1.Beyond cancer: The potential application of CD47-based therapy in non-cancer diseases.
Wei-Qing DENG ; Zi-Han YE ; Zhenghai TANG ; Xiao-Lei ZHANG ; Jin-Jian LU
Acta Pharmaceutica Sinica B 2025;15(2):757-791
CD47 is an immune checkpoint widely regarded as a 'don't eat me' signal. CD47-based anti-cancer therapy has received considerable attention, with a significant number of clinical trials conducted. While anti-cancer therapies based on CD47 remain a focal point of interest among researchers, it is noteworthy that an increasing number of studies have found that CD47-based therapy ameliorated the pathological status of non-cancer diseases. This review aims to provide an overview of the recent progress in comprehending the role of CD47-based therapy in non-cancer diseases, including diseases of the circulatory system, nervous system, digestive system, and so on. Furthermore, we sought to delineate the promising mechanisms of CD47-based therapy in treating non-cancer diseases. Our findings suggest that CD47-based agents may exert their effect by regulating phagocytosis, regulating T cells, dendritic cells, and neutrophils, and regulating the secretion of cytokines and chemokines. Additionally, we put forward the orientation of further research to bring to light the potential of CD47 and its binding partners as a target in non-cancer diseases.
2.Automatic synthesis of 18 F-MK-6240 with AllinOne synthesis module and preliminary application in Alzheimer disease
Zhenghai HUANG ; Chao REN ; Meiqi WU ; Xianzhong ZHANG ; Li HUO
Chinese Journal of Medical Imaging Technology 2024;40(12):1909-1913
Objective To observe the preliminary application value of 18 F-MK-6240 automatically synthesized with AllinOne synthesis module in Alzheimer disease(AD).Methods Based on AllinOne synthesis module,18 F-labeled intermediate 18F-MK-6240-Boc was formed with 18F-MK-6240 precursor through nucleophilic reaction with 18 F-.After hydrolyzed by acid,separated by high performance liquid chromatography and purified by solid-phase extraction,18F-MK-6240 was obtained,and quality control was performed.18F-MK-6240 PET/CT scanning was performed in 1 AD patient and 1 non-AD patient with cognitive impairment who were prospectively enrolled,and the preliminary application value of the product was observed.Results 18 F-MK-6240 was successfully automatically synthesized based on AllinOne synthesis module,the synthesis time was 80 min,no-corrected synthesis efficiency was 20.74%±2.31%,radiochemical purity was greater than 95%,and sterility test,bacterial endotoxins test,abnormal toxicity test and solvent residual test all met national standards.18F-MK-6240 PET/CT showed tau protein deposition of bilateral frontal,parietal,temporal and insular lobes in AD patients,while no tau protein deposition was observed in non-AD patients with cognitive impairment.Conclusion 18F-MK-6240 could be automatically synthesized based on AllinOne synthesis module,with qualified product quality and clinical application value in AD.
3.Automatic synthesis of 18 F-MK-6240 with AllinOne synthesis module and preliminary application in Alzheimer disease
Zhenghai HUANG ; Chao REN ; Meiqi WU ; Xianzhong ZHANG ; Li HUO
Chinese Journal of Medical Imaging Technology 2024;40(12):1909-1913
Objective To observe the preliminary application value of 18 F-MK-6240 automatically synthesized with AllinOne synthesis module in Alzheimer disease(AD).Methods Based on AllinOne synthesis module,18 F-labeled intermediate 18F-MK-6240-Boc was formed with 18F-MK-6240 precursor through nucleophilic reaction with 18 F-.After hydrolyzed by acid,separated by high performance liquid chromatography and purified by solid-phase extraction,18F-MK-6240 was obtained,and quality control was performed.18F-MK-6240 PET/CT scanning was performed in 1 AD patient and 1 non-AD patient with cognitive impairment who were prospectively enrolled,and the preliminary application value of the product was observed.Results 18 F-MK-6240 was successfully automatically synthesized based on AllinOne synthesis module,the synthesis time was 80 min,no-corrected synthesis efficiency was 20.74%±2.31%,radiochemical purity was greater than 95%,and sterility test,bacterial endotoxins test,abnormal toxicity test and solvent residual test all met national standards.18F-MK-6240 PET/CT showed tau protein deposition of bilateral frontal,parietal,temporal and insular lobes in AD patients,while no tau protein deposition was observed in non-AD patients with cognitive impairment.Conclusion 18F-MK-6240 could be automatically synthesized based on AllinOne synthesis module,with qualified product quality and clinical application value in AD.
4.Prevalence and molecular characterization of Cryptosporidium in captive-bred Mustela putorius furo in Jiangsu Province
Jinyang ZHANG ; Yonghua ZHOU ; Jie GUO ; Jiajia LI ; Yanyan WU ; Zhenghai ZHOU ; Haiyun ZHU ; Xinyu LUO ; Dongqian CHEN ; Qiaoqiao LI ; Xinchao LIU ; Wenchao LI
Chinese Journal of Schistosomiasis Control 2023;35(1):73-77
Objective To investigate the prevalence and molecular features of Cryptosporidium in captive-bred Mustela putorius furo in Jiangsu Province.. Methods A total of 290 fresh stool samples were collected from a ferret farm in Jiangsu Province on May 2017, and the small subunit rRNA (SSU rRNA) gene of Cryptosporidium was amplified in stool samples using nested PCR assay. The actin, cowp and gp60 genes were amplified in positive samples and sequenced to characterize Cryptosporidium species/genotypes. Results A total of 18 stool samples were tested positive for Cryptosporidium SSU rRNA gene, with a detection rate of 6.2%. Sequence and phylogenetic analyses of SSU rRNA, actin and cowp genes characterized Cryptosporidium isolated from captive-bred ferrets as Cryptosporidium sp. ferret genotype. In addition, gp60 gene was amplified in 10 out of 18 stool samples tested positive for Cryptosporidium. Conclusions Cryptosporidium is widely prevalent in captive-bred ferrets in Jiangsu Province, and Cryptosporidium sp. ferret genotype is the only Cryptosporidium genotype in ferrets.
5.Identification and phylogenetic analysis of five highly pathogenic avian influenza (H5N8) viruses isolated in Urumqi in 2016
Lijuan ZHANG ; Cheng ZHANG ; Han DU ; Fengze YUN ; Fei DU ; Yuhao CHANG ; Yuhai BI ; Zhenghai MA
Chinese Journal of Microbiology and Immunology 2022;42(8):615-622
Objective:To analyze the genetic evolution and molecular characteristics of H5N8 avian influenza viruses (AIVs) isolated from the poultry in a live poultry market (LPM) in Urumqi, Xinjiang.Methods:Oropharyngeal and cloacal swabs of poultry were collected from a LPM in Urumqi in 2016. AIVs were isolated by inoculating swab samples into chicken embryos. Hemagglutination test and RT-PCR were used to identify the AIVs. The genes of isolated AIVs were amplified with the universal primers of AIV and whole-genome sequencing was also performed. Pairwise sequence alignment and analysis of phylogenetic and molecular characteristics were performed using BLAST, Clustal W, MEGA-X and DNAStar software.Results:Five H5N8 AIVs were isolated from poultry. These strains shared a nucleotide identity of 99.70%-100.00%, which indicated that they were from the same source, and were named XJ-H5N8/2016. Phylogenetic analysis based on hemagglutinin( HA), NS and PB2 genes showed that these isolates were clustered together with H5N8 AIVs isolated from the migratory swans in Hubei, Shanxi and Sanmenxia, and the ducks in India during 2016 to 2017. Moreover, they were also clustered together with H5N6 AIVs isolated from minks in China and the first case of human infection in Fujian. The phylogenetic tree of neuraminidase( NA) gene indicated the five isolates clustered together with H5N8 AIVs isolated from ducks in India in 2016, and the phylogenetic trees of PB1, MP, PA and NP genes showed that they were clustered together with H5N8 AIVs isolated from wild birds and poultry in Egypt, Cameroon, Uganda, Congo and other African countries in 2017. The HA cleavage sites of XJ-H5N8/2016 contained five consecutive basic amino acids, indicating high pathogenicity. Multiple mutations in the genes of XJ-H5N8/2016 could enhance its virulence and pathogenicity to mammals. Conclusions:The five strains of H5N8 AIVs isolated from the LPM were highly pathogenic and closely related to the H5N8 AIVs isolated from migratory birds and poultry in Hubei, Shanxi, Sanmenxia area, Africa and India during 2016 to 2017. Meanwhile, some of the viral genes were also closely related to the H5N6 AIVs isolated from the minks and human in China. Multiple mutations could increase the virulence and pathogenicity of AIVs to mammals, which could pose a potential threat to public health.
6.Association of dynamic functional connectivity with bilateral precuneus at resting-state with obsessive-compulsive disorder
Zhenning DING ; Ping LI ; Dan LYU ; Yunhui CHEN ; Tinghuizi SHANG ; Xiaoyu BAI ; Zhenghai SUN ; Jian XIAO ; Guangfeng ZHANG ; Wanqiang LIU ; Yu GUO
Chinese Journal of Psychiatry 2022;55(2):106-114
Objective:To investigate the dynamic functional connectivity (dFC) of bilateral precuneus at resting-state in obsessive-compulsive disorder (OCD).Methods:Fifty patients with OCD who matched the criteria of ICD-10 and 50 healthy controls (HCs) were examined by the resting-state functional magnetic resonance imaging scanning. Voxel-based whole-brain dFC method was used to analyze the dFC of bilateral precuneus at resting-state in OCD; Pearson correlation analyses was used to analyze the relationship between the abnormal dFC values and clinical symptoms in OCD; support vector machine analyses was used to explore whether abnormal dFC could be used to identify OCD.Results:Compared with HCs, patients with OCD showed decreased dFC values between left precuneus and left medial prefrontal cortex (MPFC) (0.23±0.02 vs. 0.26±0.03, t=-6.23, P<0.05, GRF corrected), left cuneus (0.24±0.03 vs. 0.28±0.04, t=-5.30, P<0.05, GRF corrected), and left paracentral lobule (0.23±0.03 vs. 0.27±0.04, t=-5.36, P<0.05, GRF corrected); and decreased dFC values between right precuneus and left postcentral gyrus (0.23±0.04 vs. 0.27±0.04, t=-5.12, P<0.05, GRF corrected). The decreased dFC values between left precuneus and left MPFC was positively correlated with the total score of Yale-Brown obsessive compulsive scale (Y-BOCS)( r=0.289, P<0.05, uncorrected); the decreased dFC values between right precuneus and left posterior central gyrus was positively correlated with Y-BOCS total scores ( r=0.292, P<0.05, uncorrected) and obsessive subscale scores ( r=0.304, P<0.05, uncorrected). The area under the curve value of the decreased dFC values between right precuneus and left posterior central gyrus was 0.856; the Youden Index was 0.52; the sensitivity was 100%, and the specificity was 52%. Conclusions:The dFC of bilateral precuneus decreases at resting-state in patients with OCD. The abnormal dFC value between the right precuneus and the left posterior central gyrus may have implications to identify OCD.
7.Association of dynamic functional connectivity with bilateral precuneus at resting-state with obsessive-compulsive disorder
Zhenning DING ; Ping LI ; Dan LYU ; Yunhui CHEN ; Tinghuizi SHANG ; Xiaoyu BAI ; Zhenghai SUN ; Jian XIAO ; Guangfeng ZHANG ; Wanqiang LIU ; Yu GUO
Chinese Journal of Psychiatry 2022;55(2):106-114
Objective:To investigate the dynamic functional connectivity (dFC) of bilateral precuneus at resting-state in obsessive-compulsive disorder (OCD).Methods:Fifty patients with OCD who matched the criteria of ICD-10 and 50 healthy controls (HCs) were examined by the resting-state functional magnetic resonance imaging scanning. Voxel-based whole-brain dFC method was used to analyze the dFC of bilateral precuneus at resting-state in OCD; Pearson correlation analyses was used to analyze the relationship between the abnormal dFC values and clinical symptoms in OCD; support vector machine analyses was used to explore whether abnormal dFC could be used to identify OCD.Results:Compared with HCs, patients with OCD showed decreased dFC values between left precuneus and left medial prefrontal cortex (MPFC) (0.23±0.02 vs. 0.26±0.03, t=-6.23, P<0.05, GRF corrected), left cuneus (0.24±0.03 vs. 0.28±0.04, t=-5.30, P<0.05, GRF corrected), and left paracentral lobule (0.23±0.03 vs. 0.27±0.04, t=-5.36, P<0.05, GRF corrected); and decreased dFC values between right precuneus and left postcentral gyrus (0.23±0.04 vs. 0.27±0.04, t=-5.12, P<0.05, GRF corrected). The decreased dFC values between left precuneus and left MPFC was positively correlated with the total score of Yale-Brown obsessive compulsive scale (Y-BOCS)( r=0.289, P<0.05, uncorrected); the decreased dFC values between right precuneus and left posterior central gyrus was positively correlated with Y-BOCS total scores ( r=0.292, P<0.05, uncorrected) and obsessive subscale scores ( r=0.304, P<0.05, uncorrected). The area under the curve value of the decreased dFC values between right precuneus and left posterior central gyrus was 0.856; the Youden Index was 0.52; the sensitivity was 100%, and the specificity was 52%. Conclusions:The dFC of bilateral precuneus decreases at resting-state in patients with OCD. The abnormal dFC value between the right precuneus and the left posterior central gyrus may have implications to identify OCD.
8.BRICS report of 2020: The bacterial composition and antimicrobial resistance profile of clinical isolates from bloodstream infections in China
Yunbo CHEN ; Jinru JI ; Chaoqun YING ; Zhiying LIU ; Qing YANG ; Haishen KONG ; Yuanyuan DAI ; Jiliang WANG ; Haifeng MAO ; Hui DING ; Yongyun LIU ; Yizheng ZHOU ; Hong LU ; Youdong YIN ; Yan JIN ; Hongyun XU ; Lixia ZHANG ; Lu WANG ; Haixin DONG ; Zhenghai YANG ; Fenghong CHEN ; Donghong HUANG ; Guolin LIAO ; Pengpeng TIAN ; Dan LIU ; Yan GENG ; Sijin MAN ; Baohua ZHANG ; Ying HUANG ; Liang GUO ; Junmin CAO ; Beiqing GU ; Yanhong LI ; Hongxia HU ; Liang LUAN ; Shuyan HU ; Lin ZHENG ; Aiyun LI ; Rong XU ; Kunpeng LIANG ; Zhuo LI ; Donghua LIU ; Bo QUAN ; Qiang LIU ; Jilu SHEN ; Yiqun LIAO ; Hai CHEN ; Qingqing BAI ; Xiusan XIA ; Shifu WANG ; Jinhua LIANG ; Liping ZHANG ; Yinqiao DONG ; Xiaoyan QI ; Jianzhong WANG ; Xuefei HU ; Xiaoping YAN ; Dengyan QIAO ; Ling MENG ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2021;14(6):413-426
Objective:To investigate the bacterial composition and antimicrobial resistance profile of clinical isolates from bloodstream infections in China.Methods:The clinical bacterial strains isolated from blood culture were collected during January 2020 to December 2020 in member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS). Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute(CLSI, USA). WHONET 5.6 was used to analyze data.Results:During the study period, 10 043 bacterial strains were collected from 54 hospitals, of which 2 664 (26.5%) were Gram-positive bacteria and 7 379 (73.5%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (38.6%), Klebsiella pneumoniae (18.4%), Staphylococcus aureus (9.9%), coagulase-negative Staphylococci (7.5%), Pseudomonas aeruginosa (3.9%), Enterococcus faecium (3.3%), Enterobacter cloacae (2.8%), Enterococcus faecalis (2.6%), Acinetobacter baumannii (2.4%) and Klebsiella spp (1.8%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 27.6% and 74.4%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci were detected. More than 95% of Staphylococcus aureus were sensitive to rifampicin and SMZco. No vancomycin-resistant Enterococci strains were detected. Extended spectrum β-lactamase (ESBL) producing Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 48.4%, 23.6% and 36.1%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.3% and 16.1%, respectively; 9.6% of carbapenem-resistant Klebsiella pneumoniae strains were resistant to ceftazidime/avibactam combination. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii. The prevalence rate of carbapenem-resistance of Pseudomonas aeruginosa was 23.2%. Conclusions:The surveillance results in 2020 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while Escherichia coli was the most common pathogen, and ESBL-producing strains declined while carbapenem-resistant Klebsiella pneumoniae kept on high level. The proportion and the prevalence of carbapenem-resistant Pseudomonas aeruginosa were on the rise slowly. On the other side, the MRSA incidence got lower in China, while the overall prevalence of vancomycin-resistant Enterococci was low.
9.Novel reassortant 2.3.4.4B H5N6 highly pathogenic avian influenza viruses circulating among wild, domestic birds in Xinjiang, Northwest China
Qian ZHANG ; Xindi MEI ; Cheng ZHANG ; Juan LI ; Nana CHANG ; Dilihuma AJI ; Weifeng SHI ; Yuhai BI ; Zhenghai MA
Journal of Veterinary Science 2021;22(4):e43-
Background:
The H5 avian influenza viruses (AIVs) of clade 2.3.4.4 circulate in wild and domestic birds worldwide. In 2017, nine strains of H5N6 AIVs were isolated from aquatic poultry in Xinjiang, Northwest China.
Objectives:
This study aimed to analyze the origin, reassortment, and mutations of the AIV isolates.
Methods:
AIVs were isolated from oropharyngeal and cloacal swabs of poultry. Identification was accomplished by inoculating isolates into embryonated chicken eggs and performing hemagglutination tests and reverse transcription polymerase chain reaction (RT-PCR). The viral genomes were amplified with RT-PCR and then sequenced. The sequence alignment, phylogenetic, and molecular characteristic analyses were performed by using bioinformatic software.
Results:
Nine isolates originated from the same ancestor. The viral HA gene belonged to clade 2.3.4.4B, while the NA gene had a close phylogenetic relationship with the 2.3.4.4C H5N6 highly pathogenic avian influenza viruses (HPAIVs) isolated from shoveler ducks in Ningxia in 2015. The NP gene was grouped into an independent subcluster within the 2.3.4.4B H5N8 AIVs, and the remaining six genes all had close phylogenetic relationships with the 2.3.4.4B H5N8 HPAIVs isolated from the wild birds in China, Egypt, Uganda, Cameroon, and India in 2016–2017, Multiple basic amino acid residues associated with HPAIVs were located adjacent to the cleavage site of the HA protein. The nine isolates comprised reassortant 2.3.4.4B HPAIVs originating from 2.3.4.4B H5N8 and 2.3.4.4C H5N6 viruses in wild birds.
Conclusions
These results suggest that the Northern Tianshan Mountain wetlands in Xinjiang may have a key role in AIVs disseminating from Central China to the Eurasian continent and East African.
10.Novel reassortant 2.3.4.4B H5N6 highly pathogenic avian influenza viruses circulating among wild, domestic birds in Xinjiang, Northwest China
Qian ZHANG ; Xindi MEI ; Cheng ZHANG ; Juan LI ; Nana CHANG ; Dilihuma AJI ; Weifeng SHI ; Yuhai BI ; Zhenghai MA
Journal of Veterinary Science 2021;22(4):e43-
Background:
The H5 avian influenza viruses (AIVs) of clade 2.3.4.4 circulate in wild and domestic birds worldwide. In 2017, nine strains of H5N6 AIVs were isolated from aquatic poultry in Xinjiang, Northwest China.
Objectives:
This study aimed to analyze the origin, reassortment, and mutations of the AIV isolates.
Methods:
AIVs were isolated from oropharyngeal and cloacal swabs of poultry. Identification was accomplished by inoculating isolates into embryonated chicken eggs and performing hemagglutination tests and reverse transcription polymerase chain reaction (RT-PCR). The viral genomes were amplified with RT-PCR and then sequenced. The sequence alignment, phylogenetic, and molecular characteristic analyses were performed by using bioinformatic software.
Results:
Nine isolates originated from the same ancestor. The viral HA gene belonged to clade 2.3.4.4B, while the NA gene had a close phylogenetic relationship with the 2.3.4.4C H5N6 highly pathogenic avian influenza viruses (HPAIVs) isolated from shoveler ducks in Ningxia in 2015. The NP gene was grouped into an independent subcluster within the 2.3.4.4B H5N8 AIVs, and the remaining six genes all had close phylogenetic relationships with the 2.3.4.4B H5N8 HPAIVs isolated from the wild birds in China, Egypt, Uganda, Cameroon, and India in 2016–2017, Multiple basic amino acid residues associated with HPAIVs were located adjacent to the cleavage site of the HA protein. The nine isolates comprised reassortant 2.3.4.4B HPAIVs originating from 2.3.4.4B H5N8 and 2.3.4.4C H5N6 viruses in wild birds.
Conclusions
These results suggest that the Northern Tianshan Mountain wetlands in Xinjiang may have a key role in AIVs disseminating from Central China to the Eurasian continent and East African.

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