Nanosecond pulsed electric field ablates rabbit VX2 liver tumors in a non-thermal manner.

BACKGROUND: Liver tumor remains an important cause of cancer-related death. Nanosecond pulsed electric fields (nsPEFs) are advantageous in the treatment of melanoma and pancreatic cancer, but their therapeutic application on liver tumors need to be further studied. METHODS: Hep3B cells were treated with nsPEFs. The biological behaviors of cells were detected by Cell Counting Kit-8, 5-ethynyl-20-deoxyuridine, and transmission electron microscopy (TEM) assays. In vivo, rabbit VX2 liver tumor models were ablated by ultrasound-guided nsPEFs and radiofrequency ablation (RFA). Contrast-enhanced ultrasound (CEUS) was used to evaluate the ablation effect. HE staining and Masson staining were used to evaluate the tissue morphology after ablation. Immunohistochemistry was performed to determine the expression of Ki67, proliferating cell nuclear antigen, and α-smooth muscle actin at different time points after ablation. RESULTS: The cell viability of Hep3B cells was continuously lower than that of the control group within 3 days after pulse treatment. The proliferation of Hep3B cells was significantly affected by nsPEFs. TEM showed that Hep3B cells underwent significant morphological changes after pulse treatment. In vivo, CEUS imaging showed that nsPEFs could completely ablate model rabbit VX2 liver tumors. After nsPEFs ablation, the area of tumor fibrosis and the expression of Ki67, proliferating cell nuclear antigen, and α-smooth muscle actin were decreased. However, after RFA, rabbit VX2 liver tumor tissue showed complete necrosis, but the expression of PCNA and α-smooth muscle actin did not decrease compared to the tumor group. CONCLUSIONS: nsPEFs can induce Hep3B cells apoptosis and ablate rabbit VX2 liver tumors in a non-thermal manner versus RFA. The ultrasound contrast agent can monitor immediate effect of nsPEF ablation. This study provides a basis for the clinical study of nsPEFs ablation of liver cancer.

The latest research progress on minimally invasive treatments for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. Due to the high prevalence of hepatitis B virus (HBV) infection in China, the incidence of HCC in China is high, and liver cirrhosis caused by chronic hepatitis also brings great challenges to treatment. This paper reviewed the latest research progress on minimally invasive treatments for HCC, including percutaneous thermal ablation and new nonthermal ablation techniques, and introduced the principles, advantages, and clinical applications of various therapeutic methods in detail. DATA SOURCES: The data of treatments for HCC were systematically collected from the PubMed, ScienceDirect, American Chemical Society and Web of Science databases published in English, using "minimally invasive" and "hepatocellular carcinoma" or "liver cancer" as the keywords. RESULTS: Percutaneous thermal ablation is still a first-line strategy for the minimally invasive treatment of HCC. The effect of microwave ablation (MWA) on downgrading treatment before liver transplantation is better than that of radiofrequency ablation (RFA), while RFA is more widely used in the clinical practice. High-intensity focused ultrasound (HIFU) is mainly used for the palliative treatment of advanced liver cancer. Electrochemotherapy (ECT) delivers chemotherapeutic drugs to the target cells while reducing the blood supply around HCC. Irreversible electroporation (IRE) uses a microsecond-pulsed electric field that induces apoptosis and necrosis and triggers a systemic immune response. The nanosecond pulsed electric field (nsPEF) has achieved a good response in the ablation of mice with HCC, but it has not been reported in China for the treatment of human HCC. CONCLUSIONS: A variety of minimally invasive treatments provide a sufficient survival advantage for HCC patients. Nonthermal ablation will lead to a new wave with its unique advantage of antitumor recurrence and metastasis.

Characterization of oral and gut microbiome and plasma metabolomics in COVID-19 patients after 1-year follow-up.

BACKGROUND: Due to the outbreak and rapid spread of coronavirus disease 2019 (COVID-19), more than 160 million patients have become convalescents worldwide to date. Significant alterations have occurred in the gut and oral microbiome and metabonomics of patients with COVID-19. However, it is unknown whether their characteristics return to normal after the 1-year recovery. METHODS: We recruited 35 confirmed patients to provide specimens at discharge and one year later, as well as 160 healthy controls. A total of 497 samples were prospectively collected, including 219 tongue-coating, 129 stool and 149 plasma samples. Tongue-coating and stool samples were subjected to 16S rRNA sequencing, and plasma samples were subjected to untargeted metabolomics testing. RESULTS: The oral and gut microbiome and metabolomics characteristics of the 1-year convalescents were restored to a large extent but did not completely return to normal. In the recovery process, the microbial diversity gradually increased. Butyric acid-producing microbes and Bifidobacterium gradually increased, whereas lipopolysaccharide-producing microbes gradually decreased. In addition, sphingosine-1-phosphate, which is closely related to the inflammatory factor storm of COVID-19, increased significantly during the recovery process. Moreover, the predictive models established based on the microbiome and metabolites of patients at the time of discharge reached high efficacy in predicting their neutralizing antibody levels one year later. CONCLUSIONS: This study is the first to characterize the oral and gut microbiome and metabonomics in 1-year convalescents of COVID-19. The key microbiome and metabolites in the process of recovery were identified, and provided new treatment ideas for accelerating recovery. And the predictive models based on the microbiome and metabolomics afford new insights for predicting the recovery situation which benefited affected individuals and healthcare.

Development and preliminary testing of a probe-based duplex real-time PCR assay for the detection of African swine fever virus.

An outbreak of African swine fever (ASF) in China in 2018 caused substantial economic losses to the swine industry. To accurately diagnose clinical infection with ASF virus (ASFV), we developed a TaqMan probe-based duplex real-time PCR that simultaneously detected two discontinuous genes in the virus genome, thereby preventing the inaccurate results obtained with only one reaction. Two sets of ASFV gene-specific primers, along with two fluorescent TaqMan probes were designed to target conserved regions of the B646L and B438L genes. This method had high sensitivity and specificity, with a limit of detection of 10 copies/µL, and it did not cross-react with the genomes of other viral pathogens that affect pigs (i.e., CSFV, PRRSV, PEDV, PRV, PPV and PCV2). Overall, 180 clinical samples from ASFV-infected pig farms were used to compare this method with a commercial kit, which yielded excellent consistency (98.3%). This new diagnostic method should greatly improve the efficiency of ASFV surveillance and reduce economic losses, providing benefits for both animal and public health.

Pollution characteristics, spatial variation, and potential risks of phthalate esters in the water-sediment system of the Yangtze River estuary and its adjacent East China Sea.

Spatiotemporal variability in seawater, spatial variation in sediment, pollution characteristics, and risks related to 16 phthalate esters (PAEs) were investigated in the Yangtze River estuary and its adjacent East China Sea. The total concentrations of ΣPAEs in surface water were 0.588-17.7 µg L-1 in summer, 2.63-22.9 µg L-1 in winter, and 1.93-20.7 µg L-1 in spring, with average values of 2.05, 10.2, and 4.89 µg L-1, respectively. PAE concentrations exhibited notable seasonal variations with the highest value in winter and the lowest value in summer. The seasonal variation in PAE concentrations may be influenced by runoff and diluted water from the Yangtze River. The chemical composition of PAEs showed that di-n-butyl phthalate (DnBP), diisobutyl phthalate (DiBP), and di(2-ethylhexyl) phthalate (DEHP) had significantly higher (p < 0.05) concentrations than the other congeners and were the most abundant PAE species in sediment and seawater in all three seasons. In addition, DnBP and DiBP were the two main congeners in seawater, and DEHP concentrations were higher in sediment than in seawater. DEHP had higher potential risks to sensitive organisms in water environment than DnBP and DiBP, and DiBP and DnBP which presented high levels of risk in sedimentary environment. DMP and DEP in watery and sedimentary environments and DEHP in sedimentary environment showed no or low risks to sensitive organisms.

Phthalic acid esters in the sea-surface microlayer, seawater and sediments of the East China Sea: Spatiotemporal variation and ecological risk assessment.

The spatial and temporal distribution, congener profiles and ecological risk of phthalic acid esters (PAEs) were investigated in the seawater and sediment samples from the East China Sea in spring and autumn. The average concentrations of ΣPAEs in water samples were 3.16 ± 2.16 µg L-1 in autumn and 1.63 ± 1.20 µg L-1 in spring. The ΣPAEs in sediment was much higher than that in seawater, with an average value of 7.36 ± 6.70 mg kg-1 (dw). PAEs levels in the sea-surface microlayer (SML) in spring were 3.61 ± 3.36 µg L-1, indicating that the PAEs were noticeably concentrated in the SML, with an average enrichment factor of 2.10. Among the 16 PAE congeners, di-n-butyl phthalate (DnBP), diisobutyl phthalate (DiBP), and di(2-ethylhexyl) phthalate (DEHP) were the preponderant PAEs in both sediment and seawater samples. Additionally, PAE concentrations in autumn were higher than those in spring, and this difference resulted mainly from the terrigenous input and marine transportation. The horizontal distributions of PAEs showed an opposite distribution pattern to salinity and temperature, a pattern which might be influenced by the inputs of fresh water. The vertical distributions of ΣPAEs were characterized by high concentrations in the surface waters, with a slight decrease with depth, and then an increase close to the seabed. The results of ecological risk in the water-phase showed that the level of potential risk followed the order of DEHP > DiBP and DnBP > DMP and DEP, which posed a high (DEHP), medium (DiBP and DnBP) and low (DMP and DEP) risk to the sensitive organisms, respectively. For the sediment-phase, DiBP and DnBP represented a high risk to the sensitive organisms, whereas DMP, DEP and DEHP had only a low risk.

Distribution and ecotoxicological state of phthalate esters in the sea-surface microlayer, seawater and sediment of the Bohai Sea and the Yellow Sea.

The spatial distribution, chemical composition and ecological risk of 16 phthalate esters (PAEs) were investigated in the sea-surface microlayer (SML), seawater and sediment samples of the Bohai Sea (BS) and the Yellow Sea (YS). The concentration levels of the ΣPAEs spanned a range of 449-13441 ng L-1 in the SML, 453-5108 ng L-1 in seawater, and 1.24-15.8 mg kg-1 in the sediment samples, respectively, with diisobutyl phthalate (DiBP), di-n-butyl phthalate (DBP) and di-ethylhexyl phthalate (DEHP) as the dominant PAEs in both the water and sediment samples. The concentrations of ΣPAEs in the BS were higher than those in the YS. The vertical distribution of ΣPAEs in the water column showed that the concentrations were higher in the surface waters, but decreased slightly with depth, and started to increase at the bottom. Additionally, PAEs were significantly enriched in the SML, with an average enrichment factor of 1.46. The ecological risk of the PAEs was evaluated by the risk quotient (RQ) method, which indicated that DEHP posed a high risk to aquatic organisms in the whole water-phase, while the RQ values of DBP and DiBP reached a high risk levels in sedimentary environment.