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.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.
9.BRICS report of 2018-2019: the distribution and antimicrobial resistance profile of clinical isolates from blood culture in China
Yunbo CHEN ; Jinru JI ; Chaoqun YING ; Peipei WANG ; Zhiying LIU ; Qing YANG ; Haishen KONG ; Hui DING ; Yongyun LIU ; Haifeng MAO ; Ying HUANG ; Zhenghai YANG ; Yuanyuan DAI ; Guolin LIAO ; Lisha ZHU ; Liping ZHANG ; Yanhong LI ; Hongyun XU ; Junmin CAO ; Baohua ZHANG ; Liang GUO ; Haixin DONG ; Shuyan HU ; Sijin MAN ; Lu WANG ; Zhixiang LIAO ; Rong XU ; Dan LIU ; Yan JIN ; Yizheng ZHOU ; Yiqun LIAO ; Fenghong CHEN ; Beiqing GU ; Jiliang WANG ; Jinhua LIANG ; Lin ZHENG ; Aiyun LI ; Jilu SHEN ; Yinqiao DONG ; Lixia ZHANG ; Hongxia HU ; Bo QUAN ; Wencheng ZHU ; Kunpeng LIANG ; Qiang LIU ; Shifu WANG ; Xiaoping YAN ; Jiangbang KANG ; Xiusan XIA ; Lan MA ; Li SUN ; Liang LUAN ; Jianzhong WANG ; Zhuo LI ; Dengyan QIAO ; Lin ZHANG ; Lanjuan LI ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2021;14(1):32-45
Objective:To investigate the distribution and antimicrobial resistance profile of clinical bacteria isolated from blood culture in China.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2018 to December 2019. Antibiotic susceptibility tests were conducted with agar dilution or broth dilution methods recommended by US Clinical and Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 14 778 bacterial strains were collected from 50 hospitals, of which 4 117 (27.9%) were Gram-positive bacteria and 10 661(72.1%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.2%), Klebsiella pneumoniae (17.0%), Staphylococcus aureus (9.7%), coagulase-negative Staphylococci (8.7%), Pseudomonas aeruginosa (3.7%), Enterococcus faecium (3.4%), Acinetobacter baumannii(3.4%), Enterobacter cloacae (2.9%), Streptococci(2.8%) and Enterococcus faecalis (2.3%). The the prevalence of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus were 27.4% (394/1 438) and 70.4% (905/1 285), respectively. No glycopeptide-resistant Staphylococcus was detected. More than 95% of S. aureus were sensitive to amikacin, rifampicin and SMZco. The resistance rate of E. faecium to vancomycin was 0.4% (2/504), and no vancomycin-resistant E. faecalis was detected. The ESBLs-producing rates in no carbapenem-resistance E. coli, carbapenem sensitive K. pneumoniae and Proteus were 50.4% (2 731/5 415), 24.6% (493/2001) and 35.2% (31/88), respectively. The prevalence of carbapenem-resistance in E. coli and K. pneumoniae were 1.5% (85/5 500), 20.6% (518/2 519), respectively. 8.3% (27/325) of carbapenem-resistance K. pneumoniae was resistant to ceftazidime/avibactam combination. The resistance rates of A. baumannii to polymyxin and tigecycline were 2.8% (14/501) and 3.4% (17/501) respectively, and that of P. aeruginosa to carbapenem were 18.9% (103/546). Conclusions:The surveillance results from 2018 to 2019 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while E. coli was the most common pathogen, and ESBLs-producing strains were in majority; the MRSA incidence is getting lower in China; carbapenem-resistant E. coli keeps at a low level, while carbapenem-resistant K. pneumoniae is on the rise obviously.
10.Isolation, identification and phylogenetic analysis of six strains of H5N6 highly pathogenic avian influenza virus
Nana CHANG ; Qian ZHANG ; Cheng ZHANG ; Fei DU ; Mamuti AMUTIKARI ; Yuhai BI ; Zhenghai MA
Chinese Journal of Microbiology and Immunology 2021;41(4):254-261
Objective:To analyze phylogenetic structure and molecular characteristics of H5N6 avian influenza virus (AIVs) isolated from live poultry market (LPM).Methods:Oropharyngeal and cloacal swabs from poultry, and environmental samples were collected from LPM in Urumqi in December 2018, AIVs were isolated and identified by inoculation of chicken embryo, hemagglutination test and RT-PCR, the viral whole genome was amplified with the universal primers of influenza A virus, and then sequenced, pairwise sequence alignments, phylogenetic and molecular characteristics analysis were performed by BLAST, Clustal W, MEGA-X and DNAStar software.Results:Six strains of H5N6 AIVs were isolated from poultry samples, the identity between the viral genes was high (99.4%-100.0%), so the isolates were the same source. BLAST analysis revealed that the viral NP sequence had the highest identity (99.7%) with H5N6 AIVs isolated from poultry in Suzhou, while the sequence of the remaining 7 viral genes had the highest identity (99.0%-100.0%) with H5N6 AIVs isolated from environment in Guangdong during 2017 to 2018. Phylogenetic analysis showed that the viral HA belonged to Clade 2.3.4.4C, and the viral HA, NA, PB1, PA, NP, and MP were all clustered together with H5N6 AIVs isolated from mink in Eastern China in 2018, while the PB2 and NS were clustered together with H5N6 AIVs isolated from environment in Guangdong from 2017 to 2018. The HA cleavage site contained multiple basic amino acid residues, which was highly pathogenic AIVs (HPAIVs). S137A and T160A mutations of HA could increase binding to human-type receptor SAα2, 6-Gal. Additionally, the viral multiple mutations, including 59-69 deletion in NA, the L89V, G309D, R477G, I495V, I504V, D391E, and A661E in PB2, as well as the P42S, D92E, and 80-84 deletion in NS1, could enhance the viral virulence and pathogenicity to mammals. Conclusions:The 6 strains of H5N6 HPAIVs isolated from LPM have relatively close genetic relationship with H5N6 AIVs isolated from mink in Eastern China and environment in Guangdong during 2017 to 2018, the viral multiple mutations could increase its pathogenicity to mammals, which could pose a potential risk to public health.

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