[Clinical analysis of 4 acute ischemic stroke children treated with endovascular thrombectomy].

Objective: To assess the feasibility of endovascular thrombectomy (EVT) for the treatment of acute ischemic stroke (AIS) in children. Methods: Clinical data and follow-up information of 4 AIS children who received EVT in the Department of Intervention & Hemangioma at the Children's Hospital of the Capital Institute of Pediatrics from December 2020 to June 2021 were collected retrospectively. The vascular recanalization after EVT was assessed by the modified thrombolysis in cerebral infarction (mTICI) score. Efficacy outcomes were assessed with initial and postprocedural Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score, and the modified Rankin scale (mRS) score at 3 and 6 months after treatment. Safety assessments included perioperative complications and intracranial hemorrhage post-treatment. Results: A total of 5 EVT treatment were performed on 4 children with AIS, of whom 3 were male. The age of onset was 4.6, 13.8, 7.8, 8.0, 8.9 years, respectively. The time from symptom onset to initiation of EVT was 19.0, 25.0, 22.0, 4.0, 16.5 hours, respectively and all patients achieved successful recanalization of the vessel after EVT (mTICI≥2b). The PedNIHSS score was 39, 14, 25, 39, 24 before treatment and decreased to 8, 1, 12, 39, 5 at discharge. All the procedures were performed with no perioperative complications. Only 1 patient with congenital heart disease had a recurrent AIS with malignant brain oedema and brain hernia. Although the occluded vessels were successfully recanalized,the symptoms were not improved and this patient died after treatment abandonment. The other 3 patients achieved good recovery at 6 months postoperatively. The mRS score of 3 patients was 3, 1, 2 at 3 months after EVT and decreased to 2, 1, 1 at 6 months. Conclusion: EVT treatment may be feasible and safe for pediatric AIS due to large vessel occlusion even when the treatment was initiated 6 hours post stroke, but children with heart disease may have a dismal prognosis.

Assessing Adverse Health Effects of Long-Term Exposure to Low Levels of Ambient Air Pollution: Phase 1.

INTRODUCTION: This report provides a summary of major findings and key conclusions supported by a Health Effects Institute grant aimed at "Assessing Adverse Health Effects of Long-Term Exposure to Low Levels of Ambient Pollution." Our study was designed to advance four critical areas of inquiry and methods development. METHODS: First, our work focused on predicting short- and long-term exposures to ambient PM2.5 mass (particulate matter ≤ 2.5µm in aerodynamic diameter) and ozone (O3) at high spatial resolution (1 km × 1 km) for the continental United States during the period 2000-2012 and linking these predictions to health data. Second, we developed new causal inference methods for exposure-response (ER) that account for exposure error and adjust for measured confounders. We applied these methods to data from the New England region. Third, we applied standard regression methods using Medicare claims data to estimate health effects that are associated with short- and long-term exposure to low levels of ambient air pollution. We conducted sensitivity analyses to assess potential confounding bias due to lack of extensive information on behavioral risk factors in the Medicare population using the Medicare Current Beneficiary Survey (MCBS) (nationally representative sample of approximately 15,000 Medicare enrollees per year), which includes abundant data on individual-level risk factors including smoking. Finally, we have begun developing tools for reproducible research - including approaches for data sharing, record linkage, and statistical software. RESULTS: Our HEI-funded work has supported an extensive portfolio of analysis and the development of statistical methods that can be used to robustly understand the health effects of long- and short-term exposure to low levels of ambient air pollution. This report provides a high-level overview of statistical methods, data analysis, and key findings, as grouped into the following four areas: (1) Exposure assessment and data access; (2) Epidemiological studies of ambient exposures to air pollution at low levels; (3) Methodological contributions in causal inference; and (4) Open science research data platform. CONCLUSION: Our body of work, advanced by HEI, lends extensive evidence that short- and long-term exposure to PM2.5 and O3 is harmful to human health, increasing the risks of hospitalization and death, even at levels that are well below the National Ambient Air Quality Standards (NAAQS).

Clinical efficacy of sequential therapy with voriconazole on COPD patients in acute phase with pulmonary aspergillosis and effects on cytokines and pulmonary functions.

OBJECTIVE: To explore the clinical efficacy of sequential therapy with voriconazole on chronic obstructive pulmonary disease (COPD) patients in acute phase with pulmonary aspergillosis and its effects on cytokines and pulmonary functions. PATIENTS AND METHODS: A total of 110 COPD patients in acute phase with pulmonary aspergillosis who were admitted to the hospital between February 2015 and November 2016 were enrolled. We divided them randomly into two groups, i.e., the control group (n = 55) and the treatment group (n = 55). Patients in the control group took itraconazole capsules orally (200 mg/time, twice per day for three days followed by once per day). Patients in treatment group underwent sequential treatment with voriconazole through intravenous infusion at a dose of 5 mg/kg/time twice a day for 3 days followed by a dose of 4 mg/kg/time, twice a day for 8 days. Then, patients took voriconazole orally at a dose of 150 mL/time, twice a day for 6 days. Patients in two groups received the treatment for a total of 14 days. After treatment, we evaluated the levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and IL-8. The total lung capacity (TLC), diffusing capacity of the lung for carbon monoxide (DLco), and arterial oxygen saturation (SaO2), were measured as well. RESULTS: The total effectiveness rates of the treatment group and the control group were 83.63% and 61.82%. The differences had statistical significance (p < 0.01). After treatment, the incidence of chest pain, cough, sputum-coughing, hemoptysis, cyanosis, and dyspnea in the treatment group was significantly fewer than that in the control group (p < 0.05). TCL, DLco, and SaO2 in the two groups were significantly ameliorated by treatment (p < 0.05). The amelioration in the treatment group was more prominent than that in the control group (p < 0.05). The levels of TNF-α, IL-8, and IL-6 in the two groups were decreased dramatically by the treatments. The decrease in the treatment group was significantly lower than those in the control group (p < 0.05). Occurrence of adverse reactions in treatment group and control group were 8.33% and 6.25%, respectively; (p > 0.05). CONCLUSIONS: Sequential therapy with voriconazole exhibits promising clinical efficacy in COPD patients in acute phase with pulmonary aspergillosis. The treatment ameliorated the clinical symptoms and vital signs of patients significantly. It also improved the pulmonary functions and inhibited the inflammatory responses of patients with evident clinical efficacy.

The expression of HDAC7 in cancerous gastric tissues is positively associated with distant metastasis and poor patient prognosis

Purpose. To characterize the expression patterns of HDAC7 in patients with gastric cancer and evaluate the prognostic value of HDAC7 in gastric cancer. Methods. The expression of histone deacetylase 7 (HDAC7) was detected in paraffin-embedded gastric cancer samples from 86 patients by immunohistochemistry, and the differences in the expression of HDAC7 between cancerous and corresponding adjacent noncancerous tissues were compared using the Wilcoxon matched-pairs signed rank test. The correlation between HDAC7 expression and Ki-67 expression or clinicopathologic characteristics was evaluated using a Spearman rank correlation test. Prognostic outcomes that correlated with HDAC7 were examined using a Kaplan-Meier analysis and Cox proportional hazards model. Moreover, the effects of HDAC7 on the proliferation, migration and invasion of gastric cancer cells were investigated in vitro using human gastric carcinoma AGS cells. Results. We found that HDAC7 was downregulated in cancerous gastric tissues (P = 0.0019). However, the expression of HDAC7 in cancerous gastric tissues positively correlated with Ki-67 expression (P = 0.0325) and distant metastasis (P = 0.020). Moreover, overall survival was shorter for patients expressing higher levels of HDAC7 in cancerous tissues (P = 0.042). Mechanistically, the disruption of the HDAC7 gene attenuated the capacity of cell growth, migration and invasion and induced G0/G1 arrest in AGS cells. Conversely, forced over expression of HDAC7 promoted cell growth, migration and invasion and G1/S transition in AGS cells. Conclusions. These results indicate that high HDAC7 expression in cancerous gastric tissues correlates with distant metastasis and predicts a poor prognosis for patients with gastric cancer (AU)

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The expression of HDAC7 in cancerous gastric tissues is positively associated with distant metastasis and poor patient prognosis.

PURPOSE: To characterize the expression patterns of HDAC7 in patients with gastric cancer and evaluate the prognostic value of HDAC7 in gastric cancer. METHODS: The expression of histone deacetylase 7 (HDAC7) was detected in paraffin-embedded gastric cancer samples from 86 patients by immunohistochemistry, and the differences in the expression of HDAC7 between cancerous and corresponding adjacent noncancerous tissues were compared using the Wilcoxon matched-pairs signed rank test. The correlation between HDAC7 expression and Ki-67 expression or clinicopathologic characteristics was evaluated using a Spearman rank correlation test. Prognostic outcomes that correlated with HDAC7 were examined using a Kaplan-Meier analysis and Cox proportional hazards model. Moreover, the effects of HDAC7 on the proliferation, migration and invasion of gastric cancer cells were investigated in vitro using human gastric carcinoma AGS cells. RESULTS: We found that HDAC7 was downregulated in cancerous gastric tissues (P = 0.0019). However, the expression of HDAC7 in cancerous gastric tissues positively correlated with Ki-67 expression (P = 0.0325) and distant metastasis (P = 0.020). Moreover, overall survival was shorter for patients expressing higher levels of HDAC7 in cancerous tissues (P = 0.042). Mechanistically, the disruption of the HDAC7 gene attenuated the capacity of cell growth, migration and invasion and induced G0/G1 arrest in AGS cells. Conversely, forced ovperexpression of HDAC7 promoted cell growth, migration and invasion and G1/S transition in AGS cells. CONCLUSIONS: These results indicate that high HDAC7 expression in cancerous gastric tissues correlates with distant metastasis and predicts a poor prognosis for patients with gastric cancer.

Prediction for relapse and prognosis of newly diagnosed epilepsy.

OBJECTIVE: The objective of this study was to investigate the timing of therapy initiation and other clinical factors as potential predictors for relapse and prognosis of epilepsy, based on hospital-based prospective observational data in China. METHODS: One hundred and seventy-one newly diagnosed patients with one or more seizures were recruited and followed for at least 2 years. Kaplan-Meier survival analysis was used for calculating recurrence and remission rates. Univariate and multivariate analyses for risk factors were performed using Cox proportional hazards model. RESULTS: Among the 171 patients analyzed, more patients had partial (54.4%) than generalized seizures (45.6%). The range of patients' age was 6-70 years, but 70% were under 16 years of age. Multiple seizure types (HR = 2.01; 95% CI, 1.31-3.10), epileptiform electroencephalogram (EEG) abnormality (HR = 1.95; 95% CI, 1.09-3.49), and >1 seizure monthly before treatment (HR = 2.74; 95% CI, 1.69-4.51) were predictors of seizure recurrence. The best negative predictors of remission were as follows: relapse (HR = 0.13; 95% CI, 0.07-0.23) and epileptiform EEG within 1 year of treatment (HR = 0.61; 95% CI, 0.39-0.97). Delayed treatment after three or more seizures did not significantly increase the risk of recurrence (P = 0.70) or remission (P = 0.31) compared with early treatment after one or two seizures. CONCLUSIONS: Multiple seizure types, epileptiform EEG abnormality, and >1 seizure monthly before treatment predict seizure recurrence. Relapse and epileptiform EEG within 1 year of treatment predict adverse seizure outcome. Early treatment does not affect relapse or prognosis.

Immunization against hepatitis B virus by mucosal administration of antigen-antibody complexes.

Antigen-antibody complexes have been shown to enhance immune responses against several antigens given by parenteral immunization. Herein, we have evaluated the potential of administering such immunostimulatory complexes by a mucosal route. Hepatitis B surface antigen (HBsAg) complexed with antibodies against HBsAg (anti-HBs) (HBsAg/Ab) was administered to BALB/c mice by intranasal inhalation. HBsAg by itself did not induce immune responses, whereas with HBsAg/Ab complexes, both systemic and mucosal immune responses were observed and these could be modulated by adjuvants. With HBsAg/Ab (1 or 10 microg), anti-HBs antibodies induced were predominantly of the IgG1 isotype (Th2-like). In contrast, anti-HBs induced by HBsAg/Ab plus cholera toxin (CT) or oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs (CpG) (1 microg each) were predominantly IgG2a (Th1-like). Results from this study indicate that HBsAg/Ab complexes can induce strong humoral immune responses when delivered by a noninvasive route, whether used alone or in combination with other mucosal adjuvants.

Major differences between WHV and HBV in the regulation of transcription.

Studies were carried out to further characterize enhancer and promoter elements on the woodchuck hepatitis virus (WHV) genome. We were able to confirm the existence of WHV promoters analogous to the major promoters of the related human hepatitis B virus (HBV) and of an enhancer analogous to the recently described WHV E2 element (Ueda, K., Wei, Y., and Ganem, D., Virology 217, 413, 1996). However, we were unable to identity an enhancer analogous to the E1 element of (HBV), despite the fact that these two viruses share a high degree of sequence homology and genetic organization. Some factor binding sites in the E1 region appeared to be conserved between the two viruses and may be required for the activity of the overlapping X gene promoter of WHV. Others did not appear to be essential for WHV X gene promoter activity, and their functional activity, if any, was not revealed. Our failure to detect a functional enhancer element in the region of WHV homologous to the HBV E1 enhancer may indicate that (i) fundamental differences exist in transcriptional regulation of the small circular genomes of WHV and HBV; (ii) WHV contains an E1 element which is functional in the context of the intact viral genome, but which is unable to function in the context of the various expression constructs used in our experiments; or (iii) correct regulation of WHV transcription via an E1 element is dependent upon transcription factors which are not expressed in the liver-specific cell lines used in our experiments.

Susceptibility to duck hepatitis B virus infection is associated with the presence of cell surface receptor sites that efficiently bind viral particles.

To test the hypothesis that susceptibility of hepatocytes to duck hepatitis B virus (DHBV) infection requires cell surface receptors that bind the virus in a specific manner, we developed an assay for the binding of DHBV particles to monolayers of intact cells, using radiolabeled immunoglobulin G specific for DHBV envelope protein. Both noninfectious DHBV surface antigen particles and infectious virions bound to a susceptible fraction (approximately 60%) of Pekin duck hepatocytes. In contrast, binding did not occur to cells that were not susceptible to DHBV infection, including Pekin duck fibroblasts and chicken hepatocytes, and binding to Muscovy duck hepatocytes, which are only weakly susceptible (approximately 1% of cells) to DHBV infection, was virtually undetectable. Within a monolayer, individual Pekin duck hepatocytes appeared to differ markedly in the capacity to bind DHBV, which may explain difficulties that have been encountered in infecting 100% of cells in culture. We have also found that the loss of susceptibility to infection with DHBV that occurs when Pekin duck hepatocytes are maintained for more than a few days in culture correlates with a decline in the number of cells that bind virus particles efficiently. All of these results support the interpretation that the binding event detected by our assay is associated with the interaction between DHBV and specific cell surface receptors that are required for initiation of infection. Our assay may facilitate isolation and identification of hepatocyte receptors for this virus.

[Effect of a decoction of six ingredients with rehmannia on the periodontal tissues of animals with kidney diseases].

In this paper, Kidney Yin and Yang deficiency animal models were made by the medicine (hydrocortisone, thyroxin). At the same time the occlusal trauma was accompanied. It was caused by means of corprophagy (microorganism) fed and artificial damage. The authors observed the injuries and effects of the local and systemic factors caused on the periodontal tissues of rats. From the experiment the authors found the injuries of the periodontal tissues in Kidney deficiency models were severer than those of the models without Kidney deficiency. The results showed that the function of the traditional medicine was a matter of protection, regeneration and repairing to the periodontal tissues of Kidney Yin deficiency models. In addition, the weights and activities of the experimental animals fed by Decoction of Six Ingredients with Rehmannia were higher than those without taking the traditional medicine.

[The interferon system in ducks infected with viral hepatitis B]. / Sistema interferon u utok pri virusnom gepatite B.

The duck peripheral blood lymphocytes and spleen cells were shown to be relatively resistant to interferon induction by viral (NDV) and nonviral (dsRNA) inducers as well as to Con A induction of gamma-interferon. The concentration of the inducers had to be increased 4-5-fold to induce interferon production. Charry valley ducks produced more alpha-interferon than Peking ducks. The level of interferon production induced by NDV and dsRNA (Ridostin) was similar in DHBV-positive Peking ducks and in the control group, but in the infected Charry valley ducks interferon production was lower than in the controls (224 to 180 U/0.1 ml in NDV-induced and from 192 to 43.3 U/0.1 ml in dsRNA-induced). Early bursectomy brought down the interferon production in non-infected ducts, but in DHBV-positive bursectomized ducks (Y) the level of interferon was higher than in the control bursectomized ducks.