Development, Optimization, and Evaluation In Vitro/In Vivo of Oral Liquid System for Synchronized Sustained Release of Levodopa/Benserazide.

To enhance efficiency, convenience, and safety of Parkinson's disease (PD) treatment for geriatric patients, an advanced suspension of Levodopa/Benserazide hydrochloride (LD/BH) has been prepared by cation-exchange resin and used to synchronize sustained release of LD and BH by optimizing coating parameters and prescription. For the purpose, LD and BH were immobilized on the surface of cation-exchange resin, respectively. Based on HPLC results, the cation-exchange resin showed high loading capacity. The studies on drug loading mechanism indicated that both drugs were immobilized by electrostatic interaction rather than physical adsorption. After PEG modification, pretreated drug-resin complexes were coated by emulsion-solvent evaporation method. In order to control drug release in a sustained manner, coating parameters of drug-resin microcapsules were optimized respectively by single-factor analysis. Further, coating prescription of the microcapsules was optimized to synchronize sustained release of LD and BH in vitro by orthogonal design. Utilizing optimal LD-resin microcapsules and BH-resin microcapsules, LD/BH suspension, containing both of them, was prepared by an optimal formulation and characterized by accelerated test and pharmacokinetic study in vivo. The accelerated test confirmed high stability of LD/BH suspension. According to pharmacokinetic results in vivo, in contrast with LD/BH commercial tablets, LD/BH suspensions did not only synchronize sustained release of both drugs but also show good bioequivalence. As LD/BH sustained release suspension can synchronize sustained release of multiple active ingredients by oral administration, the suspension presents promising oral dosage forms for geriatric patients with PD. An advanced Levodopa/Benserazide hydrochloride (LD/BH) suspension, prepared by cation-exchange resin and optimized microencapsulation, synchronizes sustained releases of LD and BH in vivo to benefit Parkinson's disease treatment for geriatric patients.

Synthesis and Characteristics of Large-Area and High-Filling CdS Nanowire Arrays in AAO Template.

CdS nanowires arrays were successfully synthesized by a simple solvothermal process using AAO as templates. The phase structures, morphologies, and optical properties of the products were investigated by X-ray diffraction, scanning electron microscopy, high-resolution transmission electron microscopy, Raman spectroscopy, and photoluminescence spectroscopy. It was found that the nanowires were composed of hexagonal structure CdS nanoparticles and the average diameters is about 60-70 nm. A strong green emission with a maximum around 505 nm was observed from the synthesized CdS nanowires at room temperature, which was attributed to near-band-edge emission. A 3D self-seed nucleation coalescent process was proposed for the formation of CdS nanowires structures. The present synthetic route is expected to be applied to the synthesis of other II-VI groups or other group's 1D semiconducting materials.

A fluorometric aptasensor for bisphenol a based on the inner filter effect of gold nanoparticles on the fluorescence of nitrogen-doped carbon dots.

An aptamer-based fluorometric assay is described for the determination of bisphenol A (BPA). The aptamer against BPA is first attached to the surface of the red AuNPs, and this prevents the AuNPs from salt-induced formation of a blue-colored aggregate. Hence, the blue fluorescence of added nitrogen-doped carbon dots (NCDots) is quenched via an inner filter effect (IFE) caused by the red AuNPs. After addition of BPA, the BPA/aptamer complex is formed, and the AuNPs are no longer stabilized agains aggregation. This weakens the IFE and results in the recovery of the fluorescence of the NCDots which is measured best at excitation/emission wavelengths of 300/420 nm. The recovered fluorescence increases linearly in the 10 to 250 nM and 250 to 900 nM BPA concentration ranges, and the detection limit is 3.3 nM. The method was successfully applied to the determination of BPA in spiked environmental tap water samples. Graphical abstract Schematic presentation of a fluorometric aptamer based assay for bisphenol A (BPA). It is based on the inner filter effect of gold nanoparticles (AuNPs) on the fluorescence of nitrogen-doped carbon dots (NCDots).

Modified Backward Avulsion Used in the Treatment of Third-Branch Primary Trigeminal Neuralgia.

OBJECTIVE: A clinical retrospective study was performed to observe the clinical effect of a modified surgical treatment for third-branch primary trigeminal neuralgia. METHOD: Thirty patients who had suffered from neuralgia for several years underwent modified backward avulsion of the inferior alveolar nerve and were followed for 3 to 5 years. In this technique, the inferior alveolar nerve was cut off through the mandibular wisdom tooth extraction socket or the corresponding alveolar ridge window and was avulsed from the mental foramen. Simultaneously, the neural foramen was packed with autogenous bone fragments to prevent recurrence. RESULTS: After a 3- to 5-years follow-up, 19 patients were cured, 8 patients reported a partial effect of treatment, and 3 patients exhibited recurrence. The efficacy rate was 90%. Postoperatively, the patients had different degrees of numbness in the area innervated by the third branch of the trigeminal nerve but did not have any other complications. CONCLUSIONS: This study proved that modified backward avulsion is a simple, effective, and safe method that can be applied in the clinical setting to treat third-branch primary trigeminal neuralgia.

Enhanced water-soluble derivative of PC407 as a novel potential COX-2 inhibitor injectable formulation.

PC407 is an effective COX-2 inhibitor in non-steroidal anti-inflammatory drug development but the poor solubility limits their usefulness. The aim of the study was to prepare and evaluate 4-oxo-4-[4-(5-(naphthalen-2-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamido]butyrate disodium, a derivative of PC407 with enhanced water solubility for injectable formulation. The prepared derivative displayed interesting high aqueous solubility (20.3 mg/mL, much superior to the parent compound PC407, 1.6 µg/mL) with confirmed in vivo analgesic activity. This derivative represents the profiles of prodrug and potential candidate of PC407 for the development of injectable COX-2 inhibitor due to extraordinary water solubility, low toxicity, and impressive analgesic activity.

[Recent development of natural and reconstituted lipoprotein based nano drug delivery vehicles].

Lipoproteins are biological lipids carriers. The natural and reconstituted lipoprotein based drug delivery systems have been extensively developed in recent years. This article reviews the development of natural and reconstituted low-density lipoprotein and high-density lipoprotein based vehicles in the antitumor area.

High-grade transformation of head and neck adenoid cystic carcinoma demonstrates distinctive clinicopathological features and an unfavorable prognosis: a matched case-control study of the largest series in China.

PURPOSE: Amidst the rarity of High-grade transformation (HGT) in adenoid cystic carcinoma (ACC), this study offers unprecedented insights into its aggressive nature and clinical implications. METHODS: A 1:1 match comparison between 23 HGT patients and non-HGT counterparts was extracted from 412 ACC cases, focusing on dissecting distinctive clinicopathological features and prognostic outcomes. RESULTS: The predominant sites of HGT were the sinonasal and lacrimal glands (30.4% each). Notably, the solid subtype was the most prevalent pattern within HGT, accounting for 69.6% of cases. Compared to non-HGT, the HGT cohort exhibited significantly higher rates of lymph node metastasis (39.1% vs. 8.7%; P < 0.05), perineural invasion (60.9% vs. 26.1%; P < 0.05), and increased Ki-67 proliferation index (35.0% vs. 10.0%; P < 0.05). Moreover, HGT regions typically showed reduced or absent p63 expression, along with high-grade pathomorphology. HGT was associated with increased recurrence (55.0%) and distant metastasis (78.3%), leading to an average survival of 35.9 months and a 3-years mortality rate of 35.0%. Overall and progression-free survival rates were significantly decreased in the HGT group. CONCLUSION: This study represents the largest single-center cohort of HGT cases to our knowledge, highlighting its frequent occurrence in the sinonasal and lacrimal glands and association with poorer outcomes. The findings support classifying HGT in ACC as Grade 4, reflecting its severity.

Obesity and risk of fracture in postmenopausal women: a meta-analysis of cohort studies.

BACKGROUND: Obesity is associated with an increased risk of fracture in adults, but is unclear in postmenopausal women. We aim to determine the association of obesity with the risk of fracture in postmenopausal women. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched up to 11 April 2022 for cohort studies. And the included studies regarding the relationship between obesity with all cause of fracture in postmenopausal women were included in our meta-analysis. Data were screened and extracted independently by two reviewers. The relative risks (RR) were estimated using a random-effects model. Between-study heterogeneity was assessed using Cochran's Q and I2 statistics. RESULTS: Eight cohort studies comprising 671,532 postmenopausal women and 40,172 fractures were included. Overall, the pooling analysis shows that obesity in postmenopausal women is associated with an increased risk of all-cause fracture (relative ratio (RR) = 1.18; 95% confidence interval (CI):1.09-1.28, I2 = 86.3%, p = .000). Sub-analyses for each site of fracture indicate that obesity was associated with an increased risk of vertebral fracture in postmenopausal women (RR = 1.154, 95% CI: 1.020-1.305, I2 = 94.5%, p = .023), but reduced the risk of pelvic fracture (RR = 0.575, 95% CI:0.470-0.702, I2 = 0.0%, p = .000). There is no statistically significant difference in the risk of hip and humerus fractures associated with obesity in postmenopausal women. CONCLUSION: Obesity is associated with an increased risk of all-cause and vertebral fractures in postmenopausal women, but is a protective factor for pelvic fractures. Our findings suggest that postmenopausal women who regulate their weight might lower their risk of fractures.Registration: (PROSPERO: CRD42022324973)KEY MESSAGESObesity is associated with an increased risk of all-cause and vertebral fractures in postmenopausal women.Obesity maybe a protective factor for pelvic fractures in postmenopausal women.Postmenopausal women should regulate their weight to prevent fractures.

[Effects of Management Measures on Soil Water-soluble Carbon and Nitrogen and Their Three-Dimensional Fluorescence Characteristics of Pinus tabulaeformis Plantations on Loess Plateau].

The Pinus tabulaeformis plantation on the Loess Plateau was selected as the research site to study the changes of soil water-soluble carbon and nitrogen content and components of soil dissolved organic matter (SDOM) under different management measures (litter removal, young Pinus tabulaeformis forest, shrubs, grassland). The uncleared Pinus tabulaeformis plantation was used as the control. Results show that the soil water-soluble organic carbon content of shrubs and young Pinus tabulaeformis forests was significantly higher than that in other management measures. The content of soil water-soluble organic carbon decreased with an increase in soil depth, whereas soil water-soluble organic carbon/soil organic carbon (WSOC/SOC) increased. The change of soil water-soluble nitrogen content corresponded to that of water-soluble carbon. The content of soil water-soluble nitrogen content in the young Pinus tabulaeformis forest was higher than that of other management measures, and generally decreased with an increase in depth. Different management measures have significant effects on SDOM components. Based on three-dimensional fluorescence spectroscopy combined with parallel factor (EEM-PARAFAC) analysis, four components of SDOM are identified, which are mainly divided into categories, humus, protein-like, and soluble microbial metabolites in three major categories, among which the main component of the SDOM is the rich acid humus, and the highest content in the soil of the young forest of Pinus tabulaeformis is rich acid. The results suggested that management measures had certain effects on soil water-soluble carbon and nitrogen content as well as SDOM components, especially in young Pinus tabulaeformis forests and shrubs. The young Pinus tabulaeformis forest and shrubs increased the content of soil water-soluble organic carbon and water-soluble nitrogen, enhanced their ability to migrate and transform in the soil, and changed the structural composition of soil organic matter, hence enhancing the degree of humification and further improving soil quality.

Genome-based analysis of the type II PKS biosynthesis pathway of xanthones in Streptomyces caelestis and their antifungal activity.

The ethyl acetate extract from the liquid fermentation of S. caelestis Aw99c exhibited high and broad antifungal activities against plant pathogenic fungi. Bioassay guide fractionation led to the discovery of two xanthones, citreamicin ε and θ. The draft genome sequence of S. caelestis Aw99c was analyzed by a similarity-based approach to elucidate the pathway for the citreamicins. A 48 kb citreamicin (cit) gene cluster with 51 open reading frames encoding type II polyketide synthases and unique polyketide tailoring enzymes was proposed based on the genome analysis and the chemical structure derivation. In vitro antifungal assay showed that citreamicin ε exhibited significant growth inhibition against the plant pathogenic fungi with MIC values ranging from 1.56 to 12.5 µM. The cellular structural change of M. grisea treated with citreamicin ε was detected by SEM and the result showed that citreamicin ε caused disruptive surface of the mycelia.

High-frequency ultrasonic methods for determining corrosion layer thickness of hollow metallic components.

Corrosion in internal cavity is one of the most common problems occurs in many hollow metallic components, such as pipes containing corrosive fluids and high temperature turbines in aircraft. It is highly demanded to non-destructively detect the corrosion inside hollow components and determine the corrosion extent from the external side. In this work, we present two high-frequency ultrasonic non-destructive testing (NDT) technologies, including piezoelectric pulse-echo and laser-ultrasonic methods, for detecting corrosion of Ni superalloy from the opposite side. The determination of corrosion layer thickness below ∼100 µm has been demonstrated by both methods, in comparison with X-CT and SEM. With electron microscopic examination, it is found that with multilayer corrosion structure formed over a prolonged corrosion time, the ultrasonic NDT methods can only reliably reveal outer corrosion layer thickness because of the resulting acoustic contrast among the multiple layers due to their respective different mechanical parameters. A time-frequency signal analysis algorithm is employed to effectively enhance the high frequency ultrasonic signal contrast for the piezoelectric pulse-echo method. Finally, a blind test on a Ni superalloy turbine blade with internal corrosion is conducted with the high frequency piezoelectric pulser-receiver method.

[Th cell differentiation in chronic stage of viral myocarditis in mice and interference of Qingxin-II Recipe].

OBJECTIVE: To investigate part mechanisms of Th cell differentiation, and to observe the interference effect of Qingxin-II Recipe in the chronic stage of viral myocarditis (VMC), so as to provide some experimental evidences for illuminating the pathogenesis of VMC and treatment mechanisms of Qingxin-II Recipe. METHODS: According to 20%-40% death rate of experiment in advance, 100 BALB/c male mice (4 weeks old and weighing 12-15 g) were used. Twenty mice were randomly assigned to normal control group, and the other 80 mice were intraperitoneally injected with 0.1 ml normal saline containing coxsackie virus B3 at the 1st, 4th and 28th day (the virus densities were 1:2000, 1:1000 and 1:500 respectively) to induce chronic VMC. At the 42nd day, the surviving mice were randomly divided into untreated group and treatment group, with 20 mice in each group. Mice in the treatment group were orally administered with 0.2 ml Qingxin-II Recipe every day, while mice in the normal control group and the untreated group were administered with 0.2 ml normal saline. All the mice were sacrificed after 45 days, and the sera, heart and spleen cells were collected. Then the myocardial pathological changes were observed by using a light microscope, and the levels of IL-4, IL-10 and IFN-gamma in serum were detected by enzyme linked immunosorbent assay (ELISA). And the Th cell differentiation was observed by flow cytometry. RESULTS: No obvious myocardial pathological changes were observed in mice of the normal control group. Myocardial pathological changes in the treatment group were slighter than those in the untreated group. The difference of serum IL-10 level between the normal control group and the untreated group showed no significance (P>0.05), and the levels of IFN-gamma and IL-4 of the untreated group were higher than those of the normal control group (P<0.05 or P<0.01). There was no statistical difference in IL-10 level between the treatment group and the untreated group (P>0.05), while the serum levels of IL-4 and IFN-gamma of the treatment group were lower than those of the untreated group (P<0.05 or P<0.01). There was no significant difference of the Th1 cell responder between the treatment group and the untreated group (P>0.05), while the Th2 cell responder was inhibited significantly in the treatment group (P<0.05). CONCLUSION: Qingxin-II Recipe can restore the balance of Thl and Th2 cells through inhibiting the reaction of Th2.

Protective effects of isorhamnetin on apoptosis and inflammation in TNF-α-induced HUVECs injury.

Little is known about the role of isorhamnetin on endothelial cell apoptosis and inflammation when insulted by TNF-α injury. In our study, HUVECs were treated with TNF-α for 6 hours. HUVECs apoptosis were detected using flow cytometry. The expressions of ICAM-1, VCAM-1, E-selectin, NF-κB, AP-1 and eNOS were determined with western blotting or flow cytometry. The results showed TNF-α increased of apoptosis and the expression of ICAM-1, VCAM-1 and E-selectin in HUVECs, accompanied by significant augmentation of NF-κB and AP-1 expression. Pretreatment with isorhamnetin significantly reduced apoptosis in TNF-α-treated HUVECs. Moreover, isorhamnetin significantly attenuated TNF-α-induced upregulation of ICAM-1, VCAM-1, AP-1, E-selectin and NF-κB expression. Meanwhile, isorhamnetin also increased the expression of eNOS. So, isorhamnetin could suppress TNF-α-induced apoptosis and inflammation by blocking NF-κB and AP-1 signaling in HUVECs, which might be one of the underlying mechanisms for treatment of coronary heart disease.

[Studies on the influencing factors on the drug release from sodium alginate matrices].

AIM: To investigate the in vitro influencing factors on drug release from matrices with sodium alginate as the hydrophilic polymer. METHODS: Sodium alginate hydrophilic matrix tablets were prepared by direct compression method with theopylline as a model drug. The in vitro influencing factors on drug release behavior from matrices were studied by investigating the swelling, water uptake and erosion characteristics of pure sodium alginate matrices. RESULTS: The results showed that drug release rate and drug release mechanism were both related to the viscosity of sodium alginate used in matrices, pH values and ionic strength of dissolution media and rotation speeds. CONCLUSION: Sodium alginate can be tailor-made to suit the demands of applicants in sustained delivery systems as a good candidate of hydrophilic polymer.

Design of an expert system for the development and formulation of push-pull osmotic pump tablets containing poorly water-soluble drugs.

The purpose of this article was to build an expert system for the development and formulation of push-pull osmotic pump tablets (PPOP). Hundreds of PPOP formulations were studied according to different poorly water-soluble drugs and pharmaceutical acceptable excipients. The knowledge base including database and rule base was built based on the reported results of hundreds of PPOP formulations containing different poorly water-soluble drugs and pharmaceutical excipients and the experiences available from other researchers. The prediction model of release behavior was built using back propagation (BP) neural network, which is good at nonlinear mapping and learning function. Formulation design model was established based on the prediction model of release behavior, which was the nucleus of the inference engine. Finally, the expert system program was constructed by VB.NET associating with SQL Server. Expert system is one of the most popular aspects in artificial intelligence. To date there is no expert system available for the formulation of controlled release dosage forms yet. Moreover, osmotic pump technology (OPT) is gradually getting consummate all over the world. It is meaningful to apply expert system on OPT. Famotidine, a water insoluble drug was chosen as the model drug to validate the applicability of the developed expert system.