1.Discovery of a potential hematologic malignancies therapy: Selective and potent HDAC7 PROTAC degrader targeting non-enzymatic function.
Yuheng JIN ; Xuxin QI ; Xiaoli YU ; Xirui CHENG ; Boya CHEN ; Mingfei WU ; Jingyu ZHANG ; Hao YIN ; Yang LU ; Yihui ZHOU ; Ao PANG ; Yushen LIN ; Li JIANG ; Qiuqiu SHI ; Shuangshuang GENG ; Yubo ZHOU ; Xiaojun YAO ; Linjie LI ; Haiting DUAN ; Jinxin CHE ; Ji CAO ; Qiaojun HE ; Xiaowu DONG
Acta Pharmaceutica Sinica B 2025;15(3):1659-1679
HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.
2.Blades and barriers: Oral vaccines for conquering cancers and warding off infectious diseases.
Kun YANG ; Jinhua LIU ; Yi ZHAO ; Haiting XU ; Menghang ZU ; Baoyi LI ; Xiaoxiao SHI ; Rui L REIS ; Subhas C KUNDU ; Bo XIAO
Acta Pharmaceutica Sinica B 2025;15(8):3925-3950
Global public health faces substantial challenges from malignant tumors and infectious diseases. Vaccination provides an approach for treating and preventing these diseases. Oral vaccinations are particularly advantageous in disease treatment and prevention due to their non-invasive nature, high patient compliance, convenience, cost-effectiveness, and capacity to stimulate comprehensive and adaptive immune responses. However, the overwhelming majority of oral vaccines remain in experimental development, struggling with clinical and commercial translation due to their suboptimal efficacy. Thus, enhancing scientists' understanding of the interaction between vaccines and gastrointestinal immune system, creating antigen delivery systems suitable for the gut mucosal environment, developing more potent antigenic epitopes, and using personalized combination therapies are critical for advancing the next generation of oral vaccines. This article explores the fundamental principles and applications of current oral anti-tumor and anti-infective vaccines and discusses considerations necessary for designing future oral vaccines.
3.Effect of volatile oil of Ligusticum chuanxiong on transdermal properties and cytotoxicity of triptolide in vitro
Cheng JIANG ; Zhenzhong ZANG ; Lihua CHEN ; Haiting ZHU ; Shihua FU ; Weifeng ZHU ; Wenting WU ; Wei SHI ; Yongmei GUAN
China Pharmacy 2024;35(4):413-418
OBJECTIVE To explore the effect of volatile oil of Ligusticum chuanxiong on the transdermal properties and cytotoxicity of triptolide in vitro. METHODS The chemical constituents of the volatile oil of L. chuanxiong were analyzed by gas chromatography-mass spectrometry. The lower abdominal skin of KM mice was separated and divided into triptolide group, triptolide in compatibility with volatile oil of L. chuanxiong groups at 1∶10, 1∶50, 1∶100 (hereinafter referred to as “compatibility 1∶10”“compatibility 1∶50”“compatibility 1∶100” groups). After the skin of mice in each group was fully exposed to 0.2 g of the corresponding cream for 24 h, the cumulative transdermal dose (Qn) of triptolide in the receiving solution of each group was determined by high-performance liquid chromatography, and the transdermal absorption rate (Jss) was calculated. Human immortalized keratinocytes (HaCat) were used as a model, the CCK-8 method was used to detect the cell survival rate of different concentrations of the volatile oil of L. chuanxiong and triptolide before and after compatibility. RESULTS A total of 62 chemical constituents of the volatile oil of L. chuanxiong were identified, including Z-ligustilide, senkyunolide, and β-selinene. The Qn (P< 0.01) and Jss of triptolide increased within 24 h in the compatibility 1∶10 and 1∶50 groups, while the Qn (P<0.05) and Jss decreased in the compatibility 1∶100 group as compared with the triptolide group. Compared with the triptolide group, the cell survival rate of HaCat was significantly increased in the compatibility 1∶10 and 1∶50 groups when the triptolide concentrations were 36, 72 and 144 ng/mL (P<0.05 or P<0.01); while the cell survival rate of HaCat was decreased in the compatibility 1∶100 group, but the difference was not statistically significant (P>0.05). CONCLUSIONS When the compatibility ratio of triptolide and volatile oil of L. chuanxiong was 1∶10 or 1∶50, it can promote the transdermal absorption of triptolide and reduce the cytotoxicity of triptolide to HaCat.
4.Surveillance of echinococcosis in Bayingolin Mongol Autonomous Prefecture, Xinjiang Uygur Autonomous Region from 2017 to 2022
Yue ZHANG ; Jun WU ; Simayi ADILI ; Shuo WANG ; Haiting ZHANG ; Guangzhong SHI ; Jiangshan ZHAO
Chinese Journal of Schistosomiasis Control 2024;36(1):79-82
Objective To analyze the echinococcosis surveillance results in Bayingolin Mongol Autonomous Prefecture, Xinjiang Uygur Autonomous Region from 2017 to 2022, so as to provide insights into formulation of echinococcosis control measures in the prefecture. Methods Villagers were randomly sampled using a multistage sampling method from class I and II echinococcosis endemic counties in Bayingolin Mongolian Autonomous Prefecture from 2017 to 2022 for detection of human echinococcosis, while all patients undergoing ultrasound examinations in medical institutions in class III endemic counties received active echinococcosis screening. In addition, livestock in centralized slaughterhouses or slaughtering sites were screened for echinococcosis using the palpation and necropsy method, and fresh domestic dog feces samples were collected from randomly selected dog owners in each administrative village for detection of Echinococcus copro-antigen in domestic dogs. The trends in detection of human and livestock echinococcosis, detection of newly diagnosed human echinococcosis cases and detection of Echinococcus coproantigen in domestic dogs were analyzed in Bayingolin Mongol Autonomous Prefecture from 2017 to 2022. Results The mean detection rate of human echinococcosis was 0.13% (540/407 803) in Bayingolin Mongol Autonomous Prefecture from 2017 to 2022, which appeared a tendency towards a decline over years (χ2trend = 1 217.21, P < 0.001), and the highest detection of newly diagnosed echinococcosis cases was seen in Hejing County (0.28%, 191/67 865). The detection of livestock echinococcosis appeared a tendency towards a decline over years from 2017 to 2022 (χ2trend = 147.02, P < 0.001), with the highest detection rate seen in Hejing County (3.44%, 86/2 500), and the detection of Echinococcus copro-antigen in domestic dogs appeared a tendency towards a decline over years from 2017 to 2022 (χ2trend = 302.46, P < 0.001), with the highest detection rate in Qiemo County (2.74%, 118/4 313). Conclusions The detection of human and livestock echinococcosis and dog feces antigens Echinococcus copro-antigen in domestic dogs all appeared a tendency towards a decline in Bayingolin Mongol Autonomous Prefecture, Xinjiang Uygur Autonomous Region from 2017 to 2022; however, there is still a high echinococcosis transmission risk in local areas. Sustainable integrated echinococcosis control is required in Bayingolin Mongol Autonomous Prefecture.
5.Evaluation of safety and quality management effect of ventilators in intensive care unit based on data envelopment analysis model
Haiting SHI ; Ying ZHAO ; Sifang REN ; Jingjing GAO ; Dan HU ; Yongxia GAO
China Medical Equipment 2024;21(11):104-108
Objective:To explore the application effect of data envelopment analysis(DEA)model in the safety and quality management of ventilators in intensive care units.Methods:Based on the Chanis-Cooper-Rhodes(CCR)dual model,by adding constraints,the input-oriented Bank-Carnes-Cooper(BCC)model was constructed to construct the DEA model.Among the 124 related items in the DEA model,20 high-level related items were identified to carry out ventilator quality control management related to clinical service efficiency.A total of 33 ventilators in clinical use in the intensive care unit(ICU)of Jiangsu Province Hospital from October 2021 to September 2023 were selected.Among them,the ventilators used from October 2021 to September 2022 were managed by traditional quality control management methods,and the ventilators used from October 2022 to September 2023 were managed by DEA model.The satisfaction scores,management quality scores and clinical efficiency scores of participants in ventilator use management were compared between the two management methods.Results:The satisfaction scores of medical staff,patients and equipment engineers for ventilator management using the DEA model management method were(96.68±2.25)points,(96.32±2.18)points and(95.66±2.54)points,respectively,which were higher than those of the traditional quality control management method,the difference was statistically significant(t=10.940,15.220,6.674,P<0.05).The average scores of ventilator operation performance,inspection operation safety and timeliness using DEA model management method were(4.44±0.31)points,(4.53±0.37)points and(4.61±0.36)points,respectively,which were higher than those of the traditional quality control management method,the difference was statistically significant(t=12.692,14.979,17.025,P<0.05).The average scores of ventilator work efficiency,ventilator response time efficiency and ventilator treatment efficiency using the DEA model management method were(4.49±0.32)points,(4.75±0.35)points and(4.68±0.32)points,respectively,which were all higher than those of the traditional quality control management method,with statistically significant differences(t=21.179,16.785,16.347,P<0.05).Conclusion:The application of the DEA model in the management of ventilators in ICU can improve the efficiency of ventilator clinical service,improve the satisfaction of ventilator management personnel and the quality of ventilator management.
6.MRI features of fibro-adipose vascular anomaly
Haiting LI ; Wenjia HU ; Hongguang FAN ; Changxian DONG ; Yubin GONG ; Panhong FAN ; Dapeng SHI
Chinese Journal of Plastic Surgery 2023;39(3):261-265
Objective:To investigate the MRI features of fibro-adipose vascular anomaly (FAVA).Methods:The clinical, pathological and MRI data of the FAVA patients confirmed clinically and pathologically in Henan Provincial People’s Hospital from January 2016 to June 2021 were retrospectively analyzed, including 17 females and 13 males, aged 4-53 (18.5±12.8) years.Through the analysis of the MRI images of FAVA performance, including the lesion area, shape, signal, the degree of reinforcement, inner structure, outer structure and other image characteristics, summarize the MRI features.Results:The lesions located at the lower leg (12 cases), thigh (12 cases), upper arm (4 cases), forearm (1 case) and trunk (1 case). Twenty-four case of lower limbs. All cases involved the muscular layer, including 21 cases of superficial muscle layer, 7 cases of deep muscle layer, and 2 cases of both. Twenty-three cases of superficial muscle layer. Most of the affected muscles were quadriceps femoris and gastrocnemius. Morphology: all lesions were intramuscular solid masses growing parallel to the long axis of the muscle. There were 11 cases of focal type, 11 cases of locally infiltrating type, and 8 cases of diffuse type. MRI findings: all lesions showed mixed signal. On T1WI, 28 cases showed cloud-like, band-like and patchy high signal on the background of medium and high signal. On T2WI-FS, all the 30 cases showed low to medium signal areas on the background of high signal, which were dendrimer, ribbon and cloud-like. The lesions showed moderate to obvious heterogeneous progressive enhancement. Twenty-seven lesions had different shapes of vascular shadow, and 28 lesions had drainage vein shadow adjacent to the lesions, 24 of which were located at the proximal end of the lesions. Fascial tail sign was found at the periphery of the lesions in 26 cases, of which 23 cases were located at the upper and lower ends of the lesions.Conclusion:FAVA is a complex vascular malformation with unclear pathological classification. MRI usually shows a solid mass in the superficial muscle layer of the lower limbs parallel to the long axis of the muscle, with cloud-like, band-like, and patchy hyperintensity on the background of high signal on T1WI, and dendritic, band-like, and cloud-like hypointensity on the background of high signal on T2WI-FS, which is helpful for the diagnosis of FAVA. Combined with the data of fascial tail sign, draining vein and clinical manifestations, the diagnosis of FAVA can be confirmed to a certain extent, which can provide reference and basis for clinical decision making.
7.MRI features of fibro-adipose vascular anomaly
Haiting LI ; Wenjia HU ; Hongguang FAN ; Changxian DONG ; Yubin GONG ; Panhong FAN ; Dapeng SHI
Chinese Journal of Plastic Surgery 2023;39(3):261-265
Objective:To investigate the MRI features of fibro-adipose vascular anomaly (FAVA).Methods:The clinical, pathological and MRI data of the FAVA patients confirmed clinically and pathologically in Henan Provincial People’s Hospital from January 2016 to June 2021 were retrospectively analyzed, including 17 females and 13 males, aged 4-53 (18.5±12.8) years.Through the analysis of the MRI images of FAVA performance, including the lesion area, shape, signal, the degree of reinforcement, inner structure, outer structure and other image characteristics, summarize the MRI features.Results:The lesions located at the lower leg (12 cases), thigh (12 cases), upper arm (4 cases), forearm (1 case) and trunk (1 case). Twenty-four case of lower limbs. All cases involved the muscular layer, including 21 cases of superficial muscle layer, 7 cases of deep muscle layer, and 2 cases of both. Twenty-three cases of superficial muscle layer. Most of the affected muscles were quadriceps femoris and gastrocnemius. Morphology: all lesions were intramuscular solid masses growing parallel to the long axis of the muscle. There were 11 cases of focal type, 11 cases of locally infiltrating type, and 8 cases of diffuse type. MRI findings: all lesions showed mixed signal. On T1WI, 28 cases showed cloud-like, band-like and patchy high signal on the background of medium and high signal. On T2WI-FS, all the 30 cases showed low to medium signal areas on the background of high signal, which were dendrimer, ribbon and cloud-like. The lesions showed moderate to obvious heterogeneous progressive enhancement. Twenty-seven lesions had different shapes of vascular shadow, and 28 lesions had drainage vein shadow adjacent to the lesions, 24 of which were located at the proximal end of the lesions. Fascial tail sign was found at the periphery of the lesions in 26 cases, of which 23 cases were located at the upper and lower ends of the lesions.Conclusion:FAVA is a complex vascular malformation with unclear pathological classification. MRI usually shows a solid mass in the superficial muscle layer of the lower limbs parallel to the long axis of the muscle, with cloud-like, band-like, and patchy hyperintensity on the background of high signal on T1WI, and dendritic, band-like, and cloud-like hypointensity on the background of high signal on T2WI-FS, which is helpful for the diagnosis of FAVA. Combined with the data of fascial tail sign, draining vein and clinical manifestations, the diagnosis of FAVA can be confirmed to a certain extent, which can provide reference and basis for clinical decision making.
8.Effects of psychological intervention based on resourcefulness theory on management of aggression and violence attitude and resilience of emergency nurses
Meiling SHI ; Jun WU ; Xiaoyan DENG ; Mengyuan HU ; Lu YU ; Haiting XU
Chinese Journal of Modern Nursing 2023;29(6):815-821
Objective:To explore the effects of psychological intervention based on resourcefulness theory on the management of aggression and violence attitude and resilience of emergency nurses.Methods:Totally 60 nurses who worked in the Emergency Department of the 904 Hospital, the People's Liberation Army Joint Logistic Support Force from January 2020 to December 2021 were selected by convenience sampling. According to the enrollment time, the nurses enrolled from January to December 2020 were included as the control group, and the nurses enrolled from January to December 2021 were included as the intervention group, with 30 nurses in each group. Nurses in the control group received routine psychological training, while nurses in the intervention group was trained with a psychological intervention program based on resourcefulness theory based on the training provided to the control group. The nurses were surveyed and the intervention effect was evaluated by Resourcefulness Scale, Management of Aggression and Violence Attitude Scale (MAVAS), Medical Professionals Resilience Scale (MeRS), and Nurses' Work Alienation Questionnaire (NWAQ) .Results:After intervention, the scores of Resourcefulness Scale, MAVAS and MeRS of nurses in the intervention group were higher than those in the control group, and the scores of NWAQ were lower than those in the control group, with statistical significance between the two groups ( P<0.05) . Conclusions:Psychological intervention based on resourcefulness theory can enhance the resourcefulness of emergency nurses, improve their management of aggression and violence attitudes, strengthen their deep understanding of work violence and their level of resilience, reduce their sense of alienation at work, and alleviate negative psychological emotions. Therefore, it is worth promoting in clinical practice.
9.Changes of p-ERK expression in rat lungs with decompression sickness caused by fast buoyancy ascent escape
Jun MA ; Yiqun FANG ; Xiaochen BAO ; Fangfang WANG ; Na LI ; Pu YOU ; Shi ZHANG ; Haiting CHEN
Chinese journal of nautical medicine and hyperbaric medicine 2020;27(3):283-285
Objective:To explore the mechanism of inflammatory response in lung tissues of rats with decompression sickness (DCS) caused by fast buoyancy ascent escape, and to observe the changes in phosphorylation of extracellular signal-related kinase (p-ERK) expression in rats with early onset of DCS during a simulated fast buoyancy ascent escape.Methods:A total of 18 rats were divided into three groups randomly, i. e. control group (C group), escape group in which all six rats were dead (ED group), and escape group in which all six rats survived (ES group). The rats in the ES group were anesthetized and sacrificed 8 minutes after they managed the simulated insecure seawater fast buoyancy ascent escape in a hyperbaric chamber. The p-ERK protein was extracted from rat lungs and then the protein expression was analyzed by Western blotting.Results:The p-ERK expression level in the ED group was elevated significantly than that in the C group; while the p-ERK expression level in ES group was not significantly increased than that in the C group.Conclusion:The development of inflammation-like reaction in lung tissues of rats with DCS caused by fast buoyancy ascent escape may relate with the activation of p-ERK.
10.Changes of p-ERK expression in rat lungs with decompression sickness caused by fast buoyancy ascent escape
Jun MA ; Yiqun FANG ; Xiaochen BAO ; Fangfang WANG ; Na LI ; Pu YOU ; Shi ZHANG ; Haiting CHEN
Chinese journal of nautical medicine and hyperbaric medicine 2020;27(3):283-285
Objective:To explore the mechanism of inflammatory response in lung tissues of rats with decompression sickness (DCS) caused by fast buoyancy ascent escape, and to observe the changes in phosphorylation of extracellular signal-related kinase (p-ERK) expression in rats with early onset of DCS during a simulated fast buoyancy ascent escape.Methods:A total of 18 rats were divided into three groups randomly, i. e. control group (C group), escape group in which all six rats were dead (ED group), and escape group in which all six rats survived (ES group). The rats in the ES group were anesthetized and sacrificed 8 minutes after they managed the simulated insecure seawater fast buoyancy ascent escape in a hyperbaric chamber. The p-ERK protein was extracted from rat lungs and then the protein expression was analyzed by Western blotting.Results:The p-ERK expression level in the ED group was elevated significantly than that in the C group; while the p-ERK expression level in ES group was not significantly increased than that in the C group.Conclusion:The development of inflammation-like reaction in lung tissues of rats with DCS caused by fast buoyancy ascent escape may relate with the activation of p-ERK.

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