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.

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.

Cooperative hunting in a discrete predator-prey system II.

We investigate a discrete-time predator-prey system with cooperative hunting in the predators proposed by Chow et al. by determining local stability of the interior steady states analytically in certain parameter regimes. The system can have either zero, one or two interior steady states. We provide criteria for the stability of interior steady states when the system has either one or two interior steady states. Numerical examples are presented to confirm our analytical findings. It is concluded that cooperative hunting of the predators can promote predator persistence but may also drive the predator to a sudden extinction.

Measurement Uncertainty Assessment for Determination of Allura Red in Puffed Food by HPLC.

This study aimed to assess the measurement uncertainty of a new method for determination of allura redin food by high performance liquid chromatography (HPLC). The uncertainty of mathematical model of allura red is based on Europe for Analytical Chemistry(EURACHEM) guidelines. The sources and components of uncertainty were calculated, including recovery, working solution, sample mass, final volume, response of standard solution, response of sample solution. The expanded uncertainty was 0.0024 (k=2). Uncertainty of working solution was the most significant factor contributing to the total uncertainty, accounting for 86.2%. The uncertainty of volume accounted for the minimum at 0.025%. The developed method is simple and accurate, which can be used for the determination of allura redin puffed samples.

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.

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.

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.

The influence of UGT2B7 genotype on valproic acid pharmacokinetics in Chinese epilepsy patients.

PURPOSE: The aim of this study was to investigate the distribution and frequency of genetic polymorphisms in uridine diphosphate glucuronosyltransferase-2B7 (UGT2B7) in epilepsy patients and to evaluate the effect of these on the metabolism of valproic acid (VPA). METHODS: Single nucleotide polymorphisms in UGT2B7 were investigated in 102 epilepsy patients using DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism analysis. The steady-state plasma concentrations of VPA were determined in these patients, who had received VPA (approx. 500-1000 mg/day) for at least 2 weeks. RESULTS: Fourteen patients had the CC genotype at UGT2B7 C802T, 46 carried CT, and 42 carried the TT genotype. At UGT2B7 G211T, 78 patients had the GG genotype, 23 carried GT, and one individual had the TT genotype. The standardized trough plasma concentration of VPA was much lower in those patients with a T allele at UGT2B7 C802T than in those with the CC genotype (TT, 2.11 ± 1.26; CT, 2.31 ± 1.25; CC, 3.02 ± 1.32 µg kg mL(-1) mg(-1), p < 0.01). However, UGT2B7 G211T polymorphisms had no influence on the plasma concentration of VPA (GG, 2.28 ± 1.32, GT, 2.303 ± 1.38 µg kg mL(-1) mg(-1)). CONCLUSION: These results suggested that UGT2B7 C802T may be an important determinant of individual variability in the pharmacokinetics of VPA and that it may be necessary to increase the VPA dose for individuals with a T allele in order to achieve the therapeutic range of 50-100 µg/mL.

Enhanced therapeutic efficacy of combined use of sorafenib and transcatheter arterial chemoembolization for treatment of advanced hepatocellular carcinoma.

OBJECTIVE: Clinical trials suggest that combining transcatheter arterial chemoembolization with sorafenib in patients with advanced hepatocellular carcinoma shows a superior safety and tolerability profile. Our study aimed to retrospectively analyze the utility and prognostic factors of this combined therapy in these patients. METHODS: Patients with advanced hepatocellular carcinoma, treated by transcatheter arterial chemoembolization and sorafenib subsequently, between February 2010 and September 2012 in our hospital, were retrospectively analyzed. After sorafenib treatment for 12 weeks, abdominal enhanced computed tomography or magnetic resonance imaging was used to evaluate short-term outcomes and clinical benefit rate. Overall survival and adverse events were recorded during follow-up. Univariate and multivariate analyses were used to identify relationships between baseline characteristics and overall survival. RESULTS: Fifty-one advanced hepatocellular carcinoma patients were included. Common adverse events for sorafenib were hand-foot skin reaction, alopecia, diarrhea, anorexia and fatigue. The clinical benefit rate was 64% and the median survival time was 7.5 months. Median survival of patients with and without portal vein tumor thrombi was 6.0 months and 10.3 months (P < 0.001), respectively. Median survival of patients with cholinesterase ≥5000 U/l and < 5000 U/l was 10.6 months and 6.1 months (P < 0.001), respectively. Multivariate analysis identified the presence of portal vein tumor thrombi and low cholinesterase level as independent negative predictors of survival. CONCLUSIONS: Combining sorafenib and transcatheter arterial chemoembolization was safe and effective for advanced hepatocellular carcinoma patients with extrahepatic spread but without portal vein tumor thrombi. Portal vein tumor thrombi and cholinesterase level are independent predictors of prognosis following this combined therapy.

Development of a novel quantitative real-time assay using duplex scorpion primer for detection of Chlamydia trachomatis.

A novel quantitative real-time PCR method using the duplex scorpion primer for detection of Chlamydia trachomatis DNA was developed and validated. The assay employs a duplex primer; its most important feature is the intramolecular probe-target interaction. The assay had many prominent characteristics. (i) The duplex probe is simpler to synthesize and significantly easier to purify than TaqMan probe because that the fluorescent dye pair and the quencher pair are in different oligonucleotides. (ii) The method has high sensitivity, specificity, intra- and interassay reproducibilities. (iii) The assay has a quantitative dynamic range of 25 to10(9) genome copies per reaction mixture. (iv) The scorpion system can identify 98.6% samples in the validation panel without retest. There were 81 positive samples and 67 negative samples, which were confirmed by two FDA-approved NAATs (the Roche Amplicor PCR assay, Abbott LCR kit) and our new method. Any two positive results out of the possible three-comparator results would define the infected-patient gold standard. Of the positive samples, 79 (97.5%) were found positive (ranging from 31 to 227,648 copies/microl, M=4219 copies/microl), whereas no negative samples were found positive by the assay. A quantitative, fast, and easy-to-handle diagnostic approach such as the MOMP-based real-time PCR described here might improve the detection of C. trachomatis infection.

[Construction and functional analysis of the pepB gene disruptant in Aspergillus niger].

An integration plasmid pMW1-pepB for the pepB gene disruption in Aspergillus was constructed. The plasmid contained the pepB gene upstream (P) 1.4kb and downstream (T) 1.3kb homologous fragments with insertion of the expression unit of the hygromycin resistance gene (hph) between them. P and T DNA fragments were synthesized by PCR from Aspergillus niger chromosomal DNA. The integration plasmid was digested with the Hpa I restriction enzyme, the resultant 4.2kb linear fragment was introduced into the Aspergillus niger strain GICC2773 which expressing the glucoamylase/laccase fusion protein by PEG-mediated transformation. 62 Hygromycin resistance transformants were screened, and from them one strain named pepB29 was identified to be the pepB disruptant by PCR analysis. Data of functional assay of the pepB29 strain indicated that the disruption of the pepB gene secreted reduced acid proteolytic activity, and improved the heterologous protein laccase production.