Postoperative adjuvant tyrosine kinase inhibitors combined with anti-PD-1 antibodies improves surgical outcomes for hepatocellular carcinoma with high-risk recurrent factors.

Background: The clinical value of postoperative adjuvant therapy (PAT) for hepatocellular carcinoma (HCC) remains unclear. This study aimed to explore the effect of PAT with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies on the surgical outcomes of HCC patients with high-risk recurrent factors (HRRFs). Methods: HCC patients who underwent radical hepatectomy at Tongji Hospital between January 2019 and December 2021 were retrospectively enrolled, and those with HRRFs were divided into PAT group and non-PAT group. Recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups after propensity score matching (PSM). Prognostic factors associated with RFS and OS were determined by Cox regression analysis, and subgroup analysis was also conducted. Results: A total of 250 HCC patients were enrolled, and 47 pairs of patients with HRRFs in the PAT and non-PAT groups were matched through PSM. After PSM, the 1- and 2-year RFS rates in the two groups were 82.1% vs. 40.0% (P < 0.001) and 54.2% vs. 25.1% (P = 0.012), respectively. The corresponding 1- and 2-year OS rates were 95.4% vs. 69.8% (P = 0.001) and 84.3% vs. 55.5% (P = 0.014), respectively. Multivariable analyses indicated that PAT was an independent factor related to improving RFS and OS. Subgroup analysis demonstrated that HCC patients with tumor diameter > 5 cm, satellite nodules, or vascular invasion could significantly benefit from PAT in RFS and OS. Common grade 1-3 toxicities, such as pruritus (44.7%), hypertension (42.6%), dermatitis (34.0%), and proteinuria (31.9%) were observed, and no grade 4/5 toxicities or serious adverse events occurred in patients receiving PAT. Conclusions: PAT with TKIs and anti-PD-1 antibodies could improve surgical outcomes for HCC patients with HRRFs.

Transformation mechanism of methylphosphonate to methane by Burkholderia sp: Insight from multi-labeled water isotope probing and transcriptomic.

Methylphosphonate (MPn), has been identified as a likely source of methane in aerobic ocean and may be responsible for the "ocean methane paradox", that is oversaturation of dissolved methane in oxic sea waters. However, the mechanism underlying the cleavage of C-P bonds during microbial degradation is not well understood. Using multi-labeled water isotope probing (MLWIP) and transcriptome analysis, we investigated the phosphate oxygen isotope systematics and mechanisms of microbial-mediated degradation of MPn in this study. In the aerobic culture containing MPn as the only phosphorus source, there was a significant release of inorganic phosphate (149.4 µmol/L) and free methane (268.3 mg/L). The oxygen isotopic composition of inorganic phosphorus (δ18OP) of accumulated released phosphate was 4.50‰, 23.96‰, and 40.88‰, respectively, in the corresponding 18O-labeled waters of -10.3‰, 9.9‰, and 30.6‰, and the slope obtained in plots of δ18OP versus the oxygen isotopic composition of water (δ18OW) was 0.89. Consequently, 89% of the oxygen atoms (Os) in phosphate (PO4) were exchanged with 18O-labeled waters in the medium, while the rest were exchanged with intracellular metabolic water. It has been confirmed that the C-P bond cleavage of MPn occurs in the cell with both ambient and metabolic water participation. Moreover, phn gene clusters play significant roles to cleave the C-P bond of MPn for Burkholderia sp. HQL1813, in which phnJ, phnM and phnI genes are significantly up-regulated during MPn decomposition to methane. In conclusion, the aerobic biotransformation of MPn to free methane by Burkholderia sp. HQL1813 has been elucidated, providing new insights into the mechanism that bio-cleaves C-P bonds to produce methane aerobically in aqueous environments for representative phosphonates.

Anti-depressant effects of acupuncture: The insights from NLRP3 mediated pyroptosis and inflammation.

The NLRP3-mediated pyroptosis, which could affect inflammation response, plays a key role in the development of depression. Acupuncture has been shown to be an effective treatment for depression. In this study, we aimed to determine whether acupuncture could confer antidepressant activity via decreasing NLRP3-mediated pyroptosis by reducing inflammation. Here, depression model of rats was induced by chronic unpredictable mild stress (CUMS) for 4 weeks. Acupuncture group was subjected to acupuncture at the Shangxing (GV23) and Fengfu (GV16) acupoints for 20 min every other day (a total of 14 times). Fluoxetine group was administered with fluoxetine (2.1 mg/kg with the concentration of 0.21 mg/mL) by oral gavage (1 mL/100 g) once a day for 28 days. Rats' depression-like phenotypes were reflected with behavioral tests and biological detection methods. Results showed that acupuncture significantly improved the depression-like behavior of CUMS rat, suppressed the expressions of NLRP3, ASC, caspase-1, GSDMD, IL-1ß, IL-18, HMGB1, IFN-γ, IL-6 and TNF-α in the serum and hippocampus, restored the %area of microglia, astrocytes and neuronal cells in the hippocampus. These indicate that acupuncture can prevent CUMS-induced depression-like behaviors by reducing NLRP3-mediated pyroptosis and inflammation.

Cost-Effectiveness of Oral Antidiabetic Drugs: A Prospective Multicenter Study of Real-World Patients.

This real-world, multicenter, prospective study aims to analyze the cost-effectiveness of prevalent oral antidiabetic drugs, including traditional Chinese medicine and its compounds, used in China. Type 2 diabetes patients initiated on one or several of the most prevalent antidiabetic drugs were recruited on the baseline and followed up over one year with no restriction on drug discontinuation, switching, and add-on. Different drugs were evaluated on their efficacy, adverse effect (AE), health-related quality of life (HRQoL), and cost. Treatments were defined as the intent-to-treat in the primary analysis and on-treatment in the sensitivity analyses. A rich set of patients' baseline characteristics was collected and controlled using the multivariate linear model in the primary analysis and inverse probability weighting and double selection-a machine learning algorithm-in the sensitivity analyses. Estimates of "raw" outcomes, which are not adjusted by covariates and calculated as subgroup means, show that the use of Xiaoke Pill alone and in combination is among the most effective therapies with 50% and 54% of patients reaching the control target of HbA1c < 6.5%. In terms of cost, Xiaoke Pill and gliclazide, which cost participants 4,350 and 5,150 RMB per year on average, are among the least costly therapies. After adjusting patient characteristics, monotherapy and combination therapy using the Xiaoke Pill again display the best control rates, of 45% and 43% against 33% of metformin. Regarding cost, the Xiaoke Pill costs a patient 5,340 RMB per year, in sharp contrast with 8,550 RMB for metformin and 10,330 RMB for acarbose. Our study suggests that the use of Xiaoke Pill-alone or in combination-is associated with better glycemic control and lower cost than some allopathic medications such as metformin or acarbose and shows a similar incidence of hypoglycemia.

The Role of Ophiopogonin D in Atherosclerosis: Impact on Lipid Metabolism and Gut Microbiota.

Gut microbiota has been proven to play an important role in many metabolic diseases and cardiovascular disease, particularly atherosclerosis. Ophiopogonin D (OPD), one of the effective compounds in Ophiopogon japonicus, is considered beneficial to metabolic syndrome and cardiovascular diseases. In this study, we have illuminated the effect of OPD in ApoE knockout (ApoE[Formula: see text] mice on the development of atherosclerosis and gut microbiota. To investigate the potential ability of OPD to alleviate atherosclerosis, 24 eight-week-old male ApoE[Formula: see text] mice (C57BL/6 background) were fed a high-fat diet (HFD) for 12 weeks, and 8 male C57BL/6 mice were fed a normal diet, serving as the control group. ApoE[Formula: see text] mice were randomly divided into the model group, OPD group, and simvastatin group ([Formula: see text]= 8). After treatment for 12 consecutive weeks, the results showed that OPD treatment significantly decreased the plaque formation and levels of serum lipid compared with those in the model group. In addition, OPD improved oral glucose tolerance and insulin resistance as well as reducing hepatocyte steatosis. Further analysis revealed that OPD might attenuate atherosclerosis through inhibiting mTOR phosphorylation and the consequent lipid metabolism signaling pathways mediated by SREBP1 and SCD1 in vivo and in vitro. Furthermore, OPD treatment led to significant structural changes in gut microbiota and fecal metabolites in HFD-fed mice and reduced the relative abundance of Erysipelotrichaceae genera associated with cholesterol metabolism. Collectively, these findings illustrate that OPD could significantly protect against atherosclerosis, which might be associated with the moderation of lipid metabolism and alterations in gut microbiota composition and fecal metabolites.

Identification of anti-Parkinson's Disease Lead Compounds from Aspergillus ochraceus Targeting Adenosin Receptors A2A.

Two novel alkaloids compounds together with fifteen know metabolites were identified from Aspergillus ochraceus. The stereochemistry features of the new molecules were determined via HRESIMS, NMR, ECD, and XRD analyses. Amongst these, compounds two compounds exhibited potential efficacy as anti-Parkinson's disease with the EC50 values of 2.30 and 2.45 µM, respectively. ADMET prediction showed that these compounds owned favorable drug-like characteristics and safe toxicity scores towards CNS drugs. Virtual screening analyses manifested that the compounds exhibited not only robust and reliable interactions to adenosine receptors A2A , but also higher binding selectivity to A2A receptors than to A1 and A3 receptors. Molecular dynamics simulation demonstrated the reliability of molecular docking results and the stability of the complexes obtained with the novel compounds and A2A receptors in natural environments. It is the first time that anti-PD lead compounds have been identified from Aspergillus ochraceus and targeting adenosine A2A receptors.

Geographical disparities in access to hospital care in Ontario, Canada: a spatial coverage modelling approach.

OBJECTIVES: Previous studies on geographical disparities in healthcare access have been limited by not accounting for the healthcare provider's capacity, a key determinant of supply and demand relationships. DESIGN: This study proposed a spatial coverage modelling approach to evaluate disparities in hospital care access using Canadian Institute for Health Information data in 2007. SETTING: This study focusses on accessibility of inpatient and emergency cares at both levels of individual hospital and the administrative regions of Local Health Integration Network (LHIN) levels. MEASURES: We integrated a set of traffic and geographical data to precisely estimate travel time as a measure of the level of accessibility to the nearest hospital by three scenarios: walking, driving and a combination of the both. We estimated population coverage rates, using hospital capacities and population in the catchments, as a measure of the level of the healthcare availability. Hospital capacities were calculated based on numbers of medical staff and beds, occupation rates and annual working hours of healthcare providers. RESULTS: We observed significant disparities in hospital capacity, travel time and population coverage rate across the LHINs. This study included 25 teaching and 148 community hospitals. The teaching hospitals had stronger capacities with 489 209 inpatient and 130 773 emergency patients served in the year, while the population served in community hospitals were 2.64 times higher. Compared with north Ontario, more locations in the south could reach to hospitals within 30 min irrespective of the travel mode. Additionally, Northern Ontario has higher population coverage rates, for example, with 42.6~46.9% for inpatient and 15.7~44% for emergency cares, compared with 2.4~34.7% and 0.35~14.6% in Southern Ontario, within a 30 min catchment by driving. CONCLUSION: Creating a comprehensive, flexible and integrated healthcare system should be considered as an effective approach to improve equity in access to care.

Dingxin Recipe IV attenuates atherosclerosis by regulating lipid metabolism through LXR-α/SREBP1 pathway and modulating the gut microbiota in ApoE-/- mice fed with HFD.

ETHNOPHARMACOLOGICAL RELEVANCE: Dingxin Recipe (DXR) is a traditional Chinese medicine formula that has been reported to be effective and safe treatment for cardiovascular diseases, such as arrhythmias, coronary heart disease. Dingxin Recipe IV (DXR IV) was further improved from the DXR according to the traditional use. However, the mechanism of DXR IV in atherosclerosis is unclear. AIM OF THE STUDY: This study aimed to illustrate whether DXR IV improve atherosclerosis through modulating the lipid metabolism and gut microbiota in atherosclerosis mice. MATERIALS AND METHODS: 40 male ApoE-/- mice were fed on HFD for 12 weeks and were then treated with DXR IV (1.8, 0.9, or 0.45 g/kg/d) for another 12 weeks. The decroation of DXR IV contains four traditional Chinese medicines: the dried rhizome of Coptis chinensis Franch. (15.09%), the root of Salvia miltiorrhiza Bunge (28.30%), the seed of Ziziphus jujuba Mill. (37.74%) and the fruiting body of Ganoderma lucidum (Leyss.ex Fr.) Karst. (18.87%). 8 male c57BL/6 mice fed a normal diet served as control group. The atherosclerotic plaque was quantified by oil-red O staining and masson trichrome staining. Mice feces were collected. The gut micobiota were detected by 16S rRNA gene sequencing and fecal metabolites were analyzed by 1H NMR spectroscopy. The effect of DXR IV on blood lipids (TG, TC, LDL-C, HDL-C) was investigated. The lipid metabolism related genes were determined by RT-qPCR and western blotting respectively. RESULTS: DXR IV exerted the anti-atherosclerosis effect by inhibiting the excessive cholesterol deposition in aorta and regulating the level of TG, TC, LDL-C and HDL-C. The composition of gut microbiota was changed. Interestingly, the relative abundance of Muribaculaceae and Ruminococcaceae increased after DXR IV administration, whereas the abundance of Erysipelotrichaceae decreased, which have been beneficial to lipid metabolism. Nine potential metabolic biomarkers, including acetate, butyrate, propionate, alanine, succinate, valerate, xylose, choline, glutamate, were identified, which were related to fatty acid metabolism. Further, the pathway of fatty acid was detected by the RT-qPCR and western blotting. Compared with model group, the level of LXR-α and SREBP1 decreased significantly in DXR IV group while LXR-ß, SREBP2 showed no statistical significance. It indicated that DXR IV modulated lipid metabolism by LXR-α/SREBP1 but not LXRß and SREBP2. CONCLUSIONS: DXR IV exhibits potential anti-atherosclerosis effect, which is closely related to lipid metabolism and the gut microbiota. This study may provide novel insights into the mechanism of DXR IV on atherosclerosis and a basis for promising clinical usage.

Dingxin recipe alleviates atherosclerosis injury in ApoE-knockout mice via downregulation of visfatin expression and inhibition of the visfatin-induced inflammatory response.

OBJECTIVE: To further elucidate the mechanism underlying the anti-atherosclerotic effect of Dingxin recipe (DXR). METHODS: Fifty 6-week-old male ApoE-/- mice were randomly divided into the following groups: model, simvastatin (5 mg·kg－1·d－1), DXR low-dose (9.30 g·kg－1·d－1), DXR middle-dose (18.59 g·kg－1·d－1) and DXR high-dose (37.18 g·kg－1·d－1) (n = 10). Ten male C57BL/6J mice were used as the control group. All ApoE-/- mice were fed a high-fat diet (HFD) and the control mice received a common diet. After HFD for 12 weeks, the mice were treated with DXR or simvastatin for another 12 weeks. The expression of inflammatory cytokines and visfatin was determined in serum and atherosclerotic lesions by enzyme-linked immunosorbent assay. Visfatin expression was also assessed in aortic atherosclerotic plaques. Cultured vessel endothelial cells (VECs) were pretreated with DXR sera prior to visfatin. The effects of DXR were analyzed to elucidate its protective mechanism against visfatin-induced inflammation in VECs. RESULTS: DXR regulated blood lipids and reduced tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), intercellular adhesion molecules-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and visfatin expression in ApoE-/- mice, particularly at the higher doses. The areas of atherosclerotic lesions in the DXR groups were significantly smaller than those in the model group. DXR alleviated visfatin-induced VEC injury via downregulation of TNF-α, IL-6, ICAM-1 and VCAM-1 through mitogen-activated protein kinase pathways. CONCLUSION: DXR alleviated atherosclerosis injury via downregulation of visfatin expression and inhibition of the visfatin-induced inflammatory response in VECs.

Autologous Platelet-Rich Plasmapheresis in Cardiovascular Surgery: A Narrative Review.

Perioperative coagulopathy and bleeding are common complications in cardiovascular surgery with cardiopulmonary bypass and result in an increased rate of allogeneic blood transfusion. Both bleeding and transfusion can increase postoperative mortality and morbidity. Patient blood management can significantly reduce allogeneic blood transfusions, improve clinical outcomes, and conserve blood resources; however, measures to protect platelets from destruction by cardiopulmonary bypass still are lacking. As an unusual method of autologous blood transfusion, autologous platelet-rich plasmapheresis can effectively protect platelets from damage and has been used successfully in cardiovascular surgery. This narrative review aims to address some major clinical applications and debates of using autologous platelet-rich plasmapheresis in cardiovascular surgery. In addition, this review summarizes the application of autologous platelet gel, a product developed from autologous platelet-rich plasma, in cardiac surgery.

A Purified Anthraquinone-Glycoside Preparation From Rhubarb Ameliorates Type 2 Diabetes Mellitus by Modulating the Gut Microbiota and Reducing Inflammation.

Rheum palmatum L. is widely used in traditional Chinese medicine for the treatment of constipation. Here, the therapeutic effects and underlying mechanisms of purified anthraquinone-glycoside preparation from rhubarb (RAGP) on the type 2 diabetes mellitus (T2DM) rats were investigated. After 6 weeks of metformin and RAGP treatment, the weight returned to normal. Fasting blood glucose (FBG), glycated serum protein (GSP), insulin concentration and HOMA-IR index had significantly decreased, and glucagon-like peptide-1 (GLP-1) concentrations had increased. Histological abnormalities in the pancreas and ileum had improved. These effects were associated with enhanced intestinal integrity, thereby reducing the absorption of lipopolysaccharide (LPS) and inflammation. To investigate whether RAGP ameliorated insulin resistance via effects on the gut microbiota, we performed 16s rDNA sequencing of ileal gut contents. This showed an amelioration of gut dysbiosis, with greater abundance of probiotic Lactobacillus and short-chain fatty acid-producing bacteria, and lower abundance of the Lachnospiraceae NK4A136 group and LPS-producing Desulfovibrio. The mechanism of the hypoglycemic effect of RAGP involves regulation of the gut microbiota, activation of the GLP-1/cAMP pathway to ameliorate insulin resistance. Thus, this study provides a theoretical basis for the use of RAGP to treat T2DM, and it may be a novel approach to restore the gut microbiota.

Sulfur and phosphorus co-doped graphene quantum dots for fluorescent monitoring of nitrite in pickles.

Doping graphene quantum dots (GQDs) with heteroatoms can change their band gap and electronic density, thus enhancing their fluorescence quantum yield (QY). In this work, we for the first time reported a nontoxic, rapid, and one-pot hydrothermal method to synthesize sulfur and phosphorus co-doped GQDs (S, P-GQDs). Citric acid was functioned as a carbon source, whereas sodium phytate and anhydrous sodium sulfate are used as the P and S sources, respectively, in this bottom-up synthesis. The resulting S, P-GQDs exhibit high heteroatomic doping ratios of 9.66 at.% for S and 3.34 at.% for P, and higher QY than those obtained from monoatomic doped GQDs. Additionally, the as-prepared S, P-GQDs exhibit excitation-dependent behavior, pH sensitivity between 8.0 and 13.0, high tolerance of ionic strength. More importantly, the as-synthesized S, P-GQDs show a sensitive and selective behavior for sensing nitrite (NO2-) in the concentration range of 0.7-9 µmol/L, and the detection limit was as low as 0.3 µmol/L. Additionally, the S, P-GQDs was successfully used in detecting NO2- in pickled foods, showing their promise for potential applications in realistic analysis.

Shift of microbial diversity and function in high-efficiency performance biotrickling filter for gaseous xylene treatment.

Xylene is the main component of many volatile industrial pollution sources, and the use of biotechnology to remove volatile organic compounds (VOCs) has become a growing trend. In this study, a biotrickling filter for gaseous xylene treatment was developed using activated sludge as raw material to study the biodegradation process of xylene. Reaction conditions were optimized, and long-term operation was performed. The optimal pH was 7.0, gas-liquid ratio was 15:1 (v/v), and temperature was 25 °C. High-throughput sequencing technique was carried out to analyze microbial communities in the top, middle, and bottom layers of the reactor. Characteristics of microbial diversity were elucidated, and microbial functions were predicted. The result showed that the removal efficiency (RE) was stable at 86%-91%, the maximum elimination capacity (EC) was 303.61 g·m-3·hr-1, residence time was 33.75 sec, and the initial inlet xylene concentration was 3000 mg·m-3, which was the highest known degradation concentration reported. Kinetic analysis of the xylene degradation indicated that it was a very high-efficiency-activity bioprocess. The rmax was 1059.8 g·m-3·hr-1, and Ks value was 4.78 g·m-3 in stationary phase. In addition, microbial community structures in the bottom and top layers were significantly different: Pseudomonas was the dominant genus in the bottom layer, whereas Sphingobium was dominant in the top layer. The results showed that intermediate metabolites of xylene could affect the distribution of community structure. Pseudomonas sp. can adapt to high concentration xylene-contaminated environments. Implications: We combined domesticated active sludge and reinforced microbial agent on biotrickling filter. This system performed continuously under a reduced residence time at 33.75 sec and high elimination capacity at 303.61 g·m-3·hr-1 in the biotrickling reactor for about 260 days. In this case, predomestication combined with reinforcing of microorganisms was very important to obtaining high-efficiency results. Analysis of microbial diversity and functional prediction indicated a gradient distribution along with the concentration of xylene. This implied a rational design of microbial reagent and optimizing the inoculation of different sites of reactor could reduce the preparation period of the technology.

Biocompatible Interface-Modified Tissue Engineering Chamber Reduces Capsular Contracture and Enlarges Regenerated Adipose Tissue.

Adipose flap expansion using a tissue engineering chamber (TEC) presents a promising candidate for soft tissue regeneration by activating in situ adipose tissue regeneration. However, foreign body reaction (FBR) and capsular contracture caused by a silicone chamber limit large tissue reconstruction. Here, a hydrophilic and biodegradable film made of poly(ethylene glycol) diacrylate (PEG-da) with methacrylated gelatin (gelatin-MA) was presented between the host tissue and silicone chamber to tune the local wound and to prevent initiation of FBR. After a 60 day investigation, 6.1-fold-regenerated fat tissue was obtained from the PEG-gelatin group, whereas only 3-fold tissue was harvested from a silicone group. Histological staining demonstrated that the structure of the neo-formed adipose tissue in both groups was similar to mature adipose tissue. Noticeably, a more distinct and denser fibrous capsule was observed in the silicone group compared to the PEG-gelatin group. Immunohistochemistry of CD206 and TGF-ß expression indicated less M2 macrophage infiltration and a minor inflammation reaction with PEG-gelatin assistance. Less collagen deposition and myofibroblast activation in the PEG-gelatin group were demonstrated via α-SMA and type I collagen staining. All these demonstrated that a biocompatible membrane supplement can attenuate capsule formation and contracture leading to a larger tissue regeneration through the TEC technique, which could lead to new perspectives to the relationship between materials-mattered FBR and tissue regeneration.

Polydatin Attenuates Atherosclerosis in ApoE -∕- Mice through PBEF Mediated Reduction of Cholesterol Deposition.

Cholesterol metabolism becomes imbalanced during the formation of macrophage-derived foam cells. Pre-B-cell colony-enhancing factor (PBEF) has recently been found to affect lipid deposition and inflammation in atherosclerosis. Here, we aimed to study the effects and molecular mechanism of Polydatin on atherosclerosis in ApoE-knockout (ApoE -∕- ) mice. Thirty ApoE -∕- mice were fed a high-fat diet (HFD) for 12 weeks, and then treated with Polydatin for another 12 weeks. Whole aortas and cryosections were stained with oil red O. Blood lipid, PBEF and cytokine levels were measured by ELISA. The mRNAs of cholesterol metabolism-related genes were determined by qRT-PCR and protein levels by Western blotting. Cell cholesterol content and viability were determined in macrophages and RAW 264.7 cells. PBEF siRNA was used to study the effect of Polydatin on cholesterol metabolism in macrophages incubated with ox-LDL. Polydatin lowered blood lipids and decreased atherosclerotic lesions in ApoE -∕- mice. The expression of cytokines and the mRNA of cholesterol metabolism-related genes were markedly regulated by Polydatin. Meanwhile, PBEF mRNA and protein were both greatly down-regulated by Polydatin. In vitro, Polydatin protected RAW 264.7 cells treated by ox-LDL and inhibited cholesterol uptake by macrophages. The PBEF siRNA result indicates that Polydatin can modulate cholesterol metabolism in macrophages, partly through down-regulation of PBEF. In conclusion, Polydatin relieves atherosclerosis injury in ApoE -∕- mice, mainly through down-regulation of PBEF and inhibition of PBEF-inducing cholesterol deposits in macrophages.

Effectiveness and safety of sorafenib in the treatment of unresectable and advanced intrahepatic cholangiocarcinoma: a pilot study.

Patients with unresectable and advanced intrahepatic cholangiocarcinoma (ICC) usually have short survival due to a lack of effective treatment. This multicenter, single arm, open labeled, prospective study was conducted to evaluate the effectiveness and safety of sorafenib combined with best supportive care (BSC) in these patients. We enrolled 44 patients with unresectable and advanced ICC who were treated with sorafenib (400 mg, twice daily) and BSC. The primary endpoint was disease control rate (DCR) at week 12, and the secondary endpoints included time to progression (TTP), progression-free survival (PFS), overall survival (OS), duration of therapy (DOT), and adverse events (AEs). Our results showed that the DCR was 15.9%, the median TTP was 5.6 months, and the median PFS and OS were 3.2 and 5.7 months (95% confidence interval [CI]: 2.4-4.1 months; 3.7-8.5 months), respectively. The median DOT was 1.8 months (95% CI: 1.9-3.9 months). AEs of grades 1 and 2 events occurred in 75% of patients, and AE of grade 4 (severe) was observed in 1 patient. Therefore, sorafenib in combination with BSC had an acceptable DCR and safety profile in patients with unresectable and advanced ICC.

Optimization of biosurfactant-mediated oil extraction from oil sludge.

Oil extraction from oil sludge with biosurfactant formulas was optimized by a Taguchi orthogonal array design of L16 (4(5)) with five main factors, including biosurfactant type (surfactin, lichenysin, rhamnolipid and emulsan), biosurfactant concentration, pH, salinity and solvent. Oil recoveries obtained with the sixteen batch washing experiments with the selected levels of each factor were processed with Design Expert/SPSS and a specific combination of factors with a predicted oil recovery of 76.81% was obtained. The predicted optimal biosurfactant formula of 2.0g/L rhamnolipid, pH 12.0, 10g/L NaCl, and 5.0g/L n-butanol were validated by a washing experiment that yielded an oil recovery of 74.55%, which was 27.28% higher than the grand average oil recovery of the whole experiment design. Based on the optimum biosurfactant formula, the oil extraction process followed first-order kinetics as the washing rate constant and final oil recovery increased with temperature. These results will be informative and meaningful for the design of oil sludge treatment in industrial application.

Hydrocarbon degradation and bioemulsifier production by thermophilic Geobacillus pallidus strains.

Geobacillus pallidus XS2 and XS3 were isolated from oil contaminated soil samples in Yumen oilfield, China, and were able to produce bioemulsifiers on different hydrocarbons. Biodegradation assays exhibited that approximately 70% of PAH (250 mg/L) or 85% of crude oil (500 mg/L) was removed by the thermophilic bacteria after 20 days. The bioemulsifiers of the two strains were isolated and obtained a productive yield of 4.24±0.08 and 3.82±0.11g/L, respectively. GPC analysis revealed that the number-average molecular weights (M(n)) of the two bioemulsifiers were 271,785 Da and 526,369 Da, with PDI values of 1.104 and 1.027, respectively. Chemical composition studies exhibited that the bioemulsifier XS2 consisted of carbohydrates (68.6%), lipids (22.7%) and proteins (8.7%) while the bioemulsifier XS3 was composed by carbohydrates (41.1%), lipids (47.6%) and proteins (11.3%). Emulsification assays approved the effectiveness of bioemulsifiers over a wide range of temperature, pH and salinity.

Synergy of isoflurane preconditioning and propofol postconditioning reduces myocardial reperfusion injury in patients.

Either isoflurane preconditioning or high-dose propofol treatment has been shown to attenuate myocardial IRI (ischaemia/reperfusion injury) in patients undergoing CABG (coronary artery bypass graft) surgery. It is unknown whether isoflurane and propofol may synergistically attenuate myocardial injury in patients. The present study investigated the efficacy of IsoPC (isoflurane preconditioning), propofol treatment (postconditioning) and their synergy in attenuating postischaemic myocardial injury in patients undergoing CABG surgery using CPB (cardiopulmonary bypass). Patients (n = 120) selected for CABG surgery were randomly assigned to one of four groups (n = 30 each). After induction, anaesthesia was maintained either with fentanyl and midazolam (control; group C); with propofol at 100 µg x kg(-1) of body weight x min(-1) before and during CPB followed by propofol at 60 µg x kg(-1) of body weight x min(-1) for 15 min after aortic declamping (group P); with isoflurane 1-1.5% end tidal throughout the surgery (group I) or with isoflurane 1-1.5% end tidal before CPB and switching to propofol at 100 µg x kg(-1) of body weight x min(-1) during CPB followed by propofol at 60 µg x kg(-1) of body weight x min(-1) for 15 min after aortic declamping (group IP, i.e. IsoPC plus propofol postconditioning). A joint isoflurane and propofol anaesthesia regimen synergistically reduced plasma levels of cTnI (cardiac troponin I) and CK-MB (creatine kinase MB) and f-FABP (heart-type fatty acid-binding protein) (all P < 0.05 compared with control, group P or group I) and facilitated postoperative myocardial functional recovery. During reperfusion, myocardial tissue eNOS (endothelial NO synthase) protein expression in group IP was significantly higher, whereas nitrotyrosine protein expression was lower than those in the control group. In conclusion, a joint isoflurane preconditioning and propofol anaesthesia regimen synergistically attenuated myocardial reperfusion injury in patients.

Glia activation induced by peripheral administration of aluminum oxide nanoparticles in rat brains.

With the wide application of nanoscaled particles, the risk of human exposure to these particles has been markedly increased. However, knowledge about their safety falls far behind the utility of these nanoparticles. Here we have analyzed the activation of brain microglia and astrocytes, which are sensitive to changes of brain environment after peripheral exposure to nanoscaled aluminum oxide suspension. Sprague-Dawley rats (six rats per treatment) were intraperitoneally injected once every second day for 30 or 60 days with nanoscaled aluminum oxide (NSAO; 1 mg/kg or 50 mg/kg), non-nanoscaled aluminum oxide (nNSAO, 1 mg/kg), or vehicle (saline). After 60 days' exposure the numbers of ED1+, GFAP+, and nestin+ cells in cortex and hippocampus were significantly higher in NSAO-treated rats than nNSAO- or vehicle-treated rats; thus, compared with nNSAO, NSAO has potential effects on the innate immune system of rat brain. This should be considered when evaluating the toxicological effects of nanosized particles. FROM THE CLINICAL EDITOR: Sprague-Dawley rats were intraperitoneally injected with nanosized aluminum oxide, (NSAO); non-nanoscaled aluminum oxide, or vehicle (saline). The numbers of ED1+, GFAP+, and nestin+ cells in cortex and hippocampus were significantly higher in NSAO-treated rats than nNSAO- or vehicle-treated rats; thus, NSAO has potential effects on the innate immune system of rat brain.