Exploring the impact of insufficient thermal ablation on hepatocellular carcinoma: NDST2 overexpression mechanism and its role in facilitating growth and invasion of residual cancer cells.

OBJECTIVE: Incomplete thermal ablation (ITA) fosters the malignancy of residual cells in Hepatocellular carcinoma (HCC) with unclear mechanisms now. This study aims to investigate the expression changes of NDST2 following ITA of HCC and its impact on residual cancer cells. METHODS: An in vitro model of heat stress-induced liver cancer was constructed to measure the expression of NDST2 using Quantitative Real-Time PCR and Western blotting experiments. The sequencing data from nude mice were used for validation. The clinical significance of NDST2 in HCC was evaluated by integrating datasets. Gene ontology and pathway analysis were conducted to explore the potential signaling pathways regulated by NDST2. Additionally, NDST2 was knocked down in heat stress-induced HCC cells, and the effects of NDST2 on these cells were verified using Cell Counting Kit-8 assays, scratch assays, and Transwell assays. RESULTS: NDST2 expression levels are elevated in HCC, leading to a decrease in overall survival rates of HCC patients. Upregulation of immune checkpoint levels in high NDST2-expressing HCC may contribute to immune evasion by liver cancer cells. Additionally, the low mutation rate of NDST2 in HCC suggests a relatively stable expression of NDST2 in this disease. Importantly, animal and cell models treated with ITA demonstrate upregulated expression of NDST2. Knockdown of NDST2 in heat stress-induced liver cancer cells results in growth inhibition associated with gene downregulation. CONCLUSION: The upregulation of NDST2 can accelerate the progression of residual HCC after ITA, suggesting a potential role for NDST2 in the therapeutic efficacy and prognosis of residual HCC.

Can Modifications of LR-M Criteria Improve the Diagnostic Performance of Contrast-Enhanced Ultrasound LI-RADS for Small Hepatic Lesions up to 3 cm?

OBJECTIVE: To assess the diagnostic performance of the contrast-enhanced ultrasound liver imaging reporting and data system (CEUS LI-RADS) version 2017 for small hepatic lesions of ≤3 cm before and after changing the LR-M criteria. METHODS: We retrospectively analyzed the CEUS examination of 179 patients who were at high risk of hepatocellular carcinoma (HCC) with focal hepatic lesions ≤3 cm (194 lesions in total) and evaluated the diagnostic capability of the American College of Radiology and modified CEUS LI-RADS algorithms. RESULTS: Revision of the early washout time to 45 seconds increased the sensitivity of LR-5 in predicting HCC (P = .004), with no significant decrease in specificity (P = .118). It also made better the specificity of LR-M in predicting non-HCC malignancies (P = .001), with no significant decrease in sensitivity (P = .094). However, using within 3 minutes as the criterion for marked washout time improved the LR-5 sensitivity (P < .001) but decreased its specificity (P = .009) in predicting HCC, whereas the specificity of LR-M in predicting non-HCC malignancies increased (P < .001), but the sensitivity decreased (P = .027). CONCLUSIONS: CEUS LI-RADS (v2017) is a valid method for predicting HCC risk in high-risk patients. The diagnostic performance of LR-5 and LR-M could boost when the early washout time is revised to 45 seconds.

Comparison of the Feasibility and Diagnostic Performance of ACR CEUS LI-RADS and a Modified CEUS LI-RADS for HCC in Examinations Using Sonazoid.

OBJECTIVES: The present study aimed to determine the feasibility of the American College of Radiology's (ACR) contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) (version 2017) in examinations using Sonazoid and compare its diagnostic performance with that of modified LI-RADS in patients at high risk of hepatocellular carcinoma (HCC). METHODS: This retrospective study's sample population consisted of 137 participants with a total of 140 nodules who underwent CEUS with Sonazoid and pathological confirmation via surgery or biopsy from January 2020 to February 2022. The lesions were evaluated and classified based on the reference standards (ie, ACR CEUS LI-RADS and modified LI-RADS). The overall diagnostic capabilities of the two systems were evaluated in terms of accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with 95% confidence intervals (CIs). RESULTS: The participants had a median age of 51 years and an interquartile range of 43-58 years. Regarding LR-5 as a predictor of HCC, the accuracy results of the ACR LI-RADS and modified LI-RADS algorithms were 72.9 and 71.4%, respectively (P = .50). The sensitivity of both systems was the same (69.7%; 95% CI: 60.7-77.8%). Regarding LR-M as a predictor of non-HCC malignancy, the diagnostic performance of the algorithms was the same, with accuracy and sensitivity results of 76.4 and 73.3%, respectively (95% CI: 44.9-92.2%). CONCLUSION: The findings indicate that modified LI-RADS had a moderate level of diagnostic performance for HCC in examinations using Sonazoid, which was comparable to ACR LI-RADS.

Intra-individual comparison of Sonazoid contrast-enhanced ultrasound and SonoVue contrast-enhanced ultrasound in diagnosing hepatocellular carcinoma.

PURPOSE: To assess whether the diagnostic performance of Sonazoid contrast-enhanced ultrasound (SZUS) is non-inferior to that of SonoVue contrast-enhanced ultrasound (SVUS) in diagnosing hepatocellular carcinoma (HCC) in individuals with high risk. MATERIALS AND METHODS: This prospective study was conducted from October 2020 to May 2022 and included participants with a high risk of HCC who underwent SZUS and SVUS. All lesions were confirmed by clinical or pathological diagnosis. Each nodule was classified according to the Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System version 2017 (CEUS LI-RADS v2017) for SVUS and SZUS and the modified CEUS LI-RADS (using Kupffer phase defect instead of late and mild washout) for SZUS. The diagnostic performance of both two modalities for all observations was compared. Analysis of the vascular phase and Kupffer phase imaging characteristics of CEUS was performed. RESULTS: One hundred and fifteen focal liver lesions from 113 patients (94 HCCs, 12 non-HCC malignancies, and 9 benign lesions) were analysed. According to CEUS LI-RADS (v2017), SVUS and SZUS showed similar sensitivity (71.3% vs. 72.3%) and specificity (85.7% vs. 81.0%) in HCC diagnosis. However, the modified CEUS LI-RADS did not significantly improve the diagnostic efficacy of Sonazoid compared to CEUS LI-RADS v2017, having equivalent sensitivity (73.4% vs. 72.3%) and specificity (81.0% vs. 81.0%). The agreement between SVUS and SZUS for all observations was 0.610 (95% CI 0.475, 0.745), while for HCCs it was 0.452 (95% CI 0.257, 0.647). CONCLUSION: Using LI-RADS v2017, SZUS and SVUS showed non-inferior efficacy in evaluating HCC lesions. In addition, adding Kupffer phase defects to SZUS does not notably improve its diagnostic efficacy.

How does the opening of China's high-speed rail affect the spatial mismatch of haze pollution and economic growth?

A better reconciliation of haze pollution and economic growth has become the social consensus in China. The development of China's economy and air quality will be significantly impacted by its efforts to create high-speed rail (HSR). Based on panel data from 265 prefecture-level cities in China from 2003 to 2019, this paper investigates how the opening of HSR affects the spatial mismatch of haze pollution and economic growth by using the spatial mismatch index model, multi-period difference-in-differences (DID) model, and intermediary effect model. We find that the spatial mismatch in China has an overall decreasing trend. And its spatial agglomeration is dominated by low levels. Further empirical analysis shows that HSR opening can effectively restrain the spatial mismatch. Even after some robustness tests and endogenous treatment, the conclusion is still valid. In addition, population density, FDI, and industrial structure are also explicit factors affecting the spatial mismatch. Second, there is significant heterogeneity in the impact. This is reflected in the fact that HSR opening can suppress the spatial mismatch of service-oriented cities and the eastern region, while other cities and regions have no noticeable effect. Third, spatial transfer of haze pollution (STHP) and balanced development of economic growth (BEG) are two important conduction paths for the opening of HSR to affect the spatial mismatch. Specifically, HSR opening can constrain the spatial mismatch by inhibiting STHP and BEG. Based on the above findings, recommendations related to promoting a better harmony between haze pollution and economic growth are proposed.

A Heterozygous LMF1 Gene Mutation (c.1523C>T), Combined With an LPL Gene Mutation (c.590G>A), Aggravates the Clinical Symptoms in Hypertriglyceridemia.

Hypertriglyceridemia is an important contributor to atherosclerotic cardiovascular disease (ASCVD) and acute pancreatitis. Familial hypertriglyceridemia is often caused by mutations in genes involved in triglyceride metabolism. Here, we investigated the disease-causing gene mutations in a Chinese family with hypertriglyceridemia and assessed the functional significance in vitro. Whole-exome sequencing (WES) was performed revealing that the severe hypertriglyceridemic proband carried a missense mutation (c.590G > A) in exon 5 of the LPL gene, as well as a missense mutation (c.1523C > T) in exon 10 of the LMF1 gene. Conservation analysis by Polyphen-2 showed that the 508 locus in the LMF1 protein and 197 locus in the LPL protein were highly conserved between different species. I-TASSER analysis indicated that the LMF1 c.1523C > T mutation and the LPL c.590G > A mutation changed the tertiary structure of the protein. A decrease in mRNA and protein expression was observed in 293T cells transfected with plasmids carrying the LMF1 c.1523C > T mutation. Subcellular localization showed that both wild-type (WT) and mutant LMF1 protein were localized at the cell cytoplasm. In the cell medium and cell lysates, these LMF1 and LPL gene mutations both caused a decreased LPL mass. Moreover, the combination of LMF1 and LPL gene mutations significantly decreased LPL levels compared to their individual effects on the LPL concentration. Both the clinical and in vitro data suggest that severe hypertriglyceridemia was of digenic origin caused by LMF1 and LPL mutation double heterozygosity in this patient.

Diagnostic value of CEUS LI-RADS and serum tumor markers for combined hepatocellular-cholangiocarcinoma.

PURPOSE: To analyze the contrast-enhanced ultrasound (CEUS) manifestations of combined hepatocellular-cholangiocarcinoma (CHC) and to investigate the diagnostic value of the 2017 version of the CEUS Liver Imaging Reporting and Data System (LI-RADS) and serum tumor markers in CHC. METHODS: A total of 66 pathologically confirmed CHC nodules were retrospectively analyzed. We summarized the CEUS manifestations of CHC and analyzed the relationship between serum tumor markers and the enhancement pattern of CHC. We also classified CHC according to CEUS LI-RADS criteria. The Kappa test was used to assess the interreader agreement of CEUS LI-RADS between radiologists. RESULT: According to the results, 52 of 62 (83.9%) patients had elevated alpha-fetoprotein (AFP), 19 of 61 (31.1%) had elevated carbohydrate antigen 199 (CA 199), and 13 of 61 (21.3%) had both elevated AFP and CA 199. Of the 66 CHC nodules, 64 (97.0%) were identified as malignant lesions by CEUS, 13 (19.7%) showed a hepatocellular carcinoma-like enhancement pattern, and 21 (31.8%) showed a cholangiocarcinoma-like enhancement pattern. For the CEUS LI-RADS categories, 39 of 53 (73.6%) CHC nodules were classified as LR-M, 12 (22.6%) were classified as LR-5, and 2 (3.8%) were classified as LR-4. The interreader agreement for the LI-RADS categories was 0.60. CONCLUSIONS: Although CHC lacks specific CEUS features, CEUS LI-RADS and serum tumor markers can be useful tools for reducing the misdiagnosis of CHC. In addition, due to the relative complexity of the CEUS features involved in CHC, it is necessary for beginning radiologists to learn more about CEUS features.

General anesthesia combined with epidural anesthesia maintaining appropriate anesthesia depth may protect excessive production of inflammatory cytokines and stress hormones in colon cancer patients during and after surgery.

The purpose of this study was to investigate the influences of varied anesthetic methods and depths on inflammatory cytokines and stress hormone levels in radical operation among colon cancer patients during perioperative period.A total of 120 patients were collected in the study and randomly divided into 4 groups, A: general anesthesia + Narcotrend D1, B: general anesthesia + Narcotrend D2, C: general anesthesia + epidural anesthesia + Narcotrend D1, D: general anesthesia + epidural anesthesia + Narcotrend D2. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, cortisol (Cor), adrenocorticotropic hormone (ACTH), and endothelin-1 (ET-1) were measured adopting commercial kits before anesthesia (T0), 4 hours after surgery (T1), 24 hours after surgery (T2), and 72 hours after surgery (T3).There was no significant difference in basic clinical characteristics among the groups. In comparison with group A, B and C, group D showed significantly lower levels of TNF-α, IL-6, IL-10, Cor, ACTH, and ET-1 at T1 and T2 (all, P < .05). Significantly higher levels of TNF-α, IL-6, IL-10, Cor, and ACTH were detected at T1 and T2 than those at T0 (all, P < .05), whereas, at T3, the levels of inflammatory cytokines and stress hormones were all decreased near to preoperation ones.General anesthesia combined with epidural anesthesia at Narcotrend D2 depth plays an important role in reducing immune and stress response in patients with colon cancer from surgery to 24 hours after surgery.