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.

Eleven flavonol glycosides were isolated from the ethanol extract of Lysimachia clethroides by a combination of various chromatographic techniques including column chromatography over silica gel, Sephadex LH-20, and reversed-phase HPLC. Their structures were identified as astragalin (1), isoquercitrin (2), isorhamnetin-3-O-β-D-glucopyranoside (3), quercetin-3-O-β-D-6"-acetylglucopyranoside (4), quercetin-7-O-β-D-glucopyranoside (5), prunin (6), 2-hydroxynaringin-5-O-β-D-glucopyranoside (7), kaempferol-3-O-rutinonoside (8), kaempferol-3-O-robinobioside (9), rutin (10) and kaempferol-3,7-di-O-β-D-glucopyranoside (11). Among them, compounds 4, 7 and 11 were obtained from the Lysimachia genus for the first time, while compounds 3, 5 and 9 were firstly reported from this plant. In the preliminary assays, compounds 2, 6 and 8 possessed significant inhibition against aldose reduc- tase, with IC50 values of 2.69, 1.00, 1.80 μmol · L(-1), respectively; none of compounds 1-11 exhibited obvious cytotoxic activity (IC50 > 10 μmol · L(-1)).
Drugs, Chinese Herbal ; chemistry ; Flavonols ; chemistry ; Glycosides ; chemistry ; Molecular Structure ; Primulaceae ; chemistry ; Spectrometry, Mass, Electrospray Ionization

OBJECTIVETo examine modulations caused by cyclooxygenase-2 (COX-2) inhibitors on altered microenvironments and overbalanced neurotransmitters in pilocarpine-induced epileptic status rats and to investigate possible mechanisms.

METHODSCelecoxib (a COX-2 inhibitor) was administered 45 min prior to pilocarpine administration. The effects of COX-2 inhibitors on mIPSCs (miniature GABAergic inhibitory postsynaptic currents) of CA3 pyramidal cells in the hippocampus were recorded. Expressions of COX-2, c-Fos, newly generated neurons, and activated microgliosis were analyzed by immunohistochemistry, and expressions of alpha-subunit of gamma-amino butyric acid (GABA(A)) receptors and mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) activity were detected by Western blotting.

RESULTSPretreatment with celecoxib showed protection against pilocarpine-induced seizures. Celecoxib prevented microglia activation in the hilus and inhibited the abnormal neurogenesis and astrogliosis in the hippocampus by inhibiting MAPK/ERK activity and c-Fos transcription. Celecoxib also up-regulated the expression of GABA(A) receptors. NS-398 (N-2-cyclohexyloxy-4-nitrophenyl-methanesulfonamide), another COX-2 inhibitor, enhanced the frequency and decay time of mIPSCs.

CONCLUSIONThe COX-2 inhibitor celecoxib decreased neuronal excitability and prevented epileptogenesis in pilocarpine-induced status epilepticus rats. Celecoxib regulates synaptic reorganization by inhibiting astrogliosis and ectopic neurogenesis by attenuating MAPK/ERK signal activity, mediated by a GABAergic mechanism.

Animals ; Blotting, Western ; Celecoxib ; Cyclooxygenase 2 ; metabolism ; Cyclooxygenase 2 Inhibitors ; pharmacology ; Disease Models, Animal ; Fibrocystic Breast Disease ; metabolism ; Hippocampus ; drug effects ; enzymology ; pathology ; Immunohistochemistry ; MAP Kinase Signaling System ; drug effects ; Male ; Mitogen-Activated Protein Kinase Kinases ; metabolism ; Nitrobenzenes ; pharmacology ; Pilocarpine ; Proto-Oncogene Proteins c-fos ; metabolism ; Pyrazoles ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-A ; biosynthesis ; Status Epilepticus ; chemically induced ; enzymology ; pathology ; Sulfonamides ; pharmacology ; Synapses ; drug effects ; pathology

OBJECTIVETo evaluate the influence of the frequency, the weight and the motion angle on the stress and the fatigue of the forearm extensors in repetitive wrist extending at low force loading level with surface electromyography (SEMG).

METHODSSixteen male college student volunteers were recruited for the experiment. Eight tasks of wrist extending were performed for 20 minutes respectively in given weight (1.96, 4.90 N), frequency (8.0, 33.3 moves/minute) and motion angle (45 degrees, 90 degrees). The static wrist extending at the level of 20% maximum voluntary contraction (MVC) were performed before and after each task for 2 up to 3 seconds, and the SEMG signals of extensor carpi ulnaris muscle (ECU) and extensor digitorum (ED) were recorded and analyzed.

RESULTSThe weight loading level was approximately equal to 1.40% or 3.50% of the MVC force. The mean power frequency (MPF) and the median frequency (MF) were decreased with the increase of 3 kinds of loading levels. The decrease of MPF of the muscle ED was significant (P < 0.05 or P < 0.01). The MF was decreased with the increase of angle and weight loading levels (P < 0.05 or P < 0.01). The root mean square (RMS) value of SEMG could be divided into 3 or 4 groups with significant difference. All three kinds of loads had positive correlation with amplitude of SEMG according to the stepwise regression analysis.

CONCLUSIONThe fatigue level of ED is the highest. The primary load factor for the forearm extensors is the frequency followed by the weight and the angle. MF, MPF and RMS can be used as sensitive indexes for evaluating the stress and the fatigue of the forearm extensors during repetitive performance at lower force loading level.

Adolescent ; Adult ; Electromyography ; Forearm ; physiology ; Humans ; Male ; Muscle Fatigue ; physiology ; Muscle, Skeletal ; physiology ; Range of Motion, Articular ; Regression Analysis ; Workload ; Wrist Joint ; physiology

Seventeen minor triterpenoid acids (1-17) were isolated from an aqueous decoction of Uncaria rhynchophylla by a combinatory application of column chromatography using multiple stationary phases, including macroporous adsorbent resin, MCI resin, Sephadex LH-20, Toyopearl HW-40C, silica gel, and C18 reversed phase silica gel, combined with separation techniques of flash chromatography (FC) and high performance liquid chromatography (HPLC). Their structures were determined by analysis of HR-ESI-MS, UV, CD, and IR as well as 1D and 2D NMR spectroscopic data, of which eight new compounds (1-8) are named successively uncarinic acids Q-X, while the structures of 2 and 7 were confirmed by single crystal X-ray diffraction. In the in vitro assays, 27-hydroxyolean-12-en-28-oic acid (17) inhibited TGF-β-induced HSC-T6 cell activation at the concentration of 5 μmol·L^-1.

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

OBJECTIVE: To study the association of body fat ratio with precocious puberty in girls. Previous studies have shown that body mass index (BMI) is associated with the girls' age of puberty but have not revealed the association of body fat ratio with age of puberty. METHODS: Based on the consensus on the diagnosis and treatment of central precocious puberty (CPP), 128 children with precocious puberty who were admitted to the hospital from July to August, 2017, were divided into a CPP group with 87 children and a peripheral precocious puberty (PPP) group with 41 children. A total of 51 girls without any puberty development signs were enrolled as the control group. Dual-energy X-ray absorptiometry was used to measure the body fat ratios of upper limbs, legs, trunk, android area, gynoid area, and the whole body. The association between body fat ratios and precocious puberty was analyzed with reference to age, BMI, BMI-Z score, bone age, ovarian volume, and hormone levels. RESULTS: Compared with the control group, the CPP and PPP groups had significantly higher body fat ratios of upper limbs, legs, trunk, android area, gynoid area, and the whole body, legs/whole body fat ratio, and (upper limbs+legs)/trunk fat ratio (P<0.05), while there were no significant differences in the above body fat ratios and fat distribution indicators between the CPP and PPP groups (P>0.05). For the girls with precocious puberty, the high body fat ratio group had significantly higher luteinizing hormone (LH) base value, luteinizing hormone releasing hormone (LHRH)-stimulated LH peak value, and LH/follicle-stimulating hormone peak value than the low body fat ratio group (P<0.05). Compared with the control group, both the high body fat ratio and low body fat ratio groups had a significantly higher LH base value (P<0.05). CONCLUSIONS The increase in body fat may be a factor inducing precocious puberty in girls, but further studies are needed to determine the mechanism.
Adipose Tissue ; Child ; Female ; Follicle Stimulating Hormone ; Gonadotropin-Releasing Hormone ; Humans ; Luteinizing Hormone ; Puberty, Precocious ; Sexual Maturation

OBJECTIVETo evaluate the health-related quality of life and postdischarge long-term outcome after severe acute pancreatitis.

METHODSThe hospital records of patients with SAP discharged healthy from January 2003 to December 2003 were reviewed. The Rand 36-item Health Survey with accessory question was mailed to each patient. The means and deviations for each of eight scales scores of SF-36 were calculated, the study population scores were compared with general Chinese population; Univariate analysis was applied to determining the effects of variables such as age, sex, causes of disease, mode of treatment, frequency of surgery, financial burden, length of stay, chronic complications. Accessory questions were analyzed separately.

RESULTSThe means and deviations for each of eight scales (PF, RP, RE, BP, VT, MH, SF, GH) scores of SF-36 in SAP patients were 83 +/- 15, 62 +/- 42, 69 +/- 36, 80 +/- 15, 69 +/- 19, 72 +/- 15, 75 +/- 18, 65 +/- 18, compared with general people. Except RP and SF, the others were similar. In the ANOVA of Physical Component Summary, the three variables mode of treatment, financial burden and length of stay were included (P < 0.05), while in that of Mental Component Summary, the two variables of gender and financial burden were included (P < 0.05).

CONCLUSIONSThe health-related quality of life in SAP patients is similar to that of general people. Greater attention should be given to mode of treatment, length of stay and financial burden to improve quality of life.

APACHE ; Adolescent ; Adult ; Aged ; Analysis of Variance ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Pancreatitis, Acute Necrotizing ; psychology ; therapy ; Quality of Life ; Retrospective Studies ; Surveys and Questionnaires ; Survivors ; Treatment Outcome

OBJECTIVETo study the changes of amino acids in cerebral spinal fluid (CSF) in children with spastic or athetotic cerebral palsy (CP) by examining CSF levels of glutamic acid (Glu), gamma-aminobutyric acid (GABA) and aspartate (ASP).

METHODSCSF samples were obtained from 13 children with spastic CP, from 14 children with athetotic CP, and from 10 children without central nervous system and infectious diseases (control group). CSF levels of Glu, GABA and ASP were determined by high-performance liquid chromatography.

RESULTSCSF levels of GABA, ASP and Glu in the control group were 13.04+/-2.19, 10.21+/-0.45 and 8.41+/-2.26 micromol/L, respectively. Compared with the control group, CSF GABA levels in the spastic and the athetotic CP groups (8.02+/-2.03 and 10.01+/-2.68 micromol/L respectively) significantly decreased (P<0.01), whereas CSF levels of Glu (20.99+/-8.15 and 28.77+/-17.62 micromol/L respectively) and Asp (13.53+/-3.93 and 14.02+/-2.88 micromol/L respectively) in the spastic and the athetotic CP groups significantly increased (P<0.01). There were statistical differences in the GABA level between the spastic and the athetotic CP groups (P<0.05). In children with spastic CPCSF Glu level was positively correlated to muscle tension.

CONCLUSIONSCSF excitatory amino acid levels increased, while CSF inhibitory amino acid levels decreased in children with CP. There were differences for CSF amino acid levels in different types of CP. The changes of amino acid levels may contribute to the pathogenesis of CP.

Amino Acids ; cerebrospinal fluid ; Cerebral Palsy ; cerebrospinal fluid ; physiopathology ; Child, Preschool ; Chromatography, High Pressure Liquid ; Female ; Humans ; Male ; Muscle Tonus