Efficacy and safety of targeted therapy plus immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX) for unresectable hepatocarcinoma.

BACKGROUND: The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma (HCC), and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than monotherapy. However, the mechanisms underlying this innovative treatment modality have not been elucidated. AIM: To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy (HAIC) of FOLFOX in patients with unresectable HCC. METHODS: We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy, immunotherapy, and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen. RESULTS: The objective response rate was 60.4% (32/53), complete response was 24.5% (13/53), partial response was 35.9% (19/53), and stable disease was 39.6% (21/53). The median duration of response and median progression-free survival were 9.1 and 13.9 months, respectively. The surgical conversion rate was 34.0% (18/53), and 1-year overall survival was 83.0% without critical complicating diseases or adverse events (AEs). CONCLUSION: The regimen of HAIC of FOLFOX, targeted therapy, and immunotherapy was curative for patients with unresectable HCC, with no serious AEs and a high rate of surgical conversion.

C-arm CT guided percutaneous vertebroplasty for pain release in cancer patient with cervical 1 vertebral metastases: A case report.

OBJECTIVE: To evaluate the efficacy and treatment outcome of C-arm CT percutaneous vertebroplasty in the treatment of cervical 1 (C1) vertebral metastases. METHODS: This report recruited a male patient diagnosed with hepatocellular carcinoma and C1 vertebral metastases, who had suffered from severe neck pain symptoms and the analgesic showed little soothing effect. Under the guidance of C-arm CT, an 18G coaxial needle was used to puncture the left lateral mass of C1 vertebral metastases from lateral space between thyroid cartilage and the left carotid sheath, with 2 ml bone cement injected. RESULTS: Postoperative C-arm CT three-dimensional reconstruction scan showed that the bone cement was well filled and distributed in the left lateral mass of C1 vertebral body, and no leakage of bone cement was observed. The neck pain of the patients was significantly relieved one week after the operation. CONCLUSION: Under the guidance of C-arm CT, cement augmentation using percutaneous vertebroplasty in an anterior cervical direction could serve as a safe and effective pain relief approach for patients with C1 vertebral metastases.

Impact of antithrombotic drugs on the accuracy of fecal occult blood testing for advanced colorectal neoplasia screening: a meta-analysis and systematic review.

BACKGROUND: The current meta-analysis was conducted to determine whether antithrombotic drug use would affect the diagnostic accuracy of fecal occult blood testing for advanced colorectal neoplasia. METHODS: Articles published between 2000 and 2019 were systematically retrieved and screened according to the inclusion and exclusion criteria by two reviewers independently. Pooled analyses were conducted with a fixed-effect model if no apparent heterogeneity (I2 ≥ 50%) was found between studies; otherwise, the random effects model would be used. Sensitivity analysis and subgroup analysis were also conducted using Review Manager 5.3. RESULTS: Pooled analysis revealed that aspirin and nonsteroidal anti-inflammatory drugs were associated with a decrease in the positive predictive value of fecal occult blood testing for advanced colorectal neoplasia screening, with a RR of 0.89 (95% CI: 0.84-0.94) and 0.88 (95% CI: 0.84-0.93, p<0.001) respectively. Subgroup analysis based on data limited to high-quality studies, fecal immunochemical testing, or in Caucasians also showed that the use of aspirin/NSAID drugs decreased the accuracy for advanced colorectal neoplasia screening. CONCLUSION: Aspirin/NSAIDs and direct oral anticoagulants rather than warfarin may decrease the diagnostic accuracy of fecal occult blood testing for advanced colorectal neoplasia screening.

Percutaneous microwave ablation and transcatheter arterial chemoembolization for serum tumor markers and prognostics of middle-late primary hepatic carcinoma.

BACKGROUND: Primary hepatic carcinoma (PHC) has an insidious onset and is usually diagnosed in the middle and late stages. Although transcatheter arterial chemoembolization (TACE) is the preferred option for treating middle- and advanced-stage PHC, it has limited efficacy in killing tumor cells and poor long-term efficacy. TACE plus percutaneous microwave coagulation therapy (PMCT) is more effective than interventional therapy alone and can improve survival time. However, there are few reports on the effects of TACE and PMCT on serum marker levels and the prognosis of patients with advanced PHC. AIM: To investigate the effect of PMCT + TACE on serum tumor markers and the prognosis of middle-late PHC. METHODS: This retrospective study included 150 patients with middle-late PHC admitted to Zhongshan People's Hospital between March 2018 and February 2021. Patients were divided into a single group (treated with TACE, n = 75) and a combined group (treated with TACE + PMCT, n = 75). Before and after treatment, the clinical efficacy and serum tumor marker levels [carbohydrate antigen 19-9 (CA19-9), alpha-fetoprotein (AFP), and carcinoembryonic antigen (CEA)] of both groups were observed. The 1-year survival rates and prognostic factors of the two groups were analyzed. RESULTS: The combined group had 21 and 35 cases of complete remission (CR) and partial remission (PR), respectively. The single group had 13 and 25 cases of CR and PR, respectively. After 4 wk of treatment, the serum CA19-9, CEA, and AFP levels in the single and combined groups decreased, with the decrease in the combined group being more significant (P < 0.05). The 1-year survival rate of the combined group (80.00%) was higher than that of the single group (60.00%) (P < 0.05). The average survival time within 1 year in the combined group was 299.38 ± 61.13 d, longer than that in the single group (214.41 ± 72.97 d, P < 0.05). COX analysis revealed that tumor diameter, tumor number, and the treatment method were prognostic factors for patients with middle-late PHC (P < 0.05). CONCLUSION: TACE + PMCT is effective in treating patients with mid-late PHC. It reduces the levels of tumor markers, prolongs survival, and improves prognosis.

Integrated Bioinformatics Analysis and Validation of the Prognostic Value of RBM10 Expression in Hepatocellular Carcinoma.

Background: RBM10's function in hepatocellular carcinoma (HCC) has rarely been addressed. We intend to explore the prognostic significance and therapeutic meaning of RBM10 in HCC in this study. Methods: Multiple common databases were integrated to analyze the expression status and prognostic meaning of RBM10 in HCC. The relationship between RBM10 mRNA level and clinical features was also assessed. Multiple enrichment analyses of the differentially expressed genes between RBM10 high- and low- transcription groups were constructed by using R software (version 4.0.2). A Search Tool for Retrieval of Interacting Genes database was used to construct the protein-protein interaction network between RBM10 and other proteins. A tumor immune estimation resource database was employed to identify the relationship between RBM10 expression and immune cell infiltrates. The prognostic value of RBM10 expression was validated in our HCC cohort by immunohistochemistry test. Results: The transcription of RBM10 mRNA was positively correlated with tumor histologic grade (p < 0.001), T classification (p < 0.001), and tumor stage (p < 0.001). High transcription of RBM10 in HCC predicted a dismal overall survival (p = 0.0037) and recurrence-free survival (p < 0.001). Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and Gene Set Enrichment Analysis all revealed that RBM10 was involved in the regulation of cell cycle, DNA replication, and immune-related pathways. Tumor immune estimation analysis revealed that RBM10 transcription was positively related to multiple immune cell infiltrates and the expressions of PD-1 and PD-L1. Conclusion: RBM10 was demonstrated to be a dismal prognostic factor and a potential biomarker for immune therapy in HCC in that it may be involved in the immune-related signaling pathways.

[Corrigendum] TLR4 mediates inflammation and hepatic fibrosis induced by chronic intermittent hypoxia in rats.

Following the publication of the above article, the authors have realized that the first grant number featured in the Funding section of the Declarations on p. 658 appeared incorrectly: The text here should have been written as 'grant nos. 2018J01199, 2018Y0032 and 2016J01441' instead of 'grant nos. 2018J0105, 2018Y0032 and 2016J01441'. The authors regret their oversight in providing this incorrect information in the Funding section of their paper. They thank the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership of the Journal and to the funding body in question for any inconvenience caused. [the original article was published in Molecular Medicine Reports 22: 651­660, 2020; DOI: 10.3892/mmr.2020.11134].

TLR4 mediates inflammation and hepatic fibrosis induced by chronic intermittent hypoxia in rats.

Obstructive sleep apnea syndrome (OSAS) is a common and complex disorder that is associated with liver injury. Moreover, previous studies have revealed that chronic intermittent hypoxia (CIH) is associated with the development of non­alcoholic fatty liver disease and hepatic fibrosis. However, the underlying molecular mechanisms remain largely unknown. The present study aimed to investigate whether chronic intermittent hypoxia induced hepatic fibrosis, in addition to determining its underlying mechanisms, in CIH model rats using immunohistochemistry, western blotting and reverse transcription­quantitative PCR. The present results suggested that CIH caused hepatic fibrosis and increased the expression levels of interleukin (IL)­1ß, IL­8, monocyte chemotactic­1, tumor necrosis factor­α, intercellular adhesion molecule­1 and vascular cell adhesion molecule­1 in the liver; these conditions could be reversed by Toll­like receptor 4 (TLR4) short hairpin RNA lentivirus treatment. Moreover, immunohistochemistry and western blotting results indicated that TLR4 and NF­κB expression levels were significantly increased in the CIH and CIH­TLR4 empty vector lentivirus group. However, protein expression levels of TLR4, NF­κB, inhibitor of NF­κB and phosphorylated­mitogen­activated protein kinase (MAPK)­1 in the hypoxia/reoxygenation group were significantly higher compared with the control group (P<0.05), and these results were reversed by the MAPK inhibitor U0126 in vitro. Collectively, the present preliminary results suggested that inflammation and the TLR4/NF­κB/MAPK signaling pathway may be involved in CIH­induced liver fibrosis.

The Effect of Puncture Sites of Portal Vein in TIPS with ePTFE-Covered Stents on Postoperative Long-Term Clinical Efficacy.

PURPOSE: To evaluate the effect of puncture sites of the portal vein in transjugular intrahepatic portosystemic shunt (TIPS) on long-term clinical efficacy. METHODS: A retrospective review was performed, including consecutive 171 patients who underwent TIPS with ePTFE-covered stents. All patients were divided into 3 groups according to the puncture site of the portal vein: intrahepatic bifurcation of the portal vein (group A, n = 88), right branch of the portal vein (group B, n = 48), and left branch of the portal vein (group C, n = 35). The Kaplan-Meier analysis was performed to assess the effect of different puncture sites on primary patency, the incidence of hepatic encephalopathy (HE), and survival. RESULTS: The primary restenosis rate was 29.8% (51/171). The total HE rate was 31.6% (54/171). The cumulative death rate was 19.3% (33/171). The Kaplan-Meier analysis showed that group C versus group A, group C versus group B, and group A versus group B were significantly different on the primary restenosis rate, respectively (χ 2 = 11.49, P = 0.001; χ 2 = 4.54, P = 0.033; and χ 2 = 4.12, P = 0.046), and group C is better than the other two groups. What is more, group C versus group A and group C versus group B were significantly different on the incidence of HE, respectively (χ 2 = 8.07, P = 0.004; χ 2 = 9.44, P = 0.002), and group C is better than the other two groups. There was no significant difference on survival. CONCLUSION: Choosing the left branch of the portal vein as the puncture site to create the shunt in TIPS with ePTFE-covered stents may decrease the incident of primary restenosis and HE significantly.

[Effect of covered stent length in portal and hepatic veins on long-term clinical efficacy of transjugular intrahepatic portosystemic shunt].

OBJECTIVE: To evaluate the effect of the length of covered stents in the portal and hepatic veins on long-term clinical efficacy of transjugular intrahepatic portosystemic shunt (TIPS). METHODS: We retrospectively reviewed 53 cases receiving TIPSs between January, 2008 and December, 2011. All the shunts were created with Fluency stents (8 mm in diameter). Bare metal grafts of the same diameter were implanted to extend the length in the portal and hepatic veins as deemed necessary according to angiographic images. The primary patency, hepatic encephalopathy and patient survival were evaluated during the follow up. The length of the covered stents within the hepatic vein (X1) and in the portal vein (X2), and the total length of stents placed in the hepatic vein (X3) and the portal vein (X4) were measured and their effects on primary patency and the patients'outcomes were evaluated. RESULTS: The procedures were completed successfully in all the patients and the mean portosystemic pressure decreased from 29.80∓4.83 mmHg to 19.00∓3.92 mmHg (t=13.44, P<0.01) after the procedure. The patients were followed up for a median of 64 months (3 to 89 months, 39 months on average). Hepatic encephalopathy occurred in 23% (12/53) of the patients after TIPS. Shunt dysfunction occurred in 16 cases, and the cumulative primary patency rates at 1 to 5 years were 83%, 75%, 63%, 62%, and 54%, respectively. The cumulative survival rates of the patients at 1 to 5 years were 79%, 72%, 72%, 69%, and 69%, respectively. Cox proportional regression analysis showed a significant association between the length of covered-stent in the hepatic vein and the primary patency (OR=0.42, P<0.01), and there was a significant association between the length of stent in the portal vein and the patient survival. No significant correlation was found between these parameters and hepatic encephalopathy. CONCLUSION: Increasing the length of the covered stent in the hepatic vein and decreasing the stent length in the portal vein can improve the primary patency and the patient survival receiving TIPS.

[Study on the structure and optical limiting properties of lead(II) tetrakis (4-cumylphenoxy)-phthalocyanine doped silica gel glass composites].

The present paper reports the encapsulation of lead (II) tetrakis (4-cumylphenoxy)-phthalocyanine (PbPc(CP)4) into silica gel glass matrix to produce homogeneously doped composites by sol-gel technique. The existing state and structure of the doped PbPc(CP)4 were studied by UV-Vis absorption spectra and TEM images. Optical limiting properties were measured at 532 nm with 8 ns pulses. The results show that the doped PbPc(CP)4 molecules aggregate to form clusters in the gel glass composites, and PbPc(CP)4 has better optical limiting properties in the gel glass composites owing to the rigid structure of solid matrix.