Spatial-temporal analysis of hepatitis E in Hainan Province, China (2013-2022): insights from four major hospitals.

Objective: Exploring the Incidence, Epidemic Trends, and Spatial Distribution Characteristics of Sporadic Hepatitis E in Hainan Province from 2013 to 2022 through four major tertiary hospitals in the Province. Methods: We collected data on confirmed cases of hepatitis E in Hainan residents admitted to the four major tertiary hospitals in Haikou City from January 2013 to December 2022. We used SPSS software to analyze the correlation between incidence rate and economy, population density and geographical location, and origin software to draw a scatter chart and SAS 9.4 software to conduct a descriptive analysis of the time trend. The distribution was analyzed using ArcMap 10.8 software (spatial autocorrelation analysis, hotspot identification, concentration, and dispersion trend analysis). SAS software was used to build an autoregressive integrated moving average model (ARIMA) to predict the monthly number of cases in 2023 and 2024. Results: From 2013 to 2022, 1,922 patients with sporadic hepatitis E were treated in the four hospitals of Hainan Province. The highest proportion of patients (n = 555, 28.88%) were aged 50-59 years. The annual incidence of hepatitis E increased from 2013 to 2019, with a slight decrease in 2020 and 2021 and an increase in 2022. The highest number of cases was reported in Haikou, followed by Dongfang and Danzhou. We found that there was a correlation between the economy, population density, latitude, and the number of cases, with the correlation coefficient |r| value fluctuating between 0.403 and 0.421, indicating a linear correlation. At the same time, a scatter plot shows the correlation between population density and incidence from 2013 to 2022, with r2 values fluctuating between 0.5405 and 0.7116, indicating a linear correlation. Global Moran's I, calculated through spatial autocorrelation analysis, showed that each year from 2013 to 2022 all had a Moran's I value >0, indicating positive spatial autocorrelation (p < 0.01). Local Moran's I analysis revealed that from 2013 to 2022, local hotspots were mainly concentrated in the northern part of Hainan Province, with Haikou, Wenchang, Ding'an, and Chengmai being frequent hotspot regions, whereas Baoting, Qiongzhong, and Ledong were frequent cold-spot regions. Concentration and dispersion analysis indicated a clear directional pattern in the average density distribution, moving from northeast to southwest. Time-series forecast modeling showed that the forecast number of newly reported cases per month remained relatively stable in 2023 and 2024, fluctuating between 17 and 19. Conclusion: The overall incidence of hepatitis E in Hainan Province remains relatively stable. The incidence of hepatitis E in Hainan Province increased from 2013 to 2019, with a higher clustering of cases in the northeast region and a gradual spread toward the southwest over time. The ARIMA model predicted a relatively stable number of new cases each month in 2023 and 2024.

Construction of warfarin population pharmacokinetics and pharmacodynamics model in Han population based on Bayesian method.

The purpose of this paper is to study the genetic polymorphisms of related gene loci (CYP2C9*3, VKORC1-1639G > A) based on demographic and clinical factors, and use the maximum a posterior Bayesian method to construct a warfarin individualized dose prediction model in line with the Chinese Han population. Finally, the built model is compared and analyzed with the widely used models at home and abroad. In this study, a total of 5467 INR measurements are collected from 646 eligible subjects in our hospital, and the maximum a posterior Bayesian method is used to construct a warfarin dose prediction that conforms to the Chinese Han population on the basis of the Hamberg model. The model is verified and compared with foreign models. This study finds that body weight and concomitant use of amiodarone have a significant effect on the anticoagulant effect of warfarin. The model can provide an effective basis for individualized and rational dosing of warfarin in Han population more accurately. In the performance of comparison with different warfarin dose prediction models, the new model has the highest prediction accuracy, and the prediction percentage is as high as 72.56%. The dose predicted by the Huang model is the closest to the actual dose of warfarin. The population pharmacokinetics and pharmacodynamics model established in this study can better reflect the distribution characteristics of INR values after warfarin administration in the Han population, and performs better than the models reported in the literature.

Clinical analysis of temporary pacemaker implantation in 6 children with fulminant myocarditis.

BACKGROUND: There is little literature on the use of temporary pacemakers in children with fulminant myocarditis. Therefore, we summarized the use of temporary cardiac pacemakers in children with fulminant myocarditis in our hospital. METHODS: The clinical data of children with fulminant myocarditis treated with temporary pacemakers in Wuhan Children's Hospital from January 2017 to May 2022 were retrospectively analyzed. RESULTS: A total of 6 children were enrolled in the study, including 4 boys and 2 girls, with a median age of 50 months and a median weight of 15 kg. The average time from admission to pacemaker placement was 2.75 ± 0.4 h. The electrocardiogram showed that all 6 children had third-degree atrioventricular block (III°AVB). The initial pacing voltage, the sensory sensitivity of the ventricle and the pacing frequency were set to 5-10 mV, 5 V and 100-120 bpm respectively. The sinus rhythm was recovered in 5 patients within 61 h (17-134) h, and the median time of using temporary pacemaker was 132 h (63-445) h. One of the children had persistent III°AVB after the temporary pacemaker. With parental consent, the child was fitted with a permanent pacemaker on the 12th day of his illness. CONCLUSIONS: When fulminant myocarditis leads to severe bradycardia or atrioventricular block in children, temporary pacemakers have the characteristics of high safety to improve the heart function.

Active components and mechanisms of total flavonoids from Rhizoma Drynariae in enhancing cranial bone regeneration: An investigation employing serum pharmacochemistry and network pharmacology approaches.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhizoma Drynariae, as the dried rhizome of Drynaria fortunei (Kunze ex Mett.) J. Sm., is a traditional Chinese medicine for treating the injury and bone broken of falling and beating. Total flavonoids is considered as the major and effective compounds for the therapeutic efficacy of Rhizoma Drynariae. AIM OF THE STUDY: To explore the effect of total flavonoids from Rhizoma Drynariae (TFRD) on bone regeneration and the underlying mechanisms. MATERIALS AND METHODS: The effect of TFRD in various doses on bone reconstruction in cranial bone defect rats was explored in vivo. The active ingredients in TFRD-medicated serum were characterized by serum pharmacochemistry and integrated by network pharmacology analysis and target prediction. To elucidate the underlying mechanism of TFRD on bone regeneration, experimental validation in vitro was executed to assess the influence of different concentrations of TFRD-medicated serum on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). RESULTS: Micro-CT, histological examination, immunohistochemical analysis, and ELSA demonstrated that administration of TFRD could promote bone reconstruction in a rat cranial defect model. We identified 27 active components of TFRD using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Results from CCK8, ALP, and Alizarin Red S staining revealed that TFRD-medicated serum notably enhanced BMSCs proliferation and osteogenic differentiation. qRT-PCR and Western blot harvested results consistent with those predicted by network pharmacology, providing further evidence that TFRD activated the TGF-ß signaling pathway to benefit bone regeneration. CONCLUSION: The active components of TFRD modulate the TGF-ß signaling pathway to facilitate osteogenesis, thereby repairing cranial bone defects.

Application of a warfarin dosing calculator to guide individualized dosing versus empirical adjustment after fixed dosing: a pilot study.

Background: Warfarin has a narrow therapeutic window and individual variation, and patients require regular follow-up and monitoring of the International Normalized Ratio (INR) for dose adjustment. The calculation method of Warfarin Dosing Calculator (WDC) software is based on the European and American populations, and its accuracy in the Chinese population is yet to be verified. Objective: This study was to evaluate the feasibility of applying Warfarin Dosing Calculator software intervention in a real-world clinical research setting in China. Methods: The pilot study divided the included patients after valve replacement into an experimental group and a control group, with 38 cases in each group. In the control group, the initial dose was fixed at 2.5 mg/d and the dose was adjusted empirically during the study period; in the experimental group, the Warfarin Dosing Calculator software was applied to guide the dosing, and patients in both groups were followed up for 3 months. Analysis of the incidence anticoagulation outcomes and excessive anticoagulation events in both groups. Kaplan-Meier survival curves were used to analyze the correlation between different dosing regimens and first International Normalized Ratio attainment, and Logrank tests were performed. Results: The mean time required for first International Normalized Ratio compliance in the experimental group was 4.38 days less than in the control group, and the mean number of tests was 1.43 less (p < 05). Time in therapeutic range (TTR) was significantly higher in the experimental group than in the control group (p < 05). Kaplan-Meier survival curve analysis showed that the first International Normalized Ratio attainment rate was significantly higher in the experimental group than in the control group (p = 01). No major bleeding events occurred in either group, but other excessive anticoagulation events (INR>3.5 and minor bleeding) were significantly reduced in the experimental group compared with the control group (p < 05). Conclusion: Application of Warfarin Dosing Calculator software to guide individualized warfarin dosing may be better than a fixed dose of 2.5 mg/d. It may be shorten the time to first International Normalized Ratio attainment, and the attainment rate in the same time, and can better improve the mean Time in therapeutic range level value and reduce excessive anticoagulation events, which improves the safety of warfarin anticoagulation therapy in clinical practice. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=52793, ChiCTR2000032393.

Newborn Screening for G6PD Deficiency in Xiamen, China: Prevalence, Variant Spectrum, and Genotype-Phenotype Correlations.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzymatic defect. The purpose of this study was to evaluate the profile of G6PD deficiency and investigate the factors associated with the accuracy of newborn screening (NBS) in Xiamen, China. Methods: A total of 99,546 newborns were screened by modified fluorescent spot test at the Women and Children's Hospital, Xiamen University. High-risk neonates were recalled for diagnosis by either a measurement of G6PD activity or genetic testing for the presence of pathogenic G6PD variants using a quantitative G6PD enzymatic assay or the MeltPro® G6PD assay, respectively. Results: In the first-tier screening, 1,256 newborns were categorized as high risk. Of these, 1,051 were diagnosed with G6PD deficiency, indicating a prevalence of 1.39% in Xiamen, China. Among the 1,013 neonates who underwent genotyping, 851 carried hemizygous, heterozygous, homozygous, or compound heterozygous variants, for a positive predictive value (PPV) of 84.01%. In total, 12 variants and 32 genotypes were identified, and the six most common variants were c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, c.871G>A, and c.392G>T, which accounted for approximately 94% of the identified alleles. Different variants showed characteristic enzymatic activities, although high phenotypic heterogeneity was observed for each variant. The use of cold-chain transportation significantly improved the PPV of NBS. Conclusions: We determined the profile of G6PD deficiency in Xiamen, including the prevalence, variant spectrum, and genotype-phenotype correlations and confirmed that maintaining a low temperature during sample transport is essential to ensure the high screening accuracy of NBS. Our data provides epidemiological, genotypic, phenotypic, and clinical practice references to standardize future interventions for G6PD deficiency.

Preliminary investigation of microplastics in the production process of sea salt sourced from the Bohai Sea, China, using an optimised and consistent approach.

In this study, we present a preliminary investigation of the characteristic changes in microplastic during the production process of sea salt in China. Five representative samples, including seawater, saturated brine, crude salt, coarse salt, and refined salt were successively collected from the production process of sea salt sourced from the Bohai Sea in China. The pretreatment method of microplastics was optimised and evaluated by the recovery rates of particle references. Microplastic characteristics in the five samples were investigated using consistent pretreatment, microscopic, and spectroscopic analyses. Results indicated that microplastics were present in every stage of sea salt production. During the "journey" of microplastics in salt production from seawater-to-seawater evaporation, to salt crystallisation, and external force processing, the abundance of microplastics with size ranging from 18 µm to 4936 µm increased substantially from 23 ± 8 to 413 ± 61 particles kg-1, while the proportion of larger microplastics (≥1000 µm) decreased from 33% to 9%. The results illustrate the effect of the production process on microplastic contamination of sea salt.

Model analysis of meteorology and emission impacts on springtime surface ozone in Shandong.

Air quality observations showed that surface ozone (O3) concentrations over Shandong increased significantly in springtime in recent years, especially 2017. The observed 90th percentile of hourly O3 concentrations (O3-h_90) in May increased from 148.4 µg/m3 in 2016 to 176.2 µg/m3 in 2017. To investigate the reasons of significant increase of O3 in spring of 2017, seven sensitivity cases were performed with the RAMS-CMAQ modeling system to identify the impacts of meteorological conditions (M) and emissions (E) on O3 concentrations in May of Shandong during the time period 2016-2018. The regional O3-h_90 in May of Shandong were 103.0, 120.3 and 86.3 µg/m3 in 2016, 2017 and 2018, respectively. It was found that the positive effects from favorable meteorology were the dominant reasons that resulted in the high O3 concentration in May 2017. When compared to 2017 standard simulation (17E17M), the differences of meteorological conditions led to the decrease of 17.5 and 33.8 µg/m3 in regional O3-h_90 of May in 2016 (17E16M) and 2018(17E18M), while small changes (0.6 and - 0.3 µg/m3) appeared in that of May 2016 (16E17M) and 2018(18E17M) due to emission differences. Since there were few differences in the wind speeds of May between three years, the higher temperature and lower relative humidity significantly contributed to O3 formation in May 2017 compared to May of 2016 and 2018. Besides, the amount of cloud fraction (CF), which has an indirect influence on the surface temperature and photochemical production of ozone by its impacts on the insolation, was the least in May 2017 compared to that in May 2016 and 2018 over Shandong. The distributions of changes in CF had obvious negative correlations with that of O3 vertical column concentrations and temperature. Thus, the fewer cloud fraction may play a key role in O3 formation of May 2017.

Role of glucocorticoid receptor phosphorylation-mediated synaptic plasticity in anxiogenic and depressive behaviors induced by monosodium glutamate.

Psychiatric diseases and metabolic disorders frequently cooccur, yet the mechanisms underlying this interaction remain unknown. The aim of this study was to determine the role of glucocorticoid receptor (GR) phosphorylation in the comorbidity of metabolic and psychiatric disorders. Neonatal Sprague-Dawley rats were subcutaneously injected with monosodium glutamate (MSG) every 2 days for 10 days after birth. Metabolic and behavioral tests were performed 12 weeks later. Golgi staining and transmission electron microscopy (TEM) were performed to evaluate synaptic structural plasticity. Changes in GR phosphorylation and the BDNF/TrkB pathway were evaluated by western blotting and immunofluorescence. We found that MSG-treated rats displayed significant metabolic abnormalities accompanied by anxiogenic and depressive behaviors, an altered synaptic ultrastructure and the loss of dendritic spines. The expression of phosphorylated GR was reduced in the brain. Furthermore, a specific agonist of BDNF/TrkB significantly reversed the reduction in GR phosphorylation, as well as the metabolic and behavioral outcomes. These findings indicate that a decrease in BDNF/TrkB pathway-dependent GR phosphorylation is a long-term effect of MSG treatment that may contribute to metabolic and behavioral disturbances.

Clinical manifestations and pathogen characteristics in children admitted for suspected COVID-19.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread around the world. However, approaches to distinguish COVID-19 from pneumonia caused by other pathogens have not yet been reported. We retrospectively analyzed the clinical data of 97 children with probable COVID-19. A total of 13 (13.4%) patients were confirmed positive for SARS-CoV-2 infection by nucleic acid RT-PCR testing, and 41 (42.3%) patients were found to be infected with other pathogens. Notably, no pathogen was detected in 43 (44.3%) patients. Among all patients, 25 (25.8%) had familial cluster exposure history, and 52 (53.6%) had one or more coexisting conditions. Fifteen (15.5%) patients were admitted or transferred to the PICU. In the 11 confirmed COVID-19 cases, 5 (45.5%) and 7 (63.6%) were positive for IgM and IgG against SARS-CoV-2, respectively. In 22 patients with suspected COVID-19, 1 (4.5%) was positive for IgG but negative for IgM. The most frequently detected pathogen was Mycoplasma pneumonia (29, 29.9%). One patient with confirmed COVID-19 died. Our results strongly indicated that the detection of asymptomatic COVID-19 or coexisting conditions must be strengthened in pediatric patients. These cases may be difficult to diagnose as COVID-19 unless etiologic analysis is conducted. A serologic test can be a useful adjunctive diagnostic tool in cases where SARS-CoV-2 infection is highly suspected but the nucleic acid test is negative.

Clinical Characteristics of 5 COVID-19 Cases With Non-respiratory Symptoms as the First Manifestation in Children.

An outbreak of the novel coronavirus disease 2019 (COVID-19) occurred in Wuhan, China, in December 2019, which then rapidly spread to more than 80 countries. However, detailed information on the characteristics of COVID-19 in children is still scarce. Five patients with non-respiratory symptoms as the first manifestation were hospitalized from the emergency department, and were later confirmed to have COVID-19, between 23 January and 20 February 2020, at the Wuhan Children's Hospital. SARS-CoV-2 nucleic acid detection was positive for all the patients. Four of the patients were male and one was female, and their ages ranged from 2-months to 5.6 years. All lived in Wuhan. One patient had a clear history of exposure to SARS-CoV-2, one had a suspected history of exposure, while the others had no exposure history. For three of the five patients, the primary onset disease required an emergency operation or treatment, and included intussusception, acute suppurative appendicitis perforation with local peritonitis, and traumatic subdural hemorrhage with convulsion, while for the other two it was acute gastroenteritis (including one patient with hydronephrosis and a stone in his left kidney). During the course of the disease, four of the five patients had a fever, whereas one case had no fever or cough. Two patients had leukopenia, and one also had lymphopenia. In the two cases of severe COVID-19, the levels of CRP, PCT, serum ferritin, IL-6, and IL-10 were significantly increased, whereas the numbers of CD3+, CD4+, CD8+ T lymphocytes, and CD16 + CD56 natural killer cells were decreased. We also found impaired liver, kidney, and myocardial functions; the presence of hypoproteinemia, hyponatremia, and hypocalcemia; and, in one case, abnormal coagulation function. Except for one patient who had a rotavirus infection, all patients tested negative for common pathogens, including the influenza virus, parainfluenza virus, respiratory syncytial virus, adenovirus, enterovirus, mycoplasma, Chlamydia, and Legionella. Chest CT images of all the patients showed patches or ground-glass opacities in the lung periphery or near the pleura, even large consolidations. This case series is the first report to describe the clinical features of COVID-19 with non-respiratory symptoms as the first manifestation in children.

Minocycline alleviates NLRP3 inflammasome-dependent pyroptosis in monosodium glutamate-induced depressive rats.

BACKGROUND: Inflammasome activation and followed by the release of proinflammatory cytokines play a pivotal role in the development and progression of depression. However, the involvement of gasdermin D (GSDMD)-mediated pyroptosis in inflammasome-associated depression has not been studied. The present study aimed to determine the involvement of pyroptosis in the development of depression. METHODS: The rat depressive model was established by the administration of monosodium glutamate (MSG) in postnatal rats. Minocycline (an anti-inflammatory agent) and VX-765 (a specific inhibitor of caspase-1) were given as intervention treatments when rats were two-month-old. Rat depressive behaviors were evaluated by behavioral tests, including open field test, sucrose preference test, and forced swim test. Rat hippocampi were collected for western blotting and immunofluorescence examination. RESULTS: MSG administration induced depressive-like behavior in rats. MSG upregulated protein presences of caspase-1, GSDMD, interleukin-1ß (IL-1ß), interleukin-18 (IL-18), NLR pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), high mobility group box 1 protein (HMGB1), and the receptor for advanced glycation end products (RAGE) in the hippocampus. Protein presences of HMGB1, NLRP3 and GSDMD were upregulated in Olig2+ oligodendrocytes in the hippocampus. The data suggest that both HMGB1/RAGE/NLRP3 signalings and GSDMD-dependent pyroptosis were activated. Both minocycline and VX-765 treatments improved depressive-like behaviors. Minocycline treatment significantly reduced both HMGB1/RAGE/NLRP3 inflammasome signalings and GSDMD-dependent pyroptosis. VX-765 downregulated GSDMD-dependent pyroptosis, but not HMGB1/RAGE signalings, indicating that GSDMD-dependent pyroptosis is a key player in the progress of depression. CONCLUSION: In rats hippocampus, NLRP3 inflammasome activates GSDMD mediated-pyroptosis in the hippocampus of MSG-induced depressive rats.

[Expression of Serum HMGB1 and CD14+ mononuclear Toll-like Receptors in Children with Hemophagocytic Syndrome and Their Effect on Prognosis].

OBJECTIVE: To detect the expression of serum HMGB1 and CD14+ monocyte Toll-like receptors in children with hemophagocytic syndrome (HPS), and to analyze its effect on the prognosis of children. METHODS: Eight-three children with HPS admitted in Department of pediatrics of Wuhan Children's Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology were selected and enrolled in HPS group, at the same time 50 healthy children with same age were selected and enrolled in control group. The peripheral blood of children in 2 groups was collected. The flow cytometry was used to detect the expression of Toll-like receptors (TLR2, TLR4 and TLR6) in peripheral blood CD14+ monocytes, the ELISA was used to detect the expression of HMGB1 in serum of peripheral blood. The relationship of TLR2, TLR4, TLR6 and HMGB1 expression with the clinical parameters, short-term therapentic efficacy and prognosis was analyzed, the relation of TLR2, TLR4 and TLR6 expression with HMGB1 also was analyzed. RESULTS: The expression of TLR2, TLR4 and TLR6 on surface of CD14+ monocytes and fluorescence intensity in HPS group were significantly higher than those in control group (P＜0.05). The serum HMGB1 level in HPS group was significantly higher than that in control group (P＜0.05). The expression levels of TLR2, TLR4, TLR6 and HMGB1 in HPS children who were in acute phase or had decrease of albumin or hemoglobin levels, thrombocytopenia, neutrophil absolute value to low and increase of triglycerides level, in HPS group all significantly increased, the difference in children with different sex and age was no statistically significant (P＞0.05). After treatment, the expressions of TLR2, TLR4, TLR6 and HMGB in CR and NAD groups was significantly lower than that before treatment (P＜0.05), while the expressions levels of TLR2, TLR4, TLR6 and HMGB in AD and RD groups were no statistically significant different from those before treatment (P＜0.05); the expressions levels of TLR2, TLR4, TLR6 and HMGB in dealth group all were higher than those in survival group (P＜0.05). The serum HMGB1 levels in HPS children positively correlated with expression of TLR2, TLR4 and TLR6 on CD14+ monocytes (P＜ 0.05). CONCLUSION: The expression rate and level of TLR2, TLR4 and TLR6 on CD14+ monocytes in HPS children are significantly higher than those in healthy children.The expression levels of TLR2, TLR4, and TLR6 positively correlate with serum HMGB1 content, which provides reference for the diagnosis and prognosis of children with HPS.

Bilobalide protects astrocytes from oxygen and glucose deprivation-induced oxidative injury by upregulating manganese superoxide dismutase.

Bilobalide (BB), a constituent of the Ginkgo biloba extract, is a neuroprotective agent with multiple mechanisms of action. To further explore the potential therapeutic effects of BB in stroke, we investigated its effects on primary astrocytes using the oxygen and glucose deprivation-reoxygenation (OGD-R) model. Cell viability was measured by lactate dehydrogenase release assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell death was measured by annexin 5 conjgated with fluorescein isothiocyanate (V-FITC) assay, and reactive oxygen species (ROS) production was measured by 2',7'-Dichlorodihydrofluorescein Diacetate (DCFH-DA) probe. Manganese superoxide dismutase (MnSOD) expression was measured by western blot and immunofluorescence. Mitochondrial membrane potential was monitored using JC-1 staining. Our results show that OGD-R downregulated MnSOD and impaired mitochondrial function, which further enhanced ROS production in primary astrocytes. As a result, cell viability was compromised, and cell death increased. BB treatment protected astrocytes from those injuries mainly by restoring MnSOD level as MnSOD inhibitor abolished the effects of BB. In conclusion, we demonstrated that OGD-R induced astrocytic injury, but BB increased the expression of MnSOD, the ROS scavenger, to reverse the exacerbated astrocytic injury.

DNA Aptamers Targeting BACE1 Reduce Amyloid Levels and Rescue Neuronal Deficiency in Cultured Cells.

ß-amyloid (Aß) plays an essential role in the pathogenesis of Alzheimer's disease (AD). Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is indispensable for Aß production, and knockout of BACE1 has no overt phenotypes in mouse. Thus, fine modulation of BACE1 may be a safe and effective treatment for AD patients. However, the large active site of BACE1 makes it challenging to target BACE1 with classical small-molecule inhibitors. DNA aptamer can have high affinity and specificity against diverse targets, and it provides an alternative strategy to target BACE1. In this study, we used a novel cell-systematic evolution of ligands by exponential enrichment (SELEX) strategy to select specific DNA aptamers optimized to target BACE1 under physiological status. After 17 rounds of selection, we identified two DNA aptamers against BACE1: BI1 and BI2. The identified aptamers interacted with BACE1 in pull-down assay, inhibited BACE1 activity in in vitro fluorescence resonance energy transfer (FRET) assay and HEK293-APP stable cell line, reduced Aß in the culture medium of HEK293-amyloid protein precursor (APP) stable cell line and APP-PS1 primary cultured neurons, and rescued Aß-induced neuronal deficiency in APP-PS1 primary cultured neurons. In contrast, the identified aptamers had no effect on α- or γ-secretase. In addition, cholesteryl tetraetylene glycol (TEG) modification further improved the potency of the identified aptamers. Our study suggests that it is feasible and effective to target BACE1 with DNA aptamers, and the therapeutic potential of the identified aptamers deserves further investigation.

[Efficacy of analgesic and sedative treatments in children with mechanical ventilation in the pediatric intensive care unit].

OBJECTIVE: To compare the efficacy and safety of different analgesic and sedative treatments in children with mechanical ventilation in the pediatric intensive care unit (PICU). METHODS: Eighty children with mechanical ventilation in the PICU who needed analgesic and sedative treatments were equally and randomly divided into midazolam group and remifentanil+midazolam group. The sedative and analgesic effects were assessed using the Ramsay Scale and the Face, Legs, Activity, Cry and Consolability (FLACC) Scale. The following indices were recorded for the two groups: vital signs, ventilator parameters, organ function, total doses of remifentanil and midazolam, duration of mechanical ventilation, length of PICU stay, PICU cost, and incidence of adverse events. RESULTS: Satisfactory sedation was achieved in the two groups, but the remifentanil+midazolam group had a significantly shorter time to analgesia and sedation than the midazolam group. The remifentanil+midazolam group had a significantly higher percentage of patients with grade 3-4 on the Ramsay Scale and a significantly lower dose of midazolam than the midazolam group (P<0.05). Both groups showed decreases in heart rate (HR), mean arterial pressure (MAP), and spontaneous breathing frequency (RRs) after treatment. However, the remifentanil+midazolam group had significantly greater decreases in HR at 3-24 hours after treatment and MAP and RRs at 3-12 hours after treatment than the midazolam group (P<0.05). Compared with the midazolam group, the remifentanil+midazolam group had significantly higher ventilator tidal volume and transcutaneous oxygen saturation at 6 and 12 hours after treatment and significantly lower end-tidal carbon dioxide partial pressure at 6 and 12 hours after treatment (P<0.05). The remifentanil+midazolam group had significantly shorter time to awake, extubation time, duration of mechanical ventilation, and length of PICU stay than the midazolam group (P<0.05). There were no significant differences in PICU cost, incidence of adverse events, and hepatic and renal functions before and after treatment between the two groups (P>0.05). Both groups showed a significant decrease in fasting blood glucose level after treatment (P<0.05). CONCLUSIONS: For children with mechanical ventilation in the PICU, remifentanil+midazolam treatment can rapidly achieve analgesia and sedation, improve the effect of mechanical ventilation, and reduce the dose of sedative compared with midazolam alone, and is well tolerated.

Xuebijing in the treatment of patients with sepsis.

BACKGROUND: There are more than 18 million patients diagnosed with sepsis every year. In China, Xuebijing (XBJ) injection is a traditional medicine that is widely used in the treatment of sepsis. However, the efficacy of XBJ in treatment of randomized controlled trials (RCTs) remains unclear. This meta-analysis was to evaluate the clinical efficacy of XBJ based on randomized case-control studies. METHODS: PubMed, Cochrane, Embase, Wanfang, CNKI, and WeiPu (VIP) databases were searched to identify all the relative randomized case-control. The latest research was done in June, 2016. Relative risks (RR), weighted mean difference (WMD) along with 95% confidence interval (95%CI) were used to analyze the main outcomes. Statistical analysis was performed using STATA 10.0 (TX, USA). The qualities of the involved articles were accessed by the Jadad scale. RESULTS: Forty-nine randomized case-control studies met the inclusion and exclusion criteria, with 1861 patients in the control group and 2023 patients in the XBJ group. Compared with the conventional therapy, XBJ injection could significantly reduce the APACHE-IIscore (WMD: -3.70, 95%CI: -4.31-[-3.09]), PCT (WMD: -1.26µg/L, 95%CI: -1.63µg/L-[-0.88µg/L]), WBC (WMD: -1.48×109/L, 95%CI: -2.03×109/L-[-0.94×109/L]), CRP (WMD: -24.38mg/L, 95%CI:-30.49mg/L-[-18.26mg/L]), NEU (WMD: -4.68, 95%CI: -8.32-[-1.04]), T0(WMD: -0.50, 95%CI: -0.92-[-0.07]). The 28-day mortality of the XBJ group was significantly lower than the control group (RR: 0.51; 95%CI: 0.44-0.59). CONCLUSION: XBJ injection has a significant clinical efficacy in the therapy of patients with sepsis. However, there is a need for more randomized, lager-sample size, high-quality, and multicenter studies to confirm the extract efficacy of XBJ injection.

[Clinical value of serum procalcitonin in evaluating severity of infant muggy syndrome].

OBJECTIVE: To study the correlation between serum procalcitonin (PCT) level and severity of infant muggy syndrome (IMS) and the predictive value of PCT in the development of multiple organ dysfunction syndrome (MODS) in children with IMS. METHODS: Fifty children with IMS were classified into two groups according to the presence of MODS: MODS (n=29) and non-MODS (n=21). According to a 30-day follow-up result, they were classified into survival (n=36) and deceased groups (n=14). Vital signs, routine biological measurements (arterial blood gas, blood routine, CRP, liver and kidney functions, myocardial enzyme and so on) and the disease severity evaluated by the Pediatric Critical Illness Score (PCIS) within 24 hours of admission were recorded. Serum levels were measured using the semi-quantitative PCT-Q test within 24 hours of admission. RESULTS: Forty-seven children (94%) had elevated serum PCT levels (≥ 0.5 ng/mL) at admission. There were lower PCIS scores, higher rates of MODS and higher levels of serum PCT in deceased patients than survivors (P<0.05). There was a significant negative correlation between serum PCT levels and PCIS scores (r=-0.84, P<0.05). Serum PCT levels in the MODS group were significantly higher than in the non-MODS group (P<0.01). Receiver operating characteristic curve showed that, if the cut-off point of serum PCT level was 10.6 ng/mL, the sensitivity and specificity of PCT were 79.3% and 90.5% respectively, in predicting MODS, with the area under the curve of 0.924 ( P<0.01). CONCLUSIONS: Serum PCT level at admission is correlated with the severity of IMS and it may be an early predictive marker of MODS.

[Effect of hyperoxia on p53 and PCNA expression in fetal rat lung fibroblasts].

OBJECTIVE: To study the effect of hyperoxia exposure on the expression of p53 and proliferating cell nuclear antigen (PCNA) in fetal rat lung fibroblasts (LFs). METHODS: Primary rat embryonic LFs were cultured in vitro. LFs grew to subconfluence and then were randomly divided into air and hyperoxia exposure (95% O2, 5% CO2) groups. After LFs were cultured for 12 and 24 hours, the proliferation was analyzed by MTT. p53 mRNA level was detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). p53 and PCNA protein levels were determined by Western blot. RESULTS: After 12 and 24 hours of culture the growth inhibition rate of LFs was 8% and 23% respectively in the hyperoxia exposure group. p53 mRNA and protein levels increased significantly (P<0.01) in the hyperoxia exposure group after 12 and 24 hours of culture compared with the air exposure group. Hyperoxia exposure decreased PCNA expression after 24 hours of culture (P<0.01). CONCLUSIONS: Hyperoxia exposure increases p53 level and decreases PCNA expression, resulting in inhibitions of LFs proliferation and DNA repair.