The effects of fulvic acids and low-level laser therapy on orthodontic retention in rats.

BACKGROUND: Shortening retention time and minimizing relapse rates are ongoing challenges in orthodontics. This study investigated the effects of natural fulvic acids (FAs) and low-level laser therapy (LLLT) on orthodontic retention in rats. METHODS: Seventy-two male Sprague-Dawley rats underwent mesial movement of the left maxillary first molar using a 50 g force via a nickel-titanium tension spring. After three weeks of movement, the rats entered the retention phase with retainer wires and were divided into four groups: Control (no intervention), FAs (80 mg/kg orally daily), LLLT (808 nm laser twice weekly), and FAs + LLLT (both treatments). Retainers were removed on days 7, 14, and 21 for a 3-day relapse assessment. Maxillary impressions were analyzed for relapse rates using 3Shape software, alongside histological and immunohistochemical evaluations of bone morphogenetic protein-2 (BMP-2) expression in periodontal tissues, with differences among groups analyzed using an ordinary two-way analysis of variance (ANOVA). RESULTS: The relapse rate decreased over time, particularly at 10, 17, and 24 days (p < 0.001). The FAs group did not significantly affect relapse rates compared to the control group (p = 0.084). In contrast, both the LLLT and FAs + LLLT groups significantly reduced relapse rate (p < 0.001), with no significant difference between these groups (p = 0.555). Histological examination revealed active osteoclasts on day 10, decreasing by days 17 and 24. The LLLT and FAs + LLLT groups showed less local cementum resorption and better periodontal fiber arrangement. All treatment groups significantly increased BMP-2 expression (P < 0.05) compared to controls. with LLLT and FAs + LLLT differing significantly from FAs (P < 0.001), though no difference was observed between LLLT and FAs + LLLT (P = 0.578). CONCLUSIONS: FAs did not significantly reduce relapse rate with retainers, while LLLT effectively reduced relapse rates, showing no additional benefit from combining FAs with LLLT. Both FAs and LLLT increased BMP-2 expression in PDL fibroblasts but with no synergistic effect.

Advances in research on potential therapeutic approaches for Niemann-Pick C1 disease.

Niemann-Pick disease type C1 (NP-C1) is a rare and devastating recessive inherited lysosomal lipid and cholesterol storage disorder caused by mutations in the NPC1 or NPC2 gene. These two proteins bind to cholesterol and cooperate in endosomal cholesterol transport. Characteristic clinical manifestations of NP-C1 include hepatosplenomegaly, progressive neurodegeneration, and ataxia. While the rarity of NP-C1 presents a significant obstacle to progress, researchers have developed numerous potential therapeutic approaches over the past two decades to address this condition. Various methods have been proposed and continuously improved to slow the progression of NP-C1, although they are currently at an animal or clinical experimental stage. This overview of NP-C1 therapy will delve into different theoretical treatment strategies, such as small molecule therapies, cell-based approaches, and gene therapy, highlighting the complex therapeutic challenges associated with this disorder.

Theoretical Study on the Mechanism of the Hydrogenation of Azo (N═N) Bonds to Amines Catalyzed by Manganese.

The mechanism of the transition metal manganese complex Mn(PhPNN)(CO)2Br (CA-4) that catalyzed the hydrogenation of the azo (N═N) bond to amines has been investigated using the PBE0 function. The results show that the whole reaction involves three basic processes: (1) the addition of H2 to CA gives IN2, which can hydrogenate the azo (N═N) bond at the later stage; (2) hydrogenation of azobenzene by IN2, which gives 1,2-diphenylhydrazine (PhNHNHPh); and (3) hydrogenation of 1,2-diphenylhydrazine by IN2, which affords aniline (PhNH2). The results suggest that the hydrogenation of CA and hydrogenation of azobenzene by IN2 to afford PhNHNHPh are easy to occur due to the low barriers, and the overall rate-determining step is the formation of IN11 and PhNH2 by breaking the N-N bond in the stage of hydrogenation of 1,2-diphenylhydrazine by IN2, with an energy barrier of 39.1 kcal/mol. The computed results are in good agreement with the experimental results. The mechanism of the azobenzene reaction catalyzed by manganese was analyzed by charge and orbital analysis in detail. The theoretical results provide a deeper understanding of the mechanism and fully explain the experimental facts.

Natural fulvic acids inhibit non-small-cell lung cancer through the COX-2/PGE2/EP4 axis: In silico and in vivo assessments.

Purpose: Non-small-cell lung cancer (NSCLC) is a major public health concern with a high incidence worldwide. Coal-derived fulvic acids (FAs) contain functional groups in their chemical structures. Overexpression of cyclooxygenases-2 (COX-2), prostaglandin E2 (PGE2), and the PGE2 receptor EP4 subtype (EP4) can have a potential link with the increased tumor incidence and promoted tumor growth and metastasis in NSCLC. This study aimed to assess the biological roles of coal-derived FAs in the growth and development of NSCLC and to elucidate the underlying molecular mechanisms. Methods: A web-based tool for predicting small-molecule pharmacokinetics (pkCSM) was used to analyze the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of FAs. Molecular docking and dynamic simulations were performed to analyze the binding affinities of COX-2 and EP4 to FA. An acute toxicity test and an antitumor study were used to analyze the toxicity and anti-NSCLC effects of FAs. Thirty NSCLC-bearing nude mice were randomly divided into five groups (six mice per group): vehicle control, positive control with 20 mg/kg body weight (BW) 5-fluorouracil, and three treatments with 25, 50, and 100 mg/kg BW FAs. The BW and tumor volume were recorded, and the COX-2, PGE2, and EP4 protein expression were measured and analyzed. Results: Using the predictive pkCSM algorithm, we found that FA did not cause developmental toxicity. Molecular simulations revealed that COX-2 and EP4 expression was inhibited by FA. An acute toxicity test conformed that the maximum tolerated FAs dose was >3.0 g/kg BW. The animal study demonstrated that FA treatment significantly downregulated the expression of COX-2, PGE2, and EP4 in NSCLC-bearing mice compared to that in vehicle control mice (p < 0.01). Conclusions: Natural FAs may exert anti-NSCLC effects through the COX-2/PGE2/EP4 axis.

Coal humus acid functionalized high stability fluorescent copper nanoclusters for tumor identification by sequential off-on-off monitoring tryptophan and Hg2.

The abnormalities of Tryptophan (Trp) and mercury ions (Hg2+) not only easily activate diseases, including mental illness and cancer, but also seriously affect human wellbeing. Fluorescent sensors are profoundly attractive options for identifying amino acids and ions; however, most sensors remain challenging due to the multipliable cost and deviation from the asynchronous quenching detection. In particular, fluorescent copper nanoclusters with high stability that quantitatively monitoring Trp and Hg2+ successively have seldom been reported. Herein, we employ coal humus acid (CHA) as a protective ligand and successfully construct weak cyan fluorescent copper nanoclusters (CHA-CuNCs) by a rapid, environmentally benign and cost-effective method. Significantly, the fluorescence of CHA-CuNCs is obviously improved by introducing Trp, because the indole group of Trp enhances the radiative recombination and aggregation-induced emissions. Interestingly, CHA-CuNCs not only realizes the highly selective and specific detection of Trp with a linear range of 25-200 µM and a detection limit of 0.043 µM based on the turn-on fluorescence strategy, but also quickly achieves the consecutive turn-off detection of Hg2+ due to the chelation interaction between Hg2+ and pyrrole heterocycle in Trp. Moreover, this method is successfully applied in the analysis of Trp and Hg2+ in real samples. Furthermore, the confocal fluorescent imaging of tumor cells demonstrates that CHA-CuNCs can be used for bioimaging and cancer cell recognition with Trp and Hg2+ abnormalities. These findings provide new guidance for the eco-friendly synthesis of CuNCs with eminent sequential off-on-off optical sensing property, indicating good prospects in biosensing and clinical medicine applications.

Effects of GLP-1 on ovarian dysfunction in polycystic ovary syndrome: A protocol for systematic review and meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a frequent endocrine disorder in women, it is the principal cause of infertility and amenorrhea. Due to its high recurrence rate, poor prognosis and serious complications, more works on the research of PCOS are needed. Therefore, we performed a protocol for systematic review and meta-analysis to investigate the efficacy and safety of glucagon-like peptide-1 receptor agonists on ovarian dysfunction in PCOS. METHODS: This study protocol has been registered in the PROSPERO and the registration number is CRD42020188247. The procedure of this protocol will be conducted according to the Preferred Reporting Item for Systematic Review and Meta-analysis Protocols guidance. A comprehensive search of several databases from 1966 to November 2022 will be conducted. The databases includes Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and PubMed. The risk of bias of the included studies will be assessed using the Cochrane tool of risk of bias. All statistical analyses will be conducted using the software program Review Manager version 5.3. RESULTS: The results of this systematic review will be published in a peer-reviewed journal. CONCLUSION: This systematic review will provide evidence to judge whether glucagon-like peptide-1 receptor agonist is superior to metformin in patients with PCOS.

Tracheobronchial intubation using flexible bronchoscopy in children with Pierre Robin sequence: Nursing considerations for complications.

BACKGROUND: It has been shown that children with Pierre Robin sequence (PRS) have a higher risk of difficult intubation before surgery. When mask ventilation or tracheobronchial intubation is expected to be challenging, flexible bronchoscopy (FB) is advantageous in airway safety when it is used to guide tracheobronchial intubation (TI). AIM: To evaluate the complications of TI using FB in children with PRS and explore the effect of nursing services on postoperative complications. METHODS: One hundred and five children with PRS underwent TI using FB before early mandibular distraction osteogenesis. One hundred and eight children with common pneumonia who did not have a difficult airway were set as the control group. Demographic data, success rates of TI, time required for TI, number of TI attempts, and the incidence of postoperative complications were assessed. Besides, the strategies used to attenuate complications were investigated. RESULTS: The success rate of TI was 100% in children with PRS, while the success rate at the first attempt in the PRS group was significantly lower than that in the control group (88.6% vs 98.2%, P = 0.005). The time required for TI in the PRS group was markedly longer than that in the control group (P < 0.001). Children in the PRS group required repetitive operations to enter the glottis successfully (P = 0.017). The incidence of complications was noticeably higher in the PRS group (50/105, 47.6%) than in the control group (36/108, 33.3%) (P = 0.034). Seven of 105 PRS children experienced laryngeal edema (LE) (6.7%), compared with one (0.9%) in the control group (P = 0.034). Out of the seven patients who had LE, all were reintubated and managed with steroids: six recovered with inhaled steroids alone before extubated, and one was given systemic corticosteroids before recovery. CONCLUSION: FB contributes to a high success rate of TI in children with PRS. To prevent LE, operators should pay more attention to catheter material, catheter lubrication and intubation time.

Effect and Prognosis Factors of Combining Laparoscopic Radical Resection of Colon Adenocarcinoma with Docetaxel Therapy in Treating Middle and Advanced Colon Adenocarcinoma.

Objective: The aim of the study is to explore the clinical efficacy and prognosis factors of joint application of laparoscopic radical resection of colon adenocarcinoma (COAD) and docetaxel therapy in treating COAD of middle and advanced stages. Methods: The clinical data of 103 COAD patients of middle and advanced stages treated in our hospital from July 2016 to July 2018 were selected for the retrospective analysis, all patients received the treatment scheme of combining laparoscopic radical resection of COAD with docetaxel therapy for the observation of short-term efficacy, follow-up was conducted to record their 3-year survival, and relevant factors affecting patient prognosis were analyzed by the logistic regression model. Results: After treatment, the total remission rate of patients was 75.73% (78/103), the total incidence rate of adverse reactions was 16.50% (17/103); patients' level values of various serum tumor markers after treatment were significantly lower than those before treatment (P < 0.001); according to the univariate analysis results, for COAD patients with different tumor diameters, differentiated degrees, TNM stages, perineural invasion degrees, pathological types, and depths of invasion, their modality rates were statistically different (P < 0.05); and the logistic regression analysis showed that tumor diameter ≥5 cm, poor differentiation, TNM stage IV, perineural invasion, pathologically signet-ring cell carcinoma, and T 3-invasion were the independent risk factors affecting patient prognosis (P < 0.05). Conclusion: Combining laparoscopic radical resection of COAD with docetaxel therapy in treating COAD of middle and advanced stages achieves affirmed short-term efficacy, which can reduce patients' level of serum tumor markers and ensure high safety and good survival prognosis. Tumor diameter, differentiated degree, TNM stage, perineural invasion, pathological type, and T 3-invasion are the relevant factors affecting the prognosis of middle and advanced COAD.

Efficacy and Safety of Tacrolimus Therapy for a Single Chinese Cohort With Very-Late-Onset Myasthenia Gravis.

Background and Purpose: Previous studies have found tacrolimus to be a favorable drug for treating different types of myasthenia gravis (MG), but few have focused on very-late-onset MG (VLOMG). This study evaluated the efficacy and safety of tacrolimus for VLOMG therapy. Methods: This was a retrospective single-center cohort study of 70 patients with VLOMG (onset ≥65 years) who visited Peking University First Hospital in 2019. Participants were divided into the tacrolimus (Tac) group and the control group based on tacrolimus usage. We further divided the Tac group into patients treated without corticosteroids and with corticosteroids. Sociodemographic features, clinical profiles, and outcomes were compared between different therapies and further analyzed by multivariate regression. Details of tacrolimus treatment, comorbidities, and adverse drug reactions (ADRs) were described. Results: Among 70 patients, the median (interquartile range) age at onset was 71 (68-77) years, and the follow-up duration was 27 (27-29) months. Most patients were types I (28%) and III (40%) according to the MG Foundation of America (MGFA) classification. In the Tac group, tacrolimus treatment was maintained for 36 (27-38) months. The dosage at the final evaluation was 1.0 (1.0-1.75) mg/day, and the last blood concentration test was 4.25 (2.85-5.7) ng/ml. A total of 43% reached remission, and 37% improved based on MGFA postintervention status (MGFA-PIS). For the 9 patients, newly diagnosed at enrollment within this group, MG activities of daily living (MG-ADL) decreased significantly from 3 (2-5) to 2 (1-2) (p = 0.041). Regarding the 13 patients, coadministering Wuzhi capsules the tacrolimus concentration increased from 2.75 (1.4-3.8) ng/ml to 5.95 (5.1-7.0) ng/ml (p = 0.012). No significant differences in outcomes were observed between tacrolimus treatment without and with corticosteroids or between the Tac group and the control group. A total of 93% had at least one comorbidity. ADRs related to tacrolimus emerged in 25% (9/36) of patients, most of which were not serious and reversible. Conclusions: Tacrolimus is effective and safe in treating VLOMG. Tacrolimus monotherapy without corticosteroids can be used as an initial and maintenance treatment for VLOMG. Wuzhi capsules work well in elevating tacrolimus concentrations in this population.

Visible light assisted FeOOH/CeO2/C deep degradation of organic matter in coking wastewater.

In order to degrade hard-to-degrade organic pollutants such as amines, phenols, naphthalenes, pyrroles and pyridazines in coking wastewater, the nano-FeOOH/CeO2/C composite catalysts (FCHCoke) were prepared. Firstly the catalysts were characterized by XRD, TEM, BET, BJH and UV/Vis/NIR. Then UV-Vis and GC-MS were used to detect the products in the degradation process of organic pollutants, respectively. The results showed that the average pore size of FCHCoke was 2-6 nm and the carrier coke enhanced the ability of the catalyst to absorbs visible light. Each intermittent light exposure for 2 h showed a better photodegradation. Under the intermittent irradiation of visible light of for a total of 8 h, 100µgÛ°mL-1aniline and phenol were completely degraded. Dihydronaphthalene, esters, pyrrole, pyridazine, oxime and macromolecular alkanes in coking wastewater were also completely degraded. The acidity of pH=6 is more suitable for the photodegradation reaction of the catalyst. Organic degradation is the result of a combination of chemical catalysis and photocatalysis.

Synthesis and Photocatalytic Activity of TiO2/CdS Nanocomposites with Co-Exposed Anatase Highly Reactive Facets.

In this work, TiO2/CdS nanocomposites with co-exposed {101}/[111]-facets (NH4F-TiO2/CdS), {101}/{010} facets (FMA-TiO2/CdS), and {101}/{010}/[111]-facets (HF-TiO2/CdS and Urea-TiO2/CdS) were successfully synthesized through a one-pot solvothermal method by using [Ti4O9]2- colloidal solution containing CdS crystals as the precursor. The crystal structure, morphology, specific surface area, pore size distribution, separation, and recombination of photogenerated electrons/holes of the TiO2/CdS nanocomposites were characterized. The photocatalytic activity and cycling performance of the TiO2/CdS nanocomposites were also investigated. The results showed that as-prepared FMA-TiO2/CdS with co-exposed {101}/{010} facets exhibited the highest photocatalytic activity in the process of photocatalytic degradation of methyl orange (MO), and its degradation efficiency was 88.4%. The rate constants of FMA-TiO2/CdS was 0.0167 min-1, which was 55.7, 4.0, 3.7, 3.5, 3.3, and 1.9 times of No catalyst, CdS, HF-TiO2/CdS, NH4F-TiO2/CdS, CM-TiO2, Urea-TiO2/CdS, respectively. The highest photocatalytic activity of FMA-TiO2/CdS could be attributed to the synergistic effects of the largest surface energy, co-exposed {101}/{010} facets, the lowest photoluminescence intensity, lower charge-transfer resistance, and a higher charge-transfer efficiency.

Eco-Friendly Ferrimagnetic-Humic Acid Nanocomposites as Superior Magnetic Adsorbents.

Recyclable, cheap, eco-friendly, and efficient adsorbent materials are very important for the removal of pollution. In this work, we report the design and implementation of ferrimagnetic-humic acid nanocomposites as superior magnetic adsorbent for heavy metals. Ferrimagnetic and ferrimagnetic-humic acid nanocomposite particles with different morphologies were prepared using the coprecipitation method and hydrothermal synthesis method, respectively. The results show that the morphology of the nanoparticles prepared by the coprecipitation method is more uniform and the size is smaller than that by the hydrothermal synthesis method. Adsorption experiments show that the ferrimagnetic-humic acid nanoparticles prepared by the coprecipitation method has high sorption capacity for cadmium, and the maximum adsorption capacity is about 763 µg/g. At the same time, magnetic technology can be used to realize the recycling of ferrimagnetic-humic acid adsorbents.

bFGF ameliorates intestinal mucosal permeability and barrier function through tight junction proteins in burn injury rats.

BACKGROUD: To investigate the protective effect of exogenous basic fibroblast growth factor (bFGF) treatment on the intestinal mucosa in scalded rats. METHODS: Thirty-six SD rats were randomly divided into 3 groups (n = 12): sham group, scald group and bFGF group (0.5 mg/kg). Intestinal barrier dysfunction was evaluated by permeability of intestinal mucosa to fluorescein isothiocyanate (FITC)-dextran and Chiu's grading system. H&E staining was used to detect the morphological changes of intestinal mucosa. Immunohistochemistry was used to observe zonula occludens-1 (ZO-1) and occludin. Western blot assay was used to detect the expression of ZO-1, Claudin-1, occludin and myosin light-chain kinase (MLCK). RESULTS: The results demonstrated that following bFGF treatment, permeability of the intestinal epithelium barrier of was significantly decreased compared to scald group. H&E staining and Chiu's grading were consistent with previous result. The expression of ZO-1, Claudin-1, occludin in bFGF group were significantly increased compared to scald group, while MLCK protein was decreased. CONCLUSIONS: bFGF ameliorates permeability of intestinal mucosa after burns. The possible mechanism may be relate to bFGF could increase the expression level of tight junction proteins (TJPs).

Blue-emitting glutathione-capped copper nanoclusters as fluorescent probes for the highly specific biosensing of furazolidone.

Herein, a facile, straightforward and green method was developed to prepare copper nanoclusters by using glutathione (GSH) as the protecting agent and ascorbic acid as the reducing agent. The glutathione-templated copper nanoclusters (GSH-Cu NCs) were characterized through fluorescence spectroscopy, UV-vis absorption spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and fluorescence lifetime analysis. The as-synthesized Cu NCs showed blue fluorescence with a peak centered at 426 nm. The Cu NCs had excellent water solubility, stability and dispersibility. Based on the inner filter effect and static quenching mechanism, Cu NCs were employed to detect furazolidone in bovine serum samples. Under optimal detection conditions, a good linear relationship was observed between F0/F and the furazolidone concentration from 0.05 to 60 µM. The detection limit (LOD) was 0.012 µM. Furthermore, the fluorescence probe was successfully used in the quantification of furazolidone in bovine serum samples. In addition, this analytical method provides a rapid, easy and ultrasensitive fluorescence platform for the detection of furazolidone.

Ascorbic acid stabilised copper nanoclusters as fluorescent sensors for detection of quercetin.

In this report, green-emitting fluorescence copper nanoclusters (Cu NCs) were synthesized using ascorbic acid as reducing agent and protecting agent. The ascorbic acid capped Cu NCs (AA-Cu NCs) were characterized using fluorescence spectroscopy, UV-vis absorption spectroscopy, Fourier Transform Infrared Spectroscopy (FT-IR), Transmission Electron Microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). The analysis data demonstrated that the AA-Cu NCs were highly dispersed with an average diameter of 2 nm. The as-prepared Cu NCs possessed good water solubility, excellent photostability and displayed excitation-dependent fluorescence characteristics. More importantly, the fluorescence intensity of AA-Cu NCs was linearly quenched in the presence of quercetin from 0.7 to 50 µM and the detection limit (LOD) was 0.19 µM. Finally, the fluorescence sensor was successfully employed to detect quercetin in bovine serum samples.

A sensitive OFF-ON-OFF fluorescent probe for the cascade sensing of Al3+ and F- ions in aqueous media and living cells.

A simple Schiff-base ligand 2-hydroxy-1-naphthaldehyde semicarbazone (HNS) was synthesized and characterized. Based on the combined effect of inhibition of CH[double bond, length as m-dash]N isomerization and chelation-enhanced fluorescence (CHEF), HNS functions as a fluorescence "turn on" sensor for Al3+ in buffered aqueous media. Based on the strong affinity of Al3+ to F- ions, the in situ generated Al3+-HNS complex can also be utilized as an effective chemosensor for F- sensing by metal displacement approach, ensuing quenching of fluorescence by the reversible return of HNS from Al3+-HNS complex. Thus a method using a single probe for the detection of both Al3+ and F- ions is developed. The system exhibits high selectivity and sensitivity for Al3+ and F- ions and the detection limits were found to be as low as 6.75 × 10-8 M and 7.89 × 10-7 M, respectively. Furthermore, the practical applicability of this probe has been examined in living cells.

Correction: A sensitive OFF-ON-OFF fluorescent probe for the cascade sensing of Al3+ and F- ions in aqueous media and living cells.

[This corrects the article DOI: 10.1039/D0RA02848G.].

Computational Insight into the Mechanism of Ruthenium(II)-Catalyzed α-Alkylation of Arylmethyl Nitriles Using Alcohols.

The ruthenium(II)-catalyzed α-alkylation reaction of arylmethyl nitriles (phenylacetonitrile) using alcohols (ethanol) in toluene has been extensively investigated by means of SMD-M06-2X/6-311G(d,p)-LANL2dz (LAnL2dz for Ru, 6-311G(d,p) for other atoms) calculations. Detailed mechanistic schemes have been proposed and discussed. The catalytically active Ru(II) complex was generated by the base-induced KCl elimination from the catalyst precursor [(PNPPh)RuHCl(CO)]. The overall Ru(II) catalytic cycle consists of three basic processes: (1) ethanol-to-aldehyde transformation catalyzed by the 16-electron unsaturated ruthenium pincer catalyst; (2) a 16-electron unsaturated ruthenium pincer catalyst catalyzed condensation reaction of arylmethyl nitrile with aldehyde, which leads to PhC(CN)=CHCH3; (3) hydrogenation of PhC(CN)=CHCH3, which leads to the formation of the α-alkylated arylmethyl nitrile product (PhCH(CH2CH3)CN). The DFT results revealed that the rate-determining barrier of the overall reaction was 23.9 kcal/mol of the H-transfer step in the third process. The reaction of PhC(CN)=CHCH3 with the dihydride Ru complex, which is generated in the ethanol-to-aldehyde transformation process, is the more preferable hydrogenation mechanism than hydrogenation of vinyl nitrile-Ru complex by H2. Using alcohol as the reactant not only fulfills the requirement of the borrowing-H strategy but also lowers the barriers of the H-migration steps.

Comparisons of in vitro Fick's first law, lipolysis, and in vivo rat models for oral absorption on BCS II drugs in SNEDDS.

PURPOSE: The objective of this study was to compare the in vitro Fick's first law, in vitro lipolysis, and in vivo rat assays for oral absorption of Biopharmaceutical Classification Systems Class II (BCS II) drugs in self-nanoemulsifying drug delivery system (SNEDDS), and studied drugs and oils properties effects on the absorption. METHODS: The transport abilities of griseofulvin (GRI), phenytoin (PHE), indomethacin (IND), and ketoprofen (KET) in saturated water solutions and SNEDDS were investigated using the in vitro Madin-Darby canine kidney cell model. GRI and cinnarizine (CIN) in medium-chain triglycerides (MCT)-SNEDDS and long-chain triglycerides (LCT)-SNEDDS were administered in the in vivo SD rat and in vitro lipolysis models to compare the oral absorption and the distribution behaviors in GIT and build an in vitro-in vivo correlation (IVIVC). RESULTS: In the cell model, the solubility of GRI, PHE, IND, and KET increased 6-8 fold by SNEDDS, but their permeability were only 18%, 4%, 8%, and 33% of those of their saturated water solutions, respectively. However, in vivo absorption of GRI-SNEDDS was twice that of the GRI suspension and those of CIN-SNEDDS were 15-21 fold those of the CIN suspension. In the lipolysis model, the GRI% in aqueous and pellet phases of MCT were similar to that in LCT. In contrast, the CIN% in the aqueous and pellet phases were decreased but that of the lipid phase increased. In addition, an IVIVC was found between the CIN% in the lipid phase and in vivo relative oral bioavailability (F r). CONCLUSION: The in vitro cell model was still a suitable tool to study drug properties effects on biofilm transport and SNEDDS absorption mechanisms. The in vitro lipolysis model provided superior oral absorption simulation of SNEDDS and helped to build correlation with in vivo rats. The oral drug absorption was affected by drug and oil properties in SNEDDS.

Definitive Radiation Therapy Versus Postoperative Radiation Therapy for Patients With Maxillary Sinus Cancer Invading the Upper Jaw.

Maxillectomy following radiation therapy has the strongest local control over maxillary sinus cancer. However, in the advanced stage, complete resection is difficult with adequate margin and has the risk of functional disabilities after surgeries. The objective of the study was to determine the optimal treatment strategy for patients with maxillary sinus cancer invades the upper jaw. A total of 998 histologically confirmed maxillary sinus cancer invades the upper jaw patients were subjected to simple randomization. Patients were subjected to maxillectomy and received 150 mg/m/wk intra-arterial cisplatin for 4 weeks followed by radiotherapy (PR group, n = 499) or received the same chemotherapy and definitive radiotherapy only (DR group, n = 499). Disease status, overall survival, progression-free survival, and treatment-emergent adverse effects were evaluated in the follow-up period of 5 years. At the end of 5 years of follow-up, both the treatments had the same overall survival (P = 0.066). Demographic characters were independent parameters for the overall survival (P ≥ 0.05 for all). Postoperative radiotherapy had a higher progression-free survival than definitive radiotherapy (P = 0.018). Maxillectomy was useful in the reduction of the evidence of local recurrence of cancer (P = 0.027). Dysphagia, palate fistula, incomprehensible voice, and trismus were reported as treatment-emergent effects in the PR group. Definitive radiation therapy is recommended in maxillary sinus cancer that invades the upper jaw (Level of Evidence: I; research registry 4571 dated November 14, 2012).