Evaluation of connective tissue disease-related interstitial lung disease using ultrasound elastography: a preliminary study.

Background: Interstitial lung disease (ILD) is a common pulmonary complication of connective tissue disease (CTD), which can lead to shortened survival. This article explores the ability of shear wave elastography (SWE) to assess lung surface elastic properties and to distinguish healthy lungs from diseased lungs with connective tissue disease-related interstitial lung disease (CTD-ILD). We aimed to determine whether SWE can be used to assess the severity of CTD-ILD. Methods: A total of 65 CTD-ILD patients and 60 healthy volunteers were included for the case group and the control group, respectively. All participants underwent lung ultrasound (count of B-line and measurement of pleural line thickness) and SWE [measurement of Young's modulus (Emean) and shear wave velocity (SMV) (Cmean)] examinations at 50 lung sites. All participants also underwent an examination with high-resolution computed tomography (HRCT) and a pulmonary function test (PFT). For SWE assessment, the Q-box was set to its minimum size (1 mm) and manually placed on the pleural line, rather than inside the lung, to measure the stiffness of the lung surface. The intra- and inter-reliability of SWE measurements of healthy controls (HC), the receiver operating characteristic (ROC) curve for SWE for CTD-ILD, and correlations between different assessment methods were analyzed. Results: Excellent intra- and inter-reliability of SWE measurements on the mid-anterior lung site of HCs (correlation coefficient >0.97; P<0.01) were found. The results of the lung ultrasound of case group participants were significantly higher than those of HCs at each site (P<0.001). The SWE results revealed a significant increase in both Emean and Cmean in CTD-ILD patients (P<0.001) compared with HCs at certain sites (P<0.001). The areas under the curve (AUC) of Emean and Cmean for CTD-ILD were 0.646 and 0.647 (P<0.05), respectively, and the cutoff values for Emean and Cmean to distinguish CTD-ILD from healthy lungs were 15.81 kPa and 2.31 m/s, respectively. There was no significant correlation between the SWE measured values and the number of B-lines, or the HRCT and PFT results, respectively (P>0.05). Conclusions: As a noninvasive ultrasound elastography (UE) technique, SWE may provide a novel method to differentiate CTD-ILD-affected lungs and healthy lungs. It is a reliable way to measure the stiffness of a healthy lung surface in the supine position. However, the ability of SWE to evaluate the severity of CTD-ILD may be limited.

Comparison of immune response to human rhinovirus C and respiratory syncytial virus in highly differentiated human airway epithelial cells.

BACKGROUND: Human rhinovirus C (HRV-C) accounts for a large proportion of HRV-related illnesses, but the immune response to HRV-C infection has not been elucidated. Our objective was to assess the effect of HRV-C on cytokine secretion in human bronchial epithelial (HBE) cells grown at air-liquid interface (ALI) and compare it with that of respiratory syncytial virus (RSV). METHODS: HBE cells were differentiated at ALI culture and the full-length cDNA clones of HRV-C651 and HRV-C15, clinical isolates of HRV-C79 and HRV-C101, and two RSV isolates were inoculated in the HBE cells. The effect of HRV-C on cytokine secretion was assessed and compared with that of RSV. RESULTS: HRV-Cs infect and propagate in fully differentiated HBE cells and significantly increase the secretion of IFN-λ1, CCL5, IP10, IL-6, IL-8, and MCP-1. The virus loads positively correlated with the levels of the cytokines. HRV-C induced lower secretion of CCL5 (P = 0.048), IL-6 (P = 0.016), MCP-1 (P = 0.008), and IL-8 (P = 0.032), and similar secretion of IP10 (P = 0.214) and IFN-λ1 (P = 0.214) when compared with RSV. CONCLUSION: HBE ALI culture system supported HRV-C infection and propagation and HRV-C induced relatively weaker cytokine expression than RSV.

Global status of antimicrobial resistance among environmental isolates of Vibrio cholerae O1/O139: a systematic review and meta-analysis.

BACKGROUND: Vibrio cholerae O1/O139 were the predominant circulating serogroups exhibiting multi-drug resistance (MDR) during the cholera outbreak which led to cholera treatment failures. OBJECTIVE: This meta-analysis aimed to evaluate the weighted pooled resistance (WPR) rates in V. cholerae O1/O139 isolates obtained from environmental samples. METHODS: We systematically searched the articles in PubMed, Scopus, and Embase (until January 2020). Subgroup analyses were then employed by publication year, geographic areas, and the quality of studies. Statistical analyses were conducted using STATA software (ver. 14.0). RESULTS: A total of 20 studies investigating 648 environmental V. cholerae O1/O139 isolates were analysed. The majority of the studies were originated from Asia (n = 9). In addition, a large number of studies (n = 15 i.e. 71.4%) included in the meta-analysis revealed the resistance to cotrimoxazole and ciprofloxacin. The WPR rates were as follows: cotrimoxazole 59%, erythromycin 28%, tetracycline 14%, doxycycline 5%, and ciprofloxacin 0%. There was increased resistance to nalidixic acid, cotrimoxazole, furazolidone, and tetracycline while a decreased resistance to amoxicillin, ciprofloxacin, erythromycin, chloramphenicol, ampicillin, streptomycin, and ceftriaxone was observed during the years 2000-2020. A significant decrease in the doxycycline and ciprofloxacin-resistance rates in V. cholerae O1/O139 isolates was reported over the years 2011-2020 which represents a decrease in 2001-2010 (p < 0.05). CONCLUSIONS: Fluoroquinolones, gentamicin, ceftriaxone, doxycycline, kanamycin, and cefotaxime showed the highest effectiveness and the lowest resistance rate. However, the main interest is the rise of antimicrobial resistance in V. cholerae strains especially in low-income countries or endemic areas, and therefore, continuous surveillance, careful appropriate AST, and limitation on improper antibiotic usage are crucial.

Efficacy and safety of Zicuiyin decoction on diabetic kidney disease: A multicenter, randomized controlled trial.

BACKGROUD: Zicuiyin (ZCY) decoction created by Xichun Zhang in the Qing dynasty has been used on diabetes mellitus and complications for more than two centuries in China. Huangkui capsule (HKC) is a listed Chinese patent medicine to treat diabetic kidney disease (DKD). To determine whether ZCY is non-inferior to HKC in the treatment of DKD, a multicenter, parallel-control, open-label, randomized clinical trial was conducted. METHODS: In this clinical trial, 88 DKD patients were recruited at three centers in Tianjin from January 2018 to December 2019. They were randomized to receive HKC (2.5 g, TID) or ZCY (crude drug amount 75 g, 150 ml, BID) for eight weeks based on routine treatment. The primary outcome was the change of estimated glomerular filtration rate (eGFR). The secondary outcomes included change of serum creatinine (SCr), urinary albumin excretion rate, 24 h urinary protein, urinary albumin-creatinine ratio, glycosylated hemoglobin A1c, symptom scores, and microbiota compositions profiles. RESULTS: The change of eGFR in HKC and ZCY groups were -7.08 ± 24.65 and 2.57 ± 18.49 ml/min/1.73 m2, respectively (p < 0.05). The 95% lower confidence limit for the difference between the estimated means was 1.93 ml/min/1.73 m2, establishing the superiority of ZCY. Compared to HKC, ZCY could significantly decrease SCr and symptom scores (p < 0.05). There were no significant differences in other outcomes between the two groups (p > 0.05). ZCY ameliorated gut microbiota dysbiosis, including increased Prevotellaceae and Lactobacillaceae and decreased Enterobacteriales, Clostridiaceae and Micrococcaceae. No severe adverse events were reported in any group. CONCLUSIONS: ZCY had better efficacy in improving and protecting kidney function. It would be an alternative option to treat DKD, especially those who decline eGFR and gut microbiota dysbiosis. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-OON-17012076. Registered July 21, 2017.

Edaravone Improves Intermittent Hypoxia-Induced Cognitive Impairment and Hippocampal Damage in Rats.

Oxidative stress plays an essential role in obstructive sleep apnea-hypopnea syndrome-induced cognitive dysfunction in children. This study investigated the effects of edaravone, a potent free radical scavenger, on intermittent hypoxia (IH)-induced oxidative damage and cognition impairment in a young rat model of IH. IH rats were treated with edaravone for 4 weeks. Behavioral testing was performed using the Morris water maze, and hippocampal tissues were harvested for further analyses. Edaravone attenuated IH-induced cognitive impairment, reduced morphological and structural abnormalities, and increased the number of mitochondria in the IH rats. Furthermore, edaravone significantly increased the inhibition of hydroxyl free radicals; reduced expressions of superoxide anion, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine; and upregulated the expression of manganese superoxide dismutase, catalase, cAMP, protein kinase A, phosphorylated-cAMP response element-binding (p-CREB), B-cell lymphoma 2, and brain-derived neurotrophic factor in the hippocampal tissue of IH rats. Our findings suggest that edaravone attenuated IH-induced cognitive impairment and hippocampal damage by upregulating p-CREB in young rats.

Clinical and Th1/Th2 immune response features of hospitalized children with human rhinovirus infection.

This study aimed to assess the clinical characteristics and T-helper 1 (Th1)/Th2 profile of human rhinovirus (HRV) infection in children with bronchiolitis and pneumonia, compared with the respiratory syncytial virus (RSV). In September 2013 to August 2014, 335 nasopharyngeal aspirates from children below 14 with bronchiolitis and pneumonia were screened for HRV and 13 other respiratory viruses by PCR or reverse transcription PCR. Interferon (IFN)-γ, interleukin (IL)-2, IL-4, IL-6, IL-10, and tumor necrosis factor (TNF)-α were detected by multiplex enzyme-linked immunosorbent assay. HRVs were found in 66 cases (19.7%), including 35 bronchiolitis and 31 pneumonia cases. Compared with the RSV alone group, children with pneumonia had more frequent wheezing episodes in HRV (Pa = .001) and HRV + non-RSV (Pb = .002) groups, and fever in the HRV (Pf = .004) and HRV + RSV (Pg = .005) groups. Among patients with bronchiolitis, cases with HRV alone were more likely to present in winter than those with RSV alone (Pi = .010) and HRV + non-RSV (Pj = .014), and less numerous in summer compared with HRV + non-RSV (Ph = .005). Children with HRV alone were more susceptible to have a history of eczema than RSV alone among bronchiolitis (Pc < .001) and pneumonia (Pe = .033) cases. HRV bronchiolitis cases had increased IL-4/IFN-γ and decreased TNF-α/IL-10 ratios, compared with HRV pneumonia counterparts. HRV is a major non-RSV pathogen causing hospitalization in children with bronchiolitis and pneumonia and induces an imbalanced Th1/Th2 response in bronchiolitis. Compared with RSV infection, HRV bronchiolitis and pneumonia differ significantly regarding wheezing episodes, susceptibility to eczema, fever occurrence, and seasonal prevalence.

Anti-H7N9 avian influenza A virus activity of interferon in pseudostratified human airway epithelium cell cultures.

BACKGROUND: Since H7N9 influenza A virus (H7N9) was first reported in 2013, five waves of outbreaks have occurred, posing a huge threat to human health. In preparation for a potential H7N9 epidemic, it is essential to evaluate the efficacy of anti-H7N9 drugs with an appropriate model. METHODS: Well-differentiated pseudostratified human airway epithelium (HAE) cells were grown at the air-liquid interface, and the H7N9 cell tropism and cytopathic effect were detected by immunostaining and hematoxylin-eosin (HE) staining. The H7N9 replication kinetics and anti-H7N9 effect of recombinant human α2b (rhIFN-α2b) and rhIFN-λ1 were compared with different cell lines. The H7N9 viral load and interferon-stimulated gene (ISG) expression were quantified by real-time PCR assays. RESULTS: H7N9 could infect both ciliated and non-ciliated cells within the three-dimensional (3D) HAE cell culture, which reduced the number of cilia and damaged the airways. The H7N9 replication kinetics differed between traditional cells and 3D HAE cells. Interferon had antiviral activity against H7N9 and alleviated epithelial cell lesions; the antiviral activity of rhIFN-α2b was slightly better than that of rhIFN-λ1. In normal cells, rhIFN-α2b induced a greater amount of ISG expression (MX1, OAS1, IFITM3, and ISG15) compared with rhIFN-λ1, but in 3D HAE cells, this trend was reversed. CONCLUSIONS: Both rhIFN-α2b and rhIFN-λ1 had antiviral activity against H7N9, and this protection was related to the induction of ISGs. The 3D cell culture model is suitable for evaluating interferon antiviral activity because it can demonstrate realistic in vivo-like effects.

The suppression of innate immune response by human rhinovirus C.

Rhinovirus C (RV-C), a newly identified group of human rhinoviruses (RVs), is associated with exacerbation of severe asthma. The type I interferon (IFN) response induced by this virus and the mechanisms of evasion of IFN-mediated innate immunity for RV-C remain unclear. In this study, we constructed a full-length cDNA clone of RV-C (LZ651) from a clinical sample. IFN-ß mRNA and protein levels were not elevated in differentiated Human bronchial epithelial (HBE) cells at the air-liquid interface infected with RV-C, except in the early stage of infection. The ability to attenuate IFN-ß activation was ascribed to 3Cpro of RV-C, and the 40-His site of 3Cpro played an important role. Furthermore, RIG-I was degraded by 3Cpro in a caspase-dependent manner and 3Cpro cleaved MAVS at 148 Q/A, which inhibited IFN signaling. Taken together, our results demonstrate the mechanism by which RV-C circumvents the production of type I IFN in infected cells.

Enterovirus 71 suppresses interferon responses by blocking Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling through inducing karyopherin-α1 degradation.

Enterovirus 71 (EV71) has emerged as one of the most important enteroviruses since the eradication of poliovirus, and it causes severe neurological symptoms for which no effective antiviral drugs are available. Type I interferons (IFN) α/ß have been used clinically as antiviral therapy as the first line of defense against virus infections successfully for decades. However, treatment with type I interferons has not been effective in patients with EV71 infection. In this study, we found that in cells pretreated with IFN-ß, EV71 infection could still lead to a cytopathic effect, and the viral replication was not affected. The mechanism by which EV71 antagonizes interferon signaling, however, has been controversial. Our study indicated that EV71 infection did not inhibit phosphorylation of STAT1/2 induced by IFN-ß stimulation, but p-STAT1/2 transport into the nucleus was significantly blocked. We showed that EV71 infection reduced the formation of STAT/karyopherin-α1 (KPNA1) complex upon interferon stimulation and that the virus down-regulated the expression of KPNA1, a nuclear localization signal receptor for p-STAT1. Using specific caspase inhibitors and siRNA for caspase-3, we demonstrated that EV71 infection induced degradation of cellular KPNA1 in a caspase-3-dependent manner, which led to decreased induction of interferon-inducible genes and IFN response. Viral 2A and 3C proteases did not degrade KPNA1, inhibit the activity of ISRE or suppress the transcription of interferon-inducible genes induced by IFN-ß. Our study demonstrates a novel mechanism by which antiviral signaling is suppressed through degradation of KPNA1 by activated caspase-3 induced in an enteroviral infection.

Differential Regulation of TLR Signaling on the Induction of Antiviral Interferons in Human Intestinal Epithelial Cells Infected with Enterovirus 71.

Enterovirus 71 (EV71) causes hand-foot-and-mouth disease, which can lead to fatal neurological complications in young children and infants. Few gastrointestinal symptoms are observed clinically, suggesting the presence of a unique immunity to EV71 in the gut. We reported a robust induction of interferons (IFNs) in human intestinal epithelial cells (HT-29), which was suppressed in other types such as RD and HeLa cells. The underlying mechanism for the apparent difference remains obscure. In this study we report that in EV71-infected HT-29 cells, TLR/TRIF signaling was essential to IFN induction; viral replication increased and the induction of IFN-α, -ß, -ω, -κ, and -ε decreased markedly in TRIF-silenced HT-29 cells. Importantly, TRIF was degraded by viral 3Cpro in RD cells, but resisted cleavage, and IRF3 was activated and translocated into the nucleus in HT-29 cells. Taken together, our data suggest that IFNs were induced differentially in human HT-29 cells through an intact TLR/TRIF signaling, which differs from other cell types and may be implicated in viral pathogenesis in EV71 infection.

Prevalence of adenovirus in children with acute respiratory tract infection in Lanzhou, China.

BACKGROUND: Human adenovirus (HAdV) is an important agent causing respiratory tract infection in children. Information on the epidemiological and clinical features of HAdV is limited in children with acute respiratory tract infections (ARTIs) in China, especially those of a novel genotype, Ad55. METHODS: In total, 1169 nasopharyngeal aspirates were collected from children younger than 14 years with ARTIs between November 2006 and November 2009. The polymerase chain reaction (PCR) was used to screen HAdVs. All PCR-positive products were sequenced. RESULTS: 74 of 1169 (6.33%) specimens were positive for HAdVs. Among positive cases, AdV3 (58/74) was detected most frequently, followed by AdV11 (10/74), AdV2 (2/74), AdV7 (2/69), AdV6 (1/74), and AdV1 (1/74). AdV55 was found in one case. The incidence of HAdV infection peaked in children aged 3-7 years. The most common clinical diagnosis was upper respiratory infection, and the most common syndrome was fever and cough.The comparison of HAdV and RSV group revealed that Children infected with group AdV were significant older than children infected with group RSV, had more fever but less frequently wheezing, and cough, crackles, and cyanosis, The duration of hospitalization between the AdV group and RSV group was not significant, but a greater frequency of LRTIs was observed in RSV group. CONCLUSIONS: HAdV is an important viral agent in children with ARTIs in Lanzhou City, China. Multiple HAdV serotypes co-circulated with Ad3, which was predominant in this 3-year study. The novel AdV55 genotype was found in one case. No fixed seasonal rhythm could be identified.

Effectiveness of biatrial pacing in reducing early postoperative atrial fibrillation after the maze procedure.

OBJECTIVES: Interatrial conduction abnormalities have an important role in the initiation of recurrent atrial fibrillation (AF) after the maze procedure. Biatrial pacing or single atrial pacing alters the site and timing of atrial depolarization and may improve restoration of sinus rhythm after the maze procedure. To further evaluate whether biatrial pacing is superior to single atrial or no pacing, we performed a randomized prospective study on 240 patients with a full maze procedure to compare the effectiveness with different pacing approaches in the postoperative period. METHODS: Between 2002 and 2010, 240 patients undergoing mitral ± tricuspid valve surgery concomitant with the maze procedure were randomized into three equal groups: Group I using overdrive biatrial pacing, Group II utilizing single atrial pacing and Group III without pacing. The atria were paced continuously in Atrium paced, Atrium sensed, and pacemaker Inhibited in response to sensed beat (AAI) mode at a rate of 80 pulses per minute or 10 pulses above the underlying rate for 5 days. The endpoints were the onset of AF or discharge. RESULTS: The incidence of recurrent postoperative atrial fibrillation was significantly less in Group I with 9 of 80 patients (11%) incurring atrial fibrillation compared with 23 of 80 patients (28%) in Group II (P < 0.01) and 29 of 80 patients in Group III (P < 0.01). The length of hospital stay and the mean costs of hospital stay were significantly lower in the biatrial pacing group (P < 0.05). CONCLUSIONS: Biatrial overdrive pacing is well tolerated and more effective in preventing the early recurrence of atrial fibrillation after the maze procedure. The impacts of the long-term results with the maze procedure require further study.

Comprehensive surgical approach to treat atrial fibrillation in patients with variant pulmonary venous anatomy.

OBJECTIVES: Catheter radiofrequency ablation procedures yield fairly successful results for the treatment of atrial fibrillation; however, patients with anatomic variant pulmonary veins (PV) are generally thought not to benefit from catheter ablation technique, with recurrence rates observed as high as 78%. We report a comprehensive surgical approach to treat this subset of patients with a modified full maze procedure. METHODS: From January 2002 to December 2009, 72 patients undergoing cardiac surgery who had drug-refractory and/or recurrent AF after catheter ablation were identified. PV variance was observed on preoperative multislice chest computed tomography. All patients underwent multiple PV epicardial circumferential isolation and epicardial-endocardial longitudinal PV ablations along with standard maze as an adjunct to the cardiac surgical procedure. Patients were followed up at 6 months, 1 year, and 2 years postoperatively. RESULTS: Typical patterns of PV variation were observed in 72 patients. Left common PV trunk was found in 49 patients (68%), with a mean length of 21 ± 4.6 mm, diameter of 28.6 ± 4.9 mm, and wall thickness of 2.1 ± 1.7 mm. Right PV variants, including right middle and right top PVs, were found in 23 patients (32%), with a length of 20 ± 2.1 mm, diameter of 9.9 ± 3.4 mm, and wall thickness of 1.9 ± 1.7 mm. Overall restoration of sinus rhythm was confirmed in 64 patients (94%) at 1-year follow-up. Twelve patients were defibrillated into sinus rhythm within 90 days after the operation. CONCLUSIONS: A modified full maze procedure should be considered as a first choice treatment for atrial fibrillation with variant drainage of PVs because of the nature of PV size, wall thickness, and specific foci in the arrhythmogenic veins. Multiple PV isolation and epicardial-endocardial longitudinal PV ablations along with the standard maze are essential to success. Early referral for surgical ablation allows higher success rates.

[The detection and clinical feature of HcoV-nL63 in children with acute respiratory tract infection in Lanzhou city].

OBJECTIVE: To investigate the prevalence and clinical characterization of HCoV-NL63 (NL63) in children with acute respiratory tract infections (ARTIs) in Lanzhou with other respiratory viruses. The prevalence of HBoV1 in ALRTI was obviously city,China. METHOD: From November 2006 to October 2009,1169 nasopharyngeal aspirates (NPA) were collected from children under 14 years old with ARTIs. Samples were screened for NL63 using a reverse transcription-polymerase chain reaction (RT-PCR) and sequencing. Demography and clinical information were recorded. RESULT: NL63 was detected in 35 (2.99%) of the 1169 children. The peak of the positive rate were in August, September 2007, July, August 2008 (23.53%,17.65%, 50%, 33.33% separately). There are no NL63 positive samples was detected in December, 2007 to February 2009. 25 (25/35, 71.43%) were co-infected with other respiratory viruses, and human rhinovirus (HRV) were the most common additional respiratory virus. No significant differences of infective rate of NL63 was found between < or = 3 years age group and > 3 years age group. Bronchiolitis and pneumonia were the most frequent diagnoses in NL63 positive patients and the major symptoms were fever and cough in our study. Between the monoinfection group and the coinfection group of NL63-positive patients, no differences were found in symptoms and clinical diagnoses except symptoms of gastrointestinal. CONCLUSION: HCoV-NL63 is an important pathogen of acute respiratory tract infection in children in Lanzhou city. The peak of HCoV-NL63 infections was in summer. There were annual differences in the prevalence of HCoV-NL63. HCoV-NL63 infections existed a high rate of mixed infection, and mixed infection does not increase the severity of the disease.

[Molecular epidemiological and clinical features of coronavirus HKU1 in children with acute respiratory tract infection in Lanzhou].

OBJECTIVE: Human coronavirus (CoV)-HKU1 (HCoV-HKU1) was first isolated by Woo et al in Hong Kong. Several successive reports confirmed retrospectively that this new human coronavirus was circulating in different countries worldwide. However, the impact and the role of the emerging HCoV-HKU1 were not defined in children with ARTI. The objective of this study was to investigate the molecular epidemiology and clinical characteristics of HCoV-HKU1 infection in children with ARTI in Lanzhou, China. METHOD: Nasopharyngeal aspiration (NPA) samples were collected from 301 children with ARTI at the First Hospital of Lanzhou University, Gansu Province, China, between November 2007 and October 2008. Demographic data and clinical findings of these children were collected at the same time. The informed consent was obtained from their parents. This study protocol was approved by the hospital ethics committee. The reverse transcription polymerase chain reaction (RT-PCR) was employed to screen HCoV-HKU1. Furthermore, other common respiratory viruses were screened in HCoV-HKU1 positive samples. All PCR positive products were sequenced, and phylogenetic analysis was conducted. RESULT: The overall frequency of HCoV-HKU1 infection was 5.0% (15/301). The HCoV-HKU1 pol gene sequences shared a 95.8% - 99.6% nucleotide identity with the human coronavirus-HKU1 strain, whereas the amino acid identity was 90.7% - 99.3%. The phylogenetic analysis revealed that the HCoV-HKU1 strain pol gene clustered with the HCoV-HKU1 strain N15 genotype B (no. DQ415911); 11 of 15 HCoV-HKU1 positive sample tested were mixed-infection. HCoV-HKU1 was detected only from November to April. Positive specimens peaked in November. Children with HCoV-HKU1 infection varied in age from 15 day to 12-years (median age, 10 months). The clinical diagnoses of HCoV-HKU1 positive patients included those with AURI and LURI. The clinical presentations of HCoV-HKU1 positive children included fever, cough, sputum production, diarrhea, vomiting; pharynx engorgement, crackles, and wheezing. The mean hospital stay of the 14 patients was 9.9 days. Six of 15 HCoV-HKU1 positive patients had an underlying illness, and they were all inpatients (hospital stay, mean, 11.2 days). There was no statistically significant difference in the detection rate between the two groups with and without underlying illnesses. CONCLUSION: Human CoV-HKU1 infection exists in children with respiratory tract infections in Lanzhou region. A single HCoV-HKU1 genotype B was circulating locally. The symptoms and clinical diagnoses of those infected with HCoV-HKU1 had no specificity as compared with patients with other common respiratory viruses infection.

Human respiratory syncytial virus in children with acute respiratory tract infections in China.

There are limited data on the prevalence and clinical and molecular characterization of human respiratory syncytial virus (HRSV) in children with acute respiratory tract infections (ARTIs) in China. From December 2006 to March 2009, 894 nasopharyngeal aspirates (NPAs) were collected from children under 14 years of age with ARTIs. Samples were screened for HRSV and genotyped by reverse transcription-PCR (RT-PCR) and sequencing. Demographic and clinical information was recorded. A total of 38.14% (341/894) of samples were positive for HRSV. Phylogenetic analysis revealed that 60.4% of the selected 227 RSV strains were GA2, 34.4% were BA, 4.8% were GB2, and 0.4% were GB3. A total of 40.47% of all of the RSV-positive samples were coinfected with other respiratory viruses, and adenovirus was the most common additional respiratory virus. No statistical differences were found in the frequency of diagnosis and symptoms between the coinfection group and monoinfection group. Additionally, no statistical differences were found in epidemiological characterizations or disease severity between genotype BA- and GA2-positive patients, except for a greater frequency of lower respiratory tract infections (LRTIs) (mostly bronchitis)with BA. HRSV is the most important viral pathogen in Chinese children with ARTIs. Four genotypes (i.e., GA2, BA, GB2, and GB3) circulate locally, and the predominant genotype may shift between seasons. Coinfection with other viruses does not affect disease severity. HRSV genotypes were not associated with different epidemiological characterizations or disease severity.

Prevalence and clinical characteristics of human CoV-HKU1 in children with acute respiratory tract infections in China.

BACKGROUND: Human CoV-HKU1 (HCoV-HKU1) has been isolated from a 71-year-old man with pneumonia; however, the impact and role of emerging HCoV-HKU1 have not been defined in children with acute respiratory tract infection (ARTI). OBJECTIVE: To investigate the Prevalence and clinical characteristics of HCoV-HKU1 in children with ARTI in Lanzhou, China. STUDY DESIGN: The reverse transcription polymerase chain reaction (RT-PCR) or PCR was employed to screen HCoV-HKU1 and other common respiratory viruses in 645 nasopharyngeal aspirate (NPA) specimens collected from children with ARTI from November 2006 to October 2008. All PCR positive products were sequenced. And the demographic and clinical data were collected for all patients. RESULTS: Nineteen of 645 (2.95%) specimens tested positive for HCoV-HKU1, and all HCoV-HKU1 positive specimens were distributed in the winter and spring season. The HCoV-HKU1 co-infection rate with other respiratory viruses was 47.37% (9/19). There was no statistically significant difference in the detection rate between groups by age or gender, except between patients with and without underlying diseases. The phylogenetic analysis indicated that HCoV-HKU1 genotype B was circulating in the years 2007 and 2008 in children with ARTI in Lanzhou, China. CONCLUSIONS: HCoV-HKU1 is an uncommon virus existing among Chinese children with ARTI. Children with underlying diseases are more vulnerable to viral infection. Only HCoV-HKU1 genotype B circulated locally.

Prevalence and clinical and molecular characterization of human metapneumovirus in children with acute respiratory infection in China.

BACKGROUND: Human metapneumovirus (HMPV), a newly discovered paramyxovirus, has been associated with acute respiratory tract infections (ARTIs). However, the prevalence and molecular characteristics of HMPV in China are still unclear. METHODS: A total of 661 nasopharyngeal aspirates (NPA) specimens were collected from 661 children with ARTIs between December 2006 and November 2008. Specimens were screened for HMPV by reverse transcription-polymerase reaction. All positive amplification products were confirmed by sequencing. RESULTS: HMPV was detected in 45 patients (6.80%) of the 661 children. The HMPV-infected patients were from 29 days to 9 years of age. A high incidence of HMPV infection (84.4%) was observed during the winter-spring season. Of the 45 HMPV-positive patients, 25 (55.6%) were co-infected with other respiratory viruses, and respiratory syncytial virus (RSV) was the most common additional respiratory virus. The most common clinical diagnosis was bronchopneumonia (57.8%) and cough (88.9%) was the most common clinical symptom. Phylogenetic analysis of the F gene revealed that 80% of the HMPV detected were A2, 2.2% were A1, and 17.8% were B1. Statistical analyses showed that sex, ages, seasons, and severity of the disease did not correlate with HMPV genotype (P = 0.986, 0.347, 0.660, 0.252), but viral coinfection with HMPV increased hospitalization rates (P = 0.005). CONCLUSIONS: HMPV was frequently detected in the pediatric patients with ARTI in China. RSV was the most common coinfection virus and coinfection increased hospitalization rates. All HMPV subgroups except B2 cocirculated and there was no association found between HMPV genotypes and severity of disease.

Human bocavirus infection in young children with acute respiratory tract infection in Lanzhou, China.

Human bocavirus (HBoV) is a recognized human parvovirus associated with acute respiratory tract infection. However, HBoV has yet to be established as a causative agent of respiratory disease. In this study, the epidemiological and virological characteristics of HBoV infection were studied in children with acute respiratory tract infection in China. In total, 406 children younger than 14 years of age with acute respiratory tract infection were included in this prospective 1-year study. HBoV was detected in 29 (7.1%) of the 406 children. No clear seasonal fluctuation was observed in infection rates of HBoV. Of the 29 children infected with HBoV, 16 (55.2%) were coinfected with other respiratory viruses, most commonly respiratory syncytial virus (RSV). Viral coinfection with HBoV did not affect the severity of the respiratory disease (P = 0.291). The number of HBoV genome copies ranged from 5.80 x 10(2) to 9.72 x 10(8) copies/ml in nasopharyngeal aspirates among HBoV-positive specimens by real-time PCR, and neither coinfection nor the severity of disease correlated with the viral load (P = 0.148, P = 0.354, respectively). The most common clinical features were cough and acute upper respiratory infection, and acute bronchopneumonia. Additionally, the NP-1 gene of HBoV showed minimal sequence variation. These data suggest that HBoV is frequent in young children with acute respiratory tract infection in Lanzhou, China, and RSV is the most common coinfecting virus. There was no apparent association between the viral load of HBoV and coinfection or disease severity. The NP-1 gene was highly conserved in HBoV.

Prevalence and clinical characterization of a newly identified human rhinovirus C species in children with acute respiratory tract infections.

Human rhinovirus C (HRV-C) is a newly identified genotype of HRV found in patients with respiratory tract infections (RTIs); however, its epidemiological profile and clinical characteristics are not well understood. In this study, Chinese children with RTIs were screened for HRV-C and their epidemiological and clinical characteristics were analyzed. From December 2006 to November 2007, 406 nasopharyngeal aspirates from children younger than 14 years of age with RTIs were screened for HRV and other common respiratory viruses by PCR or reverse transcription-PCR. Two-hundred twenty-four (55.2%) of the specimens were infected with at least one virus, including 53 patients with HRV (13%). HRV-A, HRV-B, and HRV-C were detected in 22, 12, and 19 specimens, respectively. HRV-C was detected mainly from December 2006 to April 2007 and from October to November 2007, with peaks in December and April (10/19). Acute upper respiratory infection and bronchopneumonia were observed in 53 and 37% of the cases, respectively. The most common symptoms were cough (82%), runny nose (53%), and fever (37%). Wheezing and bronchiolitis were less common in patients infected with HRV-C than in those infected with respiratory syncytial virus (RSV). Partial sequencing of the genes coding for VP4 and VP2 revealed that the HRV-C strains were 56 to 62% identical at the amino acid level to HRV-B and HRV-A reference strains and 80 to 99% identical to HRV-C reference strains. In conclusion, HRV-C is an important cause of RTIs in children, and highly diversified strains of HRV-C are prevalent in China. HRV-C may produce different epidemiological features, and patients infected with HRV-C may exhibit different clinical features from patients infected with RSV or HRV-A/B.