Factors Associated With Prolonged Viral Shedding in Patients With Avian Influenza A(H7N9) Virus Infection.

Background: Data are limited on the impact of neuraminidase inhibitor (NAI) treatment on avian influenza A(H7N9) virus RNA shedding. Methods: In this multicenter, retrospective study, data were collected from adults hospitalized with A(H7N9) infection during 2013-2017 in China. We compared clinical features and A(H7N9) shedding among patients with different NAI doses and combination therapies and evaluated factors associated with A(H7N9) shedding, using Cox proportional hazards regression. Results: Among 478 patients, the median age was 56 years, 71% were male, and 37% died. The median time from illness onset to NAI treatment initiation was 8 days (interquartile range [IQR], 6-10 days), and the median duration of A(H7N9) RNA detection from onset was 15.5 days (IQR, 12-20 days). A(H7N9) RNA shedding was shorter in survivors than in patients who died (P < .001). Corticosteroid administration (hazard ratio [HR], 0.62 [95% confidence interval {CI}, .50-.77]) and delayed NAI treatment (HR, 0.90 [95% CI, .91-.96]) were independent risk factors for prolonged A(H7N9) shedding. There was no significant difference in A(H7N9) shedding duration between NAI combination treatment and monotherapy (P = .65) or between standard-dose and double-dose oseltamivir treatment (P = .70). Conclusions: Corticosteroid therapy and delayed NAI treatment were associated with prolonged A(H7N9) RNA shedding. NAI combination therapy and double-dose oseltamivir treatment were not associated with a reduced A(H7N9) shedding duration as compared to standard-dose oseltamivir.

Preparation of Graphene Oxide-Based Supramolecular Hybrid Nanohydrogel Through Host-Guest Interaction and Its Application in Drug Delivery.

Graphene oxide (GO) has attracted a wide attention for its excellent mechanical, thermal properties and unique two-dimensional structure. In this work, A new GO-based supramolecular hybrid nanohydrogel was prepared, in which GO as the cross-links was incorporated into the above hydrogel through non-covalent functionalization to enhance the mechanical properties and control morphology. A 1-pyrenebutyric acid (Py) modified low-molecular weight (MW) mPEG was firstly synthesized via a simple esterification reaction. Then, low-MW mPEG functionalized GO (GO-Py-PEG) was obtained due to the strong π-π stacking interaction between Py and GO. The combination of the host-guest interaction between mPEG and -CD and addition of GO lastly leaded to the formation of supramolecular hybrid nanohydrogel. Various techniques including UV-vis spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA) and transmission electron microscopy (TEM) were used to thoroughly characterize the hybrid hydrogel. More interestingly, the results of rheology studies and scanning electron microscopy (SEM) revealed that the mechanical strength and morphology of hybrid hydrogel was improved by the incorporation of GO. Meanwhile, doxorubicin hydrochloride (DOX) as a model drug was loaded into hybrid hydrogel, and the in vitro released behavior was studied under different pH values. The results showed that the formed hybrid hydrogel could release DOX over 50 h in a sustained manner. In addition, in vitro and in vivo experiments, GO-Py-PEG-α-CD@DOX hydrogel (hydrogel@DOX) dramatically shows the inhibition of tumor cell proliferation and tumor growth. At the same time, HE staining results show hydrogel@DOX can significantly reduce the side effects of DOX. We believe that the development of such hybrid hydrogels will provide important potential for medical applications.

The genetic characteristics of congenital hypothyroidism in China by comprehensive screening of 21 candidate genes.

OBJECTIVE: Congenital hypothyroidism (CH), the most common neonatal metabolic disorder, is characterized by impaired neurodevelopment. Although several candidate genes have been associated with CH, comprehensive screening of causative genes has been limited. DESIGN AND METHODS: One hundred ten patients with primary CH were recruited in this study. All exons and exon-intron boundaries of 21 candidate genes for CH were analyzed by next-generation sequencing. And the inheritance pattern of causative genes was analyzed by the study of family pedigrees. RESULTS: Our results showed that 57 patients (51.82%) carried biallelic mutations (containing compound heterozygous mutations and homozygous mutations) in six genes (DUOX2, DUOXA2, DUOXA1, TG, TPO and TSHR) involved in thyroid hormone synthesis. Autosomal recessive inheritance of CH caused by mutations in DUOX2, DUOXA2, TG and TPO was confirmed by analysis of 22 family pedigrees. Notably, eight mutations in four genes (FOXE1, NKX2-1, PAX8 and HHEX) that lead to thyroid dysgenesis were identified in eight probands. These mutations were heterozygous in all cases and hypothyroidism was not observed in parents of these probands. CONCLUSIONS: Most cases of congenital hypothyroidism in China were caused by thyroid dyshormonogenesis rather than thyroid dysgenesis. This study identified previously reported causative genes for 57/110 Chinese patients and revealed DUOX2 was the most frequently mutated gene in these patients. Our study expanded the mutation spectrum of CH in Chinese patients, which was significantly different from Western countries.