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.Investigation on Chikungunya virus infection in humans in Cangyuan County, Yunnan Province
LI Nan ; MENG Jinxin ; LI Lingli ; HE Yuwen ; WANG Jinglin
China Tropical Medicine 2023;23(12):1249-
Objective To preliminarily understand the infection of Chikungunya virus (CHIKV) in Cangyuan County, a southern border area of Yunnan Province, and provide a reference basis for the prevention and control of Chikungunya fever. Methods In April 2020, a total of 400 serum samples from individuals seeking medical care at the People's Hospital of Cangyuan County in Yunnan Province were collected. Among these, 121 samples were from healthy individuals undergoing physical examinations, and 279 samples were from patients with fever. The serum samples collected underwent CHIKV neutralizing antibody testing using a serum micro-neutralization assay. Real-time fluorescence quantitative RT-PCR was used to detect CHIKV nucleic acid in the samples, followed by analysis of the test results. Results The results of neutralizing antibodies showed that 18 of the 400 human serum samples were positive for neutralizing antibodies against CHIKV, with an overall positivity rate for serum samples of 4.5% (18/400). Among the 279 serum samples collected from patients with fever, 18 were positive for neutralizing antibodies against CHIKV, with a positive rate of 6.45% (18/279), and the neutralizing antibody titers ranged from 1∶10 to 1∶320. The results of 121 healthy human serum samples were negative for neutralizing antibodies against CHIKV. The results of real-time fluorescence quantitative RT-PCR showed that 3 of the 400 human serum samples were positive for CHIKV nucleic acid, and the positive rate was 0.75% (3/400). Among the 279 serum samples collected from patients with fever, 3 samples were positive for CHIKV nucleic acid, with a positive rate of 1.08% (3/279), and Ct values ranged from 36.58 to 37.74. While all healthy human serum samples were negative for CHIKV nucleic acid. Conclusions The findings indicate that infection of CHIKV exists in the population of Cangyuan County, a southern border area of Yunnan Province, and an outbreak of the disease is occurring. Therefore, it is necessary to strengthen the monitoring, prevention, and control of CHIKV in this area.
9.Analysis of the complete genome sequence of the Dengue virus type 1 outbreak in Xishuangbanna in 2019
MENG Jinxin ; HU Qiuming ; LI Nan ; HE Yuwen ; WANG Jinglin
China Tropical Medicine 2023;23(12):1254-
Objective This study aims to comprehensively investigate the molecular characteristics of the predominant circulating Dengue virus type 1 (DENV-1) during the 2019 Dengue fever outbreak in Xishuangbanna, providing an essential insight to support the prevention and control of dengue fever in the local area. Methods A Dengue virus type 1 (DENV-1) strain, designated as JHS45, isolated from the blood of a febrile patient in Xishuangbanna in 2019, underwent a process of inoculation and cultivation in C6/36 cells. Second-generation sequencing was employed to capture the viral genetic sequence. Bioinformatics software, including CLC, was used for assembling the sequencing data. Sequentially, sequence alignment, construction of a phylogenetic tree, and analysis of amino acid sites were conducted using software such as Lasergene and MEGA6.1. Results Cytopathic effects of JHS45 appeared in C6/36 cells after 6 days. After sequencing and assembly, a 10 687-nucleotide (nt) long sequence of the JHS45 virus was obtained (GenBank accession number: OR593353). Genetic evolutionary analysis revealed that the JHS45 virus formed an evolutionary branch with DENV-1 genotype I viruses prevalent in Xishuangbanna, Guangzhou, Henan, and Zhejiang in China during 2019, as well as the DENV-1 genotype I virus prevalent in Thailand in 2013, with nucleotide homology of 97.6% to 99.9% and amino acid homology of 99.1% to 100%. Further analysis revealed that the JHS45 strain shared a smaller evolutionary branch with the DENV-1 genotype I viruses prevalent in Xishuangbanna (MW386863) and Guangzhou (MW261839) in 2019, showing the highest homology with nucleotide and amino acid homology of 99.9% and 100%, respectively. Amino acid differential site analysis between the JHS45 strain and the DENV-1 prevalent in Xishuangbanna since 2015 revealed 40 amino acid differential sites in the coding region of the JHS45 virus, primarily concentrated in the NS3 and NS5 regions of non-structural proteins. Conclusion The comprehensive analysis of the JHS45 strain's whole genome sequence indicates it is a DENV-1 genotype I virus. The genetic evolutionary relationship between this Xishuangbanna dengue fever outbreak is closely related to the prevalent virus strains in Xishuangbanna, Guangzhou, Henan, and Zhejiang. These findings provide a robust scientific foundation for monitoring dengue fever outbreaks, conducting virus evolution studies, and shaping effective prevention and control strategies, not only within Yunnan Province but also on a broader scale throughout China.
10.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.

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