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.Diagnotic value of endoscopic retrograde cholangiopancreatography combined with modified biopsy forceps for suspected malignant biliary stricture (with video)
Junying LIU ; Mengqiang CAI ; Yurong CUI ; Wei LIU ; Zhaoxia HE ; Haiyang YU ; Jinxin LI
Chinese Journal of Digestive Endoscopy 2025;42(7):572-576
To explore the diagnostic value of endoscopic retrograde cholangiopancreatography (ERCP) combined with modified biopsy forceps for suspected malignant biliary obstruction, 72 patients with suspected malignant biliary obstruction who underwent ERCP using modified biopsy forceps from January 2017 to April 2023 in the First Affiliated Hospital of Henan University of Chinese Medicine were selected as the modified group, while 61 contemporaneous patients who underwent ERCP with traditional biopsy forceps were selected as the control group at the same time. The stenosis site was identified during the operation, and the effective pathological tissue was obtained by biopsy. Benign or malignant tumor was determined according to the medical history and clinical follow-up data. The sensitivity and specificity of the two groups were compared. The success rate of biopsy was 100.00% in the two groups. All patients had no serious complications and were diagnosed histologically. Sixty-seven cases were finally diagnosed as malignant and 5 cases were benign in the modified group. In the control group, 58 cases were malignant and 3 cases were benign. The sensitivity for diagnosis of malignant biliary stricture was 79.10% (54/67) in the modified group, and 60.34% (35/58) in the control group, with significant difference ( χ2=6.218, P= 0.013). The specificity of the two methods for the diagnosis of malignant stenosis was 100.00%. Therefore, it is safe and effective to apply ERCP combined with the modified biopsy forceps in the diagnosis of extrahepatic malignant bile duct stenosis.
3.Construction and expression of an ETEC adhesin multi-epitope fusion antigen and evaluation of its immunogenicity
Yayun YANG ; Huabo SUN ; Jiashu CHANG ; Jinxin HE ; Shaopeng GU
Chinese Journal of Veterinary Science 2025;45(2):227-234,242
Enterotoxigenic Escherichia coli(ETEC)is the main cause of diarrhea in piglets,which seriously threatens the development of animal husbandry.In order to effectively prevent and con-trol piglet diarrhea,the neutralizing epitopes of the screened K88(FTDYEGASVELRKPDGGT-NK),K99(NVGNGSGGANIN),987P(LAAPAENNTSQAN),F41(VMAADWTEGQPGDII)and F18(PPNAQTYPLSSGDLK)ETEC adhesins were assembled to construct the multi-epitope fusion antigen(MEFA),whose immunogenicity was verified by in silico simulations and in vitro.The computer simulation results showed that MEFA has excellent physicochemical properties and reasonable prediction results of secondary and tertiary structures and exhibits strong interaction force when docking with toll-like receptor 3,and the kinetic simulation shows that it can be stably presented.In vitro validation results showed that anti-K88,K99,987P,F18 and F41 IgY could spe-cifically recognize MEFA proteins.After immunization of laying hens with MEFA,the titers of IgY antibodies against the five ETEC were higher than those of non-specific IgY.In addition,specific anti-MEFA IgY significantly inhibited the adhesion of K88,K99,987P,F41 and F18 ETEC strains to piglet intestinal IPEC-J2 cell lines.These results indicate that MEFA has strong immunogenicity and can be used as an ideal vaccine candidate for the prevention of K88,K99,987P,F41 and F18 ETEC infection,and provide reference and technical support for the development of multivalent broad-spectrum ETEC vaccine candidates.
4.Construction and expression of an ETEC adhesin multi-epitope fusion antigen and evaluation of its immunogenicity
Yayun YANG ; Huabo SUN ; Jiashu CHANG ; Jinxin HE ; Shaopeng GU
Chinese Journal of Veterinary Science 2025;45(2):227-234,242
Enterotoxigenic Escherichia coli(ETEC)is the main cause of diarrhea in piglets,which seriously threatens the development of animal husbandry.In order to effectively prevent and con-trol piglet diarrhea,the neutralizing epitopes of the screened K88(FTDYEGASVELRKPDGGT-NK),K99(NVGNGSGGANIN),987P(LAAPAENNTSQAN),F41(VMAADWTEGQPGDII)and F18(PPNAQTYPLSSGDLK)ETEC adhesins were assembled to construct the multi-epitope fusion antigen(MEFA),whose immunogenicity was verified by in silico simulations and in vitro.The computer simulation results showed that MEFA has excellent physicochemical properties and reasonable prediction results of secondary and tertiary structures and exhibits strong interaction force when docking with toll-like receptor 3,and the kinetic simulation shows that it can be stably presented.In vitro validation results showed that anti-K88,K99,987P,F18 and F41 IgY could spe-cifically recognize MEFA proteins.After immunization of laying hens with MEFA,the titers of IgY antibodies against the five ETEC were higher than those of non-specific IgY.In addition,specific anti-MEFA IgY significantly inhibited the adhesion of K88,K99,987P,F41 and F18 ETEC strains to piglet intestinal IPEC-J2 cell lines.These results indicate that MEFA has strong immunogenicity and can be used as an ideal vaccine candidate for the prevention of K88,K99,987P,F41 and F18 ETEC infection,and provide reference and technical support for the development of multivalent broad-spectrum ETEC vaccine candidates.
5.Diagnotic value of endoscopic retrograde cholangiopancreatography combined with modified biopsy forceps for suspected malignant biliary stricture (with video)
Junying LIU ; Mengqiang CAI ; Yurong CUI ; Wei LIU ; Zhaoxia HE ; Haiyang YU ; Jinxin LI
Chinese Journal of Digestive Endoscopy 2025;42(7):572-576
To explore the diagnostic value of endoscopic retrograde cholangiopancreatography (ERCP) combined with modified biopsy forceps for suspected malignant biliary obstruction, 72 patients with suspected malignant biliary obstruction who underwent ERCP using modified biopsy forceps from January 2017 to April 2023 in the First Affiliated Hospital of Henan University of Chinese Medicine were selected as the modified group, while 61 contemporaneous patients who underwent ERCP with traditional biopsy forceps were selected as the control group at the same time. The stenosis site was identified during the operation, and the effective pathological tissue was obtained by biopsy. Benign or malignant tumor was determined according to the medical history and clinical follow-up data. The sensitivity and specificity of the two groups were compared. The success rate of biopsy was 100.00% in the two groups. All patients had no serious complications and were diagnosed histologically. Sixty-seven cases were finally diagnosed as malignant and 5 cases were benign in the modified group. In the control group, 58 cases were malignant and 3 cases were benign. The sensitivity for diagnosis of malignant biliary stricture was 79.10% (54/67) in the modified group, and 60.34% (35/58) in the control group, with significant difference ( χ2=6.218, P= 0.013). The specificity of the two methods for the diagnosis of malignant stenosis was 100.00%. Therefore, it is safe and effective to apply ERCP combined with the modified biopsy forceps in the diagnosis of extrahepatic malignant bile duct stenosis.
6.A qualitative study of experiential health education on complications among middle-aged and elderly hypertensive patients
Jinxin DENG ; Wen QI ; Huaye XIAO ; Ying ZHANG ; Jiawen WEI ; Yuan MENG ; Yong YANG ; Ting HE
China Modern Doctor 2024;62(34):20-23
Objective To explore the experience and feeling of experiential health education for complications in middle-aged and elderly hypertensive patients,and to provide basis for health education model for hypertensive patients. Methods By objective sampling method,10 middle-aged and elderly hypertensive patients who received experiential health education for hypertension complications in Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine from August to September 2023 were selected for semi-structured interviews,and the interview data were sorted out by Colaizzi seven-step analysis method. Results Middle-aged and elderly hypertension patients with complications of experiential health education experience can be summarized as two themes,seven subthemes,namely:the perceived benefits (improve the cognition of hypertension,complications of experience,behavior change and cognitive clarity,promote interpersonal communication),challenges (the lack of early cognitive,the limitations of traditional health education,body burden concerns). Conclusion Worry about long-term complications and lack of knowledge of disease management are common after receiving experiential health education on complications. Therefore,when designing the experiential health education program,clinical medical staff should fully consider the physiological and psychological characteristics of patients,provide personalized support,and gradually guide patients to adapt to the education process.
7.A qualitative study of experiential health education on complications among middle-aged and elderly hypertensive patients
Jinxin DENG ; Wen QI ; Huaye XIAO ; Ying ZHANG ; Jiawen WEI ; Yuan MENG ; Yong YANG ; Ting HE
China Modern Doctor 2024;62(34):20-23
Objective To explore the experience and feeling of experiential health education for complications in middle-aged and elderly hypertensive patients,and to provide basis for health education model for hypertensive patients. Methods By objective sampling method,10 middle-aged and elderly hypertensive patients who received experiential health education for hypertension complications in Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine from August to September 2023 were selected for semi-structured interviews,and the interview data were sorted out by Colaizzi seven-step analysis method. Results Middle-aged and elderly hypertension patients with complications of experiential health education experience can be summarized as two themes,seven subthemes,namely:the perceived benefits (improve the cognition of hypertension,complications of experience,behavior change and cognitive clarity,promote interpersonal communication),challenges (the lack of early cognitive,the limitations of traditional health education,body burden concerns). Conclusion Worry about long-term complications and lack of knowledge of disease management are common after receiving experiential health education on complications. Therefore,when designing the experiential health education program,clinical medical staff should fully consider the physiological and psychological characteristics of patients,provide personalized support,and gradually guide patients to adapt to the education process.
8.AKT inhibitor Hu7691 induces differentiation of neuroblastoma cells.
Shaowei BING ; Senfeng XIANG ; Zhimei XIA ; Yilong WANG ; Zhonghai GUAN ; Jinxin CHE ; Aixiao XU ; Xiaowu DONG ; Ji CAO ; Bo YANG ; Jinhu WANG ; Qiaojun HE ; Meidan YING
Acta Pharmaceutica Sinica B 2023;13(4):1522-1536
While neuroblastoma accounts for 15% of childhood tumor-related deaths, treatments against neuroblastoma remain scarce and mainly consist of cytotoxic chemotherapeutic drugs. Currently, maintenance therapy of differentiation induction is the standard of care for neuroblastoma patients in clinical, especially high-risk patients. However, differentiation therapy is not used as a first-line treatment for neuroblastoma due to low efficacy, unclear mechanism, and few drug options. Through compound library screening, we accidently found the potential differentiation-inducing effect of AKT inhibitor Hu7691. The protein kinase B (AKT) pathway is an important signaling pathway for regulating tumorigenesis and neural differentiation, yet the relation between the AKT pathway and neuroblastoma differentiation remains unclear. Here, we reveal the anti-proliferation and neurogenesis effect of Hu7691 on multiple neuroblastoma cell lines. Further evidence including neurites outgrowth, cell cycle arrest, and differentiation mRNA marker clarified the differentiation-inducing effect of Hu7691. Meanwhile, with the introduction of other AKT inhibitors, it is now clear that multiple AKT inhibitors can induce neuroblastoma differentiation. Furthermore, silencing AKT was found to have the effect of inducing neuroblastoma differentiation. Finally, confirmation of the therapeutic effects of Hu7691 is dependent on inducing differentiation in vivo, suggesting that Hu7691 is a potential molecule against neuroblastoma. Through this study, we not only define the key role of AKT in the progression of neuroblastoma differentiation but also provide potential drugs and key targets for the application of differentiation therapies for neuroblastoma clinically.
9.Chinese Medicine Polysaccharides Induce Apoptosis of Gastric Cancer Cells: A Review
Jinxin WANG ; Liqun LI ; Maoguang HUANG ; Feng LUO ; Yueying CHEN ; Junling ZHANG ; Yiyi HE ; Shengnan CAI ; Sheng XIE
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(24):202-209
Gastric cancer (GC) is a digestive tract tumor that occurs in the epithelial tissues of the gastric mucosa, seriously affecting the life and health of patients, and its mortality rate ranks the third among malignancies. Although medical technology has made great progress in recent years, the progression of GC still cannot be effectively controlled by surgery, chemotherapy, and targeted therapy. The pathogenesis of GC is extremely complex and is closely related to the tumor microenvironment, chronic inflammation, and immune escape, among which the reduction of tumor cell apoptosis is one of the important mechanisms for the occurrence and development of GC. Apoptosis refers to the process of spontaneous termination of cell life caused by genes under specific physiological or pathological conditions, which is of great significance for maintaining the stability of the internal environment. Researchers have found that in the GC state, mitochondrial endogenous apoptosis, endoplasmic reticulum stress, external death receptors, and other apoptosis pathways are regulated by multiple signaling pathways and genes, which together lead to the decline of GC cell apoptosis rate and thus promote the progression of GC. Chinese medicine is advantageous and characterized by multiple components, multiple targets, synergistic effect, and few adverse reactions. A large number of studies have shown that polysaccharide components, as effective components of Chinese medicine, have biological activities such as cancer inhibition, blood sugar control, anti-inflammation, antioxidant damage, and anti-virus, and can effectively inhibit the deterioration of GC by inducing cell apoptosis, gradually becoming a hot spot in GC drug research and development. However, systematic reviews on the apoptosis of GC induced by Chinese medicine polysaccharides are rarely reported. Therefore, this paper analyzed and summarized the studies of Chinese medicine polysaccharides in promoting apoptosis and interfering with GC, in order to provide a theoretical basis for the basic research, new drug development, and clinical application of Chinese medicine polysaccharides in the intervention of GC.
10.Nucleic acid detection and sequence analysis of arboviruses in Xichang
Yiju CHEN ; Yuwen HE ; Yiling YANG ; Jin SUN ; Zhenxing YANG ; Jinxin MENG ; Nan LI ; Chuanzhi XU ; Jinglin WANG
Chinese Journal of Laboratory Medicine 2023;46(2):143-149
Objective:To understand the prevalence of arboviruses in mosquito samples in Xichang City, Sichuan Province, and enrich the data of arbovirus activity and genetic characteristics in southwestern Sichuan Province.Methods:In June 2018, the nucleic acid was extracted from Culex tritaeniorhynchus mosquitoes collected from different pigsties in three villages and suburbs of Xichang City. The specific primers of Yunnan orbivirus, Banna virus, Tibet orbivirus (S7, S10), Flavivirus and alphavirus were used for quantitative polymerase chain reaction examination, and the positive product was cloned for sequencing analysis. Results:A total of 9 012 mosquitoes were collected, of which Cx. tritaeniorhynchus was the dominant species. A number of 88 batches of these mosquitoes were amplified, and 2 strains of Japanese encephalitis virus (JEV), 7 strains of Banna virus (BAV), 7 strains of Tibet orbivirus (TIBOV) and 1 strain of Yunnan orbivirus virus (YOUV) were detected, respectively. By the results of cluster analysis and evolutionary tree analysis, the 17 newly found virus strains were close to the Yunnan isolates, and 2 JEV strains were located in the GI-b clade. The other 7 strains of BAV were A2 evolutionary clades. Of the 7 TIBOV plants, 6 were located in the same clade. One TOUV was in the same clade as the Yunnan strain. Conclusions:Culex tritaeniorhynchus mosquitoes in Xichang city might carry JEV, BAV, YOUV and TIBOV, among them JEV was GI-b type and BAV was A2 type. The results provide data supporting the detection and analysis of arboviruses in Xichang city.

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