Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

Objective: To explore the efficacy of a novel injectable hydrogel (GelMA/P11/IL4@LIP) loaded with P11 bacteriophages and interleukin-4 (IL-4) liposomes (LIP) in preventing relapse after maxillary expansion in mice, providing experimental evidence for its clinical application. Methods: This study was approved by the experimental animal ethics committee of our hospital. First, 15 7-week-old C57BL/6 mice were used to establish a maxillary expansion model and divided into 5 groups (3 mice in each group): a control group, post expansion day 3 group (PED3 group), post expansion day 7 group (PED7 group), retention for 14 days group (RET group), and relapse for 7 days group (REL group). The mice in each group were sacrificed at their designated time points (day 0, 3, 7, 21, 28), and their maxilla and anterior cranial regions were collected. Bone parameters and the inter-crestal distance (ICD) of maxillary incisor mesial alveolar ridge were measured using micro-computed tomography (micro-CT). Histological staining was performed to evaluate bone formation and resorption, while immunohistochemistry (IHC) was performed for macrophage markers (CD86 and CD206), mesenchymal stem cell markers (glioma-associated oncogene homolog 1 [Gli1]), and osteogenic markers (Runt-related transcription factor 2 [Runx2] and Osterix [OSX]). Next, GelMA/P11/IL4@LIP was synthesized and administered to mouse models of maxillary expansion. A total of 24 7-week-old C57BL/6 mice were divided into 4 groups (6 mice in each group): a blank control group, GelMA group, GelMA/P11 group, and GelMA/P11/IL4@LIP group. All mice underwent palatal expansion. On PED7, the expanders of all 24 mice were cemented with resin to initiate the 14-day retention period. On day 1 of the retention phase, the mice in each group received injections of saline, GelMA, GelMA/P11, or GelMA/P11/IL4@LIP at the midpalatal suture. After the 14-day retention period, three mice in each group were randomly selected and sacrificed, while the other three had their expanders removed and underwent a 7-day relapse before being sacrificed on day 28 (REL). Micro-CT, histological staining, and IHC were performed to evaluate the preventive effect of GelMA/P11/IL4@LIP on post-expansion relapse. Results: The mice maxillary expansion model exhibited a decreased ICD at REL compared to RET in micro-CT analysis (P = 0.008). IHC analysis demonstrated prolonged M1 macrophage infiltration, scarce Gli1+ mesenchymal stem cells, and insufficient expression of osteogenic markers (RUNX2 and OSX) (P < 0.001). Compared to the blank control and GelMA groups, GelMA/P11/IL4@LIP hydrogel injection in the midpalatal suture led to increased ICD at REL, promoted the timely M2 polarization of macrophages, recruited Gli1+ mesenchymal stem cells, and upregulated the expression of RUNX2 and OSX (P < 0.05). Conclusion The mechanism of relapse after maxillary expansion involves the persistent infiltration of M1 macrophages, as well as the inadequate recruitment and insufficient osteogenic differentiation of MSCs in the midpalatal suture. The GelMA/P11/IL4@LIP composite enhanced orofacial mesenchymal stem cell recruitment and promoted the M2 polarization of macrophages, thereby enhancing osteogenesis in the midpalatal suture and preventing post-expansion relapse.

Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTAC^KEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC^KEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.

Objective:To explore the diagnostic value of routine magnetic resonance imaging (MRI) findings for early detection of dural arteriovenous fistulas (DAVF).Methods:A retrospective collection of 53 patients with DAVF confirmed by digital subtraction angiography (DSA) at the Affiliated Hospital of Qingdao University from September 2018 to June 2023 was conducted. All patients underwent routine non-enhanced and enhanced MRI scans before treatment, with 30 patients also receiving magnetic resonance angiography (MRA) examination. Medical records were reviewed, and basic patient information, clinical symptoms, and imaging markers [pial venous engorgement (PVE), cerebral hemorrhage, subarachnoid hemorrhage, vasogenic edema, venous infarction, medullary veins engorgement (MVE), parenchymal enhancement, encephalopathy mimics] were recorded. The Cognard grading was carried out in accordance with the manifestations shown by DSA.Results:Seventy-seven percent (41/53) of patients exhibited PVE on the brain surface, with 95% (39/41) of these cases showing localized PVE on one hemisphere or even within a single brain lobe. Approximately 64% (34/53) of these PVEs were detectable on conventional T 2-weighted imaging. Among the 30 patients who underwent MRA, only 50% (15/30) showed evidence of PVE on both T 2WI and MRA, while an additional 23% (7/30) had PVE only on MRA. About 38% (20/53) of patients presented with isolated vasogenic edema, with 70% (14/20) of these cases demonstrating PVE on T 2WI. Twenty-six percent (14/53) of patients had intracranial hemorrhage, and 11 of these patients demonstrated positive signs of PVE. Parenchymal enhancement was primarily observed in subarachnoid structures in 11% (6/53) of patients, with 5/6 showing PVE on the brain surface or spinal cord surface. Venous infarction (4%, 2/53) and MVE (4%, 2/53) were more commonly seen in high Cognard grade DAVF, whereas encephalopathy mimics (4%, 2/53) were frequently encountered in low Cognard grade DAVF. Conclusions:PVE on the brain surface is a direct sign for the diagnosis of DAVF on routine MRI, yet it is often subtle. Familiarity with common indirect signs is of great importance for the early diagnosis of DAVF.

Objective:To study the results of detection of pulmonary nodules among military flying personnel and analyze the contributors to pulmonary nodules so as to provide data for early prevention and interventions.Methods:The physical examination data of 1 465 military flying personnel was retrospectively analyzed who had received the annual health checkup and undergone chest CT examinations at Lintong Rehabilitation and Recuperation Center. They were grouped by age (<40 years and ≥40 years), flying hour (<1 000 h and ≥1 000 h) and type of personnel [pilots and air support (technical) personnel]. The detection rates of pulmonary nodules among flying personnel were compared across groups, and a multivariate Logistic regression analysis was conducted to analyze the contributing factors to pulmonary nodules.Results:Among the 1 465 military flying personnel, 212 cases (14.47%) with pulmonary nodules were detected. A total of 230 pulmonary nodules were detected, including 35 pulmonary nodules (15.22%) in the left upper lung, 42 pulmonary nodules (18.26%) in the left lower lung, 52 pulmonary nodules (22.61%) in the right upper lung, 47 pulmonary nodules (20.43%) in the right middle lung, and 54 pulmonary nodules (23.48%) in the right lower lung. The detection rate of pulmonary nodules among military flying personnel in the ≥1 000 h group was higher than in the <1 000 h group, and the difference was statistically significant ( χ2=4.14, P=0.042). More pulmonary nodules were detected among military flying personnel who smoked than among those who did not, and the difference was statistically significant ( χ2=9.34, P=0.002). Age, types of personnel, body mass index, and complications with other lung diseases made no significant difference in the detection rate of pulmonary nodules (all P>0.05). Multivariate Logistic regression analysis showed that smoking was a risk factor for pulmonary nodules ( OR=1.692, 95% CI: 1.217-2.351). Conclusions:Among military flying personnel, pulmonary nodules are more likely to occur in the right lung. Smoking is an independent risk factor for pulmonary nodules, suggesting that routine chest CT screening should be carried out during the annual physical examinations of military flying personnel in order to exercise early interventions.

Objective:To investigate the synergistic activity and mechanism of vinegar baked radix bupleurum polysaccharides(VBCP)in combination with oxaliplatin(OXA),and to provide new ideas for the clinical treatment of primary hepatocellular carci-noma.Methods:MTT assay was used to detect the cytotoxic effect of VBCP 3-4 and VBCP 3-3 in combination with OXA on Huh7 cells;ICP-MS was used to measure the uptake rate of OXA by Huh7 cells and evaluate the in vitro synergistic pathway of VBCP 3-4 in combination with OXA;Western blotting was used to measure the expression levels of related transporter proteins in Huh7 cells and explore the synergistic mechanism of VBCP 3-4 in combination and MRP1 in Huh7 cells,and the protein expression level of multidrug resistance-associated protein(MRP)2 was upregulated to 18.11%and 25.00%,respectively(P=0.008,P=0.001),while that of MRP1 was upregulated to 28.51%(P>0.05)and 39.70%(P=0.015),respectively.After the combination of VBCP 3-4 and OXA,the protein expression of MRP2,MRP1,and breast cancer resis-tance protein(BCRP)was inhibited;MRP2 was reduced by 47.38%in the high-dose combination group(P=0.000)and 15.18%in the low-dose combination group(P=0.049);MRP1 was reduced by 64.96%in the high-dose combination group(P=0.000)and 34.63%in the low-dose combination group(P=0.000);BCRP was reduced by 29.00%(P=0.020)in the high-dose combination group.Acting on Huh7 cells alone,VBCP 3-4 significantly reduced the protein expression levels of MRP2,MRP1,and BCRP,and in the high-dose VBCP 3-4 group,MRP2 and MRP1 were reduced by 24.91%and 20.79%,respectively(P=0.004,P=0.005).VBCP 3-4 downregu-lated the protein expression level of BCRP by 15.02%in the high-dose group(P=0.003)and 13.92%in the middle-dose group(P=0.030).Conclusion:VBCP 3-4 exerts a synergistic effect by inhibiting the expression of the efflux transporter proteins MRP1,MRP2,and BCRP,promoting the intake of OXA by Huh7 cells,and increasing the intracellular effective concentration.

Purpose To investigate the value of 18F-FDG PET/CT combined with MRI for detecting occult lymph node metastases in head and neck squamous cell carcinoma(HNSCC).Materials and Methods Eighteen patients with clinically node-negative,pathologically confirmed HNSCC were retrospectively enrolled from the Third Affiliated Hospital of Air Force Medical University from January 2022 to December 2023.All patients underwent preoperative 18F-FDG PET/CT and MRI,including 3D BRAVO high-resolution structural imaging,T2WI and diffusion-weighted imaging.Two nuclear medicine physicians qualitatively and semi-quantitatively assessed cervical lymph nodes for glucose metabolism and apparent diffusion coefficient(ADC)abnormalities.Using postoperative pathology as the gold standard,the diagnostic performance of PET,ADC and their combination for detecting occult metastases was compared.Results Among 54 dissected lymph nodes from 18 patients,12(22.2%)were pathologically confirmed as metastatic.Of 7 false-negative lymph nodes on diffusion weighted imaging,18F-FDG PET/CT correctly identified 4 as positive.18F-FDG PET/CT showed 6 false negatives and 6 false positives.The accuracies of 18F-FDG PET/CT and MRI for detecting occult metastases were 77.8%and 55.6%,respectively,while their combination achieved 91.1%accuracy(41/45).Metastatic lymph nodes exhibited higher maximum standardized uptake values(3.53±0.26 vs.2.71±0.14;t=3.17,P=0.008)and lower ADC values(0.91×10-3 mm2/s vs.1.07×10-3 mm2/s;t=4.15,P=0.001)compared with inflammatory nodes.Conclusion 18F-FDG PET/CT combined with diffusion weighted imaging improves detection of occult lymph node metastases in HNSCC and may guide surgical management.

Purpose To investigate the value of 18F-FDG PET/CT combined with MRI for detecting occult lymph node metastases in head and neck squamous cell carcinoma(HNSCC).Materials and Methods Eighteen patients with clinically node-negative,pathologically confirmed HNSCC were retrospectively enrolled from the Third Affiliated Hospital of Air Force Medical University from January 2022 to December 2023.All patients underwent preoperative 18F-FDG PET/CT and MRI,including 3D BRAVO high-resolution structural imaging,T2WI and diffusion-weighted imaging.Two nuclear medicine physicians qualitatively and semi-quantitatively assessed cervical lymph nodes for glucose metabolism and apparent diffusion coefficient(ADC)abnormalities.Using postoperative pathology as the gold standard,the diagnostic performance of PET,ADC and their combination for detecting occult metastases was compared.Results Among 54 dissected lymph nodes from 18 patients,12(22.2%)were pathologically confirmed as metastatic.Of 7 false-negative lymph nodes on diffusion weighted imaging,18F-FDG PET/CT correctly identified 4 as positive.18F-FDG PET/CT showed 6 false negatives and 6 false positives.The accuracies of 18F-FDG PET/CT and MRI for detecting occult metastases were 77.8%and 55.6%,respectively,while their combination achieved 91.1%accuracy(41/45).Metastatic lymph nodes exhibited higher maximum standardized uptake values(3.53±0.26 vs.2.71±0.14;t=3.17,P=0.008)and lower ADC values(0.91×10-3 mm2/s vs.1.07×10-3 mm2/s;t=4.15,P=0.001)compared with inflammatory nodes.Conclusion 18F-FDG PET/CT combined with diffusion weighted imaging improves detection of occult lymph node metastases in HNSCC and may guide surgical management.

Objective:To explore the diagnostic value of routine magnetic resonance imaging (MRI) findings for early detection of dural arteriovenous fistulas (DAVF).Methods:A retrospective collection of 53 patients with DAVF confirmed by digital subtraction angiography (DSA) at the Affiliated Hospital of Qingdao University from September 2018 to June 2023 was conducted. All patients underwent routine non-enhanced and enhanced MRI scans before treatment, with 30 patients also receiving magnetic resonance angiography (MRA) examination. Medical records were reviewed, and basic patient information, clinical symptoms, and imaging markers [pial venous engorgement (PVE), cerebral hemorrhage, subarachnoid hemorrhage, vasogenic edema, venous infarction, medullary veins engorgement (MVE), parenchymal enhancement, encephalopathy mimics] were recorded. The Cognard grading was carried out in accordance with the manifestations shown by DSA.Results:Seventy-seven percent (41/53) of patients exhibited PVE on the brain surface, with 95% (39/41) of these cases showing localized PVE on one hemisphere or even within a single brain lobe. Approximately 64% (34/53) of these PVEs were detectable on conventional T 2-weighted imaging. Among the 30 patients who underwent MRA, only 50% (15/30) showed evidence of PVE on both T 2WI and MRA, while an additional 23% (7/30) had PVE only on MRA. About 38% (20/53) of patients presented with isolated vasogenic edema, with 70% (14/20) of these cases demonstrating PVE on T 2WI. Twenty-six percent (14/53) of patients had intracranial hemorrhage, and 11 of these patients demonstrated positive signs of PVE. Parenchymal enhancement was primarily observed in subarachnoid structures in 11% (6/53) of patients, with 5/6 showing PVE on the brain surface or spinal cord surface. Venous infarction (4%, 2/53) and MVE (4%, 2/53) were more commonly seen in high Cognard grade DAVF, whereas encephalopathy mimics (4%, 2/53) were frequently encountered in low Cognard grade DAVF. Conclusions:PVE on the brain surface is a direct sign for the diagnosis of DAVF on routine MRI, yet it is often subtle. Familiarity with common indirect signs is of great importance for the early diagnosis of DAVF.

Objective:To study the results of detection of pulmonary nodules among military flying personnel and analyze the contributors to pulmonary nodules so as to provide data for early prevention and interventions.Methods:The physical examination data of 1 465 military flying personnel was retrospectively analyzed who had received the annual health checkup and undergone chest CT examinations at Lintong Rehabilitation and Recuperation Center. They were grouped by age (<40 years and ≥40 years), flying hour (<1 000 h and ≥1 000 h) and type of personnel [pilots and air support (technical) personnel]. The detection rates of pulmonary nodules among flying personnel were compared across groups, and a multivariate Logistic regression analysis was conducted to analyze the contributing factors to pulmonary nodules.Results:Among the 1 465 military flying personnel, 212 cases (14.47%) with pulmonary nodules were detected. A total of 230 pulmonary nodules were detected, including 35 pulmonary nodules (15.22%) in the left upper lung, 42 pulmonary nodules (18.26%) in the left lower lung, 52 pulmonary nodules (22.61%) in the right upper lung, 47 pulmonary nodules (20.43%) in the right middle lung, and 54 pulmonary nodules (23.48%) in the right lower lung. The detection rate of pulmonary nodules among military flying personnel in the ≥1 000 h group was higher than in the <1 000 h group, and the difference was statistically significant ( χ2=4.14, P=0.042). More pulmonary nodules were detected among military flying personnel who smoked than among those who did not, and the difference was statistically significant ( χ2=9.34, P=0.002). Age, types of personnel, body mass index, and complications with other lung diseases made no significant difference in the detection rate of pulmonary nodules (all P>0.05). Multivariate Logistic regression analysis showed that smoking was a risk factor for pulmonary nodules ( OR=1.692, 95% CI: 1.217-2.351). Conclusions:Among military flying personnel, pulmonary nodules are more likely to occur in the right lung. Smoking is an independent risk factor for pulmonary nodules, suggesting that routine chest CT screening should be carried out during the annual physical examinations of military flying personnel in order to exercise early interventions.