Colchicine,COVID‐19 and hematological parameters: A meta‐analysis

IntroductionColchicine has the potential in reducing patient morbidity and mortality in COVID‐19 infection owing to its anti‐inflammatory properties. This study aims to determine the efficacy of colchicine in optimizing inflammatory hematological biomarker levels among COVID‐19 patients.MethodsIn accordance to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) 2020 statement guidelines, a systematic search was conducted using the following keywords: Colchicine, covid*, SARS‐CoV‐2, anti‐inflammatory, trials, clinical, hematological, laboratory. Databases were searched from December 2019 until August 26, 2021: MEDLINE/PubMed, Web of Science, Cochrane, Scopus, and EMBASE. Other sources were located through ClinicalTrials.Gov, manually searching SAGE, Science Direct, Elsevier, and Google Scholar. The meta‐analysis was conducted using Review Manager 5.4.ResultsIn total, six studies were included, of which four reported c‐reactive protein (CRP) standardized mean reductions in the colchicine group (N = 165) as opposed to the control (N = 252; SMD = −0.49, p < 0.001). On noting lactate dehydrogenase (LDH) values post treatment, the colchicine group (N = 204) showed significant reductions at the end of treatment compared to control (N = 290; SMD = −0.85, p < 0.001). Finally, the D‐dimer values in colchicine groups (N = 129) compared to control (N = 216) also documented a negative effect size (SMD = −0.9, p < 0.001).ConclusionColchicine has efficacy in reducing inflammatory biomarkers observed in moderate‐to‐severe COVID‐19 patients. It may be worthwhile to consider monitoring the clinical and laboratory parameters of patients in further trials to consider colchicine as a strong candidate for an adjunct to COVID‐19 treatment.     

The correlation of D‐dimer to stroke diagnosis within 24 hours: A meta‐analysis

BackgroundDiagnosing D‐Dimer early is essential to optimize clinical treatment and quality of life and reduce mortality. This study aims to identify the difference of D‐Dimer levels (ng/ml) in patients with stroke within the 6‐ and 24‐h period compared to patients that mimic stroke.MethodsAn electronic database search across PubMed/MEDLINE, Cochrane, Web of Science, CINAHL, EMBASE, and Scopus was conducted until December 10, 2021. Studies were eligible if they included adult patients with stroke compared to stroke mimics or controls reporting D‐Dimer values. Quality assessment was conducted using GRADE. The standardized mean difference and 95% confidence intervals were calculated in addition to the difference of means in the crude form. Heterogeneity was assessed using Cochran''s Q statistic and the I ² index. A random‐effects model was used. The statistical analysis was conducted using RevMan 5.4.ResultsOut of 2901, there were 318 (11%) participants from upper‐middle‐income countries, whereas the others were from high‐income countries. Large positive effect size was found for D‐Dimer in the stroke group (Cohen''s d = 2.82 [1.73–3.9]; p < 0.00001), meaning that those with stroke had higher D‐Dimer values on presentation compared to the stroke mimics/controls. A large difference in means was found in the two groups (MD = 685.1 [324.2, 1045.99]; p < 0.00001), suggesting that there was a significantly higher laboratory value in the stroke group.ConclusionOur findings must be used in caution as the most reliable diagnostic tests for stroke are CT and MRI. Laboratory testing such as D‐Dimer values is a valuable clinical adjuvant in diagnosing total stroke.     

Neurological manifestations in patients with COVID‐19: A systematic review and meta‐analysis

IntroductionThe intensification of coronavirus disease 2019 (COVID‐19) complications, severe symptoms, and high mortality rate has led researchers to focus on this significant issue. While respiratory and cardiac complications have been described as high‐risk manifestations in patients with COVID‐19, neurological complications can also enhance mortality. This study aimed to evaluate the prevalence of neurological complications arises from SARS‐CoV‐2 and assess the mortality rate from neurological complications.Material and MethodsLiterature review was conducted by searching in PubMed/Medline, Web of Sciences, and Embase. After performing search strategies with relevant terms, a number of articles were excluded, including review articles, systematic review or meta‐analysis, duplicate publication of same researchers, congress abstracts, animal studies, case reports, case series, and articles reporting a history of neurological features prior to COVID‐19 infection. After retrieving the data, statistical analysis was performed using the STATA Version 14 software.ResultsFrom 4455 retrieved publications, 20 articles were selected for further analysis. Among 18,258 included patients, 2791 showed neurological symptoms, which were classified into different groups. Headache, confusion, and fatigue were reported as the most non‐specific neurological features in confirmed COVID‐19 patients. Psychiatric symptoms, CNS disorders, cerebrovascular disorders, CNS inflammatory disorders, PNS disorders, neuromuscular disorders, etc., were defined as specific neurological manifestations. The pooled prevalence of neurological manifestations and mortality rate of COVID‐19 patients with neurological features were estimated to be 23.0% (95% CI: 17.8–29.2) and 29.1% (95% CI: 20.3–39.8), respectively.ConclusionNeurological manifestations may commonly happen in patients with COVID‐19. This study reported a high prevalence of neurological complications and mortality rates in COVID‐19 patients. Therefore, patients with COVID‐19 who indicated neurological symptoms should be taken seriously and should receive early treatment to prevent undesirable events.     

Anakinra treatment efficacy in reduction of inflammatory biomarkers in COVID‐19 patients: A meta‐analysis

IntroductionAnakinra is being empirically considered for the treatment of COVID‐19 patients. The aim is to assess the efficacy of anakinra treatment on inflammatory marker reduction, including c‐reactive protein (CRP) concentrations, serum ferritin, and serum d‐dimer levels.MethodsAdhering to PRISMA 2020 statement guidelines, a systematic search was conducted across the following databases from December 2019 until January 10, 2022: PubMed/MEDLINE, Cochrane Central, Web of Science, Scopus, and EMBASE. The following keywords were employed: Anakinra, COVID*, SARS‐CoV‐2, inflammatory, CRP, D‐dimer, Ferritin, hematological, laboratory, clinical, trials. The findings were collated and presented in a tabulated manner, and statistically analyzed using Review Manger 5.4 (Cochrane).ResultsIn total, 2032 patients were included (881 in the anakinra and 1151 in the control/standard care group); 69.1% of them were males. Overall, the mean difference from admission until last follow‐up in CRP values was −9.66, where notable reductions were seen in the anakinra group (SMD = −0.46, p < 0.00001, N = 655). Serum ferritin mean values were reduced by 1467.16 in the anakinra group (SMD = −0.31, p = 0.004, N = 537). D‐dimer mean values were largely reduced by 4.04 in the anakinra group (SMD = −0.38, p = 0.0004, N = 375).ConclusionThis study finds that anakinra is potentially a strong candidate as an anti‐inflammatory agent to reduce mortality in COVID‐19 patients, specifically in patients with elevated inflammatory biomarkers.     

Comorbidities and mortality rate in COVID‐19 patients with hematological malignancies: A systematic review and meta‐analysis

IntroductionThe global pandemic of coronavirus disease 2019 (COVID‐19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). It seems that there is an association between blood cancer and an increased risk of severe COVID‐19. This study aimed to review the literature reporting the COVID‐19 outcomes in patients with hematological malignancies.Material and methodsIn this systematic review and meta‐analysis, Pubmed, Embase, and Web of Science databases were searched using the following keywords: COVID‐19, SARS‐CoV‐2, blood cancer, myeloma, lymphoma, and leukemia. All the published articles in English from January 1, 2019, until March 10, 2021 were collected and evaluated.ResultsIn total, 53 studies with 2395 patients were included based on inclusion criteria. Most of these studies took place in Spain (14.81%), followed by the USA (11.11%), China (9.26%), and the UK (9.26%). More than half of COVID‐19 patients with hematological malignancy were male (56.73%). Oxygen therapy played an important role in COVID‐19 treatment. Moreover, anticoagulant therapies such as enoxaparin and heparin were two great assists for these patients. Fever (74.24%), cough (67.64%), and fatigue (53.19%) were the most reported clinical manifestations. In addition, hypertension and dyslipidemia were the most common comorbidities. The mortality rate due to COVID‐19 in patients with hematological malignancies was 21.34%.ConclusionThis study demonstrated that hematologic cancer patients were more susceptible to a severe COVID‐19 than patients without blood cancer. Thus, the management of COVID‐19 in these patients requires much more attention, and their screening should perform regularly.     

Worldwide prevalence of microbial agents’ coinfection among COVID‐19 patients: A comprehensive updated systematic review and meta‐analysis

BackgroundTo provide information about pathogens’ coinfection prevalence with SARS‐CoV‐2 could be a real help to save patients’ lives. This study aims to evaluate the pathogens’ coinfection prevalence among COVID‐19 patients.MethodIn order to find all of the relevant articles, we used systematic search approach. Research‐based databases including PubMed, Web of Science, Embase, and Scopus, without language restrictions, were searched to identify the relevant bacterial, fungal, and viral coinfections among COVID‐19 cases from December 1, 2019, to August 23, 2021. In order to dig deeper, other scientific repositories such as Medrxiv were probed.ResultsA total of 13,023 studies were found through systematic search. After thorough analysis, only 64 studies with 61,547 patients were included in the study. The most common causative agents of coinfection among COVID‐19 patients were bacteria (pooled prevalence: 20.97%; 95% CI: 15.95–26.46; I ²: 99.9%) and less frequent were virus coinfections (pooled prevalence: 12.58%; 95% CI: 7.31–18.96; I ²: 98.7%). The pooled prevalence of fungal coinfections was also 12.60% (95% CI: 7.84–17.36; I ²: 98.3%). Meta‐regression analysis showed that the age sample size and WHO geographic region did not influenced heterogeneity.ConclusionWe identified a high prevalence of pathogenic microorganism coinfection among COVID‐19 patients. Because of this rate of coinfection empirical use of antibacterial, antifungal, and antiviral treatment are advisable specifically at the early stage of COVID‐19 infection. We also suggest running simultaneously diagnostic tests to identify other microbiological agents’ coinfection with SARS‐CoV‐2.     

Efficacy and safety of intralymphatic immunotherapy in allergic rhinitis: A systematic review and meta‐analysis

BackgroundIntralymphatic immunotherapy (ILIT) is a potential treatment option for allergic rhinitis (AR). We aimed to determine the efficacy (primary outcomes) and safety (secondary outcomes) of ILIT in treating patients with AR.MethodsAn electronic literature search was performed using MEDLINE and Cochrane Central Register of Controlled Trials CENTRAL (from their inception to December 2020). A random‐effects model was used to estimate the pooled prevalence with 95% confidence intervals. This study is registered with PROSPERO (CRD42019126271).ResultsWe retrieved a total of 285 articles, of which 11 satisfied our inclusion criteria. There were 452 participants with age ranged from 15 to 58 years old. Intralymphatic immunotherapy was given in three doses with intervals of four weeks between doses in 10 trials. One trial gave three and six doses with an interval of two weeks. Both primary and secondary outcomes showed no difference between ILIT and placebo for all trials. There was no difference in the combined symptoms and medication score (SMD ‐0.51, 95% CI −1.31 to 0.28), symptoms score (SMD −0.27, 95% CI −0.91 to 0.38), medication score (SMD −6.56, 95% CI −21.48 to 8.37), rescue medication (RR 12.32, 95% CI 0.72–211.79) and the overall improvement score (MD −0.07, 95% CI −2.28 to 2.14) between ILIT and placebo. No major adverse events noted.ConclusionsIntralymphatic immunotherapy possibly has a role in the treatment of AR patients. This review found it is safe but not effective, which could be contributed by the high variation amongst the trials. Future trials should involve larger numbers of participants and report standardized administration of ILIT and outcome measures.     

COVID‐19 in HIV‐positive patients: A systematic review of case reports and case series

IntroductionCoronavirus disease 2019 (COVID‐19) and acquired immune deficiency syndrome (AIDS) are two viral diseases for which there are currently no definitive treatments. Nowadays, because of the health system''s focus on the COVID‐19 epidemic, the control of human immunodeficiency virus (HIV) has received less attention. In this review, we will discuss the characteristics of COVID‐19 in HIV‐positive patients.Material and MethodsUsing the PRISMA guideline, the databases of Scopus, PubMed, and Web of Science were searched systematically from January 1, 2019 to February 24, 2021. The following keywords were used: “Human Immunodeficiency Virus,” “acquired immune deficiency syndrome,” “HIV,” “AIDS,” “COVID‐19,” “severe acute respiratory syndrome coronavirus 2,” “novel coronavirus,” “SARS‐CoV‐2,” “nCoV disease,” “SARS2,” and “2019‐nCoV disease.”ResultsTwenty‐one percent of studies were conducted in the USA (n = 13), 16% in China (n = 10), and 13% in Italy (n = 8), respectively. The majority of the patients were men (74.3%). Tenofovir disoproxil fumarate was used in 47.4% of patients, emtricitabine in 58.4%, and lamivudine in 34.8% to treat HIV. Symptoms of HIV patients with COVID‐19 included coughing (81.3%), fever (62.8%), and dyspnea (60%). Hydroxychloroquine (39.34%) and azithromycin (36.58%) were the common treatment options for COVID‐19. The total death rate in HIV‐positive patients with COVID‐19 was about 9%.ConclusionIn the current systematic review, we demonstrated that HIV‐positive patients co‐infected with COVID‐19 have high comorbidity of hypertension and diabetes mellitus. HIV/COVID‐19 co‐infection might have negatively influenced the HIV treatment and diagnosis, which indicates the need to regularly screen HIV patients in the COVID‐19 pandemic.     

Bioinformatics analysis of differentially expressed miRNAs in non‐small cell lung cancer

ObjectiveNon‐small cell lung cancer (NSCLC) contains 85% of lung cancer. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the largest NSCLC subgroups. The aim of the study was to investigate the underlying mechanism in developing more effective subtype‐specific molecular therapeutic procedures.MethodsA total of 876 specimens were used in this study: 494 LUAD tissues (ie, 449 LUAD tissues and 45 matched normal tissues) and 382 LUSC tissues (ie, 337 LUSC tissues and 45 matched normal tissues). The miRNA sequencing data were processed using R. The differential expressed miRNAs between lung cancer and normal tissues were analyzed using the limma package in R. Gene expression, Western blotting, hematoxylin and eosin staining, and luciferase assay were used to test LUAD and LUSC.ResultsLUAD and LUSC appear sharply distinct at molecular and pathological level. Let‐7a‐5p, miR‐338, miR‐375, miR‐217, miR‐627, miR‐140, miR‐147b, miR‐138‐2, miR‐584, and miR‐197 are top 10 relevant miRNAs and CLDN3, DSG3, KRT17, TMEM125, KRT5, NKX2‐1, KRT7, ABCC5, KRAS, and PLCG2 are top 10 relevant genes in NSCLC. At the same time, the miRNAs expression levels were also quite different between the two groups. Among the differential expressed miRNAs, let‐7a‐5p was significantly down‐regulated in LUAD while miR‐338 was markedly down‐regulated in LUSC. Bioinformatics analyses appeared that let‐7a‐5p directly targets high–molecular weight keratin 5 (KRT5) which were shown to be a strong risk factor for LUAD. And NK2 homeobox 1(NKX2‐1) which was associated with tumor progression in LUSC was identified as a target gene of miR‐338.ConclusionsDistinct profile of miRNAs can take a part in the development of LUAD and LUSC and thus could serve as a subtype‐specific molecular therapeutic target to protect against LUAD and LUSC.     

The potential diagnosis role of TP53 mutation in advanced bladder cancer: A meta‐analysis

BackgroundBladder cancer is one of the most common urological cancers all over the world, and NMIBC occupies almost 80% of recently diagnosed bladder cancer cases. Progress and recurrence of bladder cancer are the main problems during the disease. The level of TP53 mutation is obviously higher in the high stage than the lower. This meta‐analysis is to evaluate the potential diagnosis feature of TP53 mutation by the expression of TP53 mutation of Ta stage vs high stage in bladder cancer.MethodsA systematic search of databases was conducted, and some relevant articles were selected. Next, the meta‐analysis was carried out according to the standard guidelines.ResultsThere were seven researches in which 677 participants were selected at the basis of inclusion standard. TP53 mutation was associated highly with increased diagnosis of bladder cancer. We found that the high stage of bladder cancer has obviously higher level of TP53 mutation than the lower stage, and these patients of MIBC have higher expression of TP53 mutation compared with NMIBC. No significant publication bias has been observed in this meta‐analysis. The expression of TP53 mutation might be a diagnose‐related biomarker for lots of patients with bladder cancer.ConclusionsThe results of this meta‐analysis provided further evidences that the expression of TP53 mutation was associated with the diagnosis efficiency of advanced bladder cancer. Higher expression of TP53 mutation was observed in the high stage of bladder cancer or the MIBC, and lower expression of TP53 mutation in the Ta stage of bladder cancer or the NMIBC. The expression level of TP53 mutation was probably a critical diagnosed biomarker in advanced bladder cancer.     

Prognostic value of prognostic nutritional index and its variations in advanced non‐small‐cell lung cancer patients treated with anlotinib monotherapy

BackgroundAnlotinib is a third‐line or further therapy for advanced non‐small‐cell lung cancer (NSCLC). However, the lack of simple biomarkers to predict the curative effect of anlotinib creates significant unmet needs in exploring the markers. This study aimed to explore the relationship between the prognostic nutritional index (PNI) and its variations and efficacy of anlotinib.MethodsData for patients with advanced NSCLC who received anlotinib were collected at Ningbo Medical Center Lihuili Hospital. The data included the values of pretreatment PNI (pre‐PNI), posttreatment PNI (post‐PNI), and ΔPNI (post‐PNI minus the pre‐PNI). The Kaplan–Meier method was used to generate survival curves, whereas univariate and multivariate Cox regression analyses were used to analyze survival predictors.ResultsA high disease control rate was associated with a high pre‐PNI (p = 0.007), high post‐PNI (p = 0.000), and high ΔPNI (p = 0.006). Univariable analysis revealed that pre‐PNI ≤41.80, post‐PNI ≤42.48, and ΔPNI ≤0.20 were significant risk factors for poor survival. According to the multivariate analysis, progression‐free survival (PFS) in patients with post‐PNI ≤42.48 was significantly shorter than in patients with higher values (median PFS: 1.5 months vs. 4.0 months, p = 0.010).ConclusionsPre‐PNI, ΔPNI, and post‐PNI were found to be predictive factors for response in advanced NSCLC patients treated with anlotinib as a third‐line or further treatment. Only post‐PNI was a reliable predictor of PFS. Therefore, PNI and its variations, particularly post‐PNI, are affordable and accessible predictors of NSCLC patients treated with anlotinib in clinical work.     

CircRNAs as promising biomarker in diagnosis of breast cancer: An updated meta‐analysis

BackgroundCircular RNAs (circRNAs) have been identified to be involved in onset and progression of multiple malignant tumors. The present study aimed to systematically evaluate the diagnostic values of circRNAs in breast cancer.MethodsThe PubMed, Web of Science, Embase, CNKI, and Wanfang online databases were searched for the relevant studies before December 31, 2020. Statistical analysis of the diagnostic tests was performed based on STATA 16.0, Meta‐DiSc 1.4, and RevMan 5.3 software. The threshold effect and publication bias were measured by the Spearman correlation and Deeks’ funnel plot asymmetry test, respectively.ResultsTwenty‐one studies from 13 articles were included in this meta‐analysis. The pooled sensitivity and specificity were 0.77 and 0.71, respectively. The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and overall diagnostic odds ratio (DOR) were 2.6, 0.33, and 8, respectively. Furthermore, the area under the summary receiver operator characteristic curve was 0.80. In addition, down‐regulated circRNAs achieved a diagnostic performance higher than up‐regulated circRNAs, with area under curve (AUC) values of 0.81 and 0.74, respectively. Studies based on tissue samples presented better diagnostic accuracy than those based on plasma samples, with AUC values of 0.80 and 0.67. In addition, two circRNAs, including circ_0001073 and circTADA2A‐E5/E6, showed higher diagnostic values, with AUC value of 0.990 and 0.937, respectively. According to the results of meta‐regression, the case size (p<0.05) might be the source of the heterogeneity.ConclusionCircRNAs exhibited a high diagnostic value for breast cancer and may function as potential diagnostic biomarkers for breast cancer.     

Seven tumor‐associated autoantibodies as a serum biomarker for primary screening of early‐stage non‐small cell lung cancer

ObjectiveThe purpose of this study was to analyze the levels of tumor‐associated autoantibodies (TAAbs) in lung diseases and determine their diagnostic efficiency in early‐stage non‐small cell lung cancer (NSCLC).MethodsWe retrospectively analyzed the levels of 7‐TAAbs in 177 newly diagnosed early‐stage NSCLC patients, 202 patients with lung benign diseases and 137 healthy cases. The levels of a panel of 7‐TAAbs, including p53, GAGE7, PGP9.5, CAGE, MAGE A1, SOX2, GBU4‐5, were measured by ELISA.ResultsThe serum levels of p53, GAGE7, PGP9.5, CAGE, MAGE A1, SOX2, and GBU4‐5 were not statistically different among NSCLC, benign and healthy groups (p > 0.05). The area under the curve (AUC) of 7‐TAAbs was all lower than 0.70. The sensitivity of combined detection was the highest (23.73%), while the specificity was the lowest (88.79%). The positive rates of PGP9.5, SOX2, and combined detection were significantly different among the three groups (p < 0.05). Among them, PGP9.5 and combined detection were significantly different between the NSCLC and benign groups (p < 0.05), PGP9.5, SOX2 and combined detection were significantly different between the NSCLC and healthy groups (p < 0.05).ConclusionsThe diagnostic efficiency of 7‐TAAbs in early‐stage NSCLC was not high, so it cannot be used alone as a screening method for NSCLC.     

Circ_0000463 contributes to the progression and glutamine metabolism of non‐small‐cell lung cancer by targeting miR‐924/SLC1A5 signaling

BackgroundCircular RNAs (circRNAs) have shown pivotal regulatory roles in the pathology of non‐small cell lung cancer (NSCLC). However, the role of circ_0000463 in NSCLC progression and its associated molecular mechanism remain to be illustrated.MethodsCell proliferation ability was analyzed by colony formation assay and 5‐ethynyl‐2’‐deoxyuridine (EdU) assay. Cell migration and invasion abilities were assessed by scratch test and transwell invasion assay. Flow cytometry was employed to analyze cell apoptotic rate. The interaction between microRNA‐924 (miR‐924) and circ_0000463 or solute carrier family 1 member 5 (SLC1A5) was confirmed by dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The uptake of glutamine and the production of glutamate and α‐ketoglutarate were analyzed using their corresponding kits. Xenograft model in vivo was established to analyze the role of circ_0000463 in tumor growth.ResultsCirc_0000463 expression was elevated in NSCLC tissues and cell lines. Circ_0000463 knockdown suppressed the proliferation, migration, and invasion and promoted the apoptosis of NSCLC cells. Circ_0000463 acted as a molecular sponge for miR‐924, and circ_0000463 interference‐mediated anti‐tumor effects were largely reversed by the silence of miR‐924 in NSCLC cells. miR‐924 interacted with the 3’ untranslated region (3’UTR) of SLC1A5, and SLC1A5 overexpression largely overturned miR‐924 overexpression‐mediated anti‐tumor effects in NSCLC cells. Moreover, circ_0000463 absence suppressed the glutamine metabolism of NSCLC cells by targeting miR‐924/SLC1A5 axis. Circ_0000463 knockdown suppressed xenograft tumor growth in vivo.ConclusionCirc_0000463 absence suppressed the malignant behaviors and glutamine metabolism of NSCLC cells through mediating miR‐924/SLC1A5 axis.     

MiR‐630 suppresses non‐small cell lung cancer by targeting vimentin

ObjectiveThis study aimed to clarify the function of miR‐630 on non‐small cell lung cancer (NSCLC) cells.MethodsQuantitative real‐time PCR was utilized to detect the mRNA expression of miR‐630 and vimentin (VIM) in NSCLC tissues and cells. The protein expression of VIM, P53, Caspase‐3, Bcl‐2, Bax and JAK2/STAT3 was evaluated via Western blot. Dual‐luciferase reporter assay was applied to evaluate whether VIM is the target gene of miR‐630. The migration, invasion, proliferation and apoptosis of NSCLC cells were examined by wound‐healing assay, transwell assay, CCK‐8 assay, and flow cytometry, respectively.ResultsMiR‐630 was lowly expressed in NSCLC tissues and cells, while VIM was highly expressed in NSCLC cells. Dual‐luciferase reporter assay data validated that miR‐630 directly targeted VIM. MiR‐630 overexpression inhibited VIM expression, but the inhibition of miR‐630 upregulated VIM expression. Besides, miR‐630 mimics restrained cell migration, invasion, and proliferation, and promoted NSCLC cell apoptosis. Whereas, VIM overexpression partly attenuated the inhibitory effect of miR‐630 on NSCLC cells. Moreover, miR‐630 mimics impeded p‐JAK2 and p‐STAT3 protein expression; and miR‐630 inhibitor upregulated p‐STAT3 and VIM protein expression, which was reversed after the addition of STAT3 inhibitor C188‐9.ConclusionMiR‐630 constrained the progression of NSCLC by inhibiting JAK2/STAT3 pathway and downregulating VIM expression.     

Clinical manifestations,treatment options,and comorbidities in COVID‐19 relapse patients: A systematic review

IntroductionInterest revolving around coronavirus disease 2019 (COVID‐19) reinfection is escalating rapidly. By definition, reinfection denotes severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), PCR redetection, and COVID‐19 recurrence within three months of the initial symptoms. The main aim of the current systematic review was to evaluate the features of COVID‐19 relapse patients.Materials and methodsFor this study, we used a string of terms developed by a skilled librarian and through a systematical search in PubMed, Web of Science, and Embase for eligible studies. Clinical surveys of any type were included from January 2019 to March 2021. Eligible studies consisted of two positive assessments separated by a negative result via RT‐PCR.ResultsFifty‐four studies included 207 cases of COVID‐19 reinfection. Children were less likely to have COVID‐19 relapse. However, the most patients were in the age group of 20–40 years. Asthenia (66.6%), headache (66.6%), and cough (54.7%) were prevalent symptoms in the first SARS‐CoV‐2 infection. Asthenia (62.9%), myalgia (62.9%), and headache (61.1%) were most frequent in the second one. The most common treatment options used in first COVID‐19 infection were lopinavir/ritonavir (80%), oxygen support (69.2%), and oseltamivir (66.6). However, for the treatment of second infection, mostly antibiotics (100%), dexamethasone (100%), and remdesivir (80%) were used. In addition, obesity (32.5%), kidney failure (30.7%), and hypertension (30.1%) were the most common comorbidities. Unfortunately, approximately 4.5% of patients died.ConclusionWe found the potency of COVID‐19 recurrence as an outstanding issue. This feature should be regarded in the COVID‐19 management. Furthermore, the first and second COVID‐19 are similar in clinical features. For clinically practical comparison of the symptoms severity between two epochs of infection, uniform data of both are required. We suggest that future studies undertake a homogenous approach to establish the clinical patterns of the reinfection phenomena.     

A comprehensive profiling of soluble immune checkpoints from the sera of patients with non‐small cell lung cancer

BackgroundImmunotherapy was widely used for the treatment of non‐small cell lung cancer (NSCLC). However, whether inhibition of immune checkpoints individually or simultaneously could improve the therapeutic efficacy of NSCLC remains to be investigated. Here, we explored the aberrant levels of several checkpoints and evaluated their potential diagnostic values for NSCLC.MethodsSerum samples of 89 NSCLC patients and 57 healthy donors were collected from Nanjing Drum Tower Hospital between November 2019 and July 2020. Fourteen human immune checkpoints were quantified by Procarta‐Plex Human Immuno‐Oncology Checkpoint Panel.ResultsThe expression levels of sTIM‐3, sCD137, sCD27, sLAG‐3, sIDO, sPD‐L2, sCD152, sCD80, and sPD‐1 were all significantly increased in serum of NSCLC patients. Especially, sLAG‐3 was significantly elevated in serum of NSCLC patients at early‐stage (stages I and II), TIM‐3, CD137, and CD27 were significantly higher in the advanced NSCLC patients (stages III and IV) than in the early‐stage groups. Receiver operating characteristics (ROC) results showed that except for PD‐1, all the other immune checkpoint proteins had potential diagnostic values for NSCLC. sTIM‐3 had the highest diagnostic accuracy, followed by sLAG‐3. Combining sTIM‐3, sLAG‐3, and sCD137 could increase the accuracy to a higher level. Moreover, sCD27 was correlated with NSCLC cancer type, age, sex, and disease stage, while sCD137 was correlated with age and disease stage. sTIM‐3 and sIDO were correlated with stage and age, respectively.ConclusionsTIM‐3 and LAG‐3 were independent biomarkers for the early diagnosis of NSCLC. The combination of TIM‐3, LAG‐3, and CD137 could increase the diagnostic accuracy.     

Hsa_circ_0092887 targeting miR‐490‐5p/UBE2T promotes paclitaxel resistance in non‐small cell lung cancer

BackgroundChemoresistance is a major contributing factor to cancer treatment failure. Emerging research reveals that circular RNA (circRNA) dysregulation is implicated in chemoresistance. Our current study aimed to investigate the involvement of hsa_circ_0092887 in paclitaxel (PTX) resistance in non‐small cell lung cancer (NSCLC).MethodsRT‐qPCR as well as western blotting were used for the analysis of hsa_circ_0092887, miR‐490‐5p and UBE2T expression in PTX‐resistant NSCLC tumor tissues and cells. CCK‐8 assay was done to determine the IC50 value of PTX. CCK‐8 assay, wound healing assay, analysis of apoptosis related proteins (Bax and Bcl‐2), and xenograft mouse models were utilized to investigate the role of hsa_circ_0092887 in PTX‐resistance in NSCLC. The binding sites of miR‐490‐5p to hsa_circ_0092887 or UBE2T were predicted by bioinformatics tools and were verified by RIP and dual‐luciferase assays.ResultsExpression of hsa_Circ_0092887 was upregulated in NSCLC tumor samples/cell lines, and its expression was also higher in PTX‐resistant tumor samples/cell lines when compared with their respective controls. Silencing of hsa_circ_0092887 in PTX‐treated NSCLC cells inhibited cell proliferation and migration, induced apoptosis, and suppressed tumor growth in xenograft mouse models in vivo. MiR‐490‐5p was a direct target of hsa_circ_0092887, and UBE2T was a functional downstream target of hsa_circ_0092887/miR‐490‐5p axis. Hsa_circ_0092887 depletion‐induced anti‐cancer effects in PTX‐treated NSCLC cells were reversed by miR‐490‐5p inhibitor. Furthermore, inhibition of miR‐490‐5p strengthened UBE2T expression, thereby attenuating the anti‐cancer effects caused by UBE2T knockdown.ConclusionHsa_circ_0092887 depletion alleviated PTX‐resistance in NSCLC cells via modulating the miR‐490‐5p/UBE2T axis, and the targeted management of hsa_circ_0092887‐mediated signaling axis might contribute to PTX‐resistance intervention in NSCLC.     

E‐cigarette or vaping product use‐associated lung injury: A great COVID‐19 mimicker in young adult

EVALI and COVID‐19 share similar clinical and imaging features. Assessing the vaping or e‐cigarette use history and conducting urine toxicology tests for high‐risk patients are important with increasing COVID‐19 cases in young adults.     

Circ_SAR1A regulates the malignant behavior of lung cancer cells via the miR‐21‐5p/TXNIP axis

BackgroundLung cancer is one of the most common malignancies globally and a significant component of cancer‐related deaths. The lack of early diagnosis accounts for detecting approximately 75% of cancer patients at an intermediate to an advanced stage, with a low 5‐year survival rate. Therefore, a more comprehensive understanding of the molecular mechanisms of lung cancer development is necessary to find reliable and effective therapeutic and diagnostic biomarkers.Methodscirc_SAR1A, miR‐21‐5p, and TXNIP in lung cancer tissues, animal xenografts, and cell lines were validated by qRT‐PCR and western blotting analyses. RNase R digestion and nuclear/cytoplasm fractionation experiments were utilized to determine the stability and localization of circ_SAR1A in lung cancer cells. The binding between miR‐21‐5p and circ_SAR1A or TXNIP was confirmed by luciferase reporter, RNA pull‐down, Spearman''s correlation, and rescue assays. CCK‐8, colony formation, flow cytometry, Transwell, and western blotting were utilized to illustrate the malignant behavior of lung cancer cells.Resultscirc_SAR1A and TXNIP were down‐regulated while miR‐21‐5p was up‐regulated in lung cancer samples and cells. circ_SAR1A was located predominantly in the cytoplasm; it inhibited lung cancer growth in vitro and in vivo by sponging to miR‐21‐5p. miR‐21‐5p silencing suppressed lung cancer malignancy by targeting TXNIP.Conclusionscirc_SAR1A is a critical negative regulator of lung carcinogenesis. circ_SAR1A/miR‐21‐5p/TXNIP attenuation inhibited lung cancer progression, presenting an ideal diagnostic and a potential therapeutic target.