Percutaneous ultrasound-guided radiofrequency ablation for patients with liver metastases from gastrointestinal stromal tumors.

OBJECTIVES: This study aimed to analyze the survival outcomes and prognostic factors of radiofrequency ablation (RFA) for liver metastases from gastrointestinal stromal tumors (GISTs). METHODS: Between March 2011 and November 2022, 34 patients (16 males; age range, 25-72 [median age, 52.5] years) who underwent RFA for liver metastasis from GISTs were included. The mean maximum diameter of metastatic lesions was 2.4 ± 1.0 (range, 1.1-5.2) cm. Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. Multivariate analyses were performed using a Cox proportional hazards model. RESULTS: For 79 lesions among 34 patients, all targeted lesions were completely ablated. The mean hepatic progression-free survival (HPFS) period was 28.4 ± 3.8 (range, 1.0-45.7) months. The 1-, 3-, and 5-year HPFS rates were 67.2%, 60.5%, and 20.2%, respectively. Based on the univariate analysis, the number of metastatic tumors and tyrosine kinase inhibitors(TKI) therapy before RFA were prognostic factors for HPFS. Multivariate analysis showed that pre-RFA TKI therapy was associated with a better HPFS(p = 0.030). The mean overall survival (OS) period was 100.5 ± 14.1 (range, 3.8-159.5) months and the 1-, 3-, and 5-year survival rates were 96.9%, 77.1%, and 58.7%, respectively. Both univariate and multivariate analysis indicated that extrahepatic metastasis before RFA (p = 0.044) was a significant prognostic factor for OS. CONCLUSIONS: Liver metastases from GIST exhibit relatively mild biological behavior. RFA is safe and effective, particularly in patients without pre-RFA extrahepatic metastases. Patients received targeted therapy before RFA can obtain an extended HPFS.

Predictive nomograms of repeat intrahepatic recurrence and overall survival after radiofrequency ablation of recurrent colorectal liver metastases.

OBJECTIVES: This study was conducted to develop nomograms for predicting repeat intrahepatic recurrence (rIHR) and overall survival (OS), after radiofrequency ablation (RFA), treatment in patients with recurrent colorectal liver metastases (CLMs) after hepatectomy based on clinicopathologic features. METHODS: A total of 160 consecutive patients with recurrent CLMs after hepatectomy who were treated with ultrasound-guided percutaneous RFA from 2012 to 2022 were retrospectively included. Patients were randomly divided into a training cohort and a validation cohort, with a ratio of 8:2. Potential prognostic factors associated with rIHR and OS, after RFA, were identified by using the competing-risks and Cox proportional hazard models, respectively, and were used to construct the nomogram. The nomogram was evaluated by Harrell's C-index and a calibration curve. RESULTS: The 1-, 2-, and 3-year rIHR rates after RFA were 58.8%, 70.2%, and 74.2%, respectively. The 1-, 3- and 5-year OS rates were 96.3%, 60.4%, and 38.5%, respectively. In the multivariate analysis, mutant RAS, interval from hepatectomy to intrahepatic recurrence ≤ 12 months, CEA level >5 ng/ml, and ablation margin <5 mm were the independent predictive factors for rIHR. Mutant RAS, largest CLM at hepatectomy >3 cm, CEA level >5 ng/ml, and extrahepatic disease were independent predictors of poor OS. Two nomograms for rIHR and OS were constructed using the respective significant variables. In both cohorts, the nomogram demonstrated good discrimination and calibration. CONCLUSIONS: The established nomograms can predict individual risk of rIHR and OS after RFA for recurrent CLMs and contribute to improving individualized management.

[Zhuyu Pills promote polarization of macrophages toward M2 phenotype to prevent atherosclerosis via PPARγ/NF-κB signaling pathway].

This article aims to investigate the effect of Zhuyu Pills on atherosclerosis and decipher the underlying mechanism. The mouse model of atherosclerosis was induced by a high-fat diet, and the total modeling period was 12 weeks. A total of 47 ApoE~(-/-) mice successfully modeled were randomized into 5 groups, including 10 in the model group, 9 in each of low-, medium-, and high-dose(130.54, 261.08 and 522.16 mg·kg~(-1)·d~(-1), respectively) Zhuyu Pills groups, and 10 in the atorvastatin calcium(10.40 mg·kg~(-1)·d~(-1)) group. In addition, 10 C57BL/6J mice were included as the normal group. The mice in the normal group and model group were administrated with an equal volume of sterile distilled water, and those in other groups with corresponding agents by gavage once a day for 12 weeks. At the end of drug intervention, the levels of total cholesterol(TC), triglyceride(TG), high-density lipoprotein cholesterol(HDL-C), and low-density lipoprotein cholesterol(LDL-C) were measured by the biochemical method. Hematoxylin-eosin(HE) staining was employed to observe the plaque distribution in the aortic region. The serum levels of pro-inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin(IL)-6 in M1 macrophages and anti-inflammatory cytokines IL-13 and IL-4 in M2 macrophages were determined by enzyme-linked immunosorbent assay(ELISA). The expression levels of inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1) were examined by immunofluorescence. Real-time fluorescence quantitative polymerase chain reaction(real-time PCR) was employed to measure the mRNA levels of peroxisome proliferator-activated receptor γ(PPARγ), nuclear factor-κB(NF-κB), Arg-1, and iNOS in the aorta. Western blot was employed to determine the protein levels of PPARγ and NF-κB in the aorta. The results showed that compared with the normal group, the modeling elevated the TC, TG, and LDL-C levels, lowered the HDL-C level, caused large area thickening of the aortic intima, elevated the TNF-α and IL-6 levels, lowered the IL-4 and IL-13 levels, down-regulated the mRNA and protein levels of PPARγ and Arg-1, and up-regulated the mRNA and protein levels of iNOS and NF-κB in the aorta(P<0.01). Compared with the model group, low-, medium-, and high-dose Zhuyu Pills and atorvastatin calcium lowered the TC, TG, and LDL-C levels, elevated the HDL-C level, reduced the plaque area in a concentration-dependent manner, lowered the TNF-α and IL-6 levels, elevated the IL-4 and IL-13 levels, up-regulated the mRNA and protein levels of PPARγ and Arg-1, and down-regulated the mRNA and protein levels of NF-κB and iNOS in the aorta(P<0.05 or P<0.01). In conclusion, Zhuyu Pills may play an anti-atherosclerosis role by regulating PPARγ/NF-κB signaling pathway, inhibiting the polarization of macrophages toward the M1 phenotype, promoting the polarization of macrophages toward the M2 phenotype, and improving the inflammatory microenvironment of macrophages.

A Multicenter Randomized Controlled Study of Contrast-enhanced US versus US-guided Biopsy of Focal Liver Lesions.

Background Retrospective or single-center prospective studies with relatively small samples have shown that contrast-enhanced US (CEUS) can improve the diagnostic accuracy of percutaneous biopsy, but larger prospective studies are lacking. Purpose To assess the diagnostic performance of CEUS-guided biopsy (CEUS-GB) of focal liver lesions (FLLs) compared with US-guided biopsy (US-GB) in a prospective multicenter study. Materials and Methods In this randomized controlled study conducted in nine hospitals in China between March 2016 and August 2019, adult participants with FLLs detected with US, CT, or MRI and planned for percutaneous biopsy were randomly assigned to undergo either US-GB or CEUS-GB. Lesions diagnosed as malignant at histopathologic analysis were considered true-positive findings. Benign or indeterminate lesions required further confirmation with either repeat biopsy or clinical follow-up at 6 months or later. The primary endpoint was the diagnostic accuracy rate, and comparison between groups was made using the χ2 test. Results In this study, 2056 participants (1297 men, 759 women; mean age, 58 years ± 11 [SD]) were analyzed: 1030 underwent biopsy with US guidance and 1026 underwent biopsy with CEUS guidance. The overall diagnostic accuracy rate of CEUS-GB was 96% (983 of 1026) versus 93% (953 of 1030) for US-GB (P = .002), CEUS-GB enabled correct identification in 96% of participants (983 of 1026) compared with 92% (953 of 1030) with US-GB (P = .002). The negative predictive value (NPV) for both biopsy methods was moderate but significantly higher for CEUS-GB than for US-GB (74% vs 57%, P = .001). The difference was remarkable for lesions smaller than 2.0 cm, with CEUS-GB showing higher diagnostic accuracy (96% vs 88%, P = .004) and sensitivity (95% vs 87%, P = .007) than US-GB. Among lesions smaller than 2.0 cm, the accuracy of CEUS-GB and US-GB for detection of hepatocellular carcinoma was 93% and 80%, respectively (P = .008), while it was comparable for liver metastases (98% vs 95%, P = .63). Conclusion Contrast-enhanced US-guided biopsy of focal liver lesions is an effective and safe procedure with a higher diagnostic accuracy than US-guided biopsy, especially for lesions smaller than 2.0 cm and for hepatocellular carcinoma diagnosis. Clinical trial registration no. NCT02413437 © RSNA, 2022 Online supplemental material is available for this article.

Percutaneous ultrasound-guided radiofrequency ablation for patients with liver metastasis from pancreatic adenocarcinoma.

OBJECTIVE: To analyze the survival outcomes and prognostic factors of radiofrequency ablation (RFA) for pancreatic adenocarcinoma liver metastasis (PALM). METHODS: Between January 2010 and July 2021, 20 patients (13 males) with an average age of 58.9 ± 11.7 years who underwent RFA for PALM were included. The mean maximum diameter of PALMs was 2.6 ± 1.1 cm (1.0-6.0 cm). Survival curves were built using the Kaplan-Meier method and compared by the log-rank test. Multivariable analyses were performed by using the Cox proportional hazards model. RESULTS: Twenty patients with 29 PALMs underwent 23 RFA sessions. Technical efficacy was achieved in 28 PALMs (28/29, 96.6%). The mean overall survival (OS) after RFA was 14.6 months and the 1-, 2-year survival rates were 39.5%, 18.1%, respectively. With multivariate analysis, abnormal serum levels of CA199 (p = 0.023) and extrahepatic metastasis before RFA (p = 0.038) were identified as independent prognostic factors for OS in patients with PALM. Additionally, the mean progression-free survival (PFS) after RFA was 11.5 months and 1-, 2- year survival rates were 26.0%, 17.3%, respectively. With multivariate analysis, abnormal serum levels of CA199 (p = 0.016) and extrahepatic metastasis before RFA (p = 0.043) were also identified as independent prognostic factors for PFS in patients with PALM. CONCLUSION: RFA is a safe and effective treatment for patients with PALM, especially in patients with normal serum level of CA199 or the patients without extrahepatic metastases before RFA.

[Identification and biological characteristics of a pathogen causing leaf blight of Rehmannia glutinosa].

Leaf blight outbroke in Rehmannia glutinosa plantation in Wenxian county, Henan province in 2019. R. glutinosa plants with diseased leaves were collected from the plantation, and three strains were isolated from the diseased leaf samples. Pathogenicity test, morphological observation, and phylogenetic analysis of ITS, EF1-α, and Tub suggested that they were respectively Fusarium proliferatum, F. oxysporum, and F.acuminatum. Among them, F. acuminatum, as a pathogen of R. glutinosa leaf disease, had never been reported. To clarify the biological characteristics of F. acuminatum, this study tested the influence of light, pH, temperature, medium, carbon source, and nitrogen source on the mycelial growth rate of the pathogen during a 5-day culture period, and explored the lethal temperature. The results showed that the mycelia grew well under the photoperiod of 12 h light/12 h darkness, at 5-40 ℃(optimal temperature: 25 ℃), at pH 4-11(optimal pH: 7.0), on a variety of media(optimal medium: oatmeal agar), and in the presence of diverse carbon and nitrogen sources(optimal carbon source: soluble starch; optimal nitrogen source: sodium nitrate). The lethal temperature was verified to be 51 ℃(10 min). The conclusion is expected to lay a scientific basis for diagnosis and control of R. glutinosa leaf diseases caused by F. acuminatum.

The 10-year Survival Analysis of Radiofrequency Ablation for Solitary Hepatocellular Carcinoma 5 cm or Smaller: Primary versus Recurrent HCC.

Background Although favorable outcomes have been reported with radiofrequency ablation (RFA) for limited hepatocellular carcinoma (HCC), the efficacy of this treatment for recurrent HCC has not been thoroughly investigated. Purpose To compare the long-term outcomes and analyze the prognostic factors for outcomes after RFA for initial HCC versus as a second-line treatment for recurrent HCC. Materials and Methods This retrospective study included 560 patients with solitary tumors 5 cm or smaller (263 initial HCCs, 297 -recurrent HCCs) who underwent percutaneous US-guided RFA from January 2005 to December 2016. Of 297 patients with -recurrent HCC, 134 had previously undergone hepatectomy, 128 had undergone transarterial chemoembolization (TACE), and 35 had undergone local ablation therapy. Overall survival (OS) between initial HCC and recurrent HCC was compared before and after propensity score matching. Prognostic factors for all patients were analyzed with the log-rank test and Cox proportional hazards model. Results A total of 560 patients (mean age, 60 years ± 12 [standard deviation]; 441 men) were evaluated. Before matching, the OS rates at 1, 3, 5, and 10 years were 92.6%, 73.9%, 59.3%, and 39.6%, respectively, in patients with recurrent HCC and 92.8%, 75.4%, 63.3%, and 44.7% in patients with initial HCC (P = .27). After matching, the OS rates at 1, 3, 5, and 10 years were 94.8%, 75.7%, 61.6%, and 47.3% in the initial HCC group and 91.9%, 71.2%, 58.7%, and 45.2% in the recurrent HCC group (P = .32). Among patients with recurrent HCC, no significant difference in mean OS was noted for local recurrence versus distant recurrence (81.6 months ± 5.1 vs 83.8 months ± 6.6, P = .82) or previous treatment modality (82.0 months ± 7.3 in the resection group, 82.7 months ± 5.3 in the TACE group, and 79.3 months ± 10.8 in the local ablation group; P = .83). Local tumor progression after previous local ablation (10 of 35 [28.6%]) was higher than that after previous hepatectomy (15 of 134 [11.2%], P = .04). Multivariable analysis demonstrated that tumor size (hazard ratio, 1.58; 95% CI: 1.06, 2.36; P = .02), portal hypertension (hazard ratio, 1.52; 95% CI: 1.03, 2.26; P = .04), Child-Pugh class (hazard ratio, 2.01; 95% CI: 1.02, 3.96; P = .045), and serum α-fetoprotein level (hazard ratio, 1.62; 95% CI: 1.10, 2.39; P = .01) were independent predictive factors for recurrent HCC outcomes. Conclusion Radiofrequency ablation provides similar long-term survival for solitary hepatocellular carcinoma of 5 cm or less, regardless of whether treatment is initial or salvage therapy. © RSNA, 2021 Online supplemental material is available for this article.

Contrast-Enhanced Intraoperative Ultrasound Improved Sensitivity and Positive Predictive Value in Colorectal Liver Metastasis: a Systematic Review and Meta-Analysis.

BACKGROUND: The diagnostic accuracy of imaging modalities in colorectal cancer liver metastases (CRLM) has improved in recent years, therefore the role of current imaging techniques needs to be defined. OBJECTIVE: The aim of this study was to assess the diagnostic performance of magnetic resonance imaging, preoperative imaging (magnetic resonance imaging or computed tomography), intraoperative ultrasound, and contrast-enhanced intraoperative ultrasound in the detection of CRLM. MATERIALS AND METHODS: Eligible trials published before 30 March 2020 were identified from the EMBASE, PubMed, Web of Science, and Cochrane Library databases, and descriptive and quantitative data were extracted. Study quality was evaluated for the identified studies and a random-effects model was used to determine the integrated diagnosis estimation. Meta-regression was implemented to explore the possible contributors to heterogeneity. RESULTS: Overall, 13 studies were included for analysis, comprising 682 patients with a total of 2303 liver lesions. The pooled sensitivity, specificity, and diagnostic odds ratio of contrast-enhanced intraoperative ultrasound were 0.94 (95% confidence interval [CI] 0.89-0.97), 0.83 (95% CI 0.67-0.92), and 79 (95% CI 32-196), respectively. The overall weighted area under the curve was 0.96 (95% CI 0.94-0.97). In univariate meta-regression analysis, disappearing liver metastasis, contrast agent, and Kupffer phase were the potent sources of heterogeneity; however, in multivariate meta-regression, no definite variable was the source of the study heterogeneity. CONCLUSION: Contrast-enhanced intraoperative ultrasound demonstrated a high sensitivity and specificity for screening CRLM.

Nomogram including chemotherapy response for prediction of intrahepatic progression-free survival in patients with colorectal liver metastasis through chemotherapy followed by radiofrequency ablation.

BACKGROUND: Radiofrequency ablation (RFA) is being considered as the favorable treatment option for unresectable colorectal cancer liver metastases (CRLM) receiving chemotherapy, yet there still exist challenges for recurrence after RFA. The present study aims to establish an effective nomogram to predict intrahepatic progression-free survival (PFS) and select RFA candidates. METHODS: Patients with unresectable CRLM treated with chemotherapy followed by RFA between 2010 and 2016 were enrolled in this study. The nomogram to predict intrahepatic PFS was established based on multivariable Cox regression analysis. The predictive performance of the nomogram was assessed according to the C-index, calibration plots and Kaplan-Meier curve. RESULTS: Of a total of 158 patients, the earlier new intrahepatic metastases over local tumor progression were observed in 157 patients during the follow-up, and the mean intrahepatic PFS was 16.9 ± 1.4 months in the present cohort. The optimal cutoff value of tumor size after chemotherapy was identified as 16 mm by X-tile analysis. Based on multivariate analysis, independent prognostic factors for intrahepatic PFS included primary positive lymph nodes, multiple metastases, tumor size >16 mm, no primary lesion resection, mutant KRAS and PD response after chemotherapy. The nomogram was established to predict intrahepatic PFS based on all independent factors, which achieved favorable discrimination and calibration. CONCLUSION: This study firstly established the nomogram to predict intrahepatic PFS for unresectable CRLM patients receiving chemotherapy followed by RFA. It can facilitate the selection of RFA candidates, and help both surgeons and patients choose individualized regimens in the treatment decision.

[Identification and expression analysis of NRT1 family genes in Rehmannia glutinosa].

NRT1 family proteins play an important roles for absorbing and transporting of nitrate in different plants. In order to identify the NRT1 family genes of Rehmannia glutinosa, this study used 11 NRT1 homologous proteins of Arabidopsis as probe sequences and aligned with the transcriptome data of R. glutinosa by using NCBI BLASTN software. Resulting there were 18 NRT1 proteins were identified in R. glutinosa. On basis of this, a series of the molecular characteristics of R. glutinosa NRT1 proteins including the conserved domains, the transmembrane structure, the subcellular location and phylogenetic features were in detail analyzed. At same time, it were systematically analyzed that the temporal and spatial expression patterns and characteristics of R. glutinosa NRT1 family genes in response to different stress factors. The results indicated that 18 R. glutinosa NRT1 family genes with the length of coding region from 1 260 bp to 1 806 bp, encoded proteins ranging from 419 to 601 amino acids, and all of they owned the domains of typical peptide transporter with 7 to 12 transmembrane domains. These R. glutinosa NRT1 family proteins mostly were found to locate on cellular plasma membrane, and belonged to the hydrophobic proteins. Furthermore, the evolutionary analysis found that the 18 R. glutinosa NRT1 protein family could be divided into two subfamilies, of which 14 NRT1 family genes might occur the positive selection, and 4 genes occur the passivation selection during the evolution process of R. glutinosa. In addition the expression analysis showed that 18 R. glutinosa NRT1 family genes have the distinct expression patterns in different tissues of R. glutinosa, and their expression levels were also obvious difference in response to various stress. These findings infield that 18 R. glutinosa NRT1 family proteins might have obviously different functional roles in nitrate transport of R. glutinosa. In conclusion, this study lays a solid theoretical foundation for clarifying the absorption and transport molecular mechanism of N element during R. glutinosa growth and development, and at same time for deeply studying the molecular function of R. glutinosa NRT1 proteins in absorption and transport of nitrate.

[Effects of density on growth and gene transcription characteristics of Rehmannia glutinosa].

The present study analyzed the effects of planting density on the development, quality, and gene transcription characte-ristics of Rehmannia glutinosa using 85-5 and J9 as materials with three planting densities of 5 000, 25 000, and 50 000 plants/Mu(1 Mu≈667 m~2). The agronomic characteristics of leaves and tuberous roots, the content of catalpol and acteoside, and the changes of gene expression were determined. The results showed that the leaf size, the diameter of tuberous root, leaf biomass, tuberous root number, and tuberous root biomass per plant at low density were significantly higher than those of medium and high densities. The content of catalpol and acteoside in leaves was higher at high density. The content of catalpol in tuberous roots was higher at low density, and the change trend was similar to that in leaves, while the content of acteoside in tuberous roots was higher at high density. Transcriptome analysis found that about 1/2 of the expansin genes could change regularly in response to density treatment, which was rela-ted to the development of tuberous roots. The change trend of the gene expression of multiple catalytic enzymes involved in the biosynthesis of catalpol and acteoside was consistent with that of their content, which was presumedly involved in the accumulation and regulation of density-responsive medicinal components. Based on the analysis of the development, medicinal components, and gene expression characteristics of R. glutinosa at different densities, this study is expected to provide an important basis for regulating the quality and yield of medicinal materials of R. glutinosa by managing the planting density.

Metabolic reprogramming-associated genes predict overall survival for rectal cancer.

Metabolic reprogramming has become a hot topic recently in the regulation of tumour biology. Although hundreds of altered metabolic genes have been reported to be associated with tumour development and progression, the important prognostic role of these metabolic genes remains unknown. We downloaded messenger RNA expression profiles and clinicopathological data from The Cancer Genome Atlas and the Gene Expression Omnibus database to uncover the prognostic role of these metabolic genes. Univariate Cox regression analysis and lasso Cox regression model were utilized in this study to screen prognostic associated metabolic genes. Patients with high-risk demonstrated significantly poorer survival outcomes than patients with low-risk in the TCGA database. Also, patients with high-risk still showed significantly poorer survival outcomes than patients with low-risk in the GEO database. What is more, gene set enrichment analyses were performed in this study to uncover significantly enriched GO terms and pathways in order to help identify potential underlying mechanisms. Our study identified some survival-related metabolic genes for rectal cancer prognosis prediction. These genes might play essential roles in the regulation of metabolic microenvironment and in providing significant potential biomarkers in metabolic treatment.

Functional Characterization and Structural Basis of an Efficient Di-C-glycosyltransferase from Glycyrrhiza glabra.

A highly efficient di-C-glycosyltransferase GgCGT was discovered from the medicinal plant Glycyrrhiza glabra. GgCGT catalyzes a two-step di-C-glycosylation of flopropione-containing substrates with conversion rates of >98%. To elucidate the catalytic mechanisms of GgCGT, we solved its crystal structures in complex with UDP-Glc, UDP-Gal, UDP/phloretin, and UDP/nothofagin, respectively. Structural analysis revealed that the sugar donor selectivity was controlled by the hydrogen-bond interactions of sugar hydroxyl groups with D390 and other key residues. The di-C-glycosylation capability of GgCGT was attributed to a spacious substrate-binding tunnel, and the G389K mutation could switch di- to mono-C-glycosylation. GgCGT is the first di-C-glycosyltransferase with a crystal structure, and the first C-glycosyltransferase with a complex structure containing a sugar acceptor. This work could benefit the development of efficient biocatalysts to synthesize C-glycosides with medicinal potential.

What is the difference in ablation zone of multi-bipolar radiofrequency ablation between liver cirrhosis and normal liver background? - a prospective clinical study.

PURPOSE: To explore the differences in ablation zone between liver cirrhosis and normal liver background and investigate the effect of hepatic blood flow on ablation zone of RFA. METHODS: Between 2017 and 2019, 203 patients who had liver malignancies and underwent percutaneous RFA with Celon bipolar electrodes enrolled into this study. There were 90 patients had liver cirrhosis and 113 patients had normal liver background. They were 63 females and 140 males with average age of 59.0 ± 10.9 years old. Contrast-enhanced CT/MRI was used to evaluate the ablation zone in one month after RFA. The hepatic flow measurements on CDFI and CEUS were performed before RFA. Correlations between ablation zone versus hepatic flow were assessed using multiple linear regression analysis. RESULTS: The average ablation zone in cirrhotic liver was significantly larger than those in normal liver background with 3 cm tip of RF electrodes (length 3.5 ± 0.5 vs 3.1 ± 0.4 cm, p = 0.001; width 2.6 ± 0.3 vs 2.2 ± 0.3 cm, p < 0.001; thickness 2.5 ± 0.3 vs 2.0 ± 0.2 cm, p < 0.001). The similar result was found with three 4 cm tip of RF electrodes (width 3.6 ± 0.5 vs 3.1 ± 0.5 cm, p = 0.019; thickness 3.3 ± 0.5 vs 2.7 ± 0.5 cm, p = 0.002). The multiple linear regression analysis showed arrive time of hepatic vein and portal vein was statistically associated with ablation zone with 3 cm electrodes (p < 0.001, p = 0.001), but explained part of the variance (Adjusted R2=0.294, adjusted R2=0.212). CONCLUSION: The ablation zones of RFA with multi-bipolar electrodes in liver cirrhosis were significantly larger than those in normal liver background, being up to 6 mm in thickness. The hepatic flow parameters partly contributed to the ablation zone.

[Correlation between chemical composition,ecological factors and soil factors of Chinese herbal medicine Daphnes Cortex].

In this paper, the correlation between the chemical constituents of Chinese herbal medicines Daphnes Cortex and the ecological factors and soil factors was studied, which provided a reference for the selection of suitable areas for artificial cultivation of Daphne giraldii and wild tending. The geographic information system(GIS) was applied to obtain the ecological factor information of 23 collection sites of Daphnes Cortex, and the soil factor information was determined by the standard procedure in the soil test standard manual. Combining the information of 93 chemical constituents of Daphnes Cortex in 23 collection sites the correlation between components and ecological factors and soil factors was analyzed by statistical methods. The correlation analysis showed that the longitude, annual average rainfall, annual sunshine intensity, annual average temperature in the ecological factors, soil type, effective copper and pH value were the dominant factors affecting the chemical composition of Daphnes Cortex.

Long-term outcomes and prognostic analysis of percutaneous radiofrequency ablation in liver metastasis from breast cancer.

OBJECTIVE: To evaluate the long-term efficacy and prognostic factors of ultrasound-guided percutaneous radiofrequency ablation (RFA) for breast cancer liver metastasis (BCLM). METHODS: Between 2000 and 2015, 69 patients who underwent ultrasound-guided percutaneous RFA for BCLM and had regular follow-up examinations were included. All patients had undergone resection of the primary breast cancer and had received chemotherapy, endocrine therapy or both after surgery. The sample included two males and 67 females with an average age of 50.3 ± 10.0 years (31-76 y). The mean maximum diameter of metastatic lesions in the liver was 2.9 ± 1.4 cm (1.0-6 cm). Thirty-five patients had a single metastasis, while 34 patients had multiple liver metastases (2-5 lesions). Survival results were generated using Kaplan-Meier estimates and a multivariate analysis was performed using the Cox regression model. RESULTS: In total, 92 RFA sessions were performed and 135 BCLM lesions were treated. Major complications occurred in one of the 92 sessions (1.1%). Technical efficacy was achieved in 92.6% of lesions (125/135 lesions). Local tumor progression occurred in 11.6% (8/69) of patients and new intrahepatic metastasis occurred in 55.1% (38/69) of patients. From the time of initial RFA, the median overall survival was 26 months, and the one-, two-, three- and five -year survival rates were 81.8, 50.1, 25.3 and 11.0%, respectively. Based on the multivariate analysis, the following three factors were identified as independent prognostic factors for overall survival: tumor size (p = .017), positive estrogen receptor status (p = .009) and extrahepatic metastatic disease (p = .001). The median progression-free survival was 24 months, and the one-, two-, three- and five -year survival rates after RFA were 77.4, 47.0, 23.7 and 8.5%, respectively. Additionally, the independent prognostic factors for progression-free survival included tumor size (p = .011), ER positivity (p = .001), margin size (p = .017) and extrahepatic metastatic disease (p < .001). CONCLUSION: The results of this study showed that RFA is a safe and locally effective method for the treatment of BCLM, especially in patients with lesions measuring less than 3 cm in diameter, a single liver metastasis, positive estrogen receptor status and no extrahepatic metastases. Also, patients with margin size >10 mm had no local tumor progression.

The value of KRAS gene status in predicting local tumor progression of colorectal liver metastases following radiofrequency ablation.

PURPOSE: We investigated the relationships between KRAS gene status and local tumor progression (LTP) of colorectal liver metastases (CLMs) after treatment with percutaneous ultrasound-guided radiofrequency ablation (RFA). MATERIALS AND METHODS: Clinical and imaging data from 76 patients (154 lesions) with CLM who underwent percutaneous ultrasound-guided RFA and had KRAS gene test results between January 2012 and June 2016 were analyzed. The average lesion size was 2.3 ± 1.0 cm (range 0.9-5.7 cm); 38 cases (82 lesions) had wild-type KRAS, and 38 cases (72 lesions) had KRAS mutations. RESULTS: The technique effectiveness was 98.1% (151/154), and the LTP rate was 18.2% (28/154) after RFA, which was performed between January 2012 and November 2017. The mean and median follow-up were 32.7 ± 2.5 and 32.0 ± 2.6 months (range 1-70 months), respectively. Cumulative LTP rates at 6 months and 1, 2 and 3 years post-RFA for all patients were 7.4, 14.5, 17.8 and 19.2%, respectively. The LTP rate for patients with mutant KRAS (27.8% [20/72]) was significantly higher than that in patients with wild-type KRAS (9.8% [8/82]; p = .004). The cumulative LTP rates at 6 months and 1, 2 and 3 years post-RFA were 4.0, 11.1, 11.1 and 11.1%, respectively, for patients with wild-type KRAS and 11.2, 18.4, 25.2 and 36.2%, respectively, for patient with mutant KRAS (p = .011). Univariate (p = .011) and multivariate analyses (p = .005) showed that KRAS genotype in liver metastases was predictive of LTP. Multivariate analysis also showed that ablation margin size (p< .001) and modified clinical risk score (CRS; p = .033) were independent prognostic factors for LTP. CONCLUSIONS: KRAS gene status of liver metastatic lesions was associated with LTP rates after RFA of CLM. Ablation margin size and modified CRS were also independent prognostic factors for LTP.

[Cloning and expression analysis of LncRNA-RgAGT2 responding to consecutive monoculture in Rehmannia glutinosa].

The consecutive monoculture obstacle is a major problem in the field of Rehmannia glutinosa( R. glutinosa),has severely declined the yield and quality of R. glutinosa. Here,using hi TAIL-PCR and RACE techniques,we have cloned the full-length transcript( 1 573 bp) of Unigene 29334＿All screened by DGE as a consecutive monoculture obstacle response gene of R. glutinosa. Based on ORF Finder prediction,all ORFs detected in the full-length transcript were less than 300 nt,which suggested that the above transcript was confirmed to be a long non-coding RNA( LncRNA). With alignment in R. glutinosa transcriptome,this LncRNA was partially homologous to alanine glyoxylate transaminase 2 gene( Rg AGT2),which was named LncRNA-RgATG2. To further explore the function of LncRNA-RgAGT2,we have examined expression patterns of LncRNA-RgAGT2 and Rg AGT2 at five critical development stages( seedling,elongation,pre-expanding,mid-expanding,late-expanding) in the first and second year replanting of R. glutinosa,respectively. The results indicated that LncRNA-RgAGT2,as a potential regulator,is possible to play a vital role in Rg AGT2 expression regulation. Meanwhile,LncRNA-RgAGT2 has presented significant variation in all development stages of R. glutinosa,which could be used as a " diagnostic label" to assess consecutive monoculture obstacle. This study,for the first time,showed that LncRNA was responsible for the response and regulation of consecutive monoculture obstacle,which would be a powerful supplement to reveal the molecular mechanisms of consecutive monoculture obstacle of R. glutinosa.

Integrated analysis of transcriptomic and metabolomic data reveals critical metabolic pathways involved in rotenoid biosynthesis in the medicinal plant Mirabilis himalaica.

Mirabilis himalaica (Edgew.) Heimerl is among the most important genuine medicinal plants in Tibet. However, the biosynthesis mechanisms of the active compounds in this species are unclear, severely limiting its application. To clarify the molecular biosynthesis mechanism of the key representative active compounds, specifically rotenoid, which is of special medicinal value for M. himalaica, RNA sequencing and TOF-MS technologies were used to construct transcriptomic and metabolomic libraries from the roots, stems, and leaves of M. himalaica plants collected from their natural habitat. As a result, each of the transcriptomic libraries from the different tissues was sequenced, generating more than 10 Gb of clean data ultimately assembled into 147,142 unigenes. In the three tissues, metabolomic analysis identified 522 candidate compounds, of which 170 metabolites involved in 114 metabolic pathways were mapped to the KEGG. Of these genes, 61 encoding enzymes were identified to function at key steps of the pathways related to rotenoid biosynthesis, where 14 intermediate metabolites were also located. An integrated analysis of metabolic and transcriptomic data revealed that most of the intermediate metabolites and enzymes related to rotenoid biosynthesis were synthesized in the roots, stems and leaves of M. himalaica, which suggested that the use of non-medicinal tissues to extract compounds was feasible. In addition, the CHS and CHI genes were found to play important roles in rotenoid biosynthesis, especially, since CHS might be an important rate-limiting enzyme. This study provides a hypothetical basis for the screening of new active metabolites and the metabolic engineering of rotenoid in M. himalaica.

Percutaneous ablation of the tumor feeding artery for hypervascular hepatocellular carcinoma before tumor ablation.

OBJECTIVE: To evaluate the efficiency and safety of percutaneous ablation of the tumor feeding artery (PAA) before radiofrequency ablation (RFA) for hypervascular hepatocellular carcinoma (HCC) under ultrasound guidance. PATIENTS AND METHODS: In total, 94 patients with hypervascular HCC and tumor feeding artery visible by contrast-enhanced ultrasound were prospectively randomized to receive either PAA combined with RFA (RFA + PAA) or RFA alone. This study was registered at the clinical trials registry website (No. NCT03143140). The mean tumor size was 3.2 ± 0.9 cm (2.0-5.0 cm). The mean follow-up was 23.7 ± 9.7 months (4-44 months). The technical success, local tumor progression and intrahepatic distant recurrence rates were compared. Survival analysis was performed using the Kaplan-Meier method and compared with the log-rank test. RESULTS: The local tumor progression rate was lower for the PAA + RFA group than for the RFA group (8.5% vs 21.3%, p < .082). No significant differences in the technical success and intrahepatic distant recurrence rates were observed between the two groups (97.9% vs 91.5%, p = .203 and 40.4% vs 42.6%, p = .834). The 1- and 3-year local tumor progression-free survival rates were 91.5% and 69.9% vs 68.1% and 52.1% for the PAA + RFA vs RFA groups, respectively (p = .052). The 1- and 3-year overall survival rates were 95.7% and 69.1% vs 89.4% and 66.6% in the PAA + RFA vs RFA groups, respectively (p = .744). The major complication rate was 4.3% in both groups. CONCLUSIONS: PAA appears to be an effective and safe technique for the treatment of hypervascular HCC, with a lower local tumor progression rate than that of conventional RFA.