Controlling Nutritional Status (CONUT) Score is Associated with Overall Survival in Patients with Hepatocellular Carcinoma Treated with Conventional Transcatheter Arterial Chemoembolization: A Propensity Score Matched Analysis.

PURPOSE: This study aims to evaluate the prognostic value of controlling nutritional status (CONUT) score in determining the prognosis of patients with hepatocellular carcinoma (HCC) treated with conventional transcatheter arterial chemoembolization (cTACE). METHODS: This study retrospectively analyzed 936 patients who underwent cTACE for HCC between January 2012 and December 2018, and divided them into two groups based on their CONUT score. To balance the bias in baseline characteristics, propensity score matched (PSM) analysis was conducted. The Kaplan-Meier method was used to establish a cumulative survival curve, and the log-rank test was employed to determine differences in overall survival (OS) and progression-free survival (PFS) among the CONUT score groups. Furthermore, the Cox proportional hazard model was employed to assess the correlation between CONUT score and OS and PFS, whereby hazard ratios (HRs) and 95% confidence intervals (95% CIs) were computed. RESULTS: Before PSM, the median OS for the low (≤ 3) and high (≥ 4) CONUT group (558 vs. 378 patients) was 21.7 and 15.6 months, respectively, and the median PFS was 5.7 and 5 months. Following PSM, both the low and high CONUT score groups comprised 142 patients. The low CONUT score group exhibited a significantly longer OS compared to the high CONUT score group, as determined by the log-rank test (median OS 22.2 vs. 17.0 months, P = 0.014). No significant association was observed between CONUT group and PFS (median PFS 6.4 vs. 4.7 months, log-rank test, P = 0.121). Cox proportional hazard regression analysis revealed that a CONUT score of ≥ 4 was an independent risk factor for OS in patients with HCC who underwent cTACE (HR = 1.361; 95% CI: 1.047-1.771; P = 0.022). These findings were consistent across most subgroup analyses. CONCLUSION: A high CONUT score has been found to be a prognostic factor for poorer OS in patients with HCC who underwent cTACE. LEVEL OF EVIDENCE: Level 3, Non-randomized controlled cohort.

Prognostic value of tertiary lymphoid structures (TLS) in digestive system cancers: a systematic review and meta-analysis.

BACKGROUND: Existing literature suggests that tertiary lymphatic structure (TLS) is associated with the progression of cancer. However, the prognostic role of TLS in digestive system cancers remains controversial. This meta-analysis aims to synthesize currently available evidence in the association between TLS and the survival of digestive system cancers. METHODS: We systematically searched three digital databases (PubMed, Embase, Web of Science) for articles published from database inception to December 23, 2022. Study selection criteria are based on PECO framework: P (population: patients with digestive system cancers), E (exposure: presence of TLS), C (comparator: absence of TLS), O (outcome: overall survival, OS; recurrence-free survival, RFS; disease-free survival, DFS). The Quality in Prognostic Studies (QUIPS) tool was used to assess risk of bias for included studies. The study protocol was registered with PROSPERO (CRD42023416307). RESULTS: A total of 25 studies with 6910 patients were included into the final meta-analysis. Random-effects models revealed that the absence of TLS was associated with compromised OS, RFS, and DFS of digestive system cancers, with pooled hazard ratios (HRs) of 1.74 (95% CI: 1.50-2.03), 1.96 (95% CI: 1.58-2.44), and 1.81 (95% CI: 1.49-2.19), respectively. Subgroup analyses disclosed a stronger TLS-survival association for pancreatic cancer, compared with other digestive system cancers. CONCLUSION: TLS may be of prognostic significance for digestive system cancers. More original studies are needed to further corroborate this finding.

GDPD5 Related to Lipid Metabolism Is a Potential Prognostic Biomarker in Neuroblastoma.

Neuroblastoma (NB) is an extracranial solid tumor in children with poor prognosis in high-risk patients and its pathogenesis and prognostic markers urgently need to be explored. This study aimed to explore potential biomarkers related to NB from the aspect of lipid metabolism. Fifty-eight lipid metabolism-related differentially expressed genes between high-risk NB and non-high-risk NB in the GSE49710 dataset were analyzed using bioinformatics, including 45 down-regulated genes and 13 up-regulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified steroid hormone biosynthesis as an abnormal metabolic pathway in high-risk NB. Survival analysis established a three-gene prognostic model, including ACHE, GDPD5 and PIK3R1. In the test data, the AUCs of the established prognostic models used to predict patient survival at 1, 3 and 5 years were 0.84, 0.90 and 0.91, respectively. Finally, in the SH-SY5Y cell line, it was verified that overexpression of GDPD5 can inhibit cell proliferation and migration, as well as affect the lipid metabolism of SH-SY5Y, but not the sugar metabolism. hsa-miR-592 was predicted to be a potential target miRNA of GDPD5 by bioinformatics. In conclusion, this study develops a lipid-metabolism-related gene-based prognostic model for NB and demonstrates that GDPD5 inhibits SH-SY5Y proliferation and migration and may be targeted by hsa-miR-592 and inhibit SH-SY5Y fat synthesis.

JMJD3 deficiency alleviates lipopolysaccharide­induced acute lung injury by inhibiting alveolar epithelial ferroptosis in a Nrf2­dependent manner.

Acute respiratory distress syndrome (ARDS) is a deadly illness which presents with severe hypoxemia as well as diffuse alveolar damage. Jumonji domain­containing 3 (JMJD3), which belongs to the UTX/UTY JmjC­domain protein subfamily, is involved in infection, development, aging and immune disorders. However, the role of JMJD3 in acute lung injury (ALI) is still unclear. The present study explored the roles and potential mechanisms of JMJD3 in ALI. Alveolar epithelial cell­specific knockout of JMJD3 mice and A549 alveolar epithelial cells were used to investigate the function of JMJD3 in ALI. Lipopolysaccharide (LPS) was used to establish an in vivo and in vitro ALI model. The expression of JMJD3 in murine lung tissue and alveolar epithelial cells was detected. Pathological injury of lung tissue and alveolar epithelial cells was also investigated following inhibition of JMJD3. The results showed that JMJD3 expression was significantly increased in murine lung tissues and in A549 cells following LPS stimulation. JMJD3­deficient mice in alveolar epithelial cells exhibited alleviated lung pathological injury and ferroptosis following h stimulation. Mechanistically, it was found that JMJD3 knockout could increase the expression of nuclear factor erythroid­2­related factor­2 (Nrf2) in lung tissues challenged with h. However, Nrf2 overexpression by adenovirus could further enhance the anti­ferroptotic effect from JMJD3 silence in h­treated A549 cells. Taken together, the present study revealed that JMJD3 deficiency may relieve LPS­induced ALI by blocking alveolar epithelial ferroptosis in a Nrf2­dependent manner, which may serve as a novel therapeutic target against ALI.

[Inhibitory effect of ketogenic diet on neuroblastoma in BALB/c-nu mouse models].

OBJECTIVE: To investigate the inhibitory effect of ketogenic diet (KD) on growth of neuroblastoma in mice. METHODS: BALB/c-nu mouse models bearing neuroblastoma xenografts were established by subcutaneous injection of human neuroblastoma cell line (SH-SY5Y). When the tumor volume reached 250 mm3, the mice were randomized into SD group with standard diet and PBS treatment, KD group with ketogenic diet and PBS treatment, and CP+KD group with ketogenic diet and cyclophosphamide (60 mg·kg-1·day-1) treatment, n=8. The tumor volume, body weight, blood glucose, ketone body (ß-Hydroxybutyrate) levels, and hepatic steatosis in the mice were assessed. The expressions of caspase-3 and caspase-8 were detected by Western blotting, and Ki67 expresison was detected using immunohistochemistry (IHC). Transmission electron microscopy (TEM) was employed for the autophagosomes, and the autophagic protein Beclin1, LC3A/B and P62 were detected by IHC and Western blotting. RESULTS: On day 28 post tumor cell injection, the mice in KD and CP+KD groups could prolong the overall survival rates than that in SD group (P < 0.001). On day 22 post the injection, the tumor volume in KD group was smaller than that in SD group (P < 0.05); on 16, 19, and 22 day post the injection, the tumor volume in CP+KD group was smaller than that in SD group (P < 0.01). The mice in SD group showed greater body weight on day 19 and higher blood glucose level on day 13 post the injection than those in the other two groups (P < 0.05). Blood ketone level and hepatic steatosis score were higher and glucose ketone index (GKI) was lower in KD and CP+KD groups than those in SD group (all P < 0.05). The expressions of Ki67 and apoptotic proteins were detected in the tumor tissues of all groups. TEM revealed more autophagosomes in the tumor tissues of KD group than that of SD group. P62 expression was lowered (P < 0.01) and Beclin1 and LC3A/B expressions were up-regulated in the tumor tissues of KD group (P < 0.05), which is consisitent with IHC. CONCLUSIONS: KD has a strong anti-tumor effect in the xenograft mouse model possibly by regulating cell autophagy.

Colorectal neoplasm: magnetic resonance colonography with fat enema-initial clinical experience.

AIM: To assess Magnetic resonance colonography with fat enema as a method for detection of colorectal neoplasm. METHODS: Consecutive twenty-two patients underwent MR colonography with fat enema before colonoscopy. T1-weighted three-dimensional fast spoiled gradient-echo with inversion recovery sequence was acquired with the patient in the supine position before and 75 s after Gadopentetate Dimelumine administration. Where by, pre and post MR coronal images were obtained with a single breath hold for about 20 s to cover the entire colon. The quality of MR colonographs and patients' tolerance to fat contrast medium was investigated. Colorectal neoplasms identified by MR colonography were compared with those identified on colonoscopy and sensitivity of detecting the lesions was calculated accordingly. RESULTS: MR colonography with fat enema was well tolerated without sedation and analgesia. 120 out of 132 (90.9%) colonic segments were well distended and only 1 (0.8%) colonic segment was poor distension. After contrast enhancement scan, mean contrast-to-noise ratio (CNR) value between the normal colonic wall and lumen was 18.5 +/- 2.9 while mean CNR value between colorectal neoplasm and lumen was 20.2 +/- 3.1. By Magnetic resonance colonography, 26 of 35 neoplasms (sensitivity 74.3%) were detected. However, sensitivity of MRC was 95.5% (21 of 22) for neoplasm larger than 10 mm and 55.6% (5 of 9) for 5-10 mm neoplasm. CONCLUSION: MR colonography with fat enema and T1-weighted three-dimensional fast spoiled gradient-echo with inversion recovery sequence is feasible in detecting colorectal neoplasm larger than 10 mm.