1.Experimental Research and Clinical Application of Shenling Baizhusan in Gastric Ulcer Treatment: A Review
Changyue SUN ; Hua ZHANG ; Yuwei ZHU ; Qian LI ; Xiaowei ZHONG ; Xiaoping ZHANG ; Xiaofan CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):271-281
Gastric ulcer (GU) is a high-incidence digestive system disease characterized pathologically by disruption of gastric mucosal integrity, with clinical features including a prolonged course and periodic recurrence. Modern medicine attributes its pathogenesis to the dynamic imbalance between aggressive and defensive factors,while traditional Chinese medicine (TCM) posits its development as closely linked to spleen deficiency. Current therapies combining acid suppressants and antibiotics face challenges such as high recurrence rates,poor mucosal healing,and adverse drug reactions. Long-term use may induce metabolic disturbances like hypergastrinemia and reduced intestinal microbiota diversity. Therefore,exploring safer and longer-lasting therapeutic strategies has become a critical focus. TCM has extensive clinical experience and unique advantages in GU prevention and treatment. Studies demonstrate that the classic formula Shenling Baizhu San exhibits therapeutic properties of "invigorating spleen and tonifying Qi to restore physiological balance and eliminating dampness and regulating middle energizer to unblock Qi movement", enabling a holistic approach targeting both symptoms and root causes in GU with spleen deficiency as the core pathology by suppressing aggressive factors and strengthening defensive factors. Experimental research reveals its mechanisms involve enhancing the physicochemical barrier of the mucus layer,repairing epithelial barriers and microcirculation,modulating gastric acid secretion and gastrointestinal motility,and regulating microecological barriers and mucosal immunity. Clinical evidence confirms its synergistic effects in promoting ulcer healing,improving Helicobacter pylori eradication rates,and reducing recurrence risks. This review examined the etiology and pathogenesis of GU and systematically evaluated Shenling Baizhu San from three perspectives-clinical application,pharmacological effects, and experimental research-to provide insights for optimizing integrated traditional Chinese and Western medicine protocols and expanding its clinical applications.
2.The influence of two-way referral model on treatment and prognosis of patients with chronic heart failure
Yijun SUN ; Xinyu ZHANG ; Yue HU ; Zongwei LIN ; Jie XIAO ; Peng LI ; Xin ZHAO ; Huafang ZHANG ; Bo QIN ; Dequan JIA ; Tao ZHANG ; Jian MA ; Hongping CHEN ; Chunju ZHANG ; Xinwei GENG ; Kaiyan ZHANG ; Man ZHENG ; Fenglei ZHANG ; Yan LANG ; Hegong HOU ; Peng LIU ; Haifeng JIA ; Jianjun LU ; Kai ZHAO ; Hui ZHAO ; Jiechang XU ; Mi ZHANG ; Xiuxin LI ; Dongxia ZHANG ; Lin ZHONG ; Hui ZHAO ; Fangfang LIU ; Yan LIU ; Dongxia MIAO ; Chengwei WANG ; Hui ZHANG ; Chen WANG ; Fen WANG ; Xuejuan ZHANG ; Huixia LYU ; Xiaoping JI
Chinese Journal of Cardiology 2025;53(11):1244-1253
Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.
3.The safety and efficacy of boron neutron capture therapy (BNCT) in the treatment of recurrent malignant tumors
Junqiang HONG ; Xiaoyi LIN ; Youqun LAI ; Ye CAO ; Xiangquan KONG ; Yuanhao LIU ; Shuiying LUO ; Zhicheng XIONG ; Mei GONG ; Yalai LIN ; Qiaoyun CHEN ; Mingang YING ; Li HUO ; Xiaohua ZHU ; Xiaoping SUN ; Yiqiao DENG ; Diyun SHU ; Haige ZHANG ; Cheng HUANG ; Jianji PAN
Chinese Journal of Radiation Oncology 2025;34(10):985-992
Objective:To evaluate the safety and efficacy of accelerator-based boron neutron capture therapy (AB-BNCT) in the treatment of recurrent and refractory malignant tumors.Methods:The data of 14 patients admitted to Xiamen Humanity Hospital from September 2022 to April 2023 were prospectively collected, including 7 patients with primary brain malignancies and 7 patients with locally recurrent inoperable head and neck malignancies. All patients received intravenous infusion of boron drug (NBB-001, p-dihydroxyborylphe nylalanine, a patented freeze-dried formulation) at a total nominal dosage of 500 mg/kg (11 patients) or 750 mg/kg (3 patients), and were irradiated with neutrons (operating with NeuPex system). Adverse events after treatment were recorded and assessed. The primary efficacy endpoint was the 90 d objective response rate (ORR), while the secondary endpoints included progression-free survival (PFS) and complete response rate (CRR). Data were compiled and analyzed by SAS 9.4 software. The rate and 95% CI were calculated using Clopper-Pearson method. Results:The median dose delivered to 80% of the target volume (D 80%) was 16.80 GyE (range: 8.93-23.79 GyE). The most common adverse reactions were hyperamylasemia, alopecia, and hyperprolactinemia. Five patients experienced 8 cases of grade 3 or above adverse events, including 1 case of grade 4 acute kidney injury and 7 cases of grade 3 adverse events. All adverse events were recovered after observation or treatment. At 90 d after treatment, the ORR of all patients was 9/14 (64%, 95% CI: 35%-87%), disease control rate (DCR) was 10/14 (71%, 95% CI: 42%-92%), CRR was 2/14 (14%, 95% CI: 2%-42%); and the best overall response during the entire course included an ORR of 10/14 (71% ,95% CI: 42%-92%), DCR of 13/14 (93%, 95% CI: 66%-100%), and CRR of 3/14 (21% ,95% CI: 5%-51%). The 1-year survival rate for head and neck malignancies was 71.4%, and the 2-year survival rate was 42.8%. The 1-year survival rate for recurrent brain malignancies was 42.8%. Conclusion:AB-BNCT demonstrates favorable safety and promising efficacy in treating primary brain malignancies and recurrent/refractory head and neck malignancies, representing a potential therapeutic option.
4.Analysis of the efficacy of lamb′s tripe extract and vitamin B 12 capsule on chronic atrophic gastritis at different sites
Dongdong XIA ; Huahong XIE ; Bo JIANG ; Hong XU ; Zhanguo NIE ; Chengwei TANG ; Qiang GUO ; Xiaoping ZOU ; Shuisheng SHI ; Tao SUN ; Shourong SHEN ; Guoqing LI ; Xiaozhong GUO ; Xiaoyan ZHAO ; Jiaming QIAN ; Weixing CHEN ; Guiying ZHANG ; Aijun LIAO ; Jingyuan FANG ; Daiming FAN ; Kaichun WU
Chinese Journal of Digestion 2025;45(3):162-168
Objective:To evaluate the efficacy of lamb′s tripe extract and vitamin B 12 capsule (LTEVB 12C) on chronic atrophic gastritis (CAG) at different locations (antrum lesser curvature, antrum greater curvature, gastric angle, corpus lesser curvature, and corpus greater curvature). Methods:From August 2011 to January 2013, 715 patients with CAG in a multicenter, randomized, double-blind, placebo-controlled trial were enrolled from 16 tertiary first-class hospitals across the country, including the First Affiliated Hospital of Air Force Medical University, Nanfang Hospital of Southern Medical University, the First Hospital of Jilin University, West China Hospital of Sichuan University, etc., there were 476 cases in the LTEVB 12C group and 239 cases in the placebo group. The patients of the LTEVB 12C group received LTEVB 12C, and the patients of placebo group received LTEVB 12C mimetic, all the medications were taken 3 capsules each time and 3 times a day after meals, and the treatment course of 2 groups were both 6 months. The efficacy evaluation criteria included the effective rate (a decrease of ≥1 in histopathological score compared with baseline after 6 months of treatment) and the reversal rate (a decrease of ≥ 2 in histopathological score compared with baseline after 6 months of treatment in the patients with moderate to severe CAG). The impact of lesion sites on the therapeutic effects of LTEVB 12C was analyzed by logistic regression analysis. The two-way unordered Cochran-Mantel-Haenszel chi-square test considering the center effect and Pearson chi-square test were used for statistical analysis. Results:The effective rates of chronic inflammation at the antrum greater curvature and corpus greater curvature (23.3%, 110/473 vs. 13.0%, 31/239; 20.3%, 96/472 vs. 12.6%, 30/239), the effective rates of atrophy at the antrum lesser curvature, antrum greater curvature, gastric angle, corpus lesser curvature, and the corpus greater curvature (27.0%, 118/437 vs. 15.7%, 34/216; 29.2%, 126/432 vs. 18.5%, 38/205; 27.8%, 121/435 vs. 16.7%, 36/216; 32.5%, 127/391 vs. 19.8%, 37/187; 33.0%, 119/361 vs. 21.8%, 39/179), and the effective rates of intestinal metaplasia at the antrum lesser curvature, antrum greater curvature, gastric angle, and the corpus lesser curvature (45.0%, 112/249 vs. 29.8%, 31/104; 53.8%, 86/160 vs. 33.9%, 21/62; 45.8%, 103/225 vs. 24.0%, 25/104; 51.9%, 83/160 vs. 28.3%, 17/60) of the LTEVB 12C group were all higher than those of the placebo group, and the differences were statistically significant ( χ2=10.76, 6.39, 9.69, 7.91, 11.05, 9.62, 8.57, 5.20, 7.11, 12.45, and 6.73; all P<0.05). The reversal rates of chronic inflammation at the corpus lesser curvature and corpus greater curvature (5.2%, 12/231 vs. 0, 0/123; 4.7%, 8/170 vs. 0, 0/88), the reversal rates of atrophy at the antrum lesser curvature, antrum greater curvature, corpus lesser curvature, and the corpus greater curvature (6.8%, 22/323 vs. 1.3%, 2/151; 9.2%, 29/315 vs. 1.4%, 2/144; 14.2%, 38/267 vs. 2.5%, 3/121; 20.8%, 35/168 vs. 5.8%, 4/69), and the reversal rates of intestinal metaplasia at the antrum lesser curvature, antrum greater curvature, gastric angle, and the corpus lesser curvature (29.8%, 39/131 vs. 9.1%, 4/44; 41.0%, 32/78 vs. 12.5%, 3/24; 33.3%, 44/132 vs. 4.8%, 3/63; 50.0%, 37/74 vs. 8.7%, 2/23) of the LTEVB 12C group were all higher than those of the placebo group, and the differences were statistically significant ( χ2=6.58, 5.12, 5.60, 8.61, 11.43, 6.59, 7.30, 4.95, 15.92, 7.62; all P<0.05). There were no statistically significant differences in the effective rates and reversal rates of active inflammation at different locations between the LTEVB 12C group and the placebo group (all P>0.05). The results of logistic regression analysis (taking the antrum lesser curvature as the reference) further confirmed that the reversal rates of chronic inflammation ( OR=0.22, 95% confidence interval (95% CI): 0.07 to 0.67; OR=0.24, 95% CI: 0.07 to 0.80), atrophy ( OR=0.28, 95% CI: 0.16 to 0.49; OR=0.28, 95% CI: 0.16 to 0.49), and intestinal metaplasia ( OR=0.42, 95% CI: 0.24 to 0.77; OR=0.20, 95% CI: 0.08 to 0.52) at the corpus lesser curvature and corpus greater curvature were all higher than those at the antrum lesser curvature, and the differences were statistically significant (all P<0.05). There were no statistically siginificant differences in the reversal rates of the aforementioned pathological features between the antrum greater curvature, gastric angle, and the antrum lesser curvature (all P>0.05). Conclusion:LTEVB 12C can achieve good efficacy in the treatment of CAG, and the chronic inflammation, atrophy, and intestinal metaplasia at multiple locations are improved, especially at the corpus lesser curvature and the corpus greater curvature.
5.CT and MRI findings of giant cell reparative granuloma in lateral skull base
Pengfeng SUN ; Jiping DONG ; Xiaoping WU ; Xiangchun YANG ; Caixia PEI ; Hongsheng LIU ; Run LIU
Journal of Practical Radiology 2025;41(4):560-563
Objective To investigate the CT and MRI features of giant cell reparative granuloma(GCRG)in lateral skull base.Methods The CT,MRI and clinicopathological data of 8 patients with GCRG in lateral skull base were collected and analyzed.Results All of the eight lesions were unilateral and solitary(three on the left side and five on the right side),with widespread involvement affecting two or more bony structures of the lateral skull base.All lesions showed expansile and lytic bone destruction on CT scans,the margins were clear(7/8),and the sclerotic changes could be seen at the margin of all eight lesions.On MRI,the lesions revealed heterogeneous isointense and hypointense on T1WI,and heterogeneous hypointense with focal cystic changes on T2WI,without fluid-fluid levels.The enhanced scan showed heterogeneous enhancement.Seven cases extended to the middle cranial fossa,caused com-pression of the temporal lobe brain tissue,with thickened and strengthened adjacent meninges.Conclusion The GCRG in lateral skull base has certain characteristic appearances on CT and MRI;understanding these characteristic manifestations can provide a basis for accurate diagnosis.
6.Factors associated with conversion to cesarean delivery in parturients receiving epidural labor analgesia and development of predictive model
Linglan XU ; Lihong SUN ; Xiaoping CHEN ; Jiaxin CHEN ; Xinzhong CHEN
Chinese Journal of Anesthesiology 2025;45(9):1148-1152
Objective:To identify the risk factors associated with conversion to cesarean delivery in parturients receiving epidural labor analgesia and to construct a predictive model.Methods:In this prospective cohort study, 718 parturients with a singleton fetus at 37-42 weeks of gestation age, aged 22-45 yr, of American Society of Anesthesiologists Physical Status classification Ⅱ, who received epidural labor analgesia at the Women′s Hospital affiliated to Zhejiang University School of Medicine between November 2022 and August 2023, were included and divided into 2 groups based on the final mode of delivery: cesarean delivery group (CD group) and vaginal delivery group (VD group). Data collected included maternal age, height, body mass index at labor onset, gestational age, pregnancy complications, mode of conception, parity, premature rupture of membranes, mode of labor onset and details of labor analgesia. Risk factors for conversion to cesarean delivery were analyzed using multivariate logistic regression analysis, and a prediction model was developed. The receiver operating characteristic curve was ploted, and the area under the receiver operating characteristic curve was calculated to evaluate the accuracy of the predictive model.Results:A total of 682 parturients were included in the final statistical analysis, with 103 in CD group and 579 in VD group. Multivariate logistic regression analysis showed that maternal age≥35 yr, height<160 cm, body mass index at labor onset ≥28 kg/m 2, nulliparous parturients, the use of Foley balloon catheter or dinoprostone suppositories for cervical ripening were risk factors for cesarean delivery, and cervical dilation during analgesia was a protective factor. The area under the receiver operating characteristic curve for the predictive model constructed based on the aforementioned influencing factors yielded predicting conversion to cesarean delivery due to failed vaginal trial of labor was 0.791 (95% confidence interval 0.744-0.837, P<0.001), with a sensitivity of 73.6% and a specificity of 70.9%. Conclusions:Nulliparous parturients, maternal age≥35 yr, height<160 cm, body mass index at labor onset≥28 kg/m 2, and the use of Foley balloon catheter or dinoprostone suppositories for cervical ripening are risk factors for cesarean delivery, and cervical dilation during analgesia is a protective factor. The predictive model established based on these influencing factors has high predictive performance.
7.Study on the diagnostic value of 3D ultrasound combined with 2D 2D-TVS on uterine arteriovenous fistula
Bo LI ; Xiaoping SUN ; Xianying WANG ; Zhongyan CAO ; Fengjuan WANG
China Medical Equipment 2025;22(10):46-50
Objective:To explore the application value of three-dimensional ultrasound(3D-US)combined with two-dimensional trans vaginal sonography(2D-TVS)in diagnosing uterine arteriovenous fistula(UAVF).Methods:A total of 36 patients with suspected UAVF who admitted to Baoding Maternal and Child Health Care Hospital from January 2024 to December 2024 were retrospective selected.All of them underwent 3D-US,2D-TVS and combined examinations of 3D-US and 2D-TVS.The gynecological intravenous contrast-enhanced ultrasound was used as the"gold standard"to compare and analyze the sensitivity,specificity,accuracy rate,positive predictive value and negative predictive value of 3D-US,2D-TVS and the combined examination of them.The diagnostic efficacies of the three diagnostic methods were calculated by the four-grid table method and the analysis of the receiver operating characteristic(ROC)curve.The detection rates of 2D-TVS and combined examination of 2D-TVS and 3D-US for UAVF imaging signs were compared.Results:In 36 patients,gold standard confirmed 26 positive cases and 10 negative cases.The sensitivity,specificity,accuracy rate,positive predictive value and negative predictive value of 2D-TVS examination were respectively 69.23%,80.00%,72.22%,90.00%and 50.00%.These indicators of 3D-US examinations were respectively 84.62%,90.00%,86.11%,95.65%and 69.23%.These indicators of the combined examination were respectively 92.31%,90.00%,91.67%,96.00%and 81.82%.There were not statistically significant differences in these indicators among the three diagnostic methods(P>0.05).However,the sensitivity,accuracy rate of the combined examination were respectively higher than those of 2D-TVS examination,and the differences were statistically significant(x2=4.457,4.600,P<0.05).The detection rates of the sings included lake-like,multicolored Mosaic and blood flow spectrum of high-speed low-resistance in UAVF images of the combined examination were all higher than those of 2D-TVS examination,and the differences were statistically significant(x2=4.000,4.431,4.600,P<0.05).Conclusion:The combination of 3D-US and 2D-TVS can significantly improve the diagnostic sensitivity,accuracy and detection rate of imaging signs in the diagnosis for UAVF,which has important clinical application value.
8.Secondary infective femoral artery pseudoaneurysm after intervention sur-gery for cerebral infarction:a case report
Xiaoping WU ; Xiaowei SUN ; Jiantao LI
Chinese Journal of Infection Control 2025;24(5):701-704
This article reports the diagnosis and treatment process of a case with secondary infective femoral artery pseudoaneurysm after intervention surgery for cerebral infarction,who improved after anti-infection and surgical treatment and was discharged.The patient was a 52-year-old female who underwent percutaneous balloon dilatation of basilar artery due to basilar artery stenosis.After surgery,she developed secondary methicillin-resistant Staphy-lococcus aureus(MRSA)bloodstream infection and infective femoral artery pseudoaneurysm.After treatment with vancomycin and linezolid,femoral artery pseudoaneurysm resection,and autovascular replacement,the patient re-covered well after the surgery and discharged from hospital.CT angiography(CTA)re-examination showed artifi-cial blood vessel patency.This study is expected to provide experience for the diagnosis and treatment of such pa-tients in clinical work.
9.EGR2 maintains neuropathic pain by promoting microglial phagocytosis.
Caiyun XI ; Jianxi ZHANG ; Zhifeng HUANG ; Liqiong HE ; Kailu ZOU ; Xiaoping XU ; Qulian GUO ; Bei SUN ; Changsheng HUANG
Journal of Central South University(Medical Sciences) 2025;50(4):586-601
OBJECTIVES:
Neuropathic pain (NP) is one of the most common forms of chronic pain, yet current treatment options are limited in effectiveness. Peripheral nerve injury activates spinal microglia, altering their inflammatory response and phagocytic functions, which contributes to the progression of NP. Most current research on NP focuses on microglial inflammation, with relatively little attention to their phagocytic function. Early growth response factor 2 (EGR2) has been shown to regulate microglial phagocytosis, but its specific role in NP remains unclear. This study aims to investigate how EGR2 modulates microglial phagocytosis and its involvement in NP, with the goal of identifying potential therapeutic targets.
METHODS:
Adult male Sprague-Dawley (SD) rats were used to establish a chronic constriction injury (CCI) model of the sciatic nerve. Pain behaviors were assessed on days 1, 3, 7, 10, and 14 post-surgery to confirm successful model induction. The temporal and spatial expression of EGR2 in the spinal cord was examined using real-time quantitative PCR (RT-qPCR), Western blotting, and immunofluorescence staining. Adeno-associated virus (AAV) was used to overexpress EGR2 in the spinal cord, and behavioral assessments were performed to evaluate the effects of EGR2 modulation of NP. CCI and lipopolysaccharide (LPS) models were established in animals and microglial cell lines, respectively, and changes in phagocytic activity were measured using RT-qPCR and fluorescent latex bead uptake assays. After confirming the involvement of microglial phagocytosis in NP, AAV was used to overexpress EGR2 in both in vivo and in vitro models, and phagocytic activity was further evaluated. Finally, eukaryotic transcriptome sequencing was conducted to screen differentially expressed mRNAs, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to identify potential downstream effectors of EGR2.
RESULTS:
The CCI model successfully induced NP. Following CCI, EGR2 expression in the spinal cord was upregulated in parallel with NP development. Overexpression of EGR2 via spinal AAV injection enhanced microglial phagocytic activity and increased pain hypersensitivity in rats. Both animal and cellular models showed that CCI or LPS stimulation enhanced microglial phagocytosis, which was further amplified by EGR2 overexpression. Transcriptomic analysis of spinal cord tissues from CCI rats overexpressing EGR2 revealed upregulation of numerous genes associated with microglial phagocytosis and pain regulation. Among them, Lag3 emerged as a potential downstream target of EGR2.
CONCLUSIONS
EGR2 contributes to the maintenance of NP by enhancing microglial phagocytosis in the spinal dorsal horn.
Animals
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Microglia/metabolism*
;
Phagocytosis/physiology*
;
Rats, Sprague-Dawley
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Neuralgia/physiopathology*
;
Early Growth Response Protein 2/metabolism*
;
Male
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Rats
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Spinal Cord/metabolism*
;
Sciatic Nerve/injuries*
10.Intranodal injection of neoantigen-bearing engineered Lactococcus lactis triggers epitope spreading and systemic tumor regressions.
Junmeng ZHU ; Yi SUN ; Xiaoping QIAN ; Lin LI ; Fangcen LIU ; Xiaonan WANG ; Yaohua KE ; Jie SHAO ; Lijing ZHU ; Lifeng WANG ; Qin LIU ; Baorui LIU
Acta Pharmaceutica Sinica B 2025;15(4):2217-2236
Probiotics are natural systems bridging synthetic biology, physical biotechnology, and immunology, initiating innate and adaptive anti-tumor immune activity. We previously constructed an all-in-one engineered food-grade probiotic Lactococcus lactis (FOLactis) which could boost the crosstalk among different immune cells such as dendritic cells (DCs), natural killer cells, and T cells. Herein, considering the limited clinical efficacy of naked personalized neoantigen peptide vaccines, we decorate FOLactis with tumor antigens by employing a Plug-and-Display system comprising membrane-inserted peptides. Intranodal injection of FOLactis coated with neoantigen peptides (Ag-FOLactis) induces robust DCs presentation and neoantigen-specific cellular immunity. Notably, Ag-FOLactis not only triggers a 45-fold rise in the quantity of locally reactive neoantigen-specific T cells but also induces epitope spreading in both subcutaneous and metastatic tumor-bearing models, leading to potent inhibition of tumor growth. These findings imply that Ag-FOLactis represents a powerful platform to rapidly and easily display antigens, facilitating the development of a bio-activated platform for personalized therapy.

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