The Prognostic Value and the Oncogenic and Immunological Roles of Vacuolar Protein Sorting Associated Protein 26 A in Pancreatic Adenocarcinoma.

The identification of the prognostic markers and therapeutic targets might benefit the diagnosis and treatment of pancreatic adenocarcinoma (PAAD), one of the most aggressive malignancies. Vacuolar protein sorting associated protein 26 A (VPS26A) is a candidate prognosis gene for hepatocellular carcinoma, but its expression and function in PAAD remain unknown. The mRNA and protein expression of VPS26A in PAAD was explored and validated by bioinformatics and immunohistochemical analysis. The correlation between VPS26A expression and various clinical parameters, genetic status, diagnostic and prognostic value, survival and immune infiltration were evaluated, and the co-expressed gene-set enrichment analysis for VPS26A was performed. Cytologic and molecular experiments were further carried out to investigate the role and potential mechanism of VPS26A in PAAD. The mRNA and protein levels of VPS26A were elevated in PAAD tissues. High VPS26A expression was associated with the advanced histological type, tumor stage simplified, smoking status and tumor mutational burden score, and the poor prognosis of PAAD patients. VPS26A expression was significantly correlated with immune infiltration and immunotherapy response. VPS26A-co-expressed genes were mainly enriched in the regulation of cell adhesion and actin cytoskeleton and the immune-response-regulating signaling pathway. Our experiments further demonstrated that VPS26A promoted the proliferation, migration and invasion potentials of PAAD cell lines through activating the EGFR/ERK signaling. Our study suggested that VPS26A could be a potential biomarker and a therapeutic target for PAAD through comprehensive regulation of its growth, migration and immune microenvironment.

Establishment and evaluation of a quadruple quantitative real-time PCR assay for simultaneous detection of human coronavirus subtypes.

BACKGROUND: The newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and four seasonal human coronaviruses (HCoVs) (HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1) still circulate worldwide. The early clinical symptoms of SARS-CoV-2 and seasonal HCoV infections are similar, so rapid and accurate identification of the subtypes of HCoVs is crucial for early diagnosis, early treatment, prevention and control of these infections. However, current multiplex molecular diagnostic techniques for HCoV subtypes including SARS-CoV-2 are limited. METHODS: We designed primers and probes specific for the S and N genes of SARS-CoV-2, the N gene of severe acute respiratory syndrome coronavirus (SARS-CoV), and the ORF1ab gene of four seasonal HCoVs, as well as the human B2M gene product. We developed and optimized a quadruple quantitative real-time PCR assay (qq-PCR) for simultaneous detection of SARS-CoV-2, SARS-CoV and four seasonal HCoVs. This assay was further tested for specificity and sensitivity, and validated using 184 clinical samples. RESULTS: The limit of detection of the qq-PCR assay was in the range 2.5 × 101 to 6.5 × 101 copies/µL for each gene and no cross-reactivity with other common respiratory viruses was observed. The intra-assay and inter-assay coefficients of variation were 0.5-2%. The qq-PCR assay had a 91.9% sensitivity and 100.0% specificity for SARS-CoV-2 and a 95.7% sensitivity and 100% specificity for seasonal HCoVs, using the approved commercial kits as the reference. Compared to the commercial kits, total detection consistency was 98.4% (181/184) for SARS-CoV-2 and 98.6% (142/144) for seasonal HCoVs. CONCLUSION: With the advantages of sensitivity, specificity, rapid detection, cost-effectiveness, and convenience, this qq-PCR assay has potential for clinical use for rapid discrimination between SARS-CoV-2, SARS-CoV and seasonal HCoVs.

Recent advances on synthesis and biological activities of C-17 aza-heterocycle derived steroids.

Steroids modification for improving their biological activities is one of the most efficient and fruitful methods to develop novel medicines. Steroids with aza-heterocycles attaching to the C-17 owing various biological activities have received great attentions and some of the compounds are developed successfully as drugs. In this review, the research of the syntheses and biological activities of steroids bearing various aza-heterocycles published in the last 8 years is assembled, and some important structure-activity relationships (SARs) of active compounds are presented. According to the analysis of the literatures and our experiences in this field, the potential of aza-heterocyclic steroids as medicinal drugs is proposed.

Age and sex specific reference intervals of 13 hematological analytes in Chinese children and adolescents aged from 28 days up to 20 years: the PRINCE study.

OBJECTIVES: Pediatric Reference Intervals in China (PRINCE) is a nationwide initiative that aims to establish and validate harmonized reference intervals (RIs) for Chinese children and adolescents, in which 15,150 healthy volunteers aged up to 20 years were recruited from 11 centers to establish RIs and 7,557 children and adolescents were enrolled from 21 centers to validate RIs. METHODS: The complete blood cell counts (CBC) of venous whole blood were measured by hematology analyzers through Sysmex systems in different centers. Age- and sex-specific RIs were calculated according to the guidelines. RESULTS: Unlike adults with certain levels of analyte concentrations, hematological parameters of children changed through growth and development. Red blood cell counts, hemoglobin, and hematocrit increased with age, and revealed higher concentrations in boys than girls after puberty. White blood cell counts and platelet counts showed significant higher levels than adults before 2 years of age, and then gradually decreased without distinct sex differences. In addition, lymphocyte counts decreased with age while neutrophil counts showed an opposite trend. The lower and upper limits of pediatric RIs of CBC were different from those of adults. CONCLUSIONS: The validation of RIs indicated that the PRINCE study provided a version of RIs suitable for most of regions in China. This first harmonized pediatric RIs of CBC across China provided a robust database to understand the dynamic changes of hematologic parameters from birth to adolescence, and will contribute to clinical diagnosis and prognosis evaluation for pediatric patients as well.

Reference intervals of 14 biochemical markers for children and adolescence in China: the PRINCE study.

OBJECTIVES: The Pediatric Reference Intervals in China (PRINCE) was initiated to establish the reference intervals (RIs) of Chinese children, as well as to make it possible to compare the variability of biochemical markers among countries internationally. METHODS: Healthy participants, aged up to 20 years, from 11 provinces across China, were enrolled in PRINCE and according to a standard screening procedure, that included a questionnaire survey, physical examinations and laboratory tests. Fasting venous blood specimens were collected. All serum specimens were analyzed with Cobas C702 in the center laboratory, i.e. clinical laboratory of Beijing Children's Hospital, with certified qualification (ISO15189). The nonparametric method recommended by Clinical Laboratory Standards Institute guidelines, was used to calculate the age- and sex-specified RIs. RESULTS: Among the 15,150 participants enrolled, 12,352 children (6,093 males and 6,259 females) were included to calculate RIs. The RIs for total protein, albumin, globulin, calcium, phosphate, potassium, sodium, chlorine, alkaline phosphatase, γ-glutamyl transpeptadase, alanine aminotransferase, aspartate aminotransferase, creatinine and urea were established by age- or sex-partitions. Most biochemical markers displayed larger variability and higher dispersion during the periods between 28 days and 1 year old, and included 4-6 age partitions commonly during 1 to <20 years old. In addition, differences of RIs between sexes usually occurs around the initiation of puberty at 12-13 years old. CONCLUSIONS: The age- and sex-specified RIs of 14 biochemical markers in PRINCE study can provide a solid reference, which will be transferred into relevant RIs for other clinical laboratory's platforms according to the CLSI guidelines.

The role of SLITRK6 in the pathogenesis of Tourette syndrome: From the conclusion of a family-based study in the Chinese Han population.

BACKGROUND: Tourette syndrome (TS) is a complex neuropsychiatric disorder coupled with obvious genetic heterogeneity. Studies in recent years have confirmed the association of SLITRK genes with sensory and neuropsychiatric diseases. To detect whether SLITRK6 is involved in the progress of TS, a family-based association study was performed to explore the possible genetic association between SLITRK6 and TS in the Chinese Han population. METHODS: We genotyped 399 TS nuclear families trios, and then analyzed three tag SLITRK6 single nucleotide polymorphisms using the transmission disequilibrium test (TDT) haplotype relative risk (HRR) and haplotype-based haplotype relative risk (HHRR) methods. RESULTS: The TDT showed no statistically significant allele transfer for the three polymorphisms. The HRR and HHRR also showed a negative association. CONCLUSIONS: Despite the results suggesting that these polymorphisms may not be associated with susceptibility to TS in the Chinese Han population, we are still unable to determine the potential role of SLITRK6 in the pathogenesis of TS. Furthermore, the results still need to be confirmed in a larger sample size and in different populations.

Development and evaluation of a panel of multiplex one-tube nested real time PCR assay for simultaneous detection of 14 respiratory viruses in five reactions.

Multiplex real-time quantitative polymerase chain reaction (mRT-qPCR) assay is commonly used to detect respiratory viruses, however, the sensitivity is limited for most reports. A panel of locked nucleic acid based multiplex closed one-tube nested real-time PCR (mOTNRT-PCR) assay consisting of five separate internally controlled RT-qPCR assays was developed for detection of 14 respiratory viruses. The sensitivity and reproducibility of mOTNRT-PCR panel were evaluated using plasmid standards and the specificity was evaluated using clinical samples. The clinical performance of mOTNRT-PCR panel was further evaluated with 468 samples collected from patients with an acute respiratory infection and compared with individual real-time PCR (RT-qPCR) assay. The analytical sensitivities of mOTNRT-PCR panel ranged from 2 to 20 copies/reaction, and no cross-reaction with common respiratory viruses was observed. The coefficients of variation of intra-assay and inter-assay were between 0.35% and 8.29%. Totally 35 clinical samples detected by mOTNRT-PCR assay panel were missed by RT-qPCR and confirmed true positive by sequencing of nested PCR products. The mOTNRT-PCR assay panel provides a more sensitive and high-throughput method for the detection of 14 respiratory viruses.

Comparing the yield of oropharyngeal swabs and sputum for detection of 11 common pathogens in hospitalized children with lower respiratory tract infection.

BACKGROUND: Advances in molecular laboratory techniques are changing the prospects for the diagnosis of viral infectious diseases. Multiplex polymerase chain reaction assay (multiplex-PCR) can detect dozens of pathogens simultaneously, greatly reducing turnaround time (TAT) and improving detection sensitivity. But as a double-edged sword, due to the high sensitivity of PCR, the type of respiratory specimens is critical to diagnosis. In this work, we performed a head-to-head comparison to evaluate the multiplex-PCR yields between two samples, sputum and flocked oropharyngeal swabs (OPS). METHODS: Eleven common respiratory pathogens were tested in hospitalized children< 13 years of age who met the criteria for lower respiratory tract infection by GeXP-based multiplex-PCR of paired OPS and sputum. RESULTS: From January to June 2018, 440 children with paired OPS and sputum were tested. The positive rate was 84% (369/440) for OPS and 88% (386/440) for sputum (p = .007). The frequency of detection of HRV, RSV, Influenza A virus, HMPV, parainfluenza virus, adenovirus, M. pneumoniae, coronavirus, bocavirus and C. pneumoniae in sputa was higher than that of OPSs (all p < .001). Both types of specimens had similarly very good kappa values for most of pathogens, except for Mycoplasma pneumonia (κ = 0.61) and Chlamydia pneumoniae (κ = 0.24). Additionally, 79.3% (349/440) of cases showed consistent results between the two types of samples, and they were significantly younger than patients with inconsistent results (p = .002). CONCLUSIONS: Flocked oropharyngeal swabs and sputum performed similarly for the detection of common respiratory pathogens in hospitalized children by multiplex-PCR, except for Mycoplasma pneumoniae and Chlamydia pneumoniae. Young patients are likely to have consistent results between the two specimens.

A case control study on the prevalence of enterovirus in children samples and its association with diarrhea.

Some serotypes of enterovirus (EV) may lead to transient and symptomatic gastrointestinal infections while others are commensal residents of the human gut. To determine whether certain EV types are more often associated with diarrhea, we conducted a preliminary study on the prevalence of EV serotypes and common diarrhea viruses in fecal samples of diarrhea children and healthy controls. EV was tested with one step nest polymerase chain reaction and typed by direct sequencing while common causative diarrhea viruses rotavirus (RV), norovirus (NoV), adenovirus (AdV), bocavirus (HBoV), and astrovirus (AstV) were screened with multiplex PCR assays. Human Rhinovirus (HRV) and human EVs that were present in both groups were further quantified and their odds ratios (OR) were calculated. Enteric pathogens were detected in 89 (32.6%) of 273 children with diarrhea and included human EVs (51, 18.68%), HRV (32, 11.72%), RV (38, 13.92%), AdV (24, 8.79%), NoVGII (16, 8.79%), HBoV (8, 2.93%) and AstV (3, 1.09%). Potential enteric pathogens were found in 25 (6.93%) of 361 healthy controls and included human EV (59, 16.34%), HRV (8, 2.22%), RV (1, 0.28%), NoVGII (5, 1.39%), AstV (2, 0.55%), AdV (16, 4.43%) and HBoV (1, 0.28%). In addition, EV71, echovirus 3,9,14,25 and coxsackievirus A14 existed in healthy controls only, while HRV, echovirus11,18, coxsackievirus A2,4,6 and B2,4 were found in both patients and healthy controls. OR assessment confirmed a strong association of HRV (P < 0.001) and a weak one for echovirus 11 and coxsackievirus A6 with diarrhea (P > 0.05). Our results indicate the diversity of EV serotypes in diarrhea and healthy control groups varies, and the potential etiological role of HRV in diarrhea.

Risk factors of 90-day rehospitalization following discharge of pediatric patients hospitalized with mycoplasma Pneumoniae pneumonia.

BACKGROUND: Among pediatric patients hospitalized for Mycoplasma pneumoniae pneumonia (MPP), the risk factors for 90-day readmission after discharge is undefined. METHODS: We conducted a retrospective observational study of patients <14 years of age who were discharged with a diagnosis of MPP between January 2016 and February 2017. We collected clinical, laboratory and radiographic variables at the time of initial admission. We assessed pneumonia-related readmission within 90-day after discharge. Risk factors independently associated with rehospitalization were identified using multiple logistic regression models. RESULTS: Of the 424 MPP hospitalizations, 48 (11.3%) were readmitted within 90 days and were mainly diagnosed with pneumonia. Patients with younger age or coinfection with influenza A were more likely to be readmitted. In addition, compared with children without readmission, the readmission ones showed different clinical and laboratory characteristics at the index hospital admission. Multiple logistic regression analysis identified age (OR 0.815, 95%CI 0.706-0.940) and body temperature (OR 0.659, 95%CI 0.518-0.839) were significantly associated with lower risk of 90-day readmission. Coinfection with influenza was independently associated with a greater likelihood of 90-day readmission (OR 4.746, 95%CI 1.191-18.913). CONCLUSIONS: Readmission after MPP are common and is related to patients' age, body temperature and influenza A coinfection during initial hospital stay, indicating potential targets could be noticed to reduce the rehospitalization after pediatric MPP.

Impact and clinical profiles of Mycoplasma pneumoniae co-detection in childhood community-acquired pneumonia.

BACKGROUND: Increasing number of hospitalized children with community acquired pneumonia (CAP) is co-detected with Mycoplasma pneumoniae (Mp). The clinical characteristics and impact of Mp co-detected with other bacterial and/or viral pathogens remain poorly understood. The purpose of this study was to evaluate the demographic and clinical features of CAP children with Mp mono-detection and Mp co-detection. METHODS: A total of 4148 hospitalized children with CAP were recruited from January to December 2017 at the Children's Hospital of Hebei Province, affiliated to Hebei Medical University. A variety of respiratory viruses, bacteria and Mp were detected using multiple modalities. The demographic and clinical features of CAP children with Mp mono-detection and Mp co-detection were recorded and analyzed. RESULTS: Among the 110 CAP children with Mp positive, 42 (38.18%) of them were co-detected with at least one other pathogen. Co-detection was more common among children aged ≤3 years. No significant differences were found in most clinical symptoms, complications, underlying conditions and disease severity parameters among various etiological groups, with the following exceptions. First, prolonged duration of fever, lack of appetite and runny nose were more prevalent among CAP children with Mp-virus co-detection. Second, Mp-virus (excluding HRV) co-detected patients were more likely to present with prolonged duration of fever. Third, patients co-detected with Mp-bacteria were more likely to have abnormal blood gases. Additionally, CAP children with Mp-HRV co-detection were significantly more likely to report severe runny nose compared to those with Mp mono-detection. CONCLUSION: Mp co-detection with viral and/or bacterial pathogens is common in clinical practice. However, there are no apparent differences between Mp mono-detection and Mp co-detections in terms of clinical features and disease severity.

A multiplex one-tube nested real time RT-PCR assay for simultaneous detection of respiratory syncytial virus, human rhinovirus and human metapneumovirus.

BACKGROUND: Respiratory syncytial virus (RSV), human Rhinovirus (HRV) and human Metapneumo Virus (HMPV) are important viral pathogens causing acute respiratory tract infections in the hospitalized patients. Sensitive and accurate detection of RSV, HRV and HMPV is necessary for clinical diagnosis and treatment. RESULTS: A locked nucleic acid (LNA)-based multiplex closed one-tube nested real-time RT-PCR (mOTNRT-PCR) assay was developed for simultaneous detection of RSV, HRV and HMPV. The sensitivity, specificity, reproducibility and clinical performance of mOTNRT-PCR were evaluated and compared with individual real time PCR (RT-qPCR) assay using clinical samples. The analytical sensitivity of mOTNRT-PCR assay was 5 copies/reaction for RSV, HRV and HMPV, respectively, and no cross-reaction with other common respiratory viruses was observed. The coefficients of variation (CV) of intra-assay and inter-assay were between 0.51 to 3.67%. Of 398 nasopharyngeal aspirates samples tested, 109 (27.39%), 150 (37.69%) and 44 (11.06%) were positive for RSV, HRV and HMPV, respectively, whereas 95 (23.87%), 137 (34.42%) and 38 (9.55%) were positive for RSV, HRV and HMPV, respectively, by individual RT-qPCR assay. Thirty three samples that were positive by mOTNRT-PCR but negative by RT-qPCR were confirmed as true positives by sequencing using reported traditional two-step nested PCR assay. CONCLUSION: mOTNRT-PCR assay reveals extremely higher sensitivity than that of RT-qPCR assay for detecting RSV, HRV and HMPV in clinical settings.

A triplex quantitative real-time PCR assay for differential detection of human adenovirus serotypes 2, 3 and 7.

BACKGROUND: Human adenovirus (HAdV) serotypes 2, 3 and 7 are more prevalent than other serotypes and have been associated with severe pneumonia in pediatric children. Molecular typing of HAdV is not routinely performed in clinical diagnostic laboratories as it is time-consuming and labor-intensive. METHODS: In the present study, we developed a triplex quantitative real-time PCR assay (tq-PCR) in a single closed tube for differential detection and quantitative analysis of HAdV serotypes 2, 3 and 7. The sensitivity, specificity, reproducibility and clinical performance of tq-PCR were evaluated. RESULTS: The analytical sensitivity of the tq-PCR was 100 copies/reaction for each of HAdV serotypes 2, 3 and 7, and no cross-reaction with other common respiratory viruses or HAdV serotypes 1,4,5,6,31,55 and 57 was observed. The coefficients of variation (CV) of intra-assay and inter-assay were between 0.6% to 3.6%. Of 138 previously-defined HAdV-positive nasopharyngeal aspirates samples tested, the detection agreement between tq-PCR and nested PCR was 96.38% (133/138). CONCLUSION: The proposed tq-PCR assay is a sensitive, specific and reproducible method and has the potential for clinical use in the rapid and differential detection and quantitation of HAdV serotypes 2, 3 and 7.

Adenovirus associated with acute diarrhea: a case-control study.

BACKGROUND: Diarrhea is a major source of morbidity and mortality among young children in low-income and middle-income countries. Human adenoviruses (HAdV), particular HAdV species F (40, 41) has been recognized as important causal pathogens, however limited data exist on molecular epidemiology of other HAdV associated with acute gastroenteritis. METHODS: In the present preliminary study, we performed a case-control study involving 273 children who presented diarrheal disease and 361 healthy children matched control in Children's hospital of Hebei Province (China) to investigate the relationship between non-enteric HAdV and diarrhea. HAdV were detected and quantified using quantitative real-time PCR (qPCR) and serotyped by sequencing and phylogenetic analysis. Odds ratio (OR) was used to assess the risk factor of HAdV. RESULTS: HAdV were detected in 79 (28.94%) of 273 children with diarrhea including 7 different serotypes (HAdV 40, 41, 3, 2,1,5 and 57) with serotypes 40, 41 and 3 being the most dominant and in 26 (7.20%) of 361 healthy children containing 9 serotypes (HAdV 40, 41, 3, 2,1,5,57,6 and 31). A majority (91.14%) of HAdV positives occurred in diarrhea children and 65.38% in controls< 3 years of age. No significant difference in the viral load was found between case and control groups or between Ad41-positive patients and healthy controls. In addition to HAdV 40 and 41, HAdV 3 was also associated with diarrhea (OR = 17.301, adjusted OR = 9.205, p < 0.001). CONCLUSIONS: Our results demonstrate a high diversity of HAdV present among diarrhea and healthy children and implicate that non-enteric HAdV3 may lead to diarrhea.

Culturally Adapted CBTI for Chinese Insomnia Patients: a One-Arm Pilot Trial.

PURPOSE: Insomnia is a common mental disorder with severe consequences. Cognitive-behavioral therapy for insomnia (CBTI) has been proved effective against insomnia, but most of the research is limited to Western countries. This trial objective is to develop a Chinese culture-adapted CBTI program and assess its efficacy. METHOD: An 8-week culturally adapted CBTI program was developed that included mixed group and individual session and culturally adapted relaxation and cognitive restructuring treatment components. A one-arm clinical trial was conducted at a public hospital between March 2016 and January 2017. Seventy-two Chinese adults (15 males, 57 females; mean age, 50 years) with insomnia disorder underwent the culturally adapted CBTI program. Sleep diaries and self-report scales, as well as polysomnography (PSG, for a subgroup only), were used to assess qualitative and quantitative measures of sleep, mental health status, and quality of life at baseline, post-treatment, and 4-month follow-up. RESULTS: Pre-post analyses showed significant changes in sleep diary sleep onset latency (SOL), wake after sleep onset (WASO), and total sleep time of respectively - 37.03 min (CI, - 48.90 to - 25.16), - 28.16 min (CI, - 40.22 to - 16.10), and + 27.49 min (CI, 10.51 to 44.47). Self-reported sleep quality, mental health, and quality of life improved compared to baseline. The self-reported outcomes were mainly stable at follow-up. PSG outcomes globally failed to show improvement. CONCLUSION: The design of a CBTI program adapted to Chinese population was achieved. Culturally adapted CBTI showed promising results. More rigorously designed studies are needed to ensure efficacy.

[Case-control study on the association between four single nucleotide polymorphisms in folate metabolism way and the risk of congenital heart disease].

OBJECTIVE: To investigate the association between single nucleotide polymorphisms( SNPs) of 5, 10-methylenetetrahydrofolate reductase( MTHFR) C677T, A1298C, methionine synthase( MS) A2756G, methionine synthase reductase( MTRR) A66G and the risk of congenital heart disease( CHD). METHODS: By restricting the corresponding conditions, a case-control study was performed. We collected 200 congenital heart disease children as case group and 200 normal children as control group admitted to the Department of cardiac surgery, Children 's Hospital of Hebei Province from January 2016 to April 2017. The genotype of MTHFR C677T, A1298C, MS A2756G, and MTRR A66G polymorphisms were detected by Sanger sequencing followed PCR. Assessing the relationships between 4 SNPs and the risk of whole CHD and different types of CHD. RESULTS: The mutant allete T of MTHFR C677T had contribute to the risk of developing CHD( OR = 2. 47, 95% CI 1. 86-3. 29, P < 0. 001). Compared with the wild CC genotype, heterozygosity CT had a higher risk of CHD( OR = 2. 32, 95% CI 1. 35-3. 98, P < 0. 05), the homozygous mutant genotype TT increased the risk of CHD by 5. 37( 95% CI 3. 01-9. 60, P < 0. 001). The mutant allele C of MTHFR A1298C was a protective factor for CHD( OR = 0. 53, 95% CI 0. 36-0. 77, P < 0. 05). Compared with the wild AA genotype, heterozygosity AC had a lower risk of CHD( OR = 0. 41, 95% CI0. 26-0. 64, P < 0. 001). After typing, the allele frequencies and genotypes frequencies of the above two SNPs were still statistically significant( P < 0. 05). The combined genotype analysis of the above two SNPs showed that: compared with the CC/AA genotype, individuals with CT/AA had a higher risk of CHD( OR = 4. 65, 95% CI 2. 16-10. 02), the TT/AA type increased to 7. 05( 95% CI 3. 37-14. 79). However, the polymorphisms of MS A2756G and MTRR A66G had no significant relationship with the risk of CHD( P > 0. 05). CONCLUSION: The mutant allele T of MTHFR C677T may be a risk factor for CHD and the mutant allele C of A1298C may be a protective factor for CHD. These two SNPs may have a joint effect on the occurrence of CHD.

A comparison study between GeXP-based multiplex-PCR and serology assay for Mycoplasma pneumoniae detection in children with community acquired pneumonia.

BACKGROUND: Diagnosis of community-acquired pneumonia (CAP) caused by Mycoplasma pneumoniae (Mp) in children has been hampered by difficulty in obtaining convalescent serum and time constraints. In this study, the two diagnostic assays that targeted respectively on Mp-antibody and Mp-DNA were retrospectively investigated. METHODS: A total of 3146 children were clinically diagnosed to have CAP and were confirmed by chest X-ray during March 2015 to February 2016 in Children's hospital of Hebei Province (China). Both of the sera and sputum samples were collected in 24 h after their admission. The Mp-antibody was examined by the passive particle agglutination assay and a fourfold or greater increase of antibody titers of paired sera or≧1:160 titer of single serum was set as the serology positive. Mp-DNA in the sputum samples was tested by a multiplex-PCR method named GeXP assay (multiplex PCR combined with automated capillary electrophoresis). In order to eliminate the false positive results caused by the asymptomatic carriage after infected by M. pneumoniae, the inconsistent samples were tested by the real-time isothermal transcription-mediated RNA amplification assay (SAT). RESULTS: The inter-rated agreement test was performed in 3146 CAP patients, with a highest kappa value in the school-age children as 0.783. There were 6.29% (198/3146) cases showed inconsistent results determined by GeXP and serology assay. All of the 19 GeXP(+)/Serology (-) samples and a randomly chosen 27 from 179 GeXP(-)/Serology (+) samples were tested by SAT assay, and a 97.8% diagnosis agreement was observed between SAT and GeXP assay, but not with the serology assay. In addition, patients who were detected only by serology or only by multiplex-PCR were significantly younger than those with both methods positive (3.0 and 1.5 years vs. 5.0 years, p < 0.01). The Viral-Mp coinfection accounted for 37.0% (97/262), which was more common in winter and spring (p < 0.05) and in the infantile group (p < 0.01), compared to the pure Mp positive ones. CONCLUSION: In some children CAP cases, the Mp laboratory diagnosis was inconsistent between serology and multiplex-PCR assay. Verified by the SAT assay, the GeXP showed a more sensitive and reliable performance compared with the serology assay. Furthermore, employing the multiplex-PCR could provide more information on the associated pathogens for clinical assessment of CAP.

Insight into thiophene hydrodesulfurization on clean and S-modified MoP(010): a periodic density functional theory study.

The hydrodesulfurization (HDS) of thiophene on clean and S-modified MoP(010) is investigated to understand the HDS mechanism as well as the surface sulfur (S) atom effect using periodic density functional theory (DFT). The results show that thiophene prefers strongly flat adsorption on both the clean and S-modified surfaces, in either the molecular state or the dissociative state breaking simultaneously one C-S bond, and the adsorption of thiophene can be slightly weakened by the surface S atom. Thermodynamic and kinetic analysis indicates that the HDS of thiophene in both the molecular and dissociative adsorption states prefers to take place along the direct desulfurization (DDS) pathway rather than hydrogenation on both the clean and S-modified MoP(010) surfaces. Surface S shows a promotion effect on the HDS catalytic activity of MoP(010), because the energy barrier/rate constant of the rate-determining step on the DDS pathway is decreased/enlarged under the S modification. Compared with the situation of MoP(001), MoP(010) should have relatively low HDS activity, since a higher energy barrier as well as weaker exothermicity is involved in the reaction on the latter surface.

TGF-ß1/FGF-2 signaling mediates the 15-HETE-induced differentiation of adventitial fibroblasts into myofibroblasts.

BACKGROUND: Pulmonary adventitial fibroblasts (PAFs) are activated under stress stimuli leading to their differentiation into myofibroblasts, which is involved in vessel remodeling. 15-HETE is known as an important factor in vessel remodeling under hypoxia; however, the role of 15-HETE in PAF phenotypic alteration is not clear. RESULTS: The effect of 15-HETE on PAF phenotypic alterations was investigated in the present study. PAFs were treated with 15-HETE (0.5 µM) for 24 h, and the myofibroblast marker α-smooth muscle actin (α-SMA) was analyzed. The 15-HETE induced α-SMA expression and cell morphology. 15-HETE upregulated FGF-2 levels in PAFs, and knockdown FGF-2 by siRNAs blocked the enhanced α-SMA expression induced by 15-HETE. p38 kinase was activated, and blocked depressed 15-HETE-induced FGF-2 expression. The downstream of p38 pathway, Egr-1 activation, was also raised by 15-HETE treatment, and silenced Egr-1 suppressed the 15-HETE-induced upregulation of FGF-2. TGF-ß1 was upregulated with FGF-2 treatment, and α-SMA expression induced by FGF-2 was inhibited after the cell was transferred with TGF-ß1 siRNA. Meanwhile, FGF-2 increased α-SMA expression and improved proliferation, which was associated with p27(kip1) and cyclin E variation. CONCLUSIONS: The above results suggest that p38/Egr-1 pathway-mediated FGF-2 is involved in 15-HETE-induced differentiation of PAFs into myofibroblasts and cell proliferation.

Metallic Iron-Nickel Sulfide Ultrathin Nanosheets As a Highly Active Electrocatalyst for Hydrogen Evolution Reaction in Acidic Media.

We report on the synthesis of iron-nickel sulfide (INS) ultrathin nanosheets by topotactic conversion from a hydroxide precursor. The INS nanosheets exhibit excellent activity and stability in strong acidic solutions as a hydrogen evolution reaction (HER) catalyst, lending an attractive alternative to the Pt catalyst. The metallic α-INS nanosheets show an even lower overpotential of 105 mV at 10 mA/cm(2) and a smaller Tafel slope of 40 mV/dec. With the help of DFT calculations, the high specific surface area, facile ion transport and charge transfer, abundant electrochemical active sites, suitable H(+) adsorption, and H2 formation kinetics and energetics are proposed to contribute to the high activity of the INS ultrathin nanosheets toward HER.