The diagnostic utility of CT attenuation values in detecting calcification within costal cartilage.

BACKGROUND: To establish and verify diagnostic criteria for the identification of costal cartilage calcification based on computed tomography (CT) attenuation value. METHODS: 360 chest CT slices of 120 patients were reviewed and annotated retrospectively and receiver operating characteristic curve was used to evaluate the diagnostic ability of CT attenuation value. Another 20 slices containing calcification were randomly selected and annotated by 4 doctors for further validation. hematoxylin and eosin and collagen type X (COLX) staining was performed on the residual costal cartilage. RESULTS: In total 355,129 voxels were detected and 187.5 was confirmed as the optimal CT attenuation value threshold, with a sensitivity of 98.6% and a specificity of 99.7%, for costal cartilage calcification diagnosis. Threshold-based identification of calcification demonstrated a similarity of nearly 80% with specialists' assessments, and exhibited advantages in the identification of subtle calcifications in the further validation. We also observed that CT attenuation values among males demonstrated a centralized distribution, whereas those among females exhibited a bimodal distribution. Threshold-based identified calcification showed a positivity of COLX. CONCLUSIONS: CT attenuation value could validly and reliably diagnose calcification within costal cartilage. Further investigations involving larger cohorts of patients are required to elucidate the risk factors and underlying mechanisms of costal cartilage calcification.

Impact of enhanced recovery after surgery (ERAS) on surgical site infection and postoperative recovery outcomes: a retrospective study of 1276 cases.

This retrospective observational study aimed to evaluate the incidence of surgical site infection (SSI) in the era of enhanced recovery after surgery (ERAS) and the effect of ERAS on postoperative outcomes. Totally 1,276 patients (565 in ERAS group and 711 in non-ERAS group) who underwent operations at the department of general surgery during 2017-2021 were included. Risk factors were identified via logistic regression analysis and meta-analysis of all relevant published studies was performed. Subsequently, propensity score matching was used to match different risk factors. Overall, 40 patients were diagnosed with SSI, and the pooled incidence of SSI was 3.13%. In total, 14 (2.48%) and 26 (3.66%) patients in the ERAS and non-ERAS groups, respectively, were diagnosed with SSI (P = 0.230). Among patients for whom the ERAS protocol was adopted, 7 independent risk factors of SSI were identified. After propensity score matching, in patients without SSI, the number of hospital days was significantly lower in the ERAS group than in the non-ERAS group (2 [2, 5] vs. 3 [2, 7], P = 0.005), whereas in patients with SSI, the number of hospital days was similar between the ERAS and non-ERAS groups. ERAS had no effect on the incidence of SSI but could significantly accelerate the discharge of uninfected patients. In the era of ERAS, SSI incidence was affected by the type of surgery; number of postoperative hospital days; type of incision; serum hemoglobin, total protein, and albumin levels; and antibiotic prophylaxis. Furthermore, these results will significantly affect the implementation of the ERAS protocol and optimal preoperative management.

Improvement of fire safety for viscose fabrics based on phytic acid modified tea polyphenols complexed iron ions.

In this work, a multifunctional finishing agent named as PATFe was prepared from phytic acid (PA), tea polyphenols (TP), and Fe3+. The optimum weight ratio of PA to TP was determined by exploring the effect on flame retardant and tensile properties of viscose fabrics. Then, the effects of different concentrations of iron ions on the flame retardant and tensile properties of viscose fabrics were further investigated, and finally, multifunctional viscose fabrics, PATFe-9, were prepared. The system was investigated to confer the multifunctional effects on the flame retardant, bacteriostatic, and UV-resistant properties of viscose fabrics under the condition of lower weight gains (about 6.0 wt%). The limiting oxygen index of PATFe-9 reached 33.7 % with a weight gain of 6.1 wt%, and PATFe-9 had an inhibition effect against Staphylococcus aureus, and the ultraviolet protection factor value reached 67. It is worth noting that the breaking force retention rate of this system reached 100 %, which greatly improves the scope of use and added value of viscose fabrics.

Oral microbiome diversity and diet quality in relation to mortality.

AIM: To examine the independent and joint associations of oral microbiome diversity and diet quality with risks of all-cause and cause-specific mortality. MATERIALS AND METHODS: We included 7,055 eligible adults from the U.S. National Health and Nutrition Examination Survey (NHANES). Oral microbiome diversity was measured with α-diversity, including the Simpson Index, observed amplicon sequence variants (ASVs), Faith's phylogenetic diversity, and Shannon-Weiner index. Dietary quality was assessed using the Healthy Eating Index-2015 (HEI-2015). Cox proportional hazard models were used to assess the corresponding associations. RESULTS: During a mean follow-up of 9.0 years, we documented 382 all-cause deaths. We observed independent associations of oral microbiome diversity indices and dietary quality with all-cause mortality (hazard ratio [HR] = 0.63; 95% confidence interval [CI]: 0.49-0.82 for observed ASVs; HR = 0.68, 95% CI: 0.52-0.89 for HEI-2015). Jointly, participants with the highest tertiles of both oral microbiome diversity (in Simpson index) and HEI-2015 had the lowest hazard of mortality (HR = 0.37, 95% CI: 0.23-0.60). In addition, higher oral microbiome diversity was associated with lower risks of deaths from cardiometabolic disease and cancer. CONCLUSIONS: Higher oral microbiome α-diversity and diet quality were independently associated with lower risk of mortality.

Alkaline amino acid modification based on biological phytic acid for preparing flame-retardant and antibacterial cellulose-based fabrics.

Cellulose-based fabrics have significant advantages, but their application scenarios are limited due to their flammability. This work used biomass phytic acid and protein decomposition products, alkaline amino acids (arginine, lysine, histidine) to prepare alkaline amino acid flame retardants (PALA, PALL, PALH), and they were utilized to endow Lyocell fabrics with flame-retardant and antibacterial properties. When the weight gain was about 16.0 wt%, PALA exhibited better flame-retardant effect, and the limited oxygen index value of PALA-Lyocell reached 47.1 %. In the cone calorimetry test, PALA showed the best flame-retardant efficiency in reducing flame growth index with a 92.0 % decrease in peak heat release rate. The results of thermogravimetric analysis coupled with Fourier Transform Infrared spectroscopy (TG-FTIR) and char residues indicated that the flame-retardant property of alkaline amino acid flame retardants was formed through the combined action of gas and condensed phases. In the antibacterial test, PALA had the highest antibacterial rate against Staphylococcus aureus at 97.2 %. Mechanical property, handle feeling, and whiteness results had indicated that alkaline amino acid based flame retardants had little effect on the physical properties of Lyocell fabrics. This work confirms alkaline amino acid based flame retardants have functions of flame-retardant and antibacterial properties, providing reference for the practical value of biomass in cellulose-based fabrics.

Dynamic Screening of Thyroid Function for the Timely Diagnosis of Congenital Hypothyroidism in Very Preterm Infants: A Prospective Multicenter Cohort Study.

Background: Preterm infants presented a high prevalence of congenital hypothyroidism (CH), while the optimal screening pattern is still under debate. This study aimed at evaluating the characteristics of thyroid function by conducting weekly screening during the first month of life in very preterm infants (VPIs) to achieve timely diagnosis and treatment of CH. Methods: A prospective cohort study was carried out on VPIs born with gestational age (GA) <32 weeks (w) and admitted to the participating institutes from January 1, 2019 to December 31, 2022. Serial serum thyroid hormone levels were measured weekly within the first month after birth, and at 36 w of corrected age, or before discharge. Datasets for serial thyroid hormone levels and general information were obtained. Results: A total of 5992 VPIs were enrolled in this study, of which 456 (7.6%) [95% confidence interval (CI), 6.9-8.3%] were diagnosed with CH. The incidence of CH increased with lower GA, moving from 4.8% [CI, 3.4-6.1%] at GA 31 w to 16.9% [CI, 8.3-25.4%] at GA <26 w. Among the CH subjects, 57.7% [CI, 53.1-62.2%] were identified after the first screening and classified as delayed thyrotropin elevation (dTSH). With the decrease of GA, the proportion of dTSH also increased, moving from 38.1% [CI, 27.5-48.7%] at GA 31 w to 82.6% [CI, 65.8-99.4%] at GA <26 w. Through conducting weekly screening of thyroid function, it was remarkable that only 42.3% [CI, 37.8-46.9%] of CH subjects were diagnosed during the first screening. The cumulative rate of CH identified by rescreening performed at the second, third, and fourth week was 76.1% [CI, 72.2-80.0%], 90.6% [CI, 87.9-93.3%], and 98.9% [CI, 97.9-99.9%], respectively. Conclusion: The incidence of CH and dTSH both increase with lower GA in VPIs. Dynamic screening of thyroid function by weeks within the first month of life is crucial for the timely diagnosis and treatment of CH in VPIs, and it might effectively reduce the implications of missed diagnosis and delayed treatment. Clinical Trials Registration: ChiCTR1900025234 and ChiCTR2000037918 (Registration number).

Alterations in Faecal and Serum Metabolic Profiles in Patients with Neovascular Age-Related Macular Degeneration.

Neovascular age-related macular degeneration (nAMD) is a common and multifactorial disease in the elderly that may lead to irreversible vision loss; yet the pathogenesis of AMD remains unclear. In this study, nontargeted metabolomics profiling using ultra-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry was applied to discover the metabolic feature differences in both faeces and serum samples between Chinese nonobese subjects with and without nAMD. In faecal samples, a total of 18 metabolites were significantly altered in nAMD patients, and metabolic dysregulations were prominently involved in glycerolipid metabolism and nicotinate and nicotinamide metabolism. In serum samples, a total of 29 differential metabolites were founded, involved in caffeine metabolism, biosynthesis of unsaturated fatty acids, and purine metabolism. Two faecal metabolites (palmitoyl ethanolamide and uridine) and three serum metabolites (4-hydroxybenzoic acid, adrenic acid, and palmitic acid) were selected as potential biomarkers for nAMD. Additionally, the significant correlations among dysregulated neuroprotective, antineuroinflammatory, or fatty acid metabolites in faecal and serum and IM dysbiosis were found. This comprehensive metabolomics study of faeces and serum samples showed that alterations in IM-mediated neuroprotective metabolites may be involved in the pathophysiology of AMD, offering IM-based nutritional therapeutic targets for nAMD.

Akkermansia muciniphila inhibits nonalcoholic steatohepatitis by orchestrating TLR2-activated γδT17 cell and macrophage polarization.

Current evidence indicates that the next-generation probiotic Akkermansia muciniphila (A. muciniphila) has therapeutic potential for nonalcoholic fatty liver disease (NAFLD), especially its inflammatory stage known as nonalcoholic steatohepatitis (NASH). However, the mechanisms of A. muciniphila in NASH prevention remain unknown. Here, A. muciniphila supplementation prevented hepatic inflammation in high-fat diet-induced NASH mice, characterized by reduced hepatic proinflammatory macrophages (M1) and γδT and γδT17 cells. Consistently, hepatic M1 and γδT cells were enriched in biopsy-proven NASH patients and high-fat/high-carbohydrate diet-induced NASH mice. Antibiotics reduced hepatic M1, γδT and γδT17 cells in NASH mice. Furthermore, A. muciniphila inhibited intestinal barrier disruption and accordingly downregulated hepatic Toll-like receptor 2 (TLR2) expression in NASH mice. The activation of TLR2 by lipoteichoic acid enriched hepatic γδT17 cells (not M1) in normal diet-fed mice and neutralized the γδT cell-lowering and liver inflammation-protecting effects of A. muciniphila in NASH mice. Additionally, activated γδT cells could promote macrophage polarization via IL-17. Our study first supported that A. muciniphila prevented NASH by modulating TLR2-activated γδT17 cells and further macrophage polarization, facilitating clinical therapeutic applications.

Healthy lifestyles in relation to cardiometabolic diseases among schoolteachers: A cross-sectional study.

Background: We aimed to explore the associations of adherence to an overall healthy lifestyle with cardiometabolic diseases (CMDs) among schoolteachers in China. Methods: We conducted a cross-sectional analysis among 2983 teachers (aged 39.8 ± 9.3 years, 73.8% women) in Zhejiang Province, China. A healthy lifestyle score (0-7) was constructed based on seven low-risk factors: healthy diet, noncurrent smoking, noncurrent drinking, regular exercise, normal body mass index (BMI), adequate sleep duration, and limited sedentary behavior. CMDs included self-reported hyperlipidemia, hypertension, diabetes, coronary heart disease, and stroke. Multivariable-adjusted logistic regression models were used to evaluate the associations between healthy lifestyle and CMD. Results: A total of 493 (16.5%) participants had at least one CMD, with hyperlipidemia, hypertension, and diabetes being the three leading CMDs. Each point increment in a healthy lifestyle score was associated with 20% lower odds of having CMD (p-trend < 0.001). Compared with 0-3 low-risk factors, the odds ratios (ORs) and 95% confidence intervals (CIs) were 0.66 (0.50-0.88) for 4 low-risk factors and 0.51 (0.39-0.67) for 5-7 low-risk factors. We observed independent associations for normal BMI (OR = 0.50, 95% CI = 0.40-0.63), noncurrent drinking (OR = 0.53, 95% CI = 0.36-0.77), and limited sedentary behavior (OR = 0.77, 95% CI = 0.62-0.96) in relation to CMD. Healthy diet (OR = 0.75, 95% CI = 0.55-1.01) exhibited marginally significant association with CMD. Conclusions: Our findings suggest that adherence to an overall healthy lifestyle is associated with lower odds of CMD among schoolteachers.

Systematic analysis of microbiota in pregnant Chinese women and its association with miscarriage.

Background: Miscarriage is the most common adverse pregnancy outcome and more than 50% of its incidence remains unexplained. Earlier studies have suggested that maternal microbiota might be associated with miscarriage, but the association is insufficiently understood. Methods: We used 16S ribosomal RNA (rRNA) amplicon sequencing and metagenomic sequencing technology to characterize the bacterial composition of three sites including the rectum, vagina, and cervix of a case group of 63 pregnant women who had miscarried compared to a control group of 24 pregnant women who underwent voluntary elective abortion. Results: The alpha-diversity from the rectum and cervix was significantly decreased in the case group relative to the control group. However, we did not find significant differences in microbial diversity of vaginal samples between the two groups. Lactobacillus was the most predominant genus in the cervix and vaginal samples. Gestational age at the time of surgery was positively associated with the rectum microbiota diversity, with an effect size of 10% (P=0.004). Host factors including gestational age and red blood count (RBC) were associated with the rectal microbiota diversity. Conclusions: We detected a significantly lower rectal microbiota diversity and a pro-inflammatory tendency in the miscarriage group. This is the first study to investigate the association of microbiota from samples collected from three sites and miscarriage. Further studies are warranted to explore further the role of microbiota in miscarriage.

Role of Akkermansia muciniphila in the development of nonalcoholic fatty liver disease: current knowledge and perspectives.

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome and a common cause of liver cirrhosis and cancer. Akkermansia muciniphila (A. muciniphila) is a next-generation probiotic that has been reported to improve metabolic disorders. Emerging evidence indicates the therapeutic potential of A. muciniphila for NAFLD, especially in the inflammatory stage, nonalcoholic steatohepatitis. Here, the current knowledge on the role of A. muciniphila in the progression of NAFLD was summarized. A. muciniphila abundancy is decreased in animals and humans with NAFLD. The recovery of A. muciniphila presented benefits in preventing hepatic fat accumulation and inflammation in NAFLD. The details of how microbes regulate hepatic immunity and lipid accumulation in NAFLD were further discussed. The modulation mechanisms by which A. muciniphila acts to improve hepatic inflammation are mainly attributed to the alleviation of inflammatory cytokines and LPS signals and the downregulation of microbiota-related innate immune cells (such as macrophages). This review provides insights into the roles of A. muciniphila in NAFLD, thereby providing a blueprint to facilitate clinical therapeutic applications.

Exploratory studies of oral and fecal microbiome in healthy human aging.

Growing evidence has linked an altered host fecal microbiome composition with health status, common chronic diseases, and institutionalization in vulnerable older adults. However, fewer studies have described microbiome changes in healthy older adults without major confounding diseases or conditions, and the impact of aging on the microbiome across different body sites remains unknown. Using 16S ribosomal RNA gene sequencing, we reconstructed the composition of oral and fecal microbiomes in young (23-32; mean = 25 years old) and older (69-94; mean = 77 years old) healthy community-dwelling research subjects. In both body sites, we identified changes in minor bacterial operational taxonomic units (OTUs) between young and older subjects. However, the composition of the predominant bacterial species of the healthy older group in both microbiomes was not significantly different from that of the young cohort, which suggests that dominant bacterial species are relatively stable with healthy aging. In addition, the relative abundance of potentially pathogenic genera, such as Rothia and Mycoplasma, was enriched in the oral microbiome of the healthy older group relative to the young cohort. We also identified several OTUs with a prevalence above 40% and some were more common in young and others in healthy older adults. Differences with aging varied for oral and fecal samples, which suggests that members of the microbiome may be differentially affected by aging in a tissue-specific fashion. This is the first study to investigate both oral and fecal microbiomes in the context of human aging, and provides new insights into interactions between aging and the microbiome within two different clinically relevant sites.

Gut Microbiota Regulation of AHR Signaling in Liver Disease.

Liver health plays a vital role in human health and disease. Emerging evidence has shown the importance of the aryl hydrocarbon receptor (AHR) in liver diseases such as alcoholic liver disease, fatty liver disease, and liver failure. As a ligand-activated transcription factor, AHR can be activated by endogenous ligands of microbial metabolites such as tryptophan (Trp), kynurenine (Kyn) or indole derivatives locally or distantly. However, the therapeutic effects of the gut microbiota-regulated AHR pathway remain to be clarified. In this review, we summarize recent progress and examine the role of AHR signaling as a target for gut microbiota intervention in liver diseases. The focus on AHR signaling will identify a promising target in the gut microbiota for better understanding and therapeutic opportunities in liver diseases.

Identification of potential immune/diagnosis related gene-immunocyte subtype networks in extracellular immune response to respiratory syncytial virus infection.

INTRODUCTION: Respiratory syncytial virus (RSV) is one of the important pathogenic agents of pediatric respiratory tract infection. Weighted gene co-expression network analysis (WGCNA) is used to study autoimmune diseases, which can find potential hub genes. The diagnostic model based on hub genes and machine learning makes it possible to diagnose the extracellular immune response to RSV infection early. OBJECTIVE: The aim of the present study was to identify potential immune, diagnose and treatment related genes expressed in RSV-infected cells. METHODS: Firstly, gene expression data were downloaded from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs). Secondly, WGCNA was performed based on DEGs to obtain hub genes related to immunity score. Thirdly, protein-protein interaction (PPI) and the immune infiltration analysis of hub immune related genes were performed. Finally, diagnostic and immune related genes were identified by machine learning, followed by functional analysis. RESULTS: Totally, 2063 DEGs were identified in the extracellular immune response to RSV infection. Among which, 10 key immune and diagnosis related genes were identified, including ITGA2B, GP9, ITGB3, SELP, PPBP, MPL, CXCL8, NFE2, PTGS1 and LY6G6F. Several immune/diagnosis related gene-immunocyte subtype networks were identified, such as CXCL8-Type 17 T helper cell, LY6G6F-CD56 bright natural killer cell, PPBP-activated CD4 T cell/T follicular helper cell, NFE2/PTGS1/SELP-activated dendritic cell, GP9/ITGA2B/MPL-activated CD8 T cell. ITGB3, MPL and PTGS1 could be considered as therapeutic targets. Some significantly enriched signaling pathways were identified, including hematopoietic cell lineage (involving GP9 and ITGA2B), cytokine-cytokine receptor interaction (involving MPL), chemokine signaling pathway (involving PPBP) and arachidonic acid metabolism (involving PTGS1). CONCLUSIONS: The 10-immune related gene signature may be used as potential diagnostic markers for the extracellular immune response to RSV infection, which may provide a new field in searching for diagnostic and therapeutic molecules in the extracellular immune response to RSV infection.

Unusual global outbreak of monkeypox: what should we do?

Recently, monkeypox has become a global concern amid the ongoing COVID-19 pandemic. Monkeypox is an acute rash zoonosis caused by the monkeypox virus, which was previously concentrated in Africa. The re-emergence of this pathogen seems unusual on account of outbreaks in multiple nonendemic countries and the incline to spread from person to person. We need to revisit this virus to prevent the epidemic from getting worse. In this review, we comprehensively summarize studies on monkeypox, including its epidemiology, biological characteristics, pathogenesis, and clinical characteristics, as well as therapeutics and vaccines, highlighting its unusual outbreak attributed to the transformation of transmission. We also analyze the present situation and put forward countermeasures from both clinical and scientific research to address it.

Inhibition of lncRNA NEAT1 sensitizes medulloblastoma cells to cisplatin through modulating the miR-23a-3p-glutaminase (GLS) axis.

Medulloblastoma (MB) is a commonly occurring brain malignancy in adolescence. Currently, the combination of chemotherapy with subsequent irradiation is a regular therapeutic strategy. However, high dosage of chemotherapy is associated with drug resistance and side effects. The long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1), which is frequently overexpressed in diverse human tumors, is correlated with worse survival rate in cancer patients. Currently, the precise roles of NEAT1 in MB and chemoresistance remain unclear. Our study aimed to investigate the biological functions of NEAT1 in cisplatin-resistant medulloblastoma. We report that NEAT1 was significantly upregulated in medulloblastoma patient specimens. Silencing NEAT1 significantly suppressed MB cell proliferation and sensitized MB cells to cisplatin. In cisplatin-resistant MB cell line, DAOY Cis R, NEAT1 expression, and glutamine metabolism were remarkably upregulated in cisplatin-resistant cells. Under low glutamine supply, cisplatin-resistant cells displayed increased cisplatin sensitivity. Bioinformatical analysis and luciferase assay uncovered that NEAT1 functions as a ceRNA of miR-23a-3p to downregulate its expressions in MB cells. Moreover, miR-23a-3p was apparently downregulated in MB patient tissues and cisplatin resistant MB cells. We identified GLS (glutaminase), a glutamine metabolism enzyme, was directly targeted by miR-23a-3p in MB cells. Rescue experiments demonstrated restoration of miR-23a-3p in NEAT1-overexpressing DAOY cisplatin resistant cells successfully overcame the NEAT1-promoted cisplatin resistance by targeting GLS. In general, our results revealed new molecular mechanisms for the lncRNA-NEAT1-mediated cisplatin sensitivity of MB.

Microbial metabolites indole derivatives sensitize mice to D-GalN/LPS induced-acute liver failure via the Tlr2/NF-κB pathway.

Introduction: Acute liver failure (ALF) is a clinical condition with many causes, fast progression, and a poor prognosis. Previous research has indicated that microbial factors have a role in ALF, but a clear picture has yet to emerge. Methods: To investigate the specific involvement of microbial metabolites in ALF development, we pretreated D-GalN/LPS-induced ALF mice with indole derivatives, an influential class of gut microbial metabolites. Results: Contrary to their typical role as anti-inflammatory agents in the host, indole-3-acetic acid (IAA), indole-3-lactic acid (ILA), and indolepropionic acid (IPA) gavage sensitize mice to D-GalN/LPS-induced-ALF with a rapid rise in serum transaminases and histologic lesion. For a clearer picture, we performed comprehensive analysis for the IAA therapy. IAA markedly amplified inflammatory response and cellular damage. The transcriptome analysis indicated the participation of the TNF-α/NF-κB signaling pathway. The structure of gut microbiota in ileum and the expression of Toll-like receptor 2 (Tlr2) in the liver were also significantly changed. Discussion: In conclusion, IAA pretreatment can exacerbate D-GalN/LPS-induced ALF via probable Tlr2/NF-κB pathway involvement and ileac dysbiosis characterized by enriched gram-positive genus with potential pathogenesis. Microbial metabolites IAA may aggravate individual susceptibility to D-GalN/LPS-induced ALF. Further investigation of the underlying mechanism is needed, and intervention with indole derivatives and related commensal species should be undertaken with caution.

CircSLC7A6 promotes the progression of Wilms' tumor via microRNA-107/ ABL proto-oncogene 2 axis.

The dysregulation of circular RNAs (circRNAs) has been proved to be involved in the carcinogenesis of various cancers. Nevertheless, the biological function of circSLC7A6 remains unclear in Wilms' tumor (WT). In our study, we found that circSLC7A6 was upregulated in cancerous WT tissues and cells. Cell apoptosis was increased while cell viability, migration, and invasion were repressed by circSLC7A6 silencing. Besides, circSLC7A6 knockdown suppressed WT tumor growth in vivo. miR-107 was identified as a direct target of circSLC7A6, and circSLC7A6 could negatively regulate miR-107 expression. In addition, circSLC7A6 knockdown inhibited WT progression, while the effect was partially abolished by the downregulation of miR-107. Additionally, ABL proto-oncogene 2 axis (ABL2) was verified as a downstream gene of miR-107, and circSLC7A6 could upregulate ABL2 expression by serving as a ceRNA of miR-107. Moreover, functional assays revealed that ABL2 overexpression reversed the impact of circSLC7A6 depletion on cell proliferation, migration, invasion, and apoptosis of WT. In conclusion, the present study demonstrated that circSLC7A6 facilitated WT progression by upregulating ABL2 through inhibiting miR-107 expression. These results suggested that circSLC7A6 might serve as a potential therapeutic target for WT.

Comparison of lorlatinib, alectinib and brigatinib in ALK inhibitor-naive/untreated ALK-positive advanced non-small-cell lung cancer: a systematic review and network meta-analysis.

Because of lacking of head-to-head comparison among lorlatinib, alectinib and brigatinib for patients with ALK inhibitor-naive or untreated (ALK inhibitor-naive and chemotherapy-naive) ALK-positive advanced non-small-cell lung cancer (NSCLC), the optimal option for these patients still remains undefined. We searched published reports that described the activity and safety of those novel ALK inhibitors (lorlatinib, alectinib and brigatinib) for ALK inhibitor-naive or untreated (ALK inhibitor-naive and chemotherapy-naive) ALK-positive advanced NSCLC. Five randomized controlled trials were identified, covering 1111 subjects. In the network meta-analysis, lorlatinib seemed to prolong progression free survival than brigatinib (Hazard Ratio: 0.57, P = 0.03) and alectinib (Hazard ratio: 0.65, P = 0.05) for previously untreated patients with ALK-positive advanced NSCLC as assessed by the independent review committee. Meanwhile, lorlatinib significantly improved significant progression free survival than brigatinib (Hazard ratio: 0.57, P = 0.03) and alectinib (Hazard ratio: 0.59, P = 0.03) for ALK inhibitor-naive patients. Among lorlatinib, alectinib, brigatinib, and crizotinib, lorlatinib had the highest probability to reach the best overall confirmed response rates (probability of 48%) and intracranial confirmed response rates (probability of 44%). No significant difference was found among them in overall survival and adverse events analysis. In terms of progression free survival, our results indicated that lorlatinib was the best treatment choice for patients with ALK inhibitor-naive or untreated (ALK inhibitor-naive and chemotherapy-naive) ALK-positive advanced NSCLC. The future head-to-head trials assessing the relative efficacy of lorlatinib, alectinib and brigatinib were warranted.