1.Construction and evaluation of a "disease-syndrome combination" prediction model for pulmonary nodules based on oral microbiomics
Yifeng REN ; Shiyan TAN ; Qiong MA ; Qian WANG ; Liting YOU ; Wei SHI ; Chuan ZHENG ; Jiawei HE ; Fengming YOU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(08):1105-1114
Objective To construct a "disease-syndrome combination" mathematical representation model for pulmonary nodules based on oral microbiome data, utilizing a multimodal data algorithm framework centered on dynamic systems theory. Furthermore, to compare predictive models under various algorithmic frameworks and validate the efficacy of the optimal model in predicting the presence of pulmonary nodules. Methods A total of 213 subjects were prospectively enrolled from July 2022 to March 2023 at the Hospital of Chengdu University of Traditional Chinese Medicine, Sichuan Cancer Hospital, and the Chengdu Integrated Traditional Chinese and Western Medicine Hospital. This cohort included 173 patients with pulmonary nodules and 40 healthy subjects. A novel multimodal data algorithm framework centered on dynamic systems theory, termed VAEGANTF (Variational Auto Encoder-Generative Adversarial Network-Transformer), was proposed. Subsequently, based on a multi-dimensional integrated dataset of “clinical features-syndrome elements-microorganisms”, all subjects were divided into training (70%) and testing (30%) sets for model construction and efficacy testing, respectively. Using pulmonary nodules as dependent variables, and combining candidate markers such as clinical features, lesion location, disease nature, and microbial genera, the independent variables were screened based on variable importance ranking after identifying and addressing multicollinearity. Missing values were then imputed, and data were standardized. Eight machine learning algorithms were then employed to construct pulmonary nodule risk prediction models: random forest, least absolute shrinkage and selection operator (LASSO) regression, support vector machine, multilayer perceptron, eXtreme Gradient Boosting (XGBoost), VAE-ViT (Vision Transformer), GAN-ViT, and VAEGANTF. K-fold cross-validation was used for model parameter tuning and optimization. The efficacy of the eight predictive models was evaluated using confusion matrices and receiver operating characteristic (ROC) curves, and the optimal model was selected. Finally, goodness-of-fit testing and decision curve analysis (DCA) were performed to evaluate the optimal model. Results There were no statistically significant differences between the two groups in demographic characteristics such as age and sex. The 213 subjects were randomly divided into training and testing sets (7 : 3), and prediction models were constructed using the eight machine learning algorithms. After excluding potential problems such as multicollinearity, a total of 301 clinical feature information, syndrome elements, and microbial genera markers were included for model construction. The area under the curve (AUC) values of the random forest, LASSO regression, support vector machine, multilayer perceptron, and VAE-ViT models did not reach 0.85, indicating poor efficacy. The AUC values of the XGBoost, GAN-ViT, and VAEGANTF models all reached above 0.85, with the VAEGANTF model exhibiting the highest AUC value (AUC=0.923). Goodness-of-fit testing indicated good calibration ability of the VAEGANTF model, and decision curve analysis showed a high degree of clinical benefit. The nomogram results showed that age, sex, heart, lung, Qixu, blood stasis, dampness, Porphyromonas genus, Granulicatella genus, Neisseria genus, Haemophilus genus, and Actinobacillus genus could be used as predictors. Conclusion The “disease-syndrome combination” risk prediction model for pulmonary nodules based on the VAEGANTF algorithm framework, which incorporates multi-dimensional data features of “clinical features-syndrome elements-microorganisms”, demonstrates better performance compared to other machine learning algorithms and has certain reference value for early non-invasive diagnosis of pulmonary nodules.
2.Expert consensus on prognostic evaluation of cochlear implantation in hereditary hearing loss.
Xinyu SHI ; Xianbao CAO ; Renjie CHAI ; Suijun CHEN ; Juan FENG ; Ningyu FENG ; Xia GAO ; Lulu GUO ; Yuhe LIU ; Ling LU ; Lingyun MEI ; Xiaoyun QIAN ; Dongdong REN ; Haibo SHI ; Duoduo TAO ; Qin WANG ; Zhaoyan WANG ; Shuo WANG ; Wei WANG ; Ming XIA ; Hao XIONG ; Baicheng XU ; Kai XU ; Lei XU ; Hua YANG ; Jun YANG ; Pingli YANG ; Wei YUAN ; Dingjun ZHA ; Chunming ZHANG ; Hongzheng ZHANG ; Juan ZHANG ; Tianhong ZHANG ; Wenqi ZUO ; Wenyan LI ; Yongyi YUAN ; Jie ZHANG ; Yu ZHAO ; Fang ZHENG ; Yu SUN
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(9):798-808
Hearing loss is the most prevalent disabling disease. Cochlear implantation(CI) serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system(Favorable, Marginal, Poor). The consensus focuses on common hereditary non-syndromic hearing loss(such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1) and syndromic hereditary hearing loss(such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome), which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans
;
Cochlear Implantation
;
Prognosis
;
Hearing Loss/surgery*
;
Consensus
;
Connexin 26
;
Mutation
;
Sulfate Transporters
;
Connexins/genetics*
3.Factors influencing maxillary dental arch development in children after Sommerlad-Furlow palatoplasty.
Jue WANG ; Yuanyuan LI ; Ming WU ; Bing SHI ; Qian ZHENG ; Renkai LIU ; Chenghao LI
West China Journal of Stomatology 2025;43(2):197-203
OBJECTIVES:
This study aims to investigate factors influencing dental arch development in patients aged 0-6 years with cleft palate after Sommerlad-Furlow (SF) palatoplasty.
METHODS:
A total of 183 patients who underwent primary SF repair for cleft lip and palate before 18 months of age were included. Follow-ups were conducted at different ages, and digital dental casts of the maxillary dental arch were obtained using 3-matic Research 12.0 software. The length and width of the dental arch and palate were measured to explore developmental changes in the maxillary dental arch of the patients after the procedure. The study also investigated the influence of gender, age, cleft palate type, and relaxation incision on maxillary dental arch development.
RESULTS:
After SF, maxillary dental arch measurements showed statistically significant differences between children aged 0-2 years and those aged 3-6 years (P<0.05). However, no statistically significant differences were observed among different age groups within the 3-6 years range. Statistically significant differences were detected between males and females, with males having greater width of the posterior dental arch and palate (P=0.001) and shorter length of the anterior dental arch and entire dental arch (P<0.05). The unilateral cleft lip and palate group had shorter dental arch length (P<0.01) and wider posterior palate (P<0.01) than the cleft palate only group. Maxillary dental arch measurements had no statistically significant differences between groups with or without a relaxing incision.
CONCLUSIONS
Gender and age influence the width of the maxillary dental arch in children aged 0-6 years after SF, while age and cleft palate type affect dental arch length.
Humans
;
Child, Preschool
;
Male
;
Cleft Palate/surgery*
;
Female
;
Child
;
Infant
;
Dental Arch/growth & development*
;
Maxilla/growth & development*
;
Cleft Lip/surgery*
;
Age Factors
;
Sex Factors
;
Palate/surgery*
;
Infant, Newborn
4.Preliminary exploration and reliability analysis of clinical diagnostic method for marginal velopharyngeal insufficiency.
Xinyi HUANG ; Qirong MAO ; Heng YIN ; Min WU ; Bing SHI ; Qian ZHENG ; Jingtao LI
West China Journal of Stomatology 2025;43(3):376-382
OBJECTIVES:
A stable, reliable, and easily implementable clinical diagnostic method for marginal velopharyngeal insufficiency (MVPI) was established on the basis of the subjective hearing judgement of hypernasality and objective examination of velopharyngeal closure to address the lack of unified diagnostic criteria for MVPI.
METHODS:
Nasopharyngeal fiberscopy and speech assessment results were collected from postoperative patients with cleft palate. These results were used to analyze the differences in the distribution of nasal resonance in patients with different velopharyngeal closure ratios and the correlation between velopharyngeal closure ratios and nasal resonance status. Mild-to-moderate hypernasality with its corresponding elopharyngeal closure ratio was employed to establish the diagnostic criteria of MVPI. The reproducibility of the criteria and whether the patients with MVPI diagnosed by using the criteria exhibited significantly different speech characteristics compared with other patients were verified.
RESULTS:
A strong correlation was found between velopharyngeal closure ratios and nasal resonance (P<0.001). Mild-to-moderate hypernasality mainly corresponded to velopharyngeal closure ratios ranging from 90% to 99%, and the combination of the two characteristics as the diagnostic criteria for MVPI demonstrated good consistency (Kappa value=0.789, P<0.001). Moreover, under the diagnostic criteria, significant differences in nasal resonance (P<0.001), nasal emission (P=0.007), and misarticulation (P<0.001) were found between patients with velopharyngeal insufficiency and those with MVPI.
CONCLUSIONS
Combining the subjective hearing judgement of mild-to-moderate hypernasality with velopharyngeal closure ratios over 90% under nasopharyngeal fiberscopy provides a reliable and effective clinical method for diagnosing MVPI.
Humans
;
Velopharyngeal Insufficiency/physiopathology*
;
Reproducibility of Results
;
Cleft Palate/surgery*
;
Male
;
Female
;
Child
5.A real-world retrospective study of pelvic floor muscle training efficacy using an APP-based home device
Ji-Qiong ZHENG ; Shi-Ping ZHOU ; Zhong-Yun ZHANG ; Wei-Qing QIAN ; Zheng-Wang ZHANG
Fudan University Journal of Medical Sciences 2024;51(1):96-101
Objective To retrospectively investigate the efficacy of pelvic floor muscle training(PFMT)using APP-based home device in the real-world scenario.Methods A retrospective survey was conducted among 171 000 Chinese female users over 18 years old who freely registered APP and performed PFMT using a domestic manufactured home device from Oct 1,2019 to Mar 31,2021.The Patient Global Impression of Improvement(PGI-I)questionnaires concerning pelvic floor general condition,sexual satisfaction and other three major symptoms related to pelvic floor muscle laxity such as stress urinary incontinence(SUI),pelvic organ prolapse(POP),and vaginal laxity(VL)were broadcast public online for users to self-assess the improvement.The vaginal muscle strength values prior and post training recorded by APP were also reported.All data were collected anonymously for further stratified analysis.Results A total of 984 valid questionnaires were collected by systematic sampling.The PGI-I scores of pelvic floor general condition(P=0.000 1),sexual satisfaction(P=0.009),SUI(P=0.000 1),POP(P=0.044)and VL(P=0.034)were statistically significant in users who reported to use the device for 3 months or more compared with those less than 3 months.In addition,the increase of vaginal muscle strength was related to the improvement of PGI-I scores in SUI and POP with statistical significance.There were no significant difference in subgroups such as age,education,parity,and delivery mode.Conclusion The subjective benefit of pelvic floor function-related symptoms and the improvement of vaginal muscle strength could be observed after PFMT for three months or more using APP-based home device in Chinese women in the real-world scenario.
6.The experience on the construction of the cluster prevention and control system for COVID-19 infection in designated hospitals during the period of "Category B infectious disease treated as Category A"
Wanjie YANG ; Xianduo LIU ; Ximo WANG ; Weiguo XU ; Lei ZHANG ; Qiang FU ; Jiming YANG ; Jing QIAN ; Fuyu ZHANG ; Li TIAN ; Wenlong ZHANG ; Yu ZHANG ; Zheng CHEN ; Shifeng SHAO ; Xiang WANG ; Li GENG ; Yi REN ; Ying WANG ; Lixia SHI ; Zhen WAN ; Yi XIE ; Yuanyuan LIU ; Weili YU ; Jing HAN ; Li LIU ; Huan ZHU ; Zijiang YU ; Hongyang LIU ; Shimei WANG
Chinese Critical Care Medicine 2024;36(2):195-201
The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.
7.The First Application of Domestically Produced Self-expanding Transcatheter Aortic Valve Controllable Bending Delivery System in China
Yang CHEN ; Guoliang CHEN ; Di SONG ; Hongliang ZHANG ; Moyang WANG ; Guannan NIU ; Zheng ZHOU ; Qian ZHANG ; Qingrong LIU ; Zhenyan ZHAO ; Jie ZHAO ; Bin ZHANG ; Dejing FENG ; Wence SHI ; Jicheng XI ; Yongjian WU
Chinese Circulation Journal 2024;39(3):285-289
A domestically produced self-expanding transcatheter aortic valve controllable bending delivery system(VitaFlow? Ⅲcontrollable bending retrievable delivery system)was first used to perform transcatheter aortic valve replacement(TAVR)in a symptomatic severe aortic valve stenosis patient with severe heart failure and high risk of surgery in China on September 22,2023.The patient successfully completed TAVR under general anesthesia,with good valve position and function after the operation.Before discharge and at one month of follow-up,the patient's symptoms and degree of heart failure were significantly improved.The follow-up results of this case showed that the VitaFlow? Ⅲ controllable bending retrievable delivery system for TAVR is safe and feasible,and future prospective,multicenter clinical trials are expected to evaluate its efficacy.
8.Surveillance of bacterial resistance in tertiary hospitals across China:results of CHINET Antimicrobial Resistance Surveillance Program in 2022
Yan GUO ; Fupin HU ; Demei ZHU ; Fu WANG ; Xiaofei JIANG ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Yuling XIAO ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Jingyong SUN ; Qing CHEN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yunmin XU ; Sufang GUO ; Yanyan WANG ; Lianhua WEI ; Keke LI ; Hong ZHANG ; Fen PAN ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Wei LI ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Qian SUN ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanqing ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Wenhui HUANG ; Juan LI ; Quangui SHI ; Juan YANG ; Abulimiti REZIWAGULI ; Lili HUANG ; Xuejun SHAO ; Xiaoyan REN ; Dong LI ; Qun ZHANG ; Xue CHEN ; Rihai LI ; Jieli XU ; Kaijie GAO ; Lu XU ; Lin LIN ; Zhuo ZHANG ; Jianlong LIU ; Min FU ; Yinghui GUO ; Wenchao ZHANG ; Zengguo WANG ; Kai JIA ; Yun XIA ; Shan SUN ; Huimin YANG ; Yan MIAO ; Mingming ZHOU ; Shihai ZHANG ; Hongjuan LIU ; Nan CHEN ; Chan LI ; Jilu SHEN ; Wanqi MEN ; Peng WANG ; Xiaowei ZHANG ; Yanyan LIU ; Yong AN
Chinese Journal of Infection and Chemotherapy 2024;24(3):277-286
Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5%were gram-positive and 70.5%were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3%,76.7%and 77.9%,respectively.Overall,94.0%of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8%of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2%in the isolates from children and 95.7%in the isolates from adults.The resistance rate to carbapenems was lower than 13.1%in most Enterobacterales species except for Klebsiella,21.7%-23.1%of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1%to 13.3%.The prevalence of meropenem-resistant strains decreased from 23.5%in 2019 to 18.0%in 2022 in Pseudomonas aeruginosa,and decreased from 79.0%in 2019 to 72.5%in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.
9.Porcine SIRT5 promotes replication of foot and mouth disease virus type O in PK-15 cells
Guo-Hui CHEN ; Xi-Juan SHI ; Xin-Tian BIE ; Xing YANG ; Si-Yue ZHAO ; Da-Jun ZHANG ; Deng-Shuai ZHAO ; Wen-Qian YAN ; Ling-Ling CHEN ; Mei-Yu ZHAO ; Lu HE ; Hai-Xue ZHENG ; Xia LIU ; Ke-Shan ZHANG
Chinese Journal of Zoonoses 2024;40(5):421-429
The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.
10.Effect of LAG3 molecule on B lymphocyte subsets and its function in the liver of mice infected with Echinococcus multilocularis
Xu-Ran ZHENG ; Bing-Qing DENG ; Xue-Jiao KANG ; Yin-Shi LI ; Ainiwaer ABIDAN ; Qian YU ; Rousu ZIBIGU ; Duolikun ADILAI ; Mao-Lin WANG ; Hui WANG ; Chuan-Shan ZHANG ; Jing LI
Chinese Journal of Zoonoses 2024;40(6):529-536
This study was aimed at investigating the effect of lymphocyte activation gene-3(LAG3)on liver B lymphocyte subsets and their functions in WT and LAG3-KO mice infected with Echinococcus multilocularis(E.multilocularis).In a mouse model of E.multilocularis infection,the expression and localization of CD19 and α-SMA in liver were detected by immu nohistochemistry.CD80,CD86 and MHC-Ⅱ molecules expressed on B cells and their subsets in mice liver were detected by flow cytometry.After 12 weeks of infection,the area and percentage of CD19 in LAG3-KO group was slightly higher than that in WT group,but the difference was not statistically(t=-1.241、-1.237,P>0.05).The area and percentage of a-SMA in LAG3-KO group was higher than that in WT group(t=-3.224、-3.227,P<0.05).The proportion of CD80 and MHC-Ⅱ molecules expressed on liver B cells in LAG3-KO group was up-regulated(t=-2.379,-3.321,P<0.05).The percentage of liver B2 cells in LAG3-KO group was higher than that in WT group(t=-2.695,P<0.05).The expression of CD80 on Blb cells in LAG3-KO group was significantly up-regulated(t=-5.315,P<0.001).The proportion of CD80 of B2 cells in LAG3-KO group was lower than that in WT group(t=2.806,P<0.05).The expression of MHC-Ⅱ molecule in B2 cells in LAG3-KO group was up-regulated(t=-4.227,P<0.01).It is suggested that LAG3 molecules affected the B cell subsets and func-tion of mouse liver in the middle stage of E.multilocularis infection,especially B2 lymphocytes.LAG3 molecule exerted an in-hibitory effect on the activation of B cells and the expression of MHC-class Ⅱ molecules,suggesting that it may be involved in B cell exhaustion caused by E.multilocularis.

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