A Novel Early Warning Model for Hand, Foot and Mouth Disease Prediction Based on a Graph Convolutional Network.

Objectives: Hand, foot and mouth disease (HFMD) is a widespread infectious disease that causes a significant disease burden on society. To achieve early intervention and to prevent outbreaks of disease, we propose a novel warning model that can accurately predict the incidence of HFMD. Methods: We propose a spatial-temporal graph convolutional network (STGCN) that combines spatial factors for surrounding cities with historical incidence over a certain time period to predict the future occurrence of HFMD in Guangdong and Shandong between 2011 and 2019. The 2011-2018 data served as the training and verification set, while data from 2019 served as the prediction set. Six important parameters were selected and verified in this model and the deviation was displayed by the root mean square error and the mean absolute error. Results: As the first application using a STGCN for disease forecasting, we succeeded in accurately predicting the incidence of HFMD over a 12-week period at the prefecture level, especially for cities of significant concern. Conclusions: This model provides a novel approach for infectious disease prediction and may help health administrative departments implement effective control measures up to 3 months in advance, which may significantly reduce the morbidity associated with HFMD in the future.

Cervical Infection of Oncogenic Human Papillomavirus (HPV) Types in Beijing, China.

OBJECTIVE: This study was designed to determine the prevalence of oncogenic human papillomavirus (HPV) in cervical infections in Beijing, China, and to investigate the odds ratio (OR) of HPV single and multiple infections in abnormal cytology. METHODS: A total of 19,018 specimens from outpatients in the department of obstetric and gynecology were collected. They were detected using high-risk HPV genotyping real-time polymerase chain reaction (PCR) kit and analyzed by ThinPrep cytology test for cervical pathological diagnosis. HPV prevalence, age-specific prevalence, and OR of each type of HPV in abnormal cytology were analyzed. RESULTS: Overall, 19.1% (3,623/19,018) of the individuals were positive for HPV infection, 14.9% (2,833/19,018) were positive for a single HPV type, and 4.2% (790/19,018) were positive for multiple types. Among the 3,623 HPV-positive individuals, the most predominant HPV types were HPV52 (4.4%, 834/19,018), HPV16 (3.7%, 710/19,018), and HPV58 (3.4%, 644/19,018). The OR of multiple infections and single infection differed significantly among disease severities. The OR of dual infection was higher than that of each of the two single infection types, respectively. CONCLUSION: HPV prevalence in the outpatients was 19.1%, and the most predominant HPV types in the study were HPV52, HPV16, and HPV58. Women with multiple infectionswere more likely to have abnormal cytology.

Whole Genome Sequencing and Comparisons of Different Chinese Rabies Virus Lineages Including the First Complete Genome of an Arctic-like Strain in China.

OBJECTIVE: To learn the rabies genome molecular characteristics and compare the difference of China rabies lineages. METHODS: The complete genomes of 12 strains from different China rabies lineages were amplified and sequenced, and all the China street strain genomes (total 43), Arctic and Arctic-like genomes were aligned using ClustalX2, the genome homologies were analyzed using MegAlign software, and the phylogenetic trees were constructed by MEGA 5. RESULTS: First Arctic-like rabies genome in China (CQH1202D) was reported, and we supplemented the rabies genome data of China, ensuring at least one genome was available in each China lineage. The genome size of China V (11908nt) is obviously shorter than other lineages' (11923-11925nt) for the difference of N-P non-coding regions. Among different lineages, the genome homologies are almost under 90%. CQH1202D (China IV lineage) has close relationship with strains from South Korea and they share about 95% genome similarities. CONCLUSION: The molecular characteristics of 6 different China rabies lineages were compared and analyzed from genome level, which benefits for continued comprehensive rabies surveillance, rabies prevention and control in China.

[Study for association between high risk human papillomavirus and cervical lesions in the samples from opportunistic screening].

OBJECTIVE: To investigate the association between HPV genotypes and cervical lesion in Hybrid Capture 2 (HC2) HPV test positive samples. METHODS: 602 cervical samples randomly obtained detected as HPV positive by the HC2 high-risk probe cocktail were determined by polymerase chain reaction (PCR)-reverse dot blot (RDB), among them 344 participated Thinprep Cytology test. RESULTS: 569 (94.5%) samples were successfully amplified. The most common HPV genotypes were HPV16 (31.6%), 52 (16.7%), 58 (15.1%), 56 (8.1%), 39 (7.9%); HPV16 or HPV16/18 infection was significantly related to ASCUS, LSIL and HSIL; 24 samples suggested single HPV infection with the genotypes not available for HC2. CONCLUSION: The most common HPV genotypes in random screening were HPV16, 52 and HPV58; Our data demonstrated the pseudo-positivity of HC2 test was 4.0%; HPV16 was a index for progression of HSIL.

Visual detection of high-risk human papillomavirus genotypes 16, 18, 45, 52, and 58 by loop-mediated isothermal amplification with hydroxynaphthol blue dye.

A simple, rapid, sensitive, qualitative, colorimetric loop-mediated isothermal amplification (LAMP) with hydroxynaphthol blue dye (HNB) was established to detect high-risk human papillomavirus (HPV) genotypes 16, 18, 45, 52, and 58. All initial validation studies with the control DNA proved to be type specific. The colorimetric type-specific LAMP assay could achieve a sensitivity of 10 to 100 copies at 63°C for 65 min, comparable to that of real-time PCR. In order to evaluate the reliability of HPV type-specific LAMP, the assay was further evaluated with HPV DNAs from a panel of 294 clinical specimens whose HPV status was previously determined with a novel one-step typing method with multiplex PCR. The tested panel comprised 108 HPV DNA-negative samples and 186 HPV-DNA-positive samples of 14 genotypes. The results showed that the sensitivity of HPV type-specific LAMP for HPV types 16, 18, 45, 52, and 58 was 100%, 100%, 100%, 100%, and 100%, respectively, and the specificity was 100%, 98.5%, 100%, 98.8%, and 99.2%, respectively, compared with a novel one-step typing method with multiplex PCR. No cross-reactivity with other HPV genotypes was observed. In conclusion, this qualitative and colorimetric LAMP assay has potential usefulness for the rapid screening of HPV genotype 16, 18, 45, 52, and 58 infections, especially in resource-limited hospitals or rural clinics of provincial and municipal regions in China.

[Study of human papillomavirus in biopsy tissue specimens of esophageal carcinomas in Linzhou city].

OBJECTIVE: To investigate the prevalence of human papillomavirus (HPV), particularly of high-risk HPV in biopsy tissue specimens of esophageal carcinomas in Linzhou city. METHODS: General nested primer sets were used to detected the whole HPV genotypes, following by HPV16 and 18 type specific PCR for the HPV16 and 18 detection respectively. RESULTS: All 18 biopsy samples were HPV positive, and HPV 16 was detected in 13 of the 18 samples, HPV 18 was detected in 4 of the 18 samples. CONCLUSION: The high rate of HPV in the esophageal carcinoma samples suggested that HPV infection may be an important etiologic factor in the development of esophageal cancer in Linzhou city.

[Study of human papillomavirus in small cell neuroendocrine carcinoma of the uterine cervix].

OBJECTIVE: To observe the infection of the high risk human papillomavirus (HPV) in the specimen of the small cell neuroendocrine carcinoma of the uterine cervix (SCNEC). METHODS: We extracted the nucleic acids in the formalin-fixed and paraffin-embedded specimen from a 33-year-old patient diagnosed as small cell neuroendocrine carcinoma of uterine cervix and detected the HPV genotype with the nested PCR. RESULTS: We identified HPV18, a high-risk genotype, in the specimen. CONCLUSION: The HPV detection with the nested PCR was available for identification of the HPV genotype(s) in the paraffin-embedded specimens of small cell neuroendocrine carcinoma of the uterine cervix with a high accuracy and sensitivity.

[Analysis of human papillomavirus type 61, 83 and 84 MY fragments and preparation of standard samples].

OBJECTIVE: To investigate the mutations in nucleotide and amino acid level in HPV61, 83 and 84 Shanxi isolates. METHODS: Amplified fragments of HPV61, 83 and 84 from human papillomavirus (Human papillomavirus, HPV) molecular epidemiologic survey of Shanxi Province using HPV consensus primers MY09/11 were cloned in pMD18-T vector, and the plasmids were sequenced, then nucleotide sequences and amino acid sequences were analyzed. RESULTS: HPV61 and HPV83 isolates were consistent with reference strains U31793 and AF151983 in nucleotide sequences; four mutations of nucleotide (C6760T, T6931C, T6951C and C6987A) were found in HPV84 isolate compared with reference strain AF293960, among which C6987A resulted in D441E and the amplified sensitivity of standard sample of HPV61 using primers MY09/11 was higher than that of HPV83 and 84. CONCLUSION: HPV61 and HPV83 isolates were consistent with reference strains, four mutations of nucleotide and one mutation of amino acid were found in HPV84,the amplified sensitivity of standard sample of HPV61 using primers MY09/11 was the highest among those three isolates.

[Human papillomavirus type 16 intratypic variant infection and risk for cervical neoplasia].

OBJECTIVE: To study the distribution of human papillomavirus type 16 (HPV16) variants and their clinical significance in Han women with Cervical Intraepithelial Neoplasia (CIN). METHODS: Randomly making a collection of DNA samples of cervical cells from 77 Han out-patients infected with HPV16, PCR amplification of HPV16 DNA fragments containing E6 and E7 genes and sequenced. To study the HPV16 variants types in these out-patients and explore the relationship between the HPV16 variants and CIN by comparing the E6 genes sequenced with the reference strains downloaded from the GenBank. RESULTS Among 77 patients, the minimum age is 21 years old, the maximum age is 56 years old, and the average age is 36.39 +/- 6.86 years old. 61 patients (accounting for 79.2%) were diagnosed as CIN II and higher grade lesions while 16 patients (accounting for 20.8%) as CIN I. In this research, only European variant and Asian variant were found by Parsimony analyses of the sequences. There are 38 Asian variants and 39 European variants. With Chi2 test, Chi2 = 0.0034, P = 0.9535 > 0.05, it suggested that there was no enough evidence to support Asian- and European-variants had the different risk in the cause of cervical intraepithelial neoplasia and cervical cancer. CONCLUSION: It was not found Asian- and European-variants of HPV16 had different effect on the cervical cancer, but found only two major variants-Asian- and European-variants in Han people in this research. So we have reason to speculate that there are two major HPV16 variants (Asian- and European-variants) in China's Han women, while other variants, especially high cancer-causing Asian/American variant are not common.

[Meta analysis on etiological relationship between human papillomavirus and esophageal carcinoma].

OBJECTIVE: To study the relationship between human papillomavirus (HPV) and esophageal cancer development in China. METHODS: We searched and collected the published articles in Chinese related to HPV and esophageal cancer, and selected the articles with the PCR approach to detect HPV in the esophageal cancer specimens. RESULTS: We filtered our publication collection with standards as (1) PCR as the detection approach, (2) specimens as the paraffin-embedded sections, and (3) description of the primer in the experiments, and fifteen articles were enrolled for our meta-analysis. Among the articles, totally 980 specimens were tested, and 460 were HPV positive with the average HPV prevalence was 46.9% (95% CI: 43.8%-50.0%), varied from 8.3%-69.8% in the different locations. On the other hands, among 556 specimens whose HPV detection spectrum included HPV16, 139 showed the positivity of HPV16, the average prevalence was 25.0%, (95% CI: 21.4%-28.6%) varied from 4.4%-63.4% dependent on the locations; among 485 specimens whose HPV detection spectrum included HPV18, thirty-three specimens showed the positivity of HPV18, the average prevalence was 6.8% (95% CI: 4.6%-9.0%) varied from 0%-19.0% dependent on the locations. Third, among the fifteen articles enrolled in the meta-analysis, four articles used the same primer set for HPV detection in totally 406 paraffin-embedded specimens with the prevalence of 40.2% (95% CI: 36.0%-45.4%) varied from 20.3%-67.6% in different locations. CONCLUSION: Our analysis result suggested the HPV prevalence in the esophageal cancer samples of China and clued the possible etiological relationships between HPV infection and the esophageal cancer development.

[Human papillomavirus detection in clear cell carcinoma of the cervix].

OBJECTIVE: To investigate the infection of the high risk human papillomavirus (HPV) in the specimen of the clear cell carcinoma of the cervix. METHODS: We extracted the nucleic acids in the formalin-fixed and paraffin-embedded specimens from a 37-year-old patient with clear cell carcinoma of the cervix and detected the HPV genotype with the nested PCR. RESULTS: We identified HPV18, a high-risk genotype, in the specimens. CONCLUSION: The HPV detection with the nested PCR was available for identification of the HPV genotype(s) in the paraffin-embedded specimens of clear cell carcinoma of the cervix (CCCC) with a high accuracy and sensitivity.

[Detection of human papillomavirus in esophageal carcinoma tissues from Baoding City of Hebei Province].

OBJECTIVE: To investigate the relationship between the human papillomavirus (HPV) and esophageal carcinoma in Baoding City of Hebei Province. METHODS: We detected HPV DNA in 42 formalin-fixed and paraffin-embedded tissues from surgically resected esophageal carcinomas from Baoding City of Hebei Province, by PCR with the general primer set of GP5 + /6 + for HPV L1 gene and type-specific primer sets for HPV16 and 18 as well. RESULTS: 37 from 42 esophageal carcinoma samples were HPV positive and the rate was 88.1%. Among the samples detected, 19 were HPV16 E6 positive and rate was 45.2%, eight were HPV18 E6 positive and rate was 19.0%. CONCLUSION: The high rate of HPV in the esophageal carcinoma samples suggested that HPV plays an etiologic role in the development of esophageal cancer in Baoding City of Hebei Province.

[Human papillomavirus type 16 E5 sequence evolution analysis].

OBJECTIVE: To investigate the distribution of HPV 16 variants in Han women patients without Cervical intraepithelial neoplasia in the diagnosis and treatment center for cervical disease, department of Obstetrics and Gynecology in China-Japan friendship hospital with HPV 16 E5 sequence phylogenetic analysis. METHODS: PCR amplification of HPV 16 E5 sequences and sequenced. The association between variations types and different cervical lesions was analyzed. RESULTS: In this research, We first found that variant classification based on HPV 16 E5 DNA sequence (236 bp) alone had high rate of accuracy. In addition, for the first time, our research revealed that single-4075T can distinguished the As variant from all other variants. CONCLUSION: If E5 sequence was used for phylogenetic analysis, it will greatly reduce the experimental costs and improve efficiency and cost-effectiveness. For the first time, our research revealed that single 4075T can distinguished the As variant from all other variants.

[Detection of human papillomavirus in tissues of esophageal carcinomas by polymerase chain reaction].

OBJECTIVE: To investigate the relationship between the human papillomavirus (HPV) and esophageal carcinomas. METHODS: We detected HPV DNA in 31 fresh tissue of esophageal carcinomas from Linzhou City, Henan Province, by PCR with the general primer set of GP5+/6+ for HPV L1 gene and type-specific primer sets for HPV16 and 18 as well. RESULTS: 29 from 31 esophageal carcinoma samples were HPV positive and the rate was 93.5%. Among the samples detected, 19 were HPV16E6 positive and rate was 61.3%, eight were HPV18 E6 positive and rate was 25.8%; our result also showed five were the multiple infection containing HPV16 and 18 as well and the rate was 71.0%. CONCLUSION: The high rate of HPV in the esophageal carcinoma samples suggested that HPV plays an etiologic role in the development of esophageal cancer in Linzhou City, Henan Province.

[The differential expression of the human lung carcinoma cells infected with high pathogenic avian influenza virus A/Anhui/1/2005 (H5N1)].

OBJECTIVE: To identify genes in human cells infected with high pathogenic avian influenza viruses H5N1. METHODS: The lung carcinoma cells line A549 was infected with H5N1 and H1N1, respectively. We harvested the infected cells at the different time points after infection and screened the genes with differential expression via microarray technology. The candidate genes were selected and confirmed by quantitative real-time PCR. RESULTS: The spectrum of genes with the differential expression in the cells infected with H5N1 was obtained and 16 candidate genes were identified in the cellular apoptosis pathway, mTOR pathway, and the cellular immunity as well. CONCLUSIONS: Our results suggest that H5N1 exert a stronger impact on eliciting apoptosis of infected cells than the common influenza virus H1N1.

[Epidemiological investigation of lower genital tract infectious diseases among women in part of Beijing area].

OBJECTIVE: To understand the condition of lower genital tract infectious diseases among women in part of Beijing area including countryside population, nomadic population, high-risk group and medical workers. METHODS: Epidemiological methods were applied to investigate the condition of lower genital infectious diseases. General data were recorded in a questionnaire and several examinations of lower genital infectious disease were given to each person. The data was analyzed by statistics method. RESULTS: The morbidity of Chlamydia was the highest in the lower genital tract infectious diseases in our research. Morbidity of infusorians in person with the habit of tub bath was much higher than person with shower habit. Compared with the other three groups, out-patients of Peking University First Hospital have the highest morbidity of Chlamydia. CONCLUSION: Chlamydia has the highest morbidity in this research (12.6%), and tub bath may increase the morbidity of infusorians (P=0.02, P less than 0.05).

[A serological survey of Epstein-Barr virus infection in children in Beijing].

OBJECTIVE: To understand the prevalence of Epstein-Barr virus (EBV) infection in urban and rural areas of Beijing using the serological method. METHODS: Totally 589 serum samples were collected from children in Beijing urban and rural areas who were 0--14 years old and tested with Viron-Seron ELISA classic EBV virus capsid antigen IgG antibody (EBV VCA IgG) kit. Optical density of serum samples was obtained at the wavelength of 405 nanometers. Sero-positive or negative samples were determined according to standard curve and cut-off attached in ELISA classic EBV VCA IgG kits. The activity of EBV VCA IgG was calculated by using special formula. The percentage and activity of EBV VCA IgG from Beijing children were compared with SPSS 13.0 between the urban and rural areas. RESULTS: The percentage of EBV VCA IgG seropositive samples was 83.6%, and 80.8% in those from urban and 86.2% in those from rural areas. The peak value of EBV infection was 71% seen among children under the age of 3 years, and in urban area the rate was 67.7%, which was lower than that in the rural area (75.3%), and was 82.5% by the age of 6, which was lower than the data (up to 90%) reported 30 years ago. There was a significant difference in EBV infection rate and VCA IgG activities in children at different ages between urban and rural areas (P < 0.05). CONCLUSION: The rate of EBV infection in children living in urban area was lower by the age of 6 years. The primary infection of EBV occurred late in part of children lived in urban area.