Combination of Minimally Invasive Methods for the Treatment of Varicose Veins.

OBJECTIVE: The aim of the study was to evaluate the efficacy and safety of the combination of minimally invasive methods for the treatment of incompetent great saphenous vein and perforating veins. METHODS: Between December 2019 and October 2020, F-care radiofrequency ablation combined with ultrasound-guided foam sclerotherapy and residual perforator ligation and concomitant microphlebectomy were adopted for all eligible patients. The clinical symptoms scores, complications, and quality of life were recorded. RESULTS: 49 patients (64 limbs) with a mean age of 63.29 ± 10.14 years, and 60.9%4 were male. The 1-year truncal closure rate was 63/64 (98.4%).1 A significant improvement in the Venous Disability Score, the Venous Segmental Disease Score, the Venous Clinical Severity Score and Chronic Venous Disease Quality of Life Questionnaire Score, at 12 months after the combination of minimally invasive treatment, were observed in the study. One patient developed intermuscular vein thrombosis that was successfully managed with rivaroxaban. CONCLUSIONS: The combination of minimally invasive methods is a safe and effective method for the treatment of lower extremity varicose veins. Further large-scale, prospective, multi-center studies are needed to further verify the findings of this study.

Arterial chemotherapy for hepatocellular carcinoma in China: consensus recommendations.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.

The value of CT-based radiomics in early assessment of chemotherapeutic effect in patients with advanced lung adenocarcinoma: a preliminary study.

BACKGROUND: Computed tomography (CT) is the preferred method for evaluating the therapeutic effect of lung cancer. Radiomics parameters can provide a lot of supplementary information for clinical diagnosis and treatment. PURPOSE: To investigate the value of radiomics features of CT imaging to predict and evaluate the early efficacy of chemotherapy in patients with advanced lung adenocarcinoma. MATERIAL AND METHODS: A total of 101 patients with advanced lung adenocarcinoma were enrolled. Patients were classified into a response group and non-response group according to RECIST 1.1 standard. All patients underwent chest CT examination before and after two cycles of chemotherapy. A total of 293 radiomics features were calculated. The features between response group and non-response group were compared before and after chemotherapy. The diagnostic efficacy was evaluated using the receiver operating characteristic curve. RESULTS: The six pre-chemotherapy radiomics features were selected, with area under the curve (AUC), sensitivity, and specificity at 0.720, 68.3%, and 69.0% in the training group and 0.573, 50.0%, and 76.9% in the test group, respectively. The eleven post-chemotherapy radiomics features were selected, with AUC, sensitivity, specificity at 0.789, 75.6%, and 75.9% in the training group and 0.718, 61.1%, and 76.9% in the test group, respectively. The prognostic value of △f8, △f16, %f8, and %f16 were higher than the other features with AUCs of 0.787, 0.837, 0.763, and 0.877, respectively. CONCLUSION: Radiomics is expected to provide more valuable information for evaluating the chemotherapy efficacy of lung adenocarcinoma.

Rs4911154 of circ-ITCH aggravated tumor malignancy of thyroid nodules via the circ-ITCH/miR-22-3p/CBL axis.

Recent evidence revealed an inhibitory effect of circ-ITCH on the progression of papillary thyroid cancer via affecting the circ-ITCH/miR-22-3p/CBL axis. Rs4911154, an SNP located in circ-ITHC, was previously reported to be significantly associated with an increased risk of hepatocellular carcinoma. Ultrasound testing was used to evaluate the doubling time of thyroid nodules. 202 patients diagnosed with thyroid nodule disorders were divided into three groups according to their genotypes at rs4911154. We found that the A allele was correlated with a shortening doubling time of thyroid nodules. Moreover, the A allele contributed to reduced expression of circ-ITCH/CBL and increased expression of miR-22-3p. Besides, decreased tissue apoptosis was linked to the A allele. Luciferase assays indicated that miR-22-3p could effectively suppress the luciferase activities of CBL and circ-ITCH. Furthermore, manual up-regulation of miR-22-3p effectively suppressed the expression of CBL, while CBL siRNA apparently abolished circ-ITCH induced CBL upregulation, reduced proliferation and increased apoptosis of K1 and TPC-1 cells. A signaling pathway of circ-ITCH/miR-22-3p/CBL axis was established to explain the effect of SNP of circ-ITCH in thyroid tumor malignancy. Compared with the G allele, the A allele in rs4911154 contributed to the malignancy of thyroid nodules with decreased doubling time and down-regulated CBL expression.

Apatinib as second-line or later therapy in patients with advanced hepatocellular carcinoma (AHELP): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.

BACKGROUND: Inhibition of vascular endothelial growth factor receptor (VEGFR) has shown antitumour activity in advanced hepatocellular carcinoma, but few studies of VEGFR inhibitors have been done in populations with a high prevalence of hepatitis B virus infection. The aim of this study was to evaluate the efficacy and safety of apatinib in patients with pretreated advanced hepatocellular carcinoma. METHODS: AHELP was a randomised, double-blind, placebo-controlled, phase 3 trial done at 31 hospitals in China, in patients (aged ≥18 years) with advanced hepatocellular carcinoma who had previously been refractory or intolerant to at least one line of systemic chemotherapy or targeted therapy. Patients were randomly assigned (2:1) to receive apatinib 750 mg or placebo orally once daily in 28-day treatment cycles. Group allocation was done with a central randomisation system, with a block size of six, and was stratified by Eastern Cooperative Oncology Group performance status, previous sorafenib treatment, and presence of vascular invasion or extrahepatic metastasis. The primary endpoint was overall survival, which was defined as time from randomisation to death from any cause, and was analysed in patients who were randomly assigned and received at least one dose of the study drug. Safety analyses were done in patients who received at least one dose of the study treatment and had post-dose safety assessments. This trial is registered with ClinicalTrials.gov, NCT02329860. FINDINGS: Between April 1, 2014, and May 3, 2017, 400 eligible patients were randomly assigned to receive apatinib (n=267) or placebo (n=133). Seven patients (six in the apatinib group and one in the placebo group) did not receive study treatment and were excluded from efficacy analyses. Overall survival was significantly improved in the apatinib group compared with the placebo group (median 8·7 months [95% CI 7·5‒9·8] vs 6·8 months [5·7‒9·1]; hazard ratio 0·785 [95% CI 0·617‒0·998], p=0·048). 387 patients (257 in the apatinib group and 130 in the placebo group) had a safety assessment after study treatment and were included in safety analyses. The most common treatment-related adverse events of grade 3 or 4 were hypertension (71 [28%] patients in the apatinib group vs three [2%] in the placebo group), hand-foot syndrome (46 [18%] vs none), and decreased platelet count (34 [13%] vs one [1%]). 24 (9%) patients in the apatinib group and 13 (10%) in the placebo group died due to adverse events, but none of these deaths were deemed to be related to treatment by investigators. INTERPRETATION: Apatinib significantly improved overall survival in patients with pretreated advanced hepatocellular carcinoma compared with placebo, with a manageable safety profile. FUNDING: Jiangsu Hengrui Medicine.

A novel stem cell therapy for hepatitis B virus-related acute-on-chronic liver failure.

The aim of this study was to propose a stem cell therapy for hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) based on plasma exchange (PE) for peripheral blood stem cell (PBSC) collection and examine its safety and efficacy. Sixty patients (n=20 in each group) were randomized to PE (PE alone), granulocyte colony-stimulating factor (G-CSF) (PE after G-CSF treatment), and PBSC transplantation (PBSCT) (G-CSF, PE, PBSC collection and hepatic artery injection) groups. Patients were followed-up for 24 weeks. Liver function and adverse events were recorded. Survival analysis was performed. PBSCT improved blood ammonia levels at 1 week (P<0.05). The level of total bilirubin, international normalized ratio, and creatinine showed significant differences in the 4th week of treatment (P<0.05). The survival rates of the PE, G-CSF, and PBSCT groups were 50, 65, and 85% at 90 days (P=0.034). There was a significant difference in 90-day survival between the PE and PBSCT groups (P=0.021). The preliminary results suggested that PBSCT was safe, with a possibility of improved 90-day survival in patients with HBV-ACLF.

Microstructure and Mechanical Performance of Graphene Nanosheets Reinforced Nickel-Based Superalloy FGH95 Composite.

Graphene nanosheet (GNS)-reinforced nickel-based superalloy FGH95 (GNSs/FGH95) matrix composites are prepared via the powder metallurgy approach. Scanning electron microscopy, transmission electron microscope and static tensile tests are used to investigate the microstructure and mechanical properties of GNS-reinforced nickel-based superalloy FGH95. Mechanical properties and failure behavior at room temperature and high temperature are studied. Static tensile tests at room temperature and high temperature confirm that the strength and plasticity of GNS-reinforced FGH95 have been improved, compared to the unreinforced superalloy. The results show that with the increase of temperature, the failure behavior of GNSs/FGH95 composite changes from the interface debonding of the GNSs/matrix to the failure of the FGH95 matrix. This work suggests that GNSs/FGH95 composite has great potential to be a structural material in aero-engine fields.

A novel stem cell therapy for hepatitis B virus-related acute-on-chronic liver failure

The aim of this study was to propose a stem cell therapy for hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) based on plasma exchange (PE) for peripheral blood stem cell (PBSC) collection and examine its safety and efficacy. Sixty patients (n=20 in each group) were randomized to PE (PE alone), granulocyte colony-stimulating factor (G-CSF) (PE after G-CSF treatment), and PBSC transplantation (PBSCT) (G-CSF, PE, PBSC collection and hepatic artery injection) groups. Patients were followed-up for 24 weeks. Liver function and adverse events were recorded. Survival analysis was performed. PBSCT improved blood ammonia levels at 1 week (P<0.05). The level of total bilirubin, international normalized ratio, and creatinine showed significant differences in the 4th week of treatment (P<0.05). The survival rates of the PE, G-CSF, and PBSCT groups were 50, 65, and 85% at 90 days (P=0.034). There was a significant difference in 90-day survival between the PE and PBSCT groups (P=0.021). The preliminary results suggested that PBSCT was safe, with a possibility of improved 90-day survival in patients with HBV-ACLF.

An Approach to the Uniform Dispersion of Graphene Nanosheets in Powder Metallurgy Nickel-Based Superalloy.

In this paper, a wet-chemical based method was adopted to acquire the uniform dispersion of graphene nanosheets (GNSs) in a powder metallurgy nickel-based superalloy (FGH96) to fabricate a new GNSs reinforced FGH96 metal matrix composite. The surface of the FGH96 powder was modified using a hydrophilic surfactant named polyvinyl alcohol (PVA), which has good wettability and strong hydrogen bonding between the ⁻OH groups of PVA and oxygen groups of GNSs such as ⁻COOH, ⁻CHO, and ⁻OH. It was shown that the GNSs displayed much better dispersion uniformity on the PVA modified FGH96 powder than the unmodified one. The existence of PVA improved the adsorptive capacity of the GNSs attached on the powder surface and prevented the agglomeration in the following thermal preparation process. Consequently, the micro-hardness of PVA modified composite with 0.1 wt.% GNSs reached 497.9 HV, 3.4% higher than the unmodified FGH96 alloy. Therefore, this preparation process could act as the foundation of a common strategy for the fabrication of GNSs in metal matrix composites with good dispersion uniformity, which may have great potential application in aerospace applications.

A new apatinib microcrystal formulation enhances the effect of radiofrequency ablation treatment on hepatocellular carcinoma.

INTRODUCTION: Radiofrequency ablation (RFA) is the foremost treatment option for advanced hepatocellular carcinoma (HCC), however, rapid and aggressive recurrence of HCC often occurs after RFA due to epithelial-mesenchymal transition process. Although combination of RFA with sorafenib, a molecular targeted agent, could attenuate the recurrence of HCC, application of this molecular targeted agent poses a heavy medical burden and oral administration of sorafenib also brings severe side effects. MATERIALS AND METHODS: In this study, we prepared an apatinib microcrystal formulation (Apa-MS) that sustainably releases apatinib, a novel molecular targeted agent, for advanced HCC treatment. We injected apatinib solution or Apa-MS into subcutaneous HCC tumors. RESULTS: It was found that Apa-MS exhibited slow apatinib release in vivo and in turn inhibited the epithelial-mesenchymal transition of HCC cells for extended time. Moreover, in rodent HCC model, Apa-MS enhanced the antitumor effect of RFA treatment. CONCLUSION: Based on these results, we conclude that Apa-MS, a slow releasing system of apatinib, allows apatinib to remain effective in tumor tissues for a long time and could enhance the antitumor effect of RFA on HCC.

MEIS-1 level in unresectable hepatocellular carcinoma can predict the post-treatment outcomes of radiofrequency ablation.

Radiofrequency ablation (RFA) is a local-ablative therapy for unresectable hepatocellular carcinoma (HCC). At present, there is no predictive marker for RFA treatment outcomes. This work aimed to valuate myeloid ecotropic viral integration site 1 (MEIS-1) in predicting post-RFA treatment outcomes of unresectable HCC patients. The time to progression (TTP) and overall survival (OS) of 81 HCC patients who received RFA treatment were measured. The protein level of MEIS-1 in tumor specimens was measured by western blot. The role of MEIS-1 in RFA-treating HCC in vivo growth nude mouse model was examined via PET/CT imaging. Higher level of MEIS-1 in tumor tissue is associated with better RFA treatment outcomes. The median TTP was 9.0 (95% confidence interval [CI]: 6.8-11.3) months in patients with high MEIS-1 expression (n = 43) versus 6.0 (95% CI: 4.6-7.4) months in patients with low MEIS-1 expression (n = 38). Moreover, in rodent HCC model we found overexpression of MEIS-1 enhanced the anti-tumor effect of RFA treatment. We conclude that high level of MEIS-1 expression predicts better RFA treatment outcome in HCC.

Multi-parameter gene expression profiling of peripheral blood for early detection of hepatocellular carcinoma.

AIM: In our previous study, we have built a nine-gene (GPC3, HGF, ANXA1, FOS, SPAG9, HSPA1B, CXCR4, PFN1, and CALR) expression detection system based on the GeXP system. Based on peripheral blood and GeXP, we aimed to analyze the results of genes expression by different multi-parameter analysis methods and build a diagnostic model to classify hepatocellular carcinoma (HCC) patients and healthy people. METHODS: Logistic regression analysis, discriminant analysis, classification tree analysis, and artificial neural network were used for the multi-parameter gene expression analysis method. One hundred and three patients with early HCC and 54 age-matched healthy normal controls were used to build a diagnostic model. Fifty-two patients with early HCC and 34 healthy people were used for validation. The area under the curve, sensitivity, and specificity were used as diagnostic indicators. RESULTS: Artificial neural network of the total nine genes had the best diagnostic value, and the AUC, sensitivity, and specificity were 0.943, 98%, and 85%, respectively. At last, 52 HCC patients and 34 healthy normal controls were used for validation. The sensitivity and specificity were 96% and 86%, respectively. CONCLUSION: Multi-parameter analysis methods may increase the diagnostic value compared to single factor analysis and they may be a trend of the clinical diagnosis in the future.

What is the best combination treatment with transarterial chemoembolization of unresectable hepatocellular carcinoma? a systematic review and network meta-analysis.

OBJECTIVE: To assess the comparative efficacy and safety of combination treatment with transarterial chemoembolization (TACE) for patients with unresectable hepatocellular carcinoma (HCC) through a systematic review and network meta-analysis and to identify what is the best combination treatment with TACE. MATERIALS AND METHODS: A network meta-analysis was used to identify evidence from relevant randomized controlled trials. We searched databases for publications up to June 2017. The prespecified primary efficacy outcomes were treatment response and 6-month to 3-year overall survival (OS), while the secondary efficacy outcomes were 1- and 2-year disease-free survival (DFS); safety outcomes were advance effects of combination treatment. We conducted pairwise meta-analyses using a random-effects model and then performed random-effects network meta-analyses. RESULTS: A total of 48 trials were eligible (50 analyses), involving 5627 patients and 19 treatment arms. In comparison with other types of combination therapy arms, network meta-analysis disclosed that TACE + three-dimensional conformal radiotherapy, TACE + percutaneous ethanol injection, TACE + percutaneous microwave coagulation therapy, TACE + percutaneous acetic acid injection, and TACE + sorafenib were the more effective methods in treatment response, 6-month to 3-year OS, and 1-2 year DFS; the adverse effects of TACE + sorafenib were serious. The study was registered with PROSPERO, number CRD42017071102. CONCLUSIONS: When considering the efficacy, combination therapy with TACE seemed to offer clear advantages for patients with unresectable HCC. TACE + Three-dimensional conformal radiotherapy, TACE + Percutaneous ethanol injection, TACE + Percutaneous microwave coagulation therapy, and TACE + Percutaneous acetic acid injection are likely the best options to consider in the application of combination treatment.

Perioperative safety analysis of transcatheter arterial chemoembolization for hepatocellular carcinoma patients with preprocedural leukopenia or thrombocytopenia.

Patients with hepatocellular carcinoma (HCC) exhibit a high incidence of concomitant cirrhosis with leukopenia and/or thrombocytopenia. In the present study, perioperative changes in the white blood cell (WBC) and platelet (PLT) counts and associated complications were investigated to assess the safety of transcatheter arterial chemoembolization (TACE) for HCC patients with preprocedural leukopenia or thrombocytopenia. The records of 1,461 HCC patients who received TACE between January 2012 and December 2013 were retrospectively reviewed. The incidence of complications during the perioperative period and changes in the WBC and PLT counts were recorded. A Chi-squared test was used to evaluate the associations between postoperative infection and preprocedural WBC count and between bleeding at the puncture site and preprocedural PLT count. The WBC count of the majority of the patients increased within 3 days and returned to the preprocedural level within 30 days after TACE. The PLT count decreased within 3 days and returned to the preprocedural level within 30 days after TACE. The major complications were liver decompensation (n=66), puncture site bleeding (n=45), infection (n=33), severe thrombocytopenia (n=8), upper gastrointestinal bleeding (n=6), tumor bleeding (n=4) and agranulocytosis (n=3). A Chi-squared test revealed that postoperative infection was not associated with preprocedural WBC count and puncture site bleeding was not associated with decreased PLT count due to hypersplenism. Therefore, TACE was found to be safe for HCC patients with preprocedural thrombocytopenia or leukopenia due to hypersplenism, with a low incidence of major complications during the perioperative period.

DNA Dendrimer-Streptavidin Nanocomplex: an Efficient Signal Amplifier for Construction of Biosensing Platforms.

We develop a DNA dendrimer-streptavidin (SA) nanocomplex as a novel signal amplifier to create biosensing platforms for disease-related species. The DNA dendrimer-SA nanocomplex is fabricated by cross-linking the nonlinear hybridization chain reaction based DNA dendrimer with the SA-coupled linker DNA and possesses multiple sticky ends, a high molecular weight, and a hyperbranched nanostructure with large numbers of DNA duplexes. Taking advantage of the DNA dendrimer-SA nanocomplex and a label-free quartz crystal microbalance (QCM) technology, we first construct a mass-sensitive QCM biosensing platform for nucleic acids, which displays high selectivity and sensitivity, with a detection limit of 0.062 nM KRAS gene fragment. Then we present a fluorescent sensing strategy toward HeLa cells by functionalizing the DNA dendrimer-SA nanocomplex using the sgc8 aptamer and the SYBR Green I intercalating dye. The spiked recoveries of targets in physiological media are greater than 90%, demonstrating potential application of created biosensing platforms in clinical diagnosis. This work expands the rule set of designing DNA nanomaterials for development of biosensing strategies, and provides universal platforms for detecting disease-related species through simply altering the related capture and reporter DNA sequences.

Diagnostic value evaluation of trefoil factors family 3 for the early detection of colorectal cancer.

AIM: The purpose of this study was to evaluate the diagnostic value of trefoil factor family 3 (TFF3) for the early detection of colorectal cancer (CC). METHODS: Serum TFF3 and carcino-embryonic antigen (CEA) were detected in 527 individuals, including 115 healthy control (HC), 198 colorectal adenoma (CA), and 214 CC individuals in the training group. RESULTS: Serum TFF3 showed no significant correlation with age, gender, or tumor location but showed significant correlation with the tumor stage. Serum TFF3 in the CC group was significantly higher than in the HC or CA group. The AUC values of TFF3 for discriminating between HC and CC and between CA and CC were 0.930 (0.903, 0.958) and 0.834 (0.796, 0.873). A multivariate model combining TFF3 and CEA was built. Compared to TFF3 or CEA alone, the multivariate model showed significant improvement (P < 0.001). For discriminating between HC and CC, HC and early stage CC, HC and advanced stage CC, CA and CC, CA and early stage CC, and CA and advanced stage CC in the training group, the sensitivities were 92.99%, 91.46%, 93.18%, 73.83%, 76.83%, and 81.82%, and the specificities were 91.30%, 91.30%, 93.91%, 88.38%, 77.27%, and 88.38%, respectively. After validation, the sensitivities were 89.39%, 85.71%, 90.79%, 72.73%, 71.43%, and 78.95%, and the specificities were 87.85%, 87.85%, 2.52%, 87.85%, 80.77%, and 87.50%, respectively. CONCLUSION: The multivariate diagnostic model that included TFF3 and CEA showed significant improvement over the conventional biomarker CEA and might provide a potential method for the early detection of CC.

Acquired amegakaryocytic thrombocytopenic purpura induced by percutaneous ethanol injection during treatment of hepatocellular carcinoma: A case report.

Percutaneous ethanol injection is an important localized treatment method for patients presenting with hepatocellular carcinoma (HCC). Among the advantages of percutaneous ethanol injection are its minimal invasiveness, simplicity, low cost and low risk of complications. However, the increasing popularity of percutaneous ethanol injection has resulted in serious adverse effects attributed to individual variations. The present study describes the case of a patient who exhibited acquired amegakaryocytic thrombocytopenic purpura, caused by percutaneous ethanol injection treatment for HCC. This complication was promptly identified, and platelet transfusion and injection of recombinant human interleukin-11 resulted in a rapid recovery of the patient's platelet count. Attention should be given to this rare complication in patients administered percutaneous ethanol injection treatment for HCC.

An In Vivo Method to Identify microRNA Targets Not Predicted by Computation Algorithms: p21 Targeting by miR-92a in Cancer.

microRNA (miRNA) dysregulation is involved in the development and progression of various human cancers, including hepatocellular carcinoma (HCC). However, how to identify the miRNAs targeting specific mRNA in cells is a significant challenge because of the interaction complexity and the limited knowledge of rules governing these processes. Some miRNAs are not predictable by current computer algorithms available. Here, using p21 mRNA as target, we established a new method, called miRNA in vivo precipitation (miRIP), to identify which kind of miRNAs can actually bind to the specific mRNA in cells. Several unpredictable miRNAs that bound p21 mRNA in HepG2 and PC-3 cells were identified by the miRIP method. Among these miRNAs identified by miRIP, miR-92a was found and confirmed to interact robustly with p21 mRNA, both in HepG2 and PC-3 cells. miR-92a was found to be remarkably increased in HCC tissues, and higher expression of miR-92a significantly correlated with lower expression of p21, which is related to poor survival of HCC patients. Moreover, inhibition of miR-92a could significantly suppress HCC growth in vitro and in vivo by upregulating p21. Together, miR-92a, which is identified by miRIP, is functionally shown to be associated with HCC growth as an oncogenic miRNA by inhibiting expression of targeting gene p21. In addition, several unpredictable miRNAs that target STAT3 mRNA were also identified by the miRIP method in HepG2 cells. Our results demonstrated that the miRIP approach can effectively identify the unpredictable but intracellular existing miRNAs that target specific mRNA in vivo.