NOX4 promotes tumor progression through the MAPK-MEK1/2-ERK1/2 axis in colorectal cancer.

BACKGROUND: Metabolic reprogramming plays a key role in cancer progression and clinical outcomes; however, the patterns and primary regulators of metabolic reprogramming in colorectal cancer (CRC) are not well understood. AIM: To explore the role of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in promoting progression of CRC. METHODS: We evaluated the expression and function of dysregulated and survival-related metabolic genes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Consensus clustering was used to cluster CRC based on dysregulated metabolic genes. A prediction model was constructed based on survival-related metabolic genes. Sphere formation, migration, invasion, proliferation, apoptosis and clone formation was used to evaluate the biological function of NOX4 in CRC. mRNA sequencing was utilized to explore the alterations of gene expression NOX4 over-expression tumor cells. In vivo subcutaneous and lung metastasis mouse tumor model was used to explore the effect of NOX4 on tumor growth. RESULTS: We comprehensively analyzed 3341 metabolic genes in CRC and identified three clusters based on dysregulated metabolic genes. Among these genes, NOX4 was highly expressed in tumor tissues and correlated with worse survival. In vitro, NOX4 overexpression induced clone formation, migration, invasion, and stemness in CRC cells. Furthermore, RNA-sequencing analysis revealed that NOX4 overexpression activated the mitogen-activated protein kinase-MEK1/2-ERK1/2 signaling pathway. Trametinib, a MEK1/2 inhibitor, abolished the NOX4-mediated tumor progression. In vivo, NOX4 overexpression promoted subcutaneous tumor growth and lung metastasis, whereas trametinib treatment can reversed the metastasis. CONCLUSION: Our study comprehensively analyzed metabolic gene expression and highlighted the importance of NOX4 in promoting CRC metastasis, suggesting that trametinib could be a potential therapeutic drugs of CRC clinical therapy targeting NOX4.

Multiplex gene editing reduces oxalate production in primary hyperoxaluria type 1.

Targeting key enzymes that generate oxalate precursors or substrates is an alternative strategy to eliminate primary hyperoxaluria type I (PH1), the most common and life-threatening type of primary hyperoxaluria. The compact Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) from the Prevotella and Francisella 1 (Cpf1) protein simplifies multiplex gene editing and allows for all-in-one adeno-associated virus (AAV) delivery. We hypothesized that the multiplex capabilities of the Cpf1 system could help minimize oxalate formation in PH1 by simultaneously targeting the hepatic hydroxyacid oxidase 1 ( Hao1) and lactate dehydrogenase A ( Ldha) genes. Study cohorts included treated PH1 rats ( Agxt Q84X rats injected with AAV-AsCpf1 at 7 days of age), phosphate-buffered saline (PBS)-injected PH1 rats, untreated PH1 rats, and age-matched wild-type (WT) rats. The most efficient and specific CRISPR RNA (crRNA) pairs targeting the rat Hao1 and Ldha genes were initially screened ex vivo. In vivo experiments demonstrated efficient genome editing of the Hao1 and Ldha genes, primarily resulting in small deletions. This resulted in decreased transcription and translational expression of Hao1 and Ldha. Treatment significantly reduced urine oxalate levels, reduced kidney damage, and alleviated nephrocalcinosis in rats with PH1. No liver toxicity, ex-liver genome editing, or obvious off-target effects were detected. We demonstrated the AAV-AsCpf1 system can target multiple genes and rescue the pathogenic phenotype in PH1, serving as a proof-of-concept for the development of multiplex genome editing-based gene therapy.

Manual aspiration of a pneumothorax after CT-guided lung biopsy: outcomes and risk factors.

OBJECTIVE: Quantify the outcomes following pneumothorax aspiration and influence upon chest drain insertion. METHODS: This was a retrospective cohort study of patients who underwent aspiration for the treatment of a pneumothorax following a CT percutaneous transthoracic lung biopsy (CT-PTLB) from January 1, 2010 to October 1, 2020 at a tertiary center. Patient, lesion and procedural factors associated with chest drain insertion were assessed with univariate and multivariate analyses. RESULTS: A total of 102 patients underwent aspiration for a pneumothorax following CT-PTLB. Overall, 81 patients (79.4%) had a successful pneumothorax aspiration and were discharged home on the same day. In 21 patients (20.6%), the pneumothorax continued to increase post-aspiration and required chest drain insertion with hospital admission. Significant risk factors requiring chest drain insertion included upper/middle lobe biopsy location [odds ratio (OR) 6.46; 95% CI 1.77-23.65, p = 0.003], supine biopsy position (OR 7.06; 95% CI 2.24-22.21, p < 0.001), emphysema (OR 3.13; 95% CI 1.10-8.87, p = 0.028), greater needle depth ≥2 cm (OR 4.00; 95% CI 1.44-11.07, p = 0.005) and a larger pneumothorax (axial depth ≥3 cm) (OR 16.00; 95% CI 4.76-53.83, p < 0.001). On multivariate analysis, larger pneumothorax size and supine position during biopsy remained significant for chest drain insertion. Aspiration of a larger pneumothorax (radial depths ≥3 cm and ≥4 cm) had a 50% rate of success. Aspiration of a smaller pneumothorax (radial depth 2-3 cm and <2 cm) had an 82.6% and 100% rate of success, respectively. CONCLUSION: Aspiration of pneumothorax after CT-PTLB can help reduce chest drain insertion in approximately 50% of patients with larger pneumothoraces and even more so with smaller pneumothoraces (>80%). ADVANCES IN KNOWLEDGE: Aspiration of pneumothoraces up to 3 cm was often associated with avoiding chest drain insertion and allowing for earlier discharge.

Selective internal radiation therapy for hepatocellular carcinoma: A 15-year multicenter Australian cohort study.

BACKGROUND AND AIM: The exact place for selective internal radiation therapy (SIRT) in the therapeutic algorithm for hepatocellular carcinoma (HCC) is debated. There are limited data on its indications, efficacy, and safety in Australia. METHODS: We performed a multicenter retrospective cohort study of patients undergoing SIRT for HCC in all Sydney hospitals between 2005 and 2019. The primary outcome was overall survival. Secondary outcomes were progression-free survival and adverse events. RESULTS: During the study period, 156 patients underwent SIRT across 10 institutions (mean age 67 years, 81% male). SIRT use progressively increased from 2005 (n = 2), peaking in 2017 (n = 42) before declining (2019: n = 21). Barcelona Clinic Liver Cancer stages at treatment were A (13%), B (33%), C (52%), and D (2%). Forty-four (28%) patients had tumor thrombus. After a median follow-up of 13.9 months, there were 117 deaths. Median overall survival was 15 months (95% confidence interval 11-19). Independent predictors of mortality on multivariable analysis were extent of liver involvement, Barcelona Clinic Liver Cancer stage, baseline ascites, alpha fetoprotein, and model for end-stage liver disease score. Median progression-free survival was 6.0 months (95% confidence interval 5.1-6.9 months). Following SIRT, 11% of patients were downstaged to curative therapy. SIRT-related complications occurred in 17%: radioembolization-induced liver disease (11%), pneumonitis (3%), gastrointestinal ulceration, and cholecystitis (1% each). Baseline ascites predicted for radioembolization-induced liver disease. CONCLUSION: We present the largest Australian SIRT cohort for HCC. We have identified several factors associated with a poor outcome following SIRT. Patients with early-stage disease had the best survival with some being downstaged to curative therapy.

Association of Serum Interleukin-8 and Serum Amyloid A With Anxiety Symptoms in Patients With Cerebral Small Vessel Disease.

Objective: Cerebral small vessel disease (CSVD) is a clinical syndrome caused by pathological changes in small vessels. Anxiety is a common symptom of CSVD. Previous studies have reported the association between inflammatory factors and anxiety in other diseases, but this association in patients with CSVD remains uncovered. Our study aimed to investigate whether serum inflammatory factors correlated with anxiety in patients with CSVD. Methods: A total of 245 CSVD patients confirmed using brain magnetic resonance imaging (MRI) were recruited from December 2019 to December 2021. Hamilton Anxiety Rating Scale (HAMA) was used to assess the anxiety symptoms of CSVD patients. Patients with HAMA scores ≥7 were considered to have anxiety symptoms. The serum levels of interleukin-1ß (IL-1ß), IL-2R, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), serum amyloid A (SAA), C-reactive protein (CRP), high-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR) were detected. We compared levels of inflammatory factors between the anxiety and non-anxiety groups. Logistic regression analyses examined the correlation between inflammatory factors and anxiety symptoms. We further performed a gender subgroup analysis to investigate whether this association differed by gender. Results: In the fully adjusted multivariate logistic regression analysis model, we found that lower levels of IL-8 were linked to a higher risk of anxiety symptoms. Moreover, higher levels of SAA were linked to a lower risk of anxiety symptoms. Our study identified sex-specific effects, and the correlation between IL-8 and anxiety symptoms remained significant among males, while the correlation between SAA and anxiety symptoms remained significant among females. Conclusions: In this study, we found a suggestive association between IL-8, SAA, and anxiety symptoms in CSVD participants. Furthermore, IL-8 and SAA may have a sex-specific relationship with anxiety symptoms.

MRI detection of suspected nasopharyngeal carcinoma: a systematic review and meta-analysis.

PURPOSE: Endoscopic biopsy is recommended for diagnosis of nasopharyngeal carcinoma (NPC). A proportion of lesions are hidden from endoscopic view but detected with magnetic resonance imaging (MRI). This systematic review and meta-analysis investigated the diagnostic performance of MRI for detection of NPC. METHODS: An electronic search of twelve databases and registries was performed. Studies were included if they compared the diagnostic accuracy of MRI to a reference standard (histopathology) in patients suspected of having NPC. The primary outcome was accuracy for detection of NPC. Random-effects models were used to pool outcomes for sensitivity, specificity, and positive and negative likelihood ratio (LR). Bias and applicability were assessed using the modified QUADAS-2 tool. RESULTS: Nine studies were included involving 1736 patients of whom 337 were diagnosed with NPC. MRI demonstrated a pooled sensitivity of 98.1% (95% CI 95.2-99.3%), specificity of 91.7% (95% CI 88.3-94.2%), negative LR of 0.02 (95% CI 0.01-0.05), and positive LR of 11.9 (95% CI 8.35-16.81) for detection of NPC. Most studies were performed in regions where NPC is endemic, and there was a risk of selection bias due to inclusion of retrospective studies and one case-control study. There was limited reporting of study randomization strategy. CONCLUSION: This study demonstrates that MRI has a high pooled sensitivity, specificity, and negative predictive value for detection of NPC. MRI may be useful for lesion detection prior to endoscopic biopsy and aid the decision to avoid biopsy in patients with a low post-test probability of disease.

Noncontrast MRI for Hepatocellular Carcinoma Detection: A Systematic Review and Meta-analysis - A Potential Surveillance Tool?

BACKGROUND AND AIMS: This meta-analysis investigates the diagnostic performance of non-contrast magnetic resonance imaging (MRI) for the detection of hepatocellular carcinoma (HCC). METHODS: A systematic review was performed to May 2020 for studies which examined the diagnostic performance of non-contrast MRI (multi-sequence or diffusion-weighted imaging (DWI)- alone) for HCC detection in high risk patients. The primary outcome was accuracy for the detection of HCC. Random effects models were used to pool outcomes for sensitivity, specificity, positive likelihood ratio (LR) and negative LR. Subgroup analyses for cirrhosis and size of the lesion were performed. RESULTS: Twenty-two studies were included involving 1685 patients for per-patient analysis and 2128 lesions for per-lesion analysis. Multi-sequence non-contrast MRI (NC-MRI) using T2+DWI±T1 sequences had a pooled per-patient sensitivity of 86.8% (95%CI:83.9-89.4%), specificity of 90.3% (95%CI:87.3-92.7%), and negative LR of 0.17 (95%CI:0.14-0.20). DWI-only MRI (DW-MRI) had a pooled sensitivity of 79.2% (95%CI:71.8-85.4%), specificity of 96.5% (95%CI:94.3-98.1%) and negative LR of 0.24 (95%CI:1.62-0.34). In patients with cirrhosis, NC-MRI had a pooled per-patient sensitivity of 87.3% (95%CI:82.7-91.0%) and specificity of 81.6% (95%CI:75.3-86.8%), whilst DWI-MRI had a pooled sensitivity of 71.4% (95%CI:60.5-80.8%) and specificity of 97.1% (95%CI:91.9-99.4%). For lesions <2 cm, the pooled per-lesion sensitivity was 77.1% (95%CI:73.8-80.2%). For lesions >2 cm, pooled per-lesion sensitivity was 88.5% (95%CI:85.0-91.5%). CONCLUSION: Non-contrast MRI has a moderate negative LR and high specificity with acceptable sensitivity for the detection of HCC, even in patients with cirrhosis and with lesions <2 cm. Prospective trials to validate if non-contrast MRI can be used for HCC surveillance is warranted.

A novel CEP290 disease-causing variant identified in a patient with leber congenital amaurosis using a medical diagnostic panel sequencing.

BACKGROUND: This study aims to identify the underlying genetic cause of a Chinese patient with Leber congenital amaurosis (LCA). METHODS: Detailed clinical data and family history were collected. A medical diagnostic panel sequencing covering 4450 genes was conducted. Two candidate disease-causing mutations detected in CEP290 were then validated with Sanger sequencing and bioinformatic analysis. Reverse transcription polymerase chain reaction (RT-PCR) and cDNA sequencing were performed to understand the effect of the novel CEP290 mutation on CEP290 mRNA splicing. RESULTS: A five-month-old LCA patient with both parents was enrolled. Medical diagnostic panel sequencing revealed that the patient is a compound heterozygote for two potentially pathogenic CEP290 mutations. Among them, c.1666dupA (p.I556NfsX20) was previously reported and has a significant association with LCA phenotype. A novel CEP290 mutation (c.3310-1_3313delGCTTA) was confirmed in both the patient and her father. RT-PCR and cDNA sequencing confirmed that the novel mutation affects the CEP290 mRNA splicing and results in a complete skipping of exon 29. The frameshift resulted in an early stop codon and truncation of the mutant protein by 1371 amino acid residues (p.L1104fsX6). CONCLUSIONS: Our report provided a new mutation to the spectrum of CEP290-related diseases. The data suggested that the c.3310-1_3313delGCTTA mutation affects the CEP290 mRNA splicing and the CEP290 protein function. This valuable information is important for future studies on the mRNA splicing of CEP290 and the pathogenesis of CEP290-related diseases.

Prognostic significance of measurable residual disease based on multiparameter flow cytometry in childhood acute myeloid leukemia. / åŸºäºŽæµå¼ç»†èƒžæœ¯çš„å¯æµ‹é‡æ®‹ç•™ç— å¯¹å„¿ç«¥æ€¥æ€§é«“ç³»ç™½è¡€ç— é¢„åŽæ„ä¹‰çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To study the prognostic value of measurable residual disease (MRD) for childhood acute myeloid leukemia (AML) by analyzing MRD-guided risk stratification therapy. METHODS: A total of 93 children with AML were prospectively enrolled in this study. Chemotherapy with the 2015-AML-03 regimen was completed according to the risk stratification determined by genetic abnormality at initial diagnosis and MRD and bone marrow cytology after induction therapy I. Multiparameter flow cytometry was used to dynamically monitor MRD and analyze the prognostic effect of MRD on 3-year cumulative incidence of recurrence (CIR) rate, event-free survival (EFS) rate, and overall survival (OS) rate. RESULTS: The 93 children with AML had a 3-year CIR rate of 48%±6%, a median time to recurrence of 11 months (range 2-32 months), a 3-year OS rate of 65%±6%, and a 3-year EFS rate of 50%±5%. After induction therapy I and intensive therapy I, the MRD-positive children had a significantly higher 3-year CIR rate and significantly lower 3-year EFS and OS rates than the MRD-negative children (P<0.05). There were no significant differences in 3-year CIR, EFS, and OS rates between the MRD-positive children with a low risk at initial diagnosis and the MRD-negative children after adjustment of chemotherapy intensity (P>0.05). The multivariate analysis showed that positive MRD after intensive treatment I was a risk factor for 3-year OS rate in children with AML (P<0.05). CONCLUSIONS: MRD has predictive value for the prognosis of children with AML. Based on the MRD-guided risk stratification therapy, reasonable application of chemotherapy may improve the overall prognosis of children with AML.

The Synergistic Effect of Ginkgo biloba Extract 50 and Aspirin Against Platelet Aggregation.

PURPOSE: We aimed to investigate potential synergistic antiplatelet effects of Ginkgo biloba extract (GBE50) in combination with aspirin using in vitro models. METHODS: Arachidonic acid (AA), platelet activating factor (PAF), adenosine 5'-diphosphate (ADP) and collagen were used as inducers. The antiplatelet effects of GBE50, aspirin and 1:1 combination of GBE50 and aspirin were detected by microplate method using rabbit platelets. Synergy finder 2.0 was used to analyze the synergistic antiplatelet effect. The compounds in GBE50 were identified by UPLC-Q/TOF-MS analysis and the candidate compounds were screened by TCMSP database. The targets of candidate compounds and aspirin were obtained in TCMSP, CCGs, Swiss target prediction database and drugbank. Targets involving platelet aggregation were obtained from GenCLiP database. Compound-target network was constructed and GO and KEGG enrichment analyses were performed to identify the critical biological processes and signaling pathways. The levels of thromboxane B2 (TXB2), cyclic adenosine monophosphate (cAMP) and PAF receptor (PAFR) were detected by ELISA to determine the effects of GBE50, aspirin and their combination on these pathways. RESULTS: GBE50 combined with aspirin inhibited platelet aggregation more effectively. The combination displayed synergistic antiplatelet effects in AA-induced platelet aggregation, and additive antiplatelet effects occurred in PAF, ADP and collagen induced platelet aggregation. Seven compounds were identified as candidate compounds in GBE50. Enrichment analyses revealed that GBE50 could interfere with platelet aggregation via cAMP pathway, AA metabolism and calcium signaling pathway, and aspirin could regulate platelet aggregation through AA metabolism and platelet activation. ELISA experiments showed that GBE50 combined with aspirin could increase cAMP levels in resting platelets, and decreased the levels of TXB2 and PAFR. CONCLUSION: Our study indicated that GBE50 combined with aspirin could enhance the antiplatelet effects. They exerted both synergistic and additive effects in restraining platelet aggregation. The study highlighted the potential application of GBE50 as a supplementary therapy to treat thrombosis-related diseases.

Anti-diabetic Role of Adropin in Streptozotocin Induced Diabetic Rats via Alteration of PI3K/Akt and Insulin Signaling Pathway.

Diabetes mellitus (DM) is a hyperglycemia-related multifactorial condition with an elevated risk of microvascular and microvascular complications associated with this disease. The current experimental study was to examine the antidiabetic activity of streptozotocin (STZ)-induced adropin against diabetic rats by altering the PI3K/Akt and insulin signaling pathways. STZ (60 mg/kg) was used for the induction of DM and rats were divided into different groups and received the adropin (20, 40 and 80 mg/kg) and glibenclamide (10 mg/kg) till 28 days. Body weight, plasma insulin, blood glucose and food intake were estimated, respectively. Biochemical enzymes, carbohydrate enzymes, lipid parameters, AMPK and insulin signalling pathway parameters were estimated. GLUT4 and PPARγ expression were also estimated. Oral administration of adropin significantly (p < 0.001) increased the glycogen, glucose-6-phosphatase dehydrogenase, insulin, hexokinase and belittled the blood glucose level, fructose 1-6-biphosphatase, glucose-6-phosphatase at dose dependent manner. Adropin significantly (p < 0.001) reduced the level of triglyceride, cholesterol, low density lipoprotein, very low density lipoprotein and increased the level of high density lipoprotein at dose dependent manner. Adropin significantly (p < 0.001) activated the Akt, IRS-2, IRS-1, IR, p-AKT and PI3k, which are the key modulator molecules of PI3K/Akt, AMPK and insulin signalling pathway in DM rats. The current experimental study confirms the anti-diabetic effect of adropin on DM rats induced by AMPK and insulin signalling pathway against STZ.

State-of-the-art progress of switch fluorescence biosensors based on metal-organic frameworks and nucleic acids.

Metal-organic frameworks (MOFs) have captured substantial attention of an increasing number of scientists working in sensing analysis fields, due to their large surface area, high porosity, and tunable structure. Recently, MOFs as attractive fluorescence quenchers have been extensively investigated. Given their high quenching efficiency toward the fluorescence intensity of dyes-labeled specific biological recognition molecules, such as nucleic acids, MOFs have been widely developed to switch fluorescence biosensors with low background fluorescence signal. These strategies not only lead to specificity, simplicity, and low cost of biosensors, but also possess advantages such as ultrasensitive, rapid, and multiple detection of switch fluorescence methods. At present, researches of the analysis of switch fluorescence biosensors based on MOFs and nucleic acids mainly focus on sensing of different types of in vitro and intracellular analytes, indicating their increasing potential. In this review, we briefly introduce the principle of switch fluorescence biosensor and the mechanism of fluorescence quenching of MOFs, and mainly discuss and summarize the state-of-the-art advances of MOFs and nucleic acids-based switch fluorescence biosensors over the years 2013 to 2020. Most of them have been proposed to the in vitro detection of different types of analytes, showing their wide scope and applicability, such as deoxyribonucleic acid (DNAs), ribonucleic acid (RNAs), proteins, enzymes, antibiotics, and heavy metal ions. Besides, some of them have also been applied to the bioimaging of intracellular analytes, emerging their potential for biomedical applications, for example, cellular adenosine triphosphate (ATP) and subcellular glutathione (GSH). Finally, the remaining challenges in this sensing field and prospects for future research trends are addressed. Graphical abstract.

Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study.

OBJECTIVE: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. METHODS: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. RESULTS: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). CONCLUSION: An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.

Survival outcomes for surgical resection versus CT-guided percutaneous ablation for stage I non-small cell lung cancer (NSCLC): a systematic review and meta-analysis.

OBJECTIVE: Multiple cohort studies have compared surgical resection with CT-guided percutaneous ablation for patients with stage 1 non-small cell lung cancer (NSCLC); however, the results have been heterogeneous. This systematic review and meta-analysis aims to compare surgery with ablation for stage 1 NSCLC. METHOD: A search of five databases was performed from inception to 5 July 2020. Studies were included if overall survival (OS), cancer-specific survival (CSS), and/or disease-free survival (DFS) were compared between patients treated with surgical resection versus ablation (radiofrequency ablation (RFA) or microwave ablation (MWA)) for stage 1 NSCLC. Pooled odds ratios (OR) were calculated. RESULTS: A total of eight studies were included (total 792 patients: 460 resection and 332 ablation). There were no significant differences in 1- to 5-year OS or CSS between surgery versus ablation. There were significantly better 1- and 2-year DFS for surgery over ablation (OR 2.22, 95% CI 1.14-4.34; OR 2.60, 95% CI 1.21-5.57 respectively), but not 3- to 5-year DFS. Subgroup analysis demonstrated no significant OS difference between lobectomy and MWA, but there were significantly better 1- and 2-year OS with sublobar resection (wedge resection or segmentectomy) versus RFA (OR 2.85, 95% CI 1.33-6.10; OR 4.54, 95% CI 2.51-8.21, respectively). In the two studies which only included patients with stage 1A NSCLC, pooled outcomes demonstrated no significant differences in 1- to 3-year OS or DFS between surgery versus ablation. CONCLUSION: Surgical resection of stage 1 NSCLC remains the optimal choice. However, for non-surgical patients with stage 1A, ablation offers promising DFS, CSS, and OS. Future prospective randomized controlled trials are warranted. KEY POINTS: • Surgical resection of stage 1 NSCLC remains the optimal choice. • In patients with stage 1A NSCLC who are not surgical candidates, CT-guided microwave or radiofrequency ablation may be an alternative which offers promising disease-free survival and overall survival.

Mindin serves as a tumour suppressor gene during colon cancer progression through MAPK/ERK signalling pathway in mice.

Mindin is important in broad spectrum of immune responses. On the other hand, we previously reported that mindin attenuated human colon cancer development by blocking angiogenesis through Egr-1-mediated regulation. However, the mice original mindin directly suppressed the syngenic colorectal cancer (CRC) growth in our recent study and we aimed to further define the role of mindin during CRC development in mice. We established the mouse syngeneic CRC CMT93 and CT26 WT cell lines with stable mindin knock-down or overexpression. These cells were also subcutaneously injected into C57BL/6 and BALB/c mice as well as established a colitis-associated colorectal cancer (CAC) mouse model treated with lentiviral-based overexpression and knocked-down of mindin. Furthermore, we generated mindin knockout mice using a CRISPR-Cas9 system with CAC model. Our data showed that overexpression of mindin suppressed cell proliferation in both of CMT93 and CT26 WT colon cancer cell lines, while the silencing of mindin promoted in vitro cell proliferation via the ERK and c-Fos pathways and cell cycle control. Moreover, the overexpression of mindin significantly suppressed in vivo tumour growth in both the subcutaneous transplantation and the AOM/DSS-induced CAC models. Consistently, the silencing of mindin reversed these in vivo observations. Expectedly, the tumour growth was promoted in the CAC model on mindin-deficient mice. Thus, mindin plays a direct tumour suppressive function during colon cancer progression and suggesting that mindin might be exploited as a therapeutic target for CRC.

Resection Plus Post-operative Adjuvant Transcatheter Arterial Chemoembolization (TACE) Compared with Resection Alone for Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

PURPOSE: Multiple studies have demonstrated adjuvant transcatheter arterial chemoembolization (aTACE) after resection improved outcomes compared to resection alone for patients with hepatocellular carcinoma (HCC). Unlike pre-operative TACE which targets a lesion, aTACE is administered in the proximal hepatic artery to destroy cancer cells within the remaining liver. This systematic review and meta-analysis aims to quantify this survival and disease-free survival (DFS) benefit. METHODS: A search of five databases was performed from inception to 20 August 2019. RESULTS: A total of 26 studies (six randomized controlled trials) involving 7817 patients were included. Patients treated with resection plus aTACE had significantly better 1-year survival (OR, 2.53 [95% CI, 1.70-3.76, p < 0.001) and 1-year DFS (OR, 1.91 [95% CI, 1.60-2.28, p < 0.001) compared to resection alone. The survival benefit remained significant for 2- to 5-year survival (OR 2.39, 1.83, 2.12, 1.87, respectively) and 2- to 4-year DFS (OR 1.85, 1.24, 1.67, respectively). Subgroup analysis showed significant survival benefit with aTACE in microvascular invasion (MVI)-positive HCC, portal venous tumour thrombus (PVTT) that does not involve the main trunk, PVTT-negative, satellite nodules, with and without resection margin < 1 cm. No mortalities were reported with aTACE. CONCLUSION: Post-operative aTACE is safe and improves overall and disease-free survival, with the greatest benefit in MVI-positive patients. The current evidence weakly supports the use of adjuvant TACE for patients without PVTT, with PVTT that does not involve the main trunk, with and without a resection margin < 1 cm, and patients with satellite nodules. LEVEL OF EVIDENCE: Level 1.

Hidradenitis Suppurativa and Thyroid Disease: Systematic Review and Meta-Analysis.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by painful nodules, sinus tracts, and significant scarring. Although the pathogenesis of this disease is not well established, there is increasing evidence to suggest that it is an immune-mediated disorder. Previous studies have suggested a relationship between HS and thyroid disease, which is also driven by an autoimmune process. We sought to assess whether an association exists between HS and thyroid disease. OBJECTIVES: To determine whether HS is associated with thyroid disease via meta-analysis of case-control studies. METHODS: A systematic review and meta-analysis was performed according to recommended PRISMA guidelines. Electronic searches were performed using 6 electronic databases from their inception until August 2018. Data were extracted and analyzed according to predefined clinical endpoints. Odds ratio (OR) was used as the summary effect size. RESULTS: We identified 5 case-controls studies included for meta-analysis. There were a total of 36 103 HS cases compared with 170 517 control cases. We found a significant association between HS and thyroid disease (OR 1.36, 95% CI 1.13-1.64, I 2 = 78%, P = .001). CONCLUSIONS: This pooled analysis of existing case-control studies to date supports an association between HS and any thyroid disease. Clinicians treating patients with HS should be aware of this potential association with thyroid disease.