[The role of large-scale testing platform in the prevention and control of the COVID-19 pandemic: an empirical study based on a novel numerical model].

Objective: China adopted an unprecedented province-scale quarantine since January 23rd 2020, after the novel coronavirus (COVID-19) broke out in Wuhan in December 2019. Responding to the challenge of limited testing capacity, large-scale (>20 000 tests per day) standardized and fully-automated laboratory (Huo-Yan) was built as an ad-hoc measure. There is so far no empirical data or mathematical model to reveal the impact of the testing capacity improvement since quarantine. Methods: Based on the suspected case data released by the Health Commission of Hubei Province and the daily testing data of Huo-Yan Laboratory, the impact of detection capabilities on the realization of "clearing" and "clearing the day" of supected cases was simulated by establishing a novel non-linear and competitive compartments differential model. Results: Without the establishment of Huo-Yan, the suspected cases would increase by 47% to 33 700, the corresponding cost of quarantine would be doubled, the turning point of the increment of suspected cases and the achievement of "daily settlement" (all newly discovered suspected cases are diagnosed according to the nucleic acid testing result) would be delayed for a whole week and 11 days. If the Huo-Yan Laboratory could ran at its full capacity, the number of suspected cases could start to decrease at least a week earlier, the peak of suspected cases would be reduced by at least 44%, and the quarantine cost could be reduced by more than 72%. Ideally, if a daily testing capacity of 10 500 tests was achieved immediately after the Hubei lockdown, "daily settlement" for all suspected cases could be achieved. Conclusions: Large-scale, standardized clinical testing platform, with nucleic acid testing, high-throughput sequencing, and immunoprotein assessment capabilities, need to be implemented simultaneously in order to maximize the effect of quarantine and minimize the duration and cost of the quarantine. Such infrastructure, for both common times and emergencies, is of great significance for the early prevention and control of infectious diseases.

MiR-145 silencing promotes steroid-induced avascular necrosis of the femoral head repair via upregulating VEGF.

OBJECTIVE: To investigate the role of miR-145 silencing in the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), B-cell lymphoma-2 (Bcl-2), BCL2-Associated X(bax) and caspase-3 in avascular necrosis of femoral head (ANFH). MATERIALS AND METHODS: A total of 12 healthy wild-types (the control group) and 12 miR-145 knock-out (miR-145-/-) (the experimental group) adult New Zealand white rabbits were selected to construct ANFH model with a steroid. Four weeks later, immunohistochemistry, qRT-PCR and Western blot were performed to measure the VEGF, bFGF, Bcl-2, bax, caspase-3, ß-catenin as well as c-Myc expression. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining analysis was used to detect the apoptosis of bone cells in each group. RESULTS: Compared with the control group, the expression of VEGF, bFGF, Bcl-2, ß-catenin and c-Myc in the miR-145-/- group raised (p<0.05). Moreover, the expression level of bax and caspase-3 significantly decreased in the miR-145-/- group (p<0.05). TUNEL staining showed decreased apoptosis in the miR-145-/- group. CONCLUSIONS: MiR-145 silencing promotes bone repair of ANFH via upregulating VEGF, bFGF and inhibiting the bone cells apoptosis through Wnt/ß-catenin pathway.

Pathogenicity and distribution of highly pathogenic porcine reproductive and respiratory syndrome virus in pigs.

The pathogenesis of highly pathogenic porcine reproductive and respiratory syndrome virus (PRRSV) strain (HuN4) is poorly understood. Therefore, highly pathogenic PRRSV strain (HuN4) and its derivative strain (HuN4-F112) (obtained by propagation in MARC145 cells for 112 passages) were inoculated into a total of 48 PRRSV-sero-negative pigs (age: 4-5 weeks) by the intranasal route. Virological, pathological and in situ hybridization analyses were performed. The results exhibited that pigs infected with HuN4 showed a loss of appetite, decrease in body weight, raised body temperature and respiratory symptoms, along with interstitial pneumonia lesions. In the HuN4 group, multifocal interstitial pneumonia with macrophage infiltration was found in the lung. The lesions in the lymph node were characterized by collapsed follicles, depletion of germinal centres and reduction in lymphocytes. Perivascular cuffing and glial nodules were observed in the brains of some pigs. By comparison, the HuN4-F112 group had milder lesions. PRRSV was detected in macrophages, alveolar epithelial cells and vascular endothelial cells in the tonsil and lymph nodes. The PRRSV amounts in the pigs infected with HuN4 were 10(5) -10(9) copies/ml in the blood and 10(10) -10(11) copies/g in the lung tissues, whereas the virus amounts with HuN4-F112 were 10(2.15) -10(3.13) copies/ml in the blood and 10(3.0) -10(3.6) copies/g in the lung. Our results demonstrate that the PRRS HuN4 virus infects alveolar epithelial cells, macrophages and vascular endothelial cells causing diffuse alveolar damage and lymph node necrosis. Its higher pathogenicity compared with HuN4-F112 virus may be explained in part by higher replication rate in the previously mentioned organs.

Highly virulent porcine reproductive and respiratory syndrome virus emerged in China.

A highly pathogenic pig disease emerged in China in 2006, which was characterized by prolonged high fever, red discoloration of the body, and blue ears associated with high mortality. Porcine reproductive and respiratory syndrome virus (PRRSV) was isolated as the single most prominent virus in the samples collected from affected pigs. The full-length genomic sequence of the virus revealed two distinct deletions in the non-structural protein 2 (NSP2) in comparison to all previously reported North American genotype PRRSV. Through extensive surveys in 14 different provinces, 56 additional PRRSV isolates were obtained from affected farms. All of the isolates were found to contain identical deletions in NSP2. To confirm the etiology, eight 60-day-old PRRSV-free pigs were divided into two groups and the test group was intranasally infected at a titer of 2 x 10(5.0) tissue culture infectious dose 50 per pig. The inoculated pigs all died at 7, 8, 12, 16, or 21 days post-inoculation with their clinical and pathological findings similar to those in the field. The viruses recovered from dead pigs were identical to the inoculated virus in NSP2 and GP5 genes. Our study shows that the recently emerged PRRSV in China is characterized by two discontiguous deletions in NSP2 and is the cause for the current epizootics in China.

Effect of oral beta interferon on subsequent immune responsiveness.

Oral administration of myelin antigens reduces the incidence and severity of EAE in rat and mouse models and decreases the frequency of MBP-reactive cells and the frequency of attacks in some patients with multiple sclerosis. Low-dose oral tolerance has been shown to be mediated by Th2-type regulatory cells that secrete TGFbeta and IL-4/IL-10. Adjuvants and cytokines may modulate oral tolerance. The addition of betaIFN to the experimental therapy regimen, either orally or by intraperitoneal injection, has been shown to enhance the suppressive effects of oral myelin antigens when either are fed the suboptimal dosing regimen to suppress EAE. The current studies were conducted to elucidate the mechanism of the observed in vivo synergy of betaIFN and antigen feeding. Analysis of the in vitro proliferative response and cytokine production by lymphocytes from fed animals in response to specific antigen in culture shows that the synergistic effect may be related to both independent suppression of the immune response by oral betaIFN and enhanced production of TGFbeta and IL-4/IL-10. There was an unexpected increase in the production of gammaIFN by lymphocytes in vitro after three doses of oral betaIFN in vivo. These observations have important implications for the use of cytokines to modulate oral tolerance.