Background: COVID-19 is an extremely severe infectious disease. However, few studies have focused on the epidemiological and clinical characteristics of pediatric COVID-19. This study conducted a retrospective review of the epidemiological and clinical features of COVID-19 in children. Methods: A retrospective study was conducted on children with a definite diagnosis of COVID-19 in mainland China using the web crawler technique to collect anonymous COVID-19 updates published by local health authorities. Results: Three hundred forty-one children aged 4 days to 14 years with a median age of 7 years were included. Sixty-six percent of pediatric patients were infected via family members with COVID-19. The median incubation period was 9 days (interquartile range, 6 to 13). Asymptomatic cases accounted for 5.9%, of which 30% had abnormal chest radiologic findings. A majority of pediatric COVID-19 cases showed mild to moderate clinical features, and only a few developed severe or critical diseases (0.6% and 0.3%, respectively). Fever (77.9%) and cough (32.4%) were the predominant presenting symptoms of pediatric COVID-19. The pediatric patients had fewer underlying diseases and complications than adults. The treatment modalities for pediatric COVID-19 patients were not as complex as those of adult COVID-19 patients. The overall prognosis of pediatric COVID-19 was benign with a decent recovery. The median time from onset to cure was 16 days (interquartile range, 13 to 21). Conclusions: Compared to adults, COVID-19 in children has distinct features of epidemiology and clinical manifestations. The findings from this study might help to guide the development of measures to prevent and treat this ongoing global pandemic. Trial registration: Chinese Clinical Trial Registry (chictr.org.cn) identifier: ChiCTR2000030464.

Excessive oxidative stress in cancer cells can induce cancer cell death. Anticancer activity and drug resistance of chemotherapy are closely related to the redox state of tumor cells. Herein, five lipophilic Pt(IV) prodrugs were synthesized on the basis of the most widely used anticancer drug cisplatin, whose anticancer efficacy and drug resistance are closely related to the intracellular redox state. Subsequently, a series of cisplatin-sensitive and drug-resistant cell lines as well as three patient-derived primary ovarian cancer cells have been selected to screen those prodrugs. To verify if the disruption of redox balance can be combined with these Pt(IV) prodrugs, we then synthesized a polymer with a diselenium bond in the main chain for encapsulating the most effective prodrug to form nanoparticles (NP(Se)s). NP(Se)s can efficiently break the redox balance via simultaneously depleting GSH and augmenting ROS, thereby achieving a synergistic effect with cisplatin. In addition, genome-wide analysis via RNA-seq was employed to provide a comprehensive understanding of the changes in transcriptome and the alterations in redox-related pathways in cells treated with NP(Se)s and cisplatin. Thereafter, patient-derived xenograft models of hepatic carcinoma (PDX HCC ) and multidrugresistant lung cancer (PDX MDR ) were established to evaluate the therapeutic effect of NP(Se)s, and a significant antitumor effect was achieved on both models with NP(Se)s. Overall, this study provides a promising strategy to break the redox balance for maximizing the efficacy of platinum-based cancer therapy.

Cellular recognition of microbial DNA is an evolutionarily conserved mechanism by which the innate immune system detects pathogens. Cyclic GMP-AMP synthase (cGAS) and its downstream effector, stimulator of interferon genes (STING), are involved in mediating fundamental innate antimicrobial immunity by promoting the release of type I interferons (IFNs) and other inflammatory cytokines. Accumulating evidence suggests that the activation of the cGAS-STING axis is critical for antitumor immunity. The downstream cytokines regulated by cGAS-STING, especially type I IFNs, serve as bridges connecting innate immunity with adaptive immunity. Accordingly, a growing number of studies have focused on the synthesis and screening of STING pathway agonists. However, chronic STING activation may lead to a protumor phenotype in certain malignancies. Hence, the cGAS-STING signaling pathway must be orchestrated properly when STING agonists are used alone or in combination. In this review, we discuss the dichotomous roles of the cGAS-STING pathway in tumor development and the latest advances in the use of STING agonists.

Background: Despite great advances in the diagnosis and treatment of non-small cell lung cancer (NSCLC), early diagnosis remains a challenge because patients usually have advanced lung cancer at the time they are diagnosed. The limited efficacy of conventional chemotherapy is another major problem in the treatment of NSCLC. Based on a published set of sequencing data, we find that hsa_circ_0001946 is a circRNA molecule with a significantly different expression level in three cell lines (human normal lung fibroblasts cell line MRC-5, human NSCLC cell line A549, cisplatin-resistant cell line A549/DDP), NSCLC tissues and paired adjacent normal tissues. We believe that hsa_circ_0001946 may have an effect on the progression of NSCLC and its sensitivity to cisplatin. Methods: We focused on investigating the circular RNA, hsa_circ_0001946. RNA interference of hsa_circ_0001946 was carried out in A549 cell lines to determine the effect of reduced hsa_circ_0001946 expression on lung cancer progression and was analyzed by Cell Counting Kit-8 (CCK-8), 5-ethynyl-20-deoxyuridine, clone formation, Hoechst, wound healing, and transwell assays. The nucleotide excision repair (NER) signaling pathway was identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Moreover, cellular responses to cisplatin were assessed through CCK-8 and flow cytometry assays. Western blot analysis and host-cell reactivation assay were used to determine the effect of hsa_circ_0001946 on NER signaling. Results: In this study, we found that the reduced expression of hsa_circ_0001946 promoted the viability, proliferation, migration, and invasion of NSCLC cells, as well as inhibition of cell apoptosis. Our findings suggest that hsa_circ_0001946 can affect the sensitivity of NSCLC cells to the chemotherapeutic drug cisplatin via modulation of the NER signaling pathway. Conclusions: Our study demonstrated the role of hsa_circ_0001946 in NSCLC pathogenesis, development, and chemosensitivity, and suggests that hsa_circ_0001946 may serve as a novel biomarker for the diagnosis and prediction of platinum-based chemosensitivity in patients with NSCLC.

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Platinum-based chemotherapy agents are widely used in the treatment of various solid malignancies. However, their efficacy is limited by drug resistance. Recent studies suggest that copper efflux transporters, which are encoded by ATP7A and ATP7B, play an important role in platinum drug resistance. Over-expressions of ATP7A and ATP7B are observed in multiple cancers. Moreover, their expressions are associated with cancer prognosis and treatment outcomes of platinum-based chemotherapy. In our review, we highlight the roles of ATP7A/7B in platinum drug resistance and cancer progression. We also discuss the possible mechanisms of platinum drug resistance mediated by ATP7A/7B and provide novel strategies for overcoming resistance. This review may be helpful for understanding the roles of ATP7A and ATP7B in platinum drug resistance. © 2018 IUBMB Life, 70(3):183-191, 2018.

Polygonum multiflorum (PM) is a well‐known Chinese herbal medicine that has been reported to induce inflammation‐associated idiosyncratic liver injury. This study aimed to identify the genetic basis of susceptibility to PM‐drug‐induced liver injury (PM‐DILI) and to develop biological markers for predicting the risk of PM‐DILI in humans. The major histocompatibility complex (MHC) regions of 11 patients with PM‐DILI were sequenced, and all human leukocyte antigen (HLA)–type frequencies were compared to the Han‐MHC database. An independent replication study that included 15 patients with PM‐DILI, 33 patients with other DILI, and 99 population controls was performed to validate the candidate allele by HLA‐B PCR sequence‐based typing. A prospective cohort study that included 72 outpatients receiving PM for 4 weeks was designed to determine the influence of the risk allele on PM‐DILI. In the pilot study, the frequency of HLA‐B*35:01 was 45.4% in PM‐DILI patients compared with 2.7% in the Han Chinese population (odds ratio [OR], 30.4; 95% confidence interval [CI], 11.7‐77.8; P = 1.9 × 10−10). In the independent replication study and combined analyses, a logistic regression model confirmed that HLA‐B*35:01 is a high‐risk allele of PM‐DILI (PM‐DILI versus other DILI, OR, 86.5; 95% CI, 14.2‐527.8, P = 1.0 × 10−6; and PM‐DILI versus population controls, OR, 143.9; 95% CI, 30.1‐687.5, P = 4.8 × 10−10). In the prospective cohort study, an asymptomatic increase in transaminase levels was diagnosed in 6 patients, representing a significantly higher incidence (relative risk, 8.0; 95% CI, 1.9‐33.2; P < 0.02) in the HLA‐B*35:01 carriers (37.5%) than in the noncarriers (4.7%). Conclusion: The HLA‐B*35:01 allele is a genetic risk factor for PM‐DILI and a potential biomarker for predicting PM‐DILI in humans.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Rosiglitazone is able to increase serum adiponectin levels significantly in Type 2 diabetic patients. • The role of genetic factors that determine the marked interindividual variability in glucose‐lowering efficacy of rosiglitazone in Chinese patients is not known. • The current study was designed to evaluate the impact of the adiponectin common allele 45T/G and −11377C/G polymorphisms on the response to rosiglitazone monotherapy in Chinese patients with Type 2 diabetes (T2D). WHAT THIS STUDY ADDS • The genetic polymorphisms of adiponectin alleles 45T/G and −11377C/G as well as their common diplotypes are significantly associated with an attenuated fasting plasma glucose, postprandial plasma glucose and homeostasis model assessment for insulin resistance as well as an enhanced adiponectin concentration in Chinese patients with T2D after rosiglitazone treatment. AIMS The aim of the present study was to evaluate the impact of adiponectin allele T45G and C‐11377G genetic polymorphisms on efficacy of rosiglitazone in Chinese patients with type 2 diabetes (T2D). METHODS Patients with T2D (n = 255) and 120 healthy volunteers were enrolled to identify 45T/G and –11377C/G genotypes by polymerase chain reaction‐restriction fragment length polymorphism assay. Forty‐two T2D patients with different 45T/G or –11377C/G genotypes received orally rosiglitazone as a single‐dose therapy (4 mg day‐1 p.o.) for 12 weeks. Serum triglyceride, fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin, fasting serum insulin, postprandial serum insulin, total cholesterol, homeostasis model assessment for insulin resistance (HOMA‐IR), low‐density lipoprotein‐cholesterol, high‐density lipoprotein‐cholesterol (HDL‐c) and adiponectin concentration were determined before and after rosiglitazone treatment. RESULTS We showed an attenuated rosiglitazone effect in patients with –11377CG+GG heterozygote genotype on FPG, PPG, HOMA‐IR compared with –11377CC homozygote genotype. However, we found an enhanced rosiglitazone effect on serum adiponectin concentration in patients with –11377CC homozygote genotype compared with –11377CG+GG heterozygote genotype (P = 0.000) and in patients with 45TG + GG heterozygote genotype compared with 45TT homozygote genotype (P = 0.018). Finally, our results showed that there was an enhanced effect in patients with –11377/45 CGTT diplotype compared with other discovered diplotypes on FPG (P = 0.001) and PPG (P = 0.003) after rosiglitazone treatment. CONCLUSIONS These data suggest that the adiponectin allele 45T/G and –11377C/G polymorphisms are significantly associated with the therapeutic efficacy of multiple‐dose rosiglitazone in Chinese patients with T2D.