1.In situ tumor cell engineering reverses immune escape to enhance immunotherapy effect.
Shujun LIU ; Shijun YUAN ; Meichen LIU ; Jinhu LIU ; Shunli FU ; Tong GAO ; Shuang LIANG ; Xinyan HUANG ; Xinke ZHANG ; Yongjun LIU ; Zipeng ZHANG ; Na ZHANG
Acta Pharmaceutica Sinica B 2025;15(1):627-641
The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL+ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL+ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.
2.Targeted inhibition of macrophage STING signaling alleviates inflammatory injury and ventricular remodeling in acute myocardial infarction.
Huan YAO ; Qingman HE ; Shujun WEI ; Li XIANG ; Yuanyuan LUO ; Cong HUANG ; Weiwei LIU ; Chuan ZHENG ; Xueping LI ; Yongxiang GAO
Acta Pharmaceutica Sinica B 2025;15(8):4030-4046
Mitochondrial DNA (mtDNA) acts as a damage-associated molecular pattern to activate the stimulator of interferon genes (STING) signaling in macrophages, promoting tissue inflammation. However, its role in acute myocardial infarction (AMI) remains unclear. Macrophage-specific Sting1 knockout mice were used to validate STING's pathological role in AMI. Cardiac and liver mtDNA were used to activate macrophages in co-culture systems with cardiomyocytes to assess fibrosis and hypertrophy. Panaxatriol saponin (PTS) was tested for its ability to block mtDNA-driven macrophage activation and subsequent cardiomyocyte damage. STING-PTS binding ability was analyzed. AMI rats received PTS to evaluate its effects on myocardial inflammation and ventricular remodeling. In vivo, macrophage-specific Sting1 knockout reduced myocardial inflammation and injury after AMI. In vitro, mtDNA-activated macrophages induced cardiomyocyte fibrosis and hypertrophy through STING signaling. PTS suppressed mtDNA-driven macrophage activation by directly binding STING, thereby blocking inflammatory cascades. In AMI rats, PTS treatment attenuated acute inflammation and reversed ventricular remodeling. These findings establish the mtDNA-STING axis in macrophages as a critical driver of post-AMI inflammation and identify pharmacological STING inhibition with PTS as a promising therapeutic strategy. The study bridges genetic validation with translational applications, highlighting macrophage STING as a novel target for ischemic heart disease management.
3.Natural vaccine adjuvants from traditional Chinese medicines: Mechanisms to applications.
Xiaoyuan FAN ; Fengxiang LIU ; Fei SUN ; Yiyang WANG ; Wenwen SHEN ; Shujun WANG ; Jin SUN ; Kaiyuan WANG
Acta Pharmaceutica Sinica B 2025;15(9):4644-4672
With the rapid advancement of vaccines, the research and application of vaccine adjuvants have garnered significant attention. Despite the development of numerous vaccine adjuvants, their applications in human vaccines remain limited due to either insufficient efficacy or severe side effects. Consequently, there is growing interest in developing bioactive compounds derived from traditional Chinese medicines (TCMs) as vaccine adjuvants, owing to their natural biocompatibility, diversity, and safety. Here, we systematically review the current application status and potential value of TCM-based bioactive compounds in vaccine adjuvants. Firstly, we elaborate on the types and characteristics of active ingredients, such as polysaccharides, saponins, flavonoids, acids, and alkaloids. The mechanisms by which these compounds function as vaccine adjuvants are then discussed, including their roles in enhancing humoral immunity, cellular immunity, and relieving the immune suppression in the microenvironment. Additionally, we summarize the current strategies for structural modification and platform optimization to adapt to different application scenarios. Finally, we offer insights into the future development directions for these potential adjuvants, highlighting research priorities, technical approaches, and application prospects. In conclusion, natural vaccine adjuvants derived from TCMs present broad application prospects and hold promise for future vaccine development.
4.A multi-scale supervision and residual feedback optimization algorithm for improving optic chiasm and optic nerve segmentation accuracy in nasopharyngeal carcinoma CT images.
Jinyu LIU ; Shujun LIANG ; Yu ZHANG
Journal of Southern Medical University 2025;45(3):632-642
OBJECTIVES:
We propose a novel deep learning segmentation algorithm (DSRF) based on multi-scale supervision and residual feedback strategy for precise segmentation of the optic chiasm and optic nerves in CT images of nasopharyngeal carcinoma (NPC) patients.
METHODS:
We collected 212 NPC CT images and their ground truth labels from SegRap2023, StructSeg2019 and HaN-Seg2023 datasets. Based on a hybrid pooling strategy, we designed a decoder (HPS) to reduce small organ feature loss during pooling in convolutional neural networks. This decoder uses adaptive and average pooling to refine high-level semantic features, which are integrated with primary semantic features to enable network learning of finer feature details. We employed multi-scale deep supervision layers to learn rich multi-scale and multi-level semantic features under deep supervision, thereby enhancing boundary identification of the optic chiasm and optic nerves. A residual feedback module that enables multiple iterations of the network was designed for contrast enhancement of the optic chiasm and optic nerves in CT images by utilizing information from fuzzy boundaries and easily confused regions to iteratively refine segmentation results under supervision. The entire segmentation framework was optimized with the loss from each iteration to enhance segmentation accuracy and boundary clarity. Ablation experiments and comparative experiments were conducted to evaluate the effectiveness of each component and the performance of the proposed model.
RESULTS:
The DSRF algorithm could effectively enhance feature representation of small organs to achieve accurate segmentation of the optic chiasm and optic nerves with an average DSC of 0.837 and an ASSD of 0.351. Ablation experiments further verified the contributions of each component in the DSRF method.
CONCLUSIONS
The proposed deep learning segmentation algorithm can effectively enhance feature representation to achieve accurate segmentation of the optic chiasm and optic nerves in CT images of NPC.
Humans
;
Tomography, X-Ray Computed/methods*
;
Optic Chiasm/diagnostic imaging*
;
Optic Nerve/diagnostic imaging*
;
Algorithms
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Nasopharyngeal Carcinoma
;
Deep Learning
;
Nasopharyngeal Neoplasms/diagnostic imaging*
;
Neural Networks, Computer
;
Image Processing, Computer-Assisted/methods*
5.Comparative analysis between circumareolar small incision and three-port endoscopic surgery for the treatment of Simon Ⅱ gynecomastia
Hui LIU ; Sixuan LIU ; Junyan HU ; Jie ZHENG ; Shujun JIANG ; Feng WANG ; Hangjun GONG ; Yajie JI ; Jiandong WANG
Journal of Surgery Concepts & Practice 2025;30(4):310-315
Objective To compare the clinical efficacy between liposuction combined with circumareolar small incision and three-port endoscopic surgery for the treatment of Simon Ⅱ gynecomastia (GYN). Methods Comparative case data of 120 patients with GYN were retrospectively analyzed, 61 patients in the open group underwent circumareolar small incision mastectomy after liposuction, and 59 patients in the endoscopic group underwent three-port endoscopic mastectomy after liposuction. The two groups were compared in terms of surgery-related indexes, occurrence of postoperative complications and patient satisfaction. Results The unilateral operation time of the open group was shorter than that of the endoscopic group, the unilateral gland resection weight in the open group was more than that in the endoscopic group, the hospitalization cost of the open group was less than that of the endoscopic group (all P<0.01). There was no significant difference in unilateral liposuction volume, drainage volume on the first postoperative day, and time to drain removal between the two groups (P>0.05). The incidence of complications in the open group and the endoscopic group were 8.2% and 13.6% respectively, and there was no significant difference between the two groups (P>0.05). The difference in the overall satisfaction scores between the two groups was not statistically significant (P>0.05). Conclusions Liposuction combined with circumareolar small incision or three-port endoscopic surgery both has good cosmetic effects in the treatment of Simon Ⅱ GYN. The operation with circumareolar small incision is simple, has a shorter operation time, costs less, and does not require special equipment, which is suitable for promotion and application in medical institutions.
6.Factors affecting the prevalence of hyperuricemia in an island troop
Yongguang FANG ; Shujun SUN ; Chong TANG ; Chunyu LIU ; Qian XU ; Ying LIANG ; Huihui GUO ; Peng YANG ; Nannan CHEN
Journal of Navy Medicine 2025;46(6):574-578
Objective To analyze the factors affecting the prevalence of hyperuricemia(HUA)in an island troop.Methods A total of 1 113 soldiers stationed on an island from December 2021 to December 2022 were selected as research objects by cluster sampling.Their lifestyle and health information were collected.Physical examination and laboratory detection were conducted.Multivariate logistic regression was used to analyze the influencing factors of HUA.Results The prevalence rate of HUA was 21.02%(234/1 113).There were significant differences in the body mass index(BMI),waist-to-hip ratio,triglyceride,alanine aminotransferase,and creatinine between the soldiers with hyperuricemia and the soldiers with normal blood uric acid(P<0.05).Multivariate logistic regression analysis showed that BMI≥24(OR=1.49,95%CI:1.09-2.05),abnormal liver function(OR=2.26,95%CI:1.31-3.92),and dyslipidemia(OR=1.46,95%CI:1.01-2.12)were positively correlated with hyperuricemia;age>30 years old(OR=0.59,95%CI:0.37-0.93)and exercise time>1 h per week(OR=0.46,95%CI:0.22-0.97)were negatively correlated with HUA.Conclusion The prevalence rate of hyperuricemia is at a high level in an island troop.BMI≥24,age≤30 years old,exercise time≤1 h per week,abnormal liver function,and dyslipidemia are the risk factors for HUA.Prevention and control measures should be taken as early as possible for the soldiers with these risk factors.
7.Monitoring results of SARS-CoV-2 in urban sewage in Chongqing city in 2023
Gaomin LIU ; Jiqin ZHENG ; Yao CHEN ; Wenge TANG ; Zhifeng LI ; Shujun NIE
Chinese Journal of Experimental and Clinical Virology 2024;38(3):294-298
Objective:To offset the shortage of traditional large-scale population surveillance and provide early-warning signals in the early stage of the outbreak of COVID-19, people in Chongqing had carried out severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monitoring since 2023.Methods:After COVID-19 was managed with measures against Class B infectious diseases, we selected five sewage treatment plants with automatic sample collection facilities in four districts of the main city. Two samples of sewage from each sewage treatment plant were collected every week. Then SARS-CoV-2 from these samples was concentrated by aluminum hydroxide adsorption-precipitation, detected and analyzed by multiple real-time fluorescent RT-PCR.Results:From January 16 to December 31 of 2023, a total of 496 sewage samples were monitored, of which 285 samples were positive by SARS-CoV-2 nucleic acid assay, with a total detection rate of 57.46%. The detection rate of SARS-CoV-2 in weeks 3-5, 18-21 and 40-47 was 100.00%. The daily mean nucleic acid concentration of SARS-CoV-2 in sewage peaked in the 18th week, and then began to decline, entering a low level and fluctuated in epidemic period. The variable trend of daily mean concentration of SARS-CoV-2 nucleic acid was basically consistent with daily number of SARS-CoV-2 infected patients or SARS-CoV-2 positive rate in fever clinic counted by infectious disease monitoring system.Conclusions:The detection rate of SARS-CoV-2 in sewage of Chongqing is relatively high, especially in April to May, and sewage monitoring can indirectly reflect the status of COVID-19 infection.
8.Research on the Diagnostic Criteria for Dampness Syndrome Based on Consensus Method
Qian LI ; Wenzhen WU ; Zhixuan AI ; Lilei ZHOU ; Shujun LIU ; Xiaobo YANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(6):1660-1667
Objective To establish diagnostic criteria for dampness syndrome through scientific and normative research methods.Methods The basis for syndrome differentiation of dampness syndrome was comprehensively integrated through literature research and structured tools,and in-depth investigation was carried out on the connotation and extension of dampness syndrome,judgment basis and criteria construction through questionnaire surveys and consensus conference method.Results Thirty-six items for syndrome differentiation of dampness syndrome were obtained through literature research.Through the questionnaire surveys,some experts suggested that the diagnosis mode of dampness syndrome should be in line with the clinical practice requirements.Accordingly,we were deep in thought about the key issue of"how to establish accurate diagnostic criteria".After in-depth investigation,we found that the dampness syndrome had specific and sensitive indicators.And 11 specific and 19 sensitive indicators were determined.Furthermore,according to the experts'suggestions,the specific indicators were classified into three categories based on dampness characteristics.Meanwhile,we investigated the diagnosis attributes of Chinese medicine syndromes and summarized them into four corresponding modes.Based on this,specificity mode and similarity/consistency mode should be adopted for diagnostic criteria for dampness syndrome.In addition,the judgment form in accord with the diagnostic attributes of dampness syndrome was determined.Conclusion This diagnostic criteria can provide a basis for the clinical diagnosis of dampness syndrome.Besides,this study explored the diagnostic attributes of Chinese medicine syndromes,which could provide reference for the development of other Chinese medicine syndrome criteria.
9.Therapeutic Effect of Bushen Huoxue Prescription on Diuretic Resistance in Chronic Heart Failure
Yuchen SUN ; Yan ZHANG ; Wenhao YIN ; Shujun ZHAO ; Muchen ZHANG ; Guohua LIU ; Yaqin WANG ; Yilin ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):123-129
ObjectiveTo investigate the effects of Bushen Huoxue prescription on the cardiac function, inflammation, and quality of life of the patients with chronic heart failure resistant to diuretics. MethodA total of 78 patients who met the inclusion criteria were randomized into observation and control groups (39 cases). Both groups received standardized treatment for diuretic resistance in accordance with the guidelines. In addition, the observation group received Bushen Huoxue prescription. The cardiac function indicators, total response rate regarding symptom alleviation, exercise endurance, urine volume, body mass, quality of life, and levels of inflammatory cytokines were compared between the two groups before and after treatment. ResultBefore treatment, the two groups of patients showed no significant differences in terms of 24 h urine volume, body mass, 6 minute walk test (6MWT), Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, left ventricular ejection fraction (LVEF), stroke volume (SV), and serum levels of interleukin-6 (IL-6), interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-α). After treatment, the observation group outperformed the control group in terms of the response rates regarding traditional Chinese medicine symptom scores and New York Heart Association (NYHA) grading of cardiac function (P<0.05). After treatment, the body mass, MLHFQ score, and IL-6, TNF-α, and NT-proBNP levels decreased in both groups (P<0.05, P<0.01), and the observation group showed more significant decreases than the control group (P<0.05, P<0.01). Both groups showed increases in 24-h urine volume, 6MWT, LVEF, SV, and IL-4 after treatment (P<0.05, P<0.01), and the observation group showed more significant increases than the control group (P<0.05, P<0.01). ConclusionThe combination of Bushen Huoxue prescription with standardized treatment is effective in ameliorating the clinical symptoms of the patients with chronic heart failure resistant to diuretics. Moreover, it alleviates diuretic resistance and improves the cardiac function without causing obvious adverse reactions.
10.Correlation analysis of serum POT1,TERT,8-OHdG,SOD expression levels and syndrome type of osteoporosis
Yannan LI ; Han TIAN ; Shuhua LIU ; Delong CHEN ; Shujun DU ; Ying LI
Modern Hospital 2024;24(3):486-489
Objective To analyze the distribution characteristics of traditional Chinese medicine(TCM)syndrome types in patients with osteoporosis and the distribution differences of clinical and serological indicators in TCM syndrome types.Meth-ods A total of 69 patients with osteoporosis were collected from the Third Affiliated Hospital of Guangzhou University of Chinese Medicine and Qifu Hospital Affiliated to Jinan University.The general information,bone mineral density T value,fasting periph-eral venous blood in the morning were collected.The expression of telomerase protective factor 1(POT1),telomerase reverse transcriptase(TERT),serum 8-hydroxy-2'-deoxyguanosine(8-OHdG)and superoxide dismutase 2(SOD2)were detected by ELISA.Finally,the above data were statistically analyzed.Results There were significant differences in body weight,height,bone mineral density,POT1,TERT,and 8-OHdG among the four syndromes(P<0.05).In terms of correlation,the relation-ship between bone mineral density and each parameter in different syndrome types was explored.The bone mineral density of qi stagnation and blood stasis syndrome was positively correlated with SOD2 value.There is a positive correlation between bone min-eral density and 8-OHdG in patients with Yin deficiency of liver and kidney.TERT was positively correlated with qi stagnation and blood stasis syndrome.Liver and kidney Yin deficiency syndrome was positively correlated with weight and bone mineral den-sity,and negatively correlated with TERT value.Weight was negatively correlated with qi and blood stasis syndrome.Conclusion In TCM syndrome differentiation of osteoporosis,there were statistical differences in weight,height,bone mineral density,ser-um POT1,TERT and 8-OHdG among Qi-stagnation and blood stasis,spleen-kidney Yang deficiency,liver-kidney Yin deficiency and Qi-blood-peace syndrome.In different syndrome types,serum SOD2 and 8-OHdG were the influencing factors of bone miner-al density.Serum TERT and 8-OHdG are the main factors affecting the dialectical classification of osteoporosis.

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