The object of this study is to preparate the berberine hydrochloride (BBH) resin compound with taste masking effect. We took the BBH as the model drug and Amberlite IRP69 as the drug carriers, uncovered the curve of solubility of BBH in different cosolvent with a certain range of temperature, and then used it to calculate the parameters during the preparation of the complex such as adding quantity of BBH and the reaction temperature. Afterwards, the characteristic and in vitro release experiments were studied to verify the formation and predict the in vivo release behavior of the complex. The results showed that in the condition of using 60% ethanol as a cosolvent and stirring at 50 ℃ for 1 h, the drug loading and drug availability of the complex are at about 35% and 64%, respectively, and has a better taste-masking effect. In this study, a method was provided for preparing a taste-masking preparation of BBH.

Local focal adhesion kinase (FAK) is a non-receptor intracellular tyrosine kinase that plays an important role in tumor initiation, development, metastasis and invasion, and is considered to be an important target for the development of antineoplastic drugs. It has both kinase-dependent and non-kinase-dependent scaffolding functions. However, traditional small molecular inhibitors can only inhibit its kinase-dependent activity, so it is difficult to target the kinase-independent scaffolding function. Therefore, there is an urgent need for novel strategies to enhance FAK targeting to lay the foundation for determining the druggability and discovery of FAK inhibitors. Proteolysis targeting chimera (PROTAC) is a new drug development strategy that can recruit E3 ligase to specifically ubiquitinylate target proteins for degradation through the proteasome system. The unique mechanism of action of the PROTAC system could be used to target and degrade the FAK protein, thus eliminating the scaffolding function of FAK. In this review, FAK protein, the signaling pathway, and small molecule inhibitors are briefly described, and the latest research progress in targeting the degradation of FAK using PROTAC technology is summarized.

The non-covalent interactions between 18-crown-6 (18c6) and 20 common types of protonated amino acids were explored by electrospray ionization mass spectrometry (ESI-MS).The mass spectra showed the formation of 1:1 stoichiometric non-covalent complexes between 18c6 and amino acids.The calibration curves and linear equations for the complexes of L-Phe,L-Tyr,L-Lys and L-Asp with 18c6 were established by mass spectrometric titration and used as reference values for competitive ESI-MS.Through competitive equilibrium,the binding constants for the complexes of 18c6 with other L-amino acids and their D-isomers were derived.It was found,as a general trend,lgKa for the complexes of 18c6 with the basic amino acid and the amino acid with alkyl side chain were larger than other complexes,and among the amino acids with alkyl side chain,Gly and Ala exhibited greater 18c6 binding affinities.As for Ser and Thr,the intramolecular hydrogen bond between the nitrogen atom from terminal NH2and the oxygen atom from carboxyl may impede their protonated amino-group to attack the 18c6.Furthermore,Gln and Asn exhibited lower 18c6 binding affinities probably due to effects of electron-withdrawing group of acylamide.Finally,the chiral selectivity of 18c6 for 19 L-,or D-amino acids was measured by ESI-MS,indicating 18c6 could only recognize some neutral amino acid isomers.

BACKGROUNDWork-related musculoskeletal disorders (WMSDs) have high prevalence in sewing machine operators employed in the garment industry. Long work duration, sustained low level work and precise hand work are the main risk factors of neck-shoulder disorders for sewing machine operators. Surface electromyogram (sEMG) offers a valuable tool to determine muscle activity (internal exposure) and quantify muscular load (external exposure). During sustained and/or repetitive muscle contractions, typical changes of muscle fatigue in sEMG, as an increase in amplitude or a decrease as a shift in spectrum towards lower frequencies, can be observed. In this paper, we measured and quantified the muscle load and muscular activity patterns of neck-shoulder muscles in female sewing machine operators during sustained sewing machine operating tasks using sEMG.

METHODSA total of 18 healthy women sewing machine operators volunteered to participate in this study. Before their daily sewing machine operating task, we measured the maximal voluntary contractions (MVC) and 20%MVC of bilateral cervical erector spinae (CES) and upper trapezius (UT) respectively, then the sEMG signals of bilateral UT and CES were monitored and recorded continuously during 200 minutes of sustained sewing machine operating simultaneously which equals to 20 time windows with 10 minutes as one time window. After 200 minutes' work, we retest 20%MVC of four neck-shoulder muscles and recorded the sEMG signals. Linear analysis, including amplitude probability distribution frequency (APDF), amplitude analysis parameters such as roof mean square (RMS) and spectrum analysis parameter as median frequency (MF), were used to calculate and indicate muscle load and muscular activity of bilateral CES and UT.

RESULTSDuring 200 minutes of sewing machine operating, the median load for the left cervical erector spinae (LCES), right cervical erector spinae (RCES), left upper trapezius (LUT) and right upper trapezius (RUT) were 6.78%MVE, 6.94%MVE, 6.47%MVE and 5.68%MVE, respectively. Work load of right muscles are significantly higher than that of the left muscles (P < 0.05); sEMG signal analysis of isometric contractions indicated that the amplitude value before operating was significantly higher than that of after work (P < 0.01), and the spectrum value of bilateral CES and UT were significantly lower than those of after work (P < 0.01); according to the sEMG signal data of 20 time windows, with operating time pass by, the muscle activity patterns of bilateral CES and UT showed dynamic changes, the maximal amplitude of LCES, RCES, LUT occurred at the 20th time window, RUT at 16th time window, spectrum analysis showed that the lower value happened at 7th, 16th, 20th time windows.

CONCLUSIONSFemale sewing machine operators were exposed to high sustained static load on bilateral neck-shoulder muscles; left neck and shoulder muscles were held in more static positions; the 7th, 16th, and 20th time windows were muscle fatigue period that ergonomics intervention can protocol at these periods.

Adult ; Electromyography ; methods ; Female ; Humans ; Muscle Fatigue ; physiology ; Muscle, Skeletal ; physiology ; Neck Muscles ; physiology ; Shoulder ; physiology ; Textile Industry ; Workload ; Young Adult

OBJECTIVETo study neck and shoulder work-related muscle fatigue of female sewing machine operators.

METHODS18 health female sewing machine operators without musculoskeletal disorders work in Beijing garment industry factory as volunteers in participate of this study. The maximal voluntary contraction (MVC) and 20% MVC of bilateral upper trapezium and cervical erectors spinae was tested before sewing operations, then the whole 20 time windows (1 time window = 10 min) sewing machine operations was monitored and the surface electromyography (sEMG) signals simultaneously was recorded after monitoring the 20%MVC was tested. Use amplitude analysis method to reduction recorded EMG signals.

RESULTSDuring work, the median load for the left cervical erector spinae (LCES), right cervical erector spinae (RCES), left upper trapezium (LUT) and right upper trapezium (RUT) respectively was 6.78 ± 1.05, 6.94 ± 1.12, 5.68 ± 2.56 and 6.47 ± 3.22, work load of right is higher than the left; static load analysis indicated the value of RMS(20%MVC) before work was higher than that value after work, the increase of right CES and UT RMS(20%MVC) was more; the largest 20%MVE of bilateral CES occurred at 20th time window, and that of bilateral UT happened at 16th.

CONCLUSIONSThe work load of female sewing machine operators is sustained "static" load, and work load of right neck-shoulder is higher than left, right neck-shoulder muscle is more fatigable and much serious once fatigued.

Adult ; Electromyography ; Female ; Humans ; Muscle Fatigue ; physiology ; Posture ; Shoulder ; physiology ; Textile Industry ; Work ; Young Adult

BACKGROUNDEnamel demineralization occurs frequently during orthodontic treatment. In this study, we evaluated the changes of the density of mutans streptococcus (MS) in plaque after bracket bonding and using fluoride adhesive on maxillary incisors by real time fluorescence-quantitative polymerase chain reaction (RT-FQ PCR).

METHODSThe study was designed as a self-paired test. Brackets were bonded with fluoride adhesive on the left side, while non-fluoride adhesive on the right side for each patient. Plaque samples were taken from the surfaces around the brackets of four maxillary incisors before brackets bonding and after the bonding 4 weeks later. The amount of MS was measured by RT-FQ PCR. The data obtained were analyzed statistically using the SPSS 11.5 version and the alpha level was set at 0.05 (2-tailed).

RESULTSThe amount of MS in plaque increased significantly after bracket bonding (P < 0.01), whereas no significant differences were observed among four maxillary incisors both before and after brackets bonding (P > 0.05), and among the incisors using and not using fluoride adhesive (P > 0.05).

CONCLUSIONSThe increase of the density of MS in plaque after bracket bonding is one of the etiological factors for enamel demineralization in orthodontic patients. The result of this study did not support what we observed clinically that the incidence of enamel demineralization for lateral incisors was higher than that for central incisors. Using fluoride adhesive for bonding did not affect the amount of MS in plaque in our study. Further study is needed.

Adhesives ; Adolescent ; Dental Bonding ; Dental Plaque ; microbiology ; Female ; Fluorescence ; Fluorides ; administration & dosage ; Humans ; Male ; Orthodontic Brackets ; Polymerase Chain Reaction ; methods ; Streptococcus mutans ; genetics ; isolation & purification ; Tooth Demineralization

This study was designed to establish the method of characterization of surface free energy(SFE)and evaluate the compaction properties of pharmaceutical materials based on SFE. We investigated the contact angles of materials with water and diiodomethane under different compression pressures. The contact angles of materials at 353 MPa compression pressure were utilized to calculate the related parameters of SFE ultimately. The area under tensile strength-compression pressure curve(AUTSC)and pressure yield(Py)were employed to evaluate the compactibility of material. Additionally, Pearson correlation analysis was utilized to analyze the relationship between the SFE and the compaction properties of pharmaceutical materials. The results exhibited that SFE had a significant correlation with the compaction properties of materials(P < 0.05). Moreover, the related parameters of SFE, i.e., cohesive work(W_co)and polarity index(PI)of SFE, were positively correlated with Py of Heckel equation and negatively related with AUTSC. The higher values of W_co and PI, the stronger repulsive force among the particles, led to a worse compaction behavior. In this study, we established the method for characterization of the compaction behavior of materials based on SFE initially. This study also demonstrated that SFE could evaluate the compaction behavior effectively, which provides a better understanding of compaction behavior for pharmaceutical researchers.

Fatigue refers to the manifestation of disorders in the process of carrying out or maintaining random activities， which can be regarded as an independent disease or as a symptom in a variety of chronic diseases. The high incidence of fatigue has seriously affected people's physical and mental health， and the prevention and treatment of fatigue has become an important problem to be solved urgently. The pathogenesis of fatigue mainly includes energy consumpation， accumulation of metabolites， abnormal secretion of neurotransmitters， decline of mitochondrial function， dysfunction of hypothalamus pituitary adrenal axis， etc. At present， there is no unified understanding about the pathogenesis of fatigue at home and abroad. The gene research of fatigue is the current research frontier. Gene expression profiling provides a new method for the study of the mechanism of fatigue. The combination of gene chip technology and traditional Chinese medicine（TCM） theory is expected to bring a breakthrough in the study of the pathogenesis of fatigue. In the study of fatigue gene chip， messenger RNA（mRNA） and microRNA（miRNA） are the common research objects， but few explorations are focused on the gene expression rule of fatigue by a specific signaling pathway and the effective regulation targets of TCM for treating fatigue. In recent years， the dysfunction of reward and inhibition mechanism in the central nervous system has become a research hotspot. In particular， gamma amino butyric acid （GABA） and dopamine （DA） have attracted much attention as the main substances of inhibition and reward mechanism， respectively. GABA and DA are used as inhibition and reward mechanisms to maintain the balance， and the body will not feel fatigue. Once the balance is broken， the fatigue will be formed. At the same time， DA and GABA receptors can also regulate cyclic adenosine monophosphate signaling pathway（cAMP） to affect fatigue. The research on key genes in GABA/DA balance mechanism and related cAMP signaling pathway by gene chip technology is expected to reveal the pathogenesis of fatigue in depth. The gene chip method is used to detect the changes of key genes in GABA/DA pathway and the related cAMP signaling pathway in the fatigue population and the normal population， so as to further explore the pathogenesis of fatigue. In this paper， the key genes in GABA/DA balance mechanism and cAMP signaling pathway related to fatigue were summarized by using the review method， so as to provide the basis for further study on the pathogenesis of fatigue and effective prevention and treatment from the perspective of genetics.

OBJECTIVE: To investigate the roles of angiotensin-converting enzyme 2 (ACE2) in ozone-induced pulmonary inflammation and airway remodeling in mice. METHODS: Sixteen wild-type (WT) C57BL/6J mice and 16 ACE2 knock-out (KO) mice were exposed to either filtered air or ozone (0.8 ppm) for 3 h per day for 5 consecutive days. Masson's staining and HE staining were used to observe lung pathologies. Bronchoalveolar lavage fluid (BALF) was collected and the total cell count was determined. The total proteins and cytokines in BALF were determined by BCA and ELISA method. The transcription levels of airway remodeling-related indicators in the lung tissues were detected using real-time quantitative PCR. The airway resistance of the mice was measured using a small animal ventilator with methacholine stimulation. RESULTS: Following ozoneexposure ACE2 KO mice had significantly higher lung pathological scores than WT mice (P < 0.05). Masson staining results showed that compared with ozone-exposed WT mice, ozone-exposed ACE2 KO mice presented with significantly larger area of collagen deposition in the bronchi [(19.62±3.16)% vs (6.49±1.34)%, P < 0.05] and alveoli [(21.63±3.78)% vs (4.44±0.99)%, P < 0.05]. The total cell count and total protein contents in the BALF were both higher in ozone-exposed ACE2 KO mice than in WT mice, but these differences were not statistically significant (P > 0.05). The concentrations of IL-6, IL-1β, TNF-α, CXCL1/KC and MCP-1 in the BALF were all higher in ozone-exposed ACE2 KO mice than in ozone-exposed WT mice, but only the difference in IL-1β was statistically significant (P < 0.05). The transcription levels of MMP-9, MMP-13, TIMP 4, COL1A1, and TGF-β in the lung tissues were all significantly higher in ozone-exposed ACE2 KO mice (P < 0.01). No significant difference was found in airway resistance between ozone-exposed ACE KO mice and WT mice after challenge with 0, 10, 25, or 100 mg/mL of methacholine. CONCLUSION ACE2 participates in ozone-induced lung inflammation and airway remodeling in mice.
Airway Remodeling ; Angiotensin-Converting Enzyme 2 ; Animals ; Methacholine Chloride ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Ozone/adverse effects* ; Pneumonia

The high performance liquid chromatography(HPLC) characteristic chromatogram of Xiaoer Ganmaoning Oral Liquid(oral liquid for short) was established. The medicinal materials corresponding to characteristic peaks, their index components and ranges of similarity with the reference chromatograms were clarified. The similarity between the characteristic chromatograms of 10 batches of the oral liquid and the reference chromatogram was higher than 0.994. Eighteen characteristic peaks were identified, which were derived from different medicinal materials including Scutellariae Radix, Arctii Fructus, Lonicerae Japonicae Flos, Gardeniae Fructus and Forsythiae Fructus. Further, 11 characteristic peaks were assigned by the comparison with reference substances as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, isochlorogenic acid A, isochlorogenic acid C, baicalin, baicalein, wogonin, scutellarin, forsythiaside A and arctiin. Also, the characteristic chromatogram of precipitate in the oral liquid was established, and the similarity between characteristic chromatograms of 10 batches of the precipitate and the reference chromatogram was higher than 0.940. The 14 characteristic peaks originating from the precipitate and those from the oral liquid were consistent in retention time, and the content of all index components in the precipitate was lower than 5% of that in the oral liquid. Moreover, the stability of precipitate during the accelerated stability test was explored with filtration and Matlab-based image sensory evaluation. The precipitate mass and precipitation degree both increased over the stability test duration significantly. The stability of the oral liquid was used as a model system in this study to establish the integrated quality control system which related to medicinal materials, preparations and precipitate with HPLC characteristic chromatograms and image sensory evaluation, which lays a foundation for the exploration of the quantity value transfer of the oral liquid.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Scutellaria baicalensis/chemistry*