Microwave ablation combined with lipiodol-microsphere mixed or conventional transarterial chemoembolization for the treatment of colorectal liver metastases: A retrospective study.

PURPOSE: To investigate the clinical outcomes of microwave ablation (MWA) combined with lipiodol-microsphere mixed transarterial chemoembolization (mTACE) or conventional TACE (cTACE) for patients with colorectal liver metastases (CRLM). MATERIALS AND METHODS: This retrospective study evaluated the medical records of patients with CRLM who underwent MWA combined with mTACE or cTACE from January 2018 to September 2021. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated during the follow-up. In addition, prognostic factors affecting survival were analyzed by univariate and multivariate methods. RESULTS: A total of 79 patients with CRLM were enrolled in the study (MWA-mTACE group, n = 38; MWA-cTACE group, n = 41). The patients who underwent MWA-mTACE had higher DCR (86.8% vs. 65.9%, P = 0.029) and better PFS (median, 8.1 vs. 5.5 months, P = 0.018) than those who underwent MWA-cTACE, but no significant difference was found in ORR (34.2% vs. 22.0%, P = 0.225) and OS (median, 15.7 vs. 13.0 months, P = 0.231). Further univariate and multivariate analyses indicated that MWA-mTACE was an independent positive factor for PFS, and abnormal carcinoembryonic antigen level was a hazard factor for OS. The postoperative laboratory tests and complications in patients who underwent MWA-mTACE were similar to those who underwent MWA-cTACE. CONCLUSION: Lipiodol-microsphere mixed TACE might be an effective and safe treatment to combine with microwave ablation for patients with colorectal liver metastases.

Traditional Chinese Medicine Enema Therapy in a Patient With a Confirmed Negative SARS-CoV-2 Test in the Respiratory Tract but Positive in the Intestinal Tract: A Case Report.

We report the case of a 43-year-old man who was infected with SARS-CoV-2 in February 2020 and actively cooperated with treatment in the hospital. During the course of treatment, we found that the respiratory SARS-CoV-2 nucleic acid became negative, but remained positive in the intestinal tract. As a result, we adjusted the treatment plan to include traditional Chinese medicine enema treatment. The patient had negative intestinal SARS-CoV-2 nucleic acid test within 4 days, and the subsequent repeated review of intestinal SARS-CoV-2 nucleic acid was negative, and the virus was undetectable. It is suggested that traditional Chinese medicine enema treatment may be helpful to remove the SARS-CoV-2 in the intestines of patients with COVID-19 infection, and may support the treatment of patients with respiratory SARS-CoV-2 nucleic acid negative and positive in the intestinal tract.

Episo: quantitative estimation of RNA 5-methylcytosine at isoform level by high-throughput sequencing of RNA treated with bisulfite.

MOTIVATION: RNA 5-methylcytosine (m5C) is a type of post-transcriptional modification that may be involved in numerous biological processes and tumorigenesis. RNA m5C can be profiled at single-nucleotide resolution by high-throughput sequencing of RNA treated with bisulfite (RNA-BisSeq). However, the exploration of transcriptome-wide profile and potential function of m5C in splicing remains to be elucidated due to lack of isoform level m5C quantification tool. RESULTS: We developed a computational package to quantify Epitranscriptomal RNA m5C at the transcript isoform level (named Episo). Episo consists of three tools: mapper, quant and Bisulfitefq, for mapping, quantifying and simulating RNA-BisSeq data, respectively. The high accuracy of Episo was validated using an improved m5C-specific methylated RNA immunoprecipitation (meRIP) protocol, as well as a set of in silico experiments. By applying Episo to public human and mouse RNA-BisSeq data, we found that the RNA m5C is not evenly distributed among the transcript isoforms, implying the m5C may subject to be regulated at isoform level. AVAILABILITY AND IMPLEMENTATION: Episo is released under the GNU GPLv3+ license. The resource code Episo is freely accessible from https://github.com/liujunfengtop/Episo (with Tophat/cufflink) and https://github.com/liujunfengtop/Episo/tree/master/Episo_Kallisto (with Kallisto). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Percutaneous thermal ablation combined with simultaneous transarterial chemoembolization for hepatocellular carcinoma ≤5 cm.

BACKGROUND/AIM: Percutaneous thermal ablation combined with transarterial chemoembolization (TACE) becomes a treatment option for unresectable hepatocellular carcinoma (HCC). This study aims to investigate the safety and feasibility of percutaneous thermal ablation combined with simultaneous TACE for patients with HCC ≤ 5 cm. MATERIALS AND METHODS: From June 2010 to February 2017, a total of 280 patients with HCC ≤ 5 cm who underwent percutaneous thermal ablation combined with simultaneous TACE were included in our study. Their clinical data were collected and analyzed. RESULTS: Major complications occurred in five cases (1.8%). The complete necrosis rate was 91.9%. The median overall survival (OS) was 66.5 months (95% confidence interval [CI] = 57.7-75.2). The OS rates in 1-, 3-, 5-, and 7-year were 96.7%, 76.0%, 59.7%, and 31.1%, respectively. Tumor size (hazard ratio = 1.826; 95% CI = 1.131-2.947; P = 0.014) was considered as independent prognostic factors of long-term survival. CONCLUSION: Percutaneous thermal ablation combined with simultaneous TACE is a safe and effective treatment for HCC ≤ 5 cm.

Gold Cube-in-Cube Based Oxygen Nanogenerator: A Theranostic Nanoplatform for Modulating Tumor Microenvironment for Precise Chemo-Phototherapy and Multimodal Imaging.

Engineering a versatile oncotherapy nanoplatform integrating both diagnostic and therapeutic functions has always been an intractable challenge in targeted cancer treatment. Herein, to actualize the theme of precise medicine, a nanoplatform is developed by anchoring Mn-Cdots to doxorubicin (DOX)-loaded mesoporous silica-coated gold cube-in-cubes core/shell nanocomposites and further conjugating them to a Arg-Gly-Asp (RGD) peptide (denoted as RGD-CCmMC/DOX) to achieve an active-targeting effect. Under 635 nm irradiation, the nanoplatform acts as oxygen nanogenerator that produces O2 in situ and amplifies the content of singlet oxygen (1O2) in the hypoxic tumor microenvironment (TME), which has been demonstrated to attenuate tumor hypoxia and synchronously enhance photodynamic efficacy. Moreover, the gold cube-in-cube core in this work has been proven as a photothermal agent for hyperthermia, which exhibits a favorable photothermal effect with a 65.6% calculated photothermal conversion efficiency under 808 nm irradiation. In addition, the nanoplatform achieves heat- and pH-sensitive drug release with precise control to specific-tumor sites, executing combined chemo-phototherapy functions. Besides, it functions as a multimodal bioimaging agent of photothermal, fluorescence, and magnetic resonance imaging for the accurate diagnosis and guidance of therapy. As validated by in vivo and in vitro assays, the TME-responsive nanoplatform is highly biocompatible and effectively obliterates 4T1 tumor xenografts on nude mice after triple-synergetic treatment. This work presents a rational design of versatile nanoplatforms, which modulate the TME to enable high therapeutic performance and multiplexed imaging, which provides an innovative paradigm for targeted tumor therapy.

Combined endovascular brachytherapy, sorafenib, and transarterial chemobolization therapy for hepatocellular carcinoma patients with portal vein tumor thrombus.

AIM: To evaluate the safety and efficacy of combined endovascular brachytherapy (EVBT), transarterial chemoembolization (TACE), and sorafenib to treat hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (MPVTT). METHODS: This single-center retrospective study involved 68 patients with unresectable HCC or those who were unfit for liver transplantation and percutaneous frequency ablation according to the BCLC classification. All patients had Child-Pugh classification grade A or B, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and MPVTT. The patients received either EVBT with stent placement, TACE, and sorafenib (group A, n = 37), or TACE with sorafenib (group B, n = 31). The time to progression (TTP) and overall survival (OS) were evaluated by propensity score analysis. RESULTS: In the entire cohort, the 6-, 12-, and 24-mo survival rates were 88.9%, 54.3%, and 14.1% in group A, and 45.8%, 0%, and 0% in group B, respectively (P < 0.001). The median TTP and OS were significantly longer in group A than group B (TTP: 9.0 mo vs 3.4 mo, P < 0.001; OS: 12.3 mo vs 5.2 mo, P < 0.001). In the propensity score-matched cohort, the median OS was longer in group A than in group B (10.3 mo vs 6.0 mo, P < 0.001). Similarly, the median TTP was longer in group A than in group B (9.0 mo vs 3.4 mo, P < 0.001). Multivariate Cox analysis revealed that the EVBT combined with stent placement, TACE, and sorafenib strategy was an independent predictor of favorable OS (HR = 0.18, P < 0.001). CONCLUSION: EVBT combined with stent placement, TACE, and sorafenib might be a safe and effective palliative treatment option for MPVTT.

Acetylation Enhances TET2 Function in Protecting against Abnormal DNA Methylation during Oxidative Stress.

TET proteins, by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), are hypothesized, but not directly shown, to protect promoter CpG islands (CGIs) against abnormal DNA methylation (DNAm) in cancer. We define such a protective role linked to DNA damage from oxidative stress (OS) known to induce this abnormality. TET2 removes aberrant DNAm during OS through interacting with DNA methyltransferases (DNMTs) in a "Yin-Yang" complex targeted to chromatin and enhanced by p300 mediated TET2 acetylation. Abnormal gains of DNAm and 5hmC occur simultaneously in OS, and knocking down TET2 dynamically alters this balance by enhancing 5mC and reducing 5hmC. TET2 reduction results in hypermethylation of promoter CGIs and enhancers in loci largely overlapping with those induced by OS. Thus, TET2 indeed may protect against abnormal, cancer DNAm in a manner linked to DNA damage.

Synthesis and biological evaluation of Germanium(IV)-polyphenol complexes as potential anti-cancer agents.

Germanium (Ge) is considered to play a key role in the pharmacological effects of some medicinal plants. Here, two new Ge(IV)-polyphenol complexes were synthesized and measured for their potential biological activities. The results indicated that these Ge(IV)-polyphenol complexes possessed great anti-oxidative activities, both showing stronger hydroxyl scavenging effects than their corresponding ligands. We also demonstrated the strong intercalating abilities of Ge(IV)-polyphenol complexes into calf thymus-DNA molecules. In addition, these two Ge(IV)-polyphenol complexes showed strong proliferative inhibition effect on HepG2 cancer cells. Moreover, the morphological changes in HepG2 cells induced by Ge(IV)-polyphenol complexes were detected by atomic force microscopy. All these results collectively suggested that Ge(IV)-polyphenol complexes could be served as promising pharmacologically active substances against cancer treatment.

[Study on the chemical constituents of Buddleja davidii].

OBJECTIVE: To study the chemical constituents of Buddleja davidii. METHODS: The constituents were isolated and purified by silica gel column chromatography, polyamide column chromatography and macroporous adsorption resin and their structures were identified by spectroscopic analysis. RESULTS: Eight compounds were elucidated as : Cranioside A (1), Eutigoside A (2), 1-O-4-Dimethoxyphenylethyl-4-O-3,4-dimethoxyphenylethy-beta-D-glucopyranoside (3), Isomartynoside (4'), 4"-O-Acetylmartynoside (5), Stigmasterol glueoside (6), beta-Sitosterol (7), Daucosterol (8). CONCLUSION: All these compounds are obtained from this plant for the first time.

Apolipophorin III and transmission electron microscopy as toxicity indicators for harmaline and tea saponin in Spodoptera exigua (Noctuidae: Lepidoptera).

Apolipophorin III, traditionally known for lipid transport in insects is fairly established as toxicity indicator against harmaline and tea saponin during this study. Apolipophorin III expressed in the hemolymph and midgut tissues of 3rd, 4th, 5th larval instars and pupae of Spodoptera exigua. Apolipophorin III presence was further confirmed by achieving its partial cDNA (Genbank accession no. FJ606822) of 448bp. qRT PCR revealed that tea saponin resulted in significant reduction of gene expression in 3rd and 4th larval instars but increased in 5th instar as compared to control. Harmaline caused gradual increase of gene expression in 3rd, 4th and 5th instars after feeding on the treated diet. Fifth instar larvae synonymously resulted in the highest gene expressions against both the biochemicals. After the injection of harmaline and tea saponin abrupt increase in gene expression of 4th, 5th larval instar and pupae was observed as compared to control treatment. Transmission electron microscopy of midgut epithelium after being fed with harmaline and tea saponin depicted certain cytological changes. Harmaline treatment lead to cytoplasm vacuolization, mitochondrial disruption, spherocrystals with concentric layers, irregular nucleus and floating nuclei in cytoplasm. Tea saponin treatment resulted in denser cytoplasm, higher intracellular osmotic concentration and reduced complement of apical microvilli. Cells were found to have only a few mitochondria and glycogen deposits in comparison to control treatment.

Hepatic arterial infusion with oxaliplatin, irinotecan and doxifluridine for unresectable liver metastases of colorectal cancer.

AIM: To evaluate the therapeutic efficacy and safety of combination chemotherapy with oxaliplatin, irinotecan and doxifluridine through hepatic arterial infusion (HAI) in patients with unresectable liver metastases of colorectal cancer. PATIENTS AND METHODS: Individual patients were treated through the tumour-blood supplying arteries with oxaliplatin, irinotecan and doxifluridine and chemoembolised with irinotecan and lipiodol for the detected hypervascular lesions. RESULTS: A total of 173 cumulative cycles of chemotherapy were performed for the 32 patients, with a median of 5.0 cycles, including 96 chemoembolisations. Fifteen patients reached partial remission, 14 patients had stable disease and only 3 patients had progressive disease. The overall response rate was 46.9%. Of the 32 patients, 18 patients received first-line treatment with an overall response rate of 61.1%. The remaining 14 patients received second-line treatment, with an overall response rate of 28.6%. CONCLUSION: Combination chemotherapy through HAI is well tolerated and highly effective in patients with unresectable liver metastases of colorectal cancer.

[Features of blood supply and results of transarterial infusion and embolization in spinal metastases].

OBJECTIVE: To study the features of blood supply and results of transarterial infusion and embolization in spinal metastases. METHODS: Forty-one patients with spinal metastasis received transarterial infusion and embolization between March 2001 and June 2008. The inclusion criteria were: The metastatic lesion caused back pain; The metastatic lesion involved vertebra at or below T3 level. There were 29 males and 12 females with a mean age of 56.0 (33 - 71) years. Epirubicin was used as the chemotherapeutic agent. Lipoid Ultra-Fluid, Contour SE or gelfoam particles were used as embolitic material. RESULTS: The technical success of therapy was achieved in 52 vertebrae (100%) including 14 thoracic, 35 lumbar and 3 sacral vertebrae. 105 arteries were used for infusion and embolization (16 intercostal arteries, 78 lumbar arteries, 4 iliolumbar arteries, 4 branches of iliac arteries, and 3 median sacral arteries). Lipoid Ultra-Fluid (2 - 8 ml) was used in 15, Contour SE (300 approximately 500 microm, 20 - 100 mg) in 20, and gelfoam particles in 33 arteries. Three days after treatment, complete pain relief (CR) was achieved in 17 patients, partial pain relief (PR) in 20, and moderate pain relief (MR) in 4, with an effective rate of 90.2%. Two weeks after treatment, CR was achieved in 17 patients, PR in 21, and MR in 3, with an effective rate of 92.7%. No adverse nervous system effect occurred. 16 patients developed swelling and pain of normal tissues which were alleviated after symptomatic treatment. CONCLUSION: Transarterial infusion and embolization is an effective therapy in relieving pain resulting from spinal metastases.

Effects of crude rhubarb on intestinal permeability in septic patients.

The therapeutic effect of crude rhubarb on intestinal permeability was investigated in septic patients. Forty septic patients were enrolled in this study and randomly divided into two groups: the crude rhubarb treatment group (n = 18) and the control group (n = 22). The same treatments were given to both groups except that the crude rhubarb treatment group was administrated with crude rhubarb powders (3 g, tid, p.o). The levels of procalcitonin, D-lactate in plasma and lactulose/mannitol (L/M) ratio in the urine were determined on the first day and the sixth day after treatment with or without crude rhubarb. There were no significant differences in procalcitonin, L/M ratio and D-lactate on the first day between the crude rhubarb treatment group and the control group (p > 0.05). However, the ratio of L/M on the sixth day for the control group was 0.167 +/- 0.036, while that of the crude rhubarb treatment group was 0.062 +/- 0.013 (p < 0.05). Moreover, the levels of procalcitonin and D-lactate in the crude rhubarb treatment group were obviously lower than those in the control group on the sixth day (procalcitonin: 4.11 +/- 1.40 microg/L vs. 2.21 +/- 0.61 mug/L; D-lactate: 0.24 +/- 0.06 ng/L vs. 0.09 +/- 0.03 ng/L, p < 0.05, both). These data confirmed that crude rhubarb's effects on septic patients of ameliorating intestinal permeability.

[Epirubicin in the treatment of malignant obstructive jaundice].

OBJECTIVE: To evaluate the safety and efficiency of epirubicin in the treatment of malignant obstructive jaundice (MOJ). METHODS: Thirty-nine patients with diagnosis of MOJ, whose serum total bilirubin (TB) had not dropped to normal level after stent placement or percutaneous transhepatic biliary drainage, received trans-arterial chemoembolization (TACE). During TACE, epirubicin emulsion containing pharmorubicin at dose of 30 mg/m(2) was used. The toxicity and hepatic injury was observed according to WHO anticancer drug toxicity criterion and Child-Pugh classification criterion, respectively. The time of jaundice recurrence and survival were also observed during follow-up. RESULTS: Median total serum bilirubin in 39 patients was 72.7 micromol/L (range: 52.1 - 91.4 micromol/L) before TACE. The dose of pharmorubicin was 40 - 60 mg with a median of 55.0 mg and the amount of lipiodol was 2 - 25 ml. Decrease in white blood cell count was observed: grade I in 41.0% of patients, grade II in 35.9% and grade III - IV in 15.4%. Grade III - IV nausea and vomiting developed in 100% of the patients. Hepatic injury became aggravated in 8 from A to B class patients, in one from A to C class, and in 3 from B to C class according to Child-Pugh classification criterion. No cardiac toxicity was observed in this series. The median survival time was 6.0 months with a range of 2 to 72 months. Jaundice recurred in 19 patients (48.7%) with a medium jaundice recurrence time of 9.0 months (range: 2 - 20 months). CONCLUSION: Epirubicin-lipiodol emulsion at a dose of 30 mg/m(2) is safe and efficient in the management of patients with malignant obstructive jaundice with total serum bilirubin between 51 and 100 micromol/L after biliary drainage.

Laboratory and field evaluations of rhodojaponin-III against the imported cabbage worm Pieris rapae (L.) (Lepidoptera: Pieridae).

The activity of rhodojaponin-III (R-III), a grayanoid diterpene compound isolated from Rhododendron molle G. Don flowers, was determined under laboratory and field conditions as an antifeedant, stomach poison, contact toxicant and insect growth inhibitor against Pieris rapae (L.) larvae. The median antifeedant concentration (AFC(50)) values in no-choice leaf disc tests were 1.16 and 15.85 mg L(-1) at 24 h after treatment when tested against third and fifth instars respectively. The median lethal concentration (LC(50)) values in leaf disc tests were 2.84 and 9.53 mg L(-1) at 96 h after treatment against third and fifth instars respectively. R-III showed an almost 30 times higher contact toxicity against third instars than for fifth instars, and the median lethal dose (LD(50)) values for topical application were 1.18 and 34.09 mg kg(-1) at 72 h after treatment respectively. R-III disrupted the development of larvae to pupae or adults with median concentration for inhibiting growth (IC(50)) values of only 1.36 mg L(-1) for third instars and 11.28 mg L(-1) for fifth instars. In field trials, a greater than 80% reduction in the adjusted larval numbers was obtained against P. rapae 14 days after treatment when Rhodo 0.1% EC, a commercial botanical insecticide based on R-III, was applied at both 937.5 and 625 mL ha(-1). These results suggest that further research to develop R-III, and extracts from R. molle, as biorational pesticides or as lead compounds for integrated pest management deserve consideration.

[Effects of raw rhubarb on plasma D-lactate and procalcitonin expressions in patients with sepsis].

OBJECTIVE: To investigate the effects of raw rhubarb (RR) on levels of plasma D-lactate and procalcitonin in patients with sepsis. METHODS: Forty patients with sepsis enrolled were randomly divided into two groups, the RR group (n=18, treated with RR 9 g/d) and the control group (n=22, treated with conventional treatment). Plasma procalcitonin and D-lactate were determined before and after treatment. RESULTS: Before treatment, there was no significant difference in the levels of plasma procalcitonin and D-lactate between the two groups (procalcitonin: 6.50 +/- 2.37 microg/L vs 6.98 +/- 2.89 microg/L; D-lactate: 0.18 +/- 0.05 mmol/L vs 0.19 +/- 0.06 mmol/L, P > 0.05). However, after treatment, two indexes in the RR group were significantly lower than those in the control group (procalcitonin: 4.11 +/- 1.40 microg/L vs 2.21 +/- 0.61 microg/L; D-lactate: 0.24 +/- 0.06 ng/L vs 0.09 +/- 0.03 ng/L, both P < 0.05). CONCLUSION: RR could ameliorate the intestinal permeability and reduce the shifting of intestinal bacteria, so as to ease the condition of disease in patients with sepsis.