Self-aspiration sampling design for rapid analyses of volatile organic compounds based on atmospheric pressure chemical ionization/photoionization combined ionization source mass spectrometry.

Development of combined mass spectrometry ionization sources has enabled expansion of the application and scope of mass spectrometry. A novel hybrid ionization system combining vacuum ultraviolet (VUV) and atmospheric pressure chemical ionization (APCI) was constructed. Gaseous samples were self-aspirated into an ionization zone through a capillary by negative pressure, generated by high-speed airflow based on the Venturi effect. Compared with APCI mode alone, the signal-to-noise ratio (S/N) in APCI/VUV mode was increased by about 276-times. To increase the ionization efficiency further, correlated experimental conditions were optimized. Four types of volatile organic compounds (VOCs) were tested to evaluate the performance of the APCI/VUV ion source. Excellent linearity and limit of detection were achieved for compounds in mixed solutions. Quantitative analyses of four VOCs (toluene, cyclohexanone, styrene and ethylbenzene) using APCI/VUV-MS were done, and the relative standard deviations (RSDs) were 1.57%, 6.30%, 4.49% and 8.21%, respectively, indicating that the APCI/VUV ionization source had excellent reproducibility. Our results demonstrated that the developed method was promising for analyzing VOCs as well as being rapid, simple, and easy to operate.

Bile acids-gut microbiota crosstalk contributes to the improvement of type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) occurs that cannot effectively use the insulin. Insulin Resistance (IR) is a significant characteristic of T2DM which is also an essential treatment target in blood glucose regulation to prevent T2DM and its complications. Bile acids (BAs) are one group of bioactive metabolites synthesized from cholesterol in liver. BAs play an important role in mutualistic symbiosis between host and gut microbiota. It is shown that T2DM is associated with altered bile acid metabolism which can be regulated by gut microbiota. Simultaneously, BAs also reshape gut microbiota and improve IR and T2DM in the bidirectional communications of the gut-liver axis. This article reviewed the findings on the interaction between BAs and gut microbiota in improving T2DM, which focused on gut microbiota and its debinding function and BAs regulated gut microbiota through FXR/TGR5. Meanwhile, BAs and their derivatives that are effective for improving T2DM and other treatments based on bile acid metabolism were also summarized. This review highlighted that BAs play a critical role in the glucose metabolism and may serve as therapeutic targets in T2DM, providing a reference for discovering and screening novel therapeutic drugs.

Similarities and Differences: A Comparative Review of the Molecular Mechanisms and Effectors of NAFLD and AFLD.

Non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) are the most prevalent metabolic liver diseases globally. Due to the complex pathogenic mechanisms of NAFLD and AFLD, no specific drugs were approved at present. Lipid accumulation, oxidative stress, insulin resistance, inflammation, and dietary habits are all closely related to the pathogenesis of NAFLD and AFLD. However, the mechanism that promotes disease progression has not been fully elucidated. Meanwhile, the gut microbiota and their metabolites also play an important role in the pathogenesis and development of NAFLD and AFLD. This article comparatively reviewed the shared and specific signaling pathways, clinical trials, and potential intervention effectors of NAFLD and AFLD, revealing their similarities and differences. By comparing the shared and specific molecular regulatory mechanisms, this paper provides mutual reference strategies for preventing and treating NAFLD, AFLD, and related metabolic diseases. Furthermore, it provides enlightenment for discovering novel therapies of safe and effective drugs targeting the metabolic liver disease.

Evaluating automated emergency braking performance in simulated car-to-two-wheeler crashes in China: A comparison between C-NCAP tests and in-depth crash data.

Automated Emergency Braking (AEB) is an effective way to prevent crashes from happening or mitigate their severity. Because riders of two-wheelers (TWs) are among the most vulnerable road users, New Car Assessment Programs, like the China New Car Assessment Program (C-NCAP), have recently introduced test scenarios for the assessment of AEB for cars encountering TWs (TW-AEB). The main aim of this study was to determine how well two different C-NCAP test scenario datasets reflect real-world crash scenarios for the purpose of assessing TW-AEB performance. We used virtual counterfactual simulations to determine whether the hypothetical TW-AEB's performance, when applied to the two C-NCAP datasets, was similar to its performance when applied to a set of reconstructed car-to-TW crashes representing real-world crashes. The test datasets were the current C-NCAP scenario set and a proposed C-NCAP scenario set; the real-world crash dataset comprised 113 reconstructed crashes from the Shanghai United Road Traffic Safety Scientific Research Center database (SHUFO). The performances were compared with respect to crash avoidance rate and the characteristics of the remaining crashes. A substantially higher proportion of crashes was avoided in the current C-NCAP scenario set than in the other two (with the sensor field of view (FoV) set to 70° and the activation time to 1.1 s TTC). In fact, with these parameter settings, no crashes remained in the current C-NCAP scenarios, while only 37% and 46% of the crashes in the proposed C-NCAP scenario set and SHUFO crash set were avoided, respectively. Our findings show that TW-AEB systems which are optimized for the current C-NCAP test scenarios are likely to provide benefits in real-world crashes. However, including additional test scenarios which reflect real-world crash situations more accurately would likely lead to a higher correlation between C-NCAP scores and real-world TW-AEB performance. In particular, we recommend the introduction of longitudinal same-direction scenarios with the car or TW turning and perpendicular scenarios with high TW traveling speed, in future C-NCAP releases. Inclusion of these scenarios in C-NCAP might reward improvements of future TW-AEBs toward systems that can save more lives. Furthermore, our study shows that there is likely to be a substantial number of crashes with an impact speed higher than 40 km/h still remaining even after the widespread application of TW-AEB. Therefore, passive safety for TW riders on Chinese roads will be still needed.

Defining crash configurations for Powered Two-Wheelers: Comparing ISO 13232 to recent in-depth crash data from Germany, India and China.

The motorcyclist safety standard ISO 13232, based on crash data from Europe and the USA from the 1970s, still sets the direction for the development and evaluation of protective measures today. However, it is unclear how relevant the crash configurations in the standard are to present-day motorcycle crashes in Europe, the USA and other parts of the world. We analyzed recent in-depth crash data from Germany, India and China, examining powered two-wheeler (PTW) crash configurations in which at least one police-reported serious injury was present. After assessing the relevance of the ISO's PTW crash configurations to those we found in each country, we suggested new configurations to guide the development of safety systems that would be more effective at reducing PTW-related fatalities and serious injuries. In all three databases, passenger cars were among the top two most frequent collision partners and a car front impacting the side of the PTW was the most common configuration. Notably, although collisions with trucks constituted the most common scenario in India and ground impact (primary collision) was a common scenario in both Germany and India, the ISO did not include either configuration. Further, in three of the seven ISO crash configurations, one of the collision partners is stationary, although stationary collision partners were rare in our data. Our results show that the ISO crash configurations do not represent the most frequent PTW road crashes in Germany, India or China. However, the Chinese database was confined to crashes with a collision partner with four or more wheels. Further, weighting factors for these data were not available, so we could not extrapolate the frequency of the Chinese crash configurations across the entire population. A revised version of the ISO could serve as a basis for a full-scale PTW crash test program. However, the observed differences between countries imply that a single global standard may not be feasible. To optimize the evaluation of a PTW safety system, we recommend the inclusion of configurations which are frequent in the region or country of interest-in addition to common configurations occurring frequently all around the world.

A clustering approach to developing car-to-two-wheeler test scenarios for the assessment of Automated Emergency Braking in China using in-depth Chinese crash data.

Two-wheeled vehicles (motorized and non-motorized, referred to as TWs) are an important part of the transport system in China. They also represent an important challenge for road safety, with many TW user fatalities and injuries every year. Recently, active safety systems for cars, such as Automated Emergency Braking (AEB), promise to reduce road traffic fatalities and injuries. For these systems to work effectively, it is necessary to understand and define the complex traffic scenarios to be addressed. The aim of this study is to contribute to the development of test procedures for AEB specifically, drawing on the China In-Depth Accident Study (CIDAS) data from July 2011 to February 2016 to describe typical scenarios for crashes between cars and TWs by means of cluster analysis. In total, 672 car-to-TW crashes were extracted. The data was clustered according to five main crash characteristics: time of crash, view obstruction, pre-crash driving behavior of the car driver and the TW driver, and relative moving direction. The analysis resulted in six car-to-TW crash scenarios typical of China. In three scenarios the car and the TW travel perpendicularly to each other before the crash, in two they travel in the same direction, and in one they travel in opposite directions. Further, each scenario can be described with three characteristics (the road speed limit, the TW's first contact point on the car, and the car's first contact point on the TW) that can be included in an AEB test suite. Some scenarios were similar to those in the Euro New Car Assessment Program (Euro NCAP). For example, in one, a TW moving straight ahead was hit by a car moving perpendicularly, and in the other the car hit a TW traveling in the same direction. Both occurred in daytime, without a visual obstruction. However, in contrast to the Euro NCAP, typical scenarios in China included night-time scenarios, scenarios where the car or the TW was turning, and those in which the TW was hidden from the car by an obstruction. The results contribute to a proposed novel AEB test suite with realistic scenarios specific to China.

Comparing motor-vehicle crash risk of EU and US vehicles.

OBJECTIVE: This study examined the hypotheses that passenger vehicles meeting European Union (EU) safety standards have similar crashworthiness to United States (US) -regulated vehicles in the US driving environment, and vice versa. METHODS: The first step involved identifying appropriate databases of US and EU crashes that include in-depth crash information, such as estimation of crash severity using Delta-V and injury outcome based on medical records. The next step was to harmonize variable definitions and sampling criteria so that the EU data could be combined and compared to the US data using the same or equivalent parameters. Logistic regression models of the risk of a Maximum injury according to the Abbreviated Injury Scale of 3 or greater, or fatality (MAIS3+F) in EU-regulated and US-regulated vehicles were constructed. The injury risk predictions of the EU model and the US model were each applied to both the US and EU standard crash populations. Frontal, near-side, and far-side crashes were analyzed together (termed "front/side crashes") and a separate model was developed for rollover crashes. RESULTS: For the front/side model applied to the US standard population, the mean estimated risk for the US-vehicle model is 0.035 (sd = 0.012), and the mean estimated risk for the EU-vehicle model is 0.023 (sd = 0.016). When applied to the EU front/side population, the US model predicted a 0.065 risk (sd = 0.027), and the EU model predicted a 0.052 risk (sd = 0.025). For the rollover model applied to the US standard population, the US model predicted a risk of 0.071 (sd = 0.024), and the EU model predicted 0.128 risk (sd = 0.057). When applied to the EU rollover standard population, the US model predicted a 0.067 risk (sd = 0.024), and the EU model predicted 0.103 risk (sd = 0.040). CONCLUSIONS: The results based on these methods indicate that EU vehicles most likely have a lower risk of MAIS3+F injury in front/side impacts, while US vehicles most likely have a lower risk of MAIS3+F injury in llroovers. These results should be interpreted with an understanding of the uncertainty of the estimates, the study limitations, and our recommendations for further study detailed in the report.

Triptolide suppresses paraquat induced idiopathic pulmonary fibrosis by inhibiting TGFB1-dependent epithelial mesenchymal transition.

Idiopathic pulmonary fibrosis (IPF) and tumor are highly similar to abnormal cell proliferation that damages the body. This malignant cell evolution in a stressful environment closely resembles that of epithelial-mesenchymal transition (EMT). As a popular EMT-inducing factor, TGFß plays an important role in the progression of multiple diseases. However, the drugs that target TGFB1 are limited. In this study, we found that triptolide (TPL), a Chinese medicine extract, exerts an anti-lung fibrosis effect by inhibiting the EMT of lung epithelial cells. In addition, triptolide directly binds to TGFß and subsequently increase E-cadherin expression and decrease vimentin expression. In in vivo studies, TPL improves the survival state and inhibits lung fibrosis in mice. In summary, this study revealed the potential therapeutic effect of paraquat induced TPL in lung fibrosis by regulating TGFß-dependent EMT progression.

[Research progress about molecular identification of DNA barcoding in medicinal animal].

The use of animal medicine has a long history in China, it has the characteristics of high curative effect,strong activity, wide application and great potential. However,the circulation of animal medicine in current market mixed counterfeit variety and complex. Molecular identification technology of DNA barcoding is an emerging molecular biotechnology in recent years, it is a powerful supplement to traditional identification methods. This method can well identify animal species at the molecular level and has high accuracy, it can identify animal medicines quickly and monitor the medicine market effectively. This article summarizes the research process of molecular identification of DNA barcoding, the application of DNA barcoding in medicinal animals identification in recent years, and the limitations of DNA barcoding technology.

Alteration of oxidative stress and inflammatory cytokines induces apoptosis in diabetic nephropathy.

Diabetic nephropathy (DN) is one of the most significant long­term complications in terms of morbidity and mortality for diabetic patients; however, the exact cause remains unknown. To address this, the DN model was established, and oxidative stress indexes, including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH­Px), and inflammatory cytokines, includinginterleukin­6 (IL­6), tumor necrosis factor­alpha (TNF­α) and transforming growth factor­beta (TGF­ß), were examined by ELISA. Renal pathological alterations and cell apoptosis was examined by hematoxylin and eosin and terminal deoxynucleotidyl transferase mediated dUTP nick­end labeling staining, respectively. The expression levels of B­cell lymphoma­2 (Bcl­2), Bcl­2 associated X (Bax) and caspase­3 wereexamined by immunohistochemistry and western blotting. The DN model was correctly established, with lower body weight and the higher blood glucose in the diabetes model group. The expression levels of SOD and GSH­Px were significantly decreased in the diabetes model group; however, MDA, IL­6, TNF­α and TGF­ß were significantly increased. The kidney was severely damaged in the diabetes model group, with inflammatory cell invasion, increasing amount of interstitial matrix and hypertrophy with vacuolar degeneration of renal tubular cells. Cell apoptosis levels were significantly increased, and Bcl­2 was significantly decreased in the diabetes model group in contrast with that of the sham group; however, Bax and caspase­3 were significantly increased. It suggested that increased oxidative stress and inflammatory cytokines may enhance the apoptosis levels in DN, and may provide a significant diagnostic reference for DN in diabetes patients.

A Simple and Highly Sensitive Thymine Sensor for Mercury Ion Detection Based on Surface Enhanced Raman Spectroscopy and the Mechanism Study.

Mercury ion (Hg2+) is recognized as one of the most toxic metal ions for the environment and for human health. Techniques utilized in the detection of Hg2+ are an important factor. Herein, a simple thymine was successfully employed as the surface enhanced Raman spectroscopy sensor for Hg2+ ion detection. The limit of detection (LOD) of the developed sensor is better than 0.1 nM (0.02 ppb). This sensor can also selectively distinguish Hg2+ ions over 7 types of alkali, heavy metal and transition-metal ions. Moreover, the LOD of the sensor can even achieve 1 ppb in practical application in the nature system, which is half the maximum allowable level (10 nM, 2 ppb) stipulated in the US Environmental Protection Agency standard. Further investigation of the thymine-Hg2+-thymine coordination mechanism provides a possible means of detecting other metal ions by replacing the metal ion-specific ligands. This work paves the way for the detection of toxic metal ions and environmental problems.

Overexpression of phosphodiesterase-4 subtypes involved in surgery-induced neuroinflammation and cognitive dysfunction in mice.

Postoperative cognitive dysfunction (POCD) is characterized by cognitive impairments in patients after surgery. Hippocampal neuroinflammation induced by surgery is highly associated with POCD. Phosphodiesterase-4 (PDE4) is an enzyme that specifically hydrolyses cyclic adenosine monophosphate (cAMP), which plays an important role during neuroinflammation and the process of learning and memory. However, the role of PDE4 in the development of POCD remains unclear. Male 14-month-old C57BL/6 mice received carotid artery exposure to mimic POCD. First, we evaluated cognitive performance by a Morris water maze (MWM) and fear conditioning system (FCS) test after surgery. The expression of PDE4 subtypes, pro-inflammatory cytokines, p-CREB and PSD95 as well as cAMP levels were investigated. Then, we used rolipram, a PDE4 inhibitor, to block the effects of PDE4. The cognitive performance of the mice and the expression of PDE4 subtypes, pro-inflammatory cytokines, p-CREB and PSD95 as well as cAMP levels were examined again. Mice displayed learning and memory impairment, overexpression of PDE4B and PDE4D, elevation of pro-inflammatory cytokines, and reduction in the expression of p-CREB, PSD95 and cAMP levels after surgery. The expression of PDE4B and PDE4D in the hippocampus decreased following blocking of PDE4 by rolipram. Meanwhile, rolipram attenuated the cognitive impairment and the elevation of pro-inflammatory cytokines induced by surgery. Moreover, rolipram reversed the reduction of p-CREB and PSD95. These results indicate that PDE4 subtype overexpression may be involved in the development of surgery-induced cognitive dysfunction in mice.

Commensal Homeostasis of Gut Microbiota-Host for the Impact of Obesity.

Gut microbiota and their metabolites have been linked to a series of chronic diseases such as obesity and other metabolic dysfunctions. Obesity is an increasingly serious international health issue that may lead to a risk of insulin resistance and other metabolic diseases. The relationship between gut microbiota and the host is both interdependent and relatively independent. In this review, the causality of gut microbiota and its role in the pathogenesis and intervention of obesity is comprehensively presented to include human genotype, enterotypes, interactions of gut microbiota with the host, microbial metabolites, and energy homeostasis all of which may be influenced by dietary nutrition. Diet can enhance, inhibit, or even change the composition and functions of the gut microbiota. The metabolites they produce depend upon the dietary substrates provided, some of which have indispensable functions for the host. Therefore, diet is a key factor that maintains or not a healthy commensal relationship. In addition, the specific genotype of the host may impact the phylogenetic compositions of gut microbiota through the production of host metabolites. The commensal homeostasis of gut microbiota is favored by a balance of microbial composition, metabolites, and energy. Ultimately the desired commensal relationship is one of mutual support. This article analyzes the clues that result in patterns of commensal homeostasis. A deeper understanding of these interactions is beneficial for developing effective prevention, diagnosis, and personalized therapeutic strategies to combat obesity and other metabolic diseases. The idea we discuss is meant to improve human health by shaping or modulating the beneficial gut microbiota.

Misuse of booster cushions among children and adults in Shanghai-an observational and attitude study during buckling up.

OBJECTIVE: Traffic crashes are one of the leading causes of fatalities among Chinese children. Booster cushion usage in China is low, and there are no studies showing how a population with limited experience handles booster cushions during buckling up. The purpose of this study was to evaluate the handling of and explore the attitudes toward booster cushions among children, parents, and grandparents in Shanghai. METHODS: An observational study including a convenience sample of 254 children aged 4-12 years was conducted in 2 passenger cars at a shopping center in Shanghai. Parents, grandparents, or the children themselves buckled up the child on 2 types of booster cushions, a 2-stage integrated booster cushion (IBC) and an aftermarket booster cushion (BC). The test participants were observed during buckling up, first without and then with instructions. The test leaders conducted structured interviews. RESULTS: Ninety-eight percent of the uninstructed participants failed to buckle up without identified misuse on the aftermarket booster cushion and 31% of those uninstructed on the integrated booster cushion. The majority of misuse was severe, including placing the belt behind the arm and the lap belt routing above the guiding loops. Instruction reduced misuse to 58% (BC) and 12% (IBC), respectively, and, in particular, severe misuse. Some misuse was related to limited knowledge of how to buckle up on the booster cushion, and some misuse was intentional in order to reduce discomfort. The participants, both children and adults, reported that they preferred the IBC due to good comfort and convenience. Safety was reported as the main reason for adults using booster cushions in general, whereas children reported comfort as the most important motivation. CONCLUSIONS: Education is needed to ensure frequent and correct use of booster cushions in China and to raise safety awareness among children and adults. Furthermore, it is important that the booster cushions offer intuitively correct usage to a population with limited experience of booster cushions. This is the first study published on the handling of and attitude toward booster cushions after child restraints laws were introduced in Shanghai 2014.

Census study of real-life near-side crashes with modern side airbag-equipped vehicles in the United States.

OBJECTIVE: This study aimed to investigate the crash characteristics, injury distribution, and injury mechanisms for Maximum Abbreviated Injury Score (MAIS) 2+ injured belted, near-side occupants in airbag-equipped modern vehicles. Furthermore, differences in injury distribution for senior occupants compared to non-senior occupants was investigated, as well as whether the near-side occupant injury risk to the head and thorax increases or decreases with a neighboring occupant. METHOD: National Automotive Sampling System's Crashworthiness Data System (NASS-CDS) data from 2000 to 2012 were searched for all side impacts (GAD L&R, all principal direction of force) for belted occupants in modern vehicles (model year > 1999). Rollovers were excluded, and only front seat occupants over the age of 10 were included. Twelve thousand three hundred fifty-four MAIS 2+ injured occupants seated adjacent to the intruding structure (near-side) and protected by at least one deployed side airbag were studied. To evaluate the injury risk influenced by the neighboring occupant, odds ratio with an induced exposure approach was used. RESULT: The most typical crash occurred either at an intersection or in a left turn where the striking vehicle impacted the target vehicle at a 60 to 70° angle, resulting in a moderate change of velocity (delta-V) and intrusion at the B-pillar. The head, thorax, and pelvis were the most frequent body regions with rib fracture the most frequent specific injury. A majority of the head injuries included brain injuries without skull fracture, and non-senior rather than senior occupants had a higher frequency of head injuries on the whole. In approximately 50% of the cases there was a neighboring occupant influencing injury outcome. CONCLUSION: Compared to non-senior occupants, the senior occupants sustained a considerably higher rate of thoracic and pelvis injuries, which should be addressed by improved thorax side airbag protection. The influence on near-side occupant injury risk by the neighboring occupant should also be further evaluated. Furthermore, side airbag performance and injury assessments in intersection crashes, especially those involving senior occupants in lower severities, should be further investigated and side impact dummy biofidelity and injury criteria must be determined for these crash scenarios.

Neurokinin-1 receptor antagonists in preventing postoperative nausea and vomiting: a systematic review and meta-analysis.

Newly developed neurokinin-1 receptor (NK-1R) antagonists have been recently tried in the prevention of postoperative nausea and vomiting (PONV). This systematic review and meta-analysis was conducted to explore whether NK-1R antagonists were effective in preventing PONV.The PRISMA statement guidelines were followed. Randomized clinical trials (RCTs) that tested the preventive effects of NK-1R antagonists on PONV were identified by searching EMBASE, CINAHL, PubMed, and the Cochrane Library databases followed by screening. Data extraction was performed using a predefined form and trial quality was assessed using a modified Jadad scale. The primary outcome measure was the incidence of PONV. Meta-analysis was performed for studies using similar interventions. Network meta-analysis (NMA) was conducted to compare the anti-vomiting effects of placebo, ondansetron, and aprepitant at different doses.Fourteen RCTs were included. Meta-analysis found that 80 mg of aprepitant could reduce the incidences of nausea (3 RCTs with 224 patients, pooled risk ratio (RR) = 0.60, 95% confidence interval (CI) = 0.47 to 0.75), and vomiting (3 RCTs with 224 patients, pooled RR = 0.13, 95% CI = 0.04 to 0.37) compared with placebo. Neither 40 mg (3 RCTs with 1171 patients, RR = 0.47, 95% CI = 0.37 to 0.60) nor 125 mg (2 RCTs with 1058 patients, RR = 0.32, 95% CI = 0.13 to 0.78) of aprepitant showed superiority over 4 mg of ondansetron in preventing postoperative vomiting. NMA did not find a dose-dependent effect of aprepitant on preventing postoperative vomiting.Limited data suggested that NK-1R antagonists, especially aprepitant were effective in preventing PONV compared with placebo. More large-sampled high-quality RCTs are needed.

Postconditioning improvement effects of ulinastatin on brain injury following cardiopulmonary resuscitation.

The aim of the present study was to determine the effects of ulinastatin (UTI) on brain injury in rats subjected to cardiopulmonary resuscitation (CPR) following asphyxial cardiac arrest (CA) and identify the underlying mechanisms. In total, 100 healthy male Wistar rats were randomly divided into control and treatment groups (n=50). After 4 min of asphyxial CA, all the rats were immediately subjected to CPR. The treatment group animals were administered 15 mg/kg UTI at the onset of resuscitation. The mortality rate in the two groups was recorded at 24 h post-resuscitation. In addition, neurological function was evaluated at 24, 48 and 72 h post-resuscitation using a neurological deficit scale (NDS). Furthermore, the effects of UTI on the Toll-like receptor 4 (TLR4) signaling pathway in brain tissues were determined by assessing TLR4 mRNA expression, nuclear factor (NF)-κB activity and tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels at 1, 3, 6, 12, 24, 48 and 72 h post-resuscitation. After 24 h, the mortality rate significantly decreased in the treatment group when compared with the control animals (10 vs. 30%; P<0.05). Additionally, an overt improvement was observed in the NDS score following UTI treatment when compared with the control (P<0.01). Finally, statistically significant decreases in the levels of TLR4 mRNA expression, NF-κB activity and TNF-α and IL-6 were observed in the treatment group at each time point (P<0.01). Therefore, UTI treatment at the onset of CPR significantly inhibits the TLR4 signaling pathway, thereby alleviating the inflammatory responses following resuscitation and improving neurological function.

Etomidate with or without flumazenil anesthesia for stem cell transplantation in autistic children.

BACKGROUND: The aim of this study was to investigate etomidate administration with or without flumazenil in autistic children who underwent intrathecal transplantation of stem cells by lumbar puncture. METHODS: Forty autistic children aged 2-12, who were scheduled for stem cell transplantation via lumbar puncture under anesthesia, were randomized for a double-blind study. The children were randomly assigned to two groups: the flumazenil group (group F, n=20) and the etomidate group (group E, n=20). All children received 0.2 mg/kg of etomidate. In the case of inadequate anesthesia, patients received repeated doses of 0.1 mg/kg of etomidate until reaching deep sedation. After operation, children in group F were given flumazenil (0.01 mg/kg) and children in group E received placebo. Heart rate (HR), mean arterial pressure, oxygen saturation, respiratory rate, the Ramsay sedation score (RSS), and recovery time of all children were continuously monitored and recorded during the entire procedure. RESULTS: After anesthesia, blood pressure and HR measurements were not significantly changed in both groups compared with the baseline. There were no respiratory depression, bradycardia, hypotension, nausea, and vomiting. Five patients complained of pain on the site of injection. Myoclonus occurred in seven patients. Recovery time in group F was significantly shorter than in group E (p<0.001), and after the injection of flumazenil, RSS in group F significantly decreased than in group E. There were no significant differences in operation time. Physician satisfaction in both groups was similar. CONCLUSIONS: Etomidate resulted in stable hemodynamic responses and relatively less adverse effects, and flumazenil antagonized the anesthetic effect of etomidate; thus, etomidate with flumazenil is suitable for performing stem cell transplantation in autistic children.

Polymeric micelles based on poly(ethylene glycol) block poly(racemic amino acids) hybrid polypeptides: conformation-facilitated drug-loading behavior and potential application as effective anticancer drug carriers.

In this work, racemic hybrid polypeptides poly(ethylene glycol) (PEG)-b-poly(racemic-leucine) (PRL) copolymers with different leucine residues have been synthesized and characterized. Using docetaxel as a model molecule, the high drug-loaded spherical micelles based on PEG-PRL were prepared successfully using dialysis, with a tunable particle size from 170 nm to 250 nm obtained by changing the length of the hydrophobic blocks. Facilitated drug-loading behavior (higher drug-loading ability and easier drug-loading process) of PEG-PRL compared with their corresponding levo forms (PEG-b-poly[levo leucine]) was observed and clarified for the first time. With this facilitation, the highest drug-loading content and efficiency of PEG-PRL micelles can achieve 11.2% ± 0.4% and 67.2% ± 2.4%, respectively. All drug-loaded PEG-PRL micelles exhibit a similar release behavior with a sustained release up to 72 hours. The PEG-PRL was shown to be nontoxic against MCF-7 and human umbilical vein endothelial cells up to a concentration of 100 µg/mL, displaying a good biocompatibility. Also, the docetaxel-loaded PEG-PRL micelles were more toxic than the free drug against MCF-7 human breast cancer cells - both dose and time dependent. Therefore, these high docetaxel-loaded micelles based on racemic hybrid polypeptides appear to be a novel promising nanomedicine for anticancer therapy.