Arenobufagin-loaded PEG-PLA nanoparticles for reducing toxicity and enhancing cancer therapy.

Arenobufagin (ArBu) is a natural anticancer drug with good anti-tumor effects, but its clinical applications and drug development potential are limited due to its toxicity. The purpose of this study is to reduce the toxic side effects of ArBu and improve the efficacy of tumor treatment by incorporating it into poly(ethylene glycol)-b-poly (lactide) co-polymer (PEG-PLA). ArBu@PEG-PLA micelles were prepared by a thin film hydration method. The optimized micelles were characterized by size, stability, drug loading, encapsulation rate, and drug release. The tumor-inhibition efficacy of the micelles was evaluated on A549 cells and tumor-bearing mice. The ArBu@PEG-PLA micelles have good drug-loading capacity, release performance, and stability. They can accumulate at the tumor site through the EPR effect. The micelles induce apoptosis through a mitochondrial apoptosis pathway. Compared with the free ArBu, the ArBu@PEG-PLA micelles had lower toxicity and higher safety in the acute toxicity evaluation experiment. The in vivo anti-tumor experiment with tumor-bearing mice showed that the tumor-inhibition rate of ArBu@PEG-PLA micelles was 72.9%, which was 1.28-fold higher than that of free ArBu (57.1%), thus showing a good tumor treatment effect. This study indicates that ArBu@PEG-PLA polymeric micelles can significantly improve the toxicity and therapeutic efficacy of ArBu. These can lead to a new therapeutic strategy to reduce the toxicity of ArBu and enhance tumor treatment.

Aristolochia yachangensis, a new species of Aristolochiaceae from limestone areas in Guangxi, China.

Aristolochia yachangensis B.G.Huang, Yan Liu & Y.S.Huang, a new species from limestone areas in Guangxi, China, is described and illustrated. It is morphologically most similar to A. fangchi Y.C.Wu ex L.D.Chow & S.M.Hwang, A. petelotii O.C. Schmidt and A. championii Merr. & Chun in shape of leaf blade, anther, gynostemium and inflorescence on old woody stems. However, it can be easily distinguished from the latter by shape of inflorescence, length of upper and lower portions of perianth tube, colour of the limb and throat. A table and a key to distinguish the new species from other morphologically similar Aristolochia species are also provided.

Can the descending aortic stroke volume be estimated by transesophageal descending aortic photoplethysmography?

PURPOSE: The aim of this study was to investigate the ability of transesophageal photoplethysmography detected from the descending aorta (dPPG) for predicting low descending aortic stroke volume (dSV) level in cardiac surgical patients. METHODS: Fifteen patients scheduled for elective cardiac surgery were enrolled in our study. A transesophageal echocardiography (TEE) probe with an attached oximetry sensor was placed into the esophagus for paired dPPG signal and descending aortic Doppler blood flow signal acquisition. Metrics, including alternating current (AC), direct current (DC), area under the curve (AUC) and width (W), were extracted from the dPPG signals. The TEE-measured dSV, which was defined as the blood flow through the descending aorta during a cardiac cycle, was chosen as the standard reference. A receiver operating characteristic (ROC) curve was built to evaluate the performance of dPPG metrics in predicting low dSV level, and dSV measuring agreement between TEE and dPPG was analyzed by the Bland-Altman method. RESULTS: A total of 644 paired dPPG and Doppler signals of the descending aorta were acquired. Significant correlations were found between the dPPG metrics and TEE-measured dSV, and the correlation coefficients between TEE-measured dSV and AUC or AC were 0.64 and 0.66, respectively. AUC and AC values obviously decreased with the reduction of dSV level among the three groups (<20 mL, from 20-40 mL, and >40 mL). The areas under the ROC curve for AUC and AC in predicting low dSV level (<20 mL) were 0.85 and 0.88, respectively. Bland-Altman plot showed a small bias (0.02 mL) but a wide limit of agreement (-18.62 to 18.66 mL) in dSV measurement between dPPG and Doppler technology. CONCLUSIONS: The AC and AUC extracted from the dPPG signal provided a sensitive and qualitative prediction for dSV level. The dSV value could not be accurately measured by dPPG metrics. TRIAL REGISTRATION: Chinese Clinical Trials Register Identifier: ChiCTR-OCS-12002789.

Proteomic Analysis of the Excretory and Secretory Proteins of Haemonchus contortus (HcESP) Binding to Goat PBMCs In Vivo Revealed Stage-Specific Binding Profiles.

Haemonchus contortus is a parasitic gastrointestinal nematode, and its excretory and secretory products (HcESPs) interact extensively with the host cells. In this study, we report the interaction of proteins from HcESPs at different developmental stages to goat peripheral blood mononuclear cells (PBMCs) in vivo using liquid chromatography-tandem mass spectrometry. A total of 407 HcESPs that interacted with goat PBMCs at different time points were identified from a H. contortus protein database using SEQUEST searches. The L4 and L5 stages of H. contortus represented a higher proportion of the identified proteins compared with the early and late adult stages. Both stage-specific interacting proteins and proteins that were common to multiple stages were identified. Forty-seven interacting proteins were shared among all stages. The gene ontology (GO) distributions of the identified goat PBMC-interacting proteins were nearly identical among all developmental stages, with high representation of binding and catalytic activity. Cellular, metabolic and single-organism processes were also annotated as major biological processes, but interestingly, more proteins were annotated as localization processes at the L5 stage than at the L4 and adult stages. Based on the clustering of homologous proteins, we improved the functional annotations of un-annotated proteins identified at different developmental stages. Some unnamed H. contortus ATP-binding cassette proteins, including ADP-ribosylation factor and P-glycoprotein-9, were identified by STRING protein clustering analysis.

[Effects of thermal and mechanical cycling on the metal-ceramic bond strength of machine-milled Ti2448 alloy and pure titanium].

OBJECTIVE: To evaluate the effects of thermal and mechanical cycling on the metal-ceramic bond strength of machine-milled Ti2448 alloy and commercial pure titanium (cp Ti). METHODS: Ceramic-cp Ti (n = 30) specimens and ceramic-Ti2448 combinations (n = 30) were prepared in accordance with ISO 9693. The specimens from each metal-ceramic combination were randomly divided into three subgroups. In group A or the control group, the specimens were only stored in distilled water for 24 h at 37 °C; in groups B and C, the specimens were subjected to 3,000 cycles of thermal cycling between 5 and 55 °C for a dwell time of 60 s and to mechanical cycling of 20,000 or 40,000 cycles with 50 N load and 4 Hz in distilled water at 37 °C. A crack initiation test was performed using a universal testing machine in accordance with ISO 9693. Failure types at the metal-ceramic interface and the morphological and elemental composition of this interface were analyzed using a scanning electron microscope and an energy dispersive spectrometer. Statistical analysis was performed via two-way ANOVA and Tukey's adjustment test (α = 0.05). RESULTS: The bond strength of the ceramic-Ti2448 combination was significantly higher than that of the ceramic-cp Ti combination regardless of fatigue conditions (44.86 MPa ± 1.75 MPa and 29.21 MPa ± 2.20 MPa for Ti2448 and cp Ti, respectively; P < 0.01). The mean bond strengths of ceramic-cp Ti and ceramic-Ti2448 combinations in group C were significantly lower than that of group A (P < 0.01). Although ceramic-cp Ti combination failed adhesively at the metal-ceramic interface without the ceramic on the substrate surface, Ti2448 frameworks exhibited cohesive failure; as a result, large amounts of residual porcelain were retained on the specimens. CONCLUSION: The metal-ceramic bond strength of cp Ti and Ti2448 is decreased by thermal and mechanical cycling.

CT findings and clinical features of pancreatic hemolymphangioma: a case report and review of the literature.

Pancreatic hemolymphangioma is a very rare benign tumor. There were only 10 reports of this disease until June 2014.The aim of the present study was to describe a hemolymphangioma in the neck and body of the pancreas in a 57-year-old woman.The method used in the present study consists of description of the clinical history, image lab features, and pathological result.The patient complained of a 10-day history of epigastric discomfort. Abdominal computed tomography (CT) showed a cystic-solid tumor with an irregular shape, in the neck and body of the pancreas. The tumoral cystic wall and its internal division could be seen intensified on contrast-enhanced CT images compared with those on precontrast images. The pathological examination confirmed the diagnosis.The clinical feature of pancreatic hemolymphangioma includes a lack of specificity. The CT appearance combined with age and sex may be useful in making an early diagnosis.

Severe burn injury in late pregnancy: a case report and literature review.

The management of serious burn injuries during pregnancy is an unsolved clinical problem because of the low incidence of this disease. Although it has been documented that the effect of burns on fetal and maternal survival is detrimental, there have been conflicting reports among the different burn centers regarding the mortality of burned pregnant women and the management of burn patients during pregnancy. We report a case of severe burn in late pregnancy treated at our burn center. Additionally, we searched and summarized the literature concerning the management of pregnant patients to provide useful information for their treatment.

Characterization and quantitative amino acids analysis of analgesic peptides in cinobufacini injection by size exclusion chromatography, matrix-assisted laser desorption/ionization time of flight mass spectrometry and gas chromatography mass spectrometry.

Cinobufacini injection that comes from the water extract of Bufo bufo gargarizans Cantor skin is widely used for cancer treatment in China. Peptide is one of its major types of constituents, however the biological effects and content of this injection are little reported. In present study, the analgesic effect of peptides was determined and evaluated by in-vivo models. To characterize and quantitatively analyze these peptides, a reliable and efficient method combining size exclusion chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with amino acid analysis was developed. The peptides presented as a series of analogs with similar molecular weights mostly ranging from 2 to 8 kDa. The amino acid analysis by gas chromatography mass spectrometry (GC-MS) was developed to determine both free and combined amino acids (FAA and CAA) in cinobufacini injection. This method achieved good linearity (R(2) , 0.9909-0.9999) and low limit of detection and quantification. FAA and CAA samples were efficiently analyzed by modified Phenomenex EZ: faast procedure. For the sample analysis, the method showed good repeatability (relative standard deviation, RSD ≤ 10%). For most FAA and CAA the mean recoveries were >80% with RSD <10%. The GC-MS based method is useful for quality assurance of both FAA and CAA in cinobufacini injection.

TLR4-dependent immune response promotes radiation-induced liver disease by changing the liver tissue interstitial microenvironment during liver cancer radiotherapy.

Liver tissue interstitial fluid (TIF) a special microenvironment around liver cells, which may play a vital role in cell communication during liver injury. Moreover, toll-like receptor 4 (TLR4) is an important trigger of the immune response that may also play a role in liver injuries, including radiation-induced liver disease (RILD). Therefore, the purpose of this study was to identify the roles of the TLR4-dependent immune response and TIFs in RILD after radiation therapy (RT) for liver cancer. This study consisted of two phases, and in the primary phase, the livers of TLR4 mutant (TLR4(-)) and normal (TLR4(+)) mice were irradiated with 30 Gy. TIF was then obtained from mouse livers and assessed by cytokine array analysis 20 days after irradiation, and cytokines in the TIFs, TLR4 and RILD were analyzed. In the second or validation phase, hepatocytes were isolated from TLR4(+) or TLR4(-) mice irradiated with 8 Gy and were co-cultured with TIFs from mouse livers, apoptosis of the hepatocytes was then measured using flow cytometry. We found that severe RILD was accompanied by higher expression of granulocyte macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and vascular endothelial growth factor receptor 2(VEGFR-2) in liver TIFs, from in TLR4(+) mice compared with TLR4(-) mice (P < 0.05). In both TLR4(+) and TLR4(-) hepatocytes, apoptosis after irradiaton was increased significantly after co-culture in TIFs from TLR4(+) mice that had their livers irradiated, compared with TIFs from TLR4(-) mice that had their livers irradiated or TIFs from unirradiated mice (P < 0.05). In summary, these findings indicate that the TLR4-dependent immune response may promote RILD by enhancing the expression of GM-CSF, VEGFR-2 and TRAIL in liver TIFs.

Assessment of postoperative pain intensity by using photoplethysmography.

PURPOSE: Timely assessment of acute postoperative pain is very important for pain management. No objective and reliable method to assess postoperative pain intensity exists till now. The aim of the study was to investigate the feasibility of photoplethysmography (PPG) signals in postoperative pain assessment. METHODS: Thirty patients scheduled for elective abdominal surgery under general anesthesia were examined. Finger PPG signals and visual analogue scale (VAS) score were acquired before and 5, 10, 20, and 30 min after sufentanil administration when the patients were awake and transferred to the post-anesthesia care unit (PACU). During each pain rating, the patient's blood pressure, heart rate, and pulse oxygen saturation were recorded. The amplitude of alternating current (AC) and direct current (DC) extracted from finger PPG signals were analyzed, and the ratio of AC and DC (AC/DC) was calculated. Receiver operating characteristic (ROC) curves were built to assess the performance of AC and AC/DC to detect patients with VAS >4 in the PACU. RESULTS: After administration of sufentanil, VAS scores decreased significantly (p < 0.05), as did blood pressure and heart rate. Simultaneously, both values of AC and AC/DC increased significantly. The VAS score had significant correlations with AC (r = -0.477; p < 0.01), AC/DC (r = -0.738; p < 0.01) and heart rate (r = 0.280; p < 0.01). In contrast, no statistical correlations between VAS score and blood pressure were found. Further analysis found significant differences in both AC and AC/DC among different pain levels, but no obvious differences in blood pressures and heart rate. The area under the ROC curves were 0.754 for AC and 0.795 for AC/DC, respectively. CONCLUSION: The finger PPG signal can be used in acute postoperative pain assessment. Both AC/DC and AC had significant correlations with the pain rating levels, while blood pressure and heart rate were unreliable in pain assessment.

Relationships between edema degree and clinical and biochemical parameters in posterior reversible encephalopathy syndrome: a preliminary study.

The objective of the study was to investigate the associations between the degree of edema with the clinical and biochemical parameters such as serum lactate dehydrogenase (LDH), albumin (ALB) in posterior reversible encephalopathy syndrome (PRES) patients. Forty-nine patients with typical clinical symptoms and characteristic MR imaging findings of PRES were included in this study. Lactate dehydrogenase and ALB were analyzed with the immunoluminometric assays. Fluid-attenuated inversion recovery images were used to evaluate the distribution of the extent or severity of vasogenic edema by two observers. Correlation analysis between the scores of brain edema and the blood pressures, clinical conditions and biochemical parameters was performed. No significant difference of brain edema score was found between patients with eclampsia, chronic renal failure and other clinical condition (P > 0.05). Both mean arterial pressures and LDH level were moderately correlated with the scores of brain edema distribution (Spearman's ρ test, r = 0.405 and 0.497, respectively, P < 0.01). Serum ALB level was not correlated with the scores of brain edema distribution (P > 0.05). Larger and more diffuse lesions may be predicted by higher LDH level and blood pressure. The overall severity of the systemic process might be predicted by the degree of edema expression in PRES.

[Comparison between intermingled skin transplantation and microskin grafting in repairing massive deep burn].

OBJECTIVE: To study difference in curative effect between intermingled skin transplantation (IT) and microskin grafting (MG) in repairing massive deep burn. METHODS: Clinical materials of 101 patients with massive deep burn hospitalized from 1992 to 2008 were retrospectively summarized. Patients were divided into IT group (n = 52) and MG group (n = 49). The size of initial donor site for autologous skin, the wound size initially covered with autologous skin, the survival rate of initial autologous skin grafting, the theoretical expansion multiple of the autologous skin, the actual expansion multiple of the autologous skin, the total size of donated autologous skin, the remained wound condition, and the function of large joint of patients in two groups were compared. RESULTS: In IT group and MG group, the size of initial donor site for autologous skin was respectively (3.25 +/- 0.48)%TBSA and (3.01 +/- 0.21)%TBSA, the wound size initially covered by autologous skin was respectively (30.4 +/- 3.6)%TBSA and (41.4 +/- 1.3)%TBSA, the survival rate of autologous skin grafting was respectively (99.9 +/- 1.9)% and (87.5 +/- 6.8)%, the theoretical expansion multiple of the autologous skin was respectively 9.5 +/- 1.3 and 13.9 +/- 1.4, the actual expansion multiple of the autologous skin was respectively 9.5 +/- 1.3 and 12.0 +/- 1.5, the difference between two figures of each index was statistically significant (P < 0.05). There was no statistical significant difference between IT and MG group in respect of the total size of donated autologous skin [respectively (14.2 +/- 1.9) and (14.0 +/- 2.1)%TBSA, P > 0.05]. There were 23 patients (44.2%) with residual wounds over 0.5%TBSA in IT group, and 37 cases (75.5%) in MG group. There were 34 patients (65.4%) with good function of large joints in IT group, and 18 cases (36.7%) in MG group. CONCLUSIONS: Expansion multiple of autologous skin after MG is obviously larger than that after IT, thus limited skin source can be fully used. The wound healing quality and the restoration of large joint function of patients treated with IT are better than those of patients treated with MG.

Neuroimaging and pathological findings in a child with cerebral sparganosis. Case report.

The authors report the case of a 6-year-old boy with cerebral sparganosis due to infection with a plerocercoid tapeworm larva of Spirometra mansoni. Magnetic resonance imaging revealed an area of irregular long T2 signal in the right frontal lobe. When compared with images obtained 2 years earlier, the lesion appeared to have migrated into the parietal lobe. During surgery for the removal of a granuloma, the parasite was discovered and excised. Following surgery, the patient's neurological deficits markedly improved. The authors review the pathological and imaging features of cerebral sparganosis.

Expression, purification and characterization of the Hepatitis B virus entire envelope large protein in Pichia pastoris.

The current HBsAg vaccine has performed a vital role in preventing the transmission of HBV during the past 20 years. However, a number of individuals still show no response or a low response to the vaccine. In the present study, the HBV envelope large protein gene was cloned into the eukaryotic expression vector pPIC9k and was subsequently expressed in the yeast Pichia pastoris. The HBV large protein (L protein) was produced and secreted into the medium, where some of the L protein formed particles. The soluble L protein and particles were purified by column chromatography and sucrose density gradient centrifugation. Western blot analysis demonstrated that the particle was composed of both HBV L and S protein. To compare the antigenicity of the L protein and HBsAg, rabbits were immunized with the soluble L protein and the commercially available HBV vaccine and the increasing level of antibodies was determined by ELISA. The results showed that the anti-HBsAg antibody, from rabbits injected with the L protein at a dose of 2 and 10microg, was detected on day 14, whereas rabbits vaccinated with 10 and 2microg HBsAg did not develop antibodies until day 21 and 28, respectively. The antibody level in groups inoculated with the L protein was approximately 50% higher than in the group injected with HBsAg using the same dose. Furthermore, 2microg L protein induced a significant and rapid anti-HBsAg antibody response than 10microg HBsAg. Therefore, we suggest that the L protein is an ideal candidate for a new generation HB vaccine to protect people from HBV infection.

Raman spectroscopic analysis of supersaturated aqueous solution of MgO.B2O3-32%MgCl2-H2O during acidification and dilution.

Raman spectra of supersaturated aqueous solution of MgO.B2O3-32%MgCl2-H2O during acidification/alkalization and dilution have been studied. The assignments of the recorded Raman shift are given. The main existing forms of polyborate anions and their interaction in borate aqueous solution have been proposed through spectroscopic analysis. The experimental results indicate that the higher concentration of cation are beneficial not only to the dissolution of boric acid but also to the polymerization of polyborate anions. The existing forms and interaction among them also depend on the concentration of boron and the pH value in solution.

FT-IR and Raman spectroscopic analysis of hydrated cesium borates and their saturated aqueous solution.

Hydrated cesium borates have been synthesized by the reaction of Cs(2)CO(3) with H(3)BO(3) aqueous solution. After reaction equilibria were reached, liquid and solid phases were separated and the FT-IR difference and Raman spectra of each phase were recorded, respectively. The assignments of the recorded FT-IR absorption frequencies and Raman shift are given. The main polyborate anions and their interaction in borate aqueous solution have been proposed. The relations between the existing forms of polyborate anions and the crystallizing solid phases, Cs(2)B(4)O(7).5H(2)O and CsB(5)O(8).4H(2)O, have been gained.

The modification by systemic morphine of the responses of serotonergic and non-serotonergic neurons in nucleus raphe magnus to heating the tail.

In anaesthetised rats, 63 raphe-spinal units in nucleus raphe magnus (NRM) have been identified by means of electrophysiological methods and further classified into serotonergic (5-HT) and non-5-HT units according to their conduction velocity and spontaneous discharge rate. All units, except one, showed either excitatory (n = 39) or inhibitory (n = 23) responses to noxious heating of the tail with hot water at 52 degrees C. The threshold temperature was around 44 degrees C and both types of responses increased with stepwise increases in temperature. The excitatory or inhibitory responses of raphe-spinal units induced by noxious heating of the tail correlated well with those elicited by noxious pinching, but did not correlate with the different transmitter populations (5-HT or non-5-HT) of the NRM unit. The effects of morphine or Fentanyl administration on the heat-induced responses of NRM units was observed. The possible involvement of NRM raphe-spinal units in 'diffuse noxious inhibitory controls' (DNICs) was discussed, particularly in relation to the 'lifting of DNICs' produced by morphine.