To explore the clinical value of immune-inflammatory markers to assess the severity of coronavirus disease 2019 . Methods: 127 consecutive hospitalized patients with confirmed COVID-19 were enrolled in this study, and classified into non-severe and severe groups. Demographics, symptoms, underlying diseases and laboratory data were collected and assessed for predictive value. Results: Of 127 COVID-19 patients, 16 cases (12.60%) were classified into the severe group. High level of interleukin-6 (IL-6), C-reaction protein (CRP) and hypertension were independent risk factors for the severity of COVID-19. The risk model based on IL-6, CRP and hypertension had the highest area under the receiver operator characteristic curve (AUROC). Additionally, the baseline IL-6 was positively correlated with other immune-inflammatory parameters and the dynamic change of IL-6 in the severe cases were parallel to the amelioration of the disease. Conclusion: Our study showed that high level of IL-6, CRP and hypertension were independent risk factors for assessing the severity of COVID-19. The risk model established upon IL-6, CRP and hypertension had the highest predictability in this study. Besides, IL-6 played a pivotal role in the severity of COVID-19 and had a potential value for monitoring the process of severe cases.

Lampreys are extant representatives of agnathans. Descriptions of lamprey development, physiology and genome have provided critical insights into early evolution of vertebrate traits. However, efficient means for genetic manipulation in agnathan species have not been developed, hindering functional studies of genes in these important Evo-Devo models. Here, we report a CRISPR/Cas system optimized for lamprey genomes and use it to disrupt genomic loci in the Northeast Chinese lamprey (Lethenteron morii) with efficiencies ranging between 84~99%. The frequencies of indels observed in the target loci of golden (gol), kctd10, wee1, soxe2, and wnt7b, estimated from direct sequencing of genomic DNA samples of injected lamprey larvae, were 68/69, 47/56, 38/39, 36/37 and 36/42, respectively. These indels often occurred in both alleles. In the CRISPR/Cas9 treatment for gol or kctd10, 38.6% or 85.3% of the targeted larvae had the respective recessive null-like phenotypes, further confirming the disruption of both loci. The kctd10 gRNA, designed against an essential functional region of Kctd10, resulted in null-like phenotypes and in-frame mutations in alleles. We suggest that the CRISPR/Cas-based approach has the potential for efficient genetic perturbation in organisms less amenable to germ line transmission based approaches.

Background The effect of red blood cell (RBC) transfusion on retinopathy of prematurity (ROP) is difficult to establish, because ROP may also be influenced by other factors. Therefore, we carried out a systematic review and meta-analysis to explore the relationship between RBC transfusion and the development of ROP. Methods The PubMed, Embase, Cochrane Library and Web of Science databases were searched from their inception to September 1, 2019. Observational studies that reported the relationship between RBC transfusion and ROP after adjusting for other potential risk factors were included. The combined result was analyzed by a random effect model. Heterogeneity and publication bias were tested, and sensitivity analysis was performed. Results Of the 2628 identified records, 18 studies including 15072 preterm infants and 5620 cases of ROP were included. A random effect model was used and revealed that RBC transfusion was significantly associated with ROP (pooled OR = 1.50, 95% CI: 1.27-1.76), with moderate heterogeneity among the included studies (I 2 = 44.2%). Subgroup analysis indicated that RBC transfusion was more closely related to ROP in the group with a gestational age (GA) �32 weeks (OR = 1.77, 95% CI: 1.29-2.43) but not in the groups with a GA �34 weeks (OR = 1.36, 95% CI: 0.85-2.18) or a GA <37 weeks (OR = 1.25, 95% CI: 0.86-1.82). No obvious publication bias was found based on the funnel plot and Egger's test. Removing any single study did not significantly alter the combined result in the sensitivity analysis.

Background To explore the clinical significance of serum angiotensin-converting enzyme (ACE) activity in coronavirus disease 2019 (COVID-19). Methods In this retrospective study, a total of 136 consecutive patients with confirmed COVID-19 were recruited. Demographic and clinical data were recorded. The serum ACE activity was measured at baseline and during the recovery phase, and its relationship with clinical condition was analyzed. Results Of the 136 patients with confirmed COVID-19, the 16 severe patients were older and had a higher body mass index (BMI) and proportion of hypertension than the 120 nonsevere patients. In comparison to those of normal controls, the baseline serum ACE activities of subjects in the severe group and nonsevere group were decreased, with the lowest level in the severe group. However, the serum ACE activity increased in the recovery phase, and there were no significant differences among the severe group, nonsevere group and normal control group. Conclusion Serum ACE activity could be used as a marker to reflect the clinical condition of COVID-19 since low activity was associated with the severity of COVID-19 at baseline, and the activity increased with the remission of the disease.

Background Non-typhoidal Salmonella (NTS), a common cause of diarrheal enterocolitis, may also cause severe invasive diseases. Limited information on NTS infections in children is available in China. Methods We performed a retrospective study of children admitted to the Ningbo Women and Children's Hospital with culture-confirmed NTS infections between January 2012 and December 2019. Clinical and microbiological information were collected. We compared demographic, clinical and antibiotic resistance variables of invasive NTS (iNTS) infections and non-invasive NTS (non-iNTS) infections, and explored associations between hospitalizations for pediatric NTS infections and temperature and rainfall. Results A total of 166 pediatric hospitalizations due to NTS infection were identified during the 8year study period. Most of the 166 children were <5 years old (93.4%). The primary serotype was Salmonella Typhimurium (62.6%). Of 166 children with NTS infections, 11 had invasive infection. Compared to 155 children with non-iNTS infections, we found that iNTS infections were more likely to occur in infants �6 months or children with an underlying medical condition of leukemia at admission, but iNTS infections less often presented with a symptom of diarrhea (P <0.05 in all cases). The resistance rates of non-iNTS isolates to ceftazidime, ceftriaxone, cefepime, and aztreonam were significantly higher than those of iNTS isolates (P <0.05 in all cases). In addition, compared with iNTS isolates, non-iNTS isolates were significantly associated with resistance to �4 CLSI (Clinical and Laboratory Standard Institute) classes (P = 0.041, OR: 0.089, 95%

Myostatin (MSTN), associated with the “double muscling” phenotype, affects muscle growth and fat deposition in animals, whereas how MSTN affects adipogenesis remains to be discovered. Here we show that MSTN can act through the MEF2C/miR222/SCD5 cascade to regulate fatty acid metabolism. We generated MSTN-knockout (KO) cloned Meishan pigs, which exhibits typical double muscling trait. We then sequenced transcriptome of subcutaneous fat tissues of wild-type (WT) and MSTN-KO pigs, and intersected the differentially expressed mRNAs and miRNAs to predict that stearoyl-CoA desaturase 5 (SCD5) is targeted by miR222. Transcription factor binding prediction showed that myogenic transcription factor 2C (MEF2C) potentially binds to the miR222 promoter. We hypothesized that MSTN-KO upregulates MEF2C and consequently increases the miR222 expression, which in turn targets SCD5 to suppress its translation. Biochemical, molecular and cellular experiments verified the existence of the cascade. This novel molecular pathway sheds light on new targets for genetic improvements in pigs.

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Background The viral persistence in patients with Coronavirus Disease 2019 (COVID-19) remains to be investigated. Methods We investigated the viral loads, therapies, clinical features, and immune responses in a 70-year patient tested positive for SARS-CoV-2 for 3 months. Findings The patient exhibited the highest prevalence of abnormal indices of clinical features and immune responses at the first admission, including fever (38.3 ℃), decreased lymphocytes (0.83 × 10 9 /L) and serum potassium (3.1 mmol/L), as well as elevated serum creatinine (115 µmol/L), urea (8.6 mmol/L), and C-reactive protein (80 mg/L). By contrast, at the second and the third admission, these indices were all normal. Through three admissions, IL-2 increased from 0.14 pg/mL, 0.69 pg/ mL, to 0.91 pg/mL, while IL-6 decreased from 11.78 pg/mL, 1.52 pg/mL, to 0.69 pg/mL, so did IL-10 from 5.13 pg/mL, 1.85 pg/mL, to 1.75 pg/mL. The steady declining trend was also found in TNF-α (1.49, 1.15, and 0.85 pg/mL) and IFN-γ (0.64, 0.42, and 0.27 pg/mL). The threshold cycle values of RT-PCR were 26.1, 30.5, and 23.5 for ORFlab gene, and 26.2, 30.6, and 22.7 for N gene, showing the patient had higher viral loads at the first and the third admission than during the middle term of the disease. The patient also showed substantially improved acute exudative lesions on the chest CT scanning images. Conclusions The patient displayed declining immune responses in spite of the viral shedding for 3 months. We inferred the declining immune responses might result from the segregation of the virus from the immune system.