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Background To provide useful insights into measles elimination progress in China, measles surveillance data were reviewed, and the transmission patterns of measles viruses circulating in China during 1993–2021 were analyzed. Methods Measles incidence data from the National Notifiable Disease Reporting System of the China Center for Disease Control and Prevention were analyzed. A total of 17 570 strains were obtained from 30 of 31 provinces in mainland China during 1993–2021. The recommended genotyping window was amplified. Genotyping analysis was conducted for comparison with the reference strains. Phylogenetic analyses were performed to identify genetic relationships among different lineages within the genotypes. Results With high coverage of routine immunization and intensive supplementary immunization activities, measles incidence has shown a downward trend since 1993, despite 2 resurgences, reaching a historic low level in 2020–2021 (average 0.5 per million). During 1993–2021, 9 genotypes including domestic genotype H1; imported genotypes B3, D4, D8, D9, D11, G3, and H2; and vaccine-associated genotype A were identified. Among them, the genotype H1 strain circulated endemically in China for more than 25 years; the last strain was detected in Yunnan Province in September 2019. Multiple imported genotypes have been identified since 2009 showing different transmission patterns. Since April 2020, no imported strains have been detected, while vaccine-associated genotype A continues to be detected. Conclusions The evidence of low incidence during 2020–2021 and virological surveillance data in this study confirm that China is currently approaching measles elimination.

Measles is one of the most infectious diseases of humans. It is caused by measles virus (MeV) and can lead to serious illness, lifelong complications and even death. Whole-genome sequencing (WGS) is now available to study molecular epidemiology and identify MeV transmission pathways. In the present study, WGS of 23 MeV strains of genotype H1, collected in Mainland China between 2006 and 2018, were generated and compared to 31 WGSs from the public domain in order to analyze genomic characteristics, evolutionary rates and date of emergence of H1 genotype. The non-coding region between M and F protein genes (M/F NCR) was the most variable region throughout the genome. Whereas the nucleotide substitution rate of H1 WGS was around 0.75×10-3 substitution per site per year, the M/F NCR had an evolutionary rate 3 times higher, with 2.44×10-3 substitution per site per year. Phylogenetic analysis identified 3 distinct genetic groups. The Time of the Most Recent Common Ancestor (TMRCA) of H1 genotype was estimated at approximately 1988, while the first genetic group appeared around 1995 followed by 2 other genetic groups in 1999-2002. Bayesian skyline plot showed that the genetic diversity of H1 genotype remained stable even though the number of MeV cases decreased 50 times between 2014 (52,628) and 2020 (993). The current COVID-19 pandemic might have some effect on measles epidemic and further studies will be necessary to assess genetic diversity of H1 genotype in a post COVID area. This article is protected by copyright. All rights reserved.

Background: Non-SMC condensin I complex subunit D2 (NCAPD2) belongs to the chromosomal structural maintenance family. While the different contribution of NCAPD2 to chromosome in mitosis have been thoroughly investigated, much less is known about the expression of NCAPD2 in pan-cancer. Thus, we used a bioinformatics dataset to conduct a pan-cancer analysis of NCAPD2 to determine its regulatory role in tumors. Methods: Multiple online databases were analyzed NCAPD2 gene expression, protein level, patient survival and functional enrichment in pan-cancer. Genetic alteration and tumor stemness of NCAPD2 were analyzed using cBioPortal and SangerBox. The GSCA and CellMiner were used to explore the relationship between NCAPD2 and drug sensitivity. The diagnostic value of prognosis was evaluated by ROC curve. Subsequently, the immuneinfiltration level and immune subtype of NCAPD2 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were analyzed using TIMER1 and TISIDB. Results: NCAPD2 gene expression was significantly higher in most cancers and associated with clinical stage and poor prognosis. Genomic heterogeneity of NCAPD2 promoted the occurrence and development of tumors. GO enrichment analysis suggested NCAPD2 might be involved in DNA repair and immune response. NCAPD2 was involved in immune infiltration of LUAD and LUSC. ROC curves showed that NCAPD2 has important prognosis diagnostic value in LUAD and LUSC. Moreover, NCAPD2 was drug sensitive to topotecan, which may be an optimize immunotherapy. Conclusions: It was found that NCAPD2 was overexpressed in pan-cancers, which was associated with poor outcomes. Importantly, NCAPD2 could be a diagnosticmarker and an immune related biomarker for LUAD and LUSC.

To better understand the importation and circulation patterns of rubella virus lineages 1E-L2 and 2B-L2c circulating in China since 2018, 3,312 viral strains collected from 27 out of 31 provinces in China between 2018 and 2021 were sequenced and analyzed with the representative international strains of lineages 1E-L2 and 2B-L2c based on genotyping region. Time-scale phylogenetic analysis revealed that the global lineages 1E-L2 and 2B-L2c presented distinct evolutionary patterns. Lineage 1E-L2 circulated in relatively limited geographical areas (mainly Asia) and showed geographical and temporal clustering, while lineage 2B-L2c strains circulated widely throughout the world and exhibited a complicated topology with several independently evolved branches. Furthermore, both lineages showed extensive international transmission activities, and phylogeographic inference provided evidence that lineage 1E-L2 strains circulating in China possibly originated from Japan, while the source of lineage 2B-L2c isolated since 2018 is still unclear. After importation into China in 2018, the spread of lineage 1E-L2 presented a three-stage transmission pattern from southern to northern China, whereas lineage 2B-L2c spread from a single point in western China to all the other four regions. These two transmission patterns allowed both imported lineages to spread rapidly across China during the 2018–9 rubella epidemic and eventually established endemic circulations. This study provides critical scientific data for rubella control and elimination in China and worldwide.

Fever and rash illnesses (FRIs) are a series of common diseases with fever and rashes as clinical manifestations, most of which are caused by viral infection. The rashes of FRIs are generally nonspecific; therefore it is difficult to identify FRI-associated viruses solely based on clinical symptoms. To achieve rapid and accurate identification of FRI pathogens, a multiplex one-step real-time reverse transcription-polymerase chain reaction (RT-PCR) assay was developed and evaluated in this study. Primers and probes were selected for the detection of measles virus (MeV), rubella virus (RV), human enterovirus (EV), varicella-zoster virus (VZV), dengue virus (DENV), human parvovirus B19 (B19), Epstein-Barr virus (EBV), and human herpes virus 6 (HHV-6), which cover the most common pathogenic viruses of FRIs. Detection of the eight FRI-associated viruses, which was divided into two groups/tubes, was simultaneously performed under universal optimized reaction conditions in multiplex one-step real-time RT-PCR assay. The multiplex real-time RT-PCR showed high sensitivity and specificity in detecting the eight FRI-associated viruses. The limits of detection (LODs) for the eight viruses were in the range of 47–177 copies/reaction, and no cross reactions for the eight FRI-associated viruses were found in the multiplex assay. In addition, the results of the multiplex real-time RT-PCR assay were consistent with the results of a monoplex real-time RT-PCR assay and sequencing for clinical specimens obtained from FRI patients. With its advantages of high efficiency and rapid and accurate diagnosis, multiplex real-time RT-PCR was very feasible for the early diagnosis of FRI pathogenic viruses and would be of great help for the proper treatment, monitoring, and initiation of preventive measures for FRI cases.

We detected human metapneumovirus (HMPV) in 72 (7.1%) of 1,021 patients hospitalized with severe acute respiratory infection in Luohe, China, during 2017-2019. We detected HMPV most frequently in young children and less often in adults. HMPV genotype A2c variants 111 nt and 180 nt duplications predominated, demonstrating their continuing geographic spread.

Nationwide prospective surveillance of all-age patients with acute respiratory infections was conducted in China between 2009‒2019. Here we report the etiological and epidemiological features of the 231,107 eligible patients enrolled in this analysis. Children, China operates a national surveillance program for acute respiratory infections and sampled over 200,000 patients between 2009–2019. Here, the authors present results from this program and describe patterns by age, pathogen type, presence of pneumonia, and season.

National-based prospective surveillance of all-age patients with acute diarrhea was conducted in China between 2009‒2018. Here we report the etiological, epidemiological, and clinical features of the 152,792 eligible patients enrolled in this analysis. Rotavirus A and norovirus are the two leading viral pathogens detected in the patients, followed by adenovirus and astrovirus. Diarrheagenic Escherichia coli and nontyphoidal Salmonella are the two leading bacterial pathogens, followed by Shigella and Vibrio parahaemolyticus. Patients aged, Diarrhoea is a major cause of morbidity and mortality in China. Here, the authors present results from a large sentinel surveillance scheme from 217 hospitals in all 31 provinces in mainland China, including ~150,000 patients with acute diarrhoea and covering years 2009-2018.

During 2017–2018, Nasopharyngeal aspirates (NPAs) from 627 hospitalized patients with SARI at Luohe Center Hospital were tested by RT-PCR for human parainfluenza virus 4(HPIV-4). 14 (2.2%) of 627 samples were positive for HPIV-4. The complete nucleotide sequence of the HN gene from 9 positive samples was amplified and sequenced successfully. Genetic analysis showed that the HPIV-4 strains circulating in Luohe city are more closely related to HPIV-4A. Our study indicated that there were multiple lineages of HPIV-4 circulating in Henan Province in China during the study period, which will improve our understanding of the epidemiological and clinical characteristics of HPIV-4.

During 2017–2018, nasopharyngeal aspirates (NPAs) from 627 hospitalized patients with severe acute respiratory infection at Luohe Center Hospital were tested by RT-PCR for human parainfluenza virus 4 (HPIV-4). Fourteen (2.2%) of the 627 samples were positive for HPIV-4. The complete HN gene was amplified from nine positive samples and sequenced. Sequence comparisons showed that the HPIV-4 strains circulating in the city of Luohe are closely related to HPIV-4A strains. Our study indicated that there were multiple lineages of HPIV-4 circulating in Henan Province in China during the study period. This will improve our understanding of the epidemiological and clinical characteristics of HPIV-4. Supplementary Information The online version contains supplementary material available at 10.1007/s00705-021-05154-3.

Hand, foot and mouth disease (HFMD) was reported in May 2, 2008 to be the 38th legally notifiable disease in China's National Notifiable Disease Reporting and Surveillance System. In order to solve the infection, an extensive three-level HFMD surveillance laboratory network was established. In this study, the framework of that network is assessed and the incidence of HFMD in China from 2008 to 2017 is reported using a descriptive epidemiologic method. During these 10 years, a series of techniques have been widely applied in all the network laboratories. Using information and material obtained from the network, a virus bank and database containing 18,238 viruses were established. Nationally, 18,184,834 HFMD cases, including 152,436 severe cases and 3633 fatal cases, were reported in mainland of China. The average annual incidence in the population was 133.99/100,000 people, with a maximum incidence of 205.06/100,000 people in 2014. The incidence and mortality rates of HFMD were the highest in children aged 1–2 years. The numbers of reported cases fluctuated, with a high incidence observed every 2 years. An overall increase in the number of reported cases was also observed throughout the study period. Despite this, the incidence of severe cases and the mortality rate have been decreasing. High-risk regions are located in southern, eastern, and central China. Two peaks of HFMD infection cases were observed annually except for Northeast China. Different proportions of enterovirus serotypes were observed during the studied years. The predominant enterovirus varies from year to year, but the disease severity is always closely related to the specific serotype. EV-A71 is the dominant serotype associated with severe and fatal cases, with constituent ratios of 70.03% and 92.23%, respectively. The studied highly sensitive and efficient surveillance network provides information that is critical for prevention and control of the disease. It is extremely necessary and important to continuously conduct extensive virological surveillance for HFMD. Key words: Hand, Foot and Mouth Disease; Laboratory network; Surveillance, Epidemiological characteristics; Pathogen spectrum

Along with the implementation of measles case-based surveillance, measles vaccine-associated rash illness (VARI) cases were detected in China. To better understand the characteristics of VARI, 101 VARI cases confirmed by measles virus genotyping in 2011 to 2018 were analyzed in this study. With the decrease in measles incidence, the detection rate of VARI cases increased among the cases confirmed by genotyping. Compared with genotype H1 wild-type measles, VARI occurred throughout the year, without obvious seasonal distribution. Infants and children of ages 8 to 23 months were the main population of VARI. VARI mainly occurred within 14 days after measles vaccination. The number of VARI cases peaked on the 8th day after measles vaccination, which was later than that of genotype H1 wild-type measles cases with a measles vaccination history. VARI presents clinical symptoms similar to those of measles. The frequencies of the “3Cs” (cough, coryza, and conjunctivitis), Koplik spots, and complications in VARI cases were significantly lower than those in wild-type measles cases. In total, 94.06% of sequences from VARI cases were identical to measles vaccine strain S191 in the C-terminal 450-nucleotide sequence of the nucleoprotein (N-450) gene. A few substitutions were found in N-450 sequences of the VARI cases. The confirmation of VARI has become an emerging issue in the process of measles elimination. Rapid confirmation of VARI is critical for measles surveillance and will help to determine the response measures for measles, especially in measles preelimination and elimination settings. The suspected measles cases with measles-containing vaccine (MCV) vaccination were recommended to be tested by the laboratory to identify wild-type measles or VARI.

What is already known about this topic? Coronavirus disease 2019 (COVID-19) has become a global pandemic, while the profile of antibody response against the COVID-19 virus has not been well clarified. What is added by this report? In this study, 210 serum samples from 160 confirmed COVID-19 cases with different disease severities were recruited. The IgM, IgA, IgG, and neutralizing antibodies (NAb) against COVID-19 virus were determined. Our findings indicated that four antibodies could be detectable at low levels within 2 weeks of disease onset, then rapidly increasing and peaking from the 3rd to 5th Weeks. NAb decreased between 5th and 9th Weeks, and a higher IgM/IgA level was observed in the groups with mild/moderate severity within 2 weeks (p

Human adenovirus (HAdV-7) is a highly contagious pathogen that causes severe respiratory illnesses. However, the epidemic patterns and genetic variability of HAdV-7 circulating in mainland China have not been well elucidated. In this study, we used Chinese HAdV sentinel surveillance data obtained from 2012-2015 to investigate the clinical features of 122 HAdV-7-positive cases and performed amplification and sequence determination of three capsid genes (penton base, hexon, and fiber) from 69 isolated viruses covering from seven provinces of China. Additionally, we compared with data from representative sequences of 21 strains covering seven more provinces in China and 32 international HAdV-7 strains obtained from GenBank database to determine the phylogenetic, sequence variations, and molecular evolution of HAdV-7. The results indicated that HAdV-7 infection occurred throughout the year, and a high proportion of severe cases (27 cases, 22.1%) exhibited infantile pneumonia. Moreover, phylogenetic analysis showed that all HAdV-7 strains could be divided into two major evolutionary branches, including subtype 1 and subtype 2, and subtype 3 was also formed according to analysis of the penton base gene. Subtypes 1 and 2 co-circulated in China before 2008, and HAdV-7 strains currently circulating in China belonged to subtype 2, which was also the predominant strain circulating worldwide in recent years. Further sequence variation analysis indicated that three genes of HAdV-7 were relatively stable across time and geographic space, particularly for viruses within subtypes, which shared almost the same variation sites. Owing to continuous outbreaks caused by HAdV-7, resulting in increased illness severity and fatality rates in China, the establishment of a national HAdV surveillance system is urgently needed for the development of effective preventive and infection-control interventions for adenovirus respiratory infections in China.

Objective To evaluate the inhibitory effect of fenretinide-loaded liposomes (4-HPR-L) on subcutaneous transplanted malignant melanomas in nude mice. Methods A film-ultrasonic dispersion method was used to prepare 4-HPR-L. BALB/c nude mice were subcutaneously inoculated with A375 melanoma cells in the right axillary fossae to establish malignant melanoma-bearing nude mouse models. Ten nude mouse models were randomly and equally divided into 2 groups to be injected with near-infrared fluorescent cell membrane label (DiR) solution or DiR liposomes (DiR-L) at the same concentration in the caudal vein, and a live imaging system was used to observe the distribution of DiR or DiR-L in nude mice at 6, 12, 24 hours after the injection. Another 30 nude mice were randomly and equally divided into 3 groups to be injected with 5% (mass fraction) glucose solution at a single-dose of 0.2 ml (control group) , 25 mg/kg 4-HPR solution (4-HPR group) and 25 mg/kg 4-HPR-L solution (4-HPR-L group) respectively on days 8, 10, 12, 14, 16, 18, 20 and 22 after the inoculation with A375 cells. The mouse body weight and tumor volume were dynamically monitored in the above groups after the injection, and the survival situation was observed. The nude mice were sacrificed on day 2 after the final injection, and the heart, liver, spleen, lung, kidney and tumor tissues were resected. These tissues were subjected to hematoxylin-eosin staining and immunohistochemical staining to observe the metastasis of melanoma in mice, and terminal deoxyribonucleotidyl transferase-mediated nick end labelling was performed to detect the apoptosis in tumor cells. One-way analysis of variance and independent-sample t test were used to analyze measurement data. Results The live imaging system showed that DiR-L could be retained in melanoma for a long time, and strong fluorescence of DiR-L could be still observed in the tumors at 24 hours after injections. Quantitative fluorescence analysis revealed that the fluorescence intensity of DiR-L (22.85 ± 1.66) was significantly higher than that of DiR in tumor tissues (8.45 ± 0.97, t = 12.957, P < 0.01) . Compared with the control group and 4-HPR group, the resected tumor weight on day 2 after the final injection was significantly decreased in the 4-HPR-L group (F = 27.055, t = 4.768, 6.640, respectively, both P < 0.05) . Hematoxylin-eosin staining showed that liver metastasis occurred in 2 nude mice in the 4-HPR-L group, but in all the nude mice in the control group and 4-HPR group. All the nude mice in the 4-HPR-L group died within 76 days after inoculation, and the mice in the control group and 4-HPR group all died within 56 and 59 days respectively after inoculation. There were significant differences in the apoptotic index among the control group (12.14‰ ± 1.33‰) , 4-HPR group (67.17‰ ± 15.18‰) and 4-HPR-L group (152.73‰ ± 11.27‰; F = 167.588, P < 0.05) , and the apoptotic index was significantly higher in the 4-HPR-L group than in the control group and 4-HPR group (t = 18.162, 11.075 respectively, both P < 0.05) . Conclusion 4-HPR-L can effectively inhibit the growth of subcutaneous melanoma in nude mice and metastasis of melanoma cells, and prolong the survival duration of nude mice. Key words: Nevi and melanomas; Fenretinide; Liposomes; Models, animal; Apoptosis; A375 cells

Measles incidence has decreased dramatically in China due to the implement of measles-containing vaccine (MCV). However, a measles epidemic caused resurgence recently, even among vaccinated individuals. To evaluate the effectiveness of current immunization programs and discuss initiatives for the next step in measles elimination in mainland China, the characteristics of 121,969 laboratory-confirmed measles cases reported in the measles surveillance system (MSS) during 2014–2018 were analyzed according to the vaccination status of the cases in this study. Children under 2 years of age without MCV vaccination (44,424, 36.42% of all cases) and adults over 20 years of age with an unknown vaccination history (37,564, 30.80% of all cases) accounted for the majority of measles cases from 2014 to 2018. 42,425 (34.78%) of the 77,384 cases with available vaccination information were categorized as programmatically preventable. 38,840 (91.55%) of the 42,425 cases were aged ≥8 months without the MCV vaccination history. 34,959 (28.66%) cases were categorized as programmatically non-preventable, of whom 22,611 (64.68%) were too young to receive their first MCV dose, 6857 (19.61%) received their first dose and were too young to receive their second dose, 5491 (15.71%) received at least two doses of MCV. 15,933 (13.06%) of the 121,969 cases had a history of MCV vaccination. Measles virus infection in cases with an MCV vaccination history mainly occurred within the first month after MCV vaccination, especially in those who received a one-dose measles vaccination. MCV vaccination could reduce the frequencies of clinical symptoms and complications of measles cases. Our study confirmed that the current measles immunization programs used in mainland China is effective in reducing the measles incidence in China. Unvaccinated infants/children aged 8–23 months and high risk susceptible adults over 20 years of age with unknown vaccination histories should be the focus groups of measles immunization activities in China in the future.

[This corrects the article DOI: 10.1371/journal.pone.0232092.].

To determine the status of human cytomegalovirus (HCMV) infection in human milk in China, a total of 510 human milk samples obtained from three provinces, including 211 donor human milk samples from human milk banks and 299 milk samples obtained from the mothers of premature infants, were tested to detect HCMV DNA. Overall, 46.4% of the donated milk samples and 59.2% of the samples obtained from mothers of premature infants were positive for HCMV DNA. The concentration of HCMV DNA was approximately 103 -104 copies/ml in the HCMV-DNA-positive human milk samples. Based on the nucleotide sequence of a 299- to 305-bp fragment of the glycoprotein B (gB) gene, three HCMV genotypes (gB1, gB2 and gB3) were identified in human milk samples. Mixed infection with genotypes gB1 and gB3 was also found in four milk samples from mothers. Genotype gB1 was the predominant genotype in the HCMV-DNA-positive human milk samples, and it could be subdivided into three lineages. There were also some characteristic nucleotides and amino acids in the three HCMV genotypes, which were helpful for distinguishing the genotypes. This is the first study to clarify the HCMV infection status and genetic characteristics of human milk obtained from banks in China, which will be helpful in preventing postnatal HCMV infections and ensuring the safety of human milk banks.

A study was conducted to investigate the circulation of HRSV subgroup B (HRSVB) in China in recent years. HRSVB sequences from 365 samples collected in 1991, 2004 and 2008–2014 in China, together with 332 Chinese HRSVB sequences obtained from GenBank were analyzed to determine the geographic and yearly distribution of HRSVB. Phylogenetic analysis revealed these HRSVB sequences clustered into 4 genotypes with different frequencies: BA (83%), CB1 (11%), SAB (3.0%) and GB3 (0.7%). Between 2005 and 2013, there was a co-circulation of BA and non-BA genotypes in China. Genotypes BA9 and BA10 were two of the main BA genotypes detected in this study. Genotype BA9 was first detected in China in 2006 and became the predominant HRSVB genotype circulating in China from 2008 to 2014. Three different lineages were detected for both genotypes BA9 and BA10. Time to the most recent common ancestor for genotypes BA9 and BA10 was estimated for years 1997 and 1996, respectively. Results of this study not only contribute to the understanding of the circulation pattern, but also the phylogenetic pattern and evolution of HRSVB in China from 1991 to 2014.

We wished to study the dynamic change in variation of rubella viruses circulating during 1999-2015 in mainland China at the molecular level. Molecular evolution of Chinese rubella viruses collected during 1999 ~ 2015 was analyzed according to a surveillance database of measles/rubella laboratory networks in China. A total of 1737 rubella viruses were obtained from 20 of 31 provinces (except Xinjiang and Tibet) during 1999 ~ 2015. Four genotypes (1E, IF, 2A, 2B) were detected. The genotype-1E rubella virus was detected first in 2001. Subsequently, genotype 1E became the predominant genotype circulating during 2001~2013, and could be divided into two closely related clusters (A (2004-2015) and B (2001-2009)). However, the detection rate of the genotype-1E rubella virus decreased year-by-year from 2011, and reached the lowest level (1. 3%) in 2015. The genotype-1F rubella virus was restricted geographically to China, and no longer found after 2002; presumably its circulation in China was interrupted. All genotype-2A rubella viruses were derived from vaccine-related cases. At least four genotypes of 2B rubella viruses (lineage 1 ~ 4) circulated in mainland China during 2000 ~ 2015. The genotype-2B rubella virus was detected sporadically and was in a weak position until 2010. However, the detection rate of imported genotype-2B rubella viruses (lineage 3) was increased and became the predominant genotype during 2014~2015. Through the study of 16 consecutive years in mainland China, the evolution and epidemic situation of the rubella virus was obtained to aid virology surveillance for rubella control in China.

The human respiratory syncytial virus (HRSV) fusion (F) protein is important for HRSV infection, but few studies have examined the genetic diversity of the F gene from Chinese samples. In this study, a total of 330 HRSV F sequences collected from different regions of China between 2003 and 2014 were analyzed to understand their genetic characteristics. In addition, these sequences were compared with 1150 HRSV F sequences in Genbank from 18 other countries. In phylogenetic analysis, Chinese HRSV F sequences sorted into a number of clusters containing sequences from China as well as other countries. F sequences from different genotypes (as determined based on the G gene sequences) within a HRSV subgroup could be found in the same clusters in phylogenetic trees generated based on F gene sequences. Amino acid analysis showed that HRSV F sequences from China and other countries were highly conserved. Of interest, F protein sequences from all Chinese samples were completely conserved at the palivizumab binding site, thus predicting the susceptibility of these strains to this neutralizing antibody. In conclusion, HRSV F sequences from China between 2003 and 2014, similar to those from other countries, were highly conserved.

Due to the Expanded Program on Immunization (EPI) and supplementary immunization activities (SIAs) in China, the incidence of measles in China has decreased extensively. The incidence reached its lowest levels in contemporary history in 2012 and 2017, with incidence rates of 4.6 and 4.3 per million population, respectively. However, more than 147,000 measles cases were reported from 2013 to 2016. Furthermore, the proportions of cases in infants < 8 months and adults have been increasing since 2013, representing a considerable challenge for measles elimination in China. A total of 14,868 measles viruses were isolated from confirmed measles cases from 2011 to 2017, of which 14,631 were identified as the predominant endemic genotype, H1; 87 were identified as genotype A viruses that were vaccine associated strains; and 150 were identified as non-H1 genotype viruses. The non-H1 genotype viruses included 62 D8 viruses, 70 D9 viruses, 3 D11 viruses, 14 B3 viruses, and 1 G3 virus, which were identified as imported or import-related viruses that caused sporadic cases or small outbreaks. Most of the transmission chains detected during the period 2011-2012 were interrupted and were followed by many new transmission chains of unknown origin that spread, causing a large measles resurgence in China during 2013-2016. After 4 years of measles resurgence and continuous implementation of the routine immunization program and SIAs, the population immunity reached a sufficiently high level to interrupt most of the transmission chains; only a few strains survived, which continued to be sporadically detected in China in 2017. In the present study, the results from the combined epidemiological and molecular virological data demonstrated the great progress towards measles elimination in China by the further analysis of circulation dynamics for the endemic H1 genotype measles virus from 2011 to 2017. And this study accumulated critical baseline data on circulating wild-type measles viruses in China and provides comprehensive information to the world. These comprehensive baseline data provide evidence to support measles elimination in the future, not only in China but also in other countries worldwide. In addition, the information will be very useful to other countries for tracing their sources of measles cases and for identifying transmission links, which can help prevent potential measles outbreaks.

To clarify the protective effect of one-dose mumps-containing vaccines (MuCV) in mainland China, the antigenic variations of HN gene and cross-neutralization capacities between MuCV and wild type genotype F MuVs were studied. In total, 70 HN gene sequences of genotype F MuV representative strains obtained from 2001 to 2015, two types of MuCV strains, 139 pairs of pre- and post-vaccination serum samples from infants receiving one dose of MuCV vaccination were analyzed. Genotype-specific amino acid variations were observed in the potential antigenic epitopes between MuCV and wild-type genotype F MuVs circulating in mainland China. The mumps neutralization antibody titers induced by one-dose MuCV were found to be generally low. Moreover, significant differences in neutralization titers were observed between vaccine and wild-type strains. It could be concluded that one-dose MuCV had a cross-protective effect against the wild-type genotype F MuVs, but its effectiveness was limited, which might be caused by insufficient doses of MuCV vaccination and the genotype-specific antigenic differences between vaccine and wild-type MuVs as well. In addition, a poor linear correlation between mumps-specific IgG concentrations and neutralization titers was observed in this study, indicating the concentration of MuV-specific IgG could not fully reflect the neutralizing antibody titer in serum. Therefore, it is highly recommended to provide a second dose of MuCV to preschool children to increase MuV neutralizing antibody titers and use MuV cross-neutralization test as preferred tool for assessment of mumps-containing vaccine effectiveness on wild-type MuVs. This is the first report to assess the effectiveness of one-dose Chinese MuCV against wild-type genotype F MuVs, which would be benefit for the development of mumps vaccination strategy.

Mumps incidence in mainland China remains at a high level. Genotype F has been the predominant genotype of mumps virus (MuV) in the last 20 years in mainland China. To better understand the genetic characteristics of MuV in China, the sequences of the Small Hydrophobic (SH), Hemagglutinin-Neuraminidase (HN) and Fusion (F) genes of MuVs of genotype F collected during 2001–2015 were determined. The evolutionary rates of the HN and F genes were similar (0.5 × 10−3 substitutions/site/year) whereas the SH gene evolutionary rate was three times faster. The most recent common ancestor of genotype F was traced back to 1980. Four lineages were identified within HN and F MuV sequences. A phylogeographic analysis indicated that the genotype F viruses originally spread from the Liaoning and Shandong provinces followed by a spread to the South and East of China. This study provides important genetic baseline data for the development of prevention and control measures of mumps.

A molecular epidemiological study of human respiratory syncytial virus (HRSV) was conducted to examine the distribution of its subgroups and genotypes, as well as to identify its transmission pattern in China. A total of 705 samples collected from 9 provinces in China between January 2008 and February 2015 were identified as HRSV-positive and were subsequently sequenced. Of these, 336 samples were HRSV subgroup A (HRSVA), 368 samples were HRSV subgroup B (HRSVB), and 1 sample contained both HRSVA and HRSVB. These 705 HRSV sequences, together with 766 HRSV sequences downloaded from GenBank, were analyzed to understand the recent circulation patterns of HRSV in China. HRSVB predominated in the 2008/2009 and 2009/2010 seasons, whereas HRSVA predominated in the 2010/2011 and 2011/2012 seasons; HRSVA and HRSVB co-circulated during 2012/2013 and 2014/2015. Phylogenetic analysis showed most of the HRSVA sequences clustered into 2 genotypes, namely, NA1 and ON1. The ON1 genotype was first detected in China in 2011, and it quickly replaced the NA1 genotype to become the most prevalent HRSVA genotype circulating in China between 2013 and 2015. Continuous epidemiological surveillance and molecular characterization of HRSV should be conducted to monitor the evolution of HRSV in China.

With the implementation of mumps virus (MuV) vaccination in the expanded program on immunization (EPI) in mainland China since 2008, the incidence of mumps has decreased, and the natural epidemic pattern of mumps has slightly changed during 2013-2015. The two epidemic peaks (April-July and November-December) became less obvious than those observed from 2004 to 2012. Children and adolescents younger than 15, particularly in the five-to-nine-year-old age group, remain the target group and should be the focus of high-quality immunization activities in mainland China. However, it was also found that the incidence and reported cases of mumps decreased in each age group during 2013-2015, particularly in the five-to-nine-year-old and ten-to-fourteen-year-old age groups. The proportion of mumps cases among adults in some provinces also increased. Unlike the changes in the epidemiological characteristics of mumps affected by vaccination, the data of MuV virology surveillance indicated that most of the MuV transmission chains have not yet been effectively interrupted, and MuV remains a natural epidemic pattern in mainland China. In the MuV virology surveillance, 194 MuV strains during 2013-2015 were isolated from 10 of 31 provinces in mainland China. Based on the phylogenetic analysis of the small hydrophobic (SH) gene, both genotype F (99.0%) and G (1.0%) were identified, and genotype F was still the predominant genotype continuously circulating in mainland China. Representative genotype F and G strains isolated in China from 1995 to 2012 were selected for further analysis. The results indicated that there were multiple transmission chains within genotype F, with no obvious geographical or time differences. The high genetic diversity of genotype F strains could be a result of the continuous transmission and evolution of the MuV in mainland China. Genotype G was also detected in four provinces in mainland China. Because of the limited epidemiological data, it was uncertain whether the genotype G MuV strains found in 2011 and 2013 were imported from other countries. Therefore, combined high-quality epidemiological and virological surveillance is necessary for mumps control; it can also be used to observe the changes in epidemiological characteristics and viral transmission of mumps over time after mumps-containing vaccine (MuCV) implementation and to provide a comprehensive epidemiological and genetic baseline for mumps elimination in mainland China.

Sine oculis homeobox homolog 1 (SIX1) protein is a member of the homeobox transcription factor family. Overexpression of SIX1 contributes to cancer progression and is associated with adverse outcomes in various cancer types including breast, ovarian, uterine cervical and liver. To investigate the clinicopathological significance of SIX1 protein expression in gastric adenocarcinomas (GAC), localization of the SIX1 protein was determined in MKN-1, a gastric cancer cell line, using immunofluorescence (IF) staining; SIX1 mRNA level was detected in fresh tissues of GAC and normal gastric mucosa using quantitative real-time polymerase chain reaction (qRT-PCR); and SIX1 protein expression was assessed in 163 GAC, 35 gastric dysplasia and 26 normal gastric mucosa using immunohistochemical (IHC) staining. Correlations between SIX1 protein expression and pathological parameters of GAC were analyzed using Chi-square tests, differences in survival curves were analyzed using log-rank tests, and multivariate survival analysis was performed using the Cox proportional hazards regression model. SIX1 protein showed a mainly cytoplasmic staining pattern in GAC using IF and IHC staining. The positive SIX1 protein expression rate was 80.4% in GAC, which was significantly higher than in either gastric dysplasia (45.7%) or normal gastric mucosa (26.9%) (P