Baicalin Ameliorates Corticosterone-Induced Depression by Promoting Neurodevelopment of Hippocampal via mTOR/GSK3ß Pathway.

OBJECTIVE: To investigate the role of hippocampal neurodevelopment in the antidepressant effect of baicalin. METHODS: Forty male Institute of Cancer Research mice were divided into control, corticosterone (CORT, 40 mg/kg), CORT+baicalin-L (25 mg/kg), CORT+baicalin-H (50 mg/kg), and CORT+fluoxetine (10 mg/kg) groups according to a random number table. An animal model of depression was established by chronic CORT exposure. Behavioral tests were used to assess the reliability of depression model and the antidepressant effect of baicalin. In addition, Nissl staining and immunofluorescence were used to evaluate the effect of baicalin on hippocampal neurodevelopment in mice. The protein and mRNA expression levels of neurodevelopment-related factors were detected by Western blot analysis and real-time polymerase chain reaction, respectively. RESULTS: Baicalin significantly ameliorated the depressive-like behavior of mice resulting from CORT exposure and promoted the development of dentate gyrus in hippocampus, thereby reversing the depressive-like pathological changes in hippocampal neurons caused by CORT neurotoxicity. Moreover, baicalin significantly decreased the protein and mRNA expression levels of glycogen synthase kinase 3ß (GSK3ß), and upregulated the expression levels of cell cycle protein D1, p-mammalian target of rapamycin (mTOR), doublecortin, and brain-derived neurotrophic factor (all P<0.01). There were no significant differences between baicalin and fluoxetine groups (P>0.05). CONCLUSION: Baicalin can promote the development of hippocampal neurons via mTOR/GSK3ß signaling pathway, thus protect mice against CORT-induced neurotoxicity and play an antidepressant role.

Comparing Predictability of Non-invasive Tools for Hepatocellular Carcinoma in Treated Chronic Hepatitis C Patients.

BACKGROUND: Non-invasive tools including liver stiffness measurement (LSM) or FIB-4, assessed before or after direct acting antivirals (DAA), have been suggested to predict hepatocellular carcinoma (HCC). AIMS: This study aims to compare predictability of HCC by these methods at different time points, to validate the HCC surveillance suggestion by guidelines, and to propose personalized strategy. METHODS: Chronic hepatitis C whose LSM and FIB-4 were available at pretherapy and after sustained virological response (SVR) were enrolled. Advanced chronic liver disease (ACLD) was defined as pretherapy LSM ≥ 10 kPa or FIB-4 index ≥ 3.25 or ultrasound signs of cirrhosis plus platelet count < 150,000/µL. The predictabilities were compared by area under ROC. The cumulative HCC incidences were calculated by Kaplan-Meier analysis. RESULTS: Among 466 ACLD patients, 40 patients developed HCC during a follow-up duration of 26.8 months. Comparable predictive performances for HCC between LSM and FIB-4 at pretherapy and SVR were noted. By guidelines suggestion using pretherapy LSM = 10 kPa (advanced fibrosis) and 13 kPa (cirrhosis) for risk stratification, the annual HCC incidences of those with LSM of < 10, 10-12.9 and ≥ 13 kPa were 1.1, 3.6, and 5.0%, respectively. Combination of baseline LSM < 12 kPa and SVR FIB-4 < 3.7 could further stratify relatively low risk of HCC in ACLD patients of annal incidence of 1.2%. CONCLUSIONS: ACLD patients who met advanced fibrosis but not cirrhosis by guidelines' cut-offs still posed high risk of HCC. Baseline LSM with SVR FIB-4 can be applied to stratify low, intermediate, and high risk of HCC for personalizing surveillance strategies after SVR.

Identification of a new benzophenanthridine alkaloid from Eomecon chionantha induced necroptosis in breast cancer cells.

Benzophenanthridine alkaloids of secondary metabolites from Chinese herb medicine are the excellent anticancer agent to fight sensitive and resistant breast cancer, which is one of the major malignant tumors in females. In the present study, a new benzophenanthridine alkaloid derivatives 8,12-dimethoxysanguinarine (1, SG-A) was isolated from Eomecon chionantha. And MCF-7 cell lines were strongly inhibited by SG-A with an IC50 value of 7.45 µΜ. Furthermore, SG-A strikingly induced non-apoptotic cell death via necroptosis in MCF-7 cells through flow cytometry, Hoechest 33258 and TEM cell morphology analysis. The results suggested that SG-A was found to induce cell necroptosis in MCF-7 cells.

Hepatitis B Co-Infection Has Limited Impact on Liver Stiffness Regression in Chronic Hepatitis C Patients Treated with Direct-Acting Antivirals.

Introduction: High sustained virological response (SVR) rate (>95%) and liver stiffness regression can be achieved with direct acting antivirals treatment (DAA) in patients with chronic hepatitis C virus (CHC) infection. Reactivation of hepatitis B virus (HBV) was reported during DAA treatment in patients co-infected with HBV, although its impact on liver stiffness remains unknown. This study aims to investigate whether the liver stiffness (LSM) regression is different between HBV/HCV co-infected and mono-HCV-infected patients. Materials and Methods: CHC patients with/without HBV co-infection who received DAA treatment and achieved SVR12 between March 2015 and December 2019 in Chang Gung Memorial Hospital, Linkou branch were prospectively enrolled. LSM was assessed by transient elastography (TE, Fibroscan) at baseline and after SVR. Propensity score matching (PSM) at 3:1 ratio, adjusted for age, gender, pre-DAA alanine aminotransferase (ALT), platelet count, and LSM, between CHC with and without HBV co-infection, was performed before further analysis. Results: Among 906 CHC patients enrolled, 52 (5.7%) patients had HBV/HCV co-infection. Patients with HBV/HCV co-infection were of younger age (61.8 vs. 63.2, p = 0.31), with a higher proportion of males (53.8% vs. 38.9%, p = 0.03), and lower pretreatment LSM level (8.15 vs. 10.2 kPa, p = 0.09), while other features were comparable. After PSM, patients with HBV/HCV co-infection had insignificantly lower LSM regression compared to mono-HCV-infected patients (−0.85 kPa vs. −1.65 kPa, p = 0.250). Conclusions: The co-infection of HBV among CHC patients has limited impact on liver stiffness regression after successful DAA treatment.

Target prediction and activity verification for the antidepressant action of Huangqin (Radix Scutellariae Baicalensis).

OBJECTIVE: To decipher the antidepressant targets and mechanisms of Huangqin (Radix Scutellariae Baicalensis) (RSB) by a novel computational system based on prediction and experimental verification. METHODS: The putative targets of RSB against depression were identified from Traditional Chinese Medicine Systems Pharmacology (TCMSP) and DrugBank. Next, protein-protein interaction network of the anti-depression targets of RSB were identified, and differentially expressed genes (DEGs) of depression were mined from the NCBI database. Then, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology were used to analysis the common targets. Finally, the selected pathways and functions were verified by experimentation. RESULTS: Thirty active compounds in RSB were predicted with high confidence by TCMSP and DrugBank, and seventy-one DEGs were identified in the GEO database. Besides, eight core target proteins were screened out by descending order of degree value, including ACHE, IL6, SLC6A4, FOS, SLC6A3, MAOB, DPP4, and JUN. These target genes were further found to be associated with pathways involved in neuronal apoptosis, such as pathways in cancer, Toll-like receptor signaling pathway, and TNF signaling. The cell proliferation assay and wound-healing assay results showed that RSB does not affect PC12 cell proliferation and chemotaxis. Unexpectedly, RSB protected PC12 cells from oxidative stress induced by H2O2 via inhibiting autophagy and apoptosis. We revealed significant changes in mice treated with 400 mg/kg RSB compared with the lipopolysaccharide mice. The possible mechanism for the antidepressive action of RSB is by reducing the expression of LC3-B in CA1 neurons. CONCLUSIONS: Our research partially expounds the mechanism of the antidepressant effect of RSB by the combination of network pharmacology prediction and experimental verification. Furthermore, it is also conducive to the application of Traditional Chinese Medicine within modern medicine.

MELD score is the better predictor for 30-day mortality in patients with ruptured hepatocellular carcinoma treated by trans-arterial embolization.

BACKGROUND AND AIMS: Spontaneous hepatocellular carcinoma (HCC) rupture is a catastrophic life-threatening complication that could be rescued by trans-arterial embolization (TAE). However, deteriorated liver function with total bilirubin more than 3 mg/dL was deemed as a relative contraindication. This study was aimed to re-evaluate this relative contraindication. METHODS: Patients with ruptured HCC and treated by TAE between February 2005 and December 2016 in Chang Gung Memorial Hospital, Linkou branch were recruited. Pre-TAE characteristics including age, gender, etiology, liver biochemistry, Child-Pugh classification, Model for End-Stage Liver Disease (MELD) score, the presence of shock, tumor staging and post TAE liver function were compared between patients with and without post-TAE 30-day mortality. RESULTS: A total of 186 patients were enrolled. The successful hemostatic rate after embolization was 91.4% and the median overall survival was 224 days. The 30-day cumulative mortality rate is 20.4%. By multivariate logistic regression analysis, male [aOR: 0.25, P=0.034] MELD score [aOR: 13.61, P<0.001], tumor size [aOR: 1.21, P=0.023] are the independent predictors for 30-day mortality. MELD score has better predictability of post-TAE 30-day mortality than total bilirubin level (AUROC: 0.818 vs. 0.668). The cut-off points of MELD score 13 has higher negative predictive value of 95% for post-TAE 30-day mortality. CONCLUSION: TAE is effective for the initial hemostasis in patients with HCC rupture. MELD score ≥13 rather than only total bilirubin level >3 mg/dL be more predictive of post TAE 30-day mortality.

Utility of process capability indices in assessment of quality control processes at a clinical laboratory chain.

BACKGROUND: To evaluate the utility of the process capability indices Cp and Cpk for assessing the quality control processes at chain laboratory facilities. METHODS: In April 2020, the minimum Cp and Cpk values for 33 assays of a laboratory chain with 19 facilities were collected for further analysis and a total of 627 datasets (Cp and Cpk ) were compared. In addition, standard values for Cp and Cpk , defined as the lowest of the top 20%, were obtained for comparison and the indices were used to determine whether precision or trueness improvements were required for the corresponding assay. RESULTS: A total of 627 datasets of 33 assays from 19 laboratory facilities were collected for further analysis. Based on the Cp results, 329 (52.5%), 211 (33.7%), 65 (10.3%), and 22 (3.5%) were rated as excellent, good, marginal, and poor, respectively. While the corresponding results for Cpk were 300 (47.8%), 216 (34.4%), 79 (12.6%), and 32 (5.1%). In addition, it was noteworthy that eight (Cp criteria) and six assays (Cpk criteria) were rated as excellent or good at all 19 facilities. Comparison of the process capability indices at the Jinan KingMed Center with the standard values revealed that total protein, albumin, and urea showed trueness individual improvement, precision individual improvement, and precision common improvement, respectively, while the results of other assays were stable. CONCLUSION: Process capability indices are useful for evaluating the quality control procedures in laboratory facilities and can help improve the precision and trueness of laboratory tests.

Switching monopolar radiofrequency ablation improves long-term outcomes of medium-sized hepatocellular carcinoma.

OBJECTIVES: Radiofrequency ablation (RFA) of medium-sized (3-5 cm) hepatocellular carcinoma (HCC) is suboptimal. Switching monopolar RFA (SW-RFA) enlarges the ablative volume to better cover larger tumors. This study aims to compare the long-term outcomes of medium-sized HCC treated by either SW-RFA or single-monopolar RFA (S-RFA). METHODS: We retrospectively reviewed 139 cases (147 medium-size HCC) between 2008 and 2014. Under propensity score matching, a total of 43 paired patients with medium-size HCC and balanced clinical variables treated by either SW-RFA or S-RFA were selected for comparison. RESULTS: SW-RFA showed a higher rate of achieving an adequate safety margin (p = 0.002). After a mean follow-up period of 40.4 months, SW-RFA produced significantly lower global RFA failure rates (p < 0.001) and better overall survival (p = 0.005) compared to S-RFA. SW-RFA was independently associated with a decreased risk of global RFA failure (hazard ratio [HR]: 0.136, 95% confidence interval [CI]: 0.030-0.607, p = 0.009) and improved overall survival (HR: 0.337, 95% CI: 0.152-0.747, p = 0.007). By last follow-up, the SW-RFA group maintained a superior tumor-free rate (p = 0.010) and fewer progressions to Barcelona Clinic Liver Cancer stage C (p = 0.011). Major complication rates were comparable in both groups (SW-RFA: 2.3% vs. S-RFA: 4.7%, p = 1.000). CONCLUSIONS: The switching multi-monopolar ablation technique could be beneficial for patients with medium-sized HCCs given sustained control of larger tumors with better overall survival. KEY POINTS: • Switching monopolar ablation could provide a sustained local tumor control and better overall survival than single-monopolar ablation for the medium-sized hepatocellular carcinoma. • Compared to single-monopolar ablation, switching monopolar ablation could create a larger homogeneous coagulation volume by using a shorter total ablation time to achieve a higher rate of adequate safety margin for a medium-sized HCC. • Patients with medium-sized HCC can be maintained at a higher rate of tumor-free status and at a lower risk of progression into BCLC stage C in the follow-up period after ablation by switching monopolar than by single-monopolar ablation.

Incidence and predictors for abnormal liver function during direct-acting antiviral agents in chronic hepatitis C patients.

Abrupt alanine aminotransferase (ALT) elevation during direct-acting antiviral agents (DAA) treatment is an uncommon but noticeable adverse event in chronic hepatitis C (CHC) patients, which may lead to early termination of treatment. This study aims to investigate the incidence, outcome and predictors of the on-treatment ALT elevation during DAA therapy.CHC patients treated with DAA regimen in Chang Gung Memorial Hospital, Linkou branch during March 2015 to March 2019 were recruited. Prospective scheduled ALT assessment at baseline, 2nd, 4th, 8th, and 12th/24th weeks were recorded. Pretherapy host and viral factors were compared between patients with and without on-treatment ALT elevation. Multivariate logistic regression was used for independent factors for on-treatment ALT elevation.A total of 1563 CHC patients treated with grazoprevir/elbasvir, glecaprevir/pibrentasvir and sofosbuvir-based regimen were analyzed. On-treatment ALT elevation occurred in 10.9% patients while those treated with glecaprevir/pibrentasvir had the least possibility (5.4%). Only 1.4% patients had ≥grade 3 ALT elevation events. The presence of such events had no impact on sustained virological response 12 rates. Hepatitis B virus coinfection (aOR: 3.599, P < 0.001) and higher pretherapy ALT (1-5x, ≥5x upper limit of normal: aOR: 2.632, P = 0.024, aOR: 4.702, P = .011, respectively) were significant predictors for ALT elevation.On-treatment ALT elevation occurred in one-tenth CHC patients treated with preferred DAAs but had no impact on sustained virological response rate.

Posture and Time Arrangement Influence Shank Circumference Reduction When Performing Leg Raising Exercise.

This study recruited nine young women who performed a leg raising exercise under six test combinations of three holding postures (lying supine, placing the shanks on a yoga ball, and elevating the legs at 60° against the wall) and two time arrangements (continuous vs. intermittent) for a period of 15 min. The intermittent arrangement included an additional 1-min rest set in the middle of the 15 min test. The participants' shank circumference (SC) reductions and discomfort ratings were measured after each test combination was performed. Results indicated that the most efficient method for SC reduction was the yoga ball (5.4 mm), followed by the supine lying posture (4.6 mm) and wall-supported leg raising (3.1 mm). A significant interaction of posture × time arrangement (p < 0.01) implied that the yoga ball method combined with a 1-min rest produced the greatest SC reduction (6.7 mm). Our results also showed that participants experienced the greatest discomfort (score: 4.96) when performing wall-supported leg raising, compared with both lying supine (score: 1.34) and the yoga ball (score: 1.32). This study suggests that the effectiveness of leg raising as conventionally practiced for eliminating leg fatigue or swelling requires further consideration.

Impact of mixed cryoglobulinemia on patients with spontaneous hepatitis C virus clearance: A 13-year prospective cohort study.

BACKGROUND: The prevalence and associations of mixed cryoglobulinemia (MC) in patients with spontaneous clearance of hepatitis C virus (HCV) remain elusive. MATERIALS AND METHODS: A 13-year prospective cohort study of patients with spontaneous HCV clearance was conducted in a tertiary care centre. Baseline characteristics, incident cardiovascular and neurologic events and cancers were analysed. RESULTS: Of 104 consecutive patients (mean age: 54.08 years old; females: 71 [68%]), 37 (34.6%) had MC and 6 (5.8%) had cirrhosis. MC (+) patients were more female (86% vs 58%, P = .002), had higher rate of cirrhosis (14% vs 1.5%, P = .012), higher levels of Immunoglobulin G (IgG; P = .001), IgM (P = .002) and fibrosis-4 (FIB-4) (P = .004), but lower levels of complement C4 (P = .034) than the MC (-) patients. Female gender (95% confidence interval [CI] of odds ratio: 1.402-26.715), levels of IgG (1.000-1.004), IgM (1.009-1.037) and FIB-4 (1.217-3.966) were independently associated with MC. Baseline rheumatoid factor (RF) levels were independently associated with incident cancer (95% CI hazard ratio [HR]: 1.001-1.030 [HR: 1.015], P = .039). With a cut-off value of 11.3 IU/mL, RF levels significantly predicted incident cancer (area under curve: 0.865, P = .002). No different cumulative incidences of cardiovascular and neurologic events, cancers or mortalities were identified between MC (+) and MC (-) patient. CONCLUSIONS: Approximately 1/3 of patients with spontaneous HCV clearance yielded MC, which harboured similar characteristics of MC in patients with chronic hepatitis C. Despite the negligible role of MC in the prognosis of patients with spontaneous HCV clearance, the connection between RF and incident cancer demands further investigation.

The extrahepatic events of Asian patients with primary biliary cholangitis: A 30-year cohort study.

The extrahepatic complications of primary biliary cholangitis (PBC) in Asian patients remain elusive. A 30-year cohort study of 150 Taiwanese PBC patients treated with ursodeoxycholic acid (UDCA) was conducted. Patients with alkaline phosphatase levels >1.67 × ULN after 1-year treatment were considered suboptimal responders. At baseline, of 150 patients (mean age: 53.75 years), 128 (85.3%) were females, and 34 (22.8%) had cirrhosis. The cumulative incidences of various incident events were all-cause mortality or liver transplantation: 46.7%; extrahepatic mortality: 24.5%; extrahepatic malignancies: 8.1%; hypertension: 46.2%; dyslipidemia: 44.1%; diabetes: 30.6%; hyperuricemia: 11.2%; acute coronary syndrome: 3.1%; cerebral vascular accident (CVA): 8.9%; autoimmune diseases: 16%; and osteoporosis: 20.9%. The 5- to 20-year cumulative incidences for all-cause mortality or liver transplantation and extrahepatic mortality were 16.2-41.3% and 3.1-11.9%, respectively. Baseline associations were age and alpha-fetoprotein levels with extrahepatic mortality, 80% due to sepsis; age with extrahepatic malignancies and hypertension; gender and hyperuricemia with CVA; and UDCA response with autoimmune disease. Conclusions: Sepsis accounted for most extrahepatic mortality in PBC patients, and the longer the follow-up was, the higher the extrahepatic/all-cause mortality ratio. Baseline age is crucial for incident extrahepatic events and only CVA shows gender-dimorphism; the association between UDCA response and autoimmune disease requires further investigation.

Nomogram predicting extrahepatic metastasis of hepatocellular carcinoma based on commonly available clinical data.

BACKGROUND AND AIM: Extrahepatic metastasis (EHM) of hepatocellular carcinoma (HCC) leads to a worse prognosis. We aimed to develop a nomogram based on noninvasive pretreatment clinical data to predict EHM of HCC sooner. METHODS: Three cohorts containing 1820, 479, and 988 HCC patients were enrolled from three hospitals in different regions in Taiwan and served as the training and validation cohorts. Pretreatment clinical data were analyzed by Cox regression modeling for independent risk factors of EHM. RESULTS: Platelet count ≥ 200 × 103/µL, serum alfa-fetoprotein ≥ 100 ng/dL, tumor size ≥ 3 cm, tumor number > 1, and macrovascular invasion were independent risk factors for EHM and were used to develop a nomogram. This nomogram had concordance indices of 0.733 (95% confidence interval [CI]: 0.688-0.778) and 0.739 (95% CI: 0.692-0.787) for the prediction of EHM during a 5-year follow-up duration in the training and validation cohorts, respectively. A nomogram score > 61 implied a high risk of EHM (hazard ratio [HR] = 3.83; 95% CI: 2.77-5.31, P < 0.001). CONCLUSION: We have developed a nomogram that could accurately predict EHM of HCC and be readily available for formulating individualized treatment for all individual HCC patients to improve therapeutic efficacy.

Salinomycin acts through reducing AKT-dependent thymidylate synthase expression to enhance erlotinib-induced cytotoxicity in human lung cancer cells.

Erlotinib (TarcevaR) is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor in the treatment of human non-small cell lung cancer (NSCLC). Salinomycin, a polyether antibiotic, has been promising a novel therapeutic agent for lung cancer, and down-regulated the expression of thymidylate synthase (TS) in NSCLC cell lines. Previous study showed that against EGFR and TS was strongly synergistic cytotoxicity in NSCLC cells. In this study, we showed that erlotinib (1.25-10µM) treatment down-regulating of TS expression in an AKT inactivation manner in two NSCLC cell lines, human lung squamous cell carcinoma H1703 and adenocarcinoma H1975 cells. Knockdown of TS using small interfering RNA (siRNA) or inhibiting AKT activity with PI3K inhibitor LY294002 enhanced the cytotoxicity and cell growth inhibition of erlotinib. A combination of erlotinib and salinomycin resulted in synergistic enhancement of cytotoxicity and cell growth inhibition in NSCLC cells, accompanied with reduced protein levels of phospho-AKT(Ser473), phospho-AKT(Thr308), and TS. Overexpression of a constitutive active AKT (AKT-CA) or Flag-TS expression vector reversed the salinomycin and erlotinib-induced synergistic cytotoxicity. Our findings suggested that the down-regulation of AKT-mediated TS expression by salinomycin enhanced the erlotinib-induced cytotoxicity in NSCLC cells. These results may provide a rationale to combine salinomycin with erlotinib for lung cancer treatment.

Resistin reinforces interferon λ-3 to eliminate hepatitis C virus with fine-tuning from RETN single-nucleotide polymorphisms.

The effect of resistin (RETN) on the response to anti-HCV therapy remains unclear. A prospective cohort study was performed using 655 consecutive HCV patients, of whom 513 had completed a course of interferon-based therapy. Multivariate and GEE analyses revealed four RETN single-nucleotide polymorphisms (SNPs), rs34861192, rs3219175, rs3745367 and rs1423096, to be synergistically associated with resistin levels. After adjusting for co-factors such as interferon λ-3 (IFNL3)-rs12979860, the resistin level and the hyper-resistinemic genotype at the 4 RETN SNPs were positively and negatively associated with a sustained virological response (SVR), respectively. RETN-rs3745367 was in linkage disequilibrium with IFNL3-rs12979860. Compared to non-SVR patients, SVR patients had higher levels of pre-therapy resistin, primarily originating from intrahepatic lymphocytes, stellate cells, Kupffer cells, hepatic progenitor cells and hepatocytes. This difference diminished over the course of therapy, as only SVR patients exhibited a 24-week post-therapy decrease in resistin. Both resistin and IFNL3 mRNAs were upregulated, but only resistin mRNA was upregulated by recombinant resistin in peripheral blood mononuclear cells with and without hyper-resistinemic genotypes of the 4 RETN SNPs, respectively. Fine-tuned by RETN SNPs, intrahepatic, multi-cellular resistin reinforced IFNL3 in eliminating HCV via immunomodulation to counteract pro-inflammation. These results encourage the development of novel resistin-targeted anti-viral agents.

The Effectiveness of Multiple Electrode Radiofrequency Ablation in Patients with Hepatocellular Carcinoma with Lesions More than 3 cm in Size and Barcelona Clinic Liver Cancer Stage A to B2.

Outcomes of hepatocellular carcinoma (HCC) lesions >3.0 cm in size including Barcelona Clinic Liver Cancer (BCLC) stage B after radiofrequency ablation (RFA) with a single electrode remain unsatisfactory. This study aimed to investigate the outcomes of RFA with multiple electrodes (ME-RFA) for HCC tumors 3.1-7.0 cm in size and BCLC stage B. This retrospective study included 70 consecutive patients with 58 medium- (3.1-5.0 cm) and 17 large- (5.1-7.0 cm) sized HCCs after ME-RFA using a controller. Outcomes in terms of complete response, primary technique effectiveness, local tumor progression, and overall survival were investigated. After 1-4 applications of ME-RFA, the rates of complete response and PTE in medium-sized tumors were 79.3% and 91.4%, respectively, and in large tumors were 76.5% and 94.1%, respectively. Overall, the major complication rate was 5.7%. After a median 21-month follow-up period, both two- and three-year estimated overall survival rates were above 80%. There were no significant differences in overall survival and local tumor progression rates between medium- and large-size tumors and among BCLC stages A, B1 and B2. A complete response to ME-RFA was the only significant factor associated with improved survival (p=0.008). In conclusion, ME-RFA can effectively treat 3.1-7.0-cm sized HCCs with a comparable outcome between medium- and large-size tumors and among BCLA stages A to B2.

Percutaneous radiofrequency ablation of tumor feeding artery before target tumor ablation may reduce local tumor progression in hepatocellular carcinoma.

BACKGROUND: Local tumor progression (LTP) in early-stage hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) remains high. Tumor feeding artery ablation (FAA) before target tumor ablation was reported to reduce LTP in patients with HCC >3 cm. The aim of our study is to investigate whether FAA before target tumor ablation may reduce LTP in HCC <3 cm. METHODS: We retrospectively analysis the outcome of patients with HCC <3 cm undergoing FAA before target tumor ablation (N = 17) compared to direct RFA to target tumor alone (N = 35). RESULTS: FAA significantly reduces LTP (FAA vs. non-FAA: local tumor progression 17.6% vs. 48.6%, p = 0.038), but not in intrahepatic recurrence: 29.4% vs. 25.7%, p = 0.778; or in overall recurrence rate: 41.2% vs. 62.9%, p = 0.14). The cumulative 1-year and 2-year LTP rates in FAA group were 17.6% and 17.6%, while 11.4% and 42.9% in non-FAA group (p = 0.073), respectively. The cumulative overall recurrence rates at 1-year and 2-year were 29.4% and 35.3% in FAA group, while 14.3% and 57.1% in non-FAA group (p = 0.130), respectively. CONCLUSIONS: FAA before target tumor ablation may decrease LTP in HCC <3 cm. Further randomized control study will be helpful for validation.

A high-density microelectrode-tissue-microelectrode sandwich platform for application of retinal circuit study.

BACKGROUND: Microelectrode array (MEA) devices are frequently used in neural circuit studies, especially in retinal prosthesis. For a high throughput stimulation and recording paradigm, it is desirable to obtain the responses of multiple surface RGCs initiated from the electrical signals delivered to multiple photoreceptor cells. This can be achieved by an high density MEA-tissue-MEA (MTM) sandwich configuration. However, the retina is one of the most metabolically active tissues, consumes oxygen as rapidly as the brain. The major concern of the MTM configuration is the supply of oxygen. METHODS: We aimed to develop a high density MTM sandwich platform which consists of stacks of a stimulation MEA, retinal tissue and a recording MEA. Retina is a metabolically active tissue and the firing rate is very sensitive to oxygen level. We designed, simulated and microfabricated porous high density MEAs and an adjustable perfusion system that electrical signals can be delivered to and recorded from the clipped retinal tissue. RESULTS: The porous high-density MEAs linked with stimulation or recording devices within a perfusion system were manufactured and the MTM platform was assembled with a retina slice inside. The firing rate remained constant between 25 and 55 min before dramatically declined, indicating that within certain period of time (e.g. 30 min after habituation), the retina condition was kept by sufficient oxygen supply via the perfusion holes in the MEAs provided by the double perfusion system. CONCLUSIONS: MTM sandwich structure is an efficient platform to study the retinal neural circuit. The material and arrangement of high density microelectrodes with porous design make this MEA appropriate for sub-retina prosthesis. Finding ways to prolong the recording time and reduce the signal-to-noise ratio are important to improve our MTM prototype.

[Effects of Different Pretreatment Methods on the Phenylketonuria Screening Model by FTIR/ATR Spectroscopy].

To establish a phenylketonuria screening model by FTIR/ATR spectroscopy, and to compare the effects of different pretreatment methods, such as baseline correction, smoothing, derivation, Fourier deconvolution, on the model quality. A consensus partial least squares regression method (cPLS) was used to build the quantitative model of phenylalanine in dried blood spots. The effects of different pretreatment methods on the model performance were investigated, using the correlation coefficient (r), root mean square error of prediction (RMSEP), mean relative error (MRE) and predictive accuracy (Acc). The nine-point smoothing coupled with the first differential was found to perform the best. Compared with the model by the original spectra, its r, RMSEP, MRE and Acc were improved from 0. 822 7, 115. 8, 0. 395 and 94. 6 to 0. 889 9, 102. 2, 0. 286 and 100, respectively. With the advantages of fast speed, easy process, no reagents consumption and environmental protection, the present method is expected to become a simple and green technology for rapidly screening the neonatal phenylketonuria in a large population.