Annals of Translational Medicine

ObjectiveTo investigate the regulatory mechanism of miRNA-124 in tumor immune regulation of cervical cancer. MethodsPeripheral blood samples of cervical cancer patients and transient infection controls were collected to extract exosomal miR-124 and Stem-loop Q-PCR to detect the expression level of miR-124. QPCR, WB, and flow cytometry were used to detect the mRNA and protein expression of Th cell differentiation and function-related genes. Transfection, QPCR, and flow cytometry were used to detect the effects of miR-124 overexpression and silencing on the differentiation of Th immune memory cells. In vitro, cell-killing experiments were performed to detect the tumor-killing activity of TH immune memory cells co-cultured with the Hela cell line, and the downstream target genes of miR-124 were predicted and verified by luciferase. Multiplex PCR was used to detect the genotype of miR-124 SNP in peripheral blood DNA. QPCR and WB were used to detect the mRNA and protein expression and phosphorylation of miR-124 target gene GSK3-PSF-CD45 pathway, and GSK3 inhibitor was used to block the pathway. ResultsWe found that exosomal miRNA-124 was significantly downregulated in cervical cancer tissues and affected Th cell immune function and memory cell generation. The overexpression of miRNA-124 can directly target GSK3, phosphorylate the target gene, and inhibit the expression of GSK3, thereby increasing the expression of CD45, increasing the ability of Th immune cells to recognize and kill the HPV virus, and significantly inhibiting the proliferation and migration of cervical cancer cells.

BackgroundTo investigate the etiology and clinical characteristics of community-acquired pneumonia (CAP) among children requiring bronchoalveolar lavage (BAL) and analyze the impact of the coronavirus disease 2019 (COVID-19) pandemic on the pathogen spectrum and clinical manifestations. MethodsChildren <14 years old hospitalized with CAP requiring BLA were enrolled between February 2019 to January 2020 and August 2021 to July 2022. Multiplex reverse transcription polymerase chain reaction (mRT-PCR) was used for pathogen detection. The demographic and clinical characteristics were compared between different pathogen-type infection groups, and before and during the COVID-19 pandemic. ResultsPathogen was detected in 91.66% (1363/1487) children. Mycoplasma pneumoniae, adenovirus and human rhinovirus were the most frequently detected pathogens. The frequency of detection of virus infections and co-infections was decreased during the pandemic, but the detection of atypical bacterial infections was increased. The clinical manifestations and the results of CT scans and fiberoptic bronchoscopy showed a significant difference between different types of pathogen infection, and lung inflammation was reduced during the COVID-19 pandemic compared with before the pandemic. ConclusionsM. pneumoniae infection might be the greatest pediatric disease burden leading to CAP in northern China. Wearing masks and social distancing in public places during the COVID-19 pandemic effectively reduced the transmission of respiratory viruses, but it did not reduce the infection rate of M. pneumoniae. In addition, these interventions significantly reduced lung inflammation in children compared with before the pandemic.

BackgroundNon-small cell lung cancer (NSCLC) is a complex disease with a high mortality rate and a poor prognosis, but its molecular mechanisms and effective biomarkers are still unclear. Comprehensive analysis of multiple histological data can effectively exclude random events and is helpful in improving the reliability of the findings. In this study, we used three types of omics data, RNA-seq, microRNA-seq, and DNA methylation data, from public databases to explore the potential biomarker genes of two major subtypes of NSCLC. ResultsThrough the combined differential analysis of multi-omics, we found 873 and 1378 potential high-risk genes in LUAD and LUSC, respectively. Then, we used WGCNA and PPI analyses to identify hub-genes and LASSO regression to construct prognostic models, and we obtained 15 prognostic genes. We also used survival analysis, univariate COX analysis, and GEO datasets to validate prognostic genes. Finally, we found ten genes associated with NSCLC, and eight of them have been reported in previous research. ConclusionsIn this study, two novel biomarker genes were identified: NES and ESAM. The two genes were both gene expression down-regulation and DNA methylation up-regulation, and regulated by miR-122 and miR-154. Moreover, the NES gene can contribute to the clinical diagnosis and prognosis of NSCLC.

BackgroundDACT gene is a potential Wnt antagonist and tumor suppressor gene. However, the expression of DACT gene in acute myeloid leukemia (AML) and its role are still unknown. MethodsIn this study, we first multidimensionally analyzed the expression of DACT gene in AML through RNA seq, qRT-PCR and Western blotting analysis as well as TCGA database analysis. Then DACT3 was identified as playing a critical role in AML, and its clinical significance was further explored. The molecular mechanism of DACT3 down-regulation in AML from aspects of DNA methylation and histone acetylation were inquired. Finally, the biological functions of DACT3 in AML were investigated by cell models in vitro and animal experiments in vivo. ResultsCompared with DACT1 and DACT2, DACT3 was the most differentially expressed DACT family member in AML, suggesting that DACT3 plays the major role. The mRNA and protein expression levels of DACT3 were significantly decreased and positively correlated in AML. Moreover, low expression of DACT3 is associated with no remission disease status and poor prognosis in AML patients. In addition, down-regulation of DACT3 in AML was not completely dependent on promoter methylation, but also affected by histone deacetylation. We found that loss of DACT3 in AML is related to activation of Wnt signaling pathway. Furthermore, DACT3 inhibits the growth of AML cells in vitro and in severe immunodeficiency (SCID) mice. Importantly, DACT3 improved the sensitivity of adriamycin in treating AML cells. Further research showed that co-treatment of chidamide and azacytidine up-regulates DACT3 expression and promotes cell apoptosis via inhibiting Wnt/{beta}-catenin signaling in AML, suggesting a promising therapeutic prospects in FLT3-mutant AML. ConclusionThis is the first study revealing the epigenetic regulatory molecular mechanism of the down regulated expression of DACT3 in AML. Our data also shows that DACT3 is a candidate gene for therapeutic target and targeting DACT3 has the potential to validate the combination therapy of DNMT inhibitors and HDAC inhibitors.

PurposeTo investigate the correlations of OPN1LW/OPN1MW (LW/MW) genotypes and clinical phenotypes in individuals with protan/deutan congenital color vision deficiency(CVD), and to explore photobiomodulation (PBM) therapy effects for CVD. DesignSingle-center consecutive, retrospective, observational study Participants43 subjects (41 males and 2 females) of protan/deutan CVD from the senior ophthalmology department of the PLA General Hospital. MethodsOpen-label, single-arm, 4-week pilot trial. Analysis of genetic, clinical, and color vision tests was performed cross-sectionally and longitudinally. Registered with the Chinese Clinical Trial Registry website (ChiCTR2200056761). Main Outcome Measurestypes of LW/MW variants, correlation of genotype and phenotype, color discrimination improvements of CVD after PBM therapy. ResultsClinically, the LW gene mutation (8 cases) causes protan CVD, the MW gene mutation (17 cases) and no definite gene mutation (10 cases) cause deutan CVD, dual mutations of LW and MW cause protan (5 cases) or deutan (3 cases) CVD. After individualized therapy, the effects of the MW gene mutation and no definite gene mutation groups are better than those of the LW gene mutation and dual mutations groups. ConclusionsFor protan/deutan CVD, PBM therapy can enhance color discrimination, and the result of gene detection is helpful to diagnose the clinical phenotype and predict the therapeutic effects of color vision correction. Financial Disclosure(s)The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Acute promyelocytic leukemia (APL), form RAR fusion genes and proteins is one of the most prevalent forms of leukemia. 4-Amino-2-Trifluoromethyl-Phenyl Retinate (ATPR), a derivative of all-trans-retinoic acid (ATRA), is of potent functions in the induce of cell differentiation, growth arrest, and apoptosis. Nowadays, we aimed to investigate the therapeutic effect of ATPR on this APL pathological model, and whether the mechanism involves PI3K/AKT, ERK and Notch signaling. We established a human xenograft mouse model using NB4 cells and found that ATPR significantly increased the protein concentration in the CD11b and suppressed the PI3K/AKT signaling and activated the ERK and Notch signaling in tumor tissue. Collectively, these data suggest that ATPR shows antileukemic effects by regulating PI3K/AKT, ERK and Notch signaling.

ObjectiveTo investigated the relationship between nutritional status and PD-1/CTLA-4 in CAP patients to determine whether the nutritional status is associated with the immunosuppression generated by T cells. MethodsAccording the enrollment strategy, we enrolled 60 patients and collected their medical records.Take their blood samples and analyzed the distribution of PD-1 and CTLA-4 in different T cell subgroups. ResultsThe level of PD-1 and CTLA-4 in the CD4+, CD8+ and Tregs were inclusive with the SCAP occurrence, mortality and PSI score.The malnutrition risk group suffered higher percentage of SAP, longer hospital-stay days and higher mortality when compared with the no-risk group.The higher the PD-1/CTLA-4 levels were, the higher the NRS-2002 score was. ConclusionA high NRS-2002 score may increase the length of hospital stay and the occurrence of SCAP. Higher PD-1 and CTLA-4 levels were associated with a higher PSI grade. Nutritional status influenced the occurrence of immunosuppression. Malnutrition status may increase the risk of immunosuppression, which is regulated by PD-1 and CTLA-4.

Background & AimsThe efficacy and safety of lenvatinib (LEN) as a second/third-line treatment for unresectable hepatocellular carcinoma (HCC) after sorafenib (SOR) therapy remains unknown. We evaluated the outcomes of second/third-line treatment of LEN, investigated the sensitivity of SOR-resistant HCC cell line (PLC/PRF5-R2) to LEN, and their signal transduction pathway by protein array analysis. MethodsWe retrospectively enrolled 57 unresectable HCC patients. Radiologic responses in 53 patients were evaluated by modified Response Evaluation Criteria in Solid Tumors. Active signal transduction pathways in cells were identified by protein array analysis, including 1205 proteins. ResultsPatients comprised 34 tyrosine kinase inhibitor (TKI)-naive (first-line), nine SOR-intolerant (second-line), and ten resistant to regorafenib (third-line). Objective response rates (ORRs) were 61.8% (21/34) in TKI-naive, 33.3% (3/9) in second-line, and 20.0% (2/10) in third-line groups. The overall survival (OS) and the progression free survival (PFS) in the first-line was significantly longer than those in third-line group (p<0.05). Patients with better liver functional reserve (Child score, ALBI grade) exhibited higher ORR and longer OS. LEN was well-tolerated as second/third-line treatment. The IC50 value of LEN against PLC/PRF5-R2 cells (30 M) was significantly higher than that against PLC/PRF5 cells (6.4 M). LEN inhibited significantly more signal transduction pathways related to FRS2, a crucial FGFR downstream molecule, in PLC/PRF5 than PLC/PRF5-R2 cells. ConclusionsLEN was active and safe as a second/third-line treatment for unresectable HCC. LEN seems to be more effective for HCC patients with better hepatic reserve function or before TKI-resistance is acquired because of partial cross-resistance to SOR.

Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer and its prognosis is poor. The cholinergic system is involved in the development of lung cancer but its role is still unclear. In this study, we collected 231 cholinergic-related genes, and examined their expression in LUAD samples and normal tissues, from which 37 differentially expressed genes were screened. Then, by survival analysis, we identified 7 genes related to the prognosis of LUAD, among which acetylcholinesterase (ACHE) and butyrylcholinesterase (BCHE) were included. The expression of AChE was upregulated in LUAD samples, and its expression had a significant positive correlation with the prognosis of male patients. But the expression of BChE was down-regulated in LUAD samples, and the elevated BChE expression was associated with a good prognosis in women and non-smoking patients. We also observed a close relationship between the two genes and immune landscape of LUAD. The AChE high expression patients had a higher ratio of tumor-infiltrating immune cells than the low expression patients, while the BChE high expression group had higher ratios of both tumor-infiltrating immune cells and stromal cells. We collected a total of 113 immunomodulatory genes associated with AChE and BChE to build an immunoregulatory network, which comprised several gene clusters. We also found that the expression of AChE and BChE was associated with immune escape in LUAD. Our results showed that AChE and BChE may play an important role in the development of LUAD, and could be promising biomarkers and targets for its diagnosis and treatment.

BackgroundTo explore the potential therapeutic target to treat pancreatic cancers, Tspan1 was detected in human pancreatic cancer tissue and human pancreatic ductal adenocarcinoma cells and functional role of Tspan1 on proliferation was explored and the mechanism was investigated. Materials and MethodsTspan1 in PCC tissue and PDAC cell lines was measured by qRT-PCR and Western blot. Tspan1 was knock-downed and over-expressed in cells via transfection with Tspan1-siRNA and pLNCX-TSPAN1-cDNA, cell survival, proliferation and cell cycle were measured with MTT, Alamar blue and Flow Cytometry assay. The mRNA and protein expression were assessed by qRT-PCR and Western blotting. The expression of PI3K, Akt and p-Akt were detected, and CDK1 siRNA and specific inhibitor of Akt were used to explore the mechanism of TSPAN1 promoting PDAC cells proliferation. ResultsTspan1 expression in PCC tissue and PDAC cells was increased. Transfection of siRNA targeting Tspan1 in BxPC3 and PNAC-1 cells obviously decreased cell proliferation and down-regulated CDK1 expression. Consistently, both cell proliferation and CDK1 expression in BxPC3 and PNAC-1 cells were up-regulated with pLNCX-TSPAN1-cDNA transfection. Cell cycle analysis showed that after knockdown of Tspan1 the G2/M phase ratio was increased to cause mitosis arrest, and TSPAN1 overexpression caused cell cycle transition from G2 to M phase to promote cell proliferation. And these were dependent on the modulation of CDK1 expression via Akt. ConclusionTspan1 up-regulates CDK1 expression via activating Akt to promote human PCC cell proliferation and silencing of Tspan1 may be a potential therapeutic target to treat pancreatic cancers.

IntroductionThe incidence of lung cancer worldwide has been increasing in recent years, and the latest cancer data published by the WHO International Agency for Research on Cancer in 2021 shows that lung cancer remains the cancer with the highest mortality rate. The sensitivity of early screening methods for lung cancer is not ideal. Because early lung cancer is mostly located in nodules with a diameter of 1 cm, it is difficult to obtain a definite pathological diagnosis from living tissue specimens. Therefore, it is necessary to find less invasive and effective tests to help detect lung cancer early. Therefore, the purpose of this systematic review (SR) and meta-analysis will be to analyze and explore the correlation between promoter methylation of SHOX2 and RASSF1A genes and lung cancer, and to provide a reference for early clinical diagnosis. Methods and AnalysisThe relevant literature will be comprehensively searched in 4 international electronic databases (PubMed, Cochrane Library, EMBASE and Web of Science) and 4 Chinese electronic databases (CNKI, VIP, Wanfang, Chinese Biomedicine). We only included studies from inception until publication in May 2022. The primary outcome measure was the methylation rate of the SHOX2 and RASSF1A gene promoters in lung cancer tissue and normal lung tissue in the control group in lung cancer patients. Secondary outcome measures included methylation rates of promoters of SHOX2 and RASSF1A genes in different tissue samples. Two reviewers will conduct independent research selection, data extraction, data synthesis and quality assessment. The assessment of bias risk and data synthesis will be conducted using Review Manager 5.3 software. The Cochrane Collaborations Bias Risk Assessment Tool (QUADAS) will be used to assess the quality of the individual studies included. DiscussionThis systematic review will help to clarify the correlation between PROMOTER methylation of the SHOX2 and RASSF1A genes with lung cancer, providing clinical evidence for early clinical diagnosis. Trial registration numberCRD42022330609 (PROSPERO)

ObjectiveSystematically evaluate the risk prediction model for neonatal necrotizing enterocolitis (NEC) in China, providing reference for clinical work and future research. MethodsWe searched Chinese and English databases were systematically searched to focus on NEC risk prediction modeling studies.The search time ranged from database establishment to 25 August 2023.Two researchers independently screened the literature and extracted information.Then risk of bias and applicability were assessed by using the Prediction Model Risk of Bias Assessment Tool. ResultsA total of 10 papers involving 12 NEC risk prediction models were included, which is focusing on the populations of preterm infants mostly, building the methods of models diversity, predicting factors discrepancy widely. conclusionThe existing NEC risk prediction models in China have good predictive performance, while they often lack external validation, resulting in an overall high risk of bias. In the future, clinicians and nurses should learn from the evaluation criterions based on the PROBAST, then to test and verify them. Or machine learning algorithms usage is to construct models with operationalization and better predictive efficacy. [REGISTRATION: PROSPERO ID: CRD42024503844]

PurposeCoronavirus disease (COVID-19) pandemic is now a global health concern. However, there is no detailed analysis of the factors related to patients improvement. Patients and methodsWe compared the clinical characteristics, laboratory findings, CT images, and treatment of COVID-19 patients from two different cities in China. One hundred and sixty-nine patients were recruited from January 27 to March 17, 2020 at five hospitals in Hubei and Guangxi. They were divided into four groups according to age and into two groups according to presence of comorbidities. Multivariate statistical analyses were performed for the prognosis of the disease. ResultsFifty-two patients (30.8%) had comorbidities, and the percentage of critical COVID-19was higher in the comorbidities group (11.6%vs.0.9%, p<0.05). Older patients had higher proportion of severe or critical disease. The results showed that lymphocyte count was significantly associated with the number of days from positive COVID-19 nucleic acid test to negative test; number of days from onset of symptoms to confirmation of diagnosis was significantly associated with the time it took for symptoms to improve; and number of days from onset of symptoms to confirmation of diagnosis and disease severity were significantly associated with chest computed tomography improvement. ConclusionsAge, comorbidities, lymphocyte count, and SpO2 may predict the risk of severity of COVID-19. Early isolation, early diagnosis, and early initiation of management can slow down the progression and spread of COVID-19. Key PointsAge and comorbidities can predict the risk of severity of COVID-19, Lymphocyte count and SpO2 may predict the risk of severity of COVID-19. Early isolation, Early diagnosis can slow down the progression of COVID-19

BackgroundOur previous study demonstrated that intravenous administration of mesenchymal stromal cells (MSCs) significantly increased local cell engraftment and improved heart function. We sought to investigate whether HLA-G1 overexpressed MSCs could further increase local transplanted cells engraftment and improve heart function. Methods and ResultsMice were randomized to receive intravenous administration of saline, human umbilical cord blood derived MSCs (hUCB-MSCs) 7 days prior to acute myocardial infarction (AMI), induced by ligation of the left anterior descending coronary artery. Then, intramyocardial transplantation of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) was performed 30 minutes following AMI. Echocardiographic assessment was performed to assess heart function. In-vivo fluorescent imaging analysis were used to analyze cell engraftment. Flow cytometry of splenic regulatory T cells (Tregs) and natural killer (NK) cells was conducted to evaluate the immunomodulatory effect. Our result showed that systemic intravenous administration of hUCB-MSCs significantly increased systemic Tregs, decreased systemic NK cells, increased cell engraftment of intramyocardial transplanted hiPSC-CMs, culminating in improvement of heart function. Our in-vitro study showed that HLA-G1 overexpressed hUCB-MSCs modulated immune response by decreasing pro-inflammatory cytokines. ConclusionsSystemic intravenous administration of HLA-G1 overexpressed hUCB-MSCs modulated immune response and enhanced the survival of local transplanted hiPSC-CMs to improve heart function following AMI.

Coronavirus disease 2019 (COVID-19) is a global pandemic and has been widely reported; however, a comprehensive systemic review and meta-analysis has not been conducted. We systematically investigated the clinical characteristics of COVID-19 in mainland China to guide diagnosis and treatment. We searched the PubMed, Embase, Scopus, Web of Science, Cochrane Library, bioRxiv, medRxiv, and SSRN databases for studies related to COVID-19 published or preprinted in English or Chinese from January 1 to March 15, 2020. Clinical studies on COVID-19 performed in mainland China were included. We collected primary outcomes including signs and symptoms, chest CT imaging, laboratory tests, and treatments. Study selection, data extraction, and risk of bias assessment were performed by two independent reviewers. Qualitative and quantitative synthesis was conducted, and random-effects models were applied to pooled estimates. This study is registered with PROSPERO (number CRD42020171606). Of the 3624 records identified, 147 studies (20,662 patients) were analyzed. The mean age of patients with COVID-19 was 49.40 years, 53.45% were male, and 38.52% had at least one comorbidity. Fever and cough were the most common symptoms, followed by fatigue, expectoration, and shortness of breath. Most patients with COVID-19 had abnormal chest CT findings with ground glass opacity (70.70%) or consolidation (29.91%). Laboratory findings shown lymphopenia, increased lactate dehydrogenase, increased infection-related indicators, and fibrinolytic hyperactivity. Antiviral therapy, antibiotic therapy, and corticosteroids were administered to 89.75%, 79.13%, and 35.64% of patients, respectively. Most clinical characteristics of COVID-19 are non-specific. Patients with suspected should be evaluated by virological assays and clinically treated.

PurposeThe 2019 novel coronavirus(COVID-19) mainly transmitted by person-to-person through inhalation of respiratory droplets. We report the laboratory results of conjunctival PCR-tests and some clinical features of these patients in shenyang China. DesignThis is a cross-sectional non-randomized study SubjectsThe study include 14 confirmly diagnosed cases, 16 suspected cases and some medical observed patients. MethodsAll patients with diagnosed and suspected COVID-19 were admitted to a designated hospital in Shenyang, China. We collected conjunctival samples of these patients to do the laboratory tests by real time RT-PCR. Medical observed patients were enrolled if they had clinical symptoms. Then we analysed the PCR results and clinical data from eletronic medical records in order to find some relationships. Main Outcome MeasuresClinical condition and PCR results. of conjunctival swabs compared with other specimens ResultsOne of the identified case coverted from suspected case without typical clinical symptoms. Twenty-two medical observed cases were removed because none of them converted to identified cases. One of the suspected converted to identified case recently. The included cases in our study are imported cases with less underlying diseases and the severity of their infection was relatively moderate. All the conjunctival results of PCR-test were negative. Two cases had typical clinical symptoms but were finally confirmed by repeated pharynxswabtests. ConclusionConjunctiva may be a transmission way of COVID-19. And ocular conjunctival swabs in combination with PCR test could be a non-invasive, convenient and feasible diagnostic method for identifying the infection of COVID-19. Emphasis on the false-negative results is vital.

BackgroundDuring the current pandemic, a great effort is made to understand the COVID-19 and find an effective treatment. As of 17 August 2020, there is no specific drug or biologic agent which have been approved by the FDA for the prevention or treatment of COVID-19. MethodsWe retrospectively analyzed the clinical and radiological findings of 211 COVID-19 in-patients that were treated between March - August 2020. Confirmation of a COVID-19 diagnosis was made according to a positive RT-PCR result with a consistent high-resolution-CT (HRCT) finding. Radiological images and the rate of clinical response of patients were investigated. ResultWhile 128 patients (58.7) did not develop pneumonia, the mild, moderate and severe pneumonia ratios were 28(13.2%), 31(18.7%) and 27(22.9%). 72 patients (34.1%) whose PCR tests were positive did not show any symptom and they were followed in isolation without treatment. 52 patients (24.6%) received hydroxychloroquine plus azithromycin, 57 patients (27%) received favipiravir and 30 patients (14.2%) received favipiravir plus dexamethasone as the first line of treatment. 63.1% of pneumonia patients who received hydroxychloroquine plus azithyromycine, 28.3% of patients who received favipiravir and 10% of patients who received favipiravir plus dexamethasone showed a failure of treatment. ConclusionThe pulmonary infiltrates of COVID-19 are not infective; therefore, the characteristic of the disease should be described as COVID-19 pneumonitis instead of pneumonia. The favipiravir plus dexamethasone seems to be the only drug combination to achieve the improvement of radiological presentation and clinical symptoms in COVID-19 pneumonia patients.

ObjectiveGlucose-regulated protein 78 (Grp78) has been regarded as a main member of the endoplasmic reticulum proteins, Grp78 could protect cells from apoptosis under stress conditions. However, whether Grp78 could protect retinal pigment epithelium (RPE) cells from oxidative injury and then protect retinas from morphological changes and functional abnormalities remain undetermined. Here, we try to explore the effect of Grp78 on retinal cell injury induced by sodium iodate in vivo and in vitro. MethodsTo investigate whether Grp78 has a protective effect on RPE injury in vitro, human retinal pigment epithelium (ARPE-19) cells were treated with sodium iodate. The cell proliferation, morphology, apoptosis and ROS production assays were detected. In vivo, We established sodium iodate-induced retinal injury model in mice by intravenous injection of sodium iodate into tail vein. After that, we examined the morphology and function of retina in mice by fundus photography, OCT and ERG. Finally, we removed the retina of mice for histological examination. ResultsGrp78 significantly inhibited sodium iodate-induced reactive oxygen species (ROS), and decreased apoptosis of RPE in vitro. Furthermore, Grp78 significantly decreased the apoptosis of retinal cells in vivo, resulting in the inhibition of morphological changes of retina, and improving the function of retina. The underlying mechanisms included inhibited caspase3 and Nos, and increased expression of Bcl2, thereby protecting RPE from SI-induced ROS and apoptosis. ConclusionGrp78 could reduce the injury of retinal cells induced by sodium iodate in vitro and in vivo. These findings suggested Grp78 may become a new therapeutic target for retinal injury in clinical practice.

Since the outbreak of Coronavirus Disease 2019 (COVID-19) causing novel coronavirus (2019-nCoV)-infected pneumonia (NCIP), over 45 million affected cases have been reported worldwide. Many patients with COVID-19 have involvement of their respiratory system. According to studies in the radiology literature, chest computed tomography (CT) is recommended in suspected cases for initial detection, evaluating the disease progression and monitoring the response to therapy. The aim of this article is to review the most frequently reported imaging features in COVID-19 patients in order to provide a reliable insight into expected CT imaging manifestations in patients with positive reverse-transcription polymerase chain reaction (RT-PCR) test results, and also for the initial detection of patients with suspicious clinical presentation whose RT-PCR test results are false negative. A total of 60 out of 173 initial COVID-19 studies, comprising 7571 individuals, were identified by searching PubMed database for articles published between the months of January and June 2020. The data of these studies were related to patients from China, Japan, Italy, USA, Iran and Singapore. Among 40 reported features, presence of ground glass opacities (GGO), consolidation, bilateral lung involvement and peripheral distribution are the most frequently observed ones, reported in 100%, 91.7%, 85%, and 83.3% of articles, respectively. In a similar way, we extracted CT imaging studies of similar pulmonary syndromes outbreaks caused by other strains of coronavirus family: Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). For MERS and SARS, 2 out of 21 and 5 out of 153 initially retrieved studies had CT findings, respectively. Herein, we have indicated the most common coronavirus family related and COVID-19 specific features. Presence of GGO, consolidation, bilateral lung involvement and peripheral distribution were the features reported in at least 83% of COVID-19 articles, while air bronchogram, multi-lobe involvement and linear opacity were the three potential COVID-19 specific CT imaging findings. This is necessary to recognize the most promising imaging features for diagnosis and follow-up of patients with COVID-19. Furthermore, we identified co-existed CT imaging features.

BackgroundAs the novel coronavirus triggering COVID-19 has broken out in Wuhan, China and spread rapidly worldwide, it threatens the lives of thousands of people and poses a global threat on the economies of the entire world. However, infection with COVID-19 is currently rare in children. ObjectiveTo discuss the latest findings and research focus on the basis of characteristics of children confirmed with COVID-19, and provide an insight into the future treatment and research direction. MethodsWe searched the terms "COVID-19 OR coronavirus OR SARS-CoV-2" AND "Pediatric OR children" on PubMed, Embase, Cochrane library, NIH, CDC, and CNKI. The authors also reviewed the guidelines published on Chinese CDC and Chinese NHC. ResultsWe included 25 published literature references related to the epidemiology, clinical manifestation, accessary examination, treatment, and prognosis of pediatric patients with COVID-19. ConclusionThe numbers of children with COVID-19 pneumonia infection are small, and most of them come from family aggregation. Symptoms are mainly mild or even asymptomatic, which allow children to be a risk factor for transmission. Thus, strict epidemiological history screening is needed for early diagnosis and segregation. This holds especially for infants, who are more susceptible to infection than other age groups in pediatric age, but have most likely subtle and unspecific symptoms. They need to be paid more attention to. CT examination is a necessity for screening the suspected cases, because most of the pediatric patients are mild cases, and plain chest X-ray do not usually show the lesions or the detailed features. Therefore, early chest CT examination combined with pathogenic detection is a recommended clinical diagnosis scheme in children. The risk factors which may suggest severe or critical progress for children are: Fast respiratory rate and/or; lethargy and drowsiness mental state and/or; lactate progressively increasing and/or; imaging showed bilateral or multi lobed infiltration, pleural effusion or rapidly expending of lesions in a short period of time and/or; less than 3 months old or those who underly diseases. For those critical pediatric patients with positive SARS-CoV-2 diagnosis, polypnea may be the most common symptom. For treatment, the elevated PCT seen in children in contrast to adults suggests that the underlying coinfection/secondary infection may be more common in pediatric patients and appropriate antibacterial treatment should be considered. Once cytokine storm is found in these patients, anti-autoimmune or blood-purifying therapy should be given in time. Furthermore, effective isolation measures and appropriate psychological comfort need to be provided timely.