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Abstract Local inflammatory microenvironment in the early stage of myocardial infarction (MI) severely impaired cardiac recovery post-MI. Macrophages play a pivotal role in this process. A classical glycolytic inhibitor, 2-Deoxy-Glucose (2-DG), has been found to regulate the excessive pro-inflammatory macrophage polarization in the infarcted myocardium. This study investigated the effect of 2-DG-loaded chitosan/gelatin composite patch on the infarct microenvironment post-MI and its impact on cardiac repair. The results showed that the 2-DG patch significantly inhibited the expression of inflammatory cytokines, alleviated reactive oxygen species (ROS) accumulation, repressed the proinflammatory polarization of macrophages, attenuated local inflammatory microenvironment in the ischemic hearts, as well as improved cardiac function, reduced scar size, and promoted angiogenesis post-MI. In terms of mechanism, 2-DG exerts anti-inflammatory effects through inhibiting the NF-κB signaling pathway and reducing the assembly and activation of the NLRP3 inflammasome. These findings suggest that 2-DG composite patch may represent a promising therapeutic strategy for cardiac repair after MI.

Abstract Due to the increase in emission requirements for non-road vehicles in many countries and the reduction of agricultural personnel, tractors are developing towards high horsepower and electrification. According to the working conditions of high-horsepower tractors, a hydromechanical continuously variable transmission (HMCVT) is designed for hybrid tractors. Taking a tractor equipped with this transmission as the research object, an equivalent factor global optimization model was established and a genetic algorithm was used to optimize the equivalent factor S offline to obtain the optimal equivalent factor of the tractor under different operating mileage and the initial state of charge (SOC) of battery. By using the optimized equivalent factor, the tractor can be in the charge depleting (CD) mode for a longer time on the premise of making full use of the energy in the battery, so as to improve the auxiliary ability of the motor in the whole operation cycle to reduce the fuel consumption of the tractor. The effectiveness of the control strategy is verified by MATLAB/Simulink and hardware in the loop (HIL) tests, and the fuel economy of tractors is improved by 2.939% and 3.909% respectively in the two tests.

Abstract Lung adenocarcinoma (LUAD) is a prevalent form of non-small cell lung cancer with a rising incidence in recent years. Understanding the mutation characteristics of LUAD is crucial for effective treatment and prediction of this disease. Among the various mutations observed in LUAD, KRAS mutations are particularly common. Different subtypes of KRAS mutations can activate the Ras signaling pathway to varying degrees, potentially influencing the pathogenesis and prognosis of LUAD. This study aims to investigate the relationship between different KRAS mutation subtypes and the pathogenesis and prognosis of LUAD. A total of 63 clinical samples of LUAD were collected for this study. The samples were analyzed using targeted gene sequencing panels to obtain sequencing data. To complement the dataset, additional clinical and sequencing data were obtained from TCGA and MSK. The analysis revealed significantly higher Ki67 immunohistochemical scores in patients with missense mutations compared to controls. Moreover, the expression level of KRAS was found to be significantly correlated with Ki67 expression. Enrichment analysis indicated that KRAS missense mutations activated the SWEET_LUNG_CANCER_KRAS_DN and CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_2 pathways. Additionally, patients with KRAS missense mutations and high Ki67 IHC scores exhibited significantly higher tumor mutational burden levels compared to other groups, which suggests they are more likely to be responsive to ICIs. Based on the data from MSK and TCGA, it was observed that patients with KRAS missense mutations had shorter survival compared to controls, and Ki67 expression level could more accurately predict patient prognosis. In conclusion, when utilizing KRAS mutations as biomarkers for the treatment and prediction of LUAD, it is important to consider the specific KRAS mutant subtypes and Ki67 expression levels. These findings contribute to a better understanding of LUAD and have implications for personalized therapeutic approaches in the management of this disease.

Abstract Cervical cancer (CC) is the most common gynecological malignant tumor. Immunotherapy has become a new model for the treatment of CC, especially advanced and recurrent cancer. At present, many studies are exploring the safety and efficacy of immunotherapy for advanced or recurrent CC. In this study, CIBERSORT was used to analyze the immune cell infiltration in CC patients, to evaluate the proportion of immune cell types in CC samples, to quantify the cell composition of the immune response, and to analyze its prognostic value. The expression profile datasets of CC were downloaded from the GEO. The differentially expressed genes (DEGs) between CC and normal cervical tissues were identified via R software (version 4.1.1), and their functions and pathways were enriched and analyzed. A protein–protein interaction network was constructed to screen the hub gene. Immune cell infiltration in CC was analyzed via scientific reverse convolution algorithm (CIBERSORT), and the hub gene was analyzed via survival analysis to screen the diagnostic biomarkers of CC. A total of 144 DEGs and 12 hub genes were identified. DEGs are mainly involved in molecular functions such as serine-peptidase activity, serine-hydrolase activity, and chemokine activity. The enrichment pathway is closely related to the interaction between viral proteins and cytokines and cytokine receptors, the interleukin 17 signaling pathway, and chemokine signaling pathway. The immune cell infiltration analysis showed that T cells were the main infiltrating immune cells in CC, especially T cells CD8+ and CD4+ . The survival analysis of the hub gene showed that CEP55, MCM2, RFC4, and RRM2 had high diagnostic value. CEP55, MCM2, RFC4, and RRM2 can be used as diagnostic markers for CC. CD8+ and CD4+ T cells are closely related to the occurrence and development of CC.

Contagious ecthyma is a zoonotic disease caused by the orf virus (ORFV). Since there is no specific therapeutic drug available, vaccine immunization is the main tool to prevent and control the disease. Previously, we have reported the construction of a double-gene deletion mutant of ORFV (rGS14ΔCBPΔGIF) and evaluated it as a vaccine candidate. Building on this previous work, the current study reports the construction of a new vaccine candidate, generated by deleting a third gene (gene 121) to generate ORFV rGS14ΔCBPΔGIFΔ121. The in vitro growth characteristics, as well as the in vivo safety, immunogenicity, and protective efficacy, were evaluated. RESULTS: There was a minor difference in viral replication and proliferation between ORFV rGS14ΔCBPΔGIFΔ121 and the other two strains. ORFV rGS14ΔCBPΔGIFΔ121 induced continuous differentiation of PBMC to CD4+T cells, CD8+T cells and CD80+CD86+ cells and caused mainly Th1-like cell-mediated immunity. By comparing the triple-gene deletion mutant with the parental strain and the double-gene deletion mutant, we found that the safety of both the triple-gene deletion mutant and the double-gene deletion mutant could reach 100% in goats, while the safety of parental virus was only 50% after continually observing immunized animals for 14 days. A virulent field strain of ORFV from an ORF scab was used in the challenge experiment by inoculating the virus to the hairless area of the inner thigh of immunized animals. The result showed that the immune protection rate of triple-gene deletion mutant, double-gene mutant, and the parental virus was 100%, 66.7%, and 28.6%, respectively. In conclusion, the safety, immunogenicity, and immune-protectivity of the triple-gene deletion mutant were greatly improved to 100%, making it an excellent vaccine candidate.

The Gould and Fernandez local brokerage measure defines brokering roles based on the group membership of the nodes from the incoming and outgoing edges. This paper extends on this brokerage measure to account for weighted edges and introduces the Weighted–Normalized Gould–Fernandez measure (WNGF). The value added of this new measure is demonstrated empirically with both a macro level trade network and a micro level organization network. The measure is first applied to the EUREGIO inter-regional trade dataset and then to an organizational network in a research and development (R&D) group. The results gained from the WNGF measure are compared to those from two dichotomized networks: a threshold and a multiscale backbone network. The results show that the WNGF generates valid results, consistent with those of the dichotomized network. In addition, it provides the following advantages: (i) it ensures information retention; (ii) since no alterations and decisions have to be made on how to dichotomize the network, the WNGF frees the user from the burden of making assumptions; (iii) it provides a nuanced understanding of each node’s brokerage role. These advantages are of special importance when the role of less connected nodes is considered. The two empirical networks used here are for illustrative purposes. Possible applications of WNGF span beyond regional and organizational studies, and into all those contexts where retaining weights is important, for example by accounting for persisting or repeating edges compared to one-time interactions. WNGF can also be used to further analyze networks that measure how often people meet, talk, text, like, or retweet. WNGF makes a relevant methodological contribution as it offers a way to analyze brokerage in weighted, directed, and even complete graphs without information loss that can be used across disciplines and different type of networks.

Abstract To date, at least three lineages (Lineage 1–3) that are related to recombinant human adenovirus species C (HAdV-C) have been identified in China. Among them, Lineage 1 includes two Chinese strains, strain KR699642-CHN-20093 (CBJ11) and strain MF315029-CHN-2013 (BJ09), which were collected in Beijing in 2009 and 2013, respectively. Herein, we performed genomic and bioinformatics analysis of two HAdV-C strains (strain SX-2000-140 and strain SX-2004-327) that were isolated from the feces of two healthy children in Shanxi province of China in 2000 and 2004, respectively. Results revealed that the genomes of both Shanxi strains had the highest homology to two Chinese HAdV-C strains belonging to Lineage 1 and harbored the genetic elements of these two strains, thereby presuming that Lineage1 has been circulated in mainland of China for decades. In addition, though the viruses in Lineage 1 showed slightly different recombinant patterns resulting from the recombinant events among the five types of HAdV-C, all the Lineage 1 viruses shared the highest sequence similarities with the HAdV-2 prototype strain (NC_001405-USA-1953) across the genome, especially in the major capsid genes including hexon, and fiber. These results indicated that Lineage 1 viruses that were associated with recombinants shared a common ancestor that is closely related to the HAdV-2 virus. Our current findings confirmed that frequent recombination among the different HAdV-C types might be an important driving force for the molecular evolution of HAdV-C. Therefore, there is a strong need for further comprehensive and systematic monitoring, detection, and research on HAdV-C.

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.

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

Previous cochlear implant (CI) research has shown that at a pulse train with a long pulse phase duration (PPD) requires less current but greater charge to obtain the same loudness as a pulse train with a short PPD. This might result in different excitation patterns between long and short PPDs. At equal loudness, long PPDs might produce greater masking due to greater charge. However, because they require less current, long PPDs may produce a smaller spatial spread of excitation (SOE) compared to short PPDs by evoking a greater neural firing probability within the relatively small current field. To investigate the effects of PPD on excitation patterns, overall masking and SOE were compared for equally loud stimuli with short or long PPD in 10 adult CI ears. Forward masking patterns were measured at relatively soft, medium, and loud presentation levels. Threshold shifts were calculated in terms of percent dynamic range (DR) of the probe. The area under the curve (AUC) of the masking functions was significantly larger for the long PPD than for the short PPD masker. The difference in AUC was proportional to the difference in charge between the short and long PPD maskers. To estimate SOE, the masking patterns were first normalized to the peak masking, and then AUC was calculated. SOE was significantly larger for the short PPD than for the long PPD masker. Thus, at equal loudness, long PPDs produced greater overall masking (possibly due to greater charge) but less SOE (possibly due to less current spread) than did short PPDs. The effect of the interaction between masking and SOE by long PPD stimulation remains to be tested.

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.

In addition to high vaccination coverage, timely and accurate laboratory confirmation of measles cases is critical to interrupt measles transmission. To evaluate the role of real-time reverse transcription-polymerase chain reaction (RT-PCR) in the diagnosis of measles cases, 46,363 suspected measles cases with rash and 395 suspected measles cases without rash were analyzed in this study; the cases were obtained from the Chinese measles surveillance system (MSS) during 2014-2017 and simultaneously detected by measles-specific IgM enzyme-linked immunosorbent assay (ELISA) and real-time RT-PCR. However, some IgM-negative measles cases were identified by real-time RT-PCR. The proportion of these IgM-negative and viral nucleic acid-positive measles cases was high among measles cases with measles vaccination history, cases without rash symptoms, and cases within 3 days of specimen collection after onset. The proportion of IgM-negative and viral nucleic acid-positive measles cases in the 0-3 day group was up to 14.4% for measles cases with rash and 40% for measles cases without rash. Moreover, the proportions of IgM-negative and nucleic acid-positive measles cases gradually increased with the increase in the measles vaccination dose. Therefore, integrated with IgM ELISA, real-time RT-PCR would greatly improve the accurate diagnosis of measles cases and avoid missing the measles cases, especially for measles cases during the first few days after onset when the patients were highly contagious and for measles cases with secondary vaccine failure. In conclusion, our study reconfirmed that IgM ELISA is the gold-standard detection assay for measles cases confirmation. However, real-time RT-PCR should be introduced and used to supplement the laboratory diagnosis, especially in the setting of pre-elimination and/or elimination wherever appropriate.

Transgenic poplar lines 'Shanxin' (Populus davidiana×Populus bolleana) were generated via Agrobacterium-mediated transformation. The transgenic lines carried the expression cassettes of Cry1Ac + SCK, Cry1Ah3, and Cry9Aa3, respectively. The expression levels of the exogenous insect resistance genes in the transgenic lines were determined by Q-PCR and Western blot. Leaves of the transgenic lines were used for insect feeding bioassays on first instar larvae of the gypsy moth (Lymantria dispar) and fall webworm (Hyphantria cunea). At 5 d of feeding, the mean mortalities of larvae feeding on Cry1Ac + SCK and Cry1Ah3 transgenic poplars leaves were 97% and 91%, while mortality on Cry9Aa3 transgenic lines was about 49%. All gypsy moth and fall webworm larvae were killed in 7-9 days after feeding on leaves from Cry1Ac + SCK or Cry1Ah3 transgenic poplars, while all the fall webworm larvae were killed in 11 days and about 80% of gypsy moth larvae were dead in 14 days after feeding on those from Cry9Aa3 transgenic lines. It was concluded that the transgenic lines of Cry1Ac + SCK and Cry1Ah3 were highly toxic to larvae of both insect species while lines with Cry9Aa3 had lower toxicity,and H. cunea larvae are more sensitive to the insecticidal proteins compared to L. dispar. Transgenic poplar lines toxic to L. dispar and H. cunea could be used to provide Lepidoptera pest resistance to selected strains of poplar trees.

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.

From April to November 2016, two outbreaks of epidemic keratoconjunctivitis (EKC) occurred successively at primary and middle schools in the Tibet Autonomous Region of China, and a total of 197 clinically diagnosed cases were reported. Real-time PCR analyses confirmed that human adenovirus (HAdV) infection was related to these outbreaks. Further studies involving sequence determination and phylogenetic analysis based on the penton base, hexon, and fiber genes indicated that human adenovirus type 8 (HAdV-8), belonging to species D, was responsible for the outbreaks. This is the first report of a HAdV-8 associated EKC outbreak in mainland of China, and the results of this study are expected to provide support for future research into HAdV-8 in China.

BACKGROUND AND OBJECTIVES: Open chest trauma with seawater immersion can lead systematic inflammatory response and multiple organ dysfunction syndromes (MODS). Early intervention of seawater immersion significantly decreases mortality. This study aims to explore the curative effect of pleural lavage in the treatment of open chest trauma caused by seawater immersion on dogs. DESIGN AND SETTINGS: An in vivo experimental study was performed in healthy cross-breeding adult dogs (n=20). SUBJECTS AND METHODS: A dog model of open chest trauma caused by seawater immersion was established. All experimental dogs were divided into control group and pleural lavage group, with 10 dogs in each group. In the control group, dogs were performed ventilator-assisted breathing, and thoracic tube was kept open for adequate chest water drainage; in the pleural lavage group, dogs were further injected with 0.9% sodium chloride (35 mL/kg) immediately into the right side of the chest after the pleural effusion was drained off. The internal environment, oxygen partial pressure, and pathological changes of the lung tissue were observed and recorded. RESULTS: Following open chest trauma caused by seawater immersion, both groups showed obviously increased serum sodium and plasma osmolality and sharply decreased oxygen partial pressure. After treatment, the serum sodium and plasma osmolality decreased, whereas oxygen partial pressure increased in both groups. The pleural lavage group showed better improvement than the conventional treatment group. The pathological changes in the pleural group were lighter than in the conventional treatment group. CONCLUSION: Compared with conventional treatment, repeated pleural lavage shows improved treatment in the correction of blood hypertonic state and hypoxemia in seawater-immersed open chest trauma.

To determine the origin of the virus associated with a measles outbreak in Menglian County, Yunnan Province, People’s Republic of China, in 2009, we conducted genetic analyses. Phylogenetic analyses based on nucleoprotein (N) and hemagglutinin (H) gene sequences showed that these Menglian viruses were not closely related to sequences of any World Health Organization (WHO) reference strains representing the 23 currently recognized genotypes. The minimum nucleotide divergence between the Menglian viruses and the most closely related reference strain, genotype D7, was 3.3% for the N gene and 3.0% for the H gene. A search of the databases of GenBank, WHO, and the Health Protection Agency Measles Nucleotide Surveillance showed that the Menglian viruses, together with the 2 older non-Menglian viruses, could be members of a new proposed measles genotype, d11. The new genotype designation will allow for better description of measles transmission patterns, especially in the Southeast Asian and Western Pacific regions.

Production systems, traditionally analyzed as almost independent national systems, are increasingly connected on a global scale. Only recently becoming available, the World Input-Output Database (WIOD) is one of the first efforts to construct the global multi-regional input-output (GMRIO) tables. By viewing the world input-output system as an interdependent network where the nodes are the individual industries in different economies and the edges are the monetary goods flows between industries, we analyze respectively the global, regional, and local network properties of the so-called world input-output network (WION) and document its evolution over time. At global level, we find that the industries are highly but asymmetrically connected, which implies that micro shocks can lead to macro fluctuations. At regional level, we find that the world production is still operated nationally or at most regionally as the communities detected are either individual economies or geographically well defined regions. Finally, at local level, for each industry we compare the network-based measures with the traditional methods of backward linkages. We find that the network-based measures such as PageRank centrality and community coreness measure can give valuable insights into identifying the key industries.

The fragmentation of production across countries has become an important feature of the globalization in recent decades and is often conceptualized by the term "global value chains" (GVCs). When empirically investigating the GVCs, previous studies are mainly interested in knowing how global the GVCs are rather than how the GVCs look like. From a complex networks perspective, we use the World Input-Output Database (WIOD) to study the evolution of the global production system. We find that the industry-level GVCs are indeed not chain-like but are better characterized by the tree topology. Hence, we compute the global value trees (GVTs) for all the industries available in the WIOD. Moreover, we compute an industry importance measure based on the GVTs and compare it with other network centrality measures. Finally, we discuss some future applications of the GVTs.

Adenovirus is one of the most common causes of viral acute respiratory infections. To identify the types of human adenoviruses (HAdVs) causing respiratory illness in Beijing, a sentinel surveillance project on the viral aetiology of acute respiratory infection was initiated in 2011.Through the surveillance project, 4617 cases of respiratory infections were identified during 2011-2013. Throat swabs (pharynx and tonsil secretions) were collected from all the patients, and 15 different respiratory viruses were screened by multiplex one-step PCR method. 45 were identified as adenovirus-positive from sporadic and outbreak cases of respiratory infection by a multiplex one-step RT-PCR method, and a total of 21 adenovirus isolates were obtained. Five HAdV types among three species, including HAdV-3 (species HAdV-B), HAdV-4 (species HAdV-E), HAdV-7 (species HAdV-B), HAdV-55 (species HAdV-B), and an undefined HAdV type (species HAdV-C) were identified. The comparison results of the penton base, hexon, and fiber gene sequences of the Beijing HAdV-3, HAdV-4, HAdV-7, and HAdV-55 strains in this study and those from the GenBank database indicated significant spatial and temporal conservation and stability of sequences within the genome; however, the phylogenetic relationship indicated that both strain BJ04 and strain BJ09 isolated in 2012 and 2013, respectively, may have recombined between HAdV-1 genome and HAdV-2 genome within species HAdV-C, indicating intraspecies recombination.This study confirmed that at least 5 HAdV types including HAdV-3, HAdV-4, HAdV-7, HAdV-55 and an undefined HAdV type were co-circulating and were the causative agents of respiratory tract infections in recent years in Beijing. HAdV-3, HAdV-4, HAdV-7, and HAdV-55 showed the apparent stability of the genomes, while intraspecies recombination was identified in strain BJ04 and BJ09. The recombinants carrying penton base gene of HAdV-1 as well as hexon and fiber genes of HAdV-2 might be a novel type of HAdV worthy of further study.

A rubella outbreak occurred in Anqing city of Anhui province, China, from February to July of 2012, and a total of 241 clinically diagnosed or lab-confirmed patients were reported. The highest number of rubella cases during this outbreak was recorded in teenagers between 10 and 19 years of age who had not previously received the rubella vaccine. Genotyping results indicated that the genotype 2B rubella virus (RV) was responsible for the outbreak. However, a phylogenetic analysis showed that the genotype 2B RVs isolated in Anqing City were not related to 2B RVs found in other cities of Anhui province and in other provinces of China, thus providing evidence for importation. After importation, the transmission of Anqing RVs was interrupted owing to an effective immunization campaign against rubella, suggesting the timeliness and effectiveness of contingency vaccination. Strengthening rubella surveillance, including the integration of epidemiologic information and laboratory data, is a vital strategy for rubella control and elimination. In addition, except for routine immunization, targeted supplementary immunization activities aimed at susceptible groups according to sero-epidemiological surveillance data also play a key role in stopping the continuous transmission of rubella viruses and in preventing further congenital rubella syndrome cases.

HAdV-56 is a new recombinant type isolated from epidemic keratoconjunctivitis (EKC) patients and has been sporadically isolated in Japan several times. Here, an outbreak of EKC in the city of Dalian, China involving a large number of workers in two factories was reported; this was the first outbreak of EKC associated with HAdV-56 worldwide.

Theory of complex networks proved successful in the description of a variety of complex systems ranging from biology to computer science and to economics and finance. Here we use network models to describe the evolution of a particular economic system, namely the International Trade Network (ITN). Previous studies often assume that globalization and regionalization in international trade are contradictory to each other. We re-examine the relationship between globalization and regionalization by viewing the international trade system as an interdependent complex network. We use the modularity optimization method to detect communities and community cores in the ITN during the years 1995-2011. We find rich dynamics over time both inter- and intra-communities. In particular, the Asia-Oceania community disappeared and reemerged over time along with a switch in leadership from Japan to China. We provide a multilevel description of the evolution of the network where the global dynamics (i.e., communities disappear or reemerge) and the regional dynamics (i.e., community core changes between community members) are related. Moreover, simulation results show that the global dynamics can be generated by a simple dynamic-edge-weight mechanism.

To assess the efficacy and safety of propofol sedation for gastrointestinal endoscopy, we conducted a meta-analysis of randomized controlled trials (RCTs) comparing propofol with traditional sedative agents.RCTs comparing the effects of propofol and traditional sedative agents during gastrointestinal endoscopy were found on MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE. Cardiopulmonary complications (i.e., hypoxia, hypotension, arrhythmia, and apnea) and sedation profiles were assessed.Twenty-two original RCTs investigating a total of 1,798 patients, of whom 912 received propofol only and 886 received traditional sedative agents only, met the inclusion criteria. Propofol use was associated with shorter recovery (13 studies, 1,165 patients; WMD -19.75; 95% CI -27.65, 11.86) and discharge times (seven studies, 471 patients; WMD -29.48; 95% CI -44.13, -14.83), higher post-anesthesia recovery scores (four studies, 503 patients; WMD 2.03; 95% CI 1.59, 2.46), better sedation (nine studies, 592 patients; OR 4.78; 95% CI 2.56, 8.93), and greater patient cooperation (six studies, 709 patients; WMD 1.27; 95% CI 0.53, 2.02), as well as more local pain on injection (six studies, 547 patients; OR 10.19; 95% CI 3.93, 26.39). Effects of propofol on cardiopulmonary complications, procedure duration, amnesia, pain during endoscopy, and patient satisfaction were not found to be significantly different from those of traditional sedative agents.Propofol is safe and effective for gastrointestinal endoscopy procedures and is associated with shorter recovery and discharge periods, higher post-anesthesia recovery scores, better sedation, and greater patient cooperation than traditional sedation, without an increase in cardiopulmonary complications. Care should be taken when extrapolating our results to specific practice settings and high-risk patient subgroups.

BACKGROUND: Acute respiratory infections (ARIs) are the leading cause of children and their leading killer. ARIs are responsible for at least six percent of the world's disability and death. Viruses are one of the most common agents causing ARIs. Few studies on the viral etiology and clinical characteristics of ARIs have been performed in the northwest region of China, including Gansu Province. METHODS: Clinical and demographic information and throat swabs were collected from 279 patients from January 1st to December 30st, 2011. Multiplex RT-PCR was performed to detect 16 respiratory viral pathogens. RESULTS: 279 patients were admitted for ARIs. The patients aged from 1 month to 12 years, with the median age of 2 years. Of which, 105 (37.6%) were positive for at least one pathogen. A total of 136 respiratory viral pathogens were identified from the 105 patients. Respiratory syncytial virus (RSV) was the most frequently detected pathogen (26.5%, 36/136), followed by parainfluenza virus (PIV) 1-3 (22.1%, 30/136), human rhinovirus (HRV) (21.3%, 29/136), human coronavirus (CoV) (10.3%, 14/136) and human adenovirus (HAdV) (9.6%, 13/136). Influenza A (Flu A), human metapneumovirus (hMPV) and human bocavirus (BoCA) were found 4.4%, 3.7% and 2.2%, respectively. Influenza B (Flu B) and seasonal influenza A H1N1(sH1N1) were not detected. Single-infections were detected in 30.5% (85/279) of cases. RSV was the most common pathogens in patients under 1 year and showed seasonal variation with peaks during winter and spring. CONCLUSIONS: This paper presents data on the epidemiology of viral pathogens associated with ARIs among children in Gansu Province, China. RSV is most frequently detected in our study. The findings could serve as a reference for local CDC in drawing up further plans to prevent and control ARIs.

Genetic recombination is a well-known phenomenon for enteroviruses. To investigate the genetic characterization and the potential recombination of enterovirus 71 (EV71) circulating in China, we determined the 16 complete genome sequences of EV71 isolated from Hand Foot Mouth Disease (HFMD) patients during the large scale outbreak and non-outbreak years since 1998 in China. The full length genome sequences of 16 Chinese EV71 in present study were aligned with 186 genome sequences of EV71 available from GenBank, including 104 China mainland and 82 international sequences, covering the time period of 1970-2011. The oldest strains of each subgenotype of EV71 and prototype strains of HEV-A were included to do the phylogenetic and Simplot analysis. Phylogenetic analysis indicated that all Chinese strains were clustered into C4 subgenotype of EV71, except for HuB/CHN/2009 clustered into A and Xiamen/CHN/2009 clustered into B5 subgenotype. Most of C4 EV71 were clustered into 2 predominant evolutionary branches: C4b and C4a evolutionary brunches. Our comprehensive recombination analysis showed the evidence of genome recombination of subgenotype C4 (including C4a and C4b) sequences between structural genes from genotype C EV71 and non-structural genes from the prototype strains of CAV16, 14 and 4, but the evidence of intratypic recombination between C4 strains and B subgenotype was not enough strong. This intertypic recombination C4 viruses were first seen in 1998 and became the predominant endemic viruses circulating in China mainland for at least 14 years. A shift between C4a and C4b evolutionary brunches of C4 recombination viruses were observed, and C4a viruses have been associated with large scale nationwide HFMD outbreak with higher morbidity and mortality since 2007.

Large-scale Hand, Foot, and Mouth Disease (HFMD) outbreaks have frequently occurred in China since 2008, affecting more than one million children and causing several hundred children deaths every year. The pathogens of HFMD are mainly human enteroviruses (HEVs). Among them, human enterovirus 71 (HEV71) and coxsackievirus A16 (CVA16) are the most common pathogens of HFMD. However, other HEVs could also cause HFMD. To rapidly detect HEV71 and CVA16, and ensure detection of all HEVs causing HFMD, two real-time hybridization probe-based RT-PCR assays were developed in this study. One is a multiplex real-time RT-PCR assay, which was developed to detect and differentiate HEV71 specifically from CVA16 directly from clinical specimens within 1-2 h, and the other is a broad-spectrum real-time RT-PCR assay, which targeted almost all HEVs. The experiments confirmed that the two assays have high sensitivity and specificity, and the sensitivity was up to 0.1 TCID50/ml for detection of HEVs, HEV71, and CVA16, respectively. A total of 213 clinical specimens were simultaneously detected by three kinds of assays, including the two real-time RT-PCR assays, direct conventional RT-PCR assay, and virus isolation assay on human rhabdomyosarcoma cells (RD cells). The total positive rate of both HEV71 and CVA16 was 69.48% with real-time RT-PCR assay, 47.42% with RT-PCR assay, and 34.58% with virus isolation assay. One HFMD clinical specimen was positive for HEV, but negative for HEV71 or CVA16, which was identified as Echovirus 11 (Echo11) by virus isolation, RT-PCR, and sequencing for the VP1 gene. The two real-time RT-PCR assays had been applied in 31 provincial HFMD labs to detect the pathogens of HFMD, which has contributed to the rapid identification of the pathogens in the early stages of HFMD outbreaks, and helped to clarify the etiologic agents of HFMD in China.

BACKGROUND: Human enterovirus 85 (HEV85), whose prototype strain (Strain BAN00-10353/BAN/2000) was isolated in Bangladesh in 2000, is a recently identified serotype within the human enterovirus B (HEV-B) species. At present, only one nucleotide sequence of HEV85 (the complete genome sequence of the prototype strain) is available in the GenBank database. PRINCIPAL FINDINGS: In this study, we report the genetic characteristics of 33 HEV85 isolates that circulated in the Xinjiang Uighur autonomous region of China in 2011. Sequence analysis revealed that all these Chinese HEV85 isolates belong to 2 transmission chains, and intertypic recombination was found with the new unknown serotype HEV-B donor sequences. Two HEV85 isolates recovered from a patient presenting acute flaccid paralysis and one of his contacts were temperature-insensitive strains, and some nucleotide substitutions in the non-coding regions and in the 2C or 3D coding regions may have affected the temperature sensitivity of HEV85 strains. CONCLUSIONS: The Chinese HEV85 recombinant described in this study trapped a new unknown serotype HEV-B donor sequence, indicating that new unknown HEV-B serotypes exist or circulate in Xinjiang of China. Our study also indicated that HEV85 is a prevalent and common enterovirus serotype in Xinjiang.

The incidence of measles in China from 1991 to 2008 was reviewed, and the nucleotide sequences from 1507 measles viruses (MeV) isolated during 1993 to 2008 were phylogenetically analyzed. The results showed that measles epidemics peaked approximately every 3 to 5 years with the range of measles cases detected between 56,850 and 140,048 per year. The Chinese MeV strains represented three genotypes; 1501 H1, 1 H2 and 5 A. Genotype H1 was the predominant genotype throughout China continuously circulating for at least 16 years. Genotype H1 sequences could be divided into two distinct clusters, H1a and H1b. A 4.2% average nucleotide divergence was found between the H1a and H1b clusters, and the nucleotide sequence and predicted amino acid homologies of H1a viruses were 92.3%-100% and 84.7%-100%, H1b were 97.1%-100% and 95.3%-100%, respectively. Viruses from both clusters were distributed throughout China with no apparent geographic restriction and multiple co-circulating lineages were present in many provinces. Cluster H1a and H1b viruses were co-circulating during 1993 to 2005, while no H1b viruses were detected after 2005 and the transmission of that cluster has presumably been interrupted. Analysis of the nucleotide and predicted amino acid changes in the N proteins of H1a and H1b viruses showed no evidence of selective pressure. This study investigated the genotype and cluster distribution of MeV in China over a 16-year period to establish a genetic baseline before MeV elimination in Western Pacific Region (WPR). Continuous and extensive MeV surveillance and the ability to quickly identify imported cases of measles will become more critical as measles elimination goals are achieved in China in the near future. This is the first report that a single endemic genotype of measles virus has been found to be continuously circulating in one country for at least 16 years.

The relevance of human parainfluenza viruses (HPIVs) to the epidemiology of acute respiratory infections (ARI) in China is unclear. From May 2008 to September 2010, 443 nasopharyngeal aspirates (NPAs) from hospitalized pediatric patients (age from 1 to 93 months) in Beijing were collected and screened for HPIVs and other common respiratory viruses by real-time RT-PCR. Sixty-two of 443 samples were positive for HPIVs with 4 positive for HPIV-2 and 58 positive for HPIV-3, indicating that HPIV-3 was the predominant virus present during the study period. A phylogenetic tree based on all the available HN (hemagglutinin-neuraminidase) sequences of HPIV-3 indicated that three distinct clusters (A,B, and C) were circulating with some temporal and regional clustering. Cluster C was further divided into sub-clusters, C1, C2, C3 and C4. HPIV-3 from Beijing isolates belonged to sub-cluster C3, and were grouped with the isolates from two Provinces of China and the neighboring country of Japan. Genetic analysis based on entire HN gene revealed that the HPIV-3 isolates from Beijing were highly similar with 97.2%-100% identity at the nucleotide level and these could be divided into two closely related lineages, C3a and C3b. These findings suggested that there was co-circulation of multiple lineages of HPIV-3 in the Beijing region during the study period. This is the first study to describe the epidemiology and molecular characterization of HPIVs in China.

BACKGROUND: The rubella vaccine was introduced into the immunization program in 1995 in the Shandong province, China. A series of different rubella vaccination strategies were implemented at different stages of measles control in Shandong province. METHODOLOGY/PRINCIPAL FINDINGS: The average reported incidence rate of rubella cases remained at a low level in Shandong province after 1999. However, rubella epidemics occurred repeatedly in 2001/2002, 2006, and 2008/2009. The age of the onset of rubella cases gradually increased during 1999-2010, which showed that most cases were found among the 10 years old in 1999 and among the 17 years old in 2010. Phylogenetic analysis was performed and a phylogenetic tree was constructed based on the World Health Organization standard sequence window for rubella virus isolates. All rubella viruses isolated in Shandong province were divided into 4 genotypes: 1E, 1F, 2A, and 2B. Genotype 1E viruses accounted for the majority (79%) of all these viruses. The similarity of nucleotide and amino acid sequences among genotype 1E viruses was 98.2-100% and 99.1-100%, respectively. All Shandong genotype 1E strains, differed from international genotype 1E strains, belonged to cluster 1 and interdigitated with the viruses from other provinces in mainland China. The effective number of infections indicated by a bayesian skyline plot remained constant from 2001 to 2009. CONCLUSIONS/SIGNIFICANCE: The gradual shift of disease burden to an older age group occurred after a rubella-containing vaccine was introduced into the childhood immunization schedule in 1995 in Shandong province. Four genotypes, including 1E, 1F, 2A, and 2B, were found in Shandong province during 2000-2009. Genotype 1E, rather than genotype 1F, became the predominant genotype circulating in Shandong province from 2001. All Shandong genotype 1E viruses belong to the genotype 1E/cluster 1; they have constantly circulated, and co-evolved and co-circulated, with those from other provinces.

BACKGROUND: Large-scale outbreaks of hand, foot, and mouth disease (HFMD) occurred repeatedly in the Central Plain of China (Shandong, Anhui, and Henan provinces) from 2007 until now. These epidemics have increased in size and severity each year and are a major public health concern in mainland China. PRINCIPAL FINDINGS: Phylogenetic analysis was performed and a Bayesian Markov chain Monte Carlo tree was constructed based on the complete VP1 sequences of HEV71 isolates. These analyses showed that the HFMD epidemic in the Central Plain of China was caused by at least 5 chains of HEV71 transmission and that the virus continued to circulate and evolve over the winter seasons between outbreaks. Between 1998 and 2010, there were 2 stages of HEV71 circulation in mainland China, with a shift from evolutionary branch C4b to C4a in 2003-2004. The evolution rate of C4a HEV71 was 4.99×10(-3) substitutions per site per year, faster than the mean of all HEV71 genotypes. The most recent common ancestor estimates for the Chinese clusters dated to October 1994 and November 1993 for the C4a and C4b evolutionary branches, respectively. Compared with all C4a HEV71 strains, a nucleotide substitution in all C4b HEV71 genome (A to C reversion at nt2503 in the VP1 coding region, which caused amino acid substitution of VP1-10: Gln to His) had reverted. CONCLUSIONS: The data suggest that C4a HEV71 strains introduced into the Central Plain of China are responsible for the recent outbreaks. The relationships among HEV71 isolates determined from the combined sequence and epidemiological data reveal the underlying seasonal dynamics of HEV71 circulation. At least 5 HEV71 lineages circulated in the Central Plain of China from 2007 to 2009, and the Shandong and Anhui lineages were found to have passed through a genetic bottleneck during the low-transmission winter season.