Alloying of Cu with Ru Enabling the Relay Catalysis for Reduction of Nitrate to Ammonia.

Involving eight electron transfer process and multiple intermediates of nitrate (NO3 - ) reduction reaction leads to a sluggish kinetic and low Faradaic efficiency, therefore, it is essential to get an insight into the reaction mechanism to develop highly efficient electrocatalyst. Herein, a series of reduced-graphene-oxide-supported RuCu alloy catalysts (Rux Cux /rGO) are fabricated and used for the direct reduction of NO3 - to NH3 . It is found that the Ru1 Cu10 /rGO shows the ammonia formation rate of 0.38 mmol cm-2 h-1 (loading 1 mg cm-2 ) and the ammonia Faradaic efficiency of 98% under an ultralow potential of -0.05 V versus Reversible Hydrogen Electode (RHE), which is comparable to Ru catalyst. The highly efficient activity of Ru1 Cu10 /rGO can be attributed to the synergetic effect between Ru and Cu sites via a relay catalysis, in which the Cu shows the exclusively efficient activity for the reduction of NO3 - to NO2 - and Ru exhibits the superior activity for NO2 - to NH3 . In addition, the doping of Ru into Cu tunes the d-band center of alloy and effectively modulates the adsorption energy of the NO3 - and NO2 - , which promotes the direct reduction of NO3 - to NH3 . This synergetic electrocatalysis strategy opens a new avenue for developing highly efficient multifunctional catalysts.

Smart anti-vascular nanoagent induces positive feedback loop for self-augmented tumor accumulation.

How to achieve efficient drug accumulation in the tumor with low vascular density is a great challenge but the key to push the limit of anti-vascular therapeutic efficacy. Herein, we report a charge-reversible nanoparticles of gambogenic acid (CRNP-GNA) that would induce the positive feedback loop between increased tumor vascular permeability and improved drug accumulation. This positive feedback loop would remarkably improve tumor vascular permeability for efficient drug accumulation through few residue vessels. As compared to its charge-irreversible analogue in the latter injections, the accumulation in tumor and vascular permeability and retention indexes (VPRI) in CRNP-GNA group respectively boosted from nearly equal to 8.32 and 60 times, while its tumorous microvessel density decreased from nearly equal to only 7%. The self-augmented accumulation consequently amplified the antitumor efficacy via multiple pathways of anti-angiogenesis, vascular disruption and pro-apoptosis, where 5 out of 6 tumors in animal models were completely cured by CRNP-GNA. This work confirms that the underlying positive feedback loop for anti-vascular therapy could be induced by charge-reversible drug delivery nanosystem to achieve efficient and self-augmented drug accumulation even in the tumor with few vessels. It provides a novel strategy to conquer the dilemma between anti-vascular efficacy and drug accumulation.

Membrane-disruptive homo-polymethacrylate with both hydrophobicity and pH-sensitive protonation for selective cancer therapy.

The membrane-disruptive strategy, which involves host defense peptides and their mimetics, is a revolutionary cancer treatment based on broad-spectrum anticancer activities. However, clinical application is limited by low selectivity towards tumors. In this context, we have established a highly selective anticancer polymer, i.e. poly(ethylene glycol)-poly(2-azepane ethyl methacrylate) (PEG-PAEMA), that can mediate the membrane-disruptive activity via a subtle pH change between physiological pH and tumor acidity for selective cancer treatment. Specifically, the resulting PEG-PAEMA can assemble into neutral nanoparticles and silence the membrane-disruptive activity at physiological pH and disassemble into cationic free-chains or smaller nanoparticles with potent membrane-disruptive activity after the protonation of the PAEMA block due to tumor acidity, resulting in high selectivity towards tumors. Dramatically, PEG-PAEMA exhibited a >200-fold amplification in hemolysis and <5% in IC50 against Hepa1-6, SKOV3 and CT-26 cells at pH 6.7 as compared to those at pH 7.4, thanks to the selective membrane-disruptive mechanism. Moreover, mid- and high-dose PEG-PAEMA demonstrated higher anticancer efficacy than an optimal clinical prescription (bevacizumab plus PD-1) and, significantly, had few side effects on major organs in the tumor-bearing mice model, agreeing with the highly selective membrane-disruptive activity in vivo. Collectively, this work showcases the latent anticancer pharmacological activity of the PAEMA block, and also brings new hope for selective cancer therapy.

A Comprehensive Review on Adsorption, Photocatalytic and Chemical Degradation of Dyes and Nitro-Compounds over Different Kinds of Porous and Composite Materials.

Dye and nitro-compound pollution has become a significant issue worldwide. The adsorption and degradation of dyes and nitro-compounds have recently become important areas of study. Different methods, such as precipitation, flocculation, ultra-filtration, ion exchange, coagulation, and electro-catalytic degradation have been adopted for the adsorption and degradation of these organic pollutants. Apart from these methods, adsorption, photocatalytic degradation, and chemical degradation are considered the most economical and efficient to control water pollution from dyes and nitro-compounds. In this review, different kinds of dyes and nitro-compounds, and their adverse effects on aquatic organisms and human beings, were summarized in depth. This review article covers the comprehensive analysis of the adsorption of dyes over different materials (porous polymer, carbon-based materials, clay-based materials, layer double hydroxides, metal-organic frameworks, and biosorbents). The mechanism and kinetics of dye adsorption were the central parts of this study. The structures of all the materials mentioned above were discussed, along with their main functional groups responsible for dye adsorption. Removal and degradation methods, such as adsorption, photocatalytic degradation, and chemical degradation of dyes and nitro-compounds were also the main aim of this review article, as well as the materials used for such degradation. The mechanisms of photocatalytic and chemical degradation were also explained comprehensively. Different factors responsible for adsorption, photocatalytic degradation, and chemical degradation were also highlighted. Advantages and disadvantages, as well as economic cost, were also discussed briefly. This review will be beneficial for the reader as it covers all aspects of dye adsorption and the degradation of dyes and nitro-compounds. Future aspects and shortcomings were also part of this review article. There are several review articles on all these topics, but such a comprehensive study has not been performed so far in the literature.

Metformin Hydrochloride Mucosal Nanoparticles-Based Enteric Capsule for Prolonged Intestinal Residence Time, Improved Bioavailability, and Hypoglycemic Effect.

Metformin hydrochloride enteric-coated capsule (MH-EC) is a commonly used clinical drug for the treatment of type 2 diabetes. In this study, we described a metformin hydrochloride mucosal nanoparticles enteric-coated capsule (MH-MNPs-EC) based on metformin hydrochloride chitosan mucosal nanoparticles (MH-CS MNPs) and its preparation method to improve the bioavailability and hypoglycemic effect duration of MH-EC. In intestinal adhesion study, the residue rates of free drugs and mucosal nanoparticles were 10.52% and 67.27%, respectively after cleaned with PBS buffer. MH-CS MNPs could significantly improve the efficacy of MH and promote the rehabilitation of diabetes rats. In vitro release test of MH-MNPs-EC showed continuous release over 12 h, while commercial MH-EC released completely within about 1 h in intestinal environment (pH 6.8). Pharmacokinetic study was performed in beagle dogs compared to the commercial MH-EC. The durations of blood MH concentration above 2 µg/mL were 9 h for MH-MNPs-EC versus 2 h for commercial MH-EC. The relative bioavailability of MH-MNPs-EC was determined as 185.28%, compared with commercial MH-EC. In conclusion, MH-CS MNPs have good intestinal adhesion and can significantly prolong the residence time of MH in the intestine. MH-MNPs-EC has better treatment effect compared with MH-EC, and it is expected to be a potential drug product for the treatment of diabetes because of its desired characteristics.

Mitochondrial HSF1 triggers mitochondrial dysfunction and neurodegeneration in Huntington's disease.

Aberrant localization of proteins to mitochondria disturbs mitochondrial function and contributes to the pathogenesis of Huntington's disease (HD). However, the crucial factors and the molecular mechanisms remain elusive. Here, we found that heat shock transcription factor 1 (HSF1) accumulates in the mitochondria of HD cell models, a YAC128 mouse model, and human striatal organoids derived from HD induced pluripotent stem cells (iPSCs). Overexpression of mitochondria-targeting HSF1 (mtHSF1) in the striatum causes neurodegeneration and HD-like behavior in mice. Mechanistically, mtHSF1 facilitates mitochondrial fission by activating dynamin-related protein 1 (Drp1) phosphorylation at S616. Moreover, mtHSF1 suppresses single-stranded DNA-binding protein 1 (SSBP1) oligomer formation, which results in mitochondrial DNA (mtDNA) deletion. The suppression of HSF1 mitochondrial localization by DH1, a unique peptide inhibitor, abolishes HSF1-induced mitochondrial abnormalities and ameliorates deficits in an HD animal model and human striatal organoids. Altogether, our findings describe an unsuspected role of HSF1 in contributing to mitochondrial dysfunction, which may provide a promising therapeutic target for HD.

Mucus-Penetrating Alginate-Chitosan Nanoparticles Loaded with Berberine Hydrochloride for Oral Delivery to the Inflammation Site of Ulcerative Colitis.

The rectal enemas of berberine hydrochloride (BH) have emerged as one of the most effective strategies in the clinical treatment of ulcerative colitis (UC). However, oral dosages of BH exhibit a poor anti-inflammatory effect of UC, which may attribute to premature absorption of BH by the upper gastrointestinal tract. Moreover, the thick colonic mucus layer obstructs the penetration of the drug, resulting in low bioavailability to the inflammatory site of the colon. The aim of this study was to develop the mucus-penetrating sodium alginate-chitosan nanoparticles (SA-CS NPs) for oral delivery of BH to the site of colonic ulcer lesions. BH-loaded SA-CS NPs were developed through the ionic gelation method and analyzed for physicochemical characteristics, release performance, penetrability, site retention, and therapeutic efficacy. The results showed that the NPs have a particle size of 257 nm with a negative charge, presenting desired pH-dependent release behavior. The permeation studies elucidated that negatively charged SA-CS NPs had 2.9 times higher mucus penetration ability than positively charged CS NPs. An ex vivo retention study indicated the high retention of BH-SA-CS NPs at the colon site for more than 16 h. In vivo therapeutic effectiveness demonstrated that the prepared NPs could not only alleviate colonic injury by decreasing the disease activity index and colon mucosa damage index, but also improve the immunologic function by decreasing the spleen index. In conclusion, the BH-SA-CS NPs could enhance the mucus permeability and deliver drugs to the colonic inflammation site, providing new insights into improving the therapeutic effect of UC.

Notoginsenoside R1 Reverses Abnormal Autophagy in Hippocampal Neurons of Mice With Sleep Deprivation Through Melatonin Receptor 1A.

Sleep deprivation (SD) may cause serious neural injury in the central nervous system, leading to impairment of learning and memory. Melatonin receptor 1A (MTNR1A) plays an important role in the sleep regulation upon activation by melatonin. The present study aimed to investigate if notoginsenoside R1 (NGR1), an active compound isolated from Panax notoginseng, could alleviate neural injury, thus improve impaired learning and memory of SD mice, as well as to explore its underlying action mechanism through modulating MTNR1A. Our results showed that NGR1 administration improved the impaired learning and memory of SD mice. NGR1 prevented the morphological damage and the accumulation of autophagosomes in the hippocampus of SD mice. At the molecular level, NGR1 reversed the expressions of proteins involved in autophagy and apoptosis, such as beclin-1, LC3B, p62, Bcl-2, Bax, and cleaved-caspase 3. Furthermore, the effect of NGR1 was found to be closely related with the MTNR1A-mediated PI3K/Akt/mTOR signaling pathway. On HT-22 cells induced by autophagy inducer rapamycin, NGR1 markedly attenuated excessive autophagy and apoptosis, and the alleviative effect was abolished by the MTNR1A inhibitor. Taken together, NGR1 was shown to alleviate the impaired learning and memory of SD mice, and its function might be exerted through reduction of excessive autophagy and apoptosis of hippocampal neurons by regulating the MTNR1A-mediated PI3K/Akt/mTOR signaling pathway.

Cardioprotective Effect of Stem-Leaf Saponins From Panax notoginseng on Mice With Sleep Derivation by Inhibiting Abnormal Autophagy Through PI3K/Akt/mTOR Pathway.

Sleep deprivation (SD) may lead to serious myocardial injury in cardiovascular diseases. Saponins extracted from the roots of Panax notoginseng, a traditional Chinese medicine beneficial to blood circulation and hemostasis, are the main bioactive components exerting cardiovascular protection in the treatment of heart disorders, such as arrhythmia, ischemia and reperfusion injury, and cardiac hypertrophy. This study aimed to explore the protective effect of stem-leaf saponins from Panax notoginseng (SLSP) on myocardial injury in SD mice. SD was induced by a modified multi-platform method. Cardiac morphological changes were assessed by hematoxylin and eosin (H&E) staining. Heart rate and ejection fraction were detected by specific instruments. Serum levels of atrial natriuretic peptide (ANP) and lactate dehydrogenase (LDH) were measured with biochemical kits. Transmission electron microscopy (TEM), immunofluorescent, and Western blotting analysis were used to observe the process and pathway of autophagy and apoptosis in heart tissue of SD mice. In vitro, rat H9c2 cells pretreated with rapamycin and the effect of SLSP were explored by acridine orange staining, transient transfection, flow cytometry, and Western blotting analysis. SLSP prevented myocardial injury, such as morphological damage, accumulation of autophagosomes in heart tissue, abnormal high heart rate, serum ANP, and serum LDH induced by SD. In addition, it reversed the expressions of proteins involved in the autophagy and apoptosis and activated PI3K/Akt/mTOR signaling pathway that is disturbed by SD. On H9c2 cells induced by rapamycin, SLSP could markedly resume the abnormal autophagy and apoptosis. Collectively, SLSP attenuated excessive autophagy and apoptosis in myocardial cells in heart tissue induced by SD, which might be acted through activating PI3K/Akt/mTOR signaling pathway.

Policy Interventions, Development Trends, and Service Innovations of Internet Hospitals in China: Documentary Analysis and Qualitative Interview Study.

BACKGROUND: Internet hospitals have been encouraged by the Chinese government to develop an innovative medical service model that mainly uses new internet-based technologies to increase access to health care and improve the quality and efficiency of health care delivery. However, the academic exploration of the institutional and sectoral development of internet hospitals in China is scarce in the existing literature. OBJECTIVE: This study aimed to investigate the policy interventions, development trends, and service innovations of internet hospitals in China. It is expected that the findings from this study will contribute to the further innovation of internet hospitals in China and provide references for the international development of internet hospitals for personalized digital health and patient-centric services. METHODS: This study analyzed official policies related to internet hospitals that were implemented by the government in China since 2005. The data of formally approved internet hospitals were collected from official websites to analyze development trends. In-depth semistructured interviews were conducted with 58 key stakeholders who represented comprehensive viewpoints about the service innovations of internet hospitals between March and November 2019. RESULTS: In total, 25 policies that promoted the development of internet hospitals in China were identified. These policies encompassed informatization infrastructure construction, medical resource integration, development model design, service model design, and payment model design. Of the 268 internet hospitals that had received an official license from the government, 153 public internet hospitals had been built mainly by medical institutions. Public tertiary hospitals were the main actors in founding internet hospitals that were created to provide services that targeted patients with common diseases or chronic diseases or patients living in remote and rural areas. Promoting convenient access to high-quality medical resources and saving patients' and their families' time were the key values of internet hospitals. CONCLUSIONS: The policy interventions strongly promoted the development of internet hospitals in China. Public tertiary hospitals led the development of internet hospitals. However, internet hospitals in China have mainly played roles that are complementary to those of physical medical institutions. The service model of internet hospitals needs more distinguished innovations to provide personalized digital health and patient-centric services.

Integrating Real-World Evidence in the Regulatory Decision-Making Process: A Systematic Analysis of Experiences in the US, EU, and China Using a Logic Model.

Real world evidence (RWE) and real-world data (RWD) are drawing ever-increasing attention in the pharmaceutical industry and drug regulatory authorities (DRAs) all over the world due to their paramount role in supporting drug development and regulatory decision making. However, there is little systematic documentary analysis about how RWE was integrated for the use by the DRAs in evaluating new treatment approaches and monitoring post-market safety. This study aimed to analyze and discuss the integration of RWE into regulatory decision-making process from the perspective of DRAs. Different development strategies to develop and adopt RWE by the DRAs in the US, Europe, and China were reviewed and compared, and the challenges encountered were discussed. It was found that different strategies on development of RWE were applied by FDA, EMA, and NMPA. The extent to which RWE was adopted in China was relatively limited compared to that in the US and EU, which was highly related to the national pharmaceutical environment and development stages. A better understanding of the overall goals, inputs, activities, outputs, and outcomes in developing RWE will help inform actions to harness RWD and leverage RWE for better health care decisions.

The short-term associations of chronic obstructive pulmonary disease hospitalizations with meteorological factors and air pollutants in Southwest China: a time-series study.

Chronic obstructive pulmonary disease (COPD) is the fourth major cause of mortality and morbidity worldwide and is projected to be the third by 2030. However, there is little evidence available on the associations of COPD hospitalizations with meteorological factors and air pollutants in developing countries/regions of Asia. In particular, no study has been done in western areas of China considering the nonlinear and lagged effects simultaneously. This study aims to evaluate the nonlinear and lagged associations of COPD hospitalizations with meteorological factors and air pollutants using time-series analysis. The modified associations by sex and age were also investigated. The distributed lag nonlinear model was used to establish the association of daily COPD hospitalizations of all 441 public hospitals in Chengdu, China from Jan/2015-Dec/2017 with the ambient meteorological factors and air pollutants. Model parameters were optimized based on quasi Akaike Information Criterion and model diagnostics was conducted by inspecting the deviance residuals. Subgroup analysis by sex and age was also performed. Temperature, relative humidity, wind and Carbon Monoxide (CO) have statistically significant and consistent associations with COPD hospitalizations. The cumulative relative risk (RR) was lowest at a temperature of 19℃ (relative humidity of 67%). Both extremely high and low temperature (and relative humidity) increase the cumulative RR. An increase of wind speed above 4 mph (an increase of CO above 1.44 mg/m3) significantly decreases (increases) the cumulative RR. Female populations were more sensitive to low temperature and high CO level; elderly (74+) populations are more sensitive to high relative humidity; younger populations (< = 74) are more susceptible to CO higher than 1.44 mg/m3. Therefore, people with COPD should avoid exposure to adverse environmental conditions of extreme temperatures and relative humidity, low wind speed and high CO level, especially for female and elderly patients who were more sensitive to extreme temperatures and relative humidity.

Lactonic sophorolipid-induced apoptosis in human HepG2 cells through the Caspase-3 pathway.

Liver cancer, one of the most common types of cancer in the world, is the second leading cause of death for cancer patients. For liver cancer, there is an urgent need for an effective treatment with no or less toxic side effects. Lactonic sophorolipids (LSL), as a potential anticancer drug, has attracted wide attention of pharmaceutical researchers with its good biological activities. The effects of LSL and cell death inhibitors were measured by MTT test on HepG2 cells. Meanwhile, the morphology of the cells was observed under a microscope. The apoptosis rate was detected by flow cytometry, and the expression levels of enzyme activity of Caspase-3 and Caspase-9 were measured by detection kits. Meanwhile, mRNA levels of Apaf-1, Caspase-3, Bax, and Bcl-2 were measured by quantitative real-time RT-PCR; protein levels of Caspase-3, Cleaved Caspase-3, Bax, and Bcl-2 were measured by western blot. LSL can inhibit the proliferation of cells, and it is possible to induce apoptosis in cells. The HepG2 cells with LSL co-culture exhibited typical apoptotic morphology, and the expression levels of enzyme activity of Caspase-3 and Caspase-9 increased (P< 0.05). We also found that LSL increases cell apoptosis rate and regulates the expression of genes and proteins associated with apoptosis through the Caspase-3 pathway. These results indicate that LSL may be one of the potential drug candidates to inhibit the proliferation and induce apoptosis in HepG2 cells.Key points• LSL, which is of good biological activities such as anti-bacterium, virus elimination, and inflammatory response elimination, has been firstly used to intervene in vitro to investigate its effect on HepG2 cell proliferation.• LSL can inhibit the proliferation of cells, and it is possible to induce apoptosis in HepG2 cells through the Caspase-3 pathway.• The mechanism of LSL action on HepG2 cell proliferation was firstly also discussed, which provides a certain experimental reference for the clinical treatment of liver cancer.

Corrigendum: Cardioprotective Effect of Stem-Leaf Saponins From Panax notoginseng on Mice With Sleep Deprivation by Inhibiting Abnormal Autophagy Through PI3K/Akt/mTOR Pathway.

[This corrects the article DOI: 10.3389/fcvm.2021.694219.].

Corrigendum: Notoginsenoside R1 Reverses Abnormal Autophagy in Hippocampal Neurons of Mice With Sleep Deprivation Through Melatonin Receptor 1A.

[This corrects the article DOI: 10.3389/fphar.2021.719313.].

Effects of Borneol on the Release of Compound Danshen Colon-Specific Osmotic Pump Capsule In Vitro and Pharmacokinetics Study in Beagle Dogs.

Borneol can enhance the bioavailability of several other drugs by opening the blood-brain barrier and inhibiting P-glycoprotein (P-gp) efflux. However, whether borneol will impact the bioavailability and the mechanism of compound Danshen colon-specific osmotic pump capsule (CDCOPC) remains unclear. This study aimed to determine the effects of borneol on the in vitro release and in vivo pharmacokinetic characteristics of CDCOPC. Besides, the in vitro release behavior of CDCOPC was further assessed by chromatographic fingerprints. The in vitro release studies showed that borneol followed the zero-order release and hardly impacted the in vitro release of Salvia miltiorrhiza and Panax notoginseng in CDCOPC. Moreover, as revealed from the similarity results of fingerprints, the in vitro release of different components of CDCOPC was almost simultaneous. Compared with the commercially available tablets, the pharmacokinetics studies suggested that both CDCOPCs containing and lacking borneol could significantly prolong the retention time of these effective components; their average relative bioavailability values increased to 448.70% and 350.97%, respectively. Notably, borneol significantly improved the relative bioavailability of some components of CDCOPC, such as salvianolic acid B (SAB), tanshinone IIA (Tan IIA), notoginsenoside R1 (R1), ginsenoside Rg1 (Rg1), and ginsenoside Re (Re) from CDCOPC, while it slightly impacted ginsenoside Rb1 (Rb1) and ginsenoside Rd (Rd). Summarily, borneol is capable of improving the bioavailability of some effective components in CDCOPC, which is critical to design with CDCOPC for enhanced bioavailability. This study could also help reveal the composition principle of the compound Danshen formula (CDF).

Rapid UV-radiation synthesis of polyacrylate cryogel oil-sorbents with adaptable structure and performance.

Macro-porous poly(lauryl acrylate) cryogel sheets as oil-sorbents were prepared through UV-radiation cryo-polymerizations in 1, 4-dioxane at low temperatures (-5, -2 and 0 °C) within 30 min. The influences of total monomer concentration, crosslinking monomer amount and polymerization temperature on the formation of cryogels were studied. The chemical structure and porous morphology were characterized through the techniques of Fourier transform infrared spectroscopy, thermal gravimetric analysis, contact angle measurement and scanning electron microscopy, confirming the features of high hydrophobicity, macro-porosity and good thermal stability. As well, the comparison between conventional gels prepared at room temperature and cryogels at lower temperatures was made, showing the higher rate of cryo-polymerization than conventional polymerization under the same UV-radiation condition. The swelling investigation was carried out with several organic solvents and oils. Enhanced performance of oil absorption was observed for those cryogels considering the absorption capacity and absorption rate. Variation of initiator amount and acrylate monomers could also modulate the absorption capacity. Those cryogel oil-sorbents exhibited wide adaptability, good reusability and high-temperature tolerance. Thus, this rapid and low-cost fabrication opens out a novel pathway to prepare efficient oil-sorbents used in waste water treatment.

A Nasal Temperature and pH Dual-Responsive In Situ Gel Delivery System Based on Microemulsion of Huperzine A: Formulation, Evaluation, and In Vivo Pharmacokinetic Study.

Huperzine A (hup A), extracted from the Chinese medicinal plant Huperzia serrata, is a reversible and highly selective second-generation acetylcholine esterase (AchE) inhibitor for treating Alzheimer's disease (AD), but it suffers from low bioavailability in the brain. This study aimed to develop a nasal temperature and pH dual-responsive in situ gel delivery system based on microemulsion of hup A (hup A-M-TPISG). The optimal formulation was obtained by central composite design and response surface methodology. The optimized mucoadhesive formulation, hup A-M-TPISG, was composed of pluronic F127 (20.80%), pluronic F68 (2.8%), and chitosan (0.88%) as the gel matrix, which could gelatinize under physiological conditions (29-34°C, pH 6.5) because of its temperature and pH responsiveness. The optimized hup A-M-TPISG formulation was further evaluated by in vitro release and in vivo pharmacokinetic studies via microdialysis. The in vitro release study showed continuous and steady drug release from hup A-M-TPISG, which was in accordance with the first-order model. Moreover, the pharmacokinetic results revealed that the optimized formulation for nasal administration, with convenient administration and improved patient compliance, could achieve similar brain-targeting properties as intravenous administration. In conclusion, the hup A-M-TPISG for intranasal administration, as an effective and safe vehicle, could enhance the absorption of hup A in vivo and would be a promising noninvasive alternative for partially improving brain-targeting therapy.

Trends and Development in Enteral Nutrition Application for Ventilator Associated Pneumonia: A Scientometric Research Study (1996-2018).

Background: This study aimed to explore the intellectual landscape of the studies investigating the clinical application of enteral nutrition (EN) in patients with ventilator associated pneumonia (VAP), and to identify thematic development trends and research frontiers in this area. Methods: Scientometric research was conducted by analyzing bibliographic records retrieved from the Web of Science Core Collection Database dated between 1996 and 2018. Reference co-citation analysis, key words co-occurrence analysis and cooperation network analysis were performed using CiteSpace software. Results: A total of 124 valid records were included in the final dataset. It was found that early studies were mainly focused on the feeding pathways of EN among VAP patients. The risks associated with EN intervention in VAP patients, including gastric nutrition intolerance and aspiration pneumonia, were extensively investigated and reported. While aspiration pneumonia has remained a long-term active research area in the field of EN interventions for VAP patients, with recent research focused more on interventions aiming to improve EN support and to optimize the use of EN for VAP patients. It seems that clinical guidelines on EN interventions for VAP patients need to be established. Conclusion: The advantages of EN for VAP patients have been recognized but still require further investigation on standardizing the use. Strategic cooperation among hospital physicians, university researchers and industrial product developers is required to establish clinical guidelines and to continue developing innovative EN products to tackle VAP.