Transarterial Chemoembolization Combined with Tyrosine Kinase Inhibitors Plus Immune Checkpoint Inhibitors Versus Tyrosine Kinase Inhibitors Plus Immune Checkpoint Inhibitors in Unresectable Hepatocellular Carcinoma with First- or Lower-Order Portal Vein Tumor Thrombosis.

PURPOSE: To compare the efficacy of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) (TACE-TKI-ICI) versus TKIs plus ICIs (TKI-ICI) for unresectable hepatocellular carcinoma (HCC) with first- or lower-order portal vein tumor thrombosis (PVTT). MATERIALS AND METHODS: A retrospective study was performed in HCC patients with first- or lower-order PVTT receiving TKIs (Lenvatinib or sorafenib) plus ICIs (camrelizumab, sintilimab, or atezolizumab) with or without TACE from four institutions between January 2019 and January 2022. Propensity score-based method was performed to minimize bias by confounding factors. Tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated and compared between the two groups. RESULTS: After inverse probability of treatment weighting, two balanced pseudopopulations were created: 106 patients in the TACE-TKI-ICI group and 109 patients in the TKI-ICI group. The objective response rate was higher in the TACE-TKI-ICI group (50.9% vs. 28.4%, P < 0.001). The median PFS and OS were significantly longer in the TACE-TKI-ICI group than in the TKI-ICI group (PFS: 9.1 vs. 5.0 months, P = 0.005; OS: 19.1 vs. 12.7 months, P = 0.002). In Cox regression, TACE-TKI-ICI treatment was an independent predictor of favorable OS. Treatment-related grade 3/4 AEs were comparable between the two groups (22.6% vs. 17.9%, P = 0.437). CONCLUSION: TACE-TKI-ICI therapy contributed to better tumor control, PFS and OS than TKI-ICI therapy in unresectable HCC patients with first- or lower-order PVTT.

[Bacterial Community Diversity in Channel Sediments of Different Disturbance Sections of the Jialing River].

In order to explore the impact of different anthropogenic disturbances on the ecological environment of natural rivers, the bacterial community in the channel sediments of the Jialing River was taken as the research object, and the high-throughput sequencing technique was used to analyze the community composition and functional changes of bacteria in the channel sediments of rivers with engineering disturbance, tributary disturbance, sand mining disturbance, reclamation disturbance, and undisturbed section. The results showed that there were significant differences in the physical and chemical properties of channel sediments and bacterial community diversity in different disturbance sections of the Jialing River (P<0.05). The undisturbed section had the highest bacterial community diversity, whereas the sand mining disturbance and undisturbed section had the highest bacterial community uniformity, and tributary disturbance and reclamation disturbance both resulted in a decrease in bacterial community diversity and uniformity. The effect of engineering disturbance on bacterial community composition was significantly different from that of the other four disturbance sections. The dominant bacterial phyla were Proteobacteria, Actinobacteriota, Acidobacteriota, and Chloroflexi, and the dominant bacterial classes were γ-Proteobacteria, α-Proteobacteria, and Vicinamibacteria. Sand mining disturbance led to the increase in Actinobacteria, and engineering disturbance promoted the increase in Acidobacteria. Moisture content, total organic carbon, total nitrogen, and total phosphorus were the main environmental factors affecting the changes in sediment microbial communities. The bacterial communities mainly involved four categories of primary metabolic functions, including metabolism, genetic information processing, environmental information processing, and cellular processes, and 18 categories of secondary metabolic functions, such as global and overview maps, carbohydrate metabolism, amino acid metabolism, cofactor and vitamin metabolism, and energy metabolism. Human interference led to significant changes in energy metabolism, cofactor and vitamin metabolism, nucleotide metabolism, replication and repair, and translation (P<0.05). In conclusion, anthropogenic disturbance led to the mutation of bacterial community diversity and function, which destroyed the stability of the microbial community structure in Jialing River sediments.

Klebsiella pneumoniae invasive liver abscess syndrome with purulent meningitis and septic shock: A case from mainland China.

We present a rare case of invasive liver abscess syndrome due to Klebsiella pneumoniae (K. pneumoniae) with metastatic meningitis and septic shock. A previously healthy, 55-year-old female patient developed fever, liver abscess, septic shock, purulent meningitis and metastatic hydrocephalus. Upon admission, the clinical manifestations, laboratory and imaging examinations were compatible with a diagnosis of K. pneumoniae primary liver abscess. Her distal metastasis infection involved meningitis and hydrocephalus, which could flare abruptly and be life threatening. Even with early adequate drainage and antibiotic therapy, the patient's condition deteriorated and she ultimately died. To the best of our knowledge, this is the first case of K. pneumoniae invasive liver abscess syndrome with septic meningitis reported in mainland China. Our findings reflect the need for a better understanding of the epidemiology, risk factors, complications, comorbid medical conditions and treatment of this disease.

Bimodal visualization of colorectal uptake of nanoparticles in dimethylhydrazine-treated mice.

AIM: To investigate colorectal uptake of solid lipid nanoparticles (SLNs) in mice receiving different doses of 1,2-dimethylhydrazine (DMH) using magnetic resonance (MR) and laser-scanning confocal fluorescence microscope (LSCFM) imaging. METHODS: Eight mice were sacrificed in a pilot study to establish the experimental protocol and to visualize colorectal uptake of SLNs in normal mice. Gadopentetate dimeglumine and fluorescein isothiocyanate (FITC)-loaded SLN (Gd-FITC-SLN) enemas were performed on mice receiving DMH for 10 wk (group 1, n = 9) or 16 wk (group 2, n = 7) and FITC-SLN enema was performed on 4 DMH-treated mice (group 3). Pre- and post-enema MR examinations were made to visualize the air-inflated distal colorectum. Histological and LSCFM examinations were performed to verify colorectal malignancy and to track the distribution of SLNs. RESULTS: Homogeneous enhancement and dense fluorescence (FITC) deposition in colorectal wall were observed in normal mice and 1 DMH-treated mouse (group 1) on fluid attenuated inversion recovery (FLAIR) and LSCFM images, respectively. Heterogeneous mural enhancement was found in 6 mice (4 in group 1; 2 in group 2). No visible mural enhancement was observed in the other mice. LSCFM imaging revealed linear fluorescence deposition along the colorectal mucosa in all groups. Nine intraluminal masses and one prolapsed mass were detected by MR imaging with different enhancement modes and pathologies. Interstitial FITC deposition was identified where obvious enhancement was observed in FLAIR images. Bladder imaging agent accumulations were observed in 11 of 16 DMH-treated mice of groups 1 and 2. CONCLUSION: There are significant differences in colorectal uptake and distribution of SLNs between normal and DMH-treated mice, which may provide a new mechanism of contrast for MR colonography.