Osthole Suppresses Knee Osteoarthritis Development by Enhancing Autophagy Activated via the AMPK/ULK1 Pathway.

Knee osteoarthritis (KOA) is an increasingly prevalent heterogeneous disease characterized by cartilage erosion and inflammation. As the main chemical constituent of Angelicae Pubescentis Radix (APR), an anti-inflammatory herbal medicine, the potential biological effects and underlying mechanism of osthole on chondrocytes and KOA progression remain elusive. In this study, the potential effect and mechanism of osthole on KOA were investigated in vitro and in vivo. We found that osthole inhibited IL-1ß-induced apoptosis and cartilage matrix degeneration by activating autophagy in rat chondrocytes. In addition, osthole could activate autophagy through phosphorylation of AMPK/ULK1, and AMPK serves as a positive upstream regulator of ULK1. Furthermore, KOA rats treated with osthole showed phosphorylation of the AMPK/ULK1 pathway and autophagy activation, as well as cartilage protection. Collectively, the AMPK/ULK1 signaling pathway can be activated by osthole to enhance autophagy, thereby suppressing KOA development. Osthole may be a novel and effective therapeutic agent for the clinical treatment of KOA.

Limb Ischemia Complications of Veno-Arterial Extracorporeal Membrane Oxygenation.

Background: This study aimed to summarize and analyse the risk factors, clinical features, as well as prevention and treatment of limb ischemia complications in patients on veno-arterial extracorporeal membrane oxygenation (V-A ECMO). Methods: We retrospectively analyzed 179 adult patients who had undergone V-A ECMO support in the Cardiac Care Unit of the First Hospital of Lanzhou University between March 2019 and December 2021. Patients were divided into the limb ischemia group (LI group) and the non-limb ischemia group (nLI group) according to whether limb ischemia occurred on the ipsilateral side of femoral artery cannulation. In the LI group, patients were salvaged with a distal perfusion cannula (DPC) according to each patient's clinical conditions. The baseline data and ECMO data were compared between the two groups, and risk factors for limb ischemia complications were screened using multiple logistic regression analysis. Results: Overall, 19 patients (10.6%) had limb ischemia complications, of which 5 (2.8%) were improved after medication adjustment, 12 (8.4%) were salvaged with a DPC, and 2 had undergone surgical intervention. There were significant differences in terms of Extracorporeal Cardiopulmonary Resuscitation (ECPR), Intra-aortic balloon pump (IABP), peak vasoactive-inotropic score (VIS) within 24 h after ECMO (VIS-max), Left ventricular ejection fraction (LVEF), weaning from ECMO, and discharge rate between the two groups. ECPR, IABP, and VIS-max in the LI group were significantly higher than those in the nLI group, whereas weaning from ECMO, discharge rate, and LVEF were significantly lower in the LI group compared to those in the nLI group. Furthermore, multiple logistic regression analysis revealed that diabetes [odds ratio (OR) = 4.338, 95% confidence interval (CI): 1.193-15.772, P = 0.026], IABP (OR = 1.526, 95% CI: 1.038-22.026, P = 0.049) and VIS-max (OR = 1.054, 95% CI: 1.024-1.085, P < 0.001) were independent risk factors for limb ischemia complications in patients who underwent V-A ECMO. Conclusion: Diabetes, prevalence of IABP and VIS-max value in analyzed groups were independent risk factors for predicting limb ischemia complications in patients who underwent V-A ECMO. The cannulation strategy should be optimized during the establishment of V-A ECMO, and limb ischemia should be systematically evaluated after ECMO establishment. A DPC can be used as a salvage intervention for the complications of critical limb ischemia.

miR-215-5p regulates osteoporosis development and osteogenic differentiation by targeting XIAP.

BACKGROUND: Osteoporosis (OP) is a metabolic disease that involves microstructure destruction and fracture damage. The present study probed into the significance of miR-215-5p in OP progression. METHODS: Serum samples were collected from surgical patients and healthy controls. qRT-PCR analysis was utilized to determine the miR-215-5p level in clinical samples and human bone mesenchymal stem cells (hBMSCs) induced by ß-glycerol phosphate. A dual luciferase reporter assay was exploited to examine the targeted relationship between miR-215-5p and XIAP. The mineralization and calcium deposition of hBMSCs were assessed by detection of ALP activity, Alizarin red staining, and osteoblast marker expression. Protein expression was determined by western blot analysis. RESULTS: MiR-215-5p was significantly reduced in patients with OP and increased in hBMSCs treated with ß-glycerophosphate. Enhanced miR-215-5p level triggered augment in osteoblast markers (Alkaline phosphatase/ ALP, Osteocalcin/ OCN, and Runt-Related Transcription Factor 2/ Runx2), which was accompanied by the increase of ALP activity in hBMSCs and accumulation of Calcium. Functional experiments show that XIAP was a target of miR-215-5p and negatively modulated by miR-215-5p. XIAP expression levels were increased in OP samples, and decreased XIAP in ß-glycerophosphate-treated hBMSCs inhibited its' osteogenic differentiation. Functional loss and acquisition experiments depicted that miR-215-5p promoted the differentiation of hBMSCs by inhibiting the XIAP level, playing a protective role in the pathogenesis of OP. CONCLUSIONS: ß-glycerophosphate promoted the osteogenic differentiation of hBMSCs, increased miR-215-5p level, and decreased XIAP. miR-215-5p stimulated osteogenic differentiation of hBMSCs by targeting XIAP, shedding new insights for the detection and therapy of OP.

Veno-Arterial Extracorporeal Membrane Oxygenation in Elective High-Risk Percutaneous Coronary Interventions.

Background: The safety and feasibility of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) as mechanical circulatory support in high-risk percutaneous coronary intervention (HR-PCI) remain unclear. Methods: This retrospective study included patients with complex and high-risk coronary artery disease who underwent elective PCI with VA-ECMO support pre-operatively during March 2019-December 2020. Rates of VA-ECMO-related complications, complications during PCI, death, myocardial infarction, and stroke during hospitalisation and 1-year post-operatively were analysed. Results: Overall, 36 patients (average age: 63.6 ± 8.9 years) underwent PCI. The average duration of VA-ECMO support was 12.5 (range, 3.0-26.3) h. Intra-aortic balloon pump counterpulsation was used in 44.4% of patients. The SYNTAX score was 34.6 ± 8.4 pre-operatively and 10.8 ± 8.8 post-operatively (P < 0.001). Intraoperative complications included pericardial tamponade (N = 2, 5.6%), acute left-sided heart failure (N = 1, 2.8%), malignant arrhythmia requiring electrocardioversion (N = 2, 5.6%), and no deaths. Blood haemoglobin levels before PCI and 24 h after VA-ECMO withdrawal were 145.4 ± 20.2 g/L and 105.7 ± 21.7 g/L, respectively (P < 0.001). Outcomes during hospitalisation included death (N = 1, 2.8%), stroke (N = 1, 2.8%), lower limb ischaemia (N = 2, 5.6%), lower limb deep venous thrombosis (N = 1, 2.8%), cannulation site haematoma (N = 2, 5.6%), acute renal injury (N = 2, 5.6%), bacteraemia (N = 2, 5.6%), bleeding requiring blood transfusion (N = 5, 13.9%), and no recurrent myocardial infarctions. Within 1 year post-operatively, two patients (5.6%) were hospitalised for heart failure. Conclusions: Veno-arterial extracorporeal membrane oxygenation mechanical circulation support during HR-PCI is a safe and feasible strategy for achieving revascularisation in complex and high-risk coronary artery lesions. VA-ECMO-related complications require special attention.

Numerical Simulation of Monodisperse Lube Oil Multiple Droplet Evaporation and Autoignition under Nonconstant Cylinder Conditions of Low-Speed Two-Stroke Gas Engines.

The possibility of lube oil droplets' existence in cylinders for two-stroke low-speed gas engines is higher because of the much higher lube oil consumption rate. Some droplets are directly injected into cylinders by lube oil injectors, and some are blown into cylinders through the scavenging ports. Autoignition of cylinder oil droplets is the main cause of preignition. This research study indicates that under in-cylinder conditions, overlarge single droplets cannot autoignite due to the long evaporation time, and overly small single droplets cannot autoignite because of the low vapor concentration. To find out what kinds of oil droplet groups could autoignite and cause preignition, 3-D computational fluid dynamics simulation in OpenFOAM was carried out. The model predictions were validated against the experimental results, including the evaporation rate of n-heptane droplets and the ignition delay of lube oil droplets. Also, the simulation was used to investigate the characteristics of multiple droplets under different ambient temperatures and pressures. The evaporation lifetime and the ignition delay of a large single droplet are dozens of times longer than that of multiple droplets, which confirms that the droplet group is more dangerous than a large single droplet. The evaporation rate and ignition delay are affected by the distance and number of droplets. A larger number causes a lower average evaporation rate. A smaller distance causes a shorter ignition delay. The local vapor concentration and temperature could be greatly reduced due to the existence of multiple evaporation and ignition cores. Additionally, these findings of multiple droplets were confirmed under nonconstant cylinder conditions of a natural gas engine. This research provides a guide to design the lube oil injectors and scavenging ports so as to reduce the preignition caused by lube oil autoignition.

[Clinical Efficacy of ALL-2005 and ALL-2009 Regimen and Factors Influencing Prognosis of Newly Diagnosed ALL Patients Aged between 10-18 Years Old].

OBJECTIVE: To investigate the clinical efficacy of ALL-2005 and ALL-2009 regimen and factors influencing prognosis of newly diagnosed ALL patients aged between 10-18 years old to provide some reference for clinical diagnosis and treatment. METHODS: The clinical data including baseline clinical characteristics, induction chemotherapy effect, long-term clinical efficacy, recurrence rate and mortality of induction therapy of 119 newly diagnosed ALL patients aged between 10-18 years old from January 2008 to December 2015 were analyzed retrospectively, and the influencing factors of clinical prognosis were evaluated by univariate and multivariate analysis. RESULTS: The complete remission rate at the 5th week after induction therapy was not significantly different between ALL-2005 and ALL-2009 regimen groups (P＞0.05). The cumulative event-free survival rate and overall survival rate of 119 cases after 5-year follow-up were (63.41±3.65)% and (68.95±4.01)% respectively, and after 7-year follow-up were (61.86±3.72)% and (67.22±3.59)% respectively. The cumulative event-free survival rate and overall survival rate were not significantly different between ALL-2005 and ALL-2009 regimen groups (P＞0.05). The total recurrence rate, extramedullary recurrence rate, recurrence time and survival rate were not significantly different between ALL-2005 and ALL-2009 regimen groups (P＞0.05). The survival rate of extramedullary recurrence group was significantly higher than bone marrow recurrence group (P＜0.05). The survival rate in late term recurrence group was significantly higher than in early term recurrence group (P＜0.05). The mortality of ALL-2005 regimens was not significantly different from that of ALL-2009 regimen group (P＞0.05). Univariate analysis showed that age, sex, induction therapy, risk and fusion gene all were the factors influencing clinical prognosis (P＜0.05). Multivariate analysis by Cox regression model showed that male, non-remission after induction therapy and high risk were the independent risk factors for poor prognosis in patients (P＜0.05). The survival rate of patients with BCR-ABL+ treated with ALL-2009 regimen was significantly higher than that of patients treated with ALL-2005 regimen (P＜0.05). The event-free survival rate after 5-year follow-up of middle-risk patients treated with ALL-2005 and ALL-2009 regimens was significantly higher than that of high-risk patients (P＜0.05). The event-free survival rate after 5-year follow-up of patients with B-line ALL treated with ALL-2009 regimen was significantly higher than that of T-line ALL patients (P＜0.05). CONCLUSION: The survival rate of newly diagnosed ALL patients aged between 10-18 years old treated with ALL-2009 regimen was slightly higher than that of ALL-2005 regimen, it is more suitable for the ALL patients with BCR-ABL+, but can not reduce the recurrence rate. And the sex, the effect of induction therapy and risk closely relate with the clinical prognosis of above mentioned patients.

[Analysis of Clinical Characteristics and Prognostic Risk Factors of HLH Children with Central Nervous System Involvement].

OBJECTIVE: To investigate the clinical characteristics and prognostic risk factors of HLH children with central nervous system (CNS) involvement so as to provide more reference for further improving the prognosis of HLH children. METHODS: The clinical data of 45 HLH children with CNS involvement treated in our hospital from January 2006 to October 2016 were collected and analyzed retrospectively. The clinical characteristics of HLH children with CNS involvement were recorded, moreover the possible factors influencing the prognosis of HLH children with CNS involvement were analyzed using univariate and multivariate analysis through the establishment of Cox risk ratio model. RESULTS: Among 45 HLH children with CNS involvement, male was 19 cases and female was 26 cases. The median age of 4.0 years old (1.0-15.1). The detection showed that EBV found in 38 cases (84.44%), CMV infection in 1 case (2.22%), bacterial infection in 3 cases (6.67%), connection tissue disease in 1 case (2.22%) and indefinite etiology infection in 2 cases (4.44%). After lumbar puncture of 27 HLH children with CNS involvement, 10 cases (37.04%) showed cerebrospinal fluid abnormality. In addition, 22 cases showed the craniography abnormality. The follow-up results showed that the OS rate of 1 year was 46.67% (21/45), the OS rate of 3 years was 44.44% (20/45); the median survival time was 5.0 months. The OS analysis indicated that 1 years OS rate of diseased children with cerebrospinal fluid abnormality was significantly lower than that of diseased children with cerebrospinal fluid normality (10/45 vs 17/45) (P＜0.05), and 1 years OS rate of diseased children who not received intrathecal injection was significantly lower that of diseased children who received intrathecal (10/45 vs 17/45) (P＜0.05). The univariate analysis showed that the symptoms of nervous system, abnormal cerebrospinal fluid, absence of intrathecal injection and treatment schedule all were the risk factors affecting the prognosis of HLH children with CNS involvement (P＜0.05). The multivariate analysis by Cox risk model showed that abnormal cerebrospinal fluid and absence of intrathecal injection were independent risk factors for of HLH children with CNS involvement (P＜0.05). CONCLUSION: The clinical prognosis of HLH children with CNS involvement is relatively poor, moreover some of HLH children with CNS involvement have neural sequelae. The cerebrospinal fluid abnormality and absence of intrathecal injection are independent risk factors leading to poor prognosis for HLH clildren with CNS involvement.

Distributions, quality assessments and fluxes of heavy metals carried by submarine groundwater discharge in different types of wetlands in Jiaozhou Bay, China.

Intertidal groundwater and seawater were sampled to analyze the distribution characteristics, the contamination status and the submarine groundwater discharge (SGD)-associated fluxes of heavy metals Cu, Pb, Zn, Cd, Cr, and Hg as well as the metalloid As at four typical intertidal wetlands (including a sandy beach, a mud flat, a tidal marsh and an estuarine intertidal zone) of Jiaozhou Bay, China. Results show that the surface water near the Dagu River estuary suffers from a severe Cu pollution. The groundwater in the sandy beach and mud flat has stronger enrichment abilities of heavy metals than those at the other two sites. The contents of Pb and Zn in groundwater are mainly controlled by the sulfate reduction. At the mud flat, human activities may cause potential Pb contamination to groundwater. The heavy metal effluxes in the sandy beach are the largest of all the four wetlands.

Study Evaluation Maternity Nutrition and Pregnancy In Vitro and In Vivo-Progesterone Nanocrystal Injection.

In this study, the insoluble drug, progesterone, was formulated into a progesterone nanocrystal injection to improve the saturation solubility, release rate, and efficacy of progesterone, as well as to increase the relative bioavailability of progesterone, reduce the subsequent irritation, and minimize the toxicity; the advantages and feasibility of the progesterone nanocrystalline injection in the prevention of premature delivery and protection against pregnancy-associated risks in pregnant females was evaluated. The wet grinding method was used to prepare the progesterone nanocrystalline injection; its morphology, particle size, and potential were characterized by transmission electron microscopy. Crystal structure was analyzed by X-ray powder diffraction; the solubility of the injection and the progesterone drug substance in water, and the In Vitro release of the drug were evaluated for its nanometer effect In Vitro. Rabbits were injected with the progesterone nanocrystal injection as well as commercially available progesterone injections for evaluation in vivo. The formulation process of a progesterone nanocrystal injection is feasible. The crystal form is stable and the particle size is uniform. Moreover, we found that it improves the release rate, saturation solubility, and bioavailability of progesterone, while reducing muscle irritation. The results have clinical research significance.

Numerical Simulations of Seasonally Oscillated Groundwater Dynamics in Coastal Confined Aquifers.

Studies investigating the effects of inland recharge on coastal groundwater dynamics were carried out typically in unconfined aquifers, with few in confined aquifers. This study focused on the groundwater dynamics in confined aquifers with seasonally sinusoidally fluctuated inland groundwater head and constant sea level by numerical simulations. It is known that the mixing zone (MZ) of saltwater wedge in response to the seasonal oscillations of inland groundwater head swings around the steady-state MZ. However, our simulation results indicate that even the most landward freshwater-saltwater interface over a year is seaward from the steady-state location when the hydraulic conductivity K is ≤10-4  m/s under certain boundary conditions with given parameter values. That is, seasonal oscillations of inland groundwater head may reduce seawater intrusion in confined coastal aquifers when K ≤ 10-4  m/s. Sensitivity analysis indicates that for aquifers of K ≤ 10-4  m/s, the larger the inland head fluctuation amplitude is, the less the seawater intrudes. This is probably due to the reason that the seawater intrusion time decreases with the increase of fluctuation amplitude when K ≤ 10-4  m/s. Numerical simulations demonstrate that seasonal inland groundwater head oscillations promote the annual averaged recirculated seawater discharge across the seaward boundary.

[Related Factors Affecting Long-term Prognosis of AML Children with Positive RUNX1-RUNX1T1].

OBJECTIVE: To analyze the related factors affecting the long-term prognosis of acute myeloid leukemia (AML) children with positive RUNX1-RUNX1T1. METHODS: The clinical data of 63 chlidren with positive RUNX1-RUNX1T1 AML treated by BCH-AML 05 regimen in our hospital from January 2010 to December 2015 were collected and analyzed retrospectively. The level of RUNX1-RUNX1T1 was detected at the time of initial diagnosis (T1), after the first induction treatment (T2), after the second induction treatment (T3), after the first consolidation treatment (T4), after the second consolidation treatment (T5) and after the third consolidation treatment (T6). According to the fusion transcript levels of RUNX1-RUNX1T1 the AML children were divided into low-expression group and high-expression group; the threshold values for grouping were 104 copies/104 ß-glucuronidase (GUS), 103 copies/104 GUS, 102 copies/104 GUS, 10 copies/104 GUS, 1 copies/104 GUS and 0 copies respectively. The gained data were enrolled in the statistical analysis. RESULTS: 23 cases of 63 children died during the follow-up period, and the median follow-up time of the remaining 40 children were 30.04 (11-60) months. There were statistically significant differences in CD15 positive rate between low-expression group and high-expression group (P<0.05), however, there were no statistically significant differences in sex, age, FAB typing, platelet (Plt) count, hemoglobin (Hb) and white blood cell (WBC) count and the ratio of bone marrow immature cells at T2 between the two groups (P>0.05). Univariate analysis showed that sex, Plt counts at T1 and fusion transcript levels at T1, T2 and T6 correlated with the 5-year overall survival rate (P<0.05). Multivariate analysis showed that fusion transcript level >103 copies/104 GUS at T2 was an independent risk factor for 5-year overall survival rate (HR=2.13, 95%CI: 1.04-7.78)(P<0.05). CONCLUSION: The fusion transcript level after the first induction therapy in RUNX1-RUNX1T1-positive AML children is an independent factor influencing the long-term prognosis.

Evaluations of submarine groundwater discharge and associated heavy metal fluxes in Bohai Bay, China.

Submarine groundwater discharge (SGD) has been recognized as an important source of dissolved heavy metals to the coastal ocean. Bohai Bay, the second largest bay of Bohai Sea in China, is subjected to serious environmental problems. However, SGD and SGD-derived heavy metal fluxes in the bay are seldom reported. In this study, we present mass balance models considering the radium losses caused by recirculated seawater to estimate water age, SGD and SGD-derived heavy metal fluxes in Bohai Bay during May 2017. The water age is estimated to be 56.7-85.0 days based on tidal prism model. By combining water and salt mass balance models, submarine fresh groundwater discharge (SFGD) is estimated to be (3.5-9.3) × 107 m3 d-1. The SGD flux estimated by the radium mass balance models is (3.2-7.7) × 108 m3 d-1, an order of magnitude larger than the discharge of the Yellow River during the sampling period. SGD-derived heavy metal fluxes were estimated to be (0.2-6.0) × 107 mol d-1 for Fe, (1.2-2.7) × 107 mol d-1 for Mn, (3.0-8.2) × 105 mol d-1 for Zn, (2.7-7.4) × 104 mol d-1 for Cr and (0.6-1.8) × 103 mol d-1 for Cd, which are significantly higher than those from local rivers. This study reveals that SGD is a significant source of heavy metals (Mn, Zn and Fe) into Bohai Bay, which may have important influences on the metal budgets and ecological environments in coastal areas.

Groundwater-surface water exchange associated metals at two intertidal transects, Dan'ao Estuary, Daya Bay, China.

In the evaluation of aquatic environments in estuarine waters, the groundwater-surface water exchanges and associated metal fluxes are difficult to quantify and often ignored. This study made such an attempt based on field data at two intertidal transects in the estuarine wetland of Dan'ao River, the largest river flowing into Daya Bay, China. The results of groundwater-surface water exchange associated six common metals (Cu, Zn, As, Cd, Pb, and Cr) indicate the following: the cumulative concentrations of the six metals are ranked as seawater > groundwater > river water. Among all estuarine groundwaters, the sum of metal concentrations in rhizospheric groundwater at the upstream transect is the highest, owing to the enriching effects of mangrove rhizospheres on metals. The net fluxes of Cu, Zn, As, Cd, and Cr at the upstream transect are 4.8-13.8, 11.9-16.7, 147.8-190.2, 4.1-4.9, and 10.0-12.6 times higher than those at the downstream one. The much higher groundwater discharge rates at the upstream mangrove transect plays a vital role in increasing metal fluxes from groundwater to surface water in this estuary.

Submarine groundwater discharge and chemical behavior of tracers in Laizhou Bay, China.

Naturally occurring radon (222Rn) and radium isotopes are widely used to trace water mixing and submarine groundwater discharge (SGD) in the coastal zones. However, their activities in groundwater are variable both spatially and temporally. Here, time series sampling of 222Rn and radium was conducted to investigate their behavior in intertidal groundwater of Laizhou Bay, China. The result shows that groundwater redox conditions have an important impact on the behavior of tracers. The activities of tracers will decrease under oxidizing conditions and increase under reducing conditions. Radon and radium mass balance models were used to evaluate the flushing time and SGD based on spatial surveys in Laizhou Bay. The flushing time is estimated to be 32.9-55.3 d with coupled models, which agrees well with the result of tidal prism model. The trace-derived SGD in the whole bay ranges from 6.1 × 108 to 9.0 × 108 m3/d and the re-circulated seawater (RSGD) ranges from 5.5 × 108 to 8.5 × 108 m3/d. The average SGD and RSGD fluxes are 22.8 and 21.1 times greater than the Yellow River discharge in April 2014, respectively. The study provides a better understanding of the dynamics of coastal groundwater and behavior of tracers in a well-studied bay system.

Cationic DDA/TDB liposome as a mucosal vaccine adjuvant for uptake by dendritic cells in vitro induces potent humoural immunity.

The cationic dimethyldioctadecylammonium/trehalose 6,6,9-dibehenate (DDA/TDB) liposome is as a strong adjuvant system for vaccines, with remarkable immunostimulatory activity. The mucosal administration of vaccines is a potential strategy for inducing earlier and stronger mucosal immune responses to infectious diseases. In this study, we assessed whether the intranasal administration of cationic DDA/TDB liposomes combined with influenza antigen A (H3N2) can be used as a highly efficacious vaccine to induce mucosal and systemic antibody responses. Confocal laser scanning microscopy and a flow-cytometric analysis showed that the uptake of the cationic DDA/TDB liposome carrier was significantly higher than that of neutral 1,2-distearoyl-sn-glycero-3-phosphocholine/cholesterol (DSPC/Chol) or cationic 1,2-dioleoyl-3-trimethylammonium-propane/3ß-(N-[N',N'-dimethylaminoethane]-carbamoyl (DOTAP/DC-Chol) liposomes. Our results indicate that the cationic DDA/TDB liposome is more effective in facilitating its uptake by dendritic cells (DCs) in vitro than the DSPC/Chol or DOTAP/DC-Chol liposome. DCs treated with DDA/TDB liposomes strongly expressed CD80, CD86, and MHC II molecules, whereas those treated with DSPC/Chol or DOTAP/DC-Chol liposomes did not. C57BL/6 mice intranasally immunized with H3N2-encapsulating cationic DDA/TDB liposomes had significantly higher H3N2-specific s-IgA levels in their nasal wash fluid than those treated with other formulations. The DDA/TDB liposomes also simultaneously enhanced the serum IgG IgG2a, IgG1, and IgG2b antibody responses. In summary, DDA/TDB liposomes effectively facilitated their uptake by DCs and DCs maturation in vitro, and induced significantly higher mucosal IgA, systemic IgG, IgG1, and IgG2b antibody titres than other formulations after their intranasal administration in vivo. These results indicate that DDA/TDB liposomes are a promising antigen delivery carrier for clinical antiviral applications.

Fabrication of multicomponent amorphous bufadienolides nanosuspension with wet milling improves dissolution and stability.

Multicomponent formulations have attracted increasing attention because of their favourable patient compliance and greater therapeutic effect. The aim of this study was to develop a multicomponent nanosuspension formulation of bufadienolides, the antitumor components of a traditional Chinese medicine, toad venom, using a wet-milling technique to improve its dissolution behaviour. Croscarmellose sodium (CCS) and sodium lauryl sulfate (SLS) were chosen as the combined stabilizers of the nanosuspension. A Taguchi orthogonal array design was used for this study to optimize the formulation and process parameters. The optimized nanosuspension was characterized by its particle size distribution, zeta potential, morphology, crystallinity, molecular interactions, stability and dissolution. The results showed that the nanosuspension was a homogeneous amorphous system with average particle sizes of <100 nm and significantly improved dissolution behaviour. It was also physically stable for at least 2 months; steric and kinetic stabilization were its main stability mechanisms. These findings suggested that the use of wet milling to fabricate nanosuspensions is a promising method for achieving the fast and synchronized dissolution of multicomponent formulations, presumably increasing the bioavailability of poorly water-soluble drugs.

Design of multifunctional liposome-quantum dot hybrid nanocarriers and their biomedical application.

Luminescent semiconductor nanocrystals, also known as quantum dots (QDs), have rich surface chemistry and unique optical properties that make them useful as probes or carriers for molecular diagnostics and therapeutics. However, their potential toxicity and instability in biological environments have puzzled scientific researchers. Much research effort has been devoted to encapsulation of QDs with liposomal hybrids to make them versatile nanocarriers for simultaneous therapeutics and diagnostics (theranostics) and considerable progress has been made over recent years. We provide an overview of the use of QD-liposome complexes (QLCs) for imaging applications, in particular applications in theranostics. More specifically, the design considerations, intracellular uptake and tissue-specific targeting of QLCs are highlighted. Current findings of QLCs for theranostics are discussed. We also discuss the challenges and highlight future directions for applications of liposome-QD hybrid nanocarriers in the biomedical arena.

Submarine fresh groundwater discharge into Laizhou Bay comparable to the Yellow River flux.

Near- and off-shore fresh groundwater resources become increasingly important with the social and economic development in coastal areas. Although large scale (hundreds of km) submarine groundwater discharge (SGD) to the ocean has been shown to be of the same magnitude order as river discharge, submarine fresh groundwater discharge (SFGD) with magnitude comparable to large river discharge is never reported. Here, we proposed a method coupling mass-balance models of water, salt and radium isotopes based on field data of (223)Ra, (226)Ra and salinity to estimate the SFGD, SGD. By applying the method in Laizhou Bay (a water area of ~6000 km(2)), we showed that the SFGD and SGD are 0.57 ~ 0.88 times and 7.35 ~ 8.57 times the annual Yellow River flux in August 2012, respectively. The estimate of SFGD ranges from 4.12 × 10(7) m(3)/d to 6.36 × 10(7) m(3)/d, while SGD ranges from 5.32 × 10(8) m(3)/d to 6.20 × 10(8) m(3)/d. The proportion of the Yellow River input into Laizhou Bay was less than 14% of the total in August 2012. Our method can be used to estimate SFGD in various coastal waters.

Aesthetic reconstruction of the upper lip with novel split musculomucosal-pedicle cross-lip flap.

BACKGROUND: The upper lip can be divided into aesthetic subunits. Accordingly, we classified the upper lip defect into 3 categories: medial subunit defect, lateral subunit defect, and cross-subunit defect. The defect should be repaired aesthetically. We developed an innovative partial-thickness myocutaneous flap based on the vascular network of the submucosal and subcutaneous layers. The flap was more flexible for aesthetic reconstruction of the upper lip, even the fine anatomic structures. METHODS: For three and a half years, a total of 59 patients were used with this new technique, including those with secondary deformities from bilateral cleft lip, postinjury upper lip defects, and posthemangioma treatment defects. The inclusion criteria were that the defects of the upper lip were within 2.0 cm in adults and 1.5 cm in children generally. The split flap was elevated from the posterior portion of the orbicularis oris muscle after the inferior labial artery was divided. The flap was supplied by the vascular network derived mainly from the horizontal labiomental artery and/or the vertical labiomental artery. RESULTS: All 59 cases of musculomucosal-pedicle flaps were viable. The upper lip was reconstructed according to the aesthetic subunits. In some cases, the fine anatomic structures were reconstructed, including the philtral column, the philtral dimple, curve of the Cupid's bow, and vermilion tubercle. The patients were all satisfied with their appearance. CONCLUSIONS: This myocutaneous cross-lip flap with musculomucosal-pedicle is an effective method for aesthetic reconstruction of the upper lip. It can provide larger tissue with better flexibility and plasticity in clinical application.

[Muscles reposition in correction of nasal deformity after unilateral cleft lip].

OBJECTIVE: To investigate the effective method for correction of nasal deformity after unilateral cleft lip. METHODS: 50 cases with secondary nasal deformity after unilateral cleft lip were retrospectively analyzed. All the patients underwent nasal and lip muscle reposition operation to restore the symmetry of nasal alar. RESULTS: The nasal deformity was greatly improved in all the 50 cases. The malposition of nasal column and nasal alar was corrected. The symmetry was markedly improved. The measurement before and after operation showed significant difference ( P<0.05). CONCLUSIONS: The reasons of secondary nasal deformity after unilateral cleft lip are complicated. The muscle reposition operation can effectively improve the deformity.