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It is challenging to overcome the stratum corneum (SC) barrier to deliver drugs into the skin. Nanoparticle (NP)-based drug delivery systems show the advantages of cutaneous penetration improvement and controllable and targeted drug release. Besides, solvents, as a big group of penetration enhancers, provide another strategy, which is easily accessible, low-cost, and flexibly changeable in components. Apart from the skin penetration enhancement based on formulations, the disrupted barrier of diseased skin could change the skin penetration of drugs too. Thus, the present thesis investigated the influences of the SC barrier function, a pH-sensitive Eudragit® L00 nanoparticle, and the solvents of water and ethanol on cutaneous drug delivery. To determine the influence of the SC barrier on drug delivery, the SC thickness remaining on the skin after different numbers of tape stripping (TS) or cyanoacrylate stripping (CS) were quantified using two-photon microscopy, and the correlation of the SC reduction with the skin permeability changes was studied. The amount of SC removed by each tape decreased along with the skin depth, while a nearly constant SC thickness was removed by each CS. CS can remove the SC, viable skin layers and the hair follicle (HF), while TS can only remove the SC. Nevertheless, the removal of the entire human SC can be attained by both TS and CS, which were 4 times CS or 50 tape strips. The skin permeability to the model drug PCA linearly increased with the reduction of the SC thickness on the skin. These findings provide useful references to separating different skin layers for the quantification of drugs in the skin and establishing ex vivo barrier-disrupted skin models with different extents of barrier disruption. Especially, the barrier-disrupted skin, obtained by performing 30 tape strips on the intact porcine ear skin, could simulate atopic dermatitis (AD) skin to some extent. This ex vivo skin model could be used for evaluating dermal formulations in the initial development stage and reduce the number of animal and human studies. Next, the influences of the SC barrier on the skin penetration behavior of DxPCA-loaded pH-sensitive Eudragit® L100 NPs were investigated by EPR and CLSM using intact and barrier disrupted porcine skin. The pH-sensitive NP exhibited a triggered drug release in vitro at a pH above 5.9. When applied to the skin, the drug DxPCA was slowly released from the NPs in the case of the barrier-disrupted skin, whereas this was under the EPR detect limited for the intact skin. The disrupted SC barrier increased the exchange of the endogenous fluid of the skin with the external medium of the NP dispersion. Due to the exchange, the pH of the external medium of the NPs was increased, leading to the change in the NP structure and thus to the drug release. The improved drug release of the NPs is part of the reason for the higher drug penetration into the viable skin layers of the barrier-disrupted skin compared to the intact skin. These results indicate the feasibility of using this pH-sensitive NP to realize the targeted drug release and enhanced drug delivery into the viable skin layers of the AD skin lesions so that the side effects of the drug Dx could be reduced. Concerning the spatial localization of the NP, the EPR results indicate that the pH-sensitive NPs cannot pass through the disrupted SC of the skin, let alone the intact SC barrier. Besides, the accumulation of Nile red-loaded NPs in HFs and the transfolliclular penetration of Nile red was observed, which indicates that HFs can serve as a reservoir where drugs are sustained released from the NPs and provide a shortcut for drugs to penetrate across the HF into the deep viable skin layers. The drug release of the pH-sensitive NPs inside HFs may be due to the high sebum content and the high HF pH. Lastly, water and ethanol are omnipresent in topical formulations, serving as dispersion media for NPs, low-toxic dissolution media, and penetration enhancers. The solvent effects of ethanol, PBS and the cosolvent ethanol-PBS (1:1, V/V) on the penetration of the hydrophilic model drug PCA into the excised human skin and porcine ear skin were investigated by EPR. Absolute ethanol showed poor ability to deliver PCA into the skin due to the crystallization of PCA caused by ethanol evaporation. PBS and the cosolvent are superior to ethanol, delivering a similar high amount of PCA into the skin. Despite a similar total amount of PCA in the skin, the cosolvent delivered more drugs into the viable skin compared to PBS. This shows the solvents effects on the macroscopic localization of drugs in the skin. Nevertheless, more than 95% of the penetrated drugs accumulated in the SC regardless of the solvents, showing that the SC is a predominant barrier and the main reservoir for the skin penetration of hydrophilic PCA. Furthermore, the solvents influenced the microscopic localization of PCA in the SC. PCA distributed in both the intercellular skin lipids and corneocytes when using the three solvents. From PBS to ethanol, with more ethanol in the solvent, the fraction of PCA distributed in the intercellular lipids decreased from 74% to 37%. The reason may be that ethanol enhances the diffusion of PCA from the intercellular lipids into the corneocytes, implying the coexistence of intercellular and transcellular skin pathways for PCA. In conclusion, the studies conducted in this thesis i) provide correlation of the extent of the SC barrier disruption with the number of applied TS or CS and show the feasibility of using TS to establish an ex vivo barrier-disrupted skin model that mimics AD skin to some degree; ii) give insights of the influence of the SC barrier on the drug release of NPs on the skin and the following skin penetration of drugs, and show the promising application of the pH-sensitive NP in reducing the side effects of Dx for the treatment of AD; iii) expand the knowledge of solvent effects on the spatial localization of drugs in the SC and give a hint for the skin pathway of hydrophilic drugs.

Lin Xu,1 Bin Shen,2 Tingting Chen,3 Pin Dong2 1Department of Otolaryngology, Second Affiliated Hospital of Zhejiang University Medical College, Hangzhou, 2Department of Otolaryngology-Head& Neck Surgery, Shanghai Jiaotong University Affiliated First People’s Hospital, Shanghai, 3LishuiCentral Hospital, Lishui, Zhejiang Province, People’s Republic of China Abstract: The development of laryngeal squamous cell carcinoma (LSCC) is a multistep process involving multiple factors. MicroRNAs, a group of important negative regulators of gene expression, have also been confirmed to be involved in the LSCC pathogenesis. In the present study, we compared the expression of nine selected microRNAs in the LSCC tissues and adjacent nontumor tissues. We found that the expression of miR-203 was significantly reduced in the LSCC tissues. Predicted by using bioinformatics tools, we found that VEGFA and cyclooxygenase-2 (Cox-2) may be direct targets of miR-203. By subsequent determination through dual-luciferase assay and Western blot, we confirmed that miR-203 suppresses the expression of VEGFA and Cox-2 by directly targeting 3'-untranslated region. Meanwhile, by analyzing the relationship between miR-203 and VEGFA in clinical tissue samples, we found that a negative correlation existed in the expression of miR-203 and VEGFA (P=0.0096, r=-0.33). Similarly, the expression of miR-203 and Cox-2 also has a negative correlation (P=0.0019, r=-0.46). Subsequently, in vitro functional study indicated that miR-203 played as a tumor suppressor by repressing proliferation, migration, and invasion of Hep-2 cells. The overexpression of VEGFA partially rescued the effect of overexpressed miR-203. Overexpressed Cox-2 partially rescued the effect of miR-203 on Hep-2 cell proliferation but not on the cell migration and invasion capacity. These findings suggest that miR-203 plays as a tumor suppressor in LSCC, partially by regulating VEGFA and Cox-2, and may serve as a potential target for therapeutic intervention. Keywords: non-coding RNA, laryngeal squamous cell carcinoma, correlation analysis

The purpose of this work was to explore in-situ synchrotron wide-angle X-ray diffraction (WAXD) as a rapid and accurate tool to screen and monitor the formation of cocrystal/salts during heating. The active pharmaceutical ingredients (caffeine, carbamazepine and lamotrigine) were respectively mixed with the coformer (saccharin), and then heated by the hot stage. Real-time process monitoring was performed using synchrotron WAXD to assess cocrystal formation and subsequently compared to differential scanning calorimetry (DSC) measurements. The effect of heating rates and cocrystal growth behavior were investigated. Synchrotron WAXD was fast and sensitive to detect cocrystal formation with the appearance of characteristic diffraction rings, even at the heating rate of 30°C/min, while DSC curves showed overlapped peaks. Unlike the indirect characterization of DSC on endo/exothermic peaks, synchrotron WAXD can directly and qualitatively determine cocrystal by diffraction peaks. The diffraction intensity-temperature curves and the corresponding first-derivative curves clearly exhibited the growth behavior of cocrystal upon heating, providing useful information to optimize the process temperature of hot melt extrusion to continuously manufacture cocrystal. The study suggests that in-situ synchrotron WAXD could provide a one-step process to screen cocrystal at high efficiency and reveal the details of cocrystal/salts growth behavior.

Distribution network usually refers to the rated voltage of 110KV and below, and the function of direct power supply to users in the power system. The reliability of distribution network power supply directly affects the safety and economy of electricity use. In recent years, with the development of the national economy, the power load has greatly increased. In some areas, the construction of distribution networks cannot keep up with the increase in power load, resulting in power outages and frequent power failures in some regions. At the same time, users are increasingly demanding power quality. Whether the dispatcher or the user is eager to quantify the safety and economic analysis of the distribution network, the accuracy and level of the decision making of the intelligent distribution network dispatcher are improved. Studying the short-circuit fault and single-phase-to-ground fault fast fault location scheme is of great significance to improving the reliability of the distribution network operation. Self-healing is one of the main functions for the safe and reliable operation of smart grids. Reliable detection is the basis for realizing the self-healing function. The probability of a single-phase earth fault in a distribution network is very high because I mostly use it for neutral point grounding in medium-voltage distribution networks and use arc-suppression coils for grounding. When single-phase earthed, it is difficult to find point failures. At present, the small current ground fault line selection technology has been basically mature, and the small current ground fault location technology has achieved good results in the field of transient signals. Based on the transient characteristics of transient components, the single-phase ground fault location technology of power distribution network and the transient characteristics of single-phase grounded neutral distribution network are studied. At the same time, single-phase ground fault detection and cross-section based on parameter identification and current abrupt change are explained. Positioning method, implementation technology of single-phase earth fault feature detection function of distribution automation terminal, and architecture, interface mode and implementation method of single-phase positioning application software for distribution network.

In order to control the degree of comfort in vibration caused by human in a steel aerobridge of Shenzhen T3 terminal building, the theory of structural vibration control and TMD (Tuned Mass Damper) was used to control the vibration caused by human and conduct comfort design. At first, 3D analysis model of the structure was developed through general finite element analysis software MIDAS / GEN. And time-history analysis was carried out in different working conditions of human walking or jumping to analyze the dynamic response before and after the TMD was installed. Then, vibration test was conducted in-situ to determine its dynamic property and record its peak acceleration before and after the TMD were installed. Test data was then compared with data from the analysis model of the structure based on analysis software. The results show that the installing of TMD and making adjustment of the stiffness of the TMD based on the actual test make the structure meet requirements of degree of comfort in vibration caused by human. The effect of the vibration control is good.

In this paper, some discarded circuit boards in the plasma incinerator were incinerated by the converging - extended anode channel plasma torch, whose work principle and composition was described, and two experimental results were described, finally, the percentage of four major exhaust gas (CO, NO, SO2, O2) was reported, showing a good prospect on treating electronic waste with using the plasma torch.

This data acquisition and remote transmission system was designed accordance with the building requirement of solar chimney power generation testing apparatus. The system reads data from the sensors which were installed on the power station and stores them in a SQL database through the WLAN. Another add-on program is built to help users select and provide data in the database to facilitate their research.

Based on the 1# shield tunnel of SU ZHOU rail transit, a 3D discontinuous contact computational model of shield tunnel segment and bending bolts is built. This paper study about the stress and the deformation of shield tunnel segment with actual loads ,and the influences on shield tunnel segment by properly install the bolts. Result shows that timely apply pre-stress on the bolts could effectively decrease the deformations on segment joint by the shear resistance capacity of the bolts. The maximum deformation reduces from 3.580mm to 0.302mm. And there appear an open-angle which turn to outside or inside on segment joint. The maximum spacing of the open-angle is 0.66mm, and the maximum angle is 0.108 degree. In most position about shield tunnel segment, installed bolts reduced the axial forces and increased or reduced the bending moments.

At the main transformer for Helping on the 1st pre-test and found that the 1st variant of 66kV side of the A-phase winding DC resistance is too large, and the phase imbalance difference of 7.21%. On all aspects of the test wiring, testing and other parts were examined and treated, the test data did not change, the maintenance personnel to open 66kVA transformer phase "General cap" and found four phase winding A first end of the conductive rod (wiring board) connection some bolts loose, re-tighten again retest DC resistance test data qualified.

Chronic rhinosinusitis (CRS) is not a life-threatening disorder but may have a great impact on the patients. This study intended to evaluate the impact of functional endoscopic sinus surgery (FESS), and compare the effect and quality of life (QOL) after two different surgical approaches on patients with CRS. Sixty patients of CRS were analyzed before and after FESS. The extent of disease was evaluated by the Lund-Mackay scoring system using computed tomography (CT) and endoscopy. Subjective patient QOL scores were assessed by SF-36 questionnaire and symptom scores were recorded using the SNOT-20 questionnaire. Forty patients of multiunit CRS were randomly allocated to two groups in order to be taken radical FESS (RFESS) and conservative FESS (CFESS), respectively. The Lund-Mackay score and degree of preoperative polyps did not differ statistically between the two groups. In the 1 months follow-up settings, such domains as role physical, mental health, role emotional and general health of SF-36, and total of the SNOT-20 items scores and the most important 5-item scores of SNOT-20 all began to get better markedly (P

Summary Objective The aim of this study was to establish a multiparameter voice assessment profile using objective multiparameter test and subjective voice quality assessment. Methods We assessed 50 patients with voice disorders before and after operation. The assessment incorporates (1) subjective voice quality assessment, (2) patients' self-assessment, and (3) objective acoustic analysis. The subjective voice quality assessment uses GRABS system to evaluates the grade of hoarseness (G), proposed by the Japanese Society for Logopedics and Phoniatrics. Patients' self-assessment is modified based on the Chinese version of voice handicap index (VHI) scale, composed of functional (F), physiological (P), emotional (E) part, and a total score (T). The acoustical analysis evaluate the patients' voice sample by voice analysis software "Dr. Speech". Three parameters, jitter (J), shimmer(S), and normalized noise energy (NNE), were taken in analysis. Results We observed high correlations among subentries F, P, and the total score T vH of the VHI scale in patients' subjective assessment. Parameter E does not correlate well with other assessed parameters. The Chinese version of VHI, which incorporate multifactors including age, education, and especially the cultural difference may account for the inconsistent correction in parameter E. In the objective acoustic analysis, high correlation among the three parameters J, S, and NNE is observed. Conclusion Systemic assessment combining a subjective voice quality assessment, an objective acoustic analysis, and a self-assessment is helpful in clinical practice in the diagnosis and treatment for voice disorders. The E component in VHI scale assessment may not be a reliable parameter to evaluate treatment outcome.