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High-spin states in Cs124 were populated in the Ni64(Ni64,p3n) reaction and the Gammasphere detector array was used to measure γ-ray coincidences. Both positive- and negative-parity bands, including bands with chiral configurations, have been extended to higher spin, where a shape change has been observed. The configurations of the bands before and after the alignment are discussed within the framework of the cranked Nilsson-Strutinsky model. The calculations suggest that the nucleus undergoes a shape transition from triaxial to prolate around spin I≃22 of the positive-parity states. The alignment gain of 8â.,, observed in the positive-parity bands, is due to partial alignment of several valence nucleons. This indicates the absence of band crossing due to paired nucleons in the bands.

Excited states in Lu167 were populated in the Sb123(Ca48,4n) reaction at 203 MeV and decay γ rays measured using the Gammasphere spectrometer array. Two triaxial strongly deformed bands were identified previously and interpreted as zero- and one-phonon wobbling excitations. As a result of more extensive band search, the level scheme has been considerably extended to include ten new rotational bands and some 630γ-ray transitions. A number of interband linking transitions were revealed, so that all but two bands could be connected with each other. Configurations are proposed for all new bands based on measured observables, with the help of cranked shell model calculations. A γ-ray sequence, previously suggested as a triaxial strongly deformed band based on quasiparticle excitations coexisting with the wobbling excitation in the triaxial potential well, has now been determined to be a signature partner of a coupled band, associated with a normal deformed five-quasiparticle configuration. The possibility of two new bands being associated with triaxial deformation is discussed.

In recent attempts to search for exotic shapes, hyperdeformation (HD), and Jacobi transitions in Hf, Ba, Xe, Sn and Nd nuclei, ridge structures presumably originating from nuclei of very elongated shapes have been observed in 126Ba, with Gammasphere (GS) and in 126Xe, with Euroball-IV (EB-IV). After the promising results from GS, a second experiment in 126Ba followed at EB-IV, taking advantage of the use of the BGO Inner Ball (IB) for selecting the highest spins. The decay of the Giant Dipole Resonances (GDR) is also studied, and the analysis in progress. The Quasi-continuum transitions in the Jacobi region, show a significant decrease in energy for both 126Ba and 126Xe, compared to the Thomas-Fermi- and the LSD model predictions. Similar effects were recently found for other nuclei by Ward et al.

The highest-spin discrete states (I ∼ 60ℏ and Ex ∼ 30MeV) in normal deformed nuclei have been observed in the rare-earth isotope 156Dy using the GAMMASPHERE spectrometer. The quadrupole moments for a variety of configurations, including the 9/2+[404] (g9/2) proton, 1/2+[660] (i13/2) and 1/2-[541] (f7/2, h9/2) neutron orbitals, were measured in a wide range of ∼ 130 nuclei.

Objective: To investigate the therapeutic effects and mechanisms of Ultrasound-targeted microbubble destruction (UTMD) technology combined with CoQ10 loaded PEGylated nanoliposomes (CoQ10-PEG-lips) on diabetic cardiomyopathy (DCM) in rats. Methods: CoQ10-PEG-lips were prepared using the thin-film dispersion method combined with ultrasonic hydration, followed by quality assessment. Sixty healthy and clean male SD rats were selected, and 50 were randomly chosen using a random number table to establish a type 1 diabetes mellitus (DM) model via a single intraperitoneal injection of streptozotocin. The remaining 10 rats were assigned as the normal control group. A total of 47 rats successfully developed the DM model, and 40 were selected using the random number table method. Based on different intervention methods, these rats were then randomly divided into DM model group, CoQ10 solution group, CoQ10-PEG-Lips group, and CoQ10-PEG-Lips+UTMD group ( n =10 per group). Normal control group and DM model group rats were injected with 1 ml of normal saline through caudal vein. CoQ10 solution group and CoQ10-PEG-Lips group were injected with 1 ml of CoQ10 solution or CoQ10-PEG-Lips solution containing 10 mg/kg of CoQ10 through caudal vein, respectively. Rats in the CoQ10-PEG-Lips+UTMD group were injected with 1 ml of CoQ10-PEG-Lips solution containing 10 mg/kg of CoQ10+100 mg of freeze-dried ultrasound microbubble powder through caudal vein and were given UTMD treatment at the same time, with the intervention given twice a week. After 12 weeks of intervention, cardiac function indexes [left ventricular end-systolic diameter (LVEDs), left ventricular end-diastolic diameter (LVEDd), and left ventricular ejection fraction (LVEF)]of each group were measured by ultrasonic cardiac function detection in vivo. Simultaneously, ex-vivo histopathological examination was conducted to assess myocardial cell morphology, cross-sectional area, collagen volume fraction (CVF), and apoptosis index (AI) in each group. Additionally, molecular biology techniques were employed to measure oxidative stress-related indicators and the expression of apoptosis-related pathway proteins. Results: The prepared CoQ10-PEG-lips had a well-rounded morphology, good dispersibility, and a high encapsulation efficiency of 87.45%±3.23%. After 12 weeks of intervention, the myocardial cell morphology in the CoQ10-PEG-Lips+UTMD group was intact, with orderly arrangement, closely resembling that of the normal control group. There were no statistically significant differences between the two groups in terms of LVEDs [(1.53±0.07) mm vs (1.42±0.04) mm], LVEDd [(2.93±0.15) mm vs (2.81±0.05) mm], or LVEF (80.76%±3.42% vs 84.60%±2.10%) (all P >0.05). Similarly, there were no significant differences between the two groups in myocardial cell cross-sectional area, CVF, or AI (all P >0.05). The CoQ10-PEG-Lips+UTMD group showed statistically significant differences in the above-mentioned indicators compared to the DM group, CoQ10 solution group, and CoQ10-PEG-Lips group (all P <0.05). In the CoQ10-PEG-Lips+UTMD group, the levels of myocardial superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and the expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) were significantly higher compared to the DM model group, CoQ10 solution group, and CoQ10-PEG-Lips group (all P <0.05), while malondialdehyde levels and the expression of Bcl-2-associated X protein (Bax) and caspase-3 were lower (all P <0.05). Conclusions: Using PEG-lips to encapsulate the poorly soluble drug CoQ10 in combination with UTMD technology enables targeted delivery of the drug to the myocardium, which can help reduce myocardial cell damage, fibrosis, and apoptosis caused by diabetes mellitus (DM) by inhibiting oxidative stress damage and the Bcl-2/Bax/caspase-3 apoptosis signaling pathway, ultimately improving cardiac function in DCM rats.

Zeta chain-associated protein kinase 70 (ZAP-70) is a non-receptor tyrosine kinase that interacts with the activated T-cell receptor to transduce downstream signals, and thus plays an important role in the adaptive immune system. The biphosphorylated immunotyrosine-based activation motifs (ITAM-Y2P) binds to the N-SH2 and C-SH2 domains of ZAP-70 to promote the activation of ZAP-70. The present study explores molecular mechanisms of allosteric inactivation of ZAP-70 induced by the hot spot W165C mutation through atomically detailed molecular dynamics simulation approaches. We report microsecond-length simulations of two states of the tandem SH2 domains of ZAP-70 in complex with the ITAM-Y2P motif, including the wild-type and W165C mutant. Extensive analysis of local flexibility and dynamical correlated motions show that W165C mutation changes coupled motions of protein domains and community networks. The binding affinities of the ITAM-Y2P motif to the wild-type and W165C mutant of ZAP-70 are predicted using binding free energy calculations. The results suggest that the driving force to decrease the binding affinity in the W165C mutant derives from the difference in the protein-protein electrostatic interactions. Moreover, the per-residue free energy decomposition unravels that the contributions from residues in the phosphorylated Tyr315 (pY315) binding site, in particular pY315 of ITAM-Y2P, and Arg43, Tyr240 of ZAP-70, are the key determinants for the loss of binding affinity. This study may insights into our understanding of the pathological mechanism of ZAP-70.Communicated by Ramaswamy H. Sarma.

A novel wastewater treatment plant process was constructed to overcome the challenge of simultaneous nitrate removal and phosphorus (P) recovery. The results revealed that the P and nitrate removal efficiency rose from 39.0 % and 48.4 % to 92.8 % and 93.6 % after 136 days of operation, and the total P content in the biofilm (TP biofilm ) rose from 15.8 mg/g SS to 57.8 mg/g SS. Moreover, the increase of TP biofilm changed the metabolic mode of denitrifying polyphosphate accumulating organisms (DPAOs), increasing the P concentration of the enriched stream to 172.5 mg/L. Furthermore, the acid/alkaline fermentation led to the rupture of the cell membrane, which released poly-phosphate and ortho-phosphate of cell/EPS in DPAOs and released metal‑phosphorus (CaP and MgP). In addition, high-throughput sequencing analysis demonstrated that the relative abundance of DPAOs involved in P storage increased, wherein the abundance of Acinetobacter and Saprospiraceae rose from 8.0 % and 4.1 % to 16.1 % and 14.0 %. What's more, the highest P recovery efficiency (98.3 ± 1.1 %) could be obtained at optimal conditions for struvite precipitation (pH = 7.56 and P: N: Mg = 1.87:3.66:1) through the response surface method (RSM) simulation, and the precipitates test analysis indicated that P recovery from biofilm sludge was potentially operable. This research was of great essentiality for exploring the recovery of P from biofilm sludge., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Epicardial adipose tissue (EAT) is a type of ectopic fat with endocrine and paracrine functions. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that responds to environmental stimuli. AhR expression is associated with obesity. In this cross-sectional study, we aimed to determine the relationship between circulating AhR concentrations and EAT., Methods: A total of 30 men with obesity and 23 age-matched men as healthy controls were enrolled. Plasma AhR concentrations were determined at fasting. The EAT thickness was measured on the free wall of the right ventricle from the basal short-axis plane by magnetic resonance imaging., Results: The participants with obesity had a higher plasma AhR level than the controls (81.0 ± 24.5 vs. 65.1 ± 16.4 pg/mL, P = 0.010). The plasma AhR level was positively correlated with EAT thickness (correlation coefficient = 0.380, P = 0.005). After adjusting for fasting glucose levels, plasma AhR levels were still significantly associated with EAT thickness (95% CI 0.458‒5.357, P = 0.021) but not with body mass index (P = 0.168)., Conclusion: Plasma AhR concentrations were positively correlated with EAT thickness on the free wall of the right ventricle in men. Further investigations are needed to evaluate the causal effects and underlying mechanisms between AhR and EAT., (© 2023. BioMed Central Ltd., part of Springer Nature.)

A novel process was proposed for simultaneous denitrification and phosphorus (P) recovery. The increased nitrate concentration facilitated the activity of denitrifying P removal (DPR) in P enrichment, which stimulated P uptake and storage, making P more readily accessible for release into the recirculated stream. The total P content in the biofilm (TP biofilm ) rose to 54.6 ± 3.5 mg/g SS as the nitrate concentration increased from 15.0 to 25.0 mg/L, while the P concentration of the enriched stream reached 172.5 ± 3.5 mg/L. Moreover, the abundance of denitrifying polyphosphate accumulating organisms (DPAOs) increased from 5.6% to 28.0%, and the increased nitrate concentration facilitated the process of carbon, nitrogen, and P metabolism due to the rise in the genes involved in critical functions of metabolism. Acid/alkaline fermentation analysis indicated that the EPS release was the primary P-release pathway. Additionally, pure struvite crystals were obtained from the enriched stream and fermentation supernatant., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Four new species of the genus Chaunax found in Taiwan and the Philippines are described. Chaunax albatrossae sp. nov. belongs to the C. abei species group and is distinct from its congeners in having a dark gray mouth cavity, a dark brown to black gill chamber and gill rakers and skin covered with only short, simple spinules. Three new species belong to the C. fimbriatus species group: Chaunax erythraeus sp. nov. is distinct in having a uniformly pinkish-red body and an entirely black gill chamber; Chaunax obscurus sp. nov. is distinct in having a dark gray mouth cavity and orange-red marbling on the dorsal surface that fades after fixation; and Chaunax viridiretis sp. nov. is distinguished by its green reticulate pattern with some small, bright-white patches on the dorsal surface. The diagnostic characters used to identify the chaunacids are summarized and a key to all Chaunax species found in Taiwan and adjacent waters is provided.

In this cross-sectional study, enrollment included 818 female adults undergoing bone mineral density (BMD) assessment during the health examination. Subjects with osteoporosis had the lowest circulating platelet concentrations. The circulating platelet concentration was positively correlated with BMD. A high platelet concentration had independently low odds of osteoporosis., Purpose: Platelets play an important role in bone metabolism. However, the association between circulating platelet counts and bone mineral density (BMD) has been inconsistently reported. We aimed to investigate the relationship between platelet counts and osteoporosis in Chinese women., Methods: In this cross-sectional study, a total of 818 female adults who underwent BMD assessment during the health examination were enrolled. Blood cell counts and biochemistry data were recorded., Results: Subjects with osteoporosis had the lowest platelet counts (238 ± 59 × 10 9 /L) compared with subjects with osteopenia (256 ± 64 × 10 9 /L) and a normal BMD (269 ± 76 × 10 9 /L, P < 0.001). The circulating platelet concentration was positively correlated with the BMD of the lumbar spine (r = 0.195, P < 0.001), left hip (r = 0.145, P < 0.001), and right hip (r = 0.149, P < 0.001). According to the receiver operating characteristic curve, the cutoff platelet concentration for differentiating osteoporosis was 260 × 10 9 /L. A high platelet concentration had significantly low odds of osteoporosis after adjusting for other covariates (odds ratio = 0.574, 95% confidence interval: 0.346‒0.953, P = 0.032)., Conclusion: The circulating platelet concentration was significantly correlated with BMD in Chinese women., (© 2022. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Aim: To investigate the effect of aberrant expression of DHRS1 on hepatocellular carcinoma (HCC). Materials & methods: Kaplan-Meier and Cox regression analyses were performed to evaluate the correlation between DHRS1 and overall survival. Gene set enrichment analysis was performed to explore the potential function of DHRS1 in HCC. Results: Multiple data analysis revealed that DHRS1 mRNA and protein expression level were remarkably lower in HCC than that in normal tissues. In survival analysis, patients with low DHRS1 expression presented a poorer prognosis, and was an independent risk factor for HCC. Conclusion: Decreased DHRS1 expression may be a potential predictor of poor prognosis in HCC.

Background: Emerging infectious diseases are a constant threat to the public's health and health care systems around the world. Coronavirus disease 2019 (COVID-2019), which was defined by the World Health Organization as pandemic, has rapidly emerged as a global health threat. Outbreak evolution and prevention of international implications require substantial flexibility of frontline health care facilities in their response., Aim: To explore the effect of the implementation and management strategy of pre-screening triage in children during COVID-19., Methods: The standardized triage screening procedures included a standardized triage screening questionnaire, setup of pre-screening triage station, multi-point temperature monitoring, extensive screenings, and two-way protection. In order to ensure the implementation of the pre-screening triage, the prevention and control management strategies included training, emergency exercise, and staff protection. Statistical analysis was performed on the data from all the children hospitalized from January 20, 2020 to March 20, 2020 at solstice during the pandemic period. Data were obtained from questionnaires and electronic medical record systems., Results: A total of 17561 children, including 2652 who met the criteria for screening, 192 suspected cases, and two confirmed cases without omission, were screened from January 20, 2020 to March 20, 2020 at solstice during the pandemic period. There was zero transmission of the infection to any medical staff., Conclusion: The effective strategies for pre-screening triage have an essential role in the prevention and control of hospital infection., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Collagen is the most abundant extracellular matrix protein that is widely used in tissue engineering (TE). There is little research done on printing pure collagen. To understand the bottlenecks in printing pure collagen, it is imperative to understand collagen from a bottom-up approach. Here it is aimed to provide a comprehensive overview of collagen printing, where collagen assembly in vivo and the various sources of collagen available for TE application are first understood. Next, the current printing technologies and strategy for printing collagen-based materials are highlighted. Considerations and key challenges faced in collagen printing are identified. Finally, the key research areas that would enhance the functionality of printed collagen are presented., (© 2020 Wiley-VCH GmbH.)

The present study sought to investigate the effect of non-mitogenic acidic fibroblast growth factor (NM-aFGF) loaded PEGylated nanoliposomes (NM-aFGF-PEG-lips) combined with the ultrasound-targeted microbubble destruction (UTMD) technique on modulating diabetic cardiomyopathy (DCM)and the mechanism involved. Animal studies showed that the diabetes mellitus (DM) group exhibited typical myocardial structural and functional changes of DCM. The indexes from the transthoracic echocardiography showed that the left ventricular function in the NM-aFGF-PEG-lips + UTMD group was significantly improved compared with the DM group. Histopathological observation further confirmed that the cardiomyocyte structural abnormalities and mitochondria ultrastructural changes were also significantly improved in the NM-aFGF-PEG-lips + UTMD group compared with DM group. The cardiac volume fraction (CVF) and apoptosis index in the NM-aFGF-PEG-lips + UTMD group decreased to 10.31 ± 0.76% and 2.16 ± 0.34, respectively, compared with those in the DM group (CVF = 21.4 ± 2.32, apoptosis index = 11.51 ± 1.24%). Moreover, we also found significantly increased superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-Px) activity as well as clearly decreased lipid hydroperoxide levels and malondialdehyde (MDA) activity in the NM-aFGF-PEG-lips + UTMD group compared with those in the DM group ( p  < .05). Western blot analysis further revealed the highest level of NM-aFGF, p-AKT, p-GSK-3β1, Nrf-2, SOD2 and NQO1 in the NM-aFGF-PEG-lips + UTMD group. This study confirmed using PEGylated nanoliposomes combined with the UTMD technique can effectively deliver NM-aFGF to the cardiac tissue of diabetic rats. The NM-aFGF can then inhibit myocardial oxidative stress damage due to DM by activating the AKT/GSK/Nrf-2 signaling pathway, which ultimately improved the myocardial structural and functional lesions in diabetic rats.

Background and Objectives: Adipose tissue is a source of mesenchymal stem cells, which have the potential to differentiate into various types of cells. Adipose-derived stem cells (ADSCs) are now recognized as an accessible, abundant, and reliable stem cells suitable for tissue engineering and regenerative medicine applications. However, few literatures gave a comprehensive report on the capacities of ADSCs harvested from different sites. Especially, the capacities of ADSCs from aged mice remained unclear. In this study, we investigated several main capacities of brown adipose derived stem cells (B-ADSCs) and white adipose derived stem cells (W-ADSCs) from both young and aged mice., Methods and Results: When isolated from young mice, B-ADSCs showed a stronger proliferation rate and higher osteogenic, adipogenic and myocardial differentiation ability than W-ADSCs. Carboxy fluorescein diacetate succinimidyl ester (CFSE) labeling test suggested no significant difference in immunosuppression capacity between B-ADSCs and W-ADSCs. Similarly, no difference between these two were found in several immune related molecules, such as programmed death-ligand 1 (PD-L1), intercellular cell adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), inducible nitric oxide synthase (iNOS), tumour necrosis factor- α (TNF- α ), interleukin 10 (IL10), and suppressor of cytokine signaling 1 (socs1). When isolated from aged mice, B-ADSCs also showed a stronger proliferation rate and higher osteogenic, adipogenic and myocardial differentiation ability than W-ADSCs; however, it demonstrated an attenuated immunosuppression capacity compared to W-ADSCs., Conclusions: In summary, our data showed that ADSCs' characteristics were tissue source dependent and changed with age. It provided evidence for choosing the right tissue-specific ADSCs for clinical application and fundamental research.

Practical motor imagery electroencephalogram (EEG) data-based applications are limited by the waste of unlabeled samples in supervised learning and excessive time consumption in the pretraining period. A semisupervised deep stacking network with an adaptive learning rate strategy (SADSN) is proposed to solve the sample loss caused by supervised learning of EEG data and the extraction of manual features. The SADSN adopts the idea of an adaptive learning rate into a contrastive divergence (CD) algorithm to accelerate its convergence. Prior knowledge is introduced into the intermediary layer of the deep stacking network, and a restricted Boltzmann machine is trained by a semisupervised method in which the adjusting scope of the coefficient in learning rate is determined by performance analysis. Several EEG data sets are carried out to evaluate the performance of the proposed method. The results show that the recognition accuracy of SADSN is advanced with a more significant convergence rate and successfully classifies motor imagery.

Nonalcoholic fatty liver disease (NAFLD) is a very common liver disease, and its incidence has significantly increased worldwide. The liver X receptor α (LXRα) is a multifunctional nuclear receptor that controls lipid homeostasis. Inhibition of LXRα transactivation may be beneficial for NAFLD and hyperlipidemia treatment. Ursolic acid (UA) is a plant triterpenoid with many beneficial effects; however, the mechanism of its action on LXRα remains elusive. We evaluated the effects of UA on T0901317 (T090)-induced LXRα activation and steatosis. UA significantly decreased the LXR response element and sterol regulatory element-binding protein-1c ( SREBP-1c) gene promoter activities, mRNA, protein expression of LXRα target genes, and hepatic cellular lipid content in a T090-induced mouse model. A molecular docking study indicated that UA bound competitively with T090 at the LXRα ligand binding domain. UA stimulated AMP-activated protein kinase (AMPK) phosphorylation in hepatic cells and increased corepressor, small heterodimer partner-interacting leucine zipper protein (SMILE) but decreased coactivator, steroid receptor coactivator-1 (SRC-1) recruitment to the SREBP-1c promoter region. In contrast, UA induced SRC-1 binding but decreased SMILE binding to reverse cholesterol transport-related gene promoters in intestinal cells, increasing lipid excretion from intestinal cells. Additionally, UA reduced valproate-induced LXRα mediated and rifampin-induced pregnane X receptor mediated lipogenesis, offering potential treatments for drug-induced hepatic steatosis. Thus, UA displays liver specificity and can be selectively repressed while RCT stimulation by LXRα is preserved and enhanced. This is a novel therapeutic option to treat NAFLD and may be helpful in developing LXR agonists to prevent atherosclerosis.

Background: Interactions between transcriptional inducers of cytochrome P450 (CYP450) enzymes and therapeutic drugs may be prevented by antagonizing the activation of a nuclear receptor (NR), pregnane X receptor (PXR, NR1I2), thus improving therapeutic efficacy., Purpose: In the present study, we aim to identify that ursolic acid (UA), a widely distributed pentacyclic triterpene, may act as an effective antagonist of PXR and its sister NR receptor, constitutive androstane receptor (CAR, NR1I3)., Methods: The hepatocellular carcinoma cell line, HepG2, was used to evaluate the promoter activity of PXR and CAR target genes, CYP3A4 and CYP2B6, respectively. Catalytic activities, mRNA, and protein expression of CYP3A4 and CYP2B6 were evaluated in a differentiated HepaRG cell line. Coregulation of PXR with coregulators on CYP3A4 promoter response elements was also been characterized., Results: Transient transfection assays showed that UA effectively attenuated CYP3A4 and CYP2B6 promoter activities mediated by rifampin (RIF, human PXR agonist) and CITCO (human CAR agonist). These inhibitory effects were well correlated with the expression and catalytic activities of CYP3A4 and CYP2B6. Furthermore, the interaction of co-regulators with PXR and the transcriptional complexes in the CYP3A4 promoter activity and CYP3A4 promoter xenobiotic response element (everted repeat 6, ER6), respectively, were disrupted in the presence of UA. UA showed an antagonistic effect against PXR, and reversed the cytotoxic effects of isoniazid (INH) induced by RIF. Taken together, these results show that UA inhibits the transactivation effects of PXR and CAR, and reduces the expression and function of CYP3A4 and CYP2B6., Conclusion: The present study suggests that UA could be a powerful agent for reducing potentially dangerous interactions between transcriptional inducers of CYP enzymes and therapeutic drugs., (Copyright © 2017. Published by Elsevier GmbH.)

A novel total synthesis of tanshinone I (1) via the intermediate 3-hydroxy-8-methyl-1,4-phenanthrenedione (8) is described. The low overall yields and the use of expensive reagents in the synthesis process were minimized by the use of the Diels-Alder reaction to directly construct the 1,4-phenanthrenedione scaffold, providing tanshinone I (1) in only three steps.

Objective: The therapeutic effect of acid fibroblast growth factor 1(FGF1) on rats with diabetic cardiomyopathy (DCM) was evaluated by using nano-liposomes combined with ultrasound-targeted microbubble destruction technique (UTMD). Methods: The FGF1-loaded nano-liposomes were prepared by water-in-water emulsion method combined with lyophilization technique.TypeⅠdiabetes model was induced by intraperitoneal injection of streptozotocin (STZ, 70 mg/kg) in 60 male SD rats.Sixteen weeks later, diabetic rats were randomly divided into: placebo group (saline treatment), FGF1 group, FGF1-loaded nano-liposomes group, and FGF1-loaded nano-liposomes plus UTMD group ( n =15 each). After two weeks of intervention followed by 2 weeks intervention stop, all rats underwent cardiac catheterization, and the left ventricular end-systolic pressure (LVESP), left ventricular end-diastolic pressure (LVEDP) and the maximal increase/decrease rate of left ventricular pressure (LV±dp/dtmax) were measured.Then, the rats were sacrificed and myocardial tissue were obtained for Masson trichrome staining, TUNEL apoptotic staining and CD31 immunohistochemistry staining to quantify myocardial collagen fraction (CVF), cardiac myocyte apoptotic index and myocardial microvascular density (MVD). Results: (1)Scanning electron microscope results revealed good morphology and FGF1 encapsulation efficiency (84.3±2.8)% with high stability and dispensability of FGF1 loaded nano-liposomes.(2)The hemodynamic evaluation showed that LVESP, LV + dp/dt(max) and LV -dp/dt(max) were all significantly higher, while LVEDP was significantly lower in the FGF1-loaded nano-liposome+ UTMD group than in DCM group, FGF1 solution group, and FGF1 nano-liposome group(all P <0.05). (3)The Masson trichrome staining demonstrated that CVF was significantly higher in all DCM groups than in control group and was significantly lower in the FGF1-loaded nano-liposome+ UTMD group than in DCM group, FGF1 solution group, and FGF1 nano-liposome group (all P <0.05). (4)The CD31 immunohistochemical staining results showed that MVD was significantly lower in all DCM groups than in control group and was significantly higher in the FGF1-loaded nano-liposome+ UTMD group than in DCM group, FGF1 solution group, and FGF1 nano-liposome group (all P <0.05). (5)The TUNEL results showed that apoptotic index was significantly higher in all DCM groups than in control group and was significantly lower in the FGF1-loaded nano-liposome + UTMD group than in DCM group, FGF1 solution group, and FGF1 nano-liposome group (all P <0.05). Conclusion: FGF1 nano-liposomes combining with UTMD technique can significantly improve cardiac functions and attenuate myocardial CVF and apoptosis and enhance myocardial MVD in DCM rats.

Background: Enterovirus 71 (EV-A71) shows a potential of rapid death, but the natural history of the infection is poorly known. This study aimed to examine the natural history of EV-A71 infection., Methods: This was a prospective longitudinal observational study performed between January 1 st and October 31 st , 2012, at three hospitals in Guangdong, China. Subjects with positive EV-A71 RNA laboratory test results were included. Disease progression was documented with MRI, autopsies, and follow-up. Symptoms/signs with potential association with risk of death were analyzed., Results: Among the 288 patients, neurologic symptoms and signs were observed (emotional movement disorders, dyskinesia, involuntary movements, autonomic dysfunction, and disturbance of consciousness). Some of them occurred as initial symptoms. Myoclonic jerks/tremors were observed among >50% of the patients; nearly 40% of patients presented fatigue and 25% were with vomiting. Twenty-eight patients (9.7%) presented poor peripheral perfusion within 53.4 ± 26.1 h; 23 patients (8.0%) presented pulmonary edema and/or hemorrhage within 62.9 ± 28.6 h. Seventeen (5.9%) patients were in a coma. Seven (2.4%) patients died within 62.9 ± 28.6 h. Seventy-seven survivors underwent head and spinal cord MRI and 37.7% (29/77) showed abnormalities. Two fatal cases showed neuronal necrosis, softening, perivascular cuffing, colloid, and neuronophagia phenomenon in the brainstem., Conclusions: Patients with EV-A71 infection showed high complexity of symptoms and onset timing. Death risk may be indicated by autokinetic eyeball, eyeball ataxia, severe coma, respiratory rhythm abnormality, absent pharyngeal reflex, ultrahyperpyrexia, excessive tachycardia, pulmonary edema and/or hemorrhage, and refractory shock and ataxic respiration. Early assessment of these symptoms/signs is important for proper management.

Based on the Padé approximation method, in this paper we determine the coefficients [Formula: see text] and [Formula: see text] such that [Formula: see text] where [Formula: see text] is any given integer. Based on the obtained result, we establish a more accurate formula for approximating π , which refines some known results.

Recently, the feasibility and effects of using microbubbles (MBs) as an ultrasound (US) contrast agent for enhancing the penetration in transdermal delivery in vivo have been demonstrated, but the mechanism and efficiency are unclear. This study demonstrates the penetration depth, concentration and efficiency of transdermal α-arbutin delivery during 4 weeks after US treatment with MBs in mice. Experimental animals were randomly divided into the following four groups (n = 5 animals per group): (1) penetrating α-arbutin alone (C), (2) US combined with penetrating α-arbutin, (3) US combined with MBs and penetrating α-arbutin, and (4) US combined with diluted MBs and penetrating α-arbutin (UBD). The penetration depths in agarose phantoms and pigskin were 47 and 84% greater for group UBD, respectively, than for group C. The in vitro skin penetration by 2% α-arbutin after 3 h was 83% greater in group UBD than in group C. The degree of in vivo skin whitening (quantified as the luminosity index) in group UBD significantly increased by 25% after 1 week, 34% after 2 weeks, and then stabilized after 3 weeks at 37% in C57BL/6J mice over a 4-week experimental period. Our results indicate that combined treatment with optimal US and MBs can increase skin permeability so as to enhance α-arbutin delivery to inhibit melanogenesis without damaging the skin in mice.

Species of the anglerfish genus Chaunax occurring off southern Africa are reviewed and nine species are recognized: C. africanus, C. apus, C. flammeus, C. penicillatus, C. russatus, C. suttkusi, and three newly described species. Chaunax atimovatae sp. nov. is distinguished by having numerous tiny melanophores on the skin and a mixture of bifurcate and simple spinules on its dorsal surface, scattered rounded green spots circled by yellow on its dorsal surface, 9 or 10 rakers on the second gill arch, and 2 neuromasts in the upper preopercular, 11-14 in the pectoral, 31-37 in the lateral-line proper. Chaunax heemstraorum sp. nov. is distinguished by a combination of all dermal spinules simple, large green spots on the dorsal surface, 10-12 rakers on the second gill arch; and 3 neuromasts in the upper preopercular, 13-18 in the pectoral, 37-42 in the lateral-line proper, and usually 5 on the caudal-fin base. Chaunax hollemani sp. nov. is distinguished by cirri on top of the head, head width 16.0-18.5% SL, pre-preopercle length 26.8-28.5% SL, 9 rakers on the second gill arch, and 2 neuromasts in the upper preopercular, 11-14 in the pectoral, and 33-38 in the lateral-line proper. A key to species found in the study region is provided.

Proteasome inhibitors have revolutionized outcomes in multiple myeloma, but they are used empirically, and primary and secondary resistance are emerging problems. We have identified TJP1 as a determinant of plasma cell proteasome inhibitor susceptibility. TJP1 suppressed expression of the catalytically active immunoproteasome subunits LMP7 and LMP2, decreased proteasome activity, and enhanced proteasome inhibitor sensitivity in vitro and in vivo. This occurred through TJP1-mediated suppression of EGFR/JAK1/STAT3 signaling, which modulated LMP7 and LMP2 levels. In the clinic, high TJP1 expression in patient myeloma cells was associated with a significantly higher likelihood of responding to bortezomib and a longer response duration, supporting the use of TJP1 as a biomarker to identify patients most likely to benefit from proteasome inhibitors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In order to explore the effect of cadmium stress on root vigor and accumulation of five kinds of conventional metal elements in Salix variegata, a hydroponic experiment with different cadmium treatments were conducted. The cadmium treatments included 0 mg·L -1 (CK), 2 mg·L -1 (T 1 ), 10 mg·L -1 (T 2 ), 20 mg·L -1 (T 3 ) and 50 mg·L -1 (T 4 ). The root vigor and distribution of cadmium and five kinds of conventional metal elements (including Ca, Mg, Mn, Zn and Fe) in S. variegata were tested. The results showed that: 1) The root vigor of S. variegata decreased with increasing cadmium stress gradually. Compared to control, the root vigor decreased significantly in treatments with the cadmium concentration reaching and exceeding 10 mg·L -1 . 2) With increasing the cadmium concentration, the abilities of S. variegata to absorb and accumulate Fe in leaves were inhibited significantly; the abilities to absorb and accumulate Mg, Mn and Fe in phloem were inhi-bited significantly; the abilities to absorb and accumulate Ca, Mg, Mn, Zn and Fe in xylem had no significant differences; and the abilities to absorb and accumulate Ca, Mg, Mn, Zn and Fe in root were inhibited significantly. It could be concluded that cadmium had antagonistic effect on the accumulation of the other metal elements, especially Zn in plant root. 3) With increasing concentrations of cadmium, the translocation factors of Ca, Mg, Mn and Zn increased significantly when compared to control, while there was no significant influence on Fe. 4) Under cadmium stress, there was a significantly negative correlation between the accumulations of cadmium and Ca in S. variegate root, and a very significantly negative correlation between the accumulations of cadmium and the other four kinds of conventional metal elements, indicating that the change of conventional metal elements in S. variegate root could be one of the indices of the degree of cadmium stress.

Purpose: The association between tamoxifen (TMX) treatment and the risk of developing hyperlipidemia remains unclear., Methods: The records of 41,726 patients with breast cancer (28,266 received TMX and 13,460 did not) were obtained from the Taiwan National Health Insurance Research Database for the period from January 2000 to December 2008. Three-fold women without breast cancer were the control group (N = 125, 178). The main end point was developing hyperlipidemia during the follow-up., Results: During a mean follow-up of 9 years, the patients with breast cancer demonstrated a rate of developing hyperlipidemia that was 6% less (adjusted hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.90-0.97) than that of the control participants without breast cancer. Stratification by age group indicated that only women aged ≥ 55 years who were diagnosed with breast cancer exhibited a significantly reduced risk of hyperlipidemia compared with the control group. With the use of 2 types of adjusted models, we observed that the TMX users (aged ≥ 55 years) consistently exhibited a significantly lower risk of hyperlipidemia than the non-TMX users and control participants (adjusted HRs, 0.79 and 0.82 from models 1 and 2, respectively). Within the 8-year follow-up period, patients with breast cancer and 366 to 1500 days of TMX therapy and > 1500 days of TMX therapy had significantly lower risks of hyperlipidemia compared with patients with ≤ 365 days of TMX therapy (adjusted HR, 0.54; 95% CI, 0.50-0.59; adjusted HR, 0.21; 95% CI, 0.18-0.24, respectively)., Conclusions: In Asian patients with breast cancer, TMX use was associated with reduced risks of hyperlipidemia., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The objective of this study was to determine the association between the use of antiarrhythmic agents and the risk of malignant neoplasm of liver and intrahepatic bile ducts (MNLIHD)., Methods: We used the research database of the Taiwan National Health Insurance Program to conduct a population-based, case-control study. We identified 9944 patients with antiarrhythmic history who were first diagnosed as having MNLIHD between 2005 and 2010. We identified an additional 19,497 patients with antiarrhythmic history in the same period who did not develop MNLIHD and were frequency-matched using age, sex, and index year to form a control group. Five commercially available antiarrhythmic agents, amiodarone, mexiletine, propafenone, quinidine, and procainamide, were analyzed., Results: The adjusted odds ratio (OR) of MNLIHD was 1.60 (95% confidence interval [CI], 1.45-1.77) for amiodarone users versus nonamiodarone users. In subgroup analysis, amiodarone use was significantly associated with an increased risk of MNLIHD with an adjusted OR of 18.0 (95% CI, 15.7-20.5) for patients with comorbidities compared to an OR of 2.43 (95% CI, 1.92-3.06) for those without comorbidities. After adjustment for age, sex, statins, anti-diabetes medications, non-steroidal antiinflammatory drugs, propafenone use, quinidine use, and comorbidities, the ORs were 1.49, 1.66, and 1.79 for MNLIHD associated with annual mean defined daily doses of ≤ 30, 31-145, and >145, respectively., Conclusions: The results of the present study indicated that amiodarone might be associated with the development of MNLIHD in a dose-dependent manner, particularly among patients with comorbidities.

Background: The quality of treatment for critically ill children varies widely at different hospitals. This study aimed to analyze the characteristics of mortality in a pediatric emergency department (PED) at a tertiary children's hospital in Guangzhou, China and to investigate the risk factors associated with the mortality., Methods: The mortality of pediatric patients at the hospital from 2011 to 2013 was retrospectively analyzed using descriptive statistics., Results: Altogether 466 919 patients visited the PED during the period and 43 925 of them were admitted for further observation. In 230 deaths, the ratio of boys to girls was 1.4:1, and their age ranged from 2 hours to 16 years (median, 5 months). The time from admission to death ranged from 0 to 216 hours (median, 1.5 hours). There were 92 (40%) patients who died within 24 hours after admission and 104 (45.2%) patients who died on arrival. The prominent causes of the deaths were respiratory diseases, neuromuscular disorders, cardiovascular diseases, and sepsis, most of which were ascribed to severe infection. Sixty-five deaths were associated with more than one concomitant problem. The top concomitant problems were congenital malformation, low gestational age, and severe birth asphyxia., Conclusions: In our center, 40% of the patients in the PED died of fatal acute diseases, and pneumonia was the first leading cause of the deaths. Almost half of the deaths occurred on arrival and the rest were due to end-stage malignant diseases. This study emphasized the importance of prevention of birth deficits by reducing deaths in infants and children.

Organophosphate (OP) poisoning is a critical cause of morbidity and mortality worldwide. We conducted a nationwide longitudinal cohort study to investigate the development of deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE) among patients admitted with OP intoxication.We identified patients with OP intoxication by using the Taiwan National Health Insurance Research Database and enrolled 9223 patients who were hospitalized for OP intoxication between 2000 and 2011. OP intoxication was diagnosed based on a clinical assessment and serum acetylcholinesterase levels at the time of hospital admission. Each patient in the OP intoxication cohort was randomly frequency matched with 4 patients without OP intoxication based on their age, sex, and index year (36,892 patients as control cohort), and all patients were observed from the index date until the appearance of a DVT or a PTE event, or until December 31, 2011. We analyzed the risks of DVT and PTE by using Cox proportional hazards regression models that included the demographic variables of sex, age, and comorbidities (eg, hypertension, diabetes, cerebral vascular disease, heart failure, all cancer types, and lower leg fracture or surgery).The results revealed a significantly increased risk of developing DVT among patients with OP poisoning (adjusted hazard ratio [HR] = 1.55; 95% confidence interval [CI] = 1.03-2.34) but not PTE (adjusted HR = 1.44; 95% CI = 0.83-2.52). Among the patients without comorbidities, the OP poisoning patients compared with controls had a higher adjusted HR of 2.12 (95% CI = 1.21-3.71) for DVT.The results of this nationwide cohort study indicate that the risk of developing DVT is markedly higher in patients with OP intoxication compared with that of the general population.

Antagonizing the action of the pregnane X receptor (PXR) may have important clinical implications for preventing inducer-drug interactions and improving therapeutic efficacy. We identified a widely distributed isothiocyanate, allyl isothiocyanate (AITC), which acts as an effective antagonist of the nuclear receptor pregnane X receptor (PXR, NR1I2) and constitutive androstane receptor (CAR, NR1I3). HepG2 cells were used to assay reporter function, mRNA levels, and protein expression. Catalytic activities of the PXR and CAR target genes, CYP3A4 and CYP2B6, respectively, were also assessed in differentiated HepaRG cells. Protective effects of AITC on rifampin-induced cytotoxicity were observed, and transient transfection assays showed that AITC was able to effectively attenuate the agonist effects of rifampin and CITCO on human PXR and CAR activity, respectively. AITC-mediated reduction in the transcriptional activity of PXR and CAR correlated well with the suppression of CYP3A4 and CYP2B6 expression in HepG2 cells, which reflected the reduced catalytic activities of both of these genes following AITC treatment in differentiated HepaRG cells. Furthermore, AITC disrupts the co-regulations of PXR with several important co-regulators. Furthermore, the antagonist effect of AITC against PXR was found in HepaRG cells upon addition of acetaminophen (APAP) and amiodarone, indicating that AITC protects cells from drug-induced cytotoxicity. Taken together, our results show that AITC inhibits the transactivation effects of PXR and CAR and reduces the expression and function of CYP3A4 and CYP2B6. Additionally, AITC reversed the cytotoxic effects of APAP and amiodarone induced by PXR ligand. Results from this study suggest that AITC could be a powerful agent for reducing potentially dangerous interactions between transcriptional inducers of CYP enzymes and therapeutic drugs.

The growing interest in the use of natural herbal products and dietary supplements to treat and prevent diseases raises the question of medicinal drug safety. Allyl isothiocyanate, a hydrolysis product of a glucosinolate, sinigrin, has multiple beneficial properties, and based on this fact, allyl isothiocyanate-containing dietary supplements have been developed. To date, no studies of the effects of this compound on the cytochrome P450 2C9 have been reported. In this study, we found that allyl isothiocyanate reduced catalytic activity, messenger ribonucleic acid, and protein expression of cytochrome P450 2C9 in HepaRG cells. An investigation of the transcriptional activity of the pregnane X receptor and the constitutive androstane receptor revealed that allyl isothiocyanate disrupted the transcriptional coregulation effects of the pregnane X receptor/constitutive androstane receptor with several important coregulators and interfered with the assembly of transcriptional complexes of the cytochrome P450 2C9 pregnane X receptor/constitutive androstane receptor-response element. The decrease of cytochrome P450 2C9 expression and activity mediated by allyl isothiocyanate suggested that this agent could alter the metabolism of drugs metabolized by cytochrome P450 2C9. This may cause food/dietary supplement-drug interactions or alter the therapeutic effects, and even the toxicity of drugs coadministered with allyl isothiocyanate. Since the consumption of allyl isothiocyanate-containing food/dietary supplements continues to increase, it is important to predict and ultimately avoid interactions with concomitant drugs. It is required that these possible pharmacokinetic interactions be characterized and the recommendations available to patients and healthcare professionals be improved., (Georg Thieme Verlag KG Stuttgart · New York.)

Ultrasound (US) has recently been used to reduce localized adiposity in humans. The study described here evaluated the combined use of chitosan, which is used to treat hyperlipidemic diseases and fatty liver, and US to control weight and local fat deposition in normal mice over a 5-wk experimental period. Female ICR mice were randomly divided into four groups (n = 5 animals per group): (1) control, (2) US only, (3) chitosan only and (4) chitosan + US. Body weight, epididymal fat pad and intra-abdominal fat thickness (via US imaging) and plasma concentrations of high-density lipoprotein cholesterol, triglycerides and low-density lipoprotein cholesterol were measured in all mice before and after the 5-wk treatment period. After the 5-wk treatment period, weight had decreased significantly in the chitosan + US group (-11.2%) compared with the US only (-5.8%) and chitosan only (-9.3%) groups (p < 0.05). The reduction in epididymal fat pad thickness was significantly more marked in the chitosan + US group (28.2%) than in the other groups (p < 0.05). Furthermore, in the chitosan + US group, plasma levels of triglycerides and low-density lipoprotein cholesterol significantly decreased by 51.5% and 26%, respectively. This is the first report of effective control of weight and local fat by a combination of ultrasound and a putative fat-reducing dietary supplement in mice. The described method significantly decreases local fat pad deposition, weight and plasma lipid levels., (2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved)

Objective: To investigate the prevalence of nutritional risk and malnutrition among in-patients with liver diseases in Beijing, China, and to evaluate the relationship between nutritional risk and prognosis., Methods: A total of 331 in-patients with liver diseases under care at the Artificial Liver Center of Beijing Youan Hospital were consecutively enrolled for study between April 2012 and December 2012. Nutritional status was determined by calculating each patient's ratio of real weight to clinically ideal weight, the triceps skin fold (TSF), and the mid-upper arm muscle circumference (MAMC). Nutritional risk was estimated using the Nutritional Risk Screening questionnaire 2002 (NRS-2002). In addition, each patient's Child-Pugh stage, body mass index (BMI), power of gripping, serum albumin and pre-albumin levels, lymphocyte count, hospital length of stay, complications, alcoholism history, and outcome after discharge were recorded for analysis., Results: One-hundred-and-thirteen of the patients (34.1%) were defined as at nutritional risk upon hospital admission. The ratio of nutritional risk was lowest in patients with chronic hepatitis (17.0%) and highest in patients with acute on chronic liver failure (56.5%). The ratios of malnutrition evaluated by TSF and MAMC were 36.9% and 38.7%, respectively. Among the patients with liver cirrhosis or hepatocellular carcinoma, the ratio of Child-Pugh stage C was higher for individuals defined as at nutritional risk than for those without. When TSF-based ratio of malnutrition was higher for individuals with a history of alcoholism than for those without. BMI, power of gripping, serum albumin level, serum pre-albumin level, and lymphocyte count were all lower for individuals defined as at nutritional risk than for those without. Hospital stay, ratio of complication onset, and ratio of death were all higher for individuals defined as at nutritional risk than for those without., Conclusion: TSF and MAMC can be used to evaluate the nutritional status of in-patients with liver diseases. Patients with nutritional risk (as determined by the NRS-2002) have poorer prognosis and may benefit from nutritional intervention.

Molecular chaperones are reported to be crucial for virus propagation, but are not yet addressed in Human Enterovirus 71 (EV71). Here we describe the specific association of heat shock protein-90-beta (Hsp90β), but not alpha form (Hsp90α), with EV71 viral particles by the co-purification with virions using sucrose density gradient ultracentrifugation, and by the colocalization with viral particles, as assessed by immunogold electron microscopy. The reduction of the Hsp90β protein using RNA interference decreased the correct assembly of viral particles, without affecting EV71 replication levels. Tracking ectopically expressed Hsp90β protein associated with EV71 virions revealed that Hsp90β protein was transmitted to new host cells through its direct association with infectious viral particles. Our findings suggest a new antiviral strategy in which extracellular Hsp90β protein is targeted to decrease the infectivity of EV71 and other enteroviruses, without affecting the broader functions of this constitutively expressed molecular chaperone., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: The relationship between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphisms and intracranial aneurysm (IA) has been studied in Caucasian and Japanese populations. The present study aimed to investigate this association in a Chinese population., Methods: Patients with confirmed IA and age- and sex-matched control subjects without evidence of IA were enrolled. ACE I/D gene polymorphisms were analysed using polymerase chain reaction-restriction fragment length polymorphism., Results: A total of 220 patients with IA and 220 matched controls were enrolled. In the IA group, 64, 106 and 50 patients were of the II, ID and DD genotypes, respectively, compared with 44, 99 and 77 subjects in the control group. The ACE DD genotype and D allele frequencies were significantly lower in the IA group compared with the control group. There were no statistically significant differences in the site, shape, size and Fisher Grade of aneurysms between genotypes in patients with IA., Conclusion: The ACE DD genotype may be a protective factor for IA in a Chinese population.

The purpose of this study is to develop a new formulation for prostaglandin E₁ (PGE₁)-loaded lipid emulsion (Lipo-PGE₁) with improved stability and reduced biodegradation. High-pressure homogenization was used to prepare the Lipo-PGE₁, and high-performance liquid chromatography and accelerated test were used to evaluate its physicochemical stability. A tissue homogenate incubation test was firstly established and validated to assess its biodegradation. The factors influencing the stability of Lipo-PGE₁, including oil phase, emulsifier, pH value, and drug concentration were systematically investigated. The optimized formulation consisting of poloxamer188 1.5% (w/v), egg lecithin 0.5% (w/v), soybean oil 10.0% (w/v), oleic acid 0.24% (w/v), and glycerol 2.2% (w/v), with the pH value at 4.0, was defined and characterized. When compared with the currently available commercial product of Lipo-PGE₁, the degradation percentage of this optimized Lipo-PGE₁ reduced by 47.1% after sterilization, the drug remaining percentage increased by 13.9% after storage at 4°C over 6 months. Also, a significant reduction in biodegradation of the optimized Lipo-PGE₁ in comparison with the commercial Lipo-PGE₁ was observed by a tissue homogenate incubation test. Overall, we provided a novel formulation for Lipo-PGE₁ with a better physicochemical stability and a less biodegradation than the currently available commercial product of Lipo-PGE₁, indicating its potential superiority in clinical application.

Severe adverse events have been frequently associated with taking the commercially available formulation of α-asarone injection (α-asarone-I). Hence, we sought to develop an intravenous lipid emulsion of α-asarone (α-asarone-LE), where we hypothesized that these adverse events could be prevented. Using a central composite design-response surface methodology, we developed and optimized an emulsion formulation of α-asarone-LE that composed of 10.0% (w/v) soybean oil, 0.4% (w/v) α-asarone, 1.2% (w/v) soybean lecithin, 0.3% (w/v) F68, and 2.2% (w/v) glycerol. The mean particle size of α-asarone-LE was 226±11 nm, the ζ-potential was -25.6±1.2 mV, the encapsulation efficiency was 99.2±0.1% and the drug loading efficiency was 3.45%. Stability, safety, and efficacy studies of α-asarone-LE were systematically investigated and compared to those of α-asarone-I. The α-asarone-LE not only showed a desired stability, but also exhibited excellent safety and improved efficacy in vivo, indicating its great potential for clinical application in the future., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: To isolate and identify the pituitary adenoma stem-like cells from pituitary adenoma tissue., Methods: Total RNA was prepared with 42 cases of pituitary adenoma tissue samples frozen in liquid nitrogen, the expression of Nestin was detected by RT-PCR. Tumor spheres were cultured in serum-free conditions and the immunefluorescence were used to detect the expression of stem cell markers such as Nestin, Sox2., Results: The positive rate of Nestin mRNA expression was 88.1% (37/42). The cultured tumor spheres were found positive for Nestin, Sox2 by immunefluorescence detection., Conclusion: Stem cell markers are expressed in the pituitary adenoma tissue and the pituitary adenoma stem-like cells can be cultured in serum-free condition.

Objective: To determine the value of urine volume and urine electrolytes in postoperative management of patients with sellar tumors., Methods: Medical records of 103 patients with sellar tumors in the West China Hospital from January 2009 to December 2009 were retrospectively reviewed. The patients were managed either based on blood electrolytes (Group A, n = 56) or based on urine volume and urine electrolytes (Group B, n = 47). The incidence of balance disturbance of water and electrolytes was compared between the two groups., Results: The levels of blood electrolytes were normal in both groups 3 days after operations despite significant loss of electrolytes through urine. Balance disturbance of water and electrolytes was revealed 4-7 days after operations. Group B had a lower incidence of balance disturbance of water and electrolytes (17.02%, 8/47) compared with Group A (73.21%, 41/56, P < 0.05). No gender difference in the incidence of balance disturbance of water and electrolytes was found. Higher incidence of balance disturbance of water and electrolytes was found in craniopharyngioma (P < 0.05, vs. pituitary adenoma) and in the patients undergoing craniotomy (P < 0.05, vs. transsphenoidal approach) in Group A, but not in Group B., Conclusion: Better management of balance disturbance of water and electrolytes can be achieved for patients with sellar tumors through monitoring urine than through blood. It can also simplify the postoperative management of patients with sellar tumors.

Objective: To explore the value of dual-time-point (18)F-fluorodeoxyglucose integrated positron emission and computed tomography ((18)F-FDG PET-CT) in differentiation of malignant from benign gastrointestinal diseases., Methods: Sixty five patients with suspected gastrointestinal lesions underwent dual-time-point (18)F-FDG PET-CT imaging. Standardized uptake value (SUV) was calculated for semi-quantitative assessment. The SUV of the two acquisitions were signed SUV(early) and SUV(delayed), respectively. Then the change of SUVmax (ΔSUVmax) was calculated. The ROC curves of the SUV(early), SUV(delayed) and ΔSUV were drawn to find the best cut-off point value for differential diagnosis, and then the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated, respectively., Results: Of the malignant lesions, the SUVmax in delayed imaging were significantly higher than those in early imaging, while there were no significant differences of SUVmax between the two images of the benign lesions. The ΔSUVmax of the malignant lesions were significantly higher than that of the benign ones. Taking the SUVmax higher than 9.2 in early imaging as positive diagnostic criteria, the sensitivity was 72.7%, the specificity was 85.7%, the positive predictive value was 91.4%, the negative predictive value was 60.0%, and the accuracy was 76.9%. Taking the SUVmax higher than 10.9 in delayed imaging as positive diagnostic criteria, the sensitivity was 75.0%, the specificity was 90.5%, the positive predictive value was 94.3%, the negative predictive value was 63.3%, and the accuracy was 80.0%. Taking the ΔSUVmax higher than 5.1% as positive diagnostic criteria, the sensitivity was 95.5%, the specificity was 85.7%, the positive predictive value was 93.3%, the negative predictive value was 90.0%, and the accuracy was 92.3%. The accuracy of dual-time-point (18)F-FDG PET-CT imaging was significantly higher than that of single-time point (18)F-FDG PET-CT imaging., Conclusion: Dual-time-point (18)F-FDG PET-CT imaging is a useful method for differentiating malignant from benign gastrointestinal diseases, and it is superior to the single-time point (18)F-FDG PET-CT imaging.

The purpose of this study was to develop a lipid emulsion of tanshinone IIA (Tan IIA-LE) for intravenous administration and to investigate its feasibility for future clinical practice. The formulation was optimized using central composite design-response surface methodology (CCD-RSM), and the homogenization process was investigated systematically. The Tan IIA-LE was evaluated in terms of stability, safety and in vitro anti-hepatoma activity. The formulation of Tan IIA-LE is composed of 0.05% (w/v) Tan IIA, 20% (w/v) soybean oil-MCT mixture (1:1, w/w), 1.2% (w/v) soybean lecithin, 0.3% (w/v) F68 and 2.2% (w/v) glycerol, a high pressure homogenization at 100 MPa for 3 cycles was selected as the optimal homogenization process. The Tan IIA-LE was light-sensitive but stable for at least 12 months at room temperature in dark. The safety study demonstrated that the Tan IIA-LE did not cause venous irritation or obvious acute toxicity. Furthermore, the Tan IIA-LE displayed significant anti-tumor activity against human hepatoma cell lines in vitro. Overall, the Tan IIA-LE developed in this study was suggested to be a suitable and safe dosage form of Tan IIA for intravenous administration and has potential in liver cancer therapy in future., (Copyright © 2011 Elsevier B.V. All rights reserved.)