Inferring Metabolic States from Single Cell Transcriptomic Data via Geometric Deep Learning.

The ability to measure gene expression at single-cell resolution has elevated our understanding of how biological features emerge from complex and interdependent networks at molecular, cellular, and tissue scales. As technologies have evolved that complement scRNAseq measurements with things like single-cell proteomic, epigenomic, and genomic information, it becomes increasingly apparent how much biology exists as a product of multimodal regulation. Biological processes such as transcription, translation, and post-translational or epigenetic modification impose both energetic and specific molecular demands on a cell and are therefore implicitly constrained by the metabolic state of the cell. While metabolomics is crucial for defining a holistic model of any biological process, the chemical heterogeneity of the metabolome makes it particularly difficult to measure, and technologies capable of doing this at single-cell resolution are far behind other multiomics modalities. To address these challenges, we present GEFMAP (Gene Expression-based Flux Mapping and Metabolic Pathway Prediction), a method based on geometric deep learning for predicting flux through reactions in a global metabolic network using transcriptomics data, which we ultimately apply to scRNAseq. GEFMAP leverages the natural graph structure of metabolic networks to learn both a biological objective for each cell and estimate a mass-balanced relative flux rate for each reaction in each cell using novel deep learning models.

The Surfactant Role on a Droplet Passing through a Constricted Microchannel in a Pressure-Driven Flow: A Lattice Boltzmann Study.

The role of surfactants in the flow of a droplet driven by a pressure gradient through a constricted microchannel is simulated by using our recently developed lattice Boltzmann method. We first study the surfactant role on a droplet flowing through a microchannel with a shrunken square section under different surfactant concentrations and capillary numbers (i.e., imposed pressure gradients). As the surfactant concentration increases, the droplet flow regime first changes from the flow regime I of the droplet getting stuck at the entrance of the constricted channel to the flow regime II of the droplet flowing through the constricted channel with breakup, and then to the flow regime III of the droplet flowing through the constricted channel without breakup. As the capillary number increases, the surfactant role on the number of mother droplets breaking up and the time of mother droplets completely flowing through the constricted section tend to decrease, suggesting that the surfactant effects are gradually weakened. Then, a phase diagram describing how the surfactant concentration and capillary number affect the droplet flow regime is presented. As the surfactant concentration increases, the critical capillary number that distinguishes droplet flow regimes I from II gradually decreases, while the critical capillary number that distinguishes droplet flow regimes II from III first increases and then decreases.

Clinical study of the combined use of dexmedetomidine and remifentanil in patients with coronary heart disease undergoing 3D laparoscopic surgery with EEG bispectral index monitoring.

OBJECTIVE: This study sought to investigate the safety and clinical outcomes associated with the combined administration of dexmedetomidine (Dex) and remifentanil (Rem) in patients with coronary heart disease undergoing three-dimensional (3D) laparoscopic surgery, with concurrent monitoring of the electroencephalography (EEG) bispectral index. METHODS: This study is of a retrospective nature and involved a total of 60 patients with coronary heart disease who underwent 3D laparoscopic surgery at our hospital between June 2020 and September 2021. In a double-blind manner, these patients were randomly assigned to two groups: the control group (Group I), which consisted of 30 patients, and the treatment group (Group II) receiving a combination of Dex and Rem, also comprising 30 patients. The study's primary objective was to compare and assess the treatment outcomes in these two patient groups. RESULTS: Patients in Group II who developed postoperative coronary heart disease experienced a significant reduction in blood pressure, heart rate, and electrocardiogram values (P<0.05). Additionally, Group II exhibited lower bispectral index (BIS) and visual analog scale (VAS) values (P<0.05). CONCLUSION: In patients with coronary heart disease undergoing 3D laparoscopic surgery, the intraoperative use of Dex combined with Rem anesthesia offers several advantages. It helps stabilize hemodynamics, reducing the risk of myocardial ischemia, and significantly alleviates postoperative pain, all without increasing the likelihood of adverse postoperative reactions. Furthermore, this approach effectively dampens the intraoperative and postoperative stress response, facilitating enhanced recovery after surgery (ERAS). Overall, the clinical impact is positive, safe, and reliable.

Rayleigh-Plateau Instability of a Particle-Laden Liquid Column: A Lattice Boltzmann Study.

Colloidal particles known to be capable of stabilizing fluid-fluid interfaces have been widely applied in emulsion preparation, but their precise role and underlying influencing mechanism remain poorly understood. In this study, a perturbed liquid column with particles evenly distributed on its surface is investigated using a three-dimensional lattice Boltzmann method, which is built upon the color-gradient two-phase flow model but with a new capillary force model and a momentum exchange method for particle dynamics. The developed method is first validated by simulating the wetting behavior of a particle on a fluid interface and the classic Rayleigh-Plateau instability and is then used to explore the effects of particle concentration and contact angle on the capillary instability of the particle-laden liquid column. It is found that increasing the particle concentration can enhance the stability of the liquid column and thus delay the breakup, and the liquid column is most stable under slightly hydrophobic conditions, which corresponds to the lowest initial liquid-gas interfacial free energy. Due to different pressure gradients inside and outside the liquid column and the capillary force being directed away from the neck, hydrophobic particles tend to assemble in a less compact manner near the neck of the deformed liquid column, while hydrophilic particles prefer to gather far away from the neck. For hydrophobic particles, in addition to the influence of the initial liquid-gas interfacial free energy, the self-assembly of particles in a direction opposite to the liquid flow also contributes to opposing the rupture of the liquid column.

Factors affecting hemostasis in the control of iatrogenic renal hemorrhage.

PURPOSE: To investigate factors affecting hemostasis in iatrogenic renal hemorrhage. METHODS: Seventy-three patients with iatrogenic renal hemorrhage experiencing selective renal artery angiography between Jan 2015 and Dec 2020 were enrolled in this study. The clinical features, treatment modalities and outcomes were reviewed. Factors affecting hemostasis were analyzed by univariate and multivariate models using linear regression techniques. The optimum values of the independent factors to predict postangiographic hemostasis were conducted by receiver operating characteristic (ROC) curve analysis. RESULTS: Of the 73 iatrogenic renal hemorrhage patients, 47 (64.4%) patients had positive angiographic findings and received therapeutic embolization. Of the patients with negative angiographic findings, 20 (76.9%) and 6 (23.1%) received conservative therapy and prophylactic embolization, respectively. The red blood cell (RBC) count (OR = 0.61, P = 0.04), the hematuria time before angiography (OR = - 0.19, P < 0.01) and treatment modality were independent factors affecting hemostasis time. The ROC curve analysis showed that the RBC count of 3.5 × 109/L and the hematuria time before angiography of 7 days were the optimum indicators. Therapeutic embolization and prophylactic embolization were protective factors affecting hemostasis time compared with conservative treatment (OR = - 1.59, P = 0.02; OR = - 3.31, P < 0.01). CONCLUSIONS: The hematuria time before selective renal artery angiography, the RBC count, and embolization treatment are associated with rapid hemostasis. Embolization is an effective strategy for iatrogenic renal hemorrhage, and also enables rapid hemostasis in patients with negative angiographic findings.

Spatiotemporal Graph Convolutional Networks for Earthquake Source Characterization.

Accurate earthquake location and magnitude estimation play critical roles in seismology. Recent deep learning frameworks have produced encouraging results on various seismological tasks (e.g., earthquake detection, phase picking, seismic classification, and earthquake early warning). Many existing machine learning earthquake location methods utilize waveform information from a single station. However, multiple stations contain more complete information for earthquake source characterization. Inspired by recent successes in applying graph neural networks (GNNs) in graph-structured data, we develop a Spatiotemporal Graph Neural Network (STGNN) for estimating earthquake locations and magnitudes. Our graph neural network leverages geographical and waveform information from multiple stations to construct graphs automatically and dynamically by adaptive message passing based on graphs' edges. Using a recent graph neural network and a fully convolutional neural network as baselines, we apply STGNN to earthquakes recorded by the Southern California Seismic Network from 2000 to 2019 and earthquakes collected in Oklahoma from 2014 to 2015. STGNN yields more accurate earthquake locations than those obtained by the baseline models and performs comparably in terms of depth and magnitude prediction, though the ability to predict depth and magnitude remains weak for all tested models. Our work demonstrates the potential of using GNNs and multiple stations for better automatic estimation of earthquake epicenters.

A deep learning-based segmentation pipeline for profiling cellular morphodynamics using multiple types of live cell microscopy.

MOTIVATION: Quantitative studies of cellular morphodynamics rely on extracting leading-edge velocity time series based on accurate cell segmentation from live cell imaging. However, live cell imaging has numerous challenging issues regarding accurate edge localization. Fluorescence live cell imaging produces noisy and low-contrast images due to phototoxicity and photobleaching. While phase contrast microscopy is gentle to live cells, it suffers from the halo and shade-off artifacts that cannot be handled by conventional segmentation algorithms. Here, we present a deep learning-based pipeline, termed MARS-Net (Multiple-microscopy-type-based Accurate and Robust Segmentation Network), that utilizes transfer learning and data from multiple types of microscopy to localize cell edges with high accuracy, allowing quantitative profiling of cellular morphodynamics. SUMMARY: To accurately segment cell edges and quantify cellular morphodynamics from live-cell imaging data, we developed a deep learning-based pipeline termed MARS-Net (multiple-microscopy-type-based accurate and robust segmentation network). MARS-Net utilizes transfer learning and data from multiple types of microscopy to localize cell edges with high accuracy. For effective training on distinct types of live-cell microscopy, MARS-Net comprises a pretrained VGG19 encoder with U-Net decoder and dropout layers. We trained MARS-Net on movies from phase-contrast, spinning-disk confocal, and total internal reflection fluorescence microscopes. MARS-Net produced more accurate edge localization than the neural network models trained with single-microscopy-type datasets. We expect that MARS-Net can accelerate the studies of cellular morphodynamics by providing accurate pixel-level segmentation of complex live-cell datasets.

Protective action of pomegranate peel polyphenols in type 2 diabetic rats via the translocation of Nrf2 and FoxO1 regulated by the PI3K/Akt pathway.

The aim of this study is to investigate the protective mechanism of pomegranate peel polyphenols (PPPs) in in vivo and in vitro rat models of T2DM. Our results showed that PPPs markedly improved the symptoms of diabetes, such as insulin resistance, impaired insulin secretion, and pancreatic oxidative damage, which contributed to the attenuation of the symptoms of hyperglycemia in a high-fat diet (HFD) combined with streptozocin (STZ) induced type 2 diabetes mellitus in rats. On the one hand, PPPs promoted the translocation of Nrf2 from the cytoplasm to the nucleus, the key protein down-regulated by the PI3K/Akt pathway, activating its downstream phase 2 antioxidant enzyme system. On the other hand, the positive effect was associated with another downstream protein of the PI3K/Akt pathway, FoxO1. With the activation of Akt phosphorylation, the phosphorylated FoxO1 protein transferred from the nucleus to the cytoplasm, releasing the block of Pdx-1 and its downstream genes. The inhibitor of the PI3K/Akt pathway was also studied in INS-1 cells in order to verify the mechanism observed in vivo. Altogether, we presented evidence that PPPs activated the translocation of Nrf2 into the nucleus and resulted in increased antioxidant activity, and PPPs promoted the translocation of FoxO1 out of the nucleus resulting in an increase in insulin synthesis in vivo and in vitro. Pomegranate extracts may show great potential and application prospects as functional foods or preventive drugs to improve pancreatic beta cell dysfunction and provide a reference for future development in health care.

Red yeast rice prevents chronic alcohol-induced liver disease by attenuating oxidative stress and inflammatory response in mice.

Alcoholic liver disease (ALD) is characterized by dyslipidemia, hepatic steatosis, steatohepatitis, edema, necrosis, etc. Studies have reported that some dietary nutrition factors have beneficial effects in improving ALD. Red yeast rice (RYR), a traditional herbal supplement, has been confirmed to lower cholesterol mainly due to its component monacolin K. However, the effect of RYR on ALD has not been investigated. In this study, mice were supplemented with a daily oral gavage of 4 g/kg 50% ethanol for 8 weeks to induce a chronic ALD. RYR (150 mg kg-1  day-1 ) was supplied to ALD mice in treatment group. The results showed that RYR supplementation significantly attenuated hyperlipidemia, elevated circulating inflammatory cytokines, hepatic structural damage, and oxidative stress in mice supplemented with alcohol with no effects on body weight. Moreover, RYR significantly suppressed alcohol-induced hepatic NF-κB activation and apoptosis. Our results suggest that RYR is capable of preventing ALD mainly by attenuating hepatic oxidative stress and inflammatory response. PRACTICAL APPLICATIONS: RYR was known for cholesterol-lowering effect through its main component monacolin K. The current study revealed that RYR was capable of ameliorating ALD, which is characterized by profound dyslipidemia, hepatic steatosis, steatohepatitis, edema, etc. Our results indicated that the protective effect of RYR on ALD is largely achieved by regulating lipid metabolism, and closely related to the anti-inflammatory and antioxidant effects of RYR. This study provides research foundation for the development of RYR-related food or pharmaceutical products, especially targeting for ALD.

MagNet: A Neural Network for Directed Graphs.

The prevalence of graph-based data has spurred the rapid development of graph neural networks (GNNs) and related machine learning algorithms. Yet, despite the many datasets naturally modeled as directed graphs, including citation, website, and traffic networks, the vast majority of this research focuses on undirected graphs. In this paper, we propose MagNet, a GNN for directed graphs based on a complex Hermitian matrix known as the magnetic Laplacian. This matrix encodes undirected geometric structure in the magnitude of its entries and directional information in their phase. A "charge" parameter attunes spectral information to variation among directed cycles. We apply our network to a variety of directed graph node classification and link prediction tasks showing that MagNet performs well on all tasks and that its performance exceeds all other methods on a majority of such tasks. The underlying principles of MagNet are such that it can be adapted to other GNN architectures.

Pomegranate peel polyphenols reduce chronic low-grade inflammatory responses by modulating gut microbiota and decreasing colonic tissue damage in rats fed a high-fat diet.

Recent studies have found that a high-fat diet (HFD) causes gut microbiota imbalance and colon tissue damage, resulting in increased intestinal permeability, which is one of the main reasons for the existence of constantly circulating low-grade inflammatory cytokines. Pomegranate extracts have been shown to protect from HFD-induced metabolic inflammation (e.g., colitis) and to promote the growth of beneficial bacteria in in vitro stool cultures. However, whether the beneficial effects of pomegranate extracts on the HFD-induced metabolic inflammation are achieved by acting on intestinal tissues has not yet been studied. In our present study, we found that pomegranate peel polyphenols (PPPs) alleviated HFD-induced obesity, elevated circulating pro-inflammatory cytokines, colonic tissue damage, and depressed colonic tight junction protein expression level in rats. Moreover, PPPs normalized the HFD-induced gut microbiota imbalance by increasing the abundance of beneficial bacteria in the colon. Furthermore, we also found that PPPs, punicalagin, and urolithin A (the main microbiota metabolites of pomegranate ellagitannins) all increased the LPS-induced decreased tight junction protein expression level and reversed the LPS-induced inflammatory response in Caco-2 cells. Urolithin A exhibited the best effects among the three pomegranate components. Our results suggested that the protective effects of PPPs in HFD-induced metabolic inflammation can be due to the recovery of colonic tissue damage and the regulation of gut microbiota and that urolithin A is the major component that contributes to the in vivo effects of PPPs.

Pomegranate peel polyphenols inhibits inflammation in LPS-induced RAW264.7 macrophages via the suppression of TLR4/NF-κB pathway activation.

BACKGROUNDS: Inflammatory response mediated by activated immune cells is a vital process in host defense system while responding to various stresses. Our previous studies have indicated that pomegranate peel polyphenols (PPPs) and their main components punicalagin (PC) and ellagic acid (EA) decreased pro-inflammatory cytokines and inflammatory mediators by regulating the mitogen-activated protein kinases (MAPKs) pathway, but whether these tested polyphenols play an important role in NF-κB signaling pathway, another crucial pathway of inflammation, remains unclear. OBJECTIVE: In this study, we analyzed the anti-inflammatory effect of these polyphenols via TLR4-NF-κB pathway in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. METHODS: Different concentrations of PPPs, PC, and EA were pre-incubated with RAW264.7 macrophages and then stimulated with LPS (1 µg/mL), and the effects of reactive oxygen species and TLR4 were investigated. Moreover, NF-κB p65 nuclear translocation and phosphorylation, and degradation of IκB were measured by Western blot. Furthermore, the influence of pro-inflammatory cytokines was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Our data showed that PPPs, PC, and EA inhibited LPS-induced intracellular ROS production and suppressed the mRNA and protein expression levels of TLR4 in a dose-dependent manner. Moreover, the anti-inflammatory mechanism was involved in blocking LPS-induced phosphorylation, degradation of IκB, and nuclear translocation of p65. Additionally, PPPs and PC exhibited a stronger anti-inflammatory effect than that of EA. CONCLUSION: The results indicated that PPPs possess potent anti-inflammatory effect, and PC was the main effective component in PPPs, which provided new insights into the utilization of PPPs to prevent inflammation-associated disorders.

Investigation of the eddy current effect on the high frequency response of the Mirnov probe on J-TEXT.

This paper investigates the high frequency response of the Mirnov probe based on a test platform, which is capable of generating a uniform AC magnetic field within the frequency range of 1-300 kHz. The eddy current effect is quantitatively reflected by the phase shift ϕc and normalized amplitude δ of the measured magnetic field between cases with and without a conducting plate located near the Mirnov probe. This method compensates the resonant effect in the Mirnov probe circuit and hence reflects purely the eddy current effect. The eddy current effect increases with the decrease in the distance between the probe and the conducting plate. With the increase in frequency, the magnitude of δ decreases to a saturated value at 10 kHz but increases significantly above 100 kHz for 304-stainless steel, while the eddy current effect with graphite appears at around 10 kHz and the magnitude of δ decreases to the minimum at 125 kHz, followed by a significant increase above 125 kHz. With the increase in f, the magnitude of ϕc increased until 2.5 kHz and 40 kHz for steel and graphite, respectively, then decreased with a further increase in f. The phasor expression is introduced to describe the AC magnetic field and allows an easy expression of the eddy current field. The phase of the eddy current field decreases toward -180° with f. The amplitude of the eddy current field increases with f and reaches its maximum when the skin depth reduces to a critical value. The eddy current field decreases with a further increase in the frequency.

Formulation development and evaluation of gastroretentive floating beads with Brucea javanica oil using ionotropic gelation technology.

In the present study, a gastric retention floating system for Brucea javanica oil, composed of alginate and carrageenan, was prepared using ionotropic gelation. Parameters for floatability, drug load, encapsulation efficiency, bead morphology, in vitro release, and in vivo gastric retention were evaluated. The optimized formulation via Box-Behnken design consisted of 1.7% alginate (W/V), 1.02% carrageenan (W/V), 1.4% CaCO3 (W/V), and a gelling bath of pH 0.8. The alginate-carrageenan-Brucea javanica oil beads had a porous structure and exhibited up to 24 h of in vitro floatability with a load capacity of 45%-55% and an encapsulation efficiency of 70%-80%. A 6-h sustained release was observed in vitro. The beads had a prolonged gastric retention (> 60% at 6 h) in fasted rats, compared to non-floating beads (15% at 6 h), as measured by gamma scintigraphy with single-photon emission tomography/computed tomography (SPET/CT). In conclusion, the alginate-carrageenan-Brucea javanica oil system showed enhanced oil encapsulation efficiency, excellent floating and gastric retention abilities, and a favorable release behavior.

Enhanced gastric therapeutic effects of Brucea javanica oil and its gastroretentive drug delivery system compared to commercial products in pharmacokinetics study.

BACKGROUND: Brucea javanica oil (BJO), a traditional Chinese herbal medicine, has a variety of pharmacological activities and several BJO-related patent drugs have been widely used in China. PURPOSE: The objective of this study was to evaluate the gastric therapeutic effects of self-made BJO and its pharmaceutical potential to formulate novel BJO gastroretentive floating bead by comparing with commercial products. METHODS: BJO was extracted from the seeds of B. javanica, and its therapeutic effects were evaluated by comparing with commercial products in the treatment of human gastric cancer and gastric ulcer. Furthermore, the developed gastroretentive drug delivery system was evaluated by in vivo tests. A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for detecting the concentration of glycerol trioleate in the pharma-cokinetic study was applied. RESULTS: The antitumor activity of BJO was stronger than that of the marketed preparation; the 50% inhibitory concentration (IC50) values of BJO extracts on HGC27, SGC7901 and BGC823 gastric carcinoma were 0.3091, 1.736 and 2.743 µg/mL, respectively, whereas the values of marked BJO preparation were 15.26, 32.60 and 7.456 µg/mL, respectively. Histopathological studies demonstrated the ability of BJO to locally prevent and treat absolute ethanol-induced gastric ulcer. Developed BJO gastroretentive floating bead showed a satisfactory in vivo study. The highest glycerol trioleate concentration in the stomach after taking BJO gastroretentive floating bead was nearly two times higher when compared to the marketed BJO soft capsule. CONCLUSION: Self-made BJO has a strong therapeutic effect on the stomach, and gastroretentive drug delivery system can be a promising approach to prolong and enhance its therapy ability when treating gastric diseases.

Transplant renal artery stenosis caused by the stretch of an artey branch: a case report and literature review.

BACKGROUND: Renal transplant is the preferred treatment option for these patients with end-stage renal disease. Transplant renal artery stenosis (TRAS) is one of the most common and serious vascular complications after renal transplantation, and most of the TRAS occurred in the anastomosis. The complication must be diagnosed and treated timely, otherwise the function of transplanted kidney may be losed. CASE PRESENTATION: A 46-year-old male with end-stage renal disease of unknown cause received a cadaveric renal transplant one year ago. Although three antihypertensive medications were administrated, his blood pressure gradually increased to 190/120 mmHg 3 weeks posttransplantation. Also the level of creatinine increased to 194 µmol/L.Color Doppler ultrasonography indicated a decreased resistance index (RI) in intrarenal arteries and increased blood flow of the transplant renal artery, therefore, a vascular complication of TRAS was suspected. Arteriography was performed and demonstrated TRAS caused by stretch of an artery branch, and the TRAS occurred in the distal site of the anastomosis instead of the anastomosis. Percutaneous transluminal bare stent implantation treatment was successfully performed. Satisfactory clinical efficacy with improvement in transplant renal function and renovascular hypertension was achieved after the interventional treatment. CONCLUSION: To our knowledge this is the first reported case of TRAS caused by stretch of an artery branch. When refractory hypertension and allograft dysfunction are presented posttransplantation, TRAS should be suspected. Color Doppler ultrasonography as a non-invasive examination may provide some valuable information, three-dimention CT can be useful for further diagnosis, but is seldom necessary. Arteriography provides the definitive diagnosis of TRAS. Percutaneous transluminal stent implantation treatment of TRAS has high success rate with minimal invasion and complications. When an artery branch situated on the stenosis, a bare stent rather than covered stent is the preferred choice.

Budd-Chiari syndrome in China: A 30-year retrospective study on survival from a single center.

AIM: To investigate 30-year treatment outcomes associated with Budd-Chiari syndrome (BCS) at a tertiary hospital in China. METHODS: A total of 256 patients diagnosed with primary BCS at our tertiary hospital between November 1983 and September 2013 were followed and retrospectively studied. Cumulative survival rates and cumulative mortality rates of major causes were calculated by Kaplan-Meier analysis, and the independent predictors of survival were identified using a Cox regression model. RESULTS: Thirty-four patients were untreated; however, 222 patients were treated by medicine, surgery, or interventional radiology. Forty-four patients were lost to follow-up; however, 212 patients were followed, 67 of whom died. The symptom remission rates of treated and untreated patients were 81.1% (107/132) and 46.2% (6/13), respectively (P = 0.009). The cumulative 1-, 5-, 10-, 20-, and 30-year survival rates of the treated patients were 93.5%, 81.6%, 75.2%, 64.7%, and 58.2%, respectively; however, the 1-, 5-, 10-, 20-, and 30-year survival rates of the untreated patients were 70.8%, 70.8%, 53.1%, 0%, and unavailable, respectively (P = 0.007). Independent predictors of survival for treated patients were gastroesophageal variceal bleeding (HR = 3.043, 95%CI: 1.363-6.791, P = 0.007) and restenosis (HR = 4.610, 95%CI: 1.916-11.091, P = 0.001). The cumulative 1-, 5-, 10-, 20-, and 30-year mortality rates for hepatocellular carcinoma were 0%, 2.6%, 3.5%, 8%, and 17.4%, respectively. CONCLUSION: Long-term survival is satisfactory for treated Chinese patients with BCS. Hepatocellular carcinoma is a chronic complication and should be monitored with long-term follow-up.

[Development and inheritance of ZHENG's acupuncture school].

ZHENG's acupuncture school in Gansu,represented by ZHENG Yulin and ZHENG Kuishan,is of great influence in China. ZHENG's acupuncture school originated from Huangdi Neijing(Inner Canon of Yellow Emperor) and Nanjing(Classic of Questioning),and shaped around Yuan Dynasty and Ming Dynasty. Professor ZHENG Kuishan has formed a unique "ZHENG's acupuncture" diagnosis and treatment system by inheritance and innovation. He clinically paid attention to basic training,obtaining qi and keeping spirit,as well as syndrome differentiation,reinforcing and reducing. Also,he took the priority the pressing hand with bilaterally needle manipulation. Besides,he thought important simplicity,innovation and acupoints selecting according to time. We inherited ZHENG's acupuncture from his family,teachers'techniques,international communication,college and university education and scientific research. In this article we prescribe the development,the inheritance and the protection measures of ZHENG's acupuncture school in terms of its origination,academic thought,and inheritance research,etc.,so as to provide references for further study and inheritance.

Optimization of Ultrasonic-assisted Extraction of Fatty Acids in Seeds of Brucea Javanica (L.) Merr. from Different Sources and Simultaneous Analysis Using High-Performance Liquid Chromatography with Charged Aerosol Detection.

Our research aimed to optimize the oil extraction process and determine the fatty acids in Brucea javanica (L.) Merr. seeds. The extraction technology was optimized using response surface methodology. A Box-Behnken design was employed to investigate the effects of three independent variables on an ultrasonic-assisted extraction technique, namely, sonication time (X1: 20-40 min), liquid-solid ratio (X2: 16:1 mL/g-24:1 mL/g), and ethanol concentration (X3: 90%-100%). The optimum conditions of sonication time, liquid-solid ratio, and ethanol concentration were 40 min, 24:1 mL/g, and 100%, respectively. The content of fatty acids and the oil yield were 14.64 mg/g and 16.87%, respectively, which match well with the predicted models. The optimum number of extraction times was eventually identified as two. A new rapid method for the qualitative and quantitative analysis of the fatty acids of B. javanica (L.) Merr. seed oil using HPLC with a charged aerosol detector was described. The fatty acid contents of 14 batches of B. javanica (L.) Merr. seed oil were determined, and the relevance and difference were analyzed by fingerprint analysis. The fingerprint has five common peaks, and the similarity was greater than 0.991. HPLC analysis represents a specialized and rational approach for the quality identification and comprehensive evaluation of B. javanica (L.) Merr. seed oils.

Formulation Optimization of Gastro-Retention Tablets of Paeonol and Efficacy in Treatment of Experimental Gastric Ulcer.

This study aims to develop a gastroretentive sustained-release drug delivery system of paeonol using floating properties and to investigate its therapeutic effects in rat models. The gastric retention tablets of paeonol (GRT-Ps) were prepared by a direct compression method, and the Box-Behnken design was used to optimize its formulation. The optimized formulation containing 15% NaHCO3 and a 2 : 1 ratio of paeonol and HPMC-K4M floated within 1 min and remained afloat for more than 8 h in the simulated gastric fluid (200 mL, pH=1.2) and simultaneously showed the desired sustained drug release. Moreover, small tablets (3 mm) were prepared according to the same formulation and the process technology of big tablets (8 mm). A similar drug release behavior was observed between two kinds of tablets (f2=52), and then the evaluations of efficacy and retention capacity in vivo were conducted with small tablets. In vivo retention studies showed that the Tmax (2 h) of GRT-P in rat stomachs was significantly extended compared with the Tmax (0.5 h) of normal reference preparation. Compared with the model group, low and high doses of GRT-P could significantly inhibit the increase of malondialdehyde (MDA) in serum. Studies showed that the higher MDA content in inflammation tissue increases the inflammatory response. The ulcer inhibition rates of GRT-P in the high-dose group were 59.0 and 64.1% in the ranitidine group. Results indicated that GRT-Ps had the potential for a sustained drug release and an enhanced gastric residence time with relatively high drug concentrations in the tissue distribution.