Adult ; Aged ; Aged, 80 and over ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Esophageal Neoplasms ; metabolism ; pathology ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Macrophage Activation ; Macrophages ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Receptors, Cell Surface ; metabolism ; Survival Rate

The interaction of drug and target protein is a critical part of new drug discovery. It is the premise for drugs to exert therapeutic effects by targeting specific binding sites of target proteins and thereby affecting its pharmacological activity. Currently, a variety of techniques are exploited to detect the interaction between drug ligands and target proteins. For example, cellular thermal shift assay (CETSA) and differential scanning fluorimetry (DSF) based on thermodynamics, mass spectrometry and nuclear magnetic resonance technology, etc. In addition, high-throughput ligand screening technology provides technical convenience for the search of specific ligand, and is a powerful tool to efficiently identify the interaction between drug ligand and target protein. Here, we summarize the detection techniques of interaction between small molecules and target proteins, and discuss the application of high-throughput ligand screening technology in drug research.

Target identification and verification of natural products is an important and challenging work in the field of chemical biology. It is also an important job for researchers to apply chemical proteomics technology to biomedicine in order to identify target proteins of natural products. Target identification is critical to understanding its mechanisms and developing natural products as molecular probes and potential therapeutic drugs. Traditional approaches of small molecule target identification based on affinity have been shown to be successful, such as click-chemical probes, radioisotope labeling or photosensitized small-molecule probes. Nevertheless, these technologies require purified candidate target proteins, and modified small molecules with probes or linkers, such as adding agarose beads, biotin labels, fluorescent labeling or photo-affinity labeling. Many structure-activity relationship studies should be performed to ensure that the addition of small molecule labels undisturbed the original biological activity of the small molecules. Unfortunately, all these modifications are likely to alter their biological activity or binding specificity. To overcome the bottleneck of "target recognition", researchers have developed a series of new techniques for unmodified drug target identification. In this article, we reviewed the target identification techniques of natural product without structural modification in order to provide reference for the development of natural products.

Evaluation of the permeability mainly focuses on intestinal absorption in biopharmaceutics classification system (BCS). It is more complicated that the absorption and metabolism under multicomponent environment in biopharmaceutics classification system of Chinese materia medica (CMMBCS) compared with single component environment, which needs suitable mathematical models to be described. Therefore, with full consideration of existing single component mathematical algorithm combining with the characteristics of intestinal absorption and metabolism, we explored and designed a new mathematical algorithm of intestinal absorption and metabolism of multicomponent drug. Then we put forward a new coefficient, P (influence), the relative change rate of the single component's intestinal absorption and metabolism under multicomponent environment compared with single component environment, which described the influences of intestinal absorption and metabolism of the component under multicomponent environment. Moreover, P (influence) highlights the distinctive characteristics of multicomponent drug's intestinal absorption and metabolism, and lays the foundation for the construction of CMMBCS.
Algorithms ; Drugs, Chinese Herbal ; chemistry ; pharmacokinetics ; Humans ; Intestinal Absorption ; Intestines ; chemistry ; metabolism ; Models, Theoretical ; Solubility

ObjectiveTo identify the framework for assessing health related quality of life(HRQOL) of Kaschin-Beck disease(KBD),in order to reflect the impact of KBD on quality of life in patients with the disease.MethodsQualitative descriptive research was adopted.Semi-open ended questions were developed by using the World Health Organization(WHO) definitions of health and quality of life.Group interview and face to face interviews were conducted on 48 patients with KBD and 29 health care experts on KBD in Linyou and Yongshou counties,Shaanxi province,which were higher prevalence areas of KBD.Content template analysis was conducted and the template was based on the WHOQOL-100's framework.ResultsThe framework of HRQOL for KBD included four domains:physical activity,familial/social support,economic and psychological state.There were also eleven facets which were:pain and discomfort,physical function and activity limitation,diet and sleeping,social relationship,concerns of family responsibilities,social support,economic,housing and the surrounding environment,appearance concerns,mental health,and general state of health.The total entries were 69.ConclusionsThe framework for assessing HRQOL of KBD is established.The framework highlights the impact of KBD on the patients' quality of life with higher specificity.

ObjectiveTo explore the particular inner world of the children with attention deficit hyperactivity disorder (ADHD)with the sandplay therapy and the initial sandtray's clinical diagnosis role and value on the ADHD.MethodsThe differences of the initial sandtrays between 28 children with ADHD and 24 normal children were compared.Results 1.On the use of toys,the experimental group was significantly higher in transports ((5.04 ±6.60),(1.38 ±2.12),t=2.73) and lower in stones((0.00 ±0.00),(8.00 ± 12.33),t=-3.18).2.On the scene of sandtrays,the experimental group was significantly higher in the fight( x2 =12.96,P ＜ 0.01 ),dynamic scenes ( x2 =13.37,P ＜ 0.01 ).3.On the use of self-images,the experimental group was lower than the normal children,and the differences were significant ( x2 =4.75,P ＜ 0.05 ).4.There were no significant differences in the use of sand between two groups( x2 =3.46,P ＞ 0.05).ConclusionThe results show that the children with ADHD have significantly characteristics in sandtrays.Initial sandtray is valuable to be an aid to clinical diagnosis and intervention means.

Objective To investigate the value of Fluorine-18 fluorodeoxyglucose positron emission tomography (~(18)F-FDG-PET)in staging and detecting residual disease during follow-up of non-Hodgkin's lymphoma in children. Methods The results of~(18)F-FDG-PET of 88 podiatric NHL before and after chemotherapy was analyzed respectively.The results were compared with CT scans simultaneously.Results 67 cases were performed for initial staging.Of the 1072 anatomy regions were analyzed by PET and CT with concordalice of 88.62%regions(positive in 11.10%and negative in 77.52%1.Disconcordance were found in 11.38%regions(PET positive but CT negative in 6.8 1%,PET negative but CT positive in 4.57%).PET was significantly better than CT scan in the staging of podiatric NHL.35 scans were performed in the follow-up.The true residual disease positive rate of PET and CT were 87.50%and 57.14% respectively.The false positive rate of PET and CT were 12.50%and 50.00%respectively.Conclusion ~ (18)SF-FDG-PET imaging is of great value for the staging of the pediatric patients with NHL It's a useful technique to identify the residual disease,avoid unnecessary treatment and biopsy and Can predict eady relapse.

ObjectiveTo investigate the difference of the spontaneous neuronal activity between attention-deficit hyperactivity disorder (ADHD) and normal children with amplitude of low-frequency fluctuation (ALFF) of the resting-state fMRI,and to discuss the correlation between the activity level of brain and symptom severity.MethodsThirty-two children with ADHD of school age and thirty age-and gender-matched controls were experienced with resting-state fMRI scans while blood oxygenation level dependent (BOLD) signal was acquired to calculate the amplitude of low-frequency fluctuation (ALFF).Linear correlations were performed between the aggregate score of RS-Ⅳ and ALFF voxels in ADHD patients.ResultsCompared to the controls,the ADHD group exhibited decreased ALFF in right superior frontal gyrus ( BA9,t =- 4.61 ),left superior medial frontal gyrus ( BA10,t =- 3.63 ),left mediate frontal ( BA46,t =- 4.09 ),and left anterior cingulate cortex ( BA24,t =- 4.02).Meanwhile,it showed increased ALFF in the medial orbitofrontal cortex( BA11,t =3.52 ),right cuneus gyrus ( t =3.93 ),right mediate occipital gyrus ( BA 19,t =3.82),right cerebellum ( BA37,t =3.77),right mediate temporal gyrus( BA37,t =3.76),and left paracentral lobe ( BA6,t =3.77 ).Altered ALFF in left superior medial frontal gyrus(P=0.009,r=0.492)and the right cuneus gyrus(P=0.024,r=0.433) showed correlation with the aggregate score of RS-Ⅳ.ConclusionThe spontaneous neuronal activity decreases in prefrontal cortex and increases in default mode network of ADHD group,the activity level of left prefrontal and right cuneus gyrus is positively correlated with symptom severity.

Objective To investigate the risk factors which indicate behavior problems and degree of conflict function defects in different subtypes of attention deficit hyperactivity disorder( ADHD),and to compare behavioral problems,family environment and conflict function in children with and without ADHD.Methods 87children with ADHD and 38 matched controls performed Simon-Stroop task while questionnaires (Parent Symptom Questionnaire and Family environment Scale)were acquired from their parents.Results Questionnaire indicated that children with ADHD-combined(ADHD-C) had the highest score of conduct problem( 1.05 ± 0.44),learning problem ( 1.97 ± 0.52 ),hyperactivity-impulsion ( 1.56 ± 0.60) and hyperactivity index ( 1.45 ± 0.40 ) than ADHDⅠ(0.65±0.32,1.58 ±0.58,1.06 ±0.46,1.01 ±0.31) and matched controls ( 0.42 ±0.24,0.77 ±0.49,0.58±0.40,0.55 ±0.34) in PSQ.ADHD-Ⅰ and ADHD-C had higher score of contradiction(3.28 ± 1.70,4.61 ±2.56 ) and lower score of family cohesion (6.75 ± 2.27,6.61 ± 2.03 ),emotional expression (5.03 ± 1.54,5.06 ±1.91 ),knowledge (3.83 ± 2.30,3.61 ± 1.81 ) and entertainment (3.70 ± 2.12,3.47 ± 2.32 ) than matched controls (2.36 ± 1.44,8.06 ± 1.71,6.03 ± 1.54,4.86 ± 1.91,4.83 ± 2.29) in FES-CV.Behavior data indicated that the correct rate of children with ADHD-Ⅰ and ADHD-C in Simon-incongruent trials( Siin:0.76 ± 0.13,0.69 ±0.13 ) and Stroop-inconsistent trials( Stin:0.82 ± 0.10,0.78 ± 0.08 )were lower and reaction time of children with ADHD-Ⅰ and ADHD-C in the Siin ( (876.4 ± 97.34) ms,( 893.8 ± 130.1 ) ms) and Stin ( ( 864.4 ± 91.82 ) ms,(860.2 ± 125.0) ms) were longer than matched controls ( (Siin (0.81 ± 0.11 ) ms,(810.4 ± 136.1 ) ms; Stin (0.87 ± 0.08 ) ms,(797.4 ± 136.1 ) ms).Pearson correlation analysis suggested that some factors in the FES-CV had correlation with behavioral problems.Conclusion This finding indicates that poor family environment is the risk factor that indicate behavioral problems in children with ADHD and behavioral problems,conflict function defeet of ADHD-C are more serious than ADHD-Ⅰ and matched controls.

In this study, we investigated the pharmacokinetics parameters of SPIO-shRNA dual functional molecular probe and observed the main organ distribution by MRI in vivo. Eighteen New Zealand white rabbits were randomly divided into three groups and injected intravenously with different doses of SPIO-shRNA molecular probe, respectively. The blood samples were collected to analyze the pharmacokinetic parameters by measuring the iron content at 30 minutes before and after the injection. Twenty-four Kun Ming (KM) mice were randomly divided into 4 groups: the control group was injected intravenously with physiological saline 200 µL per mouse via the tail vein, the other 3 groups were injected intravenously with different doses of SPIO-shRNA molecular probe. MRI observation was performed in 24 hours, and the liver, spleen, kidney, brain and muscle were collected for iron quantification with Prussian blue staining to determine distribution of the SPIO-shRNA molecular probe in the main organ in vivo. Our results suggest that the molecular probe blood half-life is more than 3 hours. The data of MRI suggest the probe was distributed in liver and spleen, and the MRI signal was reduced with the increase in probe's doses (P < 0.05). The results of Prussian blue staining confirmed the results of MRI. Most of the probe could escape the phagocytosis of mononuclear phagocyte system. Our data provide the pharmacokinetic and distribution of SPIO-shRNA molecular probe in organs. Meanwhile, it suggests the choice of the time and dose of probe for MR imaging of tumor in vivo.
Animals ; Half-Life ; Magnetic Resonance Imaging ; Magnetite Nanoparticles ; Mice ; Molecular Probes ; pharmacokinetics ; RNA, Small Interfering ; chemistry ; Rabbits