Comparative prognosis and risk assessment in gallbladder neuroendocrine neoplasms versus adenocarcinomas.

Background: Gallbladder neuroendocrine neoplasms (GB-NENs) are a rare malignant disease, with most cases diagnosed at advanced stages, often resulting in poor prognosis. However, studies regarding the prognosis of this condition and its comparison with gallbladder adenocarcinomas (GB-ADCs) have yet to yield convincing conclusions. Methods: We extracted cases of GB-NENs and GB-ADCs from the Surveillance, Epidemiology, and End Results (SEER) database in the United States. Firstly, we corrected differences in clinical characteristics between the two groups using propensity score matching (PSM). Subsequently, we visualized and compared the survival outcomes of the two groups using the Kaplan-Meier method. Next, we employed the least absolute shrinkage and selection operator (LASSO) regression and Cox regression to identify prognostic factors for GB-NENs and constructed two nomograms for predicting prognosis. These nomograms were validated with an internal validation dataset from the SEER database and an external validation dataset from a hospital. Finally, we categorized patients into high-risk and low-risk groups based on their overall survival (OS) scores. Results: A total of 7,105 patients were enrolled in the study, comprising 287 GB-NENs patients and, 6,818 GB-ADCs patients. There were substantial differences in clinical characteristics between patients, and GB-NENs exhibited a significantly better prognosis. Even after balancing these differences using PSM, the superior prognosis of GB-NENs remained evident. Independent prognostic factors selected through LASSO and Cox regression were age, histology type, first primary malignancy, tumor size, and surgery. Two nomograms for prognosis were developed based on these factors, and their performance was verified from three perspectives: discrimination, calibration, and clinical applicability using training, internal validation, and external validation datasets, all of which exhibited excellent validation results. Using a cutoff value of 166.5 for the OS nomogram score, patient mortality risk can be identified effectively. Conclusion: Patients with GB-NENs have a better overall prognosis compared to those with GB-ADCs. Nomograms for GB-NENs prognosis have been effectively established and validated, making them a valuable tool for assessing the risk of mortality in clinical practice.

Multi-Functional Formaldehyde-Nitrate Batteries for Wastewater Refining, Electricity Generation, and Production of Ammonia and Formate.

As bulky pollutants in industrial and agricultural wastewater, nitrate and formaldehyde pose serious threats to the human health and ecosystem. Current purification technologies including chemical and bio-/photo-/electro-chemical methods, are generally high-cost, time-consuming, or energy-intensive. Here, we report a novel formaldehyde-nitrate battery by pairing anodic formaldehyde oxidation with cathodic nitrate reduction, which simultaneously enables wastewater purification, electricity generation, and the production of high-value-added ammonia and formate. As a result, the formaldehyde-nitrate battery remarkably exhibits an open-circuit voltage of 0.75 V, a peak power density of 3.38 mW cm-2 and the yield rates of 32.7 mg h-1 cm-2 for ammonia and 889.4 mg h-1 cm-2 for formate. In a large-scale formaldehyde-nitrate battery (25 cm2 ), 99.9 % of nitrate and 99.8 % of formaldehyde are removed from simulated industrial wastewater and the electricity of 2.03 W⋅h per day is generated. Moreover, the design of such a multi-functional battery is universally applicable to the coupling of NO3 - or NO2 - reduction with various aldehyde oxidization, paving a new avenue for wastewater purification and chemical manufacturing.

Jahn-Teller Distortions Induced by in situ Li Migration in λ-MnO2 for Boosting Electrocatalytic Nitrogen Fixation.

Lithium-mediated electrochemical nitrogen reduction reaction (Li-NRR) completely eschews the competitive hydrogen evolution reaction (HER) occurred in aqueous system, whereas the continuous deposition of lithium readily blocks the active sites and further reduces the reaction kinetics. Herein, we propose an innovative in situ Li migration strategy to realize that Li substitutes Mn sites in λ-MnO2 instead of evolving into the dead Li. Comprehensive characterizations corroborate that the intercalation of Li+ at high voltage breaks the structural integrity of MnO6 octahedron and further triggers unique Jahn-Teller distortions, which promotes the spin state regulation of Mn sites to generate the ameliorative eg orbital configuration and accelerates N≡N bond cleavage via eg -σ and eg -π* interaction. To this end, the resulted cationic disordered LiMnO4 delivers the recorded highest NH3 yield rate of 220 µg h-1 cm-2 and a Faradaic efficiency (FE) 83.80 % in organic electrolyte.

Nomogram for Estimation of Acute Liver Failure Risk in Spontaneous Ruptured Hepatocellular Carcinoma.

Purpose: Acute liver failure (ALF) is a severe complication of spontaneous ruptured hepatocellular carcinoma (SRHCC) that requires accurate prediction for effective treatment strategies. We aimed to develop a predictive nomogram to estimate the risk of ALF in patients with SRHCC undergoing treatment. Patients and Methods: We performed a retrospective analysis of historical data from 284 patients diagnosed with SRHCC at the First Hospital of Jilin University over the past decade. Variables were selected through univariate and multivariate logistic regression analyses, and a predictive nomogram was constructed. We evaluated its predictive accuracy against the Child-Pugh Score, R.MELD, and ALBI by assessing discrimination, calibration, and net clinical benefit. Results: Among the 284 patients, 65 developed ALF. The risk factors identified for model development included largest tumor size (LTS), platelet counts, prolonged prothrombin time, and elevated serum α-fetoprotein levels. The nomogram exhibited high accuracy in predicting ALF risk with a C-index of 0.91 (0.87-0.95). The Delong test showed a significant difference between the nomogram and the other three models (p<0.05). The calibration curve for the nomogram fit well, and the decision curve analysis revealed superior net benefit. The optimal cut-off point for the nomogram was determined to be 40, yielding sensitivity, specificity, positive predictive value, and negative predictive value of 83.10%, 87.20%, 65.90% and 94.60%, respectively. Conclusion: The nomogram we developed provides an optimized tool for predicting ALF in SRHCC patients. Its application can help determine individual patient's risk of ALF, enabling more rational and personalized treatment strategies.

Multiple heteroatom substitution effect on destructive quantum interference in tripodal single-molecule junctions.

Quantum interference (QI) has been identified as a promising strategy for designing molecular-scale electronic devices. Heteroatom doping can effectively tailor the local structures and electronic states of intrinsic molecules, and endow them with modified electron transport properties. Herein, the impacts of multiple heteroatom substitution on destructive quantum interference (DQI) have been investigated based on tripodal meta-linked phenyl derivatives. Orbital views based on the Hückel method qualitatively predict the meta-anchored molecules with DQI features, while the introduction of nitrogen atoms can alleviate the suppression of DQI at the Fermi level (EF). This is generally consistent with the movement or even removal of the antiresonance dips in transmission spectra. The substituent on position 2 can raise the antiresonance energy, while the substituent on position 4 or 6 can lower the antiresonance energy. When more than one nitrogen atom is incorporated, the impact of the substitution on positions 4 and 6 can be superimposed and the substitution on positions 2 and 4 can be partly cancelled. The experimental single-molecule conductance for tripodal molecules follows the trend of 0N-3SMe < 1N-3SMe < 3N-3SMe < 2N-3SMe, in agreement with the theoretical prediction. Additionally, the regulation is the intrinsic property depending on the position and number of the nitrogen atoms in the backbone and is irrelevant to the number and type of the anchoring groups. Our findings provide qualitative guidance for tuning the electron transport based on DQI in heterocycle molecular devices.

A Mechanistic Exploratory Study on the Therapeutic Efficacy of Astragaloside IV Against Diabetic Retinopathy Revealed by Network Pharmacology.

Purpose: Diabetic retinopathy (DR) is a serious complication of diabetes mellitus, which nearly happens to all the diabetic sufferers. This study aims to identify the preliminary molecular regulation involved in the therapeutic efficacy of astragaloside IV (AS- IV) for DR. Methods: Diabetic rat models were established and treated with AS-IV. Optical coherence tomography (OCT) and Hematoxylin-eosin (HE) staining was employed to demonstrate the histopathological changes. The main targets of AS-IV were identified by searching from public databases of traditional Chinese medicine (GeneCards, PharmMapper and Swiss Target Prediction). Besides, disease targets of DR were also obtained by integrated data from GEO datasets and predicted from public databases. Protein-protein interaction (PPI) network was constructed by Cytoscape with overlapping genes and 10 core targets were selected, on which Gene Ontology (GO) along with Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted. The interaction between AS-IV and these crucial genes were analyzed using molecular docking. RT-qPCR and western blot were used to verify the expression variation of core targets. Results: OCT imaging and HE staining demonstrated that AS-IV administration significantly increased retinal thickness in diabetic rats, obviously alleviating DR induced histopathological changes as well as elevated blood glucose levels. 107 common targets of AS-IV and DR were determined after intersection. PPI network analysis filtered 10 hub genes potentially targeted by AS-IV, including VEGFA, CASP3, HIF1α, STAT3, CTNNB1, SRC, AKT1, EGFR, IL1ß and IL6. Enrichment analysis indicated that these genes were mainly enriched in biological processes like T cell activation, epithelial cell proliferation and protein kinase B signaling, and involved in oxidative stress, apoptosis and inflammation-related pathways. The molecular docking prediction suggested that AS-IV exhibited stable binding to these core targets. In addition, mRNA levels of core targets in diabetic rats were differentially expressed before and after AS-IV treatment. Western blot further revealed that AS-IV treatment elevated DR-depressed protein levels of PI3K and AKT. Conclusion: Our study elucidated the effect of AS-IV in attenuating retinopathy induced by diabetes in rats and preliminarily unveiled the therapeutic efficacy of AS-IV in the treatment of DR might be attributed to activation of PI3K-AKT signaling pathway.

Diagnosis and minimally invasive treatment of type III choledochal cysts.

BACKGROUND: Type III choledochal cysts (CCs) are the rarest and least well-characterized of the five variants of biliary cysts. Only a few relevant studies have been conducted and a gold standard treatment for type III CCs is still lacking because of their scarcity. An unusual case of type III CC with choledochocele at the end of the distal common bile duct (CBD) with no bulging of the duodenum is presented here. CASE PRESENTATION: A 61-year-old woman presented to our department with repeated upper abdominal pain for one year. Laboratory examination revealed abnormal liver function and a slight increase in the white blood cell (WBC) count and proportion of neutrophils. In an MRCP of the patient, the distal CBD was found to have a cystic structure indicative of a type III CC. Endoscopic retrograde cholangiopancreatograpy (ERCP) revealed cystic findings compatible with Todani type III CCs. However, duodenoscopy did not show a bulge in the duodenum so laparoscopic cholecystectomy and Roux-en-Y hepaticojejunostomy were performed. In her 6-month follow-up, the patient reported that recovery from the operation was uneventful. CONCLUSIONS: ERCP has become the gold standard for diagnosing type III CCs. Type III CCs can be treated minimally invasively with laparoscopic cholecystectomy and Roux-en-Y hepaticojejunostomy.

Image-free real-time target tracking by single-pixel detection.

Image-based target tracking methods rely on continuous image acquisition and post-processing, which will result in low tracking efficiency. To realize real-time tracking of fast moving objects, we propose an image-free target tracking scheme based on the discrete cosine transform and single-pixel detection. Our method avoids calculating all the phase values, so the number of samples can be greatly reduced. Furthermore, complementary modulation is applied to reduce the measurement noise, and background subtraction is applied to enhance the contrast. The results of simulations and experiments demonstrate that the proposed scheme can accomplish the tracking task in a complex background with a sampling ratio of less than 0.59% of the Nyquist-Shannon criterion, thereby significantly reducing the measurement time. The tracking speed can reach 208 fps at a spatial resolution of 128 × 128 pixels with a tracking error of no more than one pixel. This technique provides a new idea for real-time tracking of fast-moving targets.

Coordination-Assisted Precise Construction of Metal Oxide Nanofilms for High-Performance Solid-State Batteries.

The application of solid-state batteries (SSBs) is challenged by the inherently poor interfacial contact between the solid-state electrolyte (SSE) and the electrodes, typically a metallic lithium anode. Building artificial intermediate nanofilms is effective in tackling this roadblock, but their implementation largely relies on vapor-based techniques such as atomic layer deposition, which are expensive, energy-intensive, and time-consuming due to the monolayer deposited per cycle. Herein, an easy and low-cost wet-chemistry fabrication process is used to engineer the anode/solid electrolyte interface in SSBs with nanoscale precision. This coordination-assisted deposition is initiated with polyacrylate acid as a functional polymer to control the surface reaction, which modulates the distribution and decomposition of metal precursors to reliably form a uniform crack-free and flexible nanofilm of a large variety of metal oxides. For demonstration, artificial Al2O3 interfacial nanofilms were deposited on a ceramic SSE, typically garnet-structured Li6.5La3Zr1.5Ta0.5O12 (LLZT), that led to a significant decrease in the Li/LLZT interfacial resistance (from 2079.5 to 8.4 Ω cm2) as well as extraordinarily long cycle life of the assembled SSBs. This strategy enables the use of a nickel-rich LiNi0.83Co0.07Mn0.1O2 cathode to deliver a reversible capacity of 201.5 mAh g-1 at a considerable loading of 4.8 mg cm-2, featuring performance metrics for an SSB that is competitive with those of traditional Li-ion systems. Our study demonstrates the potential of solution-based routes as an affordable and scalable manufacturing alternative to vapor-based deposition techniques that can accelerate the development of SSBs for practical applications.

Flavonoid-Like Components of Peanut Stem and Leaf Extract Promote Sleep by Decreasing Neuronal Excitability.

SCOPE: Peanut stem and leaf (PSL), a traditional Chinese medicine, is widely used as a dietary supplement to improve sleep quality; however, the underlying mechanism is unclear. Here, the study aims to determine whether active compounds in PSL extract exert their effects by mediating neuronal excitability. METHODS AND RESULTS: Aqueous PSL extract (500 mg kg-1 BW) increases the duration of total sleep (TS), slow wave sleep (SWS) and rapid eye movement sleep (REMS) in BALB/c mice after 7 and 14 continuous days of intragastric administration. Two PSL extract components with flavonoid-like structures: 4',7-di-O-methylnaringenin (DMN, 61 µg kg-1 BW) and 2'-O-methylisoliquiritigenin (MIL, 12 µg kg-1 BW), show similar effects on sleep in BALB/c mice. Moreover, incubation with DMN (50 µM) and MIL (50 µM) acutely reduces voltage-gated sodium and potassium currents and suppresses the firing of evoked action potential in mouse cortical neurons, indicating the inhibition on neuronal excitability. Meanwhile, RNA-seq analysis predicts the potential regulation of voltage-gated channels, which is according with the molecular docking simulation that both MIL and DMN can bind to voltage gated sodium channels 1.2 (Nav 1.2). CONCLUSIONS: DMN and MIL are the active ingredients of PSL that improve sleep quality, suggesting that PSL promotes sleep by regulating the excitability of neurons.

The crucial role of bacterial laccases in the bioremediation of petroleum hydrocarbons.

Laccases (EC 1.10.3.2) are a class of metallo-oxidases found in a variety of fungi, plants, and bacteria as well as in certain insects. They can oxidize a wide variety of organic compounds and can be widely applied in many fields, especially in the field of biodegradation and detoxification of environmental pollutants. The practical efficacy of laccases depends on their ability to capture the target substance as well as their catalytic activity, which is related to their catalytic center, substrate selectivity, and substrate tolerance. Over the past few decades, many laccases have been identified in plants and fungi. Concurrently, bacterial laccases have received increasing attention because of their high thermostability and high tolerance to organic compounds. The aim of this review is to summarize the role of bacterial laccases in the bioremediation of petroleum hydrocarbons and to outline the correlation between the molecular structure of the mononuclear T1 Cu center of bacterial laccases and their substrate preference.

[Effects of fertilizer application on yield and fertilizer utilization of Coffea arabica in southwest dry-hot region of China under different shading levels]. / 不同遮荫条件下施肥量对西南干热区小粒咖啡产量和肥料利用的影响.

The fertilizer and shading management of Coffea arabica in dry-hot area is extensive, resulting in lower yield and fertilizer utilization efficiency. A field experiment was carried out to find the coupling mode of shading and fertilizer for fertilizer-saving and high yield of C. arabica in dry-hot region. Four shading levels (100% NR, 75% NR, 60% NR, 45% NR, NR was natural radiation) and four fertilizer levels (No fertilization and 666.67, 1000, 1333.33 kg·hm-2) were set to examine the effects of different radiations and fertilizer treatments on canopy structure, yield, ferti-lizer use efficiency, soil nutrient content and microbial biomass carbon of C. arabica. The results showed that canopy structure, yield, fertilizer use efficiency, soil nutrient content and microbial biomass carbon were significantly affected by shading and fertilizer treatments. Soil nutrient content and microbial biomass carbon decreased with the increases of shading levels. Soil nutrient content increased with the increases of fertilizer application, while microbial biomass carbon increased first and then decreased, with a peak at the rate of 1000 kg·hm-2(200.30 mg·kg-1). Shading and fertilizer had significant effects on the canopy structure including leaf area index and openness. There were significant negative correlations of leaf area index with openness, gap fraction, total fixed-point factor and total radiation under canopy. Results of response surface analysis and spatial analysis showed that the combination of shading level and fertilizer application were 80% NR and 666.67 kg·hm-2, 79% NR and 1286.81 kg·hm-2, 79% NR and 967.74 kg·hm-2, 82% NR and 1075.27 kg·hm-2, respectively, when partial fertilizer productivity, yield, fertilizer agronomic efficiency and yield increase of fertilizer reached the maximum. The ranges of shading and fertilizer were 68%-77% NR and 946.24-1178.79 kg·hm-2 when the yield, agronomic efficiency and yield increasing rate by fertilizer reached 80% of the maximum value. In this experiment, the optimum combination of shading level and fertilizer application was 75% NR and 1000 kg·hm-2.

Single-Molecule Conductance through an Isoelectronic B-N Substituted Phenanthrene Junction.

Single-molecule conductance of a B-N substituted phenanthrene derivative and its isoelectronic C═C counterpart was investigated by the scanning tunneling microscopy break junction (STM-BJ) technique. The incorporation of the B-N motif results in a better single-molecule conductivity than the C═C analogue. Furthermore, the Lewis acid-base reaction between F- and the B atom of the B-N motif leads to a decrease of the conductance of the BN derivative, which can be understood due to the shifting of the energy positions of the LUMO, as revealed by quantum transport calculations, even though the HOMO-LUMO gap decreases in the B-F Lewis acid-base. These findings provide insights for modulating electron transport properties by isoelectronic structure design. The B-N isoelectronic substituted structure could be a feasible way to design single-molecule devices such as switches and chemical sensors.

Efficacy of complementary and integrative medicine on health-related quality of life in cancer patients: a systematic review and meta-analysis.

Complementary and integrative medicine (CIM) has been used for improving health-related quality of life (HRQOL) in patients with cancer. The objective of this review is to evaluate the effects of CIMs on the HRQOL of cancer patients. We identified randomized controlled trials (RCTs) involving patients with cancer at any stage by retrieving electronic databases from the inception to February 14, 2018 (Systematic Review Registration: PROSPERO CRD42018091609). The main outcomes were HRQOL scores and related domains such as physical well-being scores. The standardized mean difference was used for the analysis and heterogeneity was assessed with the I 2 statistic. A Bayesian framework was used to estimate the ranking order of efficacy in HRQOL change. Finally, 34 RCTs with 3,010 patients were included. As a whole, the results showed clearly superior efficacy of CIM in improving HRQOL. For different domains of HRQOL, different CIM interventions may play different roles. The ranking order of efficacy in change HRQOL was qigong plus mindfulness, Chinese herbal medicine, multimodal complementary medicine, qigong, nutritional supplement, mindfulness, acupuncture, yoga, and massage, and it was different among different domains. There was no evidence of publication bias. In conclusion, CIM may improve the HRQOL of cancer patients. More studies, especially focusing on male cancer patients, are needed to increase the confidence level of our findings.

Piezo-phototronic effect-modulated carrier transport behavior in different regions of a Si/CdS heterojunction photodetector under a Vis-NIR waveband.

The piezo-phototronic effect, as a three-way coupling effect of piezoelectricity, semiconductor and optical excitation in piezoelectric semiconductors to improve the performance of optoelectronic devices, has a wide range of applications in various fields. However, under different light illumination conditions, the piezo-phototronic effect would have different effects on the optoelectronic performance due to the different photo-generated carrier excitation regions. Here, the piezo-phototronic effect is utilized to modulate the carrier transport behavior of a p-Si/n-CdS heterojunction PD during the optoelectronic process in a broadband range from visible to near-infrared light. The strain-induced piezo-charges significantly improve the photoresponse performance of the heterojunction PD. The photoresponsivity increases by 1867% under -0.35‰ strain under 808 nm light illumination, with a remarkable reduction in the rise and fall times to ∼2.1 ms (reduced by 83.3% and 50.0%, respectively). However, since the photo-generated carriers are produced only at the n-CdS side under 442 nm light illumination, the photoresponse performance is greatly weakened by the piezo-phototronic effect. The corresponding working mechanism of the piezo-phototronic effect on the heterojunction photodiode under different light illumination conditions is proposed in detail. These results provide an in-depth understanding about the piezo-phototronic effect, which would enable more efficient utilization of the piezo-phototronic effect in optoelectronic devices.

Eye opening differentially modulates inhibitory synaptic transmission in the developing visual cortex.

Eye opening, a natural and timed event during animal development, influences cortical circuit assembly and maturation; yet, little is known about its precise effect on inhibitory synaptic connections. Here, we show that coinciding with eye opening, the strength of unitary inhibitory postsynaptic currents (uIPSCs) from somatostatin-expressing interneurons (Sst-INs) to nearby excitatory neurons, but not interneurons, sharply decreases in layer 2/3 of the mouse visual cortex. In contrast, the strength of uIPSCs from fast-spiking interneurons (FS-INs) to excitatory neurons significantly increases during eye opening. More importantly, these developmental changes can be prevented by dark rearing or binocular lid suture, and reproduced by the artificial opening of sutured lids. Mechanistically, this differential maturation of synaptic transmission is accompanied by a significant change in the postsynaptic quantal size. Together, our study reveals a differential regulation in GABAergic circuits in the cortex driven by eye opening may be crucial for cortical maturation and function.

0D/2D Heterojunctions of Vanadate Quantum Dots/Graphitic Carbon Nitride Nanosheets for Enhanced Visible-Light-Driven Photocatalysis.

0D/2D heterojunctions, especially quantum dots (QDs)/nanosheets (NSs) have attracted significant attention for use of photoexcited electrons/holes due to their high charge mobility. Herein, unprecedent heterojunctions of vanadate (AgVO3 , BiVO4 , InVO4 and CuV2 O6 ) QDs/graphitic carbon nitride (g-C3 N4 ) NSs exhibiting multiple unique advances beyond traditional 0D/2D composites have been developed. The photoactive contribution, up-conversion absorption, and nitrogen coordinating sites of g-C3 N4 NSs, highly dispersed vanadate nanocrystals, as well as the strong coupling and band alignment between them lead to superior visible-light-driven photoelectrochemical (PEC) and photocatalytic performance, competing with the best reported photocatalysts. This work is expected to provide a new concept to construct multifunctional 0D/2D nanocomposites for a large variety of opto-electronic applications, not limited in photocatalysis.

Toxic Constituents Index: A Toxicity-Calibrated Quantitative Evaluation Approach for the Precise Toxicity Prediction of the Hypertoxic Phytomedicine-Aconite.

Complex chemical composition is an important reason for restricting herbal quality evaluation. Despite the multi-components determination method significantly promoted the progress of herbal quality evaluation, however, which mainly concerned the total amount of multiple components and ignored the activity variation between each one, and did not accurately reflect the biological activity of botanical medicines. In this manuscript, we proposed a toxicity calibrated contents determination method for hyper toxic aconite, called toxic constituents index (TCI). Initially, we determined the minimum lethal dose value of mesaconitine (MA), aconitine (AC), and hypaconitine (HA), and established the equation TCI = 100 × (0.3387 ×X MA + 0.4778 ×X AC + 0.1835 ×X HA). Then, 10 batches of aconite were selected and their evaluation results of toxic potency (TP), diester diterpenoid alkaloids (DDAs), and TCI were compared. Linear regression analysis result suggested that the relevance between TCI and TP was the highest and the correlation coefficient R was 0.954. Prediction error values study also indicated that the evaluation results of TCI was highly consistent with that of TP. Moreover, TCI and DDAs were both applied to evaluate 14 batches of aconite samples oriented different origins; from the different evaluation results, we found when the proportion of HA was reached 25% in DDAs, the pharmacopeia method could generate false positive results. All these results testified the accuracy and universality of TCI method. We believe that this study method is rather accurate, simple, and easy operation and it will be of great utility in studies of other foods and herbs.

Synergistic anticancer properties of docosahexaenoic acid and 5-fluorouracil through interference with energy metabolism and cell cycle arrest in human gastric cancer cell line AGS cells.

AIM: To explore the synergistic effect of docosahexaenoic acid (DHA)/5-fluorouracil (5-FU) on the human gastric cancer cell line AGS and examine the underlying mechanism. METHODS: AGS cells were cultured and treated with a series of concentrations of DHA and 5-FU alone or in combination for 24 and 48 h. To investigate the synergistic effect of DHA and 5-FU on AGS cells, the inhibition of cell proliferation was determined by MTT assay and cell morphology. Flow cytometric analysis was also used to assess cell cycle distribution, and the expression of mitochondrial electron transfer chain complexes (METCs) I, II and V in AGS cells was further determined by Western blot analysis. RESULTS: DHA and 5-FU alone or in combination could markedly suppress the proliferation of AGS cells in a significant time and dose-dependent manner. DHA markedly strengthened the antiproliferative effect of 5-FU, decreasing the IC50 by 3.56-2.15-fold in an apparent synergy. The morphological changes of the cells were characterized by shrinkage, cell membrane blebbing and decreased adherence. Cell cycle analysis showed a shift of cells into the G0/G1 phase from the S phase following treatment with DHA or 5-FU (G0/G1 phase: 30.04% ± 1.54% vs 49.05% ± 6.41% and 63.39% ± 6.83%, respectively, P < 0.05; S phase: 56.76% ± 3.14% vs 34.75% ± 2.35% and 25.63% ± 2.21%, respectively, P < 0.05). Combination treatment of DHA and 5-FU resulted in a significantly larger shift toward the G0/G1 phase and subsequent reduction in S phase (G0/G1 phase: 69.06% ± 2.63% vs 49.05% ± 6.41% and 63.39% ± 6.83%, respectively, P < 0.05; S phase: 19.80% ± 4.30% vs 34.75% ± 2.35% and 25.63% ± 2.21%, respectively, P < 0.05). This synergy was also reflected in the significant downregulation of the expression of METCs in AGS cells. CONCLUSION: Synergistic anticancer properties of DHA and 5-FU may involve interference with energy production of AGS cells via downregulation of METCs and cell cycle arrest.

[Establishment of biological assess for quality control of Fuzi based on determination of premature ventricular contractions in rats].

Aconiti Lateralis Radix (Fuzi) is a toxic traditional Chinese medicine with definite efficacy. In order to improve the quality control of its different prepared products and ensure the security in clinic, it is significant to establish a method of quality evaluation related to clinic adverse effects. Aiming at the important biological marker of early cardiac toxicity reaction, there was no method to detect it. In this manuscript, a novel approach for measuring the minimal toxic dose (MTD) of premature ventricular contractions (PVC) poisoning of rats was established. Then, the determination methodology and conditions were optimized to meet the needs of the quality and biological assessment, including animal sex, weight, stability of standards and test solutions. Using this method, the MTD value of different Fuzi products were determined, such as Heishunpian, Baifupian, Zhengfupian, Baofupian, and Paotianxiong. The results showed that the MTD of Fuzi was significantly decreased after detoxification processed (P<0.05) and the MTD of Heishunpian, Zhengfupian, Baofupian and Baifupian was as much as 15.76, 22.36, 19.65 and 20.97 times to that of unprocessed Shengfuzi. In addition, Paotianxiong could not induce PVC in rats, which indicated that Paotianxiong was nontoxic and safe.This method could appropriately reflects the cardiotoxity of Fuzi and its prepared samples. Together with the chemical composition analysis, the contents of diester alkaloids were explored including aconitine, mesaconitine and hypaconitine as well as monoester alkaloids in Fuzi and its prepared products were significantly associated with PVC. Furthermore, there may be some components undetermined facilitating arrhythmia to be worth exploring. This research provides an overall and comprehensive approach to diagnose early clinical cardiotoxity and control the quality of Fuzi, which could not only be a complementary solution for the chemical evaluation, but a new method to ensure its efficacy and security of clinical application.