1.Phylogenetic and antigenic analysis on hemagglutinin gene of influenza B virus (Victoria) in 2023-2024 surveillance season in Beijing
Guilan LU ; Jiachen ZHAO ; Weixian SHI ; Li ZHANG ; Yimeng LIU ; Zhaomin FENG ; Ying SUN ; Daitao ZHANG ; Xiaomin PENG
Chinese Journal of Experimental and Clinical Virology 2024;38(4):415-421
		                        		
		                        			
		                        			Objective:To disclose phylogenetic and antigenic characteristics of hemagglutinin (HA) gene of influenza B virus (Victoria) (BV) in the 2023-2024 influenza surveillance season in Beijing, and understand the matching with influenza vaccine component strain.Methods:Pharyngeal swab specimens from influenza like-illness (ILI) in the 2023-2024 influenza surveillance season were collected from surveillance network labs in Beijing and BV strains were isolated through MDCK or chicken embryo culture. After extracting nucleic acid, HA gene was amplified and sequenced. The nucleotide and amino acid sequence identity were conducted and the maximum likelihood method in Mega 5.0 software was used to construct the phylogenetic tree of HA gene. N-glycosylation sites of HA were performed online. Furthermore, three-dimensional structure of HA was available from SWISS-MODEL homologous modeling. Hemagglutination inhibition (HI) tests were performed to analyze antigenic characteristics of HA of BV strains.Results:Fifty-four BV strains were randomly selected to be analyzed further. Compared with the HA gene of this influenza season vaccine strain (B/Austria/1359417/2021), there are three amino acid mutations among all BV strains, two of which are located in two different antigenic determinants. Furthermore, the phylogenetic tree analysis revealed that only one subgroup of 1A.3a.2 was circulating simultaneously. All BV strains are located in Clade 1A.3a.2 subgroup, and in the same subgroup with that of the vaccine component BV strain in 2023-2024. All BV strains have the same glycosylation sites as that of the vaccine component BV strain in 2023-2024. Antigenic analysis showed that all BV strains were antigenically similar with its vaccine strain.Conclusions:In the 2023-2024 influenza surveillance season, the prevalent BV strains in the population in Beijing city are located in Clade 1A. 3a. 2 subgroup. The antigen matching between BV epidemic strains and vaccine BV components is relatively high during this surveillance season.
		                        		
		                        		
		                        		
		                        	
2.Pharmacovigilance for Radiopharmaceuticals
Yue SUN ; Yuxuan ZHENG ; Zhenjiang ZHANG ; Yuxian ZHANG ; Ran ZHANG ; Chang LU ; Li ZHANG ; Ding LI ; Jiachen TU ; Jing XIE ; Huan ZHOU ; Jian GONG
Herald of Medicine 2024;43(10):1615-1619
		                        		
		                        			
		                        			Radiopharmaceuticals play an important role in the medical field,but they also carry certion risks and potential safety concerns.Medical institutions implement pharmacovigilance to ensure the safety of patients'drug use,including the safety of Radiopharmaceuticals.The operation and management of the pharmacovigilance system in the United States and the European Union are relatively mature.China can learn from their advanced concepts and establish our own radiopharmaciligence system.
		                        		
		                        		
		                        		
		                        	
3.Endoscopic ultrasonography is useful for predicting perforation in the endoscopic resection of gastric submucosal tumors originating from the muscularis propria: a retrospective case-control study
Yi LU ; Xianhua ZHUO ; Qinghua ZHONG ; Jiachen SUN ; Chujun LI ; Min ZHI
Ultrasonography 2023;42(1):78-88
		                        		
		                        			 Purpose:
		                        			Models for predicting perforation during endoscopic resection (ER) of gastric submucosal tumors (SMTs) originating from the muscularis propria (MP) are rare. Therefore, this study was conducted to determine important parameters in endoscopic ultrasonography (EUS) images to predict perforation and to build predictive models.  
		                        		
		                        			Methods:
		                        			Consecutive patients with gastric SMTs originating from the MP who received ER from May 1, 2013 to January 15, 2021 were retrospectively reviewed. They were classified into case and control groups based on the presence of perforation. Logistic multivariate analysis was used to identify potential variables and build predictive models (models 1 and 2: with and without information on tumor pathology, respectively).  
		                        		
		                        			Results:
		                        			In total, 199 EUS procedures (194 patients) were finally chosen, with 99 procedures in the case group and 100 in the control group. The ratio of the inner distance to the outer distance (I/O ratio) was significantly larger in the case group than in the control group (median ratio, 2.20 vs. 1.53; P<0.001). Multivariate analysis showed that age (odds ratio [OR], 1.036 in model 1; OR, 1.046 in model 2), the I/O ratio (OR, 2.731 in model 1; OR, 2.372 in model 2), and the pathology of the tumors (OR, 10.977 for gastrointestinal stromal tumors; OR, 15.051 for others in model 1) were risk factors for perforation. The two models to predict perforation had areas under the curve of 0.836 (model 1) and 0.755 (model 2).  
		                        		
		                        			Conclusion
		                        			EUS was useful in predicting perforation in ER for gastric SMTs originating from the MP. Two predictive models were developed. 
		                        		
		                        		
		                        		
		                        	
4.Phylogenetic and antigenic analysis of HA gene of influenza virus B (Victoria) in Beijing during 2021-2022 surveillance season
Guilan LU ; Shujuan CUI ; Jiachen ZHAO ; Yimeng LIU ; Weixian SHI ; Zhaomin FENG ; Yang PAN ; Daitao ZHANG ; Peng YANG ; Quanyi WANG ; Xiaomin PENG
Chinese Journal of Microbiology and Immunology 2023;43(8):619-626
		                        		
		                        			
		                        			Objective:To investigate the phylogenetic and antigenic characteristics of hemagglutinin (HA) gene of influenza B/Victoria lineage (BV) viruses in Beijing during the 2021-2022 influenza surveillance season, and to analyze whether the circulating BV viruses match the vaccine strain.Methods:Pharyngeal swab specimens from influenza like-illness (ILI) cases in the 2021-2022 influenza surveillance season were collected from surveillance network labs in Beijing and cultured in MDCK cells and chicken embryo to isolate BV viruses. Nucleic acids of the viruses were extracted, and the HA gene was amplified and sequenced. The nucleotide and amino acid sequence identity of the HA gene was analyzed using MEGA5.0 software. A phylogenetic tree of HA gene was constructed using the maximum likelihood method. The N-glycosylation sites in HA were predicted online. Three-dimensional structure of HA was constructed using SWISS-MODEL homologous modeling. Hemagglutination inhibition (HI) test was performed to analyze the antigenicity of BV viruses.Results:A total of 402 BV viruses were collected and 58 strains with full-length HA gene sequences were chosen for further analysis. Compared with the HA gene of this year′s vaccine strain (B/Washington/02/2019), there were 27 amino acid mutations, 11 of which were located in four different antigenic determinants. The phylogenetic analysis revealed that three subgroups of 1A.3, 1A.3a1, and 1A.3a2 co-circulated in Beijing with 54 strains (54/58, 93.10%) clustered to the Clade 1A.3a2, two strains (2/58, 3.45%) clustered to the Clade 1A.3a1, and two strains (2/58, 3.45%) in the same subgroup (Clade 1A.3) as the vaccine component BV strain in 2021-2022. Compared with the vaccine strain (B/Washington/02/2019), two BV strains had an additional N-glycosylation site at residue 197, while the other 56 strains showed no change in N-glycosylation sites. Antigenic analysis showed that 35 BV strains (35/58, 60.34%) were antigenically similar to the vaccine strain and 23 strains (23/58, 39.66%) were low-response strains.Conclusions:Three subgroups of BV viruses co-circulated in Beijing during the 2021-2022 influenza surveillance season. The predominant subgroup was Clade 1A.3a2 (93.10%), showing a certain genetic distance with the vaccine strain (B/Washington/02/2019). Nearly 40% (39.66%) of the viruses were low-response strains. This study indicated that continuous monitoring of the variations of influenza epidemic strains and timely providing laboratory basis for screening vaccine component strains were the basic technical guarantee for coping with influenza pandemic.
		                        		
		                        		
		                        		
		                        	
5.Artificial Intelligence in the Prediction of Gastrointestinal Stromal Tumors on Endoscopic Ultrasonography Images: Development, Validation and Comparison with Endosonographers
Yi LU ; Jiachuan WU ; Minhui HU ; Qinghua ZHONG ; Limian ER ; Huihui SHI ; Weihui CHENG ; Ke CHEN ; Yuan LIU ; Bingfeng QIU ; Qiancheng XU ; Guangshun LAI ; Yufeng WANG ; Yuxuan LUO ; Jinbao MU ; Wenjie ZHANG ; Min ZHI ; Jiachen SUN
Gut and Liver 2023;17(6):874-883
		                        		
		                        			 Background/Aims:
		                        			The accuracy of endosonographers in diagnosing gastric subepithelial lesions (SELs) using endoscopic ultrasonography (EUS) is influenced by experience and subjectivity. Artificial intelligence (AI) has achieved remarkable development in this field. This study aimed to develop an AI-based EUS diagnostic model for the diagnosis of SELs, and evaluated its efficacy with external validation. 
		                        		
		                        			Methods:
		                        			We developed the EUS-AI model with ResNeSt50 using EUS images from two hospitals to predict the histopathology of the gastric SELs originating from muscularis propria. The diagnostic performance of the model was also validated using EUS images obtained from four other hospitals. 
		                        		
		                        			Results:
		                        			A total of 2,057 images from 367 patients (375 SELs) were chosen to build the models, and 914 images from 106 patients (108 SELs) were chosen for external validation. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the model for differentiating gastrointestinal stromal tumors (GISTs) and non-GISTs in the external validation sets by images were 82.01%, 68.22%, 86.77%, 59.86%, and 78.12%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the external validation set by tumors were 83.75%, 71.43%, 89.33%, 60.61%, and 80.56%, respectively. The EUS-AI model showed better performance (especially specificity) than some endosonographers.The model helped improve the sensitivity, specificity, and accuracy of certain endosonographers. 
		                        		
		                        			Conclusions
		                        			We developed an EUS-AI model to classify gastric SELs originating from muscularis propria into GISTs and non-GISTs with good accuracy. The model may help improve the diagnostic performance of endosonographers. Further work is required to develop a multi-modal EUS-AI system. 
		                        		
		                        		
		                        		
		                        	
6.Preliminary investigation and analysis on the epidemic situation of Redondoviridae in Beijing
Jiachen ZHAO ; Yimeng LIU ; Lin ZOU ; Xiaomin PENG ; Guilan LU ; Cheng QIAN ; Shujuan CUI ; Daitao ZHANG ; Weixian SHI
Chinese Journal of Experimental and Clinical Virology 2023;37(2):135-139
		                        		
		                        			
		                        			Objective:To understand the epidemic situation of Redondoviridae in Beijing and analyze its epidemiologic characteristics.Methods:Pharyngeal swab samples of healthy people and patients with acute respiratory infection in Beijing, including influenza like cases and severe acute respiratory infection (SARI) cases in hospitals were collected. Real time PCR was used to detect the nucleic acid of Redondoviridae. The positive samples were amplified and sequenced to analyze their species. The age and sex distribution of patients and species distribution of Redondoviridae were obtained through statistical analysis. Multiplex PCR was used to detect other common respiratory pathogens in the positive samples of Redondoviridae in influenza like cases and SARI cases, and the pathogenicity of Redondoviridae was analyzed.Results:The positive rates of Redondoviridae in healthy people and acute respiratory infection cases were 20.48% (189/923) and 11.23% (43/390), respectively, with a statistically significant difference ( P<0.05). The positive rate of male was higher than that of female in the healthy population, and the positive rate of the elderly group was higher than that of the adult group and the underage group, with a statistically significant difference ( P<0.05). The positive rate of male patients with acute respiratory tract infection was higher than that of female patients, but there was no significant difference. The proportion of Vientovirus in the positive samples of Redondoviridae was higher than that of Brisavirus, and the difference was statistically significant ( P<0.05). Among the throat swabs of respiratory tract infection cases, 43 were positive for Redondoviridae, of whom 24 were not detected for other pathogens. Conclusions:Redondoviridae widely exists in healthy people of all age groups in Beijing, and is also found in acute respiratory infection cases. The positive rate of Redondoviridae is different in different ages and genders. Both Vientovirus and Brisavirus were detected, and the proportion of Vientovirus was significantly higher than Brisavirus.
		                        		
		                        		
		                        		
		                        	
7.Epidemic characteristics and hemagglutinin gene variation of influenza A(H3N2) in Beijing, 2022—2023
Jiachen ZHAO ; Yimeng LIU ; Xiaomin PENG ; Guilan LU ; Shujuan CUI ; Ying SUN ; Daitao ZHANG ; Weixian SHI
Chinese Journal of Experimental and Clinical Virology 2023;37(6):606-612
		                        		
		                        			
		                        			Objective:To characterize the epidemic of influenza in Beijing from 2022 to 2023 and the variation of gene and antigenicity of hemagglutinin (HA) of influenza A H3N2 virus, so as to provide scientific basis for influenza prevention and control in Beijing.Methods:Statistical analysis was carried out on the result of influenza pathogenic monitoring in Beijing from week 14, 2022 to week 20, 2023, and 79 strains of influenza A H3N2 virus were selected at different time and population sources, and their genetic variation and evolution characteristics were analyzed through HA gene amplification sequencing and antigenicity analysis.Results:From week 14, 2022 to week 20, 2023, 24 244 throat swabs of influenza like cases were collected in Beijing, and 4 987 influenza virus nucleic acid positive cases were detected, including 2 749 influenza A H3N2 positive cases, with a detection rate of 11.34%. Among the 79 strains, 50 strains (63.29%) showed low response, 94.44% of the strains from August to November 2022 had low response, and 54.10% of the strains from February to March 2023 had low response, with a statistically significant difference ( χ2=8.079, P=0.004). Compared with the vaccine strain A/Darwin/9/2021, the HA gene sequence of 79 strains of influenza A H3N2 showed nucleotide similarity of 97.47% to 98.47% and amino acid similarity of 97.05% to 98.17%. Genetic evolution analysis showed that the 18 strains isolated from August to November 2022 were all distributed in the 3C.2a1b.2a.1a.1 branch, while the 61 strains isolated from February to March 2023 all belonged to the 3C.2a1b.2a.3a.1 branch. Compared with the vaccine strain, there were multiple site mutations distributed at multiple antigenic determinants and receptor binding sites in A, B, C, D, and E. All strains had potential glycosylation sites of 8NST, 22NGT, 38NAT, 45NSS, 63NCT, 126NWT, 133NGT, 246NST, 285NGS, 483NET, while one strain missed 165NVT glycosylation sites; 55 strains between February and March 2023 missed 122NES glycosylation sites. Conclusions:The HA gene locus of influenza A H3N2 virus detected in Beijing from week 14, 2022 to week 20, 2023 showed multiple mutations, continuous monitoring of this subtype variation is crucial.
		                        		
		                        		
		                        		
		                        	
8.Analysis of emm genotypes and drug susceptibility characteristic variations of Group A Streptococcus in children in Beijing
Jiachen ZHAO ; Yimeng LIU ; Xiaomin PENG ; Shujuan CUI ; Guilan LU ; Weixian SHI ; Chunna MA ; Fu LI ; Daitao ZHANG ; Quanyi WANG ; Peng YANG
Chinese Journal of Applied Clinical Pediatrics 2022;37(21):1645-1650
		                        		
		                        			
		                        			Objective:To clarify the M protein ( emm gene) types and drug susceptibility characteristic variations of Group A Streptococcus (GAS) in children in Beijing. Methods:The GAS strains isolated from throat swab samples of children diagnosed with scarlet fever and pharyngeal infection in scarlet fever etiology surveillance sentinel hospitals in 16 districts of Beijing in 2018, 2019 and 2021 were analyzed retrospectively.PCR amplification and sequencing were used for emm genotyping, and the minimum inhibitory concentrations (MIC) of 10 antibiotics were determined by the broth microdilution method.The data were analyzed using χ2 test and Fisher′ s exact method between groups. Results:A total of 557 GAS strains were collected, and 11 emm genotypes ( emm1, emm3, emm4, emm6, emm11, emm12, emm22, emm75, emm89, emm128, and emm212) were detected.Of 557 strains, 238 trains were of emm1 type (42.73%), 271 strains were of emm12 type (48.65%) and 48 strains were of other emm types (8.62%). The detection rates of emm1, emm12 and other emm type genes in 2018, 2019, and 2021 were [37.50% (105/280 strains), 57.14% (160/280 strains), 5.36% (15/280 strains)], [49.05% (129/263 strains), 39.54% (104/263 strains), 11.41% (30/263 strains)], and [28.57% (4/14 strains), 50.00% (7/14 strains), 21.43% (3/14 strains)], respectively.In children infected with emm12 in 2018 and 2019, there were more children under 6 years old than children over 6 years old (62.50% vs.46.88%, 46.36% vs.30.36%) (χ 2=7.182, 6.973; all P<0.05). Drug susceptibility testing results suggested that 225 randomly selected GAS strains were all 100.00% sensitive to 7 antibiotics including Penicillin, Levofloxacin, Meropenem, Linezolid, Cefotaxime, Cefepime and Vancomycin.The rates of resistance to Erythromycin, Tetracycline and Clindamycin were [88.57% (93/105 strains), 87.62% (92/105 strains), 86.67% (91/105 strains)], and [94.34% (100/106 strains), 94.34% (100/106 strains), 87.74% (93/106 strains)] in 2018 and 2019, respectively.The test strains were 100.00% (14/14 strains) resistant to the above 3 antibiotics in 2021.MIC 50 and MIC 90 values of Penicillin in 2018, 2019, and 2021 were (0.03 mg/L, 0.03 mg/L), (0.03 mg/L, 0.06 mg/L), and (0.06 mg/L, 0.06 mg/L), respectively.Among 225 GAS strains, 207 strains had drug resistance and were resistant to more than one drug.Specifically, 94.69% (196/207 strains) were resistant to Erythromycin, Tetracycline and Clindamycin.About 4.35% (9/207 strains) were resistant to both Erythromycin and Clindamycin.A total of 0.97% (2/207 strains) were resistant to Erythromycin and Tetracycline. Conclusions:The emm genotypes of GAS in children in Beijing are diverse in 2018, 2019 and 2021.The dominant genotypes are emm12 and emm1, and emm12 is the main epidemiological type.GAS strains maintain highly resistant to Erythromycin, Clindamycin and Tetracycline, and sensitive to Penicillin and other antibiotics.However, MIC 50 and MIC 90 of Penicillin shows an ascending trend.
		                        		
		                        		
		                        		
		                        	
9.Enzyme ancestral sequence reconstruction and directed evolution.
Kun ZHANG ; Yifei DAI ; Jindi SUN ; Jiachen LU ; Kequan CHEN
Chinese Journal of Biotechnology 2021;37(12):4187-4200
		                        		
		                        			
		                        			The amino acid sequence of ancestral enzymes from extinct organisms can be deduced through in silico approach termed ancestral sequence reconstruction (ASR). ASR usually has six steps, which are the collection of nucleic acid/amino acid sequences of modern enzymes, multiple sequence alignment, phylogenetic tree construction, computational deduction of ancestral enzyme sequence, gene cloning, and characterization of enzyme properties. This method is widely used to study the adaptation and evolution mechanism of molecules to the changing environmental conditions on planetary time scale. As enzymes play key roles in biocatalysis, this method has become a powerful method for studying the relationship among the sequence, structure, and function of enzymes. Notably, most of the ancestral enzymes show better temperature stability and mutation stability, making them ideal protein scaffolds for further directed evolution. This article summarizes the computer algorithms, applications, and commonly used computer software of ASR, and discusses the potential application in directed evolution of enzymes.
		                        		
		                        		
		                        		
		                        			Amino Acid Sequence
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		                        			Evolution, Molecular
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		                        			Phylogeny
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		                        			Proteins/genetics*
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		                        			Sequence Alignment
		                        			
		                        		
		                        	
10.Quantitative analysis of breathing patterns based on wearable systems.
Jiachen WANG ; Hong LIANG ; Yajing WANG ; Weitao WANG ; Ke LAN ; Lu CAO ; Zhengbo ZHANG ; Yuzhu LI ; Zhiwen LIU ; Desen CAO
Journal of Biomedical Engineering 2021;38(5):893-902
		                        		
		                        			
		                        			Breathing pattern parameters refer to the characteristic pattern parameters of respiratory movements, including the breathing amplitude and cycle, chest and abdomen contribution, coordination, etc. It is of great importance to analyze the breathing pattern parameters quantificationally when exploring the pathophysiological variations of breathing and providing instructions on pulmonary rehabilitation training. Our study provided detailed method to quantify breathing pattern parameters including respiratory rate, inspiratory time, expiratory time, inspiratory time proportion, tidal volume, chest respiratory contribution ratio, thoracoabdominal phase difference and peak inspiratory flow. We also brought in "respiratory signal quality index" to deal with the quality evaluation and quantification analysis of long-term thoracic-abdominal respiratory movement signal recorded, and proposed the way of analyzing the variance of breathing pattern parameters. On this basis, we collected chest and abdomen respiratory movement signals in 23 chronic obstructive pulmonary disease (COPD) patients and 22 normal pulmonary function subjects under spontaneous state in a 15 minute-interval using portable cardio-pulmonary monitoring system. We then quantified subjects' breathing pattern parameters and variability. The results showed great difference between the COPD patients and the controls in terms of respiratory rate, inspiratory time, expiratory time, thoracoabdominal phase difference and peak inspiratory flow. COPD patients also showed greater variance of breathing pattern parameters than the controls, and unsynchronized thoracic-abdominal movements were even observed among several patients. Therefore, the quantification and analyzing method of breathing pattern parameters based on the portable cardiopulmonary parameters monitoring system might assist the diagnosis and assessment of respiratory system diseases and hopefully provide new parameters and indexes for monitoring the physical status of patients with cardiopulmonary disease.
		                        		
		                        		
		                        		
		                        			Humans
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		                        			Lung
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		                        			Pulmonary Disease, Chronic Obstructive
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		                        			Respiration
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		                        			Tidal Volume
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		                        			Wearable Electronic Devices
		                        			
		                        		
		                        	
            
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