1.Application value of simplified diagnosis and treatment strategies for chronic hepatitis C in human immunodeficiency virus/hepatitis C virus co-infection
Ying CAI ; Zhibin YANG ; Yang LUO ; Cong WANG ; Yongfen ZHU ; Ze LI ; Rusong YANG ; Qiang WU ; Wenbin DONG ; Shifu LI
Journal of Clinical Hepatology 2026;42(6):1287-1293
ObjectiveTo investigate the efficacy and safety of simplified diagnosis and treatment strategies and regimens in the treatment of patients with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection. MethodsThis multicenter prospective real-world study was conducted among 198 patients with HIV/HCV co-infection who received hepatitis C treatment in 10 designated primary hospitals for hepatitis C in Yuxi, China from July 2023 to June 2024, and according to whether genotype detection was performed, they were divided into genotype detection group with 122 patients and non-genotype detection group with 76 patients. The patients were observed in terms of sustained virologic response at 12 weeks (SVR12), safety, and liver biochemical parameters. Propensity score matching was used to match the two cohorts, using caliper matching (caliper value = 0.02) at a ratio of 1∶1. The independent-samples t test or the Wilcoxon signed-rank test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between groups. ResultsAmong the 122 patients in the genotype detection group, 63.11% (77/122) had genotype 3, while the non-genotype detection group had 76 patients; both groups achieved an SVR12 rate of 100%. From baseline to 12 weeks after treatment, both groups had a significant increase in the serum level of albumin, significant reductions in the serum levels of total bilirubin, alanine aminotransferase, aspartate aminotransferase, and alpha-fetoprotein, and a significant reduction in FibroScan value (all P<0.05). A total of 54 patients (27.27%) experienced at least one adverse reaction, and anemia was the most common adverse reaction (38 patients, 19.19%), with an incidence rate of 50.00% (33/66) in patients with liver cirrhosis. HIV viral load remained <50 IU/mL before and after treatment, and there was no significant change in CD4+ T lymphocyte count after treatment (Z=-0.969, P=0.202). Compared with the genotype detection group, the non-genotype detection group had a significantly shorter time from positive HCV RNA testing to treatment initiation (4±2 days vs 19±4 days, t=5.321, P<0.05) and significantly lower testing costs (618±97 yuan vs 789±129 yuan, t=3.661, P<0.05). ConclusionFor patients with HIV/HCV co-infection, the simplified diagnosis and treatment strategies can achieve a relatively high SVR12 rate, improve biochemical indicators, and effectively reduce time cost and economic burden, with a favorable safety profile.
2.Prediction of Mismatch Repair Deficiency Status in Endometrial Cancer Using Multiparametric MRI Radiomics and Deep Learning: A Multimodal Model with Preliminary Validation
Liru WANG ; Shangying YANG ; Boyu CHEN ; Fuze CONG ; Xinran LI ; Xinyu LIU ; Huadan XUE ; Zhengyu JIN ; Yang XIANG ; Yonglan HE ; Yuan LI
Medical Journal of Peking Union Medical College Hospital 2026;17(4):976-984
To explore the clinical value of a multimodal predictive model based on multiparametric magnetic resonance imaging(MRI) radiomics combined with deep learning(DL) features for the preoperative noninvasive assessment of mismatch repair-deficient(MMRd) status in endometrial cancer(EC). Patients diagnosed with EC at Peking Union Medical College Hospital from January 2015 to December 2021 were retrospectively enrolled and randomly divided into a training set and a validation set at a ratio of 8∶2. Relevant clinical data were collected, and radiomics features and DL features were extracted from preoperative contrast-enhanced T1-weighted imaging(CE-T1WI), fat-suppressed T2-weighted imaging(fs-T2WI), and diffusion-weighted imaging(DWI) sequences. High-dimensional feature selection and dimensionality reduction were performed sequentially using the recursive feature elimination(RFE) algorithm to generate a radiomics score(Rad-score) and a deep learning score(DL-score), respectively. Multivariate logistic regression was utilized to construct a clinical model, a pure radiomics model, a clinical-radiomics model, and an integrated multimodal model incorporating clinical indicators, Rad-score, and DL-score. Model performance was assessed and compared using area under receiver operating characteristic curve(AUC) and DeLong test. A total of 509 patients were enrolled in this study, comprising 413 in the training cohort and 96 in the validation cohort. Independent predictors: Multivariate analysis indicated that preoperative fasting blood glucose level, histological grade, lymph node metastasis status, Rad-score, and DL-score were all independent significant predictors of MMRd status in EC patients. The integrated multimodal model demonstrated optimal predictive performance with an AUC of 0.699(95% CI: 0.635-0.763) in the training set, which was superior to the clinical model(AUC=0.629, 95% CI: 0.561-0.697) and the pure radiomics model(AUC=0.641, 95% CI: 0.575-0.706). In the validation set, the integrated model maintained good generalizability, achieving an AUC of 0.655(95% CI: 0.535-0.775), and its diagnostic efficacy was higher than that of the clinical model(AUC=0.578, 95% CI: 0.450-0.705) and the pure radiomics model(AUC=0.611, 95% CI: 0.488-0.734). According to the DeLong test, the incorporation of DL features resulted in the clinicalradiomicsdeep learning model performing better than both the clinicalonly model( The initially developed clinical-radiomics-deep learning model exhibits a certain predictive potential for the MMRd status in patients with EC. The inclusion of DL features may help complement the limitations of traditional evaluations, offering a preliminary radiological reference for preoperative non-invasive screening. However, given the current diagnostic performance, its overall accuracy and clinical generalizability warrant further validation in multi-center, large-sample external cohort studies.
3.Study on image detection and target recognition based on traditional Chinese medicine
Tianchi MAO ; Xing SUN ; Jiayin ZHU ; An LIU ; Yang LI ; Jingang MA ; Cong GUO
Science of Traditional Chinese Medicine 2026;4(1):73-80
Background: Chinese herbal pieces are an essential component of traditional Chinese medicine. Accurate identification and classification of these materials are crucial in clinical practice. Objective: This study aims to enhance the recognition efficiency of Chinese herbal pieces using deep learning technology, while addressing the limitations of traditional manual classification methods in terms of both quality and efficiency. Methods: A comprehensive dataset containing 201 types of Chinese herbal pieces was established. Based on Real-time Detection Transformer (RT-DETR), we designed and integrated a Feature-focused Diffusion Network (FDN), resulting in an improved model termed RT-DETR-FDN. The proposed FDN includes a Feature-focus Module and a feature diffusion mechanism, enabling the model to capture more extensive feature information from Chinese herbal pieces and diffuse it across multiple detection scales. Results: Experimental results show that RT-DETR-FDN achieved a precision of 0.925, a recall of 0.943, and an mAP50-95 of 0.851. In addition, the model was compared with representative You Only Look Once series models commonly used in object detection. Compared with these models, RT-DETR-FDN achieved higher recognition accuracy while maintaining a lightweight architecture. Conclusion: This study integrates deep learning with traditional Chinese medicine, providing a more effective solution for the recognition of Chinese herbal pieces.
4.Influencing Factors of Depression in Patients with Postoperative Ovarian Cancer
Jialiang YAO ; Long ZHANG ; Jianhui TIAN ; Ze LIU ; Yun YANG ; Yiyang ZHOU ; Minghua LI ; Wang YAO ; Wenfei SHI ; Xinyi LU ; Pan YU ; Enchao CONG
Cancer Research on Prevention and Treatment 2026;53(5):349-359
Objective To explore the prevalence of depressive symptoms in postoperative patients with ovarian cancer and to analyze its influencing factors from multiple dimensions, including clinical characteristics, psychological factors, and laboratory indicators. Methods A cross-sectional study was conducted, which enrolled 235 postoperative patients with ovarian cancer. Depressive status was assessed using the patient health questionnaire, and the demographic, pathological, and medical record data of the patients were collected using the generalized anxiety disorder scale, Pittsburgh sleep quality index, European organization for research and treatment of cancer quality of life questionnaire core 30, and ECOG performance status score. Peripheral blood tumor marker (CA125), routine blood test, lymphocyte subsets, and serum cytokine levels were measured. Univariate and multivariate binary logistic regression analysis were used for statistical analysis. Results The prevalence of depression in postoperative patients with ovarian cancer was 39.15% (92/235). Univariate analysis showed that ECOG score ≥ 2 points, pain, anxiety, poor sleep quality, low quality of life, low life satisfaction, tumor recurrence, six or more cycles of chemotherapy, as well as higher levels of CA125, NLR, and NAR, and lower hemoglobin levels were significantly associated with depression (all P<0.05). Multivariate binary Logistic regression analysis showed that anxiety (OR=1.975, 95%CI: 1.231-3.170), sleep efficiency (OR=4.181, 95%CI: 1.211-14.43), sleep latency (OR=34.806, 95%CI: 4.258-284.542), ECOG performance status score, cognitive function (OR=0.918, 95%CI: 0.868-0.97), and life satisfaction were independent risk factors for depression (all P<0.05). Laboratory indicators were not independent influencing factors in the multivariate Logistic regression model. Conclusion Depression in postoperative patients with ovarian cancer is influenced by physiological, psychological, and social factors. Clinical management should focus on patients with anxiety, sleep disorders, poor physical condition, and low life satisfaction, and a comprehensive prevention and treatment strategy centered on psychological intervention and taking into account symptom management and social support should be implemented.
5.Effectiveness of the integrated schistosomiasis control programme in Wuhan City from 2005 to 2023
Shuai WANG ; Huatang LUO ; Yang LI ; Hao WANG ; Cong LIU ; Yuelin XIONG ; Jiajing ZHANG ; Wen ZHU
Chinese Journal of Schistosomiasis Control 2025;37(2):176-183
Objective To evaluate the effectiveness of the integrated schistosomiasis control programme in Wuhan City from 2005 to 2023, so as to provide insights into precision control and elimination of schistosomiasis. Methods The integrated measures for schistosomiasis control implemented by health, agriculture, water resources, and forestry departments of Wuhan City, and the epidemiological data of schistosomiasis in Wuhan City were collected from 2005 to 2023, and the prevalence of human schistosomiasis, prevalence of Schistosoma japonicum infections in humans and bovines, areas of S. japonicum-infected snail habitats, areas of snail habitats in inner embankments, and actual areas of snail habitats were retrieved. In addition, the trends in prevalence of schistosomiasis in humans and livestock and snail status were evaluated in Wuhan City from 2005 to 2023 using Mann-Kendall test and a Joinpoint regression model. Results Mann-Kendall test revealed a tendency towards a decline in the prevalence of human schistosomiasis (Z = -4.41, P < 0.01), prevalence of S. japonicum infections in humans (Z = -4.89, P < 0.01) and bovines (Z = -4.50, P < 0.01), areas of S. japonicum-infected snail habitats (Z = -3.91, P < 0.01), areas of snail habitats in inner embankments (Z = -2.28, P = 0.02), and actual areas of snail habitats (Z = -5.95, P < 0.01) in Wuhan City from 2005 to 2023. Joinpoint regression analysis showed an average annual reduction of 8.58% in the prevalence of human schistosomiasis in Wuhan City from 2005 to 2023 [average annual percent change (AAPC) = -8.58%, 95% confidence interval (CI): (-10.02%, -6.65%), P < 0.01], with two joinpoints in 2013 and 2016, respectively, and the tendency towards a decline showed statistical significance during the period from 2013 through 2016 [annual percent change (APC) = -34.41%, 95% CI: (-40.36%, -20.01%), P < 0.01]. The prevalence of S. japonicum human infections appeared an average annual reduction of 51.91% in Wuhan City from 2005 to 2023 [AAPC = -51.91%, 95% CI: (-58.12%, -44.25%), P < 0.01], with two joinpoints in 2014 and 2017, respectively, and the tendency towards a decline showed statistical significance during the period from 2014 through 2017 [APC = -98.17%, 95% CI: (-99.17%, -90.87%), P < 0.01]. The prevalence of S. japonicum infections in bovines appeared an average annual reduction of 53.12% in Wuhan City from 2005 to 2023 [AAPC = -53.12%, 95% CI: (-59.65%, -42.44%), P < 0.01], with two joinpoints in 2011 and 2014, respectively, and the tendency towards a decline showed statistical significance during the period from 2014 through 2017 [APC = -98.63%, 95% CI: (-99.44%, -90.93%), P < 0.01]. The areas of S. japonicum-infected snail habitats appeared an average annual reduction of 47.09% in Wuhan City from 2005 to 2023 [AAPC = -47.09%, 95% CI: (-52.92%, -38.26%), P < 0.01], with two joinpoints in 2011 and 2014, respectively, and the tendency towards a decline showed statistical significance during the period from 2011 through 2014 [APC = -97.27%, 95% CI: (-98.65%, -88.06%), P < 0.01]. The areas of snail habitats in inner embankments appeared an average annual reduction of 4.45% in Wuhan City from 2005 to 2023 [AAPC = -4.45%, 95% CI: (-5.18%, -3.82%), P < 0.01], with three joinpoints in 2011, 2015 and 2018, respectively, and statistical significance was seen in the tendency towards a decline during the period from 2005 through 2011 [APC = -16.38%, 95% CI: (-20.15%, -14.25%), P < 0.01]. In addition, the actual areas of snail habitats appeared an average annual reduction of 2.65% in Wuhan City from 2005 to 2023 [AAPC = -2.65%, 95% CI: (-2.89%, -2.40%), P < 0.01], with a joinpoint in 2013, and the tendency towards a decline showed statistical significance during the period from 2013 through 2023 [APC = -4.06%, 95% CI: (-4.66%, -3.58%), P < 0.01]. Conclusions The integrated schistosomiasis control programme achieved significant effectiveness in Wuhan City from 2005 to 2023, with a tendency towards a decline in morbidity due to schistosomiasis in humans and livestock and snail status. The integrated schistosomiasis control strategy with emphasis on management of the source of S. japonicum infections should continue to be implemented to consolidate the schistosomiasis control achievements and achieve the goal of schistosomiasis elimination in the city.
6.Influencing factors of uptake of 18F-FAPI-04 in normal liver tissue
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(2):285-289
Objective To explore the factors influencing the uptake of 18F-FAPI-04 in normal liver tissue.Methods A total of 77 patients who had undergone 18F-FAPI-04 PET/CT scan were retrospectively enrolled.We collected their medical history,as well as laboratory indicators within one week before the imaging,including blood cell count,liver function and renal function indicators.The maximal standard uptake value(SUVmax)of the liver on 18F-FAPI-04 PET/CT images was manually measured,and the correlations between the SUVmax and the laboratory indicators were analyzed.With SUVmax as the dependent variable,multiple linear regression was performed to obtain independent predictors.Results SUVmax between the groups with or without smoking,drinking,chemotherapy,active tumor,or liver metastasis was not significantly different(P>0.05).SUVmax had no significant correlation with blood cell count indexes(all P>0.05),but was positively correlated with glutamic-pyruvic transaminase,γ-glutamyl transpeptidase,direct bilirubin,globulin,blood glucose level and creatinine(r=0.196,P=0.047;r=0.180,P=0.027;r=0.196,P=0.015;r=0.171,P=0.032;r=0.296,P<0.001;r=0.270,P=0.001),and was negatively correlated with glomerular rate filtration(r=-0.209,P=0.009).Glucose level(β=0.100,P<0.001),direct bilirubin(β=0.021,P<0.001)and creatinine(β=0.003,P=0.018)were independent predictors of SUVmax.Conclusion Liver uptake of 18F-FAPI-04 is positively correlated with glutamic-pyruvic transaminase,γ-glutamyl transpeptidase,direct bilirubin,globulin,blood glucose levels and creatinine,but negatively correlated with glomerular rate filtration.Glucose level,direct bilirubin and creatinine are independent predictors of 18F-FAPI-04 uptake by the liver.
7.Predictive value of automatic breast ultrasound features combined with Ki-67 for pathological complete response after neoadjuvant chemotherapy in triple negative breast cancer
Yang ZHAO ; Ying-Cong XIAO ; Yan JU ; Xiao-Zhi DANG ; Wen-Xin XUE ; Yang LI ; Hong-Ping SONG
Medical Journal of Chinese People's Liberation Army 2025;50(6):695-702
Objective To explore the predictive value of automated breast ultrasound(ABUS)features combined with Ki-67 in predicting pathological complete response(pCR)after neoadjuvant chemotherapy(NAC)in triple-negative breast cancer(TNBC).Methods A retrospective analysis was conducted on 127 female TNBC patients treated at Xijing Hospital,Air Force Medical University from March 2019 to December 2023.All patients underwent NAC and surgical treatment after ABUS examination.Based on postoperative pathological results,patients were divided into pCR group(n=60)and non-pathological complete response(npCR)group(n=67).Differences in various parameters before NAC were compared between the two groups.LASSO regression was used to identify independent factors influencing pCR after NAC in TNBC patients,and a predictive model was constructed using multivariate logistic regression.The prediction model was internally validated using the Bootstrap method(1000 resamples).The discriminative ability of the model was evaluated using receiver operating characteristic(ROC)curves,and the area under the curves(AUCs)of different prediction models were compared using De-long's test.The accuracy of the model was assessed using calibration curves,and the clinical benefit of the model was evaluated using clinical decision curve analysis(DCA).Results Significant differences were observed between two groups in terms of age,Ki-67,menopausal status,tumor type,posterior echo,coronal plane convergence sign,coronal plane skip sign,and coronal plane white wall sign before NAC(P<0.05).LASSO regression analysis showed that Ki-67,coronal plane convergence sign,and coronal plane white wall sign were independent influencing factors of pCR after NAC in TNBC patients(P<0.05).The AUC of the multivariate logistic regression model based on Ki-67 was 0.733(95%CI 0.646-0.819),the AUC of ABUS model was 0.777(95%CI 0.695-0.858),and the AUC of ABUS combined with Ki-67 model was 0.816(95%CI 0.741-0.890).De-long's test showed that the AUC of the combined model was higher than those of ABUS feature model and Ki-67 model,with statistically significant differences(P<0.05).There was no significant difference in the AUC between ABUS feature model and Ki-67 model(P=0.40).Hosmer-Lemeshow test indicated that the combined model had a good fit(P=0.304).Internal validation results showed that the combined model had a good stability with a consistency index(C-index)of 0.820(95%CI 0.726-0.879).The calibration curve demonstrated good consistency between the predicted and actual probabilities of the combined prediction model,and the DCA curve indicated that the model had favorable clinical benefit.Conclusion The combined ABUS feature and Ki-67 model can be used to predict the probability of pCR after NAC in TNBC patients,providing a reference for the formulation of clinical treatment plans in TNBC patients.
8.Correlation between blood pressure trajectory and hearing threshold among workers exposed to occupational noise in a city's rail transit enterprise
Hongting ZHAN ; Qia WANG ; Xinmei CHEN ; Zhiping LIANG ; Cong LI ; Danyan CAO ; Aichu YANG ; Minghui XIAO
Journal of Environmental and Occupational Medicine 2025;42(6):724-731
Background Hypertension is one of the chronic diseases with the highest prevalence in China, and a history of hypertension may potentially exacerbate hearing loss. Investigating the association between long-term blood pressure trends and hearing thresholds could contribute to hearing protection efforts for occupationally noise-exposed populations. Objective By investigating hearing thresholds and blood pressure levels among occupationally noise-exposed workers in an urban rail transit enterprise, and conducting a comprehensive analysis of the association between long-term blood pressure changes and hearing thresholds, to provide data references for health management strategies targeting occupationally noise-exposed workers. Methods Workers exposed to occupational noise at a rail transit enterprise were enrolled as study subjects and underwent pure-tone audiometry. Group-based trajectory modeling was employed to identify blood pressure trajectories. Categorical data were compared using chi-square tests, while normally distributed continuous variables were analyzed via t-tests and analysis of variance (ANOVA). Generalized linear mixed models (GLMMs) were subsequently applied toexamine associations between these trajectory groups and high-frequency hearing thresholds. Results Among 2 002 occupationally noise-exposed workers, the median (P25, P75) age was 32 (28, 35) years, with a median (P25, P75) working tenure of 7 (3, 10) years. In 2019, the positive hypertension rate was 9.04%, with a mean systolic blood pressure (SBP) of (122.97±11.60) mmHg and a mean diastolic blood pressure (DBP) of (76.37±9.02) mmHg. The hearing loss prevalence was 10.1%, showing bilateral high-frequency average hearing thresholds of (17.18±8.71) dB and speech-frequency average thresholds of (13.79±3.46) dB. Three distinct trajectory groups were identified for both SBP and DBP. Compared with other trajectory groups, the high-stable DBP group exhibited significantly higher hearing loss prevalence (χ2=6.34, P=0.042) and elevated high-frequency hearing thresholds (all Ps<0.05). Specifically, within the 30-39 age subgroup, the moderate-stable DBP group demonstrated 1.96 dB lower high-frequency thresholds than the high-stable group [β(95%CI): −1.96 (−3.61, −0.32), P=0.020]. Conclusion Among occupationally noise-exposed workers in a municipal rail transit enterprise, DBP trajectories demonstrated a positive association with high-frequency hearing thresholds. Notably, in young and middle-aged occupationally noise-exposed populations, DBP may exert a more critical influence than SBP on the progression of hearing loss.
9.Investigation of Effect of Different Drying Conditions on Appearance Characteristics and Internal Indicators of Pinelliae Rhizoma Based on Standardization
Suqing LIU ; Xueli ZHANG ; Jing ZHANG ; Cong YANG ; Changfu YANG ; Jun YU ; Bingpeng ZHENG ; Huiwu LI ; Yanhua JIANG ; Chang LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):208-215
ObjectiveTo explore the effect of different drying conditions on the appearance and intrinsic quality indicators of Pinelliae Rhizoma for screening suitable drying conditions, so as to provide reference for its standardized production and quality evaluation. MethodsDifferent dried samples of Pinelliae Rhizoma were prepared by lime-assisted sweating method and intermittent drying method. Visual analysis was employed to measure the color brightness values(L*) of the surface, cross-section and powder of the samples, texture analyzer was used to determine the hardness of the samples under different drying conditions. The total starch content was calculated by measuring the contents of amylose and amylopectin in the samples with ultraviolet-visible spectroscopy. High performance liquid chromatography(HPLC) was used to determine the contents of seven nucleoside components(uracil, hypoxanthine, uridine, inosine, guanosine, β-thymidine and adenosine) in the samples. Pearson correlation analysis was conducted to explore the correlation between the external characteristics and intrinsic indicators of the different dried samples. Principal component analysis(PCA) was used to comprehensively rank the data of various indicators, and partial least squares-discriminant analysis(PLS-DA) was used to screen differential components with variable importance in the projection(VIP) value>1. Furthermore, the difference between the optimal drying condition for Pinelliae Rhizoma and the traditional sun-drying method was explored by independent samples t-test. ResultsWith the increase of temperature, the color of the intermittently dried samples gradually deepened, while their hardness gradually decreased. Concurrently, the contents of extract, total starch, uridine and adenosine exhibited an upward trend, whereas the contents of uracil, hypoxanthine and inosine displayed a downward trajectory. Compared with the intermittent drying group, the content of extract in the samples subjected to lime-assisted sweating increased. With the increase of lime dose, the hardness and the total content of nucleoside components in the samples showed a downward trend, while the total starch content showed an upward trend. Correlation analysis showed that the comprehensive score of L* was negatively correlated with the contents of uracil, hypoxanthine and inosine, and positively correlated with the contents of uridine, guanosine and adenosine. Hardness was negatively correlated with adenosine content, and positively correlated with the contents of inosine, uracil and hypoxanthine. Through comprehensive consideration and comprehensive score of principal components, the method of 5% lime-mixed sweating for 6 days emerged as the top-ranking approach. Except for the extract, the results of independent samples t-test showed that there was no significant difference between the 5% lime-mixed sweating for 6 days and the traditional sun-drying in terms of other content indicators. ConclusionThe whiteness and firmness of Pinelliae Rhizoma exhibit significant correlations with its chemical composition, while uridine, uracil, guanosine, adenosine and inosine are the key constituents responsible for the quality difference of Pinelliae Rhizoma under different drying conditions. The lime-assisted sweating method optimized in this study can be proposed as a viable alternative to the traditional sun-drying method. This method not only ensures the quality of the medicinal material but also effectively reduces the drying time and prevents mold contamination, which provides a valuable reference for the standardization of drying conditions and the establishment of quality evaluation criteria for Pinelliae Rhizoma.
10.Optimized lipid nanoparticles enable effective CRISPR/Cas9-mediated gene editing in dendritic cells for enhanced immunotherapy.
Kuirong MAO ; Huizhu TAN ; Xiuxiu CONG ; Ji LIU ; Yanbao XIN ; Jialiang WANG ; Meng GUAN ; Jiaxuan LI ; Ge ZHU ; Xiandi MENG ; Guojiao LIN ; Haorui WANG ; Jing HAN ; Ming WANG ; Yong-Guang YANG ; Tianmeng SUN
Acta Pharmaceutica Sinica B 2025;15(1):642-656
Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLANmCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

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