PBPK-PD model for predicting morphine pharmacokinetics, CNS effects and naloxone antagonism in humans.

Morphine and morphine-6-glucuronide (M6G) produce central nervous system (CNS) effects by activating mu-opioid receptors, while naloxone is used mainly for the reversal of opioid overdose, specifically for the fatal complication of respiratory depression, but also for alleviating opioid-induced side effects. In this study we developed a physiologically-based pharmacokinetic-pharmacodynamic (PBPK-PD) model to simultaneously predict pharmacokinetics and CNS effects (miosis, respiratory depression and analgesia) of morphine as well as antagonistic effects of naloxone against morphine. The pharmacokinetic and pharmacodynamic parameters were obtained from in vitro data, in silico, or animals. Pharmacokinetic and pharmacodynamic simulations were conducted using 39 and 36 clinical reports, respectively. The pharmacokinetics of morphine and M6G following oral or intravenous administration were simulated, and the PBPK-PD model was validated using clinical observations. The Emax model correlated CNS effects with free concentrations of morphine and M6G in brain parenchyma. The predicted CNS effects were compared with observations. Most clinical observations fell within the 5th-95th percentiles of simulations based on 1000 virtual individuals. Most of the simulated area under the concentration-time curve or peak concentrations also fell within 0.5-2-fold of observations. The contribution of morphine to CNS effects following intravenous or oral administration was larger than that of M6G. Pharmacokinetics and antagonistic effects of naloxone on CNS effects were also successfully predicted using the developed PBPK-PD model. In conclusion, the pharmacokinetics and pharmacodynamics of morphine and M6G, antagonistic effects of naloxone against morphine-induced CNS effects may be successfully predicted using the developed PBPK-PD model based on the parameters derived from in vitro, in silico, or animal studies.

Insights into aggregation dynamics of NACore peptides from coarse-grained simulations.

Alpha(α)-synuclein is closely related to the pathogenesis of Parkinson's disease (PD). The NACore, a fragment of α-synuclein, is considered to be the key region of α-synuclein that causes PD. The aggregation dynamics of NACores are studied via coarse-grained molecular dynamics simulations. We find that NACores can self-assemble into a large cluster at high concentrations. The aggregation dynamics can be divided into three stages. The growth kinetics for the first and second stages follows the power law, Smax ~ tγ , with the second stage faster than the first one. The characteristic lifetime for the high concentration is 40 times larger than that for the low concentration, implying the low fluidity. Understanding the aggregation dynamics of NACores is helpful to develop drugs for therapeutic prevention and intervention.

Heme oxygenase-1 therapy attenuates muscle atrophy following global brachial plexus avulsion in juvenile rats.

INTRODUCTION/AIMS: Brachial plexus injury can seriously affect distal target muscle function, and long-term denervation leads to irreversible structural damage. In the present study, we examined the effect of hemin, a heme oxygenase-1 (HO-1) inducer, on intrinsic forepaw muscle atrophy induced by pan-plexus injury in juvenile rats, as well as its underlying mechanism. METHODS: A global brachial plexus avulsion (GBPA) model of rat was established, and thirty 6-wk-old male rats were randomly divided into five groups: control, GBPA plus scramble small intering RNA (siRNA), GBPA plus scramble siRNA plus hemin, GBPA plus HO-1 siRNA, and GBPA plus HO-1 siRNA plus hemin. Hemin (50 mg/kg) was administered intraperitoneally once daily and the siRNA (5 µg) was injected intramuscularly twice a week. Intrinsic forepaw muscles were used for analysis. Myofiber cross-sectional area (CSA), capillary-to-fiber ratio (C/F), and fiber-type composition were assessed. The levels of inflammatory factors, ubiquitin-protein ligases, and autophagy-related proteins were also measured. RESULTS: We found that hemin treatment could effectively ameliorate denervated intrinsic forepaw muscle atrophy and suppress type I to II myofiber-type conversion. Hemin treatment failed to prevent muscle capillary loss after denervation. The levels of inflammatory factors (tumor necrosis factor alpha [TNFα] and interleukin 6 [IL-6]), ubiquitin-protein ligases (MuRF-1 and MAFbx), and autophagy-related proteins (BNIP3 and LC3B-II/I ratio) were increased by denervation and HO-1 therapy attenuated the increment. DISCUSSION: Upregulation of HO-1 might potentially be an effective strategy to alleviate denervation-related muscle atrophy and might be a promising adjunctive treatment to improve hand function in children with pan-plexus injury.

Three-dimensional reconstruction of mobile binocular stereo vision based on push-broom line structured light for a workpiece surface.

Stereo vision technology based on line structured light can effectively solve the problem of a three-dimensional (3D) reconstruction of a smooth surface. A method for 3D reconstruction of mobile binocular stereo vision based on push-broom line structured light for a workpiece surface is presented in this paper. The subpixel coordinates of the light strip centers of the line structured light are obtained by the Steger algorithm while the binocular module moves along the guide rail, and the polar constraint is used to achieve the matching of the extracted light strip centers. As a result, the 3D coordinates of the light strip centers in each location can be calculated because of the known interior and external parameters of the binocular module. To obtain the 3D point cloud data of the entire surface, a relative pose optimization method with respect to the initial frame is proposed, which accurately estimates the pose of the cameras in each location with respect to that in the initial location and unifies the 3D coordinates of the light strip centers in each location to the datum coordinates. The relative pose optimization method first estimates the rough values by using the direct linear transform method, and then iteratively calculates the refined solutions based on the principle of minimizing the re-projection errors. Simulation data and substantial experimental results validate the effectiveness of our method. Our method is compared to the direct linear transform method and the frame-by-frame transfer method, and the root mean square error (RMSE) of the distance from 3D point cloud to fitted plane is used to evaluate the 3D reconstruction accuracy. The repeatability experiment shows that the RMSE from our method is as low as 0.83 mm.

Lipid-Related Domestication Accounts for the Extreme Cold Sensitivity of Semiwild and Tropic Xishuangbanna Cucumber (Cucumis sativus L. var. xishuangbannanesis).

Xishuangbanna (XIS) cucumber (Cucumis sativus L. var. xishuangbannanesis) is a semiwild variety originating from low latitude tropic areas, and therefore shows extreme cold sensitivity and heat tolerance. Here, we mapped the quantitative trait loci (QTLs) that control the cold sensitivity and heat tolerance of XIS cucumber seedlings. Using bulked segregant analysis (BSA), we identified three QTLs (HTT1.1, HTT3.1, and HTT3.2, with a total length of 11.98 Mb) for heat tolerance and two QTLs (LTT6.1 and LTT6.2, with a total length of 8.74 Mb) for cold sensitivity. The QTL LTT6.1 was then narrowed down to a length of 641 kb by using kompetitive allele-specific PCR (KASP) markers. Based on structural variants (SVs) and single-nucleotide polymorphisms (SNPs), we found the LTT6.1 is covered by a high divergent region including a 50 kb deletion in the XIS49 genome, which affects the gene structure of lipase abhydrolase domain containing 6 (ABHD6, Csa_6G032560). Accordingly, there is a very big difference in lipid composition, but not in other osmoprotectants like free amino acids and fatty acids, between XIS49 and cultivated cucumber CL. Moreover, we calculated the composite likelihood ratio (CLR) and identified selective sweeps from 115 resequencing data, and found that lipid- and fatty-acid-related processes are major aspects in the domestication of the XIS group cucumber. LTT6.1 is a particularly special region positioned nearby lipid-related selective sweeps. These studies above suggested that the lipid-related domestication of XIS cucumbers should account for their extreme cold sensitivity.

The mechanism and effects of remdesivir-induced developmental toxicity in zebrafish: Blood flow dysfunction and behavioral alterations.

The antiviral drug remdesivir has been used to treat the growing number of coronavirus disease 2019 (COVID-19) patients. However, the drug is mainly excreted through urine and feces and introduced into the environment to affect non-target organisms, including fish, which has raised concerns about potential ecotoxicological effects on aquatic organisms. Moreover, studies on the ecological impacts of remdesivir on aquatic environments have not been reported. Here, we aimed to explore the toxicological impacts of microinjection of remdesivir on zebrafish early embryonic development and larvae and the associated mechanism. We found that 100 µM remdesivir delayed epiboly and impaired convergent movement of embryos during gastrulation, and dose-dependent increases in mortality and malformation were observed in remdesivir-treated embryos. Moreover, 10-100 µM remdesivir decreased blood flow and swimming velocity and altered the behavior of larvae. In terms of molecular mechanisms, 80 differentially expressed genes (DEGs) were identified by transcriptome analysis in the remdesivir-treated group. Some of these DEGs, such as manf, kif3a, hnf1ba, rgn, prkcz, egr1, fosab, nr4a1, and ptgs2b, were mainly involved in early embryonic development, neuronal developmental disorders, vascular disease and the blood flow pathway. These data reveal that remdesivir can impair early embryonic development, blood flow and behavior of zebrafish embryos/larvae, probably due to alterations at the transcriptome level. This study suggests that it is important to avoid the discharge of remdesivir to aquatic ecosystems and provides a theoretical foundation to hinder remdesivir-induced ecotoxicity to aquatic environments.

Abnormalities of the Halogen Bonds in the Complexes between Y2CTe (Y = H, F, CH3) and XF (X = F, Cl, Br, I).

In this work, the hydrogen bonds and halogen bonds in the complexes between Y2CTe (Y = H, F, CH3) and XF (X = F, Cl, Br, I) have been studied by quantum chemical calculations. We found three interesting abnormalities regarding the interactions. Firstly, the strength of halogen bonds increases in the order of IF < BrF < ClF < F2. Secondly, the halogen bonds formed by F2 are very strong, with an interaction energy in the range between −199.8 and −233.1 kJ/mol. Thirdly, all the halogen bonds are stronger than the hydrogen bonds in the systems we examined. All these results are against the general understanding of halogen bonds. These apparent abnormal properties are reconciled with the high polarizability of the Te atom and the strong inducing effect of F on the Te atom of Y2CTe. These findings provide a new perspective on halogen bonds. Additionally, we also proposed bonding distance-based methods to compare the strength of halogen/hydrogen bonds formed between different donor atoms and the same acceptor atom.

Pretreatment with Methylene Blue Protects Against Acute Seizure and Oxidative Stress in a Kainic Acid-Induced Status Epilepticus Model.

BACKGROUND The aim of the present study was to investigate the potential anticonvulsant effect of methylene blue (MB) in a kainic acid (KA)-induced status epilepticus (SE) model. The effects of MB on levels of oxidative stress and glutamate (Glu) also were explored. MATERIAL AND METHODS Sixty C57BL/6 mice were randomly divided into 5 equal-sized groups: (1) controls; (2) KA; (3) MB 0.5 mg/kg+KA; (4) MB 1 mg/kg+KA; and (5) vehicle+KA. The SE model was established by intra-amygdala microinjection of KA. Behavioral observations and simultaneous electroencephalographic records of the seizures in different groups were analyzed to determine the potential anticonvulsant effect of MB. The influences of MB on oxidative stress markers and glutamate were also detected to explore the possible mechanism. RESULTS MB afforded clear protection against KA-induced acute seizure, as measured by the delayed latency of onset of generalized seizures and SE, decreased percentage of SE, and increased survival rate in mice with acute epilepsy. MB markedly increased the latency to first onset of epileptiform activity and decreased the average duration of epileptiform events, as well as the percentage of time during which the epileptiform activity occurred. Administration of MB prevented KA-induced deterioration of oxidative stress markers and Glu. CONCLUSIONS MB is protective against acute seizure in SE. This beneficial effect may be at least partially related to its potent antioxidant ability and influence on Glu level.

Potential of thrombospondin-1 in treatment of polycystic ovary syndrome rat model: a preliminary study.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disease in reproductive women, and the endocrine levels are also affected by diseases. The aim of this study was to determine the effect of thrombospondin-1 (TSP-1) on PCOS rat model. METHODS: We established the PCOS rat model, the serum hormones including TSP-1 expression were determined and morphological characteristics were investigated to evaluate the model. These above endocrine and morphological features were investigated again to evaluate the effect of TSP-1 treatment. RESULTS: In the PCOS model group, the serum hormones change (higher luteinizing hormone, testosterone and estrogen) and decreased TSP-1 expression levels were found compared with the control group. Besides, the morphological characteristics of PCOS were also observed in the model group. After TSP-1 treatment, the higher TSP-1, ANGPT2, PDGFB and PDGFD expression levels, the lower LH and T levels, decreased vessel density as well as VEGFA and ANGPT1 expression levels were found compared with the control group, and the ovary morphological changes were also observed in the TSP-1 experimental group. CONCLUSIONS: TSP-1 delivery system might be an alternative therapy for PCOS treatment.

Production of butanol from distillers' grain waste by a new aerotolerant strain of Clostridium beijerinckii LY-5.

A new aerotolerant strain of Clostridium beijerinckii LY-5 was isolated from the pit mud of the Chinese Baijiu-making process for butanol production. Plackett-Burman design and artificial neural network were used to optimize the fermentation medium and a total of 13.54 ± 0.22 g/L butanol and 19.91 ± 0.52 g/L ABE were attained under aerotolerant condition. Moreover, distillers' grain waste (DGW), the main by-product in the Baijiu production process, was utilized as potential substrate for butanol production. DGW was hydrolyzed by α-amylase and glucoamylase and then fermented after a detoxifying process of overliming. Butanol and ABE concentrations were 9.02 ± 0.18 and 9.57 ± 0.19 g/L with the yield of 0.21 and 0.23 g/g sugar, respectively. The higher ratio of butanol to ABE might be caused by the inhibitors in DGW medium affecting the metabolic pathways of C. beijerinckii LY-5 and approximately 1.48 ± 0.04 g/L isopropanol was found at the end of fermentation. This work highlights the feasibility of using DGW as a promising feedstock for butanol production by a new aerotolerant strain of C. beijerinckii LY-5, with benefit to the environment.

[Review of chemical constituents,pharmacological effects and clinical applications of Danggui Buxue Decoction and prediction and analysis of its Q-markers].

Danggui Buxue Decoction is a classic prescription of Qi and blood tonification, which is mainly applied in treating fatigue, internal damage Qi weakness, blood deficiency, and outward going of floating Yang. Modern pharmacology shows that it can promote hematopoiesis, regulate immunity, and protect heart and cerebral vessels. The prescription, often used for the treatment of anemia and other diseases in clinic, is composed of Astragali Radix and Angelicae Sinensis Radix at a dosage ratio of 5∶1. It is a modern compound prescription for invigorating Qi and generating blood. Based on the review of the chemical constituents, pharmacological effects, and clinical applications of Danggui Buxue Decoction, its Q-marker was predicted and analyzed according to the "five principles" of Chinese medicine Q-marker--quality transmissibility and traceability, ingredient specificity, component validity, component measurabi-lity, and formula compatibility environment. The results suggested that calycosin, calycosin-7-O-ß-D-glucoside, formononetin, ononin, astragaloside A, ferulic acid, and ligustilide could be used as Q-markers of Danggui Buxue Decoction, which provides reference for establishing the quality system of Danggui Buxue Decoction.

Evaluation of Ovarian Tumors with Multidetector Computed Tomography and Tumor Markers: Differentiation of Stage I Serous Borderline Tumors and Stage I Serous Malignant Tumors Presenting as Solid-Cystic Mass.

BACKGROUND The aim of this study was to determine multidetector computed tomography (MDCT) features and tumor markers for differentiating stage I serous borderline ovarian tumors (SBOTs) from stage I serous malignant ovarian tumors (SMOTs). MATERIAL AND METHODS In total, 48 patients with stage I SBOTs and 54 patients with stage I SMOTs who underwent MDCT and tumor markers analysis were analyzed. MDCT features included location, shape, margins, texture, papillary projections, vascular abnormalities, size, and attenuation value. Tumor markers included serum cancer antigen 125 (CA125), carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and human epididymis protein 4 (HE4). Parameters of clinical characteristic, MDCT features, and tumor markers were compared using a chi-square test and Mann-Whitney U tests. A binary logistic regression analysis was performed to detect predictors for SMOTs. A receiver operating characteristic (ROC) curve analysis was used to assess the potential diagnostic value of the quantitative parameters. Kappa and intraclass correlation coefficients were used to evaluate interobserver reproducibility for MDCT features. RESULTS Median ages between patients with SBOTs and SMOTs were significantly different. Compared with SBOTs, vascular abnormalities were significantly more common in SMOTs. CA125, HE4, the maximum thickness of the wall, the maximum thickness of the septa, and the maximum diameter of the solid portions were significantly higher in patients with SMOTs. A binary logistic regression analysis revealed that age, vascular abnormalities, and the maximum diameter of the solid portion were independent factors of SMOTs. ROC analysis was used to assess the potential diagnostic value for predicting SMOTs. Moderate or good interobserver reproducibility for MDCT features were identified. CONCLUSIONS Age, vascular abnormalities, and the maximum diameter of the solid portion were independent factors for differentiating SBOTs from SMOTs. The combined analysis of age, vascular abnormalities, and the maximum diameter of the solid portion may allow better differentiation between SBOTs and SMOTs.

[Review of chemical constituents, pharmacological effects and clinical applications of Suanzaoren Decoction and prediction and analysis of its Q-markers].

Suanzaoren Decoction is a classic prescription for nourishing the heart and liver, nourishing blood and tranquilizing the mind. It has the functions of sedation and hypnosis, anti-anxiety, anti-depression, anti-convulsion and so on. Modern clinic is mostly used to treat different types of insomnia, depression, neurasthenia, tension headache and vertigo. In this paper, the chemical consti-tuents, pharmacological effects and clinical application of Suanzaoren Decoction are reviewed. Based on this, the quality marker(Q-marker) of Suanzaoren Decoction was predicted and analyzed according to the "five principles" of Q-marker of traditional Chinese medicine--transmission and traceability, specificity, effectiveness, measurability and compatibility environment of compound prescriptions. The results indicated that jujuboside, spinosin, ferulic acid, senkyunolide Ⅰ, sarsasapogenin, mangiferin, liquiritoside and glycyrrhizic acid were predicted and analyzed, and those can be used as Q-markers of Suanzaoren Decoction. Subsequently, the above components can be selected as indicators to control and evaluate the quality of Suanzaoren Decoction and its preparations, and establish a quality traceability system.

Synthesis and antitumor activity of biotinylated camptothecin derivatives as potent cytotoxic agents.

A series of biotinylated camptothecin derivatives were designed and synthesized. The key to the synthesis was achieved by employing an esterification reaction and click chemistry. All of the new derivatives were tested for cytotoxicity against five human tumor cell lines, including HL-60, SMMC-7721, A-549, MCF-7, and SW480 with IC50 values ranging from 0.13 to 21.53 µM. Most of the derivatives exhibited potent cytotoxicity, especially compound 17 (IC50 = 0.13-3.31 µM) and compound 18 (IC50 = 0.23-1.48 µM), which exhibited the highest potencies. The structure-activity relationships (SARs) of the biotinylated camptothecin derivatives were discussed for exploring novel anticancer agents.

3α,19-Dihydroxyl-ent-pimara-8(14),15-diene, a new diterpenoid from the rhizomes of Ricinus communis.

A new natural product, 3α,19-dihydroxyl-ent-pimara-8(14),15-diene (1), which possesses an α-orientation hydroxymethyl at C-4 and ∆8,14 groups, as well as eight known compounds, was isolated from the rhizomes of Ricinus communis. The structure of 1 was elucidated by extensive spectroscopic methods and its absolute configurations were confirmed by X-ray crystallographic analysis. The inhibitory rate of 1 against protein tyrosine phosphatase 1B (PTP1B) was 49.49% at the concentration of 6.58 × 10-5 mol/L.

Selection of cuffed endotracheal tube for children with congenital heart disease based on an ultrasound-based linear regression formula.

It remains to be discovered whether a formula predicting the subglottic transverse diameter measured by ultrasound (SGDformula) for the selection of an appropriate endotracheal tube (ETT) for children without congenital heart disease (CHD) is useful for children with CHD. A formula for predicting SGD was established after assessing 60 children ≤ 8 years without CHD and validated on 60 children with CHD. We selected the cuffed ETT size based on the SGD by ultrasound (SGDultra). Subsequently, the fit of the ETT cuff in 60 children with CHD was examined via air-leak test. The maximum allowed difference between the SGDformula and the ETT size that fit was 0.2 mm. The agreement among and accuracy of SGDultra, SGDformula, and the ETT used in children was analyzed. For children without CHD, we adopted a linear formula, given by SGDformula (mm) = 0.4 × age + 5.3. For children with CHD, allometric formula was adopted, given by SGDformula (mm) = 5.4 × age0.18. A stronger agreement exists between SGDultra and ETT size compared to that between SGDformula and ETT size. And the mean bias (SGDformula-ETT size and SGDultra-ETT size) was 0.21 mm (95% confidence interval, - 0.59 to 1.01 mm) and 0.00 mm (- 0.79 to 0.84 mm). For the CHD group, the ultrasound-based method yielded a 78% success rate of ETT size choice, while the formula-based method permitted an appropriate ETT size in only 32% of subjects (P < 0.001). Our analysis showed that measuring the SGDultra was more accurate in predicting the correct OD of the ETT in children with CHD undergoing cardiovascular surgery, based on the correlation and agreement with ETT OD.

Full recycling of citric acid wastewater through anaerobic digestion, air-stripping and pH control.

Anaerobic digestion effluent (ADE) from the anaerobic digestion treatment of citric acid wastewater can be reused as a potential substitute for process water in the citric acid fermentation. However, excessive sodium contained in ADE significantly decreases citric acid production. In this paper, the inhibition mechanism of sodium on citric acid fermentation was investigated. We demonstrated that excessive sodium did not increase oxidative stress for Aspergillus niger, but reduced the pH of the medium significantly over the period 4-24 h, which led to lower activities of glucoamylase and isomaltase secreted by A. niger, with a decrease of available sugar concentration and citric acid production. ADE was pretreated by air-stripping prior to recycle and 18 g/L calcium carbonate was added at the start of fermentation to control the pH of the medium. The inhibition caused by ADE was completely alleviated and citric acid production substantially increased from 118.6 g/L to 141.4 g/L, comparable to the fermentation with deionized water (141.2 g/L). This novel process could decrease wastewater discharges and fresh water consumption in the citric acid industry, with benefit to the environment.

Low prevalence of antibodies against Toxoplasma gondii in dairy cattle from China's central region.

BACKGROUND: Toxoplasma gondii is an intracellular protozoan that can infect humans and other animals, including cattle. Cattle are one of the world's main sources of meat, and people who consume raw or undercooked meat and milk of cattle infected with T. gondii can become infected. In this study, a total of 5292 dairy cattle serum samples, collected from 17 cities (Henan Province, China) from January 2015 to September 2017, were screened for antibodies against T. gondii. RESULTS: Antibodies to T. gondii were found in 1.93% (102/5292) (95% CI, 1.56-2.30) of dairy cattle using a modified agglutination test (cut-off 1:100). The results showed that geographic location and season may be risk factors for T. gondii infection of cattle (P < 0.05), and the seroprevalence of T. gondii in cattle along the Yellow River is higher than other areas. CONCLUSIONS: This is the first large-scale investigation on the seroprevalence of T. gondii infection in cattle from Central China. This survey shows that the T. gondii infection rate of dairy cattle is low; however, these findings provide additional information on the epidemiology of Chinese T. gondii. The possibility of dairy cattle exposure to T. gondii in Central China can not be ignored, and the consumption of raw or undercooked beef or milk may pose a risk to human health.

Prognostic Value of ALT, AST, and AAR in Hepatocellular Carcinoma with B-Type Hepatitis-Associated Cirrhosis after Radical Hepatectomy.

BACKGROUND: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and AST to ALT ratio (AAR) were shown to be associated with prognosis in some groups of hepatocellular carcinoma (HCC). However, their clinicopathologic and prognostic roles in HCC patients with B-type hepatitis-associated cirrhosis (HBAC) have not been comprehensively investigated. The present study aimed to address the issues. METHODS: A total of 125 patients with HCC and HBAC after radical hepatectomy were included. The correlations of ALT, AST, and AAR with clinicopathologic parameters, overall/recurrence-free survival, overall/early recurrence, and post-recurrence survival were evaluated using univariate and multivariate analyses. RESULTS: ALT and AST, which positively correlated with each other, had significant relationships with tumornode-metastasis (TNM) stage and Edmondson-Steiner grade. In univariate analyses, ALT and AST were predictive for early recurrence, overall and recurrence-free survival, while ALT and AST was associated with overall recurrence and post-recurrence survival, respectively. However, only AST was marginally significant in multivariate tests for early recurrence and post-recurrence survival. As for AAR, no significant prognostic relevance was found. CONCLUSIONS: Our data suggest that ALT and AST, but not AAR, might be potential predictors of post-resectional outcome in HCC with HBAC. These effects might depend on their associations with crucial clinicopathologic variables.

Correlation between replicative senescence of endometrial gland epithelial cells in shedding and non-shedding endometria and endometriosis cyst during menstruation.

To investigate correlation between abnormal replicative senescence of endometrial gland epithelial cells (EGECs) in shedding and non-shedding endometria and endometriosis cyst during menstruation. Musashi-1 expression, ß-catenin expression, and EGECs ultrastructure in shedding and non-shedding endometrium when menstruation were observed through real-time PCR and transmission electron microscopy technologies. (1) Musashi-1 and ß-catenin exhibited a high expression in shedding and non-shedding endometria in experimental group, showing a positive correlation between each other; and were significantly higher than that in control group. However; there was no correlation between these two in control group. (2) Transmission electron microscopy results: In experimental group, organelles in EGECs in shedding endometrium obtained were abundant on the first day of menstruation, nuclei were irregular, double nucleoli could be observed, and chromatin was rich. Furthermore, morphology of EGECs in non-shedding endometrium was irregular, organelles were abundant, basement membrane was irregular with abnormal curvature, and a large amount of collagenic fibers were found in intercellular spaces. On the fifth day of menstruation, the cilia and microvilli on secretory cells in endometrium increased and prolongated, and organelles became extremely rich. EGECs have potentials of division, proliferation, invasion and migration; and is associated with formation of endometriosis cysts.