ACCURACY OF NEW INTRAOCULAR LENS CALCULATION FORMULAE IN EYES UNDERGOING SILICONE OIL REMOVAL/PARS PLANA VITRECTOMY-CATARACT SURGERY.

PURPOSE: To investigate the performance of novel intraocular lens calculation formulae (Barrett Universal II, Emmetropia Verifying Optical, and Kane) and conventional formulae (Haigis, Hoffer Q, Holladay 1, and Sanders-Retzlaff-Kraff/T [SRK/T]) in patients who underwent pars plana vitrectomy or silicone oil removal combined with cataract surgery. METHODS: In total, 301 eyes from 301 patients who underwent pars plana vitrectomy/silicone oil removal with concomitant cataract surgery were enrolled and divided into the following four groups according to preoperative diagnosis: silicone oil-filled eyes after pars plana vitrectomy, epiretinal membrane, primary retinal detachment, and macular hole. RESULTS: Barrett Universal II exhibited the smallest mean absolute error (0.65 diopters [D]) and median absolute error (0.39 D) in total. In patients with primary retinal detachment, each formula exhibited the worst refractive outcomes in diverse vitreoretinal pathologies ( P < 0.01), and no difference in accuracy between the seven formulas was observed ( P = 0.075). For long eyes, the second linear (Wang-Koch 2) version of the Wang-Koch adjustment significantly reduced the median absolute error for Holladay 1 and SRK/T ( P < 0.001 and P = 0.019). CONCLUSION: In combined surgery, both new and conventional formulas using the second linear version of the Wang-Koch 2 adjustment demonstrated satisfactory performance, with Barrett Universal II exhibiting the best overall performance. However, in patients with primary retinal detachment, all seven formulas showed less favorable performance.

Crystal structure of the plant feruloyl-coenzyme A monolignol transferase provides insights into the formation of monolignol ferulate conjugates.

Lignin is a highly complex phenolic polymer which is essential for plants, but also makes it difficult for industrial processing. Engineering lignin by introducing relatively labile linkages into the lignin backbone can render it more amenable to chemical depolymerization. It has been reported that introducing a feruloyl-coenzyme A monolignol transferase from Angelica sinensis (AsFMT) into poplar could incorporate monolignol ferulate conjugates (ML-FAs) into lignin polymers, suggesting a promising way to manipulate plants for readily deconstructing. FMT catalyzes a reaction between monolignols and feruloyl-CoA to produce ML-FAs and free CoA-SH. However, the mechanisms of substrate specificity and catalytic process of FMT remains poorly understood. Here we report the structure of AsFMT, which adopts a typical fold of BAHD acyltransferase family. Structural comparisons with other BAHD homologs reveal several unique structural features of AsFMT, different from those of the BAHD homologs. Further molecular docking studies showed that T375 in AsFMT may function as an oxyanion hole to stabilize the reaction intermediate and also proposed a role of H278 in the binding of the nucleophilic hydroxyl group of monolignols. Together, this study provides important structural insights into the reactions catalyzed by AsFMT and will shed light on its future application in lignin engineering.

Synthesis and Characterization of Novel Radiopaque Polycarbonate.

Polymeric materials implanted in the human body are usually invisible under X-ray, and the mixing of heavy metal salts into polymeric materials by physical compounding often poses compatibility problems. A new iodine-containing cyclic carbonate monomer, 4-iodo-N-(2-oxo-1,3-dioxan-5-yl)benzamide (IBTMC), is synthesized, which has a degradable carbonate group as its basic structural unit and iodine atoms attached to the side chain in the form of covalent bonds. The ring-opening polymerization of IBTMC is achieved at room temperature under the catalysis of the solid superbase 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD). The structure and X-ray developing ability of the synthesized polycarbonate are characterized by 1 H-NMR, X-ray photoelectron spectroscopy (XPS), energy dispersive X-ray spectroscopy (EDS), Gel Permeation Chromatography (GPC), and micro-computed tomography (Micro-CT). The iodine atoms remain bound to the polymer as covalent bonds after a series of reactions and exhibit a high level of X-ray opacity. In vitro degradation experiments of the polymer prove that the polymer is degradable.

Removal of Acidic Organic Ionic Dyes from Water by Electrospinning a Polyacrylonitrile Composite MIL101(Fe)-NH2 Nanofiber Membrane.

A nanofiber metal-organic framework filter, a polyacrylonitrile (PAN) nanofiber membrane composite with an iron/2-amino-terephthalic acid-based metal-organic framework (MIL101(Fe)-NH2), was prepared by one-step electrospinning. MIL101(Fe)-NH2 was combined into the polymer nanofibers in situ. PAN-MIL101(Fe)-NH2 composite nanofiber membranes (NFMs) were prepared from a homogeneous spinning stock containing MIL101(Fe)-NH2 prebody fluid and PAN. Crystallization of MIL101(Fe)-NH2 and solidification of the polymer occurred simultaneously during electrospinning. The PAN-MIL101(Fe)-NH2 composite NFM showed that MIL101(Fe)-NH2 was uniformly distributed throughout the nanofiber and was used to adsorb and separate acidic organic ionic dyes from the aqueous solution. The results of Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, and X-ray diffraction analysis showed that MIL101(Fe)-NH2 crystals were effectively bonded in the PAN nanofiber matrix, and the crystallinity of MIL101(Fe)-NH2 crystals remained good, while the distribution was uniform. Owing to the synergistic effect of PAN and the MIL101(Fe)-NH2 crystal, the PAN-MIL101(Fe)-NH2 composite NFM showed a fast adsorption rate for acidic ionic dyes. This study provides a reference for the rapid separation and purification of organic ionic dyes from wastewater.

Pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor in children with acute leukaemia.

AIMS: This open-label, phase I study evaluated the pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for the treatment of chemotherapy-induced neutropenia in children with acute leukaemia. METHODS: PEG-rhG-CSF was administered as a single 100 mcg/kg (3 mg maximum dose) subcutaneous injection at the end of each chemotherapy period when neutropenia occurred. Blood samples were obtained from patients treated with PEG-rhG-CSF. PEG-rhG-CSF serum concentrations were determined by an enzyme-linked immunosorbent assay. Population pharmacokinetic (PPK) analysis was implemented using the nonlinear mixed-effects model. Short-term safety was evaluated through adverse events collection (registered at clinicaltrials.gov identifier: 03844360). RESULTS: A total of 16 acute leukaemia patients (1.8-13.6 years) were included, of whom two (12.5%) had grade 3 neutropenia, six (37.5%) had grade 4 neutropenia, and eight (50.0%) had severe neutropenia. For PPK modelling, 64 PEG-rhG-CSF serum concentrations were obtainable. A one-compartment model with first-order elimination was used for pharmacokinetic data modelling. The current weight was a significant covariate. The median (range) of clearance (CL) and area under the serum concentration-time curve (AUC) were 5.65 (1.49-14.45) mL/h/kg and 16514.75 (6632.45-54423.30) ng·h/mL, respectively. Bone pain, pyrexia, anaphylaxis and nephrotoxicity were not observed. One patient died 13 days after administration, and the objective assessment of causality was that an association with PEG-rhG-CSF was "possible". CONCLUSIONS: The AUC of PEG-rhG-CSF (100 mcg/kg, 3 mg maximum dose) in paediatric patients with acute leukaemia were similar to those of PEG-rhG-CSF (100 mcg/kg) in children with sarcoma. PEG-rhG-CSF is safe, representing an important therapeutic option for chemotherapy-induced neutropenia in paediatric patients with acute leukaemia.

Efficacy and tolerance of GELOXD/P-GEMOXD in newly diagnosed nasal-type extranodal NK/T-cell lymphoma: A multicenter retrospective study.

OBJECTIVES: Nasal-type extranodal natural killer NK/T-cell lymphoma (ENKTCL) is a distinct type of non-Hodgkin lymphoma with poor prognosis. This research aimed to evaluate the efficacy and safety of the GELOXD or P-GEMOXD regimens in patients with ENKTCL. METHODS: Newly diagnosed ENKTCL patients treated with either the GELOXD or the P-GEMOXD regimen were identified from three cancer centers between January 2010 and December 2016. Kaplan-Meier and Cox regression analyses were used to calculate overall survival (OS) and progression-free survival (PFS) and to investigate prognostic factors. RESULTS: One hundred and eighty-four cases were identified from three cancer centers. After 1-5 treatment cycles of GELOXD or P-GEMOXD chemotherapy, 155 (84%) patients showed a complete response (CR). The 3-year OS (73.0% vs 38.2%, P = .001) and PFS (72.8% vs 32.4%, P = .000) rates were significantly higher in early-stage patients compared with advanced-stage patients. A multivariate analysis revealed that patient CR status was a significant independent factor in disease prognosis. Grade 3/4 leukopenia occurred in 43 (23.4%) patients. Major non-hematological toxicities included nausea (n = 117, 63.6%) and vomiting (n = 66, 35.9%). CONCLUSIONS: The GELOXD and P-GEMOXD chemotherapy regimens are well tolerated and provide favorable survival outcomes in patients with ENKTCL.

Preparation and Evaluation of Oseltamivir Molecularly Imprinted Polymer Silica Gel as Liquid Chromatography Stationary Phase.

To improve the chromatographic performance of an oseltamivir (OS) molecularly imprinted polymer (MIP), silica gel coated with an MIP layer for OS (OSMIP@silica gel) was prepared by the surface molecular imprinting technology on the supporter of porous silica gel microspheres. A nonimprinted polymer with the silica gel (NIP@silica gel) was also prepared for comparison. The obtained particles were characterized through FT⁻IR, scanning electron microscopy, specific surface area analysis, and porosity measurements. The results indicated that the polymer was successfully synthesized and revealed the structural differences between imprinted and nonimprinted polymers. The results of static adsorption experiments showed that adsorption quantity of the OSMIP@silica gel for OS was higher than that for NIP@silica gel, and the OSMIP@silica gel had two kinds of affinity sites for OS but the NIP@silica gel had one. The chromatographic performance of the OSMIP@silica gel column had significant improvement. The imprinting factor of the OSMIP@silica gel column for OS was 1.64. Furthermore, the OSMIP@silica gel column showed good affinity and selectivity for template OS and another neuraminidase inhibitor, peramivir, but not for quinocetone. These results indicated that the prepared OSMIP could be used to simulate the activity center of neuraminidase, and the OSMIP@silica gel column could be also employed in future studies to search for more active neuraminidase inhibitor analogues from traditional Chinese herbs.

Design and synthesis of pregnenolone/2-cyanoacryloyl conjugates with dual NF-κB inhibitory and anti-proliferative activities.

Twenty-five novel pregnenolone/2-cyanoacryloyl conjugates (6-30) were designed and prepared, with the aim of developing novel anticancer drugs with dual NF-κB inhibitory and anti-proliferative activities. Compounds 22 and 27-30 showed inhibition against TNF-α-induced NF-κB activation in luciferase assay, which was confirmed by Western blotting. Among them, compound 30 showed potent NF-κB inhibitory activity (IC50=2.5µM) and anti-proliferative against MCF-7, A549, H157, and HL-60 cell lines (IC50=6.5-36.2µM). The present study indicated that pregnenolone/2-cyanoacryloyl conjugate I can server asa novel scaffold for developing NF-κB inhibitors and anti-proliferative agents in cancer chemotherapy.

The association between periodontal disease and the risk of myocardial infarction: a pooled analysis of observational studies.

BACKGROUND: Several meta-analyses have indicated that periodontal disease (PD) are related to cardiovascular diseases (CVDs). However, the association between PD and myocardial infarction (MI) remains controversial. Here we aimed to assess the association between PD and MI by meta-analysis of observational studies. METHODS: PubMed, EMBASE and the Cochrane Library were searched through July, 2016. Observational studies including cohort, cross-sectional and case-control studies reporting odds ratio (OR) or relative risk (RR) with 95% confidence intervals (CIs) were included in the analysis. Either fixed or random-effects model were applied to evaluate the pooled risk estimates. Sensitivity and subgroup analyses were also carried out to identify the sources of heterogeneity. Publication bias was assessed by the Begg's, Egger's test and funnel plot. RESULTS: We included 22 observational studies with 4 cohort, 6 cross-sectional and 12 case-control studies, including 129,630 participants. Patients with PD have increased risk of MI (OR 2.02; 95% CI 1.59-2.57). Substantial heterogeneity in risk estimates was revealed. Subgroup analyses showed that the higher risk of MI in PD patients exists in both cross-sectional studies (OR 1.71; 95% CI 1.07-2.73) and case-control studies (OR 2.93; 95% CI 1.95-4.39), and marginally in cohort studies (OR 1.18; 95% CI 0.98-1.42). Further, subgroup meta-analyses by location, PD exposure, participant number, and study quality showed that PD was significantly associated with elevated risk of MI. CONCLUSION: Our meta-analysis suggested that PD is associated with increased risk of future MI. However, the causative relation between PD and MI remains not established based on the pooled estimates from observational studies and more studies are warranted.

Skeletal site-specific response to ovariectomy in a rat model: change in bone density and microarchitecture.

OBJECTIVES: Ovariectomized (OVX) rat model has been widely used in osteoporosis-related studies. However, the discrepancies in age and skeletal sites being investigated make it difficult to compare the results from different studies. The purpose of this study was to provide information of systemic skeletal site-specific changes in a stable OVX rat model. MATERIAL AND METHODS: Thirty-three 6-month Spraque-Dawley female rats were used. Fifteen rats underwent ovariectomy, and fifteen received sham surgery. Three animals without any surgery were sacrificed at week 0 to serve as baseline. Three animals in the OVX and sham group, respectively, were euthanized at week 2, 4, 12, 24 and 36 post-surgery. Ten bone sites, including parietal bone, interparietal bone, maxilla, mandible, humerus, ulna, femur, tibia, lumber vertebra, and ilium, were subjected to micro-CT. RESULTS: Overall, long bones, lumber vertebra, and ilium showed similar trend of bone loss post-OVX, with tibia and femur suffered the most bone loss and spine the least (decreased by 75.0%, 70.4% and 36.6% in bone mineral density BMD at week 36 from base line, respectively). Upon OVX, jaw bones and cranial bones only showed a minor reduction in BMD (decreased by 1~3% from baseline) at week 36. Significant deterioration of trabecular structure was detected in long bones, lumber vertebra, and ilium post-OVX, while jaw bones remained relatively stable. CONCLUSIONS: This study for the first time assessed the systemic site-specific bone loss and microarchitecture changes in OVX rat model. It provided valuable information for selecting bone site and observation time in osteoporosis-related study.

Suppression of phase coarsening in immiscible, co-continuous polymer blends under high temperature quiescent annealing.

The properties of polymer blends greatly depend on the morphologies formed during processing, and the thermodynamic non-equilibrium nature of most polymer blends makes it important to maintain the morphology stability to ensure the performance stability of structural materials. Herein, the phase coarsening of co-continuous, immiscible polyamide 6 (PA6)-acrylonitrile-butadiene-styrene (ABS) blends in the melt state was studied and the effect of introduction of nano-silica particles on the stability of the phase morphology was examined. It was found that the PA6-ABS (50/50 w) blend maintained the co-continuous morphology but coarsened severely upon annealing at 230 °C. The coarsening process could be divided into two stages: a fast coarsening process at the initial stage of annealing and a second coarsening process with a relatively slow coarsening rate later. The reduction of the coarsening rate can be explained from the reduction of the global curvature of the interface. With the introduction of nano-silica, the composites also showed two stages of coarsening. However, the coarsening rate was significantly decreased and the phase morphology was stabilized. Rheological measurements indicated that a particle network structure was formed when the concentration of nano-silica particles was beyond 2 wt%. The particle network inhibited the movement of molecular chains and thus suppressed the coarsening process.

Research on path planning for clear aligner flexible manufacturing.

In recent years, clear aligner can enhance individual appearance with dental defects, so it used more and more widely. However, in manufacturing process, there are still some problems, such as low degree of automation and high equipment cost. The problem of coordinate system mismatch between gingival curve point cloud and dental CAD model is faced to. The PCA-ICP registration algorithm is proposed, which includes coarse match algorithm and improve-ICP registration algorithm. The principal component analysis (PCA) based method can roughly find the posture relationship between the two point clouds. Using z-level dynamic hierarchical, the ICP registration can accurately find the posture between these two clouds. The final registration maximum distance error is 0.03 mm, which is smaller than robot machining error. Secondly, the clear aligner machining process is conducted to verify the registration effectiveness. Before machining, the path is generated based on the well registered gingival curve. After full registration, the tool path is calculated by establishing a local coordinate system between the workpiece and the tool to avoid interference. This path is calculated and generated as an executable program for ABB industrial robots. Finally, the robot was used for flexible cutting of clear aligners and was able to extract products, ensuring the effectiveness of the proposed research. This method can effectively solve the limitations of traditional milling path planning under such complex conditions.

Escape sites from the endo-lysosomal trafficking route manipulate exocytosis of nanoparticles in polar epithelium.

The endo-lysosomal pathway is a major barrier for the trans-epithelial transport of nanoparticles (NPs), but escape strategies could facilitate trans-epithelial delivery. Based on the polarization properties of the epithelium, different escape compartments may result in different exocytosis fates of NPs and further affect the delivery efficiency. Therefore, optimizing the escape sites is critical for trans-epithelial delivery. Here, commonly used PEG-coated-poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles were fabricated as model nanoparticles (MNPs) and the intestinal epithelium was chosen as the polarized epithelium. The MNPs were incubated with different endosomolytic agents for early endosomal escape, late endosomal escape and lysosomal escape, respectively. According to in vitro and in vivo studies, MNPs escaping from early endosomes and late endosomes exhibited stronger capacity for trans-epithelial transport than those escaping from lysosomes. By further probing into the mechanism, we surprisingly found that although MNPs escaping from early endosomes quickly egressed from the apical side of epithelia, they were subsequently followed by "reuptake" via caveolae and trafficked through the endoplasmic reticulum-Golgi apparatus (ER/GA) secretory pathway, achieving efficient trans-epithelial transport; MNPs escaping from late endosomes, which were located near the nucleus, were prone to enter the ER/GA for efficient basolateral exocytosis. However, MNPs escaping from lysosomes were detained within cells by autophagosomes. Collectively, our research suggested that early endosomes and late endosomes were ideal escape sites for trans-epithelial delivery.

Polyvinylpyrrolidone hydrogel coating for ureteral stent: Safety and performance evaluation.

BACKGROUND: Ureteral stents are commonly used in urology. However, complications such as encrustation and infection on the surface of the stent, and injury to the ureteral mucosa can occur after implantation, causing discomfort for patients. OBJECTIVE: We intend to confirm the biosafety of polyvinylpyrrolidone (PVP) hydrophilic coating and its lubrication properties for surface modification of ureteral stents to reduce friction and improve patient comfort. METHODS: Based on our previous studies, we have developed a PVP hydrophilic coating for surface modification of ureteral stents. We firstly investigated the cytotoxicity, intradermal irritation, delayed type hypersensitivity, and acute systemic reactions of stent coating extracts. We further characterized the break strength, retention strength, and dynamic friction of the stent. RESULTS: The cell survival rate of all experimental groups was greater than 70%. No hypersensitivity reaction, systemic toxicity reaction, or obvious intradermal reaction were observed. The above results indicate that the test results of the modified stent meet the requirements of ISO 10993-5: 2009 (Cytotoxicity); ISO 10993-10:2021 (Sensitization and Irritation); ISO 10993-11:2017 (Acute Systemic Toxicity). After soaking in artificial urine for an extended period, there was no obvious change in its super-slip performance. CONCLUSION: Our results confirm the safety and lubrication characteristics of PVP hydrophilic coating for ureteral stent surface modification. The performance of this coating has the potential to reduce complications after stent implantation, thereby improving patient comfort, reducing medical burden, and has a good clinical application prospect.

Integration of lactic acid biorefinery with treatment of red mud from alumina refinery: win-win paradigm for waste valorization.

The cost of detoxification and neutralization poses certain challenges to the development of an economically viable lactic acid biorefinery with lignocellulosic biomass as feedstock. Herein, red mud, an alkaline waste, was explored as both a detoxifying agent and a neutralizer. Red mud treatment of lignocellulosic hydrolysate effectively removed the inhibitors generated in dilute acid pretreatment, improving the lactic acid productivity from 1.0 g/L·h-1 to 1.9 g/L·h-1 in later fermentation. In addition, red mud could replace CaCO3 as a neutralizer in lactic acid fermentation, which in turn enabled simultaneous bioleaching of valuable metals (Sc, Y, Nd, and Al) from red mud. The neutralization of alkali in red mud by acids retained in lignocellulosic hydrolysate and lactic acid produced from fermentation led to effective dealkalization, rendering a maximum alkali removal efficiency of 92.2 %. Overall, this study offered a win-win strategy for the valorization of both lignocellulosic biomass and red mud.

Recent Developments in Layer-by-Layer Assembly for Drug Delivery and Tissue Engineering Applications.

Surfaces with biological functionalities are of great interest for biomaterials, tissue engineering, biophysics, and for controlling biological processes. The layer-by-layer (LbL) assembly is a highly versatile methodology introduced 30 years ago, which consists of assembling complementary polyelectrolytes or biomolecules in a stepwise manner to form thin self-assembled films. In view of its simplicity, compatibility with biological molecules, and adaptability to any kind of supporting material carrier, this technology has undergone major developments over the past decades. Specific applications have emerged in different biomedical fields owing to the possibility to load or immobilize biomolecules with preserved bioactivity, to use an extremely broad range of biomolecules and supporting carriers, and to modify the film's mechanical properties via crosslinking. In this review, the focus is on the recent developments regarding LbL films formed as 2D or 3D objects for applications in drug delivery and tissue engineering. Possible applications in the fields of vaccinology, 3D biomimetic tissue models, as well as bone and cardiovascular tissue engineering are highlighted. In addition, the most recent technological developments in the field of film construction, such as high-content liquid handling or machine learning, which are expected to open new perspectives in the future developments of LbL, are presented.

Dispersal and transport of microplastic particles under different flow conditions in riverine ecosystem.

Microplastic (MP) pollution is a global issue owing to its potential threats to ecosystems and human health. MP pollution in river ecosystems is widely investigated, but the transport process under different hydrological conditions remain unclear. In this study, an approach of particle tracking in conjunction with hydrodynamic modeling was developed to investigate the dispersal and transport processes of microplastic particles in riverine ecosystem. The concentration and dispersal pattern of polyamide (PA), polyethylene (PE), polypropylene (PP), polystyrene (PS), and polyethylene terephthalate (PET) particles under base flow and flood events with recurrence intervals of 10-year, 20-year and 50-year were identified. Results indicated that rainfall intensity had a significant impact on the microplastic transport in rivers. Higher suspension concentration and lower sedimented concentration were observed in high flow periods, and the sedimented concentration showed a slow increasing trend in the flood recession stage. High water velocity facilitated the microplastic particles to be migrated for a longer distance, and high water flow was conducive to transport more microplastics from source points. Besides, microplastic particles with high density had worse mobility in water and more prone to deposition. PET were likely to be transported for a relatively shorter distance, while PP had higher mobility and took less time to reach the same simulation point. This study put forward an effective approach to understand the transport of MPs in the river. The results obtained are useful to identify pollution hotspots and track pollution paths.

Deciphering photocatalytic degradation of methylene blue by surface-tailored nitrogen-doped carbon quantum dots derived from Kraft lignin.

Lignin in black liquor can be used to manufacture carbon nanomaterials on a large scale. However, the effect of nitrogen doping on the physicochemical properties and photocatalytic performance of carbon quantum dots (NCQDs) remains to be explored. In this study, NCQDs with different properties were prepared hydrothermally by using kraft lignin as the raw material and EDA as a nitrogen dopant. The amount of EDA added affects the carbonization reaction and surface state of NCQDs. Raman spectroscopy showed that the surface defects increased from 0.74 to 0.84. Photoluminescence spectroscopy (PL) showed that NCQDs had different intensities of fluorescence emission at 300-420 nm and 600-900 nm. Meanwhile, NCQDs can photo-catalytically degrade 96 % of MB under simulated sunlight irradiation within 300 min. After three months of storage, the fluorescence intensity of NCQDs remained above 94 %, showing remarkable fluorescence stability. After four times of recycling, the photo-degradation rate of NCQDs was maintained above 90 %, confirming its outstanding stability. As a result, a clear understanding of the design of carbon-based photo-catalyst fabricated from the waste of the paper-making industry has been gained.

Therapeutic delivery of siRNA silencing HIF-1 alpha with micellar nanoparticles inhibits hypoxic tumor growth.

The particular characteristics of the tumor microenvironment have the potential to strongly promote tumor growth, metastasis and angiogenesis and induce drug resistance. Therefore, the development of effective, systemic therapeutic approaches specifically based on the tumor microenvironment is highly desirable. Hypoxia-inducible factor-1α (HIF-1α) is an attractive therapeutic target because it is a key transcription factor in tumor development and only accumulates in hypoxic tumors. We report here that a cationic mixed micellar nanoparticle (MNP) consisting of amphiphilic block copolymers poly(ε-caprolactone)-block-poly(2-aminoethylethylene phosphate) (PCL(29)-b-PPEEA(21)) and poly(ε-caprolactone)-block-poly(ethylene glycol) (PCL(40)-b-PEG(45)) was a suitable carrier for HIF-1α siRNA to treat hypoxic tumors, which showed an average diameter of 58.0 ± 3.4 nm. The complex MNP(siRNA), formed by the interaction of MNP and siRNA, was transfected into PC3 prostate cancer cells efficiently, while the inhibition of HIF-1α expression by MNP loaded with HIF-1α siRNA (MNP(siHIF)) blocked PC3 cell proliferation, suppressed cell migration and disturbed angiogenesis under in vitro hypoxic mimicking conditions. It was further demonstrated that systemic delivery of MNP(siHIF) effectively inhibited tumor growth in a PC3 prostate cancer xenograft murine model without activating innate immune responses. Moreover, delivery of MNP(siHIF) sensitized PC3 tumor cells to doxorubicin chemotherapy in vitro and in vivo by downregulating MDR1 gene expression which was induced by hypoxia. The underlying concept of use of MNP(siHIF) to block HIF-1α holds promise as an example of a clinical approach using specific siRNA therapy for cancer treatment aimed at the hypoxic tumor microenvironment.

[Correlation between periodontitis and metabolic syndrome of the middle-aged and aged population in Shijingshan community of Beijing].

OBJECTIVE: To survey the metabolic status of the middle-aged and aged population with periodontitis in Shijingshan community of Beijing, and investigate the relationship between periodontitis and metabolic syndrome (MS). METHODS: The middle-aged and aged population in the community were investigated by questionnaires, periodontal clinical examinations and blood biochemical tests in 2005. A total of 903 subjects were enrolled, who were divided into two groups by severity of periodontitis. Their waist circumferences, values of high-density lipoprotein cholesterol (HDL-C), systolic blood pressure, fasting glucose, MS and its individual components (central obesity, insulin resistance, hypertriglyceridemia, low HDL-C and hypertension) were compared between the two groups. The Logistic regression model was set to analyze the relationship between periodontitis and MS. RESULTS: There was a significantly higher mean of systolic blood pressure, fasting glucose in the subjects with moderate-severe periodontitis than that with no-mild periodontitis. With severity of periodontitis increasing, the prevalence of MS, high blood glucose and low HDL-C increased significantly. After adjustment for gender, age, and smoking, the subjects with moderate-severe periodontitis were 1.524, 1.527 and 2.349 times more likely to suffer from MS, high blood glucose and low HDL-C than those with no-mild periodontitis, respectively. CONCLUSION: With severity of periodontitis increasing, the prevalence of MS, high blood glucose and low HDL-C increased significantly in the middle-aged and aged population of the community in Beijing. Severity of periodontitis is associated with MS, high blood glucose and low HDL-C.