1.Preparation and immunogenicity evaluation of mRNA vaccine against porcine epidemic diarrhea.
Limin YANG ; Junhong WANG ; Mingguo XU ; Hu WANG ; Xiaojuan ZHANG ; Wenjun LIU ; Chuangfu CHEN
Chinese Journal of Biotechnology 2023;39(7):2624-2633
Porcine epidemic diarrhea (PED) is a highly contagious disease that causes high mortality in suckling piglets. Although several licensed inactivated and live attenuated vaccines were widely used, the infection rate remains high due to unsatisfactory protective efficacy. In this study, mRNA vaccine candidates against PED were prepared, and their immunogenicity was evaluated in mice and pregnant sows. The mRNA PED vaccine based on heterodimer of viral receptor binding region (RBD) showed good immunogenicity. It elicited robust humoral and cellular immune responses in mice, and the neutralizing antibody titer reached 1:300 after a single vaccination. Furthermore, it induced neutralizing antibody level similar to that of the inactivated vaccine in pregnant sows. This study developed a new design of PED vaccine based on the mRNA-RBD strategy and demonstrated the potential for clinical application.
Pregnancy
;
Swine
;
Animals
;
Female
;
Mice
;
Antibodies, Viral
;
Swine Diseases/epidemiology*
;
Viral Vaccines/genetics*
;
Antibodies, Neutralizing
;
Vaccines, Attenuated
;
Diarrhea/veterinary*
2.Analysis of the characteristics of viral infections in children with diarrhea in Beijing from 2018 to 2022.
Yang JIAO ; Ling GUO ; Tao Li HAN ; Xiao QI ; Yan GAO ; Yue ZHANG ; Jian Hong ZHAO ; Bei Bei LI ; Zheng ZHANG ; Ling Li SUN
Chinese Journal of Preventive Medicine 2023;57(7):976-982
Objective: To explore the characteristics of viral infections in children with diarrhea in Beijing from 2018 to 2022. Methods: Real-time PCR and enzyme-linked immunosorbent assay were used to detect viral nucleic acid of Norovirus (NoV), Sappovirus (SaV), Astrovirus (AstV), Enteric Adenovirus (AdV) or antigen of Rotavirus (RV) in 748 stool samples collected from Beijing Capital Institute of Pediatrics from January 2018 to December 2021. Subsequently, the reverse transcription PCR or PCR method was used to amplify the target gene of the positive samples after the initial screening, followed by sequencing, genotyping and evolution analysis, so as to obtain the characteristics of these viruses. Phylogenetic analysis was performed using Mega 6.0. Results: From 2018 to 2021, the overall detection rate of the above five common viruses was 37.6%(281/748)in children under 5 years old in Beijing. NoV, Enteric AdV and RV were still the top three diarrhea-related viruses, followed by AstV and SaV, accounting for 41.6%, 29.2%, 27.8%, 8.9% and 7.5%, respectively. The detection rate of co-infections with two or three diarrhea-related viruses was 4.7% (35/748). From the perspective of annual distribution, the detection rate of Enteric AdV was the highest in 2021, while NoV was predominant in the other 4 years. From the perspective of genetic characteristics, NoV was predominant by GⅡ.4, and after the first detection of GⅡ.4[P16] in 2020, it occupied the first two gene groups together with GⅡ.4[P31]. Although the predominant RV was G9P[8], the rare epidemic strain G8P[8] was first detected in 2021. The predominant genotypes of Enteric AdV and AstV were Ad41 and HAstV-1. SaV was sporadic spread with a low detection rate. Conclusion: Among the diarrhea-related viruses infected children under 5 years of age in Beijing, the predominant strains of NoV and RV have changed and new sub-genotypes have been detected for the first time, while the predominant strains of AstV and Enteric AdV are relatively stable.
Child, Preschool
;
Humans
;
Infant
;
Beijing/epidemiology*
;
Diarrhea/epidemiology*
;
Feces
;
Norovirus/genetics*
;
Phylogeny
;
Rotavirus/genetics*
;
Virus Diseases/epidemiology*
;
Viruses/genetics*
3.Study on the features of Clostridioides difficile infection among diarrhea patients in Kunming from 2018 to 2020.
Gui Man LI ; Wen Peng GU ; Min HOU ; Sen Quan JIA ; Yuan Yuan WANG ; Lu Lu BAI ; Jian Wen YIN ; Yong Ming ZHOU ; Xiao Qing FU ; Jin Xing LU ; Yuan WU
Chinese Journal of Epidemiology 2023;44(4):624-628
Objective: We analyze the characteristics of Clostridioides difficile (C. difficile) infection among diarrhea patients in Kunming from 2018 to 2020 and provide evidence for follow-up surveillance and prevention. Methods: A total of 388 fecal samples of diarrhea patients from four sentinel hospitals in Yunnan Province from 2018 to 2020 were collected. Real-time quantitative PCR was used to detect the fecal toxin genes of C. difficile. The positive fecal samples isolated the bacteria, and isolates were identified by mass spectrometry. The genomic DNA of the strains was extracted for multi-locus sequence typing (MLST). The fecal toxin, strain isolation, and clinical patient characteristics, including co-infection with other pathogens, were analyzed. Results: Among the 388 fecal samples, 47 samples with positive reference genes of C. difficile were positive, with a total positive rate of 12.11%. There were 4 (8.51%) non-toxigenic and 43 (91.49%) toxigenic ones. A total of 18 strains C. difficile were isolated from 47 positive specimens, and the isolation rate of positive specimens was 38.30%. Among them, 14 strains were positive for tcdA, tcdB, tcdC, tcdR, and tcdE. All 18 strains of C. difficile were negative for binary toxins. The MLST results showed 10 sequence types (ST), including 5 strains of ST37, accounting for 27.78%; 2 strains of ST129, ST3, ST54, and ST2, respectively; and 1 strain of ST35, ST532, ST48, ST27, and ST39, respectively. Fecal toxin gene positive (tcdB+) results were statistically associated with the patient's age group and with or without fever before the visit; positive isolates were only statistically associated with the patient's age group. In addition, some C. difficile patients have co-infection with other diarrhea-related viruses. Conclusions: The infection of C. difficile in diarrhea patients in Kunming is mostly toxigenic strains, and the high diversity of strains was identified using the MLST method. Therefore, the surveillance and prevention of C. difficile should be strengthened.
Humans
;
Bacterial Toxins/genetics*
;
Enterotoxins/genetics*
;
Clostridioides difficile/genetics*
;
Multilocus Sequence Typing
;
Coinfection
;
Bacterial Proteins/genetics*
;
China/epidemiology*
;
Clostridium Infections/epidemiology*
;
Diarrhea/microbiology*
4.Genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021.
Li XIE ; Chao YANG ; Min JIANG ; Ya Qun QIU ; Rui CAI ; Lu Lu HU ; Yi Xiang JIANG ; Lei WANG ; Qiong Cheng CHEN ; Shuang WU ; Xiao Lu SHI ; Qing Hua HU ; Ying Hui LI
Chinese Journal of Preventive Medicine 2023;57(3):386-392
Objective: To characterize the prevalence and genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021. Methods: Based on the Shenzhen Infectious Diarrhea Surveillance System, acute diarrheal patients were actively monitored in sentinel hospitals from 2013 to 2021. Whole-genome sequencing (WGS) of Vibrio parahaemolyticus isolates was performed, and the genomic population structure, serotypes, virulence genes and multilocus sequence typing were analyzed. Outbreak clusters from 2019 to 2021 were explored based on single-nucleotide polymorphism analysis. Results: A total of 48 623 acute diarrhea cases were monitored in 15 sentinel hospitals from 2013 to 2021, and 1 135 Vibrio parahaemolyticus strains were isolated, with a positive isolation rate of 2.3%. Qualified whole-genome sequencing data of 852 isolates were obtained. Eighty-nine serotypes, 21 known ST types and 5 new ST types were identified by sequence analysis, and 93.2% of strains were detected with toxin profile of tdh+trh-. 8 clonal groups (CGs) were captured, with CG3 as the absolute predominance, followed by CG189. The CG3 group was dominated by O3:K6 serotype and ST3 sequence type, while CG189 group was mainly O4:KUT, O4:K8 serotypes and ST189a and ST189 type. A total of 13 clusters were identified, containing 154 cases. About 30 outbreak clusters with 29 outbreak clusters caused by CG3 strains from 2019 to 2021. Conclusion: Vibrio parahaemolyticus is a major pathogen of acute infectious diarrhea in Shenzhen City, with diverse population structures. CG3 and CG189 have been prevalent and predominant in Shenzhen City for a long time. Scattered outbreaks and persistent sources of contamination ignored by traditional methods could be captured by WGS analysis. Tracing the source of epidemic clone groups and taking precise prevention and control measures are expected to significantly reduce the burden of diarrhea diseases caused by Vibrio parahaemolyticus infection in Shenzhen City.
Humans
;
Vibrio parahaemolyticus/genetics*
;
Diarrhea/epidemiology*
;
Foodborne Diseases/epidemiology*
;
Serogroup
;
Genomics
;
Dysentery
;
Vibrio Infections/epidemiology*
;
Serotyping
5.Genotyping Characteristics of Human Fecal Escherichia coli and Their Association with Multidrug Resistance in Miyun District, Beijing.
Wei Wei ZHANG ; Xiao Lin ZHU ; Le Le DENG ; Ya Jun HAN ; Zhuo Wei LI ; Jin Long WANG ; Yong Liang CHEN ; Ao Lin WANG ; Er Li TIAN ; Bin CHENG ; Lin Hua XU ; Yi Cong CHEN ; Li Li TIAN ; Guang Xue HE
Biomedical and Environmental Sciences 2023;36(5):406-417
OBJECTIVE:
To explore the genotyping characteristics of human fecal Escherichia coli( E. coli) and the relationships between antibiotic resistance genes (ARGs) and multidrug resistance (MDR) of E. coli in Miyun District, Beijing, an area with high incidence of infectious diarrheal cases but no related data.
METHODS:
Over a period of 3 years, 94 E. coli strains were isolated from fecal samples collected from Miyun District Hospital, a surveillance hospital of the National Pathogen Identification Network. The antibiotic susceptibility of the isolates was determined by the broth microdilution method. ARGs, multilocus sequence typing (MLST), and polymorphism trees were analyzed using whole-genome sequencing data (WGS).
RESULTS:
This study revealed that 68.09% of the isolates had MDR, prevalent and distributed in different clades, with a relatively high rate and low pathogenicity. There was no difference in MDR between the diarrheal (49/70) and healthy groups (15/24).
CONCLUSION
We developed a random forest (RF) prediction model of TEM.1 + baeR + mphA + mphB + QnrS1 + AAC.3-IId to identify MDR status, highlighting its potential for early resistance identification. The causes of MDR are likely mobile units transmitting the ARGs. In the future, we will continue to strengthen the monitoring of ARGs and MDR, and increase the number of strains to further verify the accuracy of the MDR markers.
Humans
;
Escherichia coli/genetics*
;
Escherichia coli Infections/epidemiology*
;
Multilocus Sequence Typing
;
Genotype
;
Beijing
;
Drug Resistance, Multiple, Bacterial/genetics*
;
Anti-Bacterial Agents/pharmacology*
;
Diarrhea
;
Microbial Sensitivity Tests
6.A Campylobacteriosis Outbreak Caused by One Asymptomatic Food Handler Carrier.
Ai Xia YAN ; Gui Lan ZHOU ; Peng GAO ; Ying KANG ; Shou Fei LI ; Yuan Yuan WANG ; Feng Shuang WANG ; Hai Rui WANG ; Ying LI ; Mao Jun ZHANG
Biomedical and Environmental Sciences 2023;36(8):779-782
In August 2021, three students with diarrhea from the same school visited a local hospital in the S district of Beijing. An epidemic investigation showed that there were more students with diarrhea in the same school and they had one meal together. Campylobacter jejuni was isolated from both patients with diarrhea and asymptomatic food handlers; however, the latter also carried Campylobacter coli. Phylogenomic analysis showed that there was a campylobacteriosis outbreak among the students, and the asymptomatic food handler may have been the source of the infection. Routine inspection and surveillance for Campylobacter is needed for the food producing staff, particularly those cooking in the cafeteria in schools or other public food services.
Humans
;
Campylobacter Infections/epidemiology*
;
Gastroenteritis
;
Diarrhea
;
Campylobacter
;
Disease Outbreaks
7.Environmental influences on food allergy.
Xiao Wei ZHANG ; Si Yu LIU ; Xin LI ; Hong Bing CHEN
Chinese Journal of Preventive Medicine 2023;57(12):1921-1928
Food allergy is an abnormal immune response triggered by food allergens, resulting in symptoms such as vomiting, diarrhea, gastroesophageal reflux, pruritus, dyspnea, and in severe cases, anaphylactic shock and mortality. The prevalence of food allergy varies within the population, with a significantly higher incidence observed among children compared to adults. This escalating trend in pediatric food allergy has emerged as a prominent concern jeopardizing children's well-being, thus prompting extensive investigations within the realm of global public health. Over the past three decades, there has been a progressive increase in the global prevalence of food allergy, accompanied by a heightened severity of allergic manifestations. Environmental factors have been identified as crucial determinants in this escalating phenomenon. Extensive research has demonstrated the pivotal role played by the environment in both the onset and progression of food allergies. The present article aims to consolidate the effects of diverse environmental factors on food allergy, elucidating their underlying mechanisms. Emphasis is placed on delineating the impact of distinct environmental factors on food allergy, thereby furnishing valuable insights for comprehending the risk factors associated with this condition. Furthermore, this comprehensive analysis contributes to the advancement of scientific strategies for the prevention and management of food allergy, promoting the development and advancement of preventive medicine.
Adult
;
Humans
;
Child
;
Food Hypersensitivity/epidemiology*
;
Risk Factors
;
Diarrhea
8.Environmental influences on food allergy.
Xiao Wei ZHANG ; Si Yu LIU ; Xin LI ; Hong Bing CHEN
Chinese Journal of Preventive Medicine 2023;57(12):1921-1928
Food allergy is an abnormal immune response triggered by food allergens, resulting in symptoms such as vomiting, diarrhea, gastroesophageal reflux, pruritus, dyspnea, and in severe cases, anaphylactic shock and mortality. The prevalence of food allergy varies within the population, with a significantly higher incidence observed among children compared to adults. This escalating trend in pediatric food allergy has emerged as a prominent concern jeopardizing children's well-being, thus prompting extensive investigations within the realm of global public health. Over the past three decades, there has been a progressive increase in the global prevalence of food allergy, accompanied by a heightened severity of allergic manifestations. Environmental factors have been identified as crucial determinants in this escalating phenomenon. Extensive research has demonstrated the pivotal role played by the environment in both the onset and progression of food allergies. The present article aims to consolidate the effects of diverse environmental factors on food allergy, elucidating their underlying mechanisms. Emphasis is placed on delineating the impact of distinct environmental factors on food allergy, thereby furnishing valuable insights for comprehending the risk factors associated with this condition. Furthermore, this comprehensive analysis contributes to the advancement of scientific strategies for the prevention and management of food allergy, promoting the development and advancement of preventive medicine.
Adult
;
Humans
;
Child
;
Food Hypersensitivity/epidemiology*
;
Risk Factors
;
Diarrhea
9.Molecular epidemiological characteristics of the virus in 96 children with acute diarrhea in Changdu of Tibet, China.
Jun-Wen MAO ; Ya-Li YANG ; Chang-Chun SHI ; Zhu CHEN ; Chun LI ; Yong-Ming WANG ; Lin-Bin LI ; Jun-Hua CHEN
Chinese Journal of Contemporary Pediatrics 2022;24(3):266-272
OBJECTIVES:
To study the molecular epidemiological characteristics of the virus in children with acute viral diarrhea in Changdu of Tibet, China.
METHODS:
Fecal specimens were collected from 96 children with acute diarrhea who visited the People's Hospital of Changdu, Tibet, from November 2018 to November 2020 and were tested for adenovirus, norovirus, astrovirus, sapovirus, and rotavirus. Gene sequencing was performed for the genotypes of these viruses.
RESULTS:
The overall positive rate of the five viruses was 39% (37/96), among which astrovirus had the highest positive rate of 17%, followed by norovirus (9%), rotavirus (8%), adenovirus (7%), and sapovirus (5%). There was no significant difference in the positive rate of the five viruses among different age groups (P>0.05). Only the positive rate of astrovirus was significantly different among the four seasons (P<0.05). For adenovirus, 6 children had F41 type and 1 had C2 type; for norovirus, 6 had GⅠ.3 type, 1 had GⅠ.7 type, 1 had GⅡ.3 type, and 2 had GⅡ.4 Sydney_2012 type; HAstrV-1 type was observed in all children with astrovirus infection; for sapovirus, 1 child each had sporadic GⅠ.2, GⅠ.6, and GⅡ.1 sapovirus and 2 children had unknown type; 6 children had rotavirus G9[P8].
CONCLUSIONS
Astrovirus and norovirus are important pathogens in children with acute diarrhea in Changdu, Tibet. The positive rate of adenovirus, norovirus, astrovirus, sapovirus, and rotavirus is not associated with age, and only the positive rate of astrovirus has obvious seasonality. F41 type is the dominant genotype of adenovirus; GⅠ.3 is the dominant genotype of norovirus; HAstrV-1 is the dominant genotype of astrovirus; sporadic GⅠ.2, GⅠ.6, and GⅡ.1 are the dominant genotypes of sapovirus; G9[P8] is the dominant genotype of rotavirus.
Child
;
China
;
Diarrhea/epidemiology*
;
Feces
;
Gastroenteritis
;
Humans
;
Tibet/epidemiology*
;
Viruses/genetics*
10.HucMSC-Ex alleviates inflammatory bowel disease via the lnc78583-mediated miR3202/HOXB13 pathway.
Yuting XU ; Li ZHANG ; Dickson Kofi Wiredu OCANSEY ; Bo WANG ; Yilin HOU ; Rong MEI ; Yongmin YAN ; Xu ZHANG ; Zhaoyang ZHANG ; Fei MAO
Journal of Zhejiang University. Science. B 2022;23(5):423-431
As a group of nonspecific inflammatory diseases affecting the intestine, inflammatory bowel disease (IBD) exhibits the characteristics of chronic recurring inflammation, and was proven to be increasing in incidence (Kaplan, 2015). IBD induced by genetic background, environmental changes, immune functions, microbial composition, and toxin exposures (Sasson et al., 2021) primarily includes ulcerative colitis (UC) and Crohn's disease (CD) with complicated clinical symptoms featured by abdominal pain, diarrhea, and even blood in stools (Fan et al., 2021; Huang et al., 2021). UC is mainly limited to the rectum and the colon, while CD usually impacts the terminal ileum and colon in a discontinuous manner (Ordás et al., 2012; Panés and Rimola, 2017). In recent years, many studies have suggested the lack of effective measures in the diagnosis and treatment of IBD, prompting an urgent need for new strategies to understand the mechanisms of and offer promising therapies for IBD.
Chronic Disease
;
Colitis, Ulcerative/therapy*
;
Crohn Disease/epidemiology*
;
Diarrhea
;
Homeodomain Proteins
;
Humans
;
Inflammatory Bowel Diseases
;
Mesenchymal Stem Cells/cytology*
;
MicroRNAs
;
RNA, Long Noncoding
;
Recurrence
;
Umbilical Cord/cytology*

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