The combination of tyrosine kinase inhibitors (TKIs) and transarterial chemoembolization (TACE) fulfills an important role in the treatment of unresectable hepatocellular carcinoma (uHCC). Among the ...combination therapies, both lenvatinib and sorafenib combined with TACE are recommended as first-¬line treatments for uHCC. However, at present, limited data are available concerning the efficacy and safety of these two combination therapies in uHCC.
A detailed systematic search for studies on lenvatinib plus TACE (LEN+TACE) and sorafenib plus TACE (SOR+TACE) was conducted in the online databases PubMed, Embase and The Cochrane Library. The outcome data including overall survival (OS), progression free survival (PFS), time to progression (TTP), tumor response and adverse events (AEs), were independently extracted by two authors in a standardized way.
One randomized controlled trial and five cohort studies with 598 patients (LEN+TACE: 261, SOR+TACE: 337) were included in the meta-analysis. A higher rate of odds ratio (OR) for the objective response rate (ORR) OR: 3.63; 95% confidence intervals (95% CI): 1.89-6.95; I squared statistic (I2) = 57%, P < 0.001 and disease control rate (DCR) (OR: 3.78; 95% CI: 2.00-7.16; I2 = 52%, P = 0.0001) were observed in the LEN+SOR group compared with the SOR+TACE group. The LEN+TACE group also had significant longer OS hazard ratio (HR): 0.67; 95% CI: 0.52-0.85; I2 = 1%, P = 0.001, PFS (HR: 0.49; 95% CI: 0.38-0.62; I2 = 0%, P? 0.001) and TTP (HR: 0.62; 95% CI: 0.45-0.84; I2 = 0%, P = 0.002) compared with the SOR+TACE group. The incidence of hypertension (OR: 3.05; 95% CI: 1.45-6.39; P = 0.003) and proteinuria (OR: 5.25; 95% CI: 1.73-15.89; P = 0.003) were significantly higher in the LEN+TACE group than SOR+TACE group, while LEN+TACE group exhibited a lower rate of hand-foot-skin reaction (HFSR) (OR: 0.51; 95% CI: 0.27-0.95; P = 0.03) compared with the SOR+TACE group.
The combination therapy of LEN+TACE showed significant superiority compared with SOR+TACE in terms of its efficacy for patients with uHCC. SOR+TACE should be recommended as a replacement therapy when serious AEs occur during the administration of LEN+TACE as the combination therapy.
GTP cyclohydrolase 1 (GCH1) deficiency is critical for endothelial nitric oxide synthase uncoupling in endothelial dysfunction. MicroRNAs (miRs) are a class of regulatory RNAs that negatively ...regulate gene expression. We investigated whether statins prevent endothelial dysfunction via miR-dependent GCH1 upregulation.
Endothelial function was assessed by measuring acetylcholine-induced vasorelaxation in the organ chamber. MiR-133a expression was assessed by quantitative reverse transcription polymerase chain reaction and fluorescence in situ hybridization.
We first demonstrated that GCH1 mRNA is a target of miR-133a. In endothelial cells, miR-133a was robustly induced by cytokines/oxidants and inhibited by lovastatin. Furthermore, lovastatin upregulated GCH1 and tetrahydrobiopterin, and recoupled endothelial nitric oxide synthase in stressed endothelial cells. These actions of lovastatin were abolished by enforced miR-133a expression and were mirrored by a miR-133a antagomir. In mice, hyperlipidemia- or hyperglycemia-induced ectopic miR-133a expression in the vascular endothelium, reduced GCH1 protein and tetrahydrobiopterin levels, and impaired endothelial function, which were reversed by lovastatin or miR-133a antagomir. These beneficial effects of lovastatin in mice were abrogated by in vivo miR-133a overexpression or GCH1 knockdown. In rats, multiple cardiovascular risk factors including hyperglycemia, dyslipidemia, and hyperhomocysteinemia resulted in increased miR-133a vascular expression, reduced GCH1 expression, uncoupled endothelial nitric oxide synthase function, and induced endothelial dysfunction, which were prevented by lovastatin.
Statin inhibits aberrant miR-133a expression in the vascular endothelium to prevent endothelial dysfunction by targeting GCH1. Therefore, miR-133a represents an important therapeutic target for preventing cardiovascular diseases.
Objective
To evaluate the effect of art therapy on cancer patients' quality of life and physical and psychological symptoms.
Methods
The databases PubMed, Embase, Web of Science, The Cochrane ...Library, Clinical Trial.gov, the China National Knowledge Infrastructure (CNKI), Wanfang and the Chinese Biomedical Literature Database (CBM) were searched from their inception up to 20 August 2019. Trials examining the effects of art therapy on physical and psychological symptoms and quality of life versus a control group were included. The methodological quality of the included randomised controlled trials was assessed using the risk of bias tool of Cochrane Handbook. Meanwhile, the Newcastle‐Ottawa Quality Assessment Scale (NOS) was used to evaluate the methodological quality of the non‐randomised studies.
Results
Twelve studies involving 587 cancer patients were included. The results revealed that art therapy significantly reduced anxiety symptoms (standard mean difference SMD = −0.46, 95% confidence interval CI −0.90, 0.02, p = .04), depression symptoms (SMD = −0.47, 95% CI −0.72, 0.21, p < .01), and fatigue (SMD = −0.38, 95% CI −0.68, −0.09, p = .01) in cancer patients. Art therapy also significantly improved the quality of life of cancer patients (SMD = 0.43, 95% CI 0.18, 0.68, p < .01).
Conclusions
Art therapy had a positive effect on quality of life and symptoms in cancer patients and can be used as a complementary treatment for cancer patients.
Renal sympathetic denervation (RD) is a promising method of neuromodulation for the management of cardiac arrhythmia.
We tested the hypothesis that RD is antiarrhythmic in ambulatory dogs because it ...reduces the stellate ganglion nerve activity (SGNA) by remodeling the stellate ganglion (SG) and brain stem.
We implanted a radiotransmitter to record SGNA and electrocardiogram in 9 ambulatory dogs for 2 weeks, followed by a second surgery for RD and 2 months SGNA recording. Cell death was probed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.
Integrated SGNA at baseline and 1 and 2 months after RD were 14.0 ± 4.0, 9.3 ± 2.8, and 9.6 ± 2.0 μV, respectively (P = .042). The SG from RD but not normal control dogs (n = 5) showed confluent damage. An average of 41% ± 10% and 40% ± 16% of ganglion cells in the left and right SG, respectively, were TUNEL positive in RD dogs compared with 0% in controls dogs (P = .005 for both). The left and right SG from RD dogs had more tyrosine hydroxylase-negative ganglion cells than did the left SG of control dogs (P = .028 and P = .047, respectively). Extensive TUNEL-positive neurons and glial cells were also noted in the medulla, associated with strongly positive glial fibrillary acidic protein staining. The distribution was heterogeneous, with more cell death in the medial than lateral aspects of the medulla.
Bilateral RD caused significant central and peripheral sympathetic nerve remodeling and reduced SGNA in ambulatory dogs. These findings may in part explain the antiarrhythmic effects of RD.
Carnosic acid (CA), a natural catechol rosin diterpene, is used as an additive in animal feeds and human foods. However, the effects of CA on mammalian reproductive processes, especially early ...embryonic development, are unclear. In this study, we added CA to parthenogenetically activated porcine embryos in an in vitro culture medium to explore the influence of CA on apoptosis, proliferation, blastocyst formation, reactive oxygen species (ROS) levels, glutathione (GSH) levels, mitochondrial membrane potential, and embryonic development-related gene expression. The results showed that supplementation with 10 μM CA during in vitro culture significantly improved the cleavage rates, blastocyst formation rates, hatching rates, and total numbers of cells of parthenogenetically activated porcine embryos compared with no supplementation. More importantly, supplementation with CA also improved GSH levels and mitochondrial membrane potential, reduced natural ROS levels in blastomeres, upregulated Nanog, Sox2, Gata4, Cox2, Itga5, and Rictor expression, and downregulated Birc5 and Caspase3 expression. These results suggest that CA can improve early porcine embryonic development by regulating oxidative stress. This study elucidates the effects of CA on early embryonic development and their potential mechanisms, and provides new applications for improving the quality of in vitro-developed embryos.
In COPD, functional status is improved by pulmonary rehabilitation (PR) but requires specific facilities. Tai Chi, which combines psychological treatment and physical exercise and requires no special ...equipment, is widely practiced in China and is becoming increasingly popular in the rest of the world. We hypothesized that Tai Chi is equivalent (ie, difference less than ±4 St. George's Respiratory Questionnaire SGRQ points) to PR.
A total of 120 patients (mean FEV
, 1.11 ± 0.42 L; 43.6% predicted) bronchodilator-naive patients were studied. Two weeks after starting indacaterol 150 μg once daily, they randomly received either standard PR thrice weekly or group Tai Chi five times weekly, for 12 weeks. The primary end point was change in SGRQ prior to and following the exercise intervention; measurements were also made 12 weeks after the end of the intervention.
The between-group difference for SGRQ at the end of the exercise interventions was -0.48 (95% CI PR vs Tai Chi, -3.6 to 2.6; P = .76), excluding a difference exceeding the minimal clinically important difference. Twelve weeks later, the between-group difference for SGRQ was 4.5 (95% CI, 1.9 to 7.0; P < .001), favoring Tai Chi. Similar trends were observed for 6-min walk distance; no change in FEV
was observed.
Tai Chi is equivalent to PR for improving SGRQ in COPD. Twelve weeks after exercise cessation, a clinically significant difference in SGRQ emerged favoring Tai Chi. Tai Chi is an appropriate substitute for PR.
ClinicalTrials.gov; No.: NCT02665130; URL: www.clinicaltrials.gov.
In order to screen out the feeding ratio of high‐quality algae strains in Hyriopsis cumingii, this experiment investigated the effects of different ratio of mixed feeding of two algae strains ...(Scenedesmus dimorphus and Cyclotella sp.) on the growth, bead production performance, trace elements, and amino acid composition of the newborn shell of H. cumingii. The results showed that the mixed feeding of two types of microalgae with different densities had significant effects on the growth performance, bead production quality, trace elements, and amino acid composition of the newly formed shell of H. cumingii (p < 0.05); the best body weight gain rate and shell growth rate were obtained by feeding S. dimorphus (30 × 105 cell/mL) and Cyclopella sp.(8 × 105 cell/mL); the pearl weight gain rate, amino acid ratio, Ca2+ and Mn2+ content were best when feeding Cyclotella sp. (16 × 105 cell/mL), but there was no significant difference compared with S. dimorphus (30 × 105 cell/mL) and Cyclopella sp.(8 × 105 cell/mL). In summary, the optimal feeding amount for the intensive breeding process of H. cumingii is S. dimorphus (30 × 105 cell/mL) and Cyclopella sp. (8 × 105 cell/mL).
The aim of this study was to determine the optimal weaning protocols for rearing juvenile cuttlefish
Sepia pharaonis
, as well as to understand the feeding habits of cuttlefish and develop effective ...aqua-cultural practices. The effects of four experimental weaning protocols (i.e., food type, cuttlefish size, food ration (bw d
−1
) and feeding frequency (meals d
−1
)) on the growth, survival and muscle proximate composition of cuttlefish juvenile were studied in quintuplicate. The weaning period lasted 2 weeks. The results showed that cuttlefish fed with frozen white shrimp (
Exopalaemon carinicauda
) displayed a significantly higher survival, growth parameters, ingestion rate, food conversion rate, and muscle protein content when compared with the other prepared frozen foods. The larger individuals revealed better growth performance than smaller individuals, especially in terms of survival and specific growth rate, indicating that larger individuals were more receptive to frozen prey. Furthermore, size grading should be conducted to ensure better growth during weaning. As food rations increased, the survival, growth and muscle protein content of juveniles were promoted, whereas the most appropriate food ration for cuttlefish juvenile was 35% bw d
−1
. Similarly, higher feeding frequency could stimulate the appetite of animals reared on weaning, and enhance survival, growth, and protein deposition compared to low feeding frequency. These results suggest that the optimal feeding protocols of juvenile weaning is as follows: the ideal prepared food is frozen shrimp, the weight of juveniles should be 4.0 g (32 days old) or more, the food ration should be 35% (bw d
−1
), and the optimum feeding frequency is 4 meals day
−1
. This study offers a promising starting point to successfully breed this candidate aquaculture species.
This study presents two optical frequency quadrupling techniques for generating high-purity millimeter-wave signals with optical carrier suppression. To our best knowledge, this investigation ...demonstrates for the first time that a frequency quadrupling system requires only a single integrated Mach-Zehnder modulator without an optical narrowband filter to remove undesired optical sidebands. Since no optical filter is needed, fast frequency tuning is straightforward and this approach is particularly attractive for the optical up-conversion in the wavelength-division-multiplexing radio-over-fiber systems. This study provides both theoretical analysis and experimental demonstration. The generated optical millimeter-wave signals are of very high quality with optical carrier and undesired harmonic distortion suppression ratio of more than 36 dB.
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