Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

This study was aimed at comprehensively understanding the epidemic status of acute hemorrhagic conjunctivitis(AHC)and influencing factors related outbreak in Fujian Province,to provide valuable insights for AHC prevention and control in this region.We conducted a descriptive statistical analysis of epidemiological data for AHC cases.Additionally,clinical samples collected from a 2023 outbreak were subjected to pathogen detection,determination of full-length nucleotide sequences within the VP1 region,genotype identification,and comprehensive analysis.The peak incidence of AHC in 2023 was observed in September and accounted for a substantial proportion(86.39%,5 205/6 025)of the total cases throughout the year.The three areas with the highest incidence rates were Sanming(118.57/100 000),Longyan(53.83/100 000)and Zhangzhou(16.02/100 000).From 2011 to 2022,the inci-dence of AHC in Longyan City was the highest for consecutive 12 years.During the peak AHC outbreak period in Fujian Province in 2023,all 62 conjunctival swabs collected were identified as CVA24v,and 60 complete VP1 sequences were obtained through se-quencing.The nucleotide sequence identity among these 60 sequences ranged from 98.7%to 100%,whereas the amino acid identity ranged from 98.4%to 100%.The highest nucleotide sequence identity was observed for the 2023 strain isolated from Zhongshan,Guangdong Province(rang:99.0%～100%).The 2023 strains in Fujian Province belonged to the GIV genotype,and L16I represented a potential unique amino acid variation within the sequence.CVA24v was the causative agent responsible for this AHC epidemic,and its GIV genotype is currently the dominant type in China.Future efforts should prioritize AHC prevention and control measures cen-tered in key cities.Monitoring and early warning of AHC in the whole province should be strengthened before September each year,and the variation of pathogen nucleic should also be tracked in time.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

This study was aimed at comprehensively understanding the epidemic status of acute hemorrhagic conjunctivitis(AHC)and influencing factors related outbreak in Fujian Province,to provide valuable insights for AHC prevention and control in this region.We conducted a descriptive statistical analysis of epidemiological data for AHC cases.Additionally,clinical samples collected from a 2023 outbreak were subjected to pathogen detection,determination of full-length nucleotide sequences within the VP1 region,genotype identification,and comprehensive analysis.The peak incidence of AHC in 2023 was observed in September and accounted for a substantial proportion(86.39%,5 205/6 025)of the total cases throughout the year.The three areas with the highest incidence rates were Sanming(118.57/100 000),Longyan(53.83/100 000)and Zhangzhou(16.02/100 000).From 2011 to 2022,the inci-dence of AHC in Longyan City was the highest for consecutive 12 years.During the peak AHC outbreak period in Fujian Province in 2023,all 62 conjunctival swabs collected were identified as CVA24v,and 60 complete VP1 sequences were obtained through se-quencing.The nucleotide sequence identity among these 60 sequences ranged from 98.7%to 100%,whereas the amino acid identity ranged from 98.4%to 100%.The highest nucleotide sequence identity was observed for the 2023 strain isolated from Zhongshan,Guangdong Province(rang:99.0%～100%).The 2023 strains in Fujian Province belonged to the GIV genotype,and L16I represented a potential unique amino acid variation within the sequence.CVA24v was the causative agent responsible for this AHC epidemic,and its GIV genotype is currently the dominant type in China.Future efforts should prioritize AHC prevention and control measures cen-tered in key cities.Monitoring and early warning of AHC in the whole province should be strengthened before September each year,and the variation of pathogen nucleic should also be tracked in time.

Objective:To investigate the molecular epidemiological characteristics of coxsackievirus A16 (CVA16) in Fujian province from 2020 to 2023.Methods:The epidemiological characteristics of CVA16 associated hand, food and mouth disease (HFMD) in Fujian province from 2020 to 2023 was analyzed. The complete VP1 gene of CVA16 was amplified by RT-PCR and then sequenced, and genetic evolution was analyzed by MEGA X and other softwares.Results:From 2020 to 2023, there were 13 120 cases of HFMD in Fujian province, and the proportion of HFMD which caused by CVA16 was 16.5% (2 160/13 120). From 2020 to 2023, the proportion of accounted cases was 4.7% (94/2 019), 14.1% (457/3 243), 47.6% (1 521/3 199) and 1.9% (88/4 659) respectively. HFMD caused by CVA16 was mainly concentrated in children aged 1 to 5 years, and most of them were 3 years old. The genetic evolution and genotype analysis of 92 complete VP1 gene sequences obtained from 2020 to 2023 showed that the genetic distance between CVA16 strains in Fujian province and the prototype strain was far away. The CVA16 genotype in Fujian province from 2020 to 2023 has three clusters of B1a, B1b and B1c, among which the composition ratio of B1a and B1b in Fujian province in 2020 was 40% and 60% respectively. In 2021, B1a and B1b accounted for 81.8% and 18.2% respectively. Only B1a in 2022; in 2023, there were B1a, B1b and B1c, which respectively accounted for 44.4%, 7.4% and 48.2%. During the period from January to September, B1a was the main cluster. After October we observed an emergence of B1c cluster, which had never been found in Fujian province and was rare in China, was detected and became the dominant cluster.Conclusions:The evolutionary cluster of CVA16 dominant changed from B1b in 2020 to B1a in 2021-2023. After October 2023, the newly discovered B1c became the dominant cluster in Fujian province.

Objective:To improve the efficiency and success rate of human adenovirus 3 (HAdV-3) whole genome sequencing, a high-throughput sequencing method for the whole genome of HAdV-3 based on multiplex PCR was established.Methods:Multiplex PCR primers suitable for the whole genome amplification of HAdV-3 were designed. The whole genome sequence of HAdV-3 was amplified by multiplex PCR, and the specificity of the amplification product was preliminarily verified by agarose gel electrophoresis. High-throughput sequencing of the multiplex PCR products was performed using Illumina second-generation sequencing. After obtaining the sequence, software such as CLC and IGV were used to analyze the effective data amount, average sequencing depth, and whole genome coverage obtained by high-throughput sequencing, then the sequencing quality was evaluated. Based on the whole genome sequencing result, a phylogenetic tree was constructed to confirm the virus type and analyze homology of the sequences, and then the accuracy of this method was evaluated.Results:A total of 70 (35 pairs) multiplex PCR amplification primers for the whole genome of HAdV-3 were designed, with amplicon size of approximately 1 200 bp. And the expected whole genome coverage could reach 99.8% (with a total genome length of approximately 35 240 bp). Agarose gel electrophoresis analysis showed that the size of the multiplex PCR products was consistent with expectations, and the amplification specificity was high. The high-throughput sequencing result showed that the whole genome sequences obtained by this method were complete and intact, and the genome coverage was consistent with expectations. Sequence quality analysis showed that the high-throughput sequencing method based on multiplex PCR could obtain more effective data and greater sequencing depth, resulting in more uniform whole genome coverage. Phylogenetic analysis showed that the evolutionary typing result of viral DNA sequenced after multiplex PCR amplification were consistent with those of viral DNA sequenced directly and had high homology, indicating that the multiplex PCR method had high amplification fidelity and the results obtained in combination with high-throughput sequencing were accurate.Conclusions:A high-throughput sequencing method for the whole genome of HAdV-3 based on multiplex PCR was established in this study successfully. This method could improve the efficiency and success rate of HAdV-3 whole genome sequencing, aiming to provide better technical support and reference for HAdV-3 pathogen surveillance and epidemic source-tracing based on whole genome sequencing.

Objective This study aimed to examine and propagate the medication experience and group formula of traditional Chinese medicine (TCM) Master XIONG Jibo in diagnosing and treating arthralgia syndrome (AS) through data mining. Methods Data of outpatient cases of Professor XIONG Jibo were collected from January 1, 2014 to December 31, 2018, along with cases recorded in A Real Famous Traditional Chinese Medicine Doctor: XIONG Jibo's Clinical Medical Record 1, which was published in December 2019. The five variables collected from the patients’ data were TCM diagnostic information, TCM and western medicine diagnoses, syndrome, treatment, and prescription. A database was established for the collected data with Excel. Using the Python environment, a customized modified natural language processing (NLP) model for the diagnosis and treatment of AS by Professor XIONG Jibo was established to preprocess the data and to analyze the word cloud. Frequency analysis, association rule analysis, cluster analysis, and visual analysis of AS cases were performed based on the Traditional Chinese Medicine Inheritance Computing Platform (V3.0) and RStudio (V4.0.3). Results A total of 610 medical records of Professor XIONG Jibo were collected from the case database. A total of 103 medical records were included after data screening criteria, which comprised 187 times (45 kinds) of prescriptions and 1 506 times (125 kinds) of Chinese herbs. The main related meridians were the liver, spleen, and kidney meridians. The properties of Chinese herbs used most were mainly warm, flat, and cold, while the flavors of herbs were mainly bitter, pungent, and sweet. The main patterns of AS included the damp heat, phlegm stasis, and neck arthralgia. The most commonly used herbs for AS were Chuanniuxi (Cyathulae Radix), Huangbo (Phellodendri Chinensis Cortex), Cangzhu (Atractylodis Rhizoma), Qinjiao (Gentianae Macrophyllae Radix), Gancao (Glycyrrhizae Radix et Rhizoma), Huangqi (Astragali Radix), and Chuanxiong (Chuanxiong Rhizoma). The most common effect of the herbs was “promoting blood circulation and removing blood stasis”, followed by “supplementing deficiency (Qi supplementing, blood supplementing, and Yang supplementing)”, and “dispelling wind and dampness”. The data were analyzed with the support ≥ 15% and confidence = 100%, and after de-duplication, five second-order association rules, 39 third-order association rules, 39 fourth-order association rules, and two fifth-order association rules were identified. The top-ranking association rules of each were “Cangzhu (Atractylodis Rhizoma) → Huangbo (Phellodendri Chinensis Cortex)” “Cangzhu (Atractylodis Rhizoma) + Chuanniuxi (Cyathulae Radix) → Huangbo (Phellodendri Chinensis Cortex)” “Chuanniuxi (Cyathulae Radix) + Danggui (Angelicae Sinensis Radix) + Gancao (Glycyrrhizae Radix et Rhizoma) → Qinjiao (Gentianae Macrophyllae Radix)” and “Chuanniuxi (Cyathulae Radix) + Danggui (Angelicae Sinensis Radix) +Gancao (Glycyrrhizae Radix et Rhizoma) + Huangbo (Phellodendri Chinensis Cortex) → Qinjiao (Gentianae Macrophyllae Radix)”, respectively. Five clusters were obtained using cluster analysis of the top 30 herbs. The herbs were mainly drying dampness, supplementing Qi, and promoting blood circulation. The main prescriptions of AS were Ermiao San (二妙散), Gegen Jianghuang San (葛根姜黄散), and Huangqi Chongteng Yin (黄芪虫藤饮). The herbs of core prescription included Cangzhu (Atractylodis Rhizoma), Chuanniuxi (Cyathulae Radix), Gancao (Glycyrrhizae Radix et Rhizoma), Huangbo (Phellodendri Chinensis Cortex), Mugua (Chaenomelis Fructus), Qinjiao (Gentianae Macrophyllae Radix), Danggui (Angelicae Sinensis Radix), and Yiyiren (Coicis Semen). Conclusion Clearing heat and dampness, relieving collaterals and pain, and invigorating Qi and blood are the most commonly used therapies for the treatment of AS by Professor XIONG Jibo. Additionally, customized NLP model could improve the efficiency of data mining in TCM.

Objective:To study the epidemiological and molecular characteristics of coxackievirus A2 (CV-A2) associated with hand, foot and mouth disease (HFMD) in Fujian province, 2011-2020.Methods:Descriptive epidemiological method was used to analyze the epidemiological characteristics of CV-A2. Case information was collected in the laboratory of Fujian Provincial Center for Disease Control and Prevention from 2011 to 2020. The VP1 gene obtained by first-generation sequencing and the complete genome obtained by second-generation sequencing were made phylogenetic analysis and recombination analysis by Mega X and Simplot3.5.1.Results:From 2011 to 2020, there were 35 HFMD-associated CV-A2 cases in Fujian province, most of whom aged 1 to 2 years (28 / 35), and the gender ratio of male to female was 2.5∶1 (25 / 10). Phylogenetic tree of VP1 region showed that CV-A2 in Fujian province was mainly distributed in the evolutionary branches of D1 and C1 subgenotype, only one strain (2019FJPT064) belonged to C1 subgenotype and the other 27 strains were grouped under D1 subgenotype. Among them, 4 isolates from 2011 to 2012 belonged to cluster 1 of D1 subgenotype, and the other two isolates from 2011 to 2012 and those after 2012 belonged to cluster 2 of D1 subgenotype. The complete genome length of 6 CV-A2 strains were about 7 393 to 7 402 bp. The homology of the nucleic acid sequences in the VP1 region of 6 CV-A2 strains and the CV-A2 prototype strain were 80.3%-81.7%, while in the other regions were 72.7%-86.2%. The phylogenetic tree of P2 region showed that 6 CV-A2 strains had a close evolutionary distance with the coxackievirus A4 (CV-A4) and the phylogenetic tree of P3 region showed that 2011FJFZ027, 2012FJQZ311 and 2020FJPTN040 had close evolutionary distance with coxackievirus A6 (CV-A6), coxackieviru A14 (CV-A14), coxackievirus A8 (CV-A8), respectively. Recombination analysis showed that 2011FJFZ027, 2012FJQZ311 and 2020FJPTN040 maybe evolved from recombinant CV-A6 strain (GenBank accession number: KR706309), CV-A14 strain (GenBank accession number: KP036482) and CV-A8 strains (GenBank accession number: KM609475 and MT648786) in non-structural protein region.Conclusions:HFMD-associated CV-A2 was sporadic in Fujian province from 2011 to 2020. The D1 subgenotype of CV-A2 was persistently circulating in Fujian province. From 2011 to 2012, the cluster 1 of D1 subgenotype was the dominant type, and then it shifted to the cluster 2 to take its place after 2012. CV-A2 strains in Fujian were frequently recombined in diversity patterns.

Objective:To investigate the gene characteristics and recombination of coxsackievirus A5(CV-A5)in Fujian province.Methods:The VP1 regions of CV-A5 strains from positive samples of hand, foot and mouth disease (HFMD) collected from all cities in Fujian province from 2011 to 2020 were amplified by reverse transcription nested polymerase chain reaction (RT-nPCR), then sequenced and identified the subgenotypes. CV-A5 strains were isolated in rhabdomyosarcoma (RD) cells. The isolated virus strains were sequenced by next generation sequencing to obtain the whole genome sequences. MEGA7.0 was used for phylogenetic analysis. RDP4 and SimPlot 3.5.1 softwares were used to analyze viral gene recombination.Results:Total thirty-one HFMD related CV-A5 cases were detected in Fujian province from 2011 to 2020, mainly in children aged 1 to 2 years (16/31), with a male/female ratio of 2.1∶1 (21/10), including 3 severe cases and 1 deceased case. CV-A5 subgenotyping was successful in 27 cases, all of them belonged to E1 subgenotype. The whole genome sequences of six CV-A5 strains were obtained, and the homology with the prototype strain Swartz was 81.1%-81.6%. Phylogenetic analysis results based on the sequences of whole genome, P1, P2 and P3 regions showed that the virus strain 2017FJFZ239 is a suspected recombinant strain, which was distributed in the same branch as CV-A5 reference strains (GenBank accession number: MW079817 and MN663160) in P2 and P3 regions. Analyzing with RDP4 showed that the virus strain 2017FJFZ239 had the same recombination event with CV-A5 reference strains (GenBank accession number: MW079817 and MN663160) and the potential parental sequences were CV-A2 (GenBank accession number: KX595284) and CV-A5 (GenBank accession number: KP289362). Further analyzing with SimPlot showed that the virus strain 2017FJFZ239 may recombine with CV-A2 strain (GenBank accession number: KX595284) in non-structural protein 2B, 2C and P3 regions.Conclusions:From 2011 to 2020, HFMD related CV-A5 in Fujian province belongs to E1 subgenotype, and there is a recombinant strain.