Evaluation of disease severity and prediction of severe cases in children hospitalized with influenza A (H1N1) infection during the post-COVID-19 era: a multicenter retrospective study.

BACKGROUND: The rebound of influenza A (H1N1) infection in post-COVID-19 era recently attracted enormous attention due the rapidly increased number of pediatric hospitalizations and the changed characteristics compared to classical H1N1 infection in pre-COVID-19 era. This study aimed to evaluate the clinical characteristics and severity of children hospitalized with H1N1 infection during post-COVID-19 period, and to construct a novel prediction model for severe H1N1 infection. METHODS: A total of 757 pediatric H1N1 inpatients from nine tertiary public hospitals in Yunnan and Shanghai, China, were retrospectively included, of which 431 patients diagnosed between February 2023 and July 2023 were divided into post-COVID-19 group, while the remaining 326 patients diagnosed between November 2018 and April 2019 were divided into pre-COVID-19 group. A 1:1 propensity-score matching (PSM) was adopted to balance demographic differences between pre- and post-COVID-19 groups, and then compared the severity across these two groups based on clinical and laboratory indicators. Additionally, a subgroup analysis in the original post-COVID-19 group (without PSM) was performed to investigate the independent risk factors for severe H1N1 infection in post-COIVD-19 era. Specifically, Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select candidate predictors, and logistic regression was used to further identify independent risk factors, thus establishing a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were utilized to assess discriminative capability and accuracy of the model, while decision curve analysis (DCA) was used to determine the clinical usefulness of the model. RESULTS: After PSM, the post-COVID-19 group showed longer fever duration, higher fever peak, more frequent cough and seizures, as well as higher levels of C-reactive protein (CRP), interleukin 6 (IL-6), IL-10, creatine kinase-MB (CK-MB) and fibrinogen, higher mechanical ventilation rate, longer length of hospital stay (LOS), as well as higher proportion of severe H1N1 infection (all P < 0.05), compared to the pre-COVID-19 group. Moreover, age, BMI, fever duration, leucocyte count, lymphocyte proportion, proportion of CD3+ T cells, tumor necrosis factor α (TNF-α), and IL-10 were confirmed to be independently associated with severe H1N1 infection in post-COVID-19 era. A prediction model integrating these above eight variables was established, and this model had good discrimination, accuracy, and clinical practicability. CONCLUSIONS: Pediatric H1N1 infection during post-COVID-19 era showed a higher overall disease severity than the classical H1N1 infection in pre-COVID-19 period. Meanwhile, cough and seizures were more prominent in children with H1N1 infection during post-COVID-19 era. Clinicians should be aware of these changes in such patients in clinical work. Furthermore, a simple and practical prediction model was constructed and internally validated here, which showed a good performance for predicting severe H1N1 infection in post-COVID-19 era.

Biochemical component analysis of human myopic corneal stroma using the Raman spectrum.

PURPOSE: This study aimed to measure the Raman spectrum of the human corneal stroma lens obtained from small incision lenticule extraction surgery (SMILE) in Asian myopic eyes using a confocal Raman micro-spectrometer built in the laboratory. METHODS: Forty-three myopic patients who underwent SMILE with equivalent diopters between - 4.00 and - 6.00 D were selected, and the right eye data were collected. Corneal stroma lenses were obtained during surgery, and the Raman spectra were measured after air drying. The complete Raman spectrum of human myopic corneal stroma lens tissue was obtained within the range of 700-4000 cm-1. RESULTS: Thirteen characteristic peaks were found, with the stronger peaks appearing at 937 cm-1, corresponding to proline, valine, and the protein skeleton of the human myopic corneal stroma lens; 1243 cm-1, corresponding to collagen protein; 1448 cm-1, corresponding to the collagen protein and phospholipids; and 2940 cm-1, corresponding to the amino acid and lipids, which was the strongest Raman peak. CONCLUSION: These results demonstrated that Raman spectroscopy has much potential as a fast, cost-effective, and reliable diagnostic tool in the diagnosis and treatment of eye diseases, including myopia, keratoconus, and corneal infection.

Historical trends in the anthropogenic heavy metal levels in the tidal flat sediments of Lianyungang, China.

The sedimentation of metals can preserve the historical record of contaminant input from local and regional sources and provide information on the historical changes in regional water and sediment quality. We report the 210Pb activities and the heavy metal (Cd, Cr, Cu, Mn, Pb and Zn) depth profiles from sediment cores retrieved in 2010. The mean sedimentation rates of 0.85-1.5 cm/yr are determined by 210Pb dating. The sediments in the tidal flat have recorded heavy metal deposition and thus allow the establishment of a connection between the temporal evolution of the heavy metal pollution and the historical changes in the economic development of Lianyungang. The enrichment factors (EF) are calculated to estimate the level of contamination stored in these sediments. The results show that in the studied sites, Cr and Cu display low EF values and are mainly from lithogenic origin. For the other studied trace metals, a great variability in the sedimentary record is observed. Significant anthropogenic enrichment over the last 50 years is revealed at the tidal flat that receives fluvial inputs. Zinc is the element with the highest EF values, followed by the order of Pb > Cd > Mn > Cu and Cr. The temporal variations of the heavy metals peak during the late 1980s to the early 2000s and show a decreasing trend afterward. The pollution intensity of the tidal flat is determined by using EF and the geo-accumulation index (I(geo)), which show that, based on the l(geo) scale, the tidal flat of Haizhou Bay is unpolluted to moderately polluted.

Heavy metal pollution and assessment in the tidal flat sediments of Haizhou Bay, China.

The heavy metal inventory and the ecological risk of the tidal flat sediments in Haizhou Bay were investigated. Results show that the average concentrations of heavy metals in the surface sediments exceeded the environment background values of Jiangsu Province coastal soil, suggesting that the surface sediments were mainly polluted by heavy metals (Cd, Cr, Cu, Mn, Pb and Zn). In addition, the profiles of heavy metals fluxes can reflect the socio-economic development of Lianyungang City, and heavy metals inputs were attributed to anthropogenic activities. Cr, Cu, Pb and Zn were mainly present in the non-bioavailable residual form in surface sediments, whereas Cd and Mn were predominantly in the highly mobile acid soluble and reducible fractions. The ecological risk of the polluted sediments stemmed mainly from Cd and Pb. According to the Sediment quality guidelines (SQGs), however, the adverse biological effects caused by the heavy metals occasionally occurred in tidal flat.

[History of heavy metal pollution from tidal flat in Haizhou Bay].

Coastal zone could be considered as an important sink of regional source to sink and preserve historical records of environmental evolution. Four sediment cores, collected from tidal flat at Haizhou Bay near Lianyungang City, were examined for concentrations of heavy metals including Cd, Cr, Cu, Mn, Pb and Zn in core sediments to investigate the historical input of trace metals. In addition, sediment rates of cores LH3 and LH4 were determined based on radionuclide 210Pb. The results showed that grain size control effect was not the main factor that influenced the distribution of heavy metals. Heavy metals concentrations in the surface sediments were higher than these regional background values. Furthermore, Al element as a proxy of grain size was selected for normalization and calculation of metal enrichment factor (EF) and anthropogenic heavy metal fluxes. The results revealed that heavy metals in tidal flats were continuously enriched in the past decades, meanwhile, tidal flats have been significantly subjected to contaminations due to anthropogenic activities. Moreover, the depth profiles of heavy metals fluxes correspond to scenario of social-economy development of Lianyungang, which is an important urban area near Haizhou Bay. From 1950s to 2005, anthropogenic fluxes of metals increased with fluctuations, whereas, since 2005 anthropogenic fluxes declined, which may be correlated to the adjustment of industrial structure as well as the strengthened environmental regulation.

Paper-based enzyme immobilization for flow injection electrochemical biosensor integrated with reagent-loaded cartridge toward portable modular device.

Paper-based enzyme immobilization for a flow injection electrochemical biosensor integrated with a reagent-loaded cartridge toward a portable device was developed. A paper disk was immobilized with enzyme, then it was integrated in a flow cell as an electrochemical biosensor. A silicon tube reagent-loaded cartridge was integrated into the system, a complicated procedure was simplified as a one-click operation toward development for point-of-care applications. In this research, glucose oxidase (GOx) was employed as a model enzyme, silver ion as an inhibition reagent for GOx, and EDTA as a regeneration reagent. When GOx was inhibited by silver ions, glucose was introduced for electrochemical measurements before and after inhibited enzyme regeneration and the difference was caused by silver inhibition. The modular device has great potential for other applications, e.g., detection of enzyme activity and substrate. The platform based on double-test mode provided accurate results due to elimination of an average or control value in comparison with classical routine approaches.

Dual effects of interleukin-18: inhibiting hepatitis B virus replication in HepG2.2.15 cells and promoting hepatoma cells metastasis.

Interleukin-18 (IL-18) has been reported to inhibit hepatitis B virus (HBV) replication in the liver of HBV transgenic mice; however, the molecular mechanism of its antiviral effect has not been fully understood. In the present study, it was shown that IL-18 and its receptors (IL-18R) were constitutively expressed in hepatoma cell lines HepG2 and HepG2.2.15 as well as normal liver cell line HL-7702. We demonstrated that IL-18 directly inhibited HBV replication in HepG2.2.15 cells via downregulating the activities of HBV core and X gene promoters. The suppressed HBV replication by IL-18 could be rescued by the administration of BAY11-7082, an inhibitor of transcription factor NF-κB. On the other hand, it was of interest that IL-18 promoted HepG2 cell metastasis and migration dose dependently in both wound-healing assays and Transwell assays. The underlying mechanism could be partially attributable to the increased activities of extracellular matrix metalloproteinase (MMP)-9, MMP-3, and MMP-2 by IL-18, which upregulated the mRNA levels of MMP-3 and MMP-9 in a NF-κB-dependent manner. Furthermore, it was confirmed that expression of IL-18/IL-18R and most MMPs were remarkably upregulated in hepatocellular carcinoma (HCC) liver cancer tissue specimens, suggesting that IL-18/IL-18R-triggered signaling pathway was closely related to HCC metastasis in vivo. Therefore, we revealed the dual effects of IL-18 in human hepatocytes: it not only inhibited HBV replication but also promoted hepatoma cells metastasis and migration. NF-κB played a critical role in both effects. Our work contributed to a deeper understanding of the biological function of IL-18 in human hepatocytes.

Tracking vaccine-safety inquiries to detect signals and monitor public concerns.

BACKGROUND: The Centers for Disease Control and Prevention frequently receives inquiries from health care providers, public health officials, and the general public seeking data or guidance on vaccine-safety issues. Past inquiries to public health authorities identified potential problems including viscerotropic illness rarely associated with yellow fever vaccination. OBJECTIVE: To systematically describe vaccine-safety inquiries received at the Centers for Disease Control and Prevention. METHODS: External and internal inquiries were recorded in a database from May 1, 2002 to May 31, 2009. Key variables analyzed included the source of the question, the type of information being sought, and the vaccine type(s) associated with the inquiry. RESULTS: A total of 983 vaccine-safety inquiries were answered and analyzed. Health care workers were the source of 43% of the questions, and the general public accounted for 19% of the questions. Nearly half of the requests (49%) concerned information about the Vaccine Adverse Event Reporting System, and nearly one-fourth (21%) were requests from providers for clinical guidance. The most frequent specific topics of inquiry and vaccines involved were neurologic adverse events (AEs) temporally associated with vaccination (17%) and safety of all vaccines or childhood vaccines (20%), respectively. CONCLUSIONS: Questions about rare but potentially serious AEs and general concerns about vaccine safety were encountered relatively frequently. The substantial number of clinically focused inquiries may indicate a need for more provider support tools and resources. Tracking of inquiries can supplement information received through vaccine AE reporting and contribute to an enhanced scientific and communications response to vaccine-safety concerns.

Epidemiology, genetics and treatments for myopia.

Myopia is a significant public health problem and its prevalence is increasing over time and genetic factors in disease development are important. The prevalence and incidence of myopia within sampled population often varies with age, country, sex, race, ethnicity, occupation, environment, and other factors. Myopia growth is under a combination of genes and their products in time and space to complete the coordination role of the guidance. Myopia-related genes include about 70 genetic loci to which primary myopias have been mapped, although the number is constantly increasing and depends to some extent on definition. Of these, several are associated with additional abnormalities, mostly as part of developmental syndromes. These tend to result from mutations in genes encoding transcriptional activators, and most of these have been identified by sequencing candidate genes in patients with developmental anomalies. Currently, COL1A1 (collagen alpha-1 chain of type I), COL2A1 (collagen alpha-1 chain of type II), ACTC1 (actin, alpha, cardiac muscle 1), PAX6 (paired box gene 6) and NIPBL (nipped-B homolog), and so on have been mapped. Myopia is most commonly treated with spectacles or glasses. The most common surgical procedure performed to correct myopia is laser in situ keratomileusis (LASIK). This review of the recent advances on epidemiology, genetic locations and treatments of myopia are summarized.

The membrane protein of SARS-CoV suppresses NF-kappaB activation.

Severe acute respiratory syndrome coronavirus (SARS-CoV) infects many organs, such as lung, liver, and immune organs and causes life-threatening atypical pneumonia, SARS causes high morbidity and mortality rates. The molecular mechanism of SARS pathogenesis remains elusive. Inflammatory stimuli can activate IkappaB kinase (IKK) signalsome and subsequently the nuclear factor kappa B (NF-kappaB), which influences gene expression of cyclooxygenase-2 (Cox-2) along with other transcription factors. In this work, we found that the membrane (M) protein of SARS-CoV physically interacted with IKKbeta using a co-immunoprecipitation assay (IPA). Expression of M suppressed tumor necrosis factor alpha (TNF-alpha) induced NF-kappaB activation using a luciferase reporter assay. Further investigation showed M protein suppressed Cox-2 expression using a luciferase reporter gene assay, RT-PCR and Western blot analysis. The carboxyl terminal of M protein was sufficient for the M protein function. Together, these results indicate that SARS-CoV M suppresses NF-kappaB activity probably through a direct interaction with IKKbeta, resulting in lower Cox-2 expression. Suppression of NF-kappaB activity and Cox-2 expression may contribute to SARS pathogenesis.

HCV NS2 protein inhibits cell proliferation and induces cell cycle arrest in the S-phase in mammalian cells through down-regulation of cyclin A expression.

Chronic hepatitis C virus (HCV) infection often leads to liver cancer. NS2 protein is a HCV hydrophobic transmembrane protein that associates with several cellular proteins in mammalian cells. In this report, we investigated the functions of NS2 protein by examining its effects on cell growth and cell cycle progression. Stable NS2-expressing HeLa and Vero cell lines were established by transfection of the cells with pcDNA3.1(-)-NS2 followed by selection of the transfected cells in the presence of G418. We found that the proliferation rates of both NS2-expressing cell lines were inhibited by 40-50% compared with the control cells that were transfected with pcDNA3.1(-) control vector. Cell cycle analysis of these NS2-expressing cell lines shows that the proportion of cells in the S-phase increased significantly compared to that of control cells that do not express NS2 protein, suggesting NS2 protein induces cell cycle arrest in the S-phase. Further studies showed that the induction of cell cycle arrest in the S-phase by NS2 protein is associated with the decrease of cyclin A level. In contrast, the expression of NS2 protein does not affect the levels of cyclin-dependent kinase CDK2, CDK4, cyclin D1, or cyclin E. Our results suggest that HCV NS2 protein inhibits cell growth and induces the cell cycle arrest in the S-phase through down-regulation of cyclin A expression, which may be beneficial to HCV viral replication. Our findings not only provide information in the understanding mechanism of HCV infection, but also provide guidance for the future development of potential therapeutics for the prevention and treatment of the viral infection.

In vitro and in vivo protective effects of proteoglycan isolated from mycelia of Ganoderma lucidum on carbon tetrachloride-induced liver injury.

AIM: To investigate the possible mechanism of the protective effects of a bioactive fraction,Ganoderma lucidum proteoglycan (GLPG) isolated from Ganoderma lucidum mycelia, against carbon tetrachloride-induced liver injury. METHODS: A liver injury model was induced by carbon tetrachloride. Cytotoxicity was measured by MTT assay. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined with an automatic multifunction-biochemical analyzer and the levels of superoxide dismutase (SOD)and TNF-alpha were determined following the instructions of SOD kit and TNF radioimmunoassay kit. Liver sections were stained with hematoxylin and eosin (H and E) for histological evaluation and examined under light microscope. RESULTS: We found that GLPG can alleviate the L-02 liver cells injury induced by carbon tetrachloride (CCl4) through the measurements of ALT and AST activities and the administration of GLPG to L-02 cells did not display any toxicity. Furthermore, histological analysis of mice liver injury induced by CCl4 with or without GLPG pretreatment indicated that GLPG can significantly suppress the toxicity induced by CCl4 in mice liver. We also found that GLPG reduced TNF-alpha level induced by CCl4 in the plasma of mice, whereas increased SOD activity in the rat serum. CONCLUSION: GLPG has hepatic protective activity against CCl4-induced injury both in vitro and in vivo. The possible anti-hepatotoxic mechanisms may be related to the suppression of TNF-alpha level and the free radical scavenging activity.

[The purification of HBV full-length PreS protein in Pichia pastoris].

The Pichia pastoris strain GS115-PreS could produce a high expression level of full-length PreS protein that secreted to the supernatant after methanol induction in the fermentation. The Western blot analysis showed a single band with expected molecular mass of 48kD and that the major component of the particles was the full-length PreS protein (PreS1 + PreS2 + S) and small envelope protein (S) of 48 and 28 kD, respectively. Electron microscopy image showed PreS particles with 30 nm in diameter. The supernatants of the fermentation were desalted and concentrated. Purified PreS protein was obtained by DEAE-SFF anion exchange column chromatography and the PreS particles were obtained by ultracentrifugation and sucrose density gradient. The ELISA assay results proved that both full-length PreS protein and particles showed high immunogenicity and specificity. P/N ratio further demonstrated that the immunogenicity of the particles is higher than the full-length PreS protein.

[Detection of antibody against hepatitis C virus first envelope (HCV-E1) protein and its clinical application].

BACKGROUND: To study the antibody against hepatitis C virus first envelope (HCV-E1) protein in the sera from patients with HCV and to evaluate the application of HCV-E1 antigen in detection of HCV antibody. METHODS: Purified E1 engineering protein was used as antigen to develop an ELISA for detecting E1 antibody in 80 national reference sera, 821 blood donors' sera and l20 sera from clinical patients with hepatitis. RESULTS: Anti-HCV E1 was positive in 70% (28/40) and negative in 100% (40/40) of 80 national reference sera, and 1.9% (16/821) was positive in blood of the sera donors' and 68% (492/720) positive in sera of patients with hepatitis. Most anti-HCV E1 positive sera were positive for core, NS 3 and NS 5A, but only a few sera were positive for E1 antigen. Of the sera from 218 clinical patients, 813 blood donors and 848 normal people that were anti-HCV negative tested by commercial anti HCV ELISA kit, 1.4%, 1.1% and 0.9% were anti-HCV E1 positive, respectively. Investigation of seroconversion on three patients showed that anti-E1 was first detectable. CONCLUSIONS: Detection of anti-HCV E1 by engineered E1 protein is sensitive and specific. The prevalence and early presence of E1 antibody in HCV infected patients reflect the active status of the disease to a certain extent. Detection of the antibody is useful in clinical diagnosis.