1.Remodeling tumor immunosuppressive microenvironment through dual activation of immunogenic panoptosis and ferroptosis by H2S-amplified nanoformulation to enhance cancer immunotherapy.
Yingli LUO ; Maoyuan LINGHU ; Xianyu LUO ; Dongdong LI ; Jilong WANG ; Shaojun PENG ; Yinchu MA
Acta Pharmaceutica Sinica B 2025;15(3):1242-1254
The deficiency in immunogenicity and the presence of immunosuppression within the tumor microenvironment significantly hindered the efficacy of immunotherapy. Consequently, a nanoformulation containing metal sulfide of FeS and GSDMD plasmid (NPFeS/GD) had been developed to effectively augment antitumor immune responses through dual activation of immunogenic PANoptosis and ferroptosis, as well as reprogramming immunosuppressive effects via H2S amplification. The bioactive NPFeS/GD exhibited controlled release of GSDMD plasmid, H2S, and Fe2+ in response to the tumor microenvironment. Fe2+, H2S, and the expression of GSDMD protein could effectively elicit highly immunogenic PANoptosis and ferroptosis. Furthermore, releasing H2S could mitigate the overexpression of indoleamine 2,3-dioxygenase1 (IDO1) induced by immunogenic PANoptotic and ferroptotic cell death and disrupt the activity of IDO1. Consequently, NPFeS/GD effectively triggered the antitumor innate and adaptive immune responses through induction of PANoptotic and ferroptotic cell death and reshaped the tumor immunosuppressive microenvironment to enhance antitumor immunotherapy for metastasis inhibition. This study unveiled the significant potential of immunogenic PANoptosis and ferroptosis in H2S gas therapy for enhancing tumor immunotherapy, offering novel insights and ideas for the rational design of nanomedicine to enhance tumor immunogenicity while reprogramming the tumor immunosuppressive microenvironment.
2.Investigation of the Mechanism of Atractylodes Ⅰ Inhibiting Colorectal Cancer via the AKT/S6K1 Signaling Pathway
Wei TIAN ; Qiuying YAN ; Jingwen LUO ; Qibiao WU ; Weixing SHEN ; Haibo CHENG ; Changliang XU ; Dongdong SUN
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(8):1037-1046
OBJECTIVE To investigate the pharmacological efficacy and mechanism of action of Atractylenolide Ⅰ(Atr-Ⅰ)in inhibiting colorectal cancer.METHODS Among three active compounds of Atractylodes macrocephala,Atr-Ⅰ exhibited the highest anti-tumor potency by MTT assay.The optimal concentration of Atr-Ⅰ was determined.The effect of Atr-Ⅰ on LoVo cell prolifera-tion was assessed via a clonogenic assay,while its impact on apoptosis and cell cycle progression was evaluated using flow cytometry.The influence of Atr-Ⅰ on the migration and invasion of LoVo cell line was examined through wound healing and Transwell migration assays.Western blot analysis was performed to explore the effects and mechanisms of Atr-Ⅰ on proteins associated with mi-gration,proliferation,and epithelial-mesenchymal transition(EMT)in LoVo cells.The CT26 mouse subcutaneous tumor model was established,and histopathological analysis was conducted using hematoxylin-eosin(HE)staining.Western blot was also used to assess the effects of Atr-Ⅰ on EMT-related proteins in mouse tissues to elucidate underlying mechanisms.RESULTS Atr-Ⅰ significantly reduced colorectal cancer cell viability,with statistically significant differences between treatment and control groups(P<0.05,P<0.01).Atr-Ⅰ induced apoptosis in LoVo cells,with the treatment group showing significant differences compared to the control(P<0.05,P<0.01).Cell cycle analysis revealed that Atr-Ⅰ exerted anti-tumor effects by inducing G2/M phase arrest,with increased G2 phase cell numbers in the LoVo treatment group compared to the control(P<0.05).Wound healing and Transwell migration assays confirmed that Atr-Ⅰ significantly inhibited tumor cell migration and invasion(P<0.05,P<0.01).Western blot analysis demonstra-ted that Atr-Ⅰ specifically suppressed the expression of c-Myc and Bcl-2(P<0.05),as well as cell cycle-related proteins CDK1,Cyclin B1,and Cyclin D1(P<0.05),and angiogenesis-related proteins VEGF and MMP9(P<0.05).Additionally,Atr-Ⅰ down-regulated EMT-related protein N-cadherin and upregulated E-cadherin expression(P<0.05).It also reduced the expression of p-AKT and p-S6K1(P<0.05).CONCLUSION Atr-Ⅰ exhibits potent anti-tumor effects against colorectal cancer,potentially through modulation of the AKT/S6K1 signaling pathway.
3.Investigation of the Mechanism of Atractylodes Ⅰ Inhibiting Colorectal Cancer via the AKT/S6K1 Signaling Pathway
Wei TIAN ; Qiuying YAN ; Jingwen LUO ; Qibiao WU ; Weixing SHEN ; Haibo CHENG ; Changliang XU ; Dongdong SUN
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(8):1037-1046
OBJECTIVE To investigate the pharmacological efficacy and mechanism of action of Atractylenolide Ⅰ(Atr-Ⅰ)in inhibiting colorectal cancer.METHODS Among three active compounds of Atractylodes macrocephala,Atr-Ⅰ exhibited the highest anti-tumor potency by MTT assay.The optimal concentration of Atr-Ⅰ was determined.The effect of Atr-Ⅰ on LoVo cell prolifera-tion was assessed via a clonogenic assay,while its impact on apoptosis and cell cycle progression was evaluated using flow cytometry.The influence of Atr-Ⅰ on the migration and invasion of LoVo cell line was examined through wound healing and Transwell migration assays.Western blot analysis was performed to explore the effects and mechanisms of Atr-Ⅰ on proteins associated with mi-gration,proliferation,and epithelial-mesenchymal transition(EMT)in LoVo cells.The CT26 mouse subcutaneous tumor model was established,and histopathological analysis was conducted using hematoxylin-eosin(HE)staining.Western blot was also used to assess the effects of Atr-Ⅰ on EMT-related proteins in mouse tissues to elucidate underlying mechanisms.RESULTS Atr-Ⅰ significantly reduced colorectal cancer cell viability,with statistically significant differences between treatment and control groups(P<0.05,P<0.01).Atr-Ⅰ induced apoptosis in LoVo cells,with the treatment group showing significant differences compared to the control(P<0.05,P<0.01).Cell cycle analysis revealed that Atr-Ⅰ exerted anti-tumor effects by inducing G2/M phase arrest,with increased G2 phase cell numbers in the LoVo treatment group compared to the control(P<0.05).Wound healing and Transwell migration assays confirmed that Atr-Ⅰ significantly inhibited tumor cell migration and invasion(P<0.05,P<0.01).Western blot analysis demonstra-ted that Atr-Ⅰ specifically suppressed the expression of c-Myc and Bcl-2(P<0.05),as well as cell cycle-related proteins CDK1,Cyclin B1,and Cyclin D1(P<0.05),and angiogenesis-related proteins VEGF and MMP9(P<0.05).Additionally,Atr-Ⅰ down-regulated EMT-related protein N-cadherin and upregulated E-cadherin expression(P<0.05).It also reduced the expression of p-AKT and p-S6K1(P<0.05).CONCLUSION Atr-Ⅰ exhibits potent anti-tumor effects against colorectal cancer,potentially through modulation of the AKT/S6K1 signaling pathway.
4.Expert consensus on odontogenic maxillary sinusitis multi-disciplinary treatment
Lin JIANG ; Wang CHENGSHUO ; Wang XIANGDONG ; Chen FAMING ; Zhang WEI ; Sun HONGCHEN ; Yan FUHUA ; Pan YAPING ; Zhu DONGDONG ; Yang QINTAI ; Ge SHAOHUA ; Sun YAO ; Wang KUIJI ; Zhang YUAN ; Xian MU ; Zheng MING ; Mo ANCHUN ; Xu XIN ; Wang HANGUO ; Zhou XUEDONG ; Zhang LUO
International Journal of Oral Science 2024;16(1):1-14
Odontogenic maxillary sinusitis(OMS)is a subtype of maxillary sinusitis(MS).It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion.Due to the lack of unique clinical features,OMS is difficult to distinguish from other types of rhinosinusitis.Besides,the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis.Its current diagnosis and treatment are thus facing great difficulties.The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS.However,this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality.Based on systematically reviewed literature and practical experiences of expert members,our consensus focuses on characteristics,symptoms,classification and diagnosis of OMS,and further put forward multi-disciplinary treatment decisions for OMS,as well as the common treatment complications and relative managements.This consensus aims to increase attention to OMS,and optimize the clinical diagnosis and decision-making of OMS,which finally provides evidence-based options for OMS clinical management.
5.Diagnostic value of Treponema pallidum antibody index detected by electrochemiluminescence immunoassay in neurosyphilis
Sirui WU ; Yuanfang WANG ; Lan LUO ; Jielun DENG ; Dongdong LI ; Yi XIE
Chinese Journal of Microbiology and Immunology 2024;44(6):545-552
Objective:To evaluate the value of Treponema pallidum ( Tp)-specific antibody index in the diagnosis, staging, and typing of neurosyphilis (NS). Methods:Fifty patients diagnosed with NS at the West China Hospital of Sichuan University from March 2020 to December 2022 were recruited as the experimental group, and 50 non-NS syphilis patients were enrolled during the same period as the control group. Cerebrospinal fluid (CSF) and matched serum samples along with clinical data were collected. Clinical and Laboratory Standards Institute (CLSI) EP06-Ed2 file was used to analyze the linear range of electrochemiluminescence immunoassay for Tp-specific antibody detection, and the Tp antibody index was calculate for all subjects. The correlation of Tp antibody index, IgG index, IgG synthesis rate, and albumin quotient with other clinical indicators was evaluated by the coefficient of correlation, and the diagnostic efficacy of these indicators in NS was analyzed using the receiver operating characteristic (ROC) curve. Results:All the deviations from linearity of electrochemiluminescence immunoassay for detecting Tp antibodies in serum and CSF samples were within the allowable deviation from linearity. Compared with the non-NS group, the NS group showed a significant increase in the Tp antibody index ( P<0.05), with no significant differences observed among the groups of different subtypes, severity, or receiving treatment or not ( P>0.05). Tp antibody index, IgG index, and IgG synthesis rate were positively correlated with serum Tp antibody, CSF Tp antibody, trace protein, and nucleated cell count ( P<0.05). Taking 14.99 as the cut-off value for NS diagnosis, the diagnostic sensitivity of Tp antibody index was 74.0% (95%CI: 60.5%-84.1%), and the specificity was 94.0% (95%CI: 83.8%-98.4%), with the area under the ROC curve of 0.897, which was larger than that of albumin quotient, IgG index, and IgG synthesis rate. Conclusions:This study finds a significant increase in the Tp antibody index in NS patients with good diagnostic sensitivity and specificity, providing reference for the diagnosis of NS.
6.Characterization of natural peptides in Pheretima by integrating proteogenomics and label-free peptidomics
Xiaoxiao LUO ; Qirui BI ; Dongdong HUANG ; Yun LI ; Changliang YAO ; Jianqing ZHANG ; Wenlong WEI ; Jiayuan LI ; Zhenwei LI ; Jingxian ZHANG ; Shen JI ; Yurong WANG ; De-An GUO
Journal of Pharmaceutical Analysis 2023;13(9):1070-1079
Pheretima,also called"earthworms",is a well-known animal-derived traditional Chinese medicine that is extensively used in over 50 Chinese patent medicines(CPMs)in Chinese Pharmacopoeia(2020 edi-tion).However,its zoological origin is unclear,both in the herbal market and CPMs.In this study,a strategy for integrating in-house annotated protein databases constructed from close evolutionary relationship-sourced RNA sequencing data from public archival resources and various sequencing al-gorithms(restricted search,open search,and de novo)was developed to characterize the phenotype of natural peptides of three major commercial species of Pheretima,including Pheretima aspergillum(PA),Pheretima vulgaris(PV),and Metaphire magna(MM).We identified 10,477 natural peptides in the PA,7,451 in PV,and 5,896 in MM samples.Five specific signature peptides were screened and then validated using synthetic peptides;these demonstrated robust specificity for the authentication of PA,PV,and MM.Finally,all marker peptides were successfully applied to identify the zoological origins of Brain Heart capsules and Xiaohuoluo pills,revealing the inconsistent Pheretima species used in these CPMs.In conclusion,our integrated strategy could be used for the in-depth characterization of natural peptides of other animal-derived traditional Chinese medicines,especially non-model species with poorly annotated protein databases.
7.Intervention effect of health management with integrated traditional Chinese and western medicine on risk factors in middle-aged and elderly high-risk population of stroke in the community
Yiqian ZHU ; Jianfeng LUO ; Dongdong CHEN ; Min ZHANG ; Hua YANG
Chinese Journal of General Practitioners 2022;21(9):872-876
From January to July 2017, 872 high-risk middle-aged and elderly patients of stroke who visited general practice clinics in 10 community health service centers in Shanghai were enrolled in the study. Cluster randomization was used to select 427 patients from 5 community centers as the intervention group, and 445 patients from other 5 community centers as the control group. The intervention group received health education and traditional Chinese exercise training on the basis of conventional treatment;while the control group received conventional treatment only. After 12 months of intervention physical examinations and related laboratory tests were performed,and the risk factors were compared between two groups before and after the intervention. The results showed that there were significant differences in the systolic and diastolic blood pressure,blood urea nitrogen (BUN),creatinine (Cr) and homocysteine before and after the intervention in both groups (all P<0.05); and compared the control group the improvement of above indicators was more marked in the intervention group. There was no significant difference in cholesterol, triglyceride, and low-density lipoprotein between the two groups before and after the intervention ( P>0.05). The health management with integrated traditional Chinese and western medicine can effectively control some risk factors of stroke for middle-aged and elderly people, which is beneficial for the prevention and control of stroke in the community.
8.Construction of clinical scoring system for predicting microvascular invasion in preoperative hepatocellular carcinoma
Yongzhu HE ; Kun HE ; Ruiqin HUANG ; Peng PENG ; Dongdong HUANG ; Jiahou RUAN ; Zeliang WANG ; Qijie LUO ; Shaowei YE ; Zemin HU
Chinese Journal of General Surgery 2021;36(2):114-117
Objective:To analyze the risk factors of hepatocellular carcinoma microvascular invasion (MVI) and to construct a preoperative prediction clinical scoring system.Methods:A retrospective analysis was made on 113 patients with hepatocellular carcinoma undergoing hepatectomy at Zhongshan Hospital from March 2018 to Jun 2019.Postoperative pathology confirmed 35 cases with microvascular invasion.Results:The multivariate logistic regression model showed that the maximum tumor diameter( OR: 1.028, 95% CI: 1.001-1.005), the smoothness of the capsule edge( OR: 0.208, 95% CI: 0.062-0.699), the positive circulating tumor cells (CTC)( OR: 3.728, 95% CI: 1.029-13.501) and abnormal prothrombin(PIVKA-Ⅱ)( OR: 1.001, 95% CI: 1.000-1.002) were risk factors for MVI. The area, sensitivity and specificity of the clinical score constructed by assigning 1 point to each risk factor were 0.906, 74.29% and 92.31%, respectively. Clinical scores of 0, 1, 2, 3, and 4 predict MVI positive rates of 0 (0/26), 9.09% (3/33), 28.57% (6/21), 77.78% (14/ 18), 85.71% (12/14). Conclusions:Tumor maximum diameter>62 mm, PIVKA-Ⅱ>115 mAU/ml, unsmooth tumor capsule and CTC in peripheral blood are independent high risk factors in patients with MVI.
9.Analysis on application of nuclear technology and radiation workers′ occupational health management in non-medical institutions in Huai′an City
Binbin HUO ; Zhiyong XU ; Dongdong HE ; Yinghua WANG ; Huan YANG ; Gongcheng LUO
Chinese Journal of Radiological Health 2021;30(1):10-13
Objective To investigate and analyze the current situation of nuclear technology utilization and radiation workers' occupational health management in non-medical institutions in Huai'an City, and to strengthen the prevention and control of occupational radiation diseases. Methods 37 non-medical institutions of nuclear technology utilization in Huai'an City were surveyed by questionnaire, including radioisotope and radiation apparatus, personal dose monitoring of radiation workers, implementation of occupational health examination, protective equipment, etc. Results The industry covers manufacturing industry, transportation, warehousing and postal industry, scientific research and technical service industry, residential service, repair and other service industries, 0 class I radiation device, 15 class II radiation devices, 67 class III radiation devices; 0 class I and II radiation sources, 1 class III radiation device, 16 class IV radiation sources, 51 class V radiation sources, 1 unsealed radioactive material Class B workplace; 493 radiation workers, 90.5% with certificates, 85.4% with personal dose monitoring rate, rate of 37.8% with radiation protection monitoring equipment, and 68.0% with occupational health examination rate. It has 13 institutions equipped with personal protective equipment, 23 with dose alarming devices and 14 with radiation protection monitors. 30 radiation workplace tests have been carried out in the past two years. Conclusion The occupational health management of radiation workers in non-medical institutions is weak. At present, the responsibility of occupational health supervision has been assigned to the health department. Therefore, the health administrative department should strengthen the supervision of non-medical nuclear technology utilization institutions and improve the emergency mechanism of radiation emergencies in Huai'an city.
10.Chinese Society of Allergy and Chinese Society of Otorhinolaryngology-Head and Neck Surgery Guideline for Chronic Rhinosinusitis
Zheng LIU ; Jianjun CHEN ; Lei CHENG ; Huabin LI ; Shixi LIU ; Hongfei LOU ; Jianbo SHI ; Ying SUN ; Dehui WANG ; Chengshuo WANG ; Xiangdong WANG ; Yongxiang WEI ; Weiping WEN ; Pingchang YANG ; Qintai YANG ; Gehua ZHANG ; Yuan ZHANG ; Changqing ZHAO ; Dongdong ZHU ; Li ZHU ; Fenghong CHEN ; Yi DONG ; Qingling FU ; Jingyun LI ; Yanqing LI ; Chengyao LIU ; Feng LIU ; Meiping LU ; Yifan MENG ; Jichao SHA ; Wenyu SHE ; Lili SHI ; Kuiji WANG ; Jinmei XUE ; Luoying YANG ; Min YIN ; Lichuan ZHANG ; Ming ZHENG ; Bing ZHOU ; Luo ZHANG
Allergy, Asthma & Immunology Research 2020;12(2):176-237
The current document is based on a consensus reached by a panel of experts from the Chinese Society of Allergy and the Chinese Society of Otorhinolaryngology-Head and Neck Surgery, Rhinology Group. Chronic rhinosinusitis (CRS) affects approximately 8% of Chinese adults. The inflammatory and remodeling mechanisms of CRS in the Chinese population differ from those observed in the populations of European descent. Recently, precision medicine has been used to treat inflammation by targeting key biomarkers that are involved in the process. However, there are no CRS guidelines or a consensus available from China that can be shared with the international academia. The guidelines presented in this paper cover the epidemiology, economic burden, genetics and epigenetics, mechanisms, phenotypes and endotypes, diagnosis and differential diagnosis, management, and the current status of CRS in China. These guidelines—with a focus on China—will improve the abilities of clinical and medical staff during the treatment of CRS. Additionally, they will help international agencies in improving the verification of CRS endotypes, mapping of eosinophilic shifts, the identification of suitable biomarkers for endotyping, and predicting responses to therapies. In conclusion, these guidelines will help select therapies, such as pharmacotherapy, surgical approaches and innovative biotherapeutics, which are tailored to each of the individual CRS endotypes.
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Asian Continental Ancestry Group
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International Agencies
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Precision Medicine

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