Objective:To evaluate the expression level of hsa-miR-422a in hypertrophic scars and to identify the target genes of hsa-miR-422a along with their biological functions using bioinformatics approaches.Methods:From June 2020 to December 2020, tissue samples of 3 hypertrophic scar and 3 normal skin were collected from patients (3 males, 3 females, aged 20-42 years) in Department of Plastic and Reconstructive Surgery, Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine. Primary fibroblasts were isolated and cultured. Real-time quantitative PCR was performed to quantify the expression of hsa-miR-422a. To construct a ceRNA network, starbase and Target Scandata bases were utilized to predict genes as well as long noncoding RNAs (lncRNAs) that may sponge hsa-miR-422a. GO and KEGG pathway enrichment analyses were conducted on the target genes of hsa-miR-422a; protein-protein interaction (PPI) networks were constructed to identify the hub genes whose functions were predicted by functional enrichment analyses. The expression of hub genes was validated through real-time quantitative PCR in hypertrophic scars.Results:The expression of hsa-miR-422a was significantly lower in the hypertrophic scar tissue samples and fibroblasts compared to that in the normal skin ( P<0.05). 133 target genes as well as 1033 lncRNAs were predicted by starBase and TargetScandata bases and used to construct an hsa-miR-422a-centered ceRNA network. PPI networks of the target genes revealed 10 hub genes, including MAPK1, GRB2, and IGF1R, which were discovered to be related to protein serine/threonine/tyrosine kinase activity, ubiquitin protein ligase binding, fibroblast growth factor receptor signaling pathway, muscle cell proliferation, and many others; besides, they may be involved in FoxO, mTOR, Toll-like receptor, Ras, MAPK, PI3K-Akt signaling pathways and signaling pathways regulating pluripotency of stem cells. Three hub genes (MAPK1, GRB2, and IGF1R) were significantly upregulated in hypertrophic scars ( P<0.05). Conclusions:hsa-miR-422a is significantly downregulated in the hypertrophic scars and may target hub genes such as MAPK1 in ceRNA networks, ultimately modulating hypertrophic scar formation.

Humans ; Severe Acute Respiratory Syndrome ; diagnosis ; therapy

Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.