Retrospective analysis of laboratory results in 18 cases of severe asthma treated with omalizumab.

OBJECTIVE: The aim of this study was to explore the laboratory results in severe as asthma patients with omalizumab therapy and provide evidence for estimating omalizumab efficacy. METHODS: Retrospective study of 18 patients with severe asthma received omalizumab therapy in Shanghai General Hospital from 2020 to 2022 was performed. The basic data of patients were collected. The absolute number and the percentage of basophil and eosinophil in peripheral blood, total IgE level in serum, and as pulmonary function were detected at the beginning of treatment and 4 months after treatment. Differences between two groups were analyzed using Paired T test. RESULTS: The most common allergens collected from patients with moderate to severe asthma were dust mite (positive ratio 55.56%), mixed mold (16.67%), cat and dog dander, and Aspergillus fumigatus (11.11%). There was no significant difference in eosinophil and basophil counts in peripheral blood between the two groups. However, serum total IgE levels increased from (437.55±279.35) KU/L to (1071.42±721.28) KU/L (P=0.004), and FEV1/FVC ratio increased from (65.53±14.15)% to (73.91±13.63)% (P=0.005) after 4 months of treatment. CONCLUSIONS: The existing laboratory indicators for evaluation of omalizumab efficacy are still very limited, and new biomarkers need to be further developed. Elevated serum IgE levels at four weeks of treatment and FEV1/FVC may be potential indicators for omalizumab monitoring.

Large viewing angle integral imaging 3D display system based on a symmetrical compound lens array.

We propose a large viewing angle integral imaging 3D display system based on a symmetrical compound lens array (SCLA). The display system comprises a high-resolution 2D display panel, an SCLA, and a light shaping diffuser. The high-resolution 2D display panel presents an elemental image array, the SCLA modulates the light rays emitted from the 2D display panel to form 3D images in space, and the light shaping diffuser eliminates the gaps between 3D pixels of the 3D images. We find that the lateral aberration is a crucial factor that affects the resolution of the reconstructed 3D image. The symmetrical structure of the SCLA enables a reduced focal length and the elimination of lateral aberration, improving the viewing angle and the 3D image resolution simultaneously. The experimental results confirm that the proposed display system increases the viewing angle to 68.6°, achieving a comparable resolution of the full field of view while maintaining a simple structure.

A nickel-catalyzed silylation reaction of alkyl aryl sulfoxides with silylzinc reagents.

Ni(PEt3)Cl2-catalyzed silylation of alkyl aryl sulfoxides with silylzinc reagents was carried out. This protocol allows alkyl aryl sulfoxides to convert to arylsilicon compounds under mild reaction conditions, tolerates a range of functional groups and is suitable for a wide scope of substrates.

Nickel-catalyzed coupling of R2P(O)Me (R = aryl or alkoxy) with (hetero)arylmethyl alcohols.

α-Alkylation of methyldiarylphosphine oxides with (hetero)arylmethyl alcohols was performed under nickel catalysis. Various arylmethyl and heteroarylmethyl alcohols can be used in this transformation. A series of methyldiarylphosphine oxides were alkylated with 30-90% yields. Functional groups on the aromatic rings of methyldiarylphosphine oxides or arylmethyl alcohols including OMe, NMe2, SMe, CF3, Cl, and F groups can be tolerated. The conditions are also suitable for the α-alkylation reaction of dialkyl methylphosphonates.

An Optimized and Feasible Preparation Technique for the Industrial Production of Hydrogel Patches.

For hydrogel patches, the laboratory tests could not fully reveal the existing problems of full scale of industrial production, and there are few studies about the preparation technique for the industrial manufacturing process of hydrogel patches. So, the purpose of this work was to elucidate the effects of mainly technological operation and its parameters on the performance of hydrogel patches at the industrial-scale production. The results revealed the following: (1) the aqueous phase was obtained by polyvinylpyrrolidone (PVP) along with tartaric acid dissolved in purified water, then feeding this into a vacuum mixer as a whole in one batch, thus extended the crosslinking reaction time of hydrogel paste (matrix) and allowed the operation of coating/cutting-off to be carried out easily, and there was no permeation of backing layer; (2) the gel strength of the hydrogel patches increased with the increase of working temperature, however, once the temperature exceeded 35 ± 2 °C, the hydrogel paste would lose water severely and the resultant physical crosslinking structure which has lower gel/cohesive strength would easily bring gelatinization/residues during application; (3) the relative humidity (RH) of the standing-workshop was dynamically controlled (namely at 35 ± 2 °C, keeping the RH at 55 ± 5% for 4 days, then 65 ± 5% for 2 days), which would make patches with satisfactory characteristics such as better flexibility, higher adhesive force, smooth flat matrix surface, and without gelatinization/residues and warped edge during the using process; (4) the aging of the packaged hydrogel patches was very sensitive to storage temperature, higher temperature, higher gel strength and lower adhesiveness. The storage temperature of 10 ± 2 °C could effectively prevent matrix aging and adhesion losing, which would also facilitate the expiration date of patches extended obviously. In conclusion, this work provides an optimized and feasible preparation technique for the industrial production of the hydrogel patches and establishes the hydrogel patches as a novel carrier for transdermal drug delivery.

Palladium(ii)-catalyzed C-C and C-O bond formation for the synthesis of C1-benzoyl isoquinolines from isoquinoline N-oxides and nitroalkenes.

C1-Benzoyl isoquinolines can be generated via a palladium(ii)-catalyzed C-C and C-O coupling of isoquinoline N-oxides with aromatic nitroalkenes. The reaction proceeds through remote C-H bond activation and subsequent intramolecular oxygen atom transfer (OAT). In this reaction, the N-O bond was designed as a directing group in the C-H bond activation as well as the source of an oxygen atom.

Propylene glycol-embodying deformable liposomes as a novel drug delivery carrier for vaginal fibrauretine delivery applications.

The purpose of this work was to develop and characterize the fibrauretine (FN) loaded propylene glycol-embodying deformable liposomes (FDL), and evaluate the pharmacokinetic behavior and safety of FDL for vaginal drug delivery applications. FDL was characterized for structure, particle size, zeta potential, deformability and encapsulation efficiency; the ability of FDL to deliver FN across vagina tissue in vitro and the distribution behavior of FN in rat by vaginal drug delivery were investigated, the safety of FDL to the vagina of rabbits and rats as well as human vaginal epithelial cells (VK2/E6E7) were also evaluated. Results revealed that: (i) the FDL have a closed spherical shape and lamellar structure with a homogeneous size of 185±19nm, and exhibited a negative charge of -53±2.7mV, FDL also have a good flexibility with a deformability of 92±5.6 (%phospholipids/min); (ii) the dissolving capacity of inner water phase and hydrophilicity of phospholipid bilayers of deformable liposomes were increased by the presence of propylene glycol, this may be elucidated by the fluorescent probes both lipophilic Nile red and hydrophilic calcein that were filled up the entire volume of the FDL uniformly, so the FDL with a high entrapment capacity (were calculated as percentages of total drug) for FN was 78±2.14%; (iii) the permeability of FN through vaginal mucosa was obviously improved by propylene glycol-embodying deformable liposomes, no matter whether the FN loaded in liposomes or not, although FN loaded in liposomes caused the highest permeability and drug reservoir in vagina; (iv) the FN mainly aggregated in the vagina and uterus, then the blood, spleen, liver, kidney, heart and lungs for vaginal drug delivery, this indicating vaginal delivery of FDL have a better 'vaginal local targeting effect'; and (v) the results of safety evaluation illustrate that the FDL is non-irritant and well tolerated in vivo, thereby establishing its vaginal drug delivery potential. These results indicate that the propylene glycol-embodying deformable liposomes may be a promising drug delivery carrier for vaginal delivery of fibrauretine.

[Effects of Forsythia suspensa Volatile Oil Loaded Nanomicellar on Transdermal and Transmucosal Drug Delivery of Phillyrin in Vitro].

Objective: To prepare all components loaded liquid preparation of Forsythia suspensa( ACLL) by the technology of nanomicellar solubilization,and to investigate the effects of Forsythia suspensa volatile oil loaded nanomicellar on the transdermal and transmucosal drug delivery of phillyrin. Methods: The volatile oil and hydrosoluble components of Forsythia suspensa were obtained by double extraction synchronously,and the major components of volatile oil were determined by GC-MS. Then the ACLL prepared by the volatile oil was added to the aqueous solution in the form of nanomicellar. The characteristics of ACLL were evaluated by the TEM,PCS and CLSM. The amount of phillyrin( PN) was determined by HPLC system. The side-by-side diffusion cell was used to investigate the effects of Forsythia suspense volatile oil loaded nanomicellar on the PN transdermal and transmucosal drug delivery, with the hydrosoluble components loaded liquid( HCLL) used as control group. Results: The Forsythia suspense volatile oil was slight yellowish and transparent liquid with a fragrant odor,the major components as follows ß-pinene( 49. 01%),α-pinene( 15. 78%), ß-ocimene( 13. 79%),linalool( 5. 91%), α-thujene( 2. 07%), ß-geranene( 1. 91%),terpinolene( 1. 84%),etc. The Forsythia suspense volatile oil loaded nanomicellar had a closed spherical shape as the TEM and CLSM images appeared. The calculated mean size was 193. 3 nm,the Zeta potential values of- 83. 8 m V. During the whole experiment, the ACLL resulted in a remarkable enhancement of PN transdermal and transmucosal absorption compared with HCLL. At 7. 0 h, the accumulated permeation amount of PN from the ACLL was 2. 04 and 1. 16 folds than that of HCLL for transdermal and transmucosal absorption,respectively. Conclusion: The permeability of PN is obviously enhanced by Forsythia suspense volatile oil loaded nanomicellar for transdermal and transmucosal absorption, these results elucidate the advantages and the mechanism of pharmacological action of all components of traditional Chinese medicine.

A facile synthesis of 2,5-disubstituted oxazoles via a copper-catalyzed cascade reaction of alkenes with azides.

A novel and efficient approach to the synthesis of 2,5-disubstituted oxazoles is developed via a 1,3-dipolar cycloaddition/ring cleavage/1,2-H migration/denitrogenation/copper-catalyzed aerobic oxidative dehydrogenative cyclization cascade. The desired products can be obtained from readily available aromatic terminal alkenes and azides employing air as the oxidant under mild conditions, and it offers an attractive alternative method for the synthesis of oxazole derivatives.

Post-expansile hydrogel foam aerosol of PG-liposomes: a novel delivery system for vaginal drug delivery applications.

The purpose of this work was to develop and characterize a novel delivery system of post-expansile hydrogel foam aerosol of propylene glycol-embodying liposomes (PG-liposomes) (PEHFL) for vaginal drug delivery applications. Matrine (MT) was used as a model drug to investigate the vaginal mucous membrane permeation behavior of MT from PEHFL versus PG-liposomes foam aerosol (PLFA), hydrogel foam aerosol (HFA) and hydrogel (HYG). The MT loaded PG-liposomes were characterized for shape, particle size, polydispersity, zeta potential and encapsulation efficiency; the foams of PEHFL were also characterized for swelling behavior, mucoadhesive force and duration. Results revealed that: (i) the MT loaded PG-liposomes had a mean size of 122 ± 16 nm, a good polydispersity index of 0.147 ± 0.023, and exhibited a negative charge of -47.5 ± 0.4 mV, the MT entrapment capacity in PG-liposomes (was calculated as percentages of total drug) was 80.8 ± 2.6%; (ii) the foams of PEHFL had a laggingly swelling process after spurted from a sealed container, and the higher the temperature of the surrounding environment, the greater the degree of swelling, this swelling state of foams would greatly enhance drug spread uniformly in vaginal canal and contact the vaginal walls tightly; (iii) the foams of PEHFL had a mucoadhesive force about 1460 ± 123 mN/cm(2), and could sustain 85 ± 11 min in vitro; (iv) the overall mean permeated MT through unit mass of porcine vaginal tissue from PEHFL was 2.64, 2.34 and 7.59 times higher than that from PLFA, HFA and HYG, respectively (t-test, P<0.05); and the quantity of MT remaining in the vaginal tissue at the end of the 12h experiment was also significantly greater (t-test, P<0.05) from the PEHFL than from PLFA, HFA and HYG. All of these results indicate that the main advantages of PEHFL over conventional dosage forms are the ability to enhance the vaginal mucosa permeability of MT, spread uniformly in vaginal canal especially the highly folded epithelial surfaces, prolong the residence time at the site of administration and induce MT delayed release. In conclusion, the PEHFL may be a promising delivery system for vaginal delivery of medication.

Super-short solid silicon microneedles for transdermal drug delivery applications.

In this study, the super-short microneedles with a length of 70-80 microm were fabricated using silicon wet etching technology. As evident from the visual inspection of pierced human skin, appearance of blue spots array after Evans Blue (EB) application indicated that the super-short microneedles were able to pierce into skin by pressing and swaying against the microneedles backing layer continually with a finger. The micro-conduits created in skin were validated by histological examination. Transport studies revealed that: (i) skin pretreated with super-short microneedles resulted in a remarkable enhancement of the galanthamine (GAL) transport, and the permeated amount increased as the insertion force increased; (ii) the super-short microneedles with flat tips were better than that with sharp tips for enhancing skin permeability; (iii) the longer time of super-short microneedles detained in skin resulted in a higher increase of skin permeability; (iv) there was no linear correlation between the GAL permeated through skin and the number of microneedles. The EIIIA(+) (526 bp) segment, a very sensitive marker of tissue injury, did not expressed in the skin pierced by super-short microneedles. Meanwhile, the skin pretreated with super-short microneedles did not infected after incubation with the Staphylococcus aureus. These results suggest that super-short microneedles may be a safe and efficient alternative for transdermal drug delivery of hydrophilic molecules.