Long-term outcomes of combined radiofrequency ablation and multipronged ethanol ablation for the treatment of unfavorable hepatocellular carcinoma

PURPOSETo evaluate the local efficacy, safety, and long-term outcomes of combined radiofrequency ablation (RFA) and multipronged ethanol ablation (EA) in the treatment of unfavorable hepatocellular carcinoma (HCC) and to determine the prognostic factors for survival.METHODSBetween August 2009 and December 2017, 98 patients with 110 unfavorable HCC nodules who underwent combined RFA and multipronged EA were retrospectively enrolled in the study. Unfavorable HCC was defined as a medium (3.1–5.0 cm) or large (5.1–7.0 cm) HCC nodule, a tumor located at a high-risk site, or a perivascular tumor. The treatment response, overall survival (OS), and recurrence-free survival (RFS) were analyzed. The Kaplan–Meier method and Cox proportional hazards regression model were used to evaluate the prognostic factors.RESULTSComplete ablation was obtained in 80.9% (89/110) of the tumors after initial treatment. Major complications were observed in 3 (3.1%) patients. The cumulative incidence of local tumor progression (LTP) was 23.5% at five years, and no variable was found to be an independent predictive factor for LTP. The five-year OS and RFS rates were 41.9% and 34.0%, respectively. Multivariate analysis showed that the serum alpha-fetoprotein level, tumor size, presence of residual tumor after ablation, and extrahepatic metastases were significant prognostic factors for OS (P = 0.023, P = 0.030, P = 0.001, and P = 0.010, respectively). Tumor type and the number of tumors were predictive factors for RFS (P = 0.029 and P = 0.001, respectively). A perivascular tumor was not an independent predictive factor for OS or RFS.CONCLUSIONCombined RFA and multipronged EA is a safe and effective treatment for unfavorable HCC, especially for perivascular tumors

Effects of caesarean section on maternal health in low risk nulliparous women: a prospective matched cohort study in Shanghai, China

<p>Abstract</p> <p>Background</p> <p>Rates of caesarean section are progressively increasing in many parts of the world. As a result of psychosocial factors there has been an increasing tendency for pregnant women without justifiable medical indications for caesarean section to ask for this procedure in China. A critical examination of this issue in relation to maternal outcomes is important. At present there are no clinical trials to help assess the risks and benefits of caesarean section in low risk women. To fill the gap left by trials, this indication-matched cohort study was carried out to examine prospectively the outcomes of caesarean section on women with no absolute obstetric indication compared with similar women who had vaginal delivery.</p> <p>Methods</p> <p>An indication-matched cohort study was undertaken to compare maternal outcomes following caesarean section with those undergoing vaginal delivery, in which the two groups were matched for non-absolute indications. 301 nulliparous women with caesarean section were matched successfully with 301 women who delivered vaginally in the Maternal and Children's Hospitals (MCHs) in Shanghai, China. Logistic regression model or binomial regression model was used to estimate the relative risk (RR) directly. Adjusted RRs were calculated adjusting for propensity score and medical indications.</p> <p>Results</p> <p>The incidence of total complications was 2.2 times higher in the caesarean section group during hospitalization post-partum, compared with the vaginal delivery group (RR = 2.2; 95% CI: 1.1-4.4). The risk of haemorrhage from the start of labour until 2 hours post-partum was significantly higher in the caesarean group (RR = 5.6; 95% CI: 1.2-26.9). The risk of chronic abdominal pain was significantly higher for the caesarean section group (RR = 3.6; 95% CI: 1.2-10.9) than for the vaginal delivery group within 12 months post-partum. The two groups had similar incidences of anaemia and complicating infections such as wound complications or urinary tract infection.</p> <p>Conclusions</p> <p>In nulliparous women who were at low risk, caesarean section was associated with a higher rate of post-partum morbidity. Those requesting the surgical procedure with no conventional medical indication, should be advised of the potential risks.</p

The four-step total synthesis of (-)-chaetominine

National Basic Research Program (973 Program) of China [2010CB833200]; NSF of China [21332007, 21072160]; Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT) of Ministry of Education, ChinaThe total synthesis of the alkaloid (-)-chaetominine (1) has been achieved in four steps with an overall yield of 33.4%. Key features of our strategy include a one-pot cascade indole epoxidation - epoxide ring-opening cyclization - lactamization reaction sequence, and the use of a nitro group as a latent amino group for the one-pot construction of the quinazolinone ring. This constitutes a step economical, redox economical and protecting group-free total synthesis

Insights into the release of triclosan from microplastics in aquatic environment assessed with diffusive gradient in thin-films

Organic chemicals associated with microplastics (MPs) can be released and thus pose potential risks during weathering processes. However, the thermodynamics and kinetics of their release processes still need to be better understood. Herein, the adsorption and desorption kinetics of triclosan on polystyrene (PS) and polyvinyl chloride (PVC) were investigated by using both batch experiments and diffusive gradients in thin-films (DGT) technique. The pseudo-second-order model fitted the data best, implying that both intraparticle diffusion and external liquid film diffusion influence the adsorption and desorption processes. DGT continuously accumulated triclosan from MP suspensions but slower than theoretical values, indicating some restrictions to desorption. The DGT-induced fluxes in Soils/Sediment (DIFS) model, employed to interpret DGT data, gave distribution coefficients for labile species (K ) of 5000 mL g (PS) and 1000 mL g (PVC) and the corresponding response times (T ) were 10 s and 1000 s, respectively. Higher K but smaller T for PS than PVC showed that more triclosan adsorbed on PS could be rapidly released, while there were some kinetic limitations for triclosan on PVC. A novel finding was that pH and ionic strength individually and interactively affected the supply of triclosan to DGT. This is the first study to quantify interactions of organics with MPs by using DGT, aiding our understanding of MPs' adsorption/desorption behavior in the aquatic environment

Functional Expression of Spider Neurotoxic Peptide Huwentoxin-I in E. coli

The coding sequence of huwentoxin-I, a neurotoxic peptide isolated from the venom of the Chinese spider Ornithoctonus huwena, was amplified by PCR using the cDNA library constructed from the spider venom glands. The cloned fragment was inserted into the expression vector pET-40b and transformed into the E. coli strain BL21 (DE3). The expression of a soluble fusion protein, disulfide interchange protein (DsbC)-huwentoxin-I, was auto-induced in the periplasm of E. coli in the absence of IPTG. After partial purification using a Ni-NTA column, the expressed fusion protein was digested using enterokinase to release heteroexpressed huwentoxin-I and was further purified using RP-HPLC. The resulting peptide was subjected to gel electrophoresis and mass spectrometry analysis. The molecular weight of the heteroexpressed huwentoxin-I was 3750.69, which is identical to that of the natural form of the peptide isolated from spider venom. The physiological properties of the heteroexpressed huwentoxin-I were further analyzed using a whole-cell patch clamp assay. The heteroexpressed huwentoxin-I was able to block currents generated by human Nav1.7 at an IC50 of 640 nmole/L, similar to that of the natural huwentoxin-I, which is 630 nmole/L

Cellular Mechanism Underlying Hydrogen Sulfide Mediated Epithelial K+ Secretion in Rat Epididymis

As a novel gasotransmitter, hydrogen sulfide (H2S) elicits various physiological actions including smooth muscle relaxation and promotion of transepithelial ion transport. However, the pro-secretory function of H2S in the male reproductive system remains largely unclear. The aim of this study is to elucidate the possible roles of H2S in modulating rat epididymal intraluminal ionic microenvironment essential for sperm storage. The results revealed that endogenous H2S-generating enzymes cystathionine β-synthetase (CBS) and cystathionine γ-lyase (CSE) were both expressed in rat epididymis. CBS located predominantly in epithelial cells whilst CSE expressed primarily in smooth muscle cells. The relative expression level of CBS and CSE escalated from caput to cauda regions of epididymis, which was paralleled to the progressively increasing production of endogenous H2S. The effect of H2S on epididymal epithelial ion transportation was investigated using short-circuit current (ISC), measurement of intracellular ion concentration and in vivo rat epididymal microperfusion. Our data showed that H2S induced transepithelial K+ secretion via adenosine triphosphate-sensitive K+ (KATP) channel and large conductance Ca2+-activated K+ (BKCa) channel. Transient receptor potential vanilloid 4 (TRPV4) channel-mediated Ca2+ influx was implicated in the activation of BKCa channel. In vivo studies further demonstrated that H2S promoted K+ secretion in rat epididymal epithelium. Inhibition of endogenous H2S synthesis caused a significant decrease in K+ concentration of cauda epididymal intraluminal fluid. Moreover, our data demonstrated that high extracellular K+ concentration actively depressed the motility of cauda epididymal sperm in a pH-independent manner. Collectively, the present study demonstrated that H2S was vital to the formation of high K+ concentration in epididymal intraluminal fluid by promoting the transepithelial K+ secretion, which might contribute to the maintenance of the cauda epididymal sperm in quiescent dormant state before ejaculation

Screening Level of PAHs in Sediment Core from Lake Hongfeng, Southwest China

Using data from a 25-year retrospective of polycyclic aromatic hydrocarbons (PAHs) in sediment core from Lake Hongfeng, Southwest China, their possible sources and potential toxicologic significance were investigated. The total PAH concentrations (16 priority PAHs as proposed by the United States Environmental Protection Agency) in sediments ranged from 2936.1 to 5282.3 ng/g and gradually increased from the analyzed deeper sediments to surface sediments. PAHs were dominated by low molecular-weight components, especially phenanthrene (PHEN) and fluorene (FLU). However, a significantly increased number of high molecular-weight (HMW) PAHs was found in upper segments. The temporal trends of individual PAH species suggest that there may have been a change in energy use from low- to high-temperature combustion, especially after approximately 2001. PAH input to Lake Hongfeng originated mainly from domestic coal combustion and biomass burning, whereas fuel combustion characteristics have also been found in recent years. Sediment-quality assessment implied that potential adverse biologic impact could be a probability for most low-ring PAHs (including naphthalene, acenaphthylene, acenaphthylene, FLU, PHEN, and anthracene). Nevertheless, more concern should be paid to HMW PAHs in the future due to their rapidly increasing trends in upper sediments. Because only one core was analyzed in this study, more work is needed to confirm the sources and toxicity of PAHs in Lake Hongfeng

RANKL Is a Downstream Mediator for Insulin-Induced Osteoblastic Differentiation of Vascular Smooth Muscle Cells

Several reports have shown that circulating insulin level is positively correlated with arterial calcification; however, the relationship between insulin and arterial calcification remains controversial and the mechanism involved is still unclear. We used calcifying vascular smooth muscle cells (CVSMCs), a specific subpopulation of vascular smooth muscle cells that could spontaneously express osteoblastic phenotype genes and form calcification nodules, to investigate the effect of insulin on osteoblastic differentiation of CVSMCs and the cell signals involved. Our experiments demonstrated that insulin could promote alkaline phosphatase (ALP) activity, osteocalcin expression and the formation of mineralized nodules in CVSMCs. Suppression of receptor activator of nuclear factor κB ligand (RANKL) with small interfering RNA (siRNA) abolished the insulin-induced ALP activity. Insulin induced the activation of extracellular signal-regulated kinase (ERK)1/2, mitogen-activated protein kinase (MAPK) and RAC-alpha serine/threonine-protein kinase (Akt). Furthermore, pretreatment of human osteoblasts with the ERK1/2 inhibitor PD98059, but not the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, or the Akt inhibitor, 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (HIMO), abolished the insulin-induced RANKL secretion and blocked the promoting effect of insulin on ALP activities of CVSMCs. Recombinant RANKL protein recovered the ALP activities decreased by RANKL siRNA in insulin-stimulated CVSMCs. These data demonstrated that insulin could promote osteoblastic differentiation of CVSMCs by increased RANKL expression through ERK1/2 activation, but not PI3K/Akt activation