Polymorphism of drug is known to influence the stability, dissolution, bioavailability and other performance characteristics of the products. Therefore, the crystal form of the drug must be identified and determined in order to ensure consistent product performance. Even if the identification and characterization of crystal forms are performed thoroughly and the effective crystal form is selected for preparation, it is important to ensure that the effective crystal form in the final product remains unchanged. Therefore, it is essential to quantitate the content of the effective crystal form in the product to control the quality and performance of them. X-ray powder diffraction, FT-Raman, mid-IR, near-IR, terahertz pulsed spectroscopy, solid-state NMR spectroscopy, and DSC are the quantitative methods of crystal form used in the recent 10 years. This review briefly highlights the basic principles and the progress of these methods and discusses the perspective as they apply to pharmaceutical research and development.
Calorimetry, Differential Scanning ; methods ; Chemistry, Pharmaceutical ; methods ; Crystallization ; Fourier Analysis ; Magnetic Resonance Spectroscopy ; methods ; Pharmaceutical Preparations ; chemistry ; Spectroscopy, Fourier Transform Infrared ; methods ; Spectroscopy, Near-Infrared ; methods ; Spectrum Analysis, Raman ; methods ; Technology, Pharmaceutical ; methods ; Terahertz Spectroscopy ; methods ; X-Ray Diffraction ; methods

Objective To investigate DNA methylation markers in the whole blood of patients with systemic lupus erythematosus(SLE),in hope to facilitate the evaluation of SLE severity.Methods Whole blood samples were obtained from 58 patients with SLE(including 14 cases of severe SLE,25 moderate SLE,19 inactive SLE)and 50 healthy controls.Bisulphite sequencing was performed to determine the methylation status of interleukin-2 common receptor gamma chain(IL-2RG)promoter region,and real-time reverse transcriptionPCR to quantify the expression level of IL-2RG mRNA,in these subjects.Results The methylation level of IL2RG promoter region was 0.217 ± 0.140,0.325 ± 0.230,0.342 ± 0.085 and 0.175 ± 0.036 in the patients withsevere,moderate and inactive SLE and healthy controls,respectively.A significant increase was observed in the methylation level of IL-2RG promoter region in the patients with inactive SLE compared with the patients with severe SLE and healthy controls(both P ＜ 0.01),and in the patients with SLE compared with the healthy controls(0.263 ± 0.047 vs.0.175 ± 0.036,P ＜ 0.05).The expression level of IL-2RG mRNA was significantly lower in the patients with SLE than in the healthy controls(2.550 ± 0.823 vs.4.293 ± 1.283,P ＜ 0.05).A negative correlation was observed between the expression level of IL-2RG mRNA and methylation level of IL2RG promoter region in 20 patients with SLE(r =-0.44,P ＜ 0.05).Conclusion The methylation status of IL2RG promoter region is statistically higher in patients with SLE than in healthy controls,and significantly different between patients with active SLE and those with stable SLE.

Macrophages are involved in many important biological processes and membrane proteins are the key effector molecules for their functions. However, membrane proteins are difficult to analyze by 2-DE based method because of their intrinsic tendency to self-aggregate during the first dimension separation (IEF). To circumvent the obstacle hampering membrane protein analysis, we combined one-dimensional SDS-PAGE with capillary liquid chromatography-tandem mass spectrometry (LC-MS/MS). Using this technique, we identified 458 GO annotated membrane proteins with extremely high confidence, including most known markers of peritoneal macrophages (e.g., CD11b, F4/80, CD14, CD18, CD86, CD44, CD16 and Toll-like receptor). Thirteen other CD antigens and 18 Ras-related small GTPase were also identified. In addition to those known macrophage membrane proteins, a significant number of novel proteins have also been identified. This research provides a valuable data set of macrophage membrane proteins, thus allowing for more comprehensive study of membrane proteins and a better understanding of the function mechanisms of macrophages in many biological processes.

Objective （ ） To explore the application value of bone suppression imaging BSI in the diagnosis of occupational （ pneumoconiosis） Methods - pneumoconiosis hereinafter referred to as " " . A total of 330 chest films of high kV digital （ ） radiograph DR of patients with suspected pneumoconiosis were selected by convenient sampling method. BSI is applied to the ， ， ， ， chest films and the differences of small opacity shape small opacity aggregation the number of large opacity lung areas small （ ）， opacity profusion and diagnostic stage of pneumoconiosis were analyzed by simple DR reading DR group simple BSI reading （ ） （ ） Results BSI group and DR and BSI combined reading combined group . There was no significant difference in the distribution of small shadows and the detection rate of small shadows aggregation and large shadows in pneumoconiosis among （ P ） ， the three film reading methods all >0.05 . For the concentration distribution of each lung area there was statistically （P< ）， significant difference between the DR group and the BSI group 0.05 but there was no statistically significant difference ， （ P ） between the DR group and the combined group and between the BSI group and the combined group all >0.05 . The results of ， consistency analysis showed that the DR group and the BSI group and the DR group and the combined group had high （ ， P< consistency in the judgment of small shadow intensity in the lung region both weighted Kappa coefficient were 0.75 all ） 0.01 . There was a high consistency between BSI group and DR group and combined group and DR group in the diagnosis of （ ， ， P< ） ， pneumoconiosis stage weighted Kappa coefficient were 0.77 0.79 all 0.01 . Compared with the DR group the diagnostic ， rate of pneumoconiosis stage Ⅰwas significantly reduced and the diagnostic rate of pneumoconiosis stage Ⅱ was significantly （ P< ） ， increased in the BSI group and the combined group all 0.01 . However there was no significant difference in the diagnosticrate of pneumoconiosis stage Ⅲ >0.05 . Both the BSI reading and DR and BSI combined reading can improve ， the display of pneumoconiosis lesions to varying degrees and therefore can improve the diagnosis of pneumoconiosis. In ， addition the identification and diagnosis of pneumoconiosis lesions in the BSI reading is comparable to that in the combined ， group which has a good application value in the diagnosis of pneumoconiosis.

Objective To compare the cognitive effects of guqin (the oldest Chinese instrument) music and piano music.Methods Behavioral and event-related potential (ERP) data in a standard two-stimulus auditory oddball task were recorded and analyzed. Results This study replicated the previous results of culture-familiar music effect on Chinese subjects: the greater P300 amplitude in frontal areas in a culture-familiar music environment. At the same time, the difference between guqin music and piano music was observed in N1 and later positive complex (LPC: including P300 and P500): a relatively higher participation of right anterior-temporal areas in Chinese subjects. Conclusion The results suggest that the special features of ERP responses to guqin music are the outcome of Chinese tonal language environments given the similarity between Guqin's tones and Mandarin lexical tones.

A novel peptide, named BF2-X, was designed based on the structure-activity analysis of an analogue of Buforin II, named BF2-A. The BF2-X was a hybrid peptide containing the N-terminal residues 5 to 13 of BF2-A and three repeats of the C-terminal regular alpha-helical motif RLLR, and the residues 8 valine were replaced by leucine. The results of bioinformatics analysis had showed that compared with BF2-A, the helicity, positive charge, hydrophobicity rate and C-terminal amphipathy of BF2-X had remarkably enhanced. Both peptides showed a random coil structure in an aqueous solution, while displaying a typical alpha-helical structure in 50% trifluoroethanol solution (a membrane mimic condition). BF2-X exhibited higher alpha-helical contents than BF2-A in hydrophobic environment. BF2-X displayed potent antimicrobial activities against a broad spectrum of microorganisms. And BF2-X showed stronger antimicrobial activities against bacteria tested than parent peptide BF2-A. These results suggest that the alpha-helical content was directly correlated with the enhanced antibacterial activity. Both peptides had no hemolytic action on mouse erythrocyte.
Amino Acid Sequence ; Animals ; Anti-Bacterial Agents ; chemical synthesis ; chemistry ; pharmacology ; Antimicrobial Cationic Peptides ; chemical synthesis ; chemistry ; pharmacology ; Bacteria ; drug effects ; Circular Dichroism ; Hemolysis ; drug effects ; Hydrophobic and Hydrophilic Interactions ; Mice ; Protein Structure, Secondary ; Proteins ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

OBJECTIVETo study the clinicopathologic features of tuberous sclerosis complex (TSC).

METHODSThe clinicopathologic data of the patients diagnosed as TSC with refractory epilepsy and resection of epileptic focus were retrospectively analyzed.

RESULTSFourteen cases were included, the mean age was (15.8±12.9) years, with a male predominance (male to female ratio=10:4). Frontal lobe was the most common (13/14) site of involvement. MRI showed multiple patchy long T1 and long T2 signals. CT images showed multiple subependymal high density calcified nodules in nine cases. Histology showed mild to severe disruption of the cortical lamination, cortical and subcortical tubers with giant cells and/or dysmorphic neurons. The giant cells showed strong immunoreactivity for vimentin and nestin, while the dysmorphic neurons partially expressed MAP2 and NF. Vimentin also stained strongly the "reactive" astrocytes. Thirteen cases had follow-up information: Engel class I in six cases, Engel class II in six cases, and Engel class III in one case.

CONCLUSIONSDiagnosis of TSC relies on combined pathologic, clinical and neuroradiological features. Immunohistochemical staining can be helpful. Resection of epileptic focus is an effective method to treat refractory epilepsy in TSC.

Adolescent ; Astrocytes ; chemistry ; pathology ; Child ; Drug Resistant Epilepsy ; surgery ; Epilepsy ; complications ; metabolism ; pathology ; Epilepsy, Frontal Lobe ; complications ; metabolism ; pathology ; Female ; Giant Cells ; chemistry ; pathology ; Humans ; Magnetic Resonance Imaging ; Male ; Nestin ; analysis ; Neurons ; metabolism ; pathology ; Retrospective Studies ; Tuberous Sclerosis ; complications ; metabolism ; pathology ; Vimentin ; analysis

OBJECTIVETo study the effect of Q-switched 1 064 nm Nd:YAG laser treatment on the proliferation of dermal collagen and expression of immunoglobulin binding protein/glucose related protein 78 (BiP/GRP78) in rats' skin and the mechanism of endoplasmic reticulum stress.

METHODSDorsal skin of 25 Wistar rats was divided into two parts equally after hair removal. Q-switched 1 064nm Nd:YAG laser was applied to treat rats' dorsal skin for 4 times at an interval of 2 days in the experiment part. The control part received no laser treatments. The rats' dorsal skin samples were taken on the 14th and 30th day after laser treatment to measure the dermis thickness and collagen bundles under HE stain and to measure the hydroxyproline content by alkaline hydrolysis method after laser treatment. The expression of BiP/GRP78 was also detected by immunohistochemical method. Statistics was used to analyze the data.

RESULTSThe dermis thickness increased by 29. 6% on the 14th day and 16.7% on the 30th day after laser treatment. The collagen bundles became thicker and denser. The hydroxyproline in the skin was also raised after laser treatment (P < 0.05). The immunohistochemical result showed the expression of BiP/GRP78 increased to 100% after laser treatment, showing a significant difference from the control group(X2 = 28.76, P < 0.01).

CONCLUSIONSThe Q-switched 1064 nm Nd:YAG laser treatment can induce endoplasmic reticulum stress, so as to enhance the protein folding and synthesizing precisely. The proliferation of dermis collagen is the base of effect of non-ablative skin rejuvenation.

Animals ; Endoplasmic Reticulum Stress ; Female ; Hydroxyproline ; chemistry ; Lasers, Solid-State ; Rats ; Rats, Wistar ; Rejuvenation ; Skin ; radiation effects ; Skin Aging

OBJECTIVETo investigate the association of advanced oxidation protein products (AOPP) with oxidative stress in colon cancer cells exposed to intermittent hypoxia (IH).

METHODSColon cancer SW480 cells were exposed to IH, continuous hypoxia, or normoxia. Enzyme-linked immunosorbent assay (ELISA) was employed to examine the levels of AOPP and vascular endothelial growth factor (VEGF), xanthine oxidase assay was used to determine malonaldehyde (MDA) and glutathione peroxidase (GSH-PX), and Western blotting and immunofluorescence assay were performed for detection of transforming growth factor-β(1) (TGF-β(1)) expression.

RESULTSCompared with the normoxia group, the two hypoxia groups showed significantly increased AOPP and MDA levels (P<0.05) and lowered SOD and GSH-PX levels (P<0.05). The concentration of AOPP was positively correlated to MDA, VEGF, and TGF-β(1) levels (P<0.05), but inversely to SOD. No significant correlation was found between AOPP and GSH-PX levels.

CONCLUSIONCompared with continuous hypoxia, IH results in more obvious protein oxidation in relation to oxidative stress. The increased expression of VEGF and TGF-β(1) in the context of hypoxia is closely related to AOPP level.

Advanced Oxidation Protein Products ; metabolism ; Cell Hypoxia ; Cell Line, Tumor ; Colonic Neoplasms ; metabolism ; Humans ; Oxidative Stress ; Transforming Growth Factor beta1 ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism

To research the effect of Ginseng Radix et Rhizoma and Aconiti Lateralis Radix Praeparata compatibility on cardiac toxicity in rats by UPLC-Q-TOF/MS, and explore the endogenous markers and molecule mechanism. Different compatibility of Shenfu decoction were given to male Wistar rats at dosage of 20 g · kg(-1) for 7 days, collected the serum, and analyze the endogenous metabolites effected by Shenfu formulation by principal component analysis and partial least-squares analysis. Results showed that content of glutathione, phosphatidylcholine and citric acid decreased in mixed-decoction group, while ascorbic acid, uric acid, D-galactose, tryptophan, L-phenylalanine increased. The results showed cardiac toxicity of Aconiti Lateralis Radix Praeparata in Shenfu mixed-decoction. Shenfu co-decoction group showed a similar or weaker trend compared with control group, but most of them do not have a statistically significant. The results indicated the scientific basis of Shenfu compatibility by comparison of co-decoction group with mixed-decoction group. Shenfu compatibility can reduce cardiac toxicity induced by Aconiti Lateralis Radix Praeparata, and citric acid, glutathione, phosphatidyl choline, uric acid might be regarded as potential markers of cardiotoxicity.
Animals ; Biomarkers ; Cardiotoxicity ; Drugs, Chinese Herbal ; toxicity ; Glutathione ; blood ; Least-Squares Analysis ; Male ; Metabolomics ; methods ; Principal Component Analysis ; Rats ; Rats, Wistar