1.Protein palmitoylation: A potential therapeutic target in cardiovascular diseases.
Sijia ZHAO ; Yanyan YANG ; Hong LI ; Pin SUN ; Xiangqin HE ; Chao WANG ; Jingjing ZHANG ; Yu TIAN ; Tao YU ; Zhirong JIANG
Acta Pharmaceutica Sinica B 2025;15(10):5127-5144
Palmitoylation, an essential covalent attachment of a fatty acid (usually C16 palmitate) to cysteine residues within proteins, is crucial for regulating protein functionality and enzymatic activities. This lipid modification facilitates the anchoring of proteins to cellular membranes, dictating their subcellular distribution and influencing protein transport dynamics and intracellular positioning. Additionally, it plays a role in regulating protein degradation through the ubiquitin-proteasome system. Palmitoylation is implicated in the pathogenesis and progression of cardiovascular diseases by modulating substrates and prompting additional post-translational modifications, as well as by interacting with other molecular alterations. Moreover, an intervention strategy focusing on palmitoylation processes is anticipated to offer novel therapeutic avenues for cardiovascular pathologies and address extant challenges in clinical settings. This review consolidates current research on the role and importance of palmitoylation in cardiovascular diseases by exploring its regulatory functions, the catalyzing enzymes, and the involved substrates. It highlights recent discoveries connecting palmitoylation-targeted therapies to cardiovascular health and examines potential approaches and future challenges in cardiovascular treatment.
2.Long-term outcomes after infliximab discontinuation in patients with Crohn's disease: a single-center retrospective observational study
Danping ZHENG ; Yun QIU ; Yingfan ZHANG ; Baili CHEN ; Yao HE ; Zhirong ZENG ; Minhu CHEN
Chinese Journal of Inflammatory Bowel Diseases 2025;09(4):297-302
Objective:To assess the long-term risk of relapse in patients with Crohn's disease (CD) who discontinued infliximab (IFX) monoclonal antibody and to identify risk factors associated with relapse.Methods:A single-center retrospective observational study was conducted from February 2006 to October 2016. The study included CD patients who were treated with scheduled IFX infusions at the First Affiliated Hospital of Sun Yat-sen University and assessed in corticosteroid-free clinical remission at the time of withdrawal were included. The primary outcome was clinical relapse. We evaluated the risk of relapse using Kaplan-Meier method. Factors associated with time to relapse was identified using the multiple Cox proportional hazards regression analysis.Results:We included 97 eligible patients, and 75 (77.3%) experienced a relapse after a median follow-up time of 124 months. Among them, 45 patients (46.4%) relapsed within 3 years after IFX withdrawal. The 1-, 2-, 3-, 5-, and 10-year relapse-free survival were 79.4%, 59.8%, 52.6%, 42.0% and 22.6%, respectively. Risk factors for relapse included age ≤ 16 ( HR = 2.62, 95% CI: 1.30-5.31; P = 0.007) and failure to achieve biological remission (CRP > 3 mg/L, HR = 2.37, 95% CI: 1.29-4.36; P = 0.006) at drug withdrawal. Induction with biologics or systemic steroids were both effective (89%-100% relieved) in relapsers. Conclusions:Nearly half of CD patients relapsed within 3 years after discontinuation of IFX treatment. Early age of discontinuation and failure to achieve serum biological remission at the time of discontinuation are independent predictors of clinical relapse.
3.Value of using ultrasound features to improve the Ovarian-Adnexal Image Reporting and Data System Category 4 in the benign-malignant differential diagnosis of ovarian-adnexal masses
Lei WU ; Yingnan WU ; Jing ZHAO ; Liping GONG ; Shuang ZHANG ; Jiawei TIAN ; Zhirong HE ; Litao SUN
Chinese Journal of Ultrasonography 2025;34(3):232-238
Objective:To explore the value of ultrasound features modified version 2022 of the Ovarian-Adnexal Imaging Reporting and Data System(O-RADS)Category 4 in the differential diagnosis of benign and malignant ovarian-adnexal tumors.Methods:Retrospective analysis was conducted in 501 cases with ovarian masses classified into 4 categories according to the 2022 version of O-RADS who were collected from 4 clinical centers[the Second Afliated Hospital of Harbin Medical University(188 cases),Zhejiang Provincial People's Hospital(146 cases),Sichuan Provincial Maternity and Child Health Care Hospital(90 cases),and Fuling Hospital of Chongqing University(77 cases)]from January 2018 to July 2024 with concomitant surgical resection.The 424 cases from 3 of the clinical centers(the Second Hospital of Harbin Medical University,Zhejiang Provincial People's Hospital,and Sichuan Maternal and Child Health Hospital)were randomly divided into a training group(339 cases)and an internal validation group(85 cases)according to an 8∶2 randomization,while the cases from the other clinical center(Fuling Hospital of Chongqing University)were selected as the external validation group(77 cases),and the pathological diagnosis was used as the “gold standard”.Univariate and multifactorial logistic regression analyses were performed on the ultrasound characteristics of the training group to screen the independent predictors associated with ovarian carcinogenesis,and to formulate the stratification rules for the 4 types of masses in O-RADS. The ROC curve of this stratification method was plotted and the area under the curve(AUC)was calculated,and it was validated in the internal validation group and the external validation group;and the diagnostic accuracy was compared with that of the 2022 version of O-RADS.Results:Univariate logistic analysis showed that cysts with solid components,≥ 4 papillary projections,smooth inner wall of the cyst,color flow score ≥ 3 points,and acoustic shadowing were independent predictors of ovarian cancer(all P < 0.05);while multifactorial logistic analysis showed that cysts with a solid component and a color flow score ≥3 points were independent risk factors of ovarian cancer(all P < 0.05),and smooth cyst walls and acoustic shadows were independent protective factors(all P < 0.05).The diagnostic accuracies of the modified training group,internal validation group,and external validation group were 73.7%,68.2%,70.1%,respectively,which were significantly higher than the diagnostic accuracies of the 2022 version of the O-RADS(38.9%,37.6%,33.8%)(all P < 0.05).The diagnostic sensitivity,specificity and AUC of the training group were 0.871,0.652,0.762,respectively,while the internal validation group were 0.844,0.585,0.714,and 0.846,0.627,0.737 in the external validation group. Conclusions:Improvement of the 2022 version of O-RADS category 4 using ultrasound features may improve the identification of benign and malignant ovarian-adnexal tumors.
4.Long-term outcomes after infliximab discontinuation in patients with Crohn's disease: a single-center retrospective observational study
Danping ZHENG ; Yun QIU ; Yingfan ZHANG ; Baili CHEN ; Yao HE ; Zhirong ZENG ; Minhu CHEN
Chinese Journal of Inflammatory Bowel Diseases 2025;09(4):297-302
Objective:To assess the long-term risk of relapse in patients with Crohn's disease (CD) who discontinued infliximab (IFX) monoclonal antibody and to identify risk factors associated with relapse.Methods:A single-center retrospective observational study was conducted from February 2006 to October 2016. The study included CD patients who were treated with scheduled IFX infusions at the First Affiliated Hospital of Sun Yat-sen University and assessed in corticosteroid-free clinical remission at the time of withdrawal were included. The primary outcome was clinical relapse. We evaluated the risk of relapse using Kaplan-Meier method. Factors associated with time to relapse was identified using the multiple Cox proportional hazards regression analysis.Results:We included 97 eligible patients, and 75 (77.3%) experienced a relapse after a median follow-up time of 124 months. Among them, 45 patients (46.4%) relapsed within 3 years after IFX withdrawal. The 1-, 2-, 3-, 5-, and 10-year relapse-free survival were 79.4%, 59.8%, 52.6%, 42.0% and 22.6%, respectively. Risk factors for relapse included age ≤ 16 ( HR = 2.62, 95% CI: 1.30-5.31; P = 0.007) and failure to achieve biological remission (CRP > 3 mg/L, HR = 2.37, 95% CI: 1.29-4.36; P = 0.006) at drug withdrawal. Induction with biologics or systemic steroids were both effective (89%-100% relieved) in relapsers. Conclusions:Nearly half of CD patients relapsed within 3 years after discontinuation of IFX treatment. Early age of discontinuation and failure to achieve serum biological remission at the time of discontinuation are independent predictors of clinical relapse.
5.Value of using ultrasound features to improve the Ovarian-Adnexal Image Reporting and Data System Category 4 in the benign-malignant differential diagnosis of ovarian-adnexal masses
Lei WU ; Yingnan WU ; Jing ZHAO ; Liping GONG ; Shuang ZHANG ; Jiawei TIAN ; Zhirong HE ; Litao SUN
Chinese Journal of Ultrasonography 2025;34(3):232-238
Objective:To explore the value of ultrasound features modified version 2022 of the Ovarian-Adnexal Imaging Reporting and Data System(O-RADS)Category 4 in the differential diagnosis of benign and malignant ovarian-adnexal tumors.Methods:Retrospective analysis was conducted in 501 cases with ovarian masses classified into 4 categories according to the 2022 version of O-RADS who were collected from 4 clinical centers[the Second Afliated Hospital of Harbin Medical University(188 cases),Zhejiang Provincial People's Hospital(146 cases),Sichuan Provincial Maternity and Child Health Care Hospital(90 cases),and Fuling Hospital of Chongqing University(77 cases)]from January 2018 to July 2024 with concomitant surgical resection.The 424 cases from 3 of the clinical centers(the Second Hospital of Harbin Medical University,Zhejiang Provincial People's Hospital,and Sichuan Maternal and Child Health Hospital)were randomly divided into a training group(339 cases)and an internal validation group(85 cases)according to an 8∶2 randomization,while the cases from the other clinical center(Fuling Hospital of Chongqing University)were selected as the external validation group(77 cases),and the pathological diagnosis was used as the “gold standard”.Univariate and multifactorial logistic regression analyses were performed on the ultrasound characteristics of the training group to screen the independent predictors associated with ovarian carcinogenesis,and to formulate the stratification rules for the 4 types of masses in O-RADS. The ROC curve of this stratification method was plotted and the area under the curve(AUC)was calculated,and it was validated in the internal validation group and the external validation group;and the diagnostic accuracy was compared with that of the 2022 version of O-RADS.Results:Univariate logistic analysis showed that cysts with solid components,≥ 4 papillary projections,smooth inner wall of the cyst,color flow score ≥ 3 points,and acoustic shadowing were independent predictors of ovarian cancer(all P < 0.05);while multifactorial logistic analysis showed that cysts with a solid component and a color flow score ≥3 points were independent risk factors of ovarian cancer(all P < 0.05),and smooth cyst walls and acoustic shadows were independent protective factors(all P < 0.05).The diagnostic accuracies of the modified training group,internal validation group,and external validation group were 73.7%,68.2%,70.1%,respectively,which were significantly higher than the diagnostic accuracies of the 2022 version of the O-RADS(38.9%,37.6%,33.8%)(all P < 0.05).The diagnostic sensitivity,specificity and AUC of the training group were 0.871,0.652,0.762,respectively,while the internal validation group were 0.844,0.585,0.714,and 0.846,0.627,0.737 in the external validation group. Conclusions:Improvement of the 2022 version of O-RADS category 4 using ultrasound features may improve the identification of benign and malignant ovarian-adnexal tumors.
6.Prediction of premature mortality of major chronic and non-communicable diseases and exploration of influencing factors in Anhui Province
Qin HE ; Yan ZHANG ; Xiuya XING ; Dan DAI ; Qianyao CHENG ; Wei XU ; Zhenqiu ZHA ; Rui LI ; Yeji CHEN ; Huadong WANG ; Zhirong LIU
Chinese Journal of Epidemiology 2024;45(5):700-707
Objective:To analyze and predict the future trend of the premature mortality of major chronic and non-communicable diseases in Anhui Province, evaluate the implementation of the "Healthy China 2030" Plan, and explore its influencing factors.Methods:Using data from death-cause surveillance and statistical yearbooks in Anhui, the trend prediction and analysis on influencing factors were conducted by using methods such as time series accumulation and logarithmic linear Joinpoint regression, principal component regression.Results:In Anhui, 28.10% of the deaths were premature ones, of which 84.40% were attributed to chronic and non-communicable diseases. In premature deaths attributed to chronic and non-communicable diseases, the deaths caused by malignant tumor and cardiovascular disease accounted for 45.88% and 41.65% respectively. The prediction results showed that the premature mortality of major chronic and non-communicable diseases would decrease in Anhui in the future, and by 2030, the goal in the "Healthy China 2030" Plan would be reached only in rural area. To reduce premature death, it is necessary to pay attention to the prevention and control of malignant tumor and cardiovascular disease. Men in urban area are the key population. Factors that reflect urban infrastructure had a significant impact on premature mortality of major chronic non-communicable diseases, such as garden and green space area per capita. Factors such as concentration of PM 2.5 had a negative impact on premature mortality of chronic non-communicable diseases, while factors such as garden and green space area per capita had a positive impact. Conclusions:Disease burden caused by chronic and non-communicable diseases, such as malignant tumor, exits in Anhui. Men in urban area are key population in the prevention and control of chronic and non-communicable diseases in the future.
7.Combination of AAV-delivered tumor suppressor PTEN with anti-PD-1 loaded depot gel for enhanced antitumor immunity.
Yongshun ZHANG ; Lan YANG ; Yangsen OU ; Rui HU ; Guangsheng DU ; Shuang LUO ; Fuhua WU ; Hairui WANG ; Zhiqiang XIE ; Yu ZHANG ; Chunting HE ; Cheng MA ; Tao GONG ; Ling ZHANG ; Zhirong ZHANG ; Xun SUN
Acta Pharmaceutica Sinica B 2024;14(1):350-364
Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.
8.Immunostimulatory gene therapy combined with checkpoint blockade reshapes tumor microenvironment and enhances ovarian cancer immunotherapy.
Yunzhu LIN ; Xiang WANG ; Shi HE ; Zhongxin DUAN ; Yunchu ZHANG ; Xiaodong SUN ; Yuzhu HU ; Yuanyuan ZHANG ; Zhiyong QIAN ; Xiang GAO ; Zhirong ZHANG
Acta Pharmaceutica Sinica B 2024;14(2):854-868
Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.
9.Diagnosis and treatment strategies of inflammatory bowel disease complicated with herpes virus infection
Yaming LU ; Xiaoman ZU ; Baili CHEN ; Zhirong ZENG ; Minhu CHEN ; Yao HE
Chinese Journal of Inflammatory Bowel Diseases 2023;07(4):338-341
Inflammatory bowel disease (IBD) is susceptible to opportunistic infection due to immune dysfunction and immunomodulatory drug therapy, which results in complex condition, and the infection of herpes virus is common. Timely screening of herpes virus infection has an important significance to rational selection of antiviral therapy and/or withdrawal of immunomodulators. This artical systematically summarizes the diagnosis and treatment strategies of IBD complicated with eight types of herpes virus infection, in order to provide references for clinical work.
10.Diagnosis and treatment strategies of inflammatory bowel disease complicated with herpes virus infection
Yaming LU ; Xiaoman ZU ; Baili CHEN ; Zhirong ZENG ; Minhu CHEN ; Yao HE
Chinese Journal of Inflammatory Bowel Diseases 2023;07(4):338-341
Inflammatory bowel disease (IBD) is susceptible to opportunistic infection due to immune dysfunction and immunomodulatory drug therapy, which results in complex condition, and the infection of herpes virus is common. Timely screening of herpes virus infection has an important significance to rational selection of antiviral therapy and/or withdrawal of immunomodulators. This artical systematically summarizes the diagnosis and treatment strategies of IBD complicated with eight types of herpes virus infection, in order to provide references for clinical work.

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