signaling pathway and its related molecule Fos to be associated with the improvement of POCD mice by SAL-Nanos. Subsequent studies found that SAL-Nanos can significantly suppress the level of LPS-induced microglia inflammation, improve cell viability, and reduce Fos expression. In addition, Fos knockdown could effectively suppress LPS-induced inflammatory factor levels. It was further demonstrated by in vivo assays that inhibition of Fos expression can significantly alleviate the inflammation level in hippocampal tissues of POCD mice, inhibit apoptosis, and improve memory. SAL-Nanos exhibit a more significant therapeutic effect on POCD mice compared to SAL, and its relief effect on POCD mice may inhibit neuroinflammation by down-regulating Fos expression.

To investigate the clinicopathological features of cranial-nasal-orbital communicating lesions and identify key diagnostic indicators for differentiating benign and malignant neoplasms. The retrospective cohort study analyzed 74 histologically confirmed cases stratified by anatomical involvement at the Wuhan Union Hospital between January 2010 and December 2020: Group A (orbital-nasal group, n=29), Group B (orbital-cranial group, n=27), and Group C (cranial-nasal-orbital group, n=18). Clinicopathological profiles including symptom presentation, histopathology, and invasion patterns were systematically evaluated. The cohort comprised 49 (66.2%) benign and 25 (33.8%) malignant lesions. Compared with benign lesions, malignant lesions had a shorter onset time (12mo vs 2.5mo, P=0.004) and resulted in poorer vision (0.6 vs 1.53, P=0.025). Headache was reported in 28.6% of patients with benign lesions, but none in those with malignant lesions (P=0.002). Conjunctival congestion and edema were observed in 32.7% of patients with benign lesions and 60% of patients with malignant lesions (P=0.028). The ethmoid sinus was the most frequently invaded site (35 cases). Malignant lesions showed greater invasion in the nasal cavity (28.0% vs 0, P=0.000) and anterior cranial fossa (40.0% vs 8.2%, P=0.003) than benign lesions. The orbital-cranial group was more likely to invade through osseous foramina compared with the orbital-nasal group (P=0.002). Neurogenic tumors predominated benign cases (34.7%), whereas blood derived (28%) and glandular tumors (28%) were most prevalent in malignant subgroups. The proportion of malignant tumors in multi-disciplinary combined surgery was higher than that of benign lesions (61.5% vs 38.5%). Malignant cranial-nasal-orbital communicating lesions exhibit distinct clinicopathological signatures characterized by rapid progression, aggressive anterior fossa and nasal region, and severe visual morbidity.